Triazaspiro[5.5]undecane derivatives and drugs containing the same as the active ingredient

TECHNICAL FIELD

[0001] The present invention relates to triazaspiro[5.5]undecane derivatives and pharmaceutical compositions comprising thereof, as an active ingredient.

[0002] More particularly, it relates to triazaspiro[5.5]undecane derivatives of the formula (I)

[0003] (wherein all the symbols have the same meaning as defined hereinafter), quaternary ammonium salts thereof, N-oxides thereof, non-toxic salts thereof, the methods for preparation thereof and pharmaceutical compositions comprising thereof, as an active ingredient.

BACKGROUND OF THE INVENTION

[0004] Chemokine is known as a basic protein having endogeneous leukocyte chemotactic and activating abilities and strong heparin-binding ability. At present, it is considered that chemokine is related to not only the control of infiltration of specific leukocyte at the time of inflammations and immune responses but also the development and homing of lymphocyte under physiological conditions and migration of hemocyte precursor cells and somatic cells.

[0005] Differentiation, proliferation and cell death of hemocytes are controlled by various types of cytokine. In the living body, inflammations are found topically and differentiation, maturation and the like of lymphocytes are carried out at certain specified sites. That is, various necessary cells migrate into certain specified sites and accumulate therein to cause a series of inflammations and immune responses. Accordingly, migration of cells is also an indispensable phenomenon in addition to differentiation, proliferation and death of cells.

[0006] Migration of hemocytes in the living body starts firstly in the development stage by the shift of hematopoiesis started in the AGM region into permanent hematopoiesis in bone marrow via fetal liver. Furthermore, precursor cells of T cells and thymus dendritic cells migrate from the fetal liver into the bone marrow and then into the thymus gland and cytodifferentiate under thymus environment. The T cell which received clone selection migrates into secondary lymphoid tissues and takes part in an immune response in the periphery. The Langerhans' cell of the skin activated and differentiated by capturing an antigen migrates into the T cell region of a topical lymph node and activates naive T cell therein as a dendritic cell. The memory T cell performs its homing again into the lymph node via lymphatic and blood vessels. Also, B cell, T cell in the intestinal epithelium, γδ T cell, NKT cell and dendritic cell migrate from bone marrow without passing through the thymus gland and differentiate to take part in an immune response.

[0007] Chemokine is deeply related to the migration of these various cells. For example, MIP3β, SLC and its receptor CCR7 play an important role in the migration and homing of naïve T cell, memory T cell and the mature dendritic cell which captured an antigen into a topical lymphoid tissue for the dendritic cells to encounter efficiently with the T cells. The T cell and dendritic cell necessary for controlling antigen-specific immune responses are hardly observed in the secondary lymph node of a PLT mouse having deficiency in the expression of SLC (J. Exp. Med., 18(3), 451 (1999)).

[0008] MDC, TARC and its receptor CCR4 play an important role in the migration of Th2 cell into topical sites in immune and inflammatory responses in which the Th2 cell is related. In a rat fluminant hepatitis model (P. acnes+LPS), an anti-TARC antibody suppressed increase of the amount of ALT in blood and increase of the expressing amounts of TNFα and FasL in the liver and also improved lethality of the rats (J. Clin. Invest., 102, 1933 (1998)). Also, an anti-MDC antibody decreased the number of eosinophils accumulated in the lung interstitium and suppressed airway hypersensitivity in a mouse OVA-induced airway hypersensitivity model (J. Immunology, 163, 403 (1999)).

[0009] MCP-1 and its receptor CCR2 are related to the infiltration of macrophage into inflammation sites. An anti-MCP-1 antibody showed an effect to suppress infiltration of monocyte and macrophage into glomerulus in a rat anti-Thy1.1 antibody glomerular nephritis model (Kidney Int., 51, 770 (1997)).

[0010] Thus, chemokine receptors are greatly related to the control of inflammation and immune responses through a mechanism in which they are expressed at certain specified periods in variously specific cells and the effector cells are accumulated in a region where chemokine is produced.

[0011] Acquired immunodeficiency syndrome (called AIDS) which is induced by human immunodeficiency virus (hereinafter referred to as “HIV”) is one of the diseases of which their therapeutic methods are most earnestly desired in recent years. Once infection with HIV is completed in a CD4-positive cell which is a principal target cell, HIV repeats its proliferation in the body of the patient and, sooner or later, completely destroys T cell which takes charge of the immunological function. During this process, the immunological function is gradually reduced to cause fever, diarrhea, lymph node enlargement and the like various immunodeficiency conditions which are apt to cause complications with pneumocystis carinii pneumonia and the like various opportunistic infections. Such conditions are the onset of AIDS, and it is well known that they induce and worsen Kaposi sarcoma and the like malignant tumors.

[0012] As the recent preventive and therapeutic methods for AIDS, attempts have been made to, e.g., (1) inhibit growth of HIV by the administration of a reverse transcriptase inhibitor or a protease inhibitor and (2) prevent or alleviate opportunistic infections by the administration of a drug having immunopotentiation activity.

[0013] Helper T cells which take charge of the central of immune system are mainly infected with HIV. It is known since 1985 that HIV uses the membrane protein CD4 expressing on the membrane of T cells in the infection (Cell, 52, 631 (1985)). The CD4 molecule is composed of 433 amino acid residues, and its expression can be found in macrophages, some B cells, vascular endothelial cells, Langerhans' cells in skin tissues, dendritic cells in lymphoid tissues, glia cells of the central nervous system and the like, in addition to the mature helper T cells. However, since it has been revealed that the infection with HIV is not completed by the CD4 molecule alone, a possibility has been suggested on the presence of factors other than the CD4 molecule, which are related to the infection of cells with HIV.

[0014] In 1996, a cell membrane protein called Fusin was identified as a factor other than the CD4 molecule, which is related to the HIV infection (Science, 272, 872 (1996)). It was confirmed that this Fusin molecule is a receptor (namely, CXCR4) of stromal derived factor-1 (hereinafter referred to as “SDF-1”). In addition, it was confirmed also in vitro that the SDF-1 specifically inhibits infection of T cell tropic (X4) HIV (Nature, 382, 829 (1996), Nature, 32, 833 (1996)). That is, it is considered that the HIV infection was inhibited by the binding of SDF-1 to CXCR4 preceding HIV, thereby depriving HIV of a foothold for infecting cells.

[0015] Also at that time, it was discovered that another chemokine receptor CCR5, which is a receptor of RANTES, MIP-1α and MIP-1β, is also used at the time of the infection with a macrophage tropic (R5) HIV (Science, 212, 1955 (1996)).

[0016] Accordingly, substances which can compete with CXCR4 and CCR5 for HIV, or which can bind to HIV virus thus causing the virus unable to bind to CXCR4 and CCR5, could become HIV infection inhibitors. Also, there is a case in which a low molecular compound initially discovered as an HIV infection inhibitor was actually a CXCR4 antagonist (Nature Medicine, 4, 72 (1998)).

[0017] Based on the above, it is considered that the chemokine/chemokine receptors are deeply related to the inflammation, immune disease or HIV infection. For example, it is considered that they are related to the inhibition of various inflammatory diseases, asthma, atopic dermatitis, nettle rash, allergic diseases (allergic bronchopulmonary aspergillosis, allergic eosinophilic gastroenteritis and the like), glomerular nephritis, nephropathy, hepatitis, arthritis, chronic rheumatoid arthritis, psoriasis, rhinitis, conjunctivitis and ischemia-reperfusion injury, in the treatment of multiple sclerosis, ulcerative colitis, acute respiratory distress syndrome, shock accompanied by bacterial infection, diabetes mellitus and autoimmune diseases, and in transplanted organ rejection reactions, immunosuppression, metastasis prevention and acquired immunodeficiency syndrome.

[0018] On the other hand, in specification of WO97/11940, it is described that compounds of the formula (Z)

[0019] (wherein the atoms AiZ and BiZ are independently selected from carbon, nitrogen, oxygen or sulfur, provided that at least one atom of AiZ is carbon, and at least one atom BiZ is carbon;

[0020] the rings of the spirobicycle formed by AiZ and BiZ, respectively, may optionally be partly unsaturated,

[0021] pZ and qZ are independently numbers from 2 to 6,

[0022] mZ is a number from 0 to pZ,

[0023] R10Z is the same or different and is a non-interfering substituent independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, ═O, ═S etc.,

[0024] nZ is a number from 0 to qZ,

[0025] R0Z is the same or different and is a non-interfering substituent independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, ═O, ═S etc.,

[0026] the linking group -(LZ)- is a bond or a divalent substituted or unsubstituted chain of from 1 to 10 atoms selected from the group consisting of carbon, nitrogen, sulfur, and oxygen,

[0027] QZ is a basic group containing one or more basic radicals, and

[0028] R3Z is an acidic group containing one or more acid radicals) are useful in inhibition platelet aggregation.

[0029] In specification of WO98/25605, it is described that compounds of the formula (Y)

[0030] (wherein mY or lY are each independently 0, 1, 2, 3, 4 or 5,

[0031] R1Y is hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl etc.,

[0032] WY is a bond, C1-3 alkyl or C1-3 alkyl substituted with oxo etc.,

[0033] QY is —NR2—, —O—, —S—, —S(O)— or —SO2—,

[0034] XY is a bond, C1-3 alkyl or C1-3 alkyl substituted with oxo etc.,

[0035] YY-ZY ring is phenyl, naphthyl or hetero aryl.

[0036] With the proviso that the definition of each symbol is a excerpt partially.) are useful as modulators of the chemokine receptors.

DISCLOSURE OF THE INVENTION

[0037] The present inventors have investigated to find compounds regulating chemokine/chemokine receptors, so that the present inventors have found that the purpose has been achieved by triazaspiro[5.5]undecane derivatives of the formula (I).

[0038] The present invention relates to

[0039] i) triazaspiro[5.5]undecane derivatives of the formula (I)

[0040] [wherein R1 is

[0041] (1) hydrogen,

[0042] (2) C1-18 alkyl,

[0043] (3) C2-18 alkenyl,

[0044] (4) C2-18 alkynyl,

[0045] (5) —COR6,

[0046] (6) —CONR7R8,

[0047] (7) —COOR9,

[0048] (8) —SO2R10,

[0049] (9) —COCOOR11,

[0050] (10) —CONR12COR13,

[0051] (11) Cyc 1, or

[0052] (12) C1-18 alkyl, C2-18 alkenyl or C2-18 alkynyl substituted by 1-5 of optionally selected from (a) halogen, (b) —CONR7R8, (c) —COOR9, (d) —OR14, (e) —SR15, (f) —NR16R17, (g) —NR18COR19, (h) —SO2NR20R21, (i) —OCOR22, (j) —NR23SO2R24, (k) —NR25COOR26, (l) —NR27CONR28R29, (m) Cyc1, (n) keto or (o) —N(SO2R24)2,

[0053] (wherein R6-R9, R11-R21, R23, R25 and R27-R29 are each independently,

[0054] (1) hydrogen,

[0055] (2) C1-8alkyl,

[0056] (3) C2-8 alkenyl,

[0057] (4) C2-8 alkynyl,

[0058] (5) Cyc 1, or

[0059] (6) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by 1-5 of optionally selected from (a) Cyc 1, (b) halogen, (c) —OR30, (d) —SR31, (e) —NR32R33, (f) —COOR34, (g) —CONR35R36, (h) —NR37COR38, (i) —NR39SO2R40 or (j) —N(SO2R40)2, or

[0060] R7 and R8, R20 and R21, R23 and R29, taken together, are 1) C2-6 alkylene, 2) -(C2-6 alkylene)-O-(C2-6 alkylene)-, 3) -(C2-6 alkylene)-S-(C2-6 alkylene)- or 4) -(C2-6 alkylene)-NR195-(C2-6 alkylene)-, (wherein R195 is hydrogen, C1-8 alkyl, phenyl or C1-8alkyl substituted by phenyl.),

[0061] R10, R22, R24 and R26 are each independently,

[0062] (1) C1-8alkyl,

[0063] (2) C2-8 alkenyl,

[0064] (3) C2-8 alkynyl,

[0065] (4) Cyc 1, or

[0066] (5) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by 1-5 of optionally selected from (a) Cyc 1, (b) halogen, (c) —OR30, (d) —SR31, (e) —NR32R33, (f) —COOR34, (g) —CONR35R36, (h) —NR37COR38, (i) —NR39SO2R40 or (j) —N(SO2R40)2,

[0067] (wherein R30-R37 and R39 are each independently, hydrogen, C1-8 alkyl, Cyc 1 or C1-8 alkyl substituted by Cyc 1, or

[0068] R35 and R36, taken together, are 1) C2-6 alkylene, 2) -(C2-6 alkylene)-O-(C2-6 alkylene)-, 3) -(C2-6 alkylene)-S-(C2-6 alkylene)- or 4) -(C2-6 alkylene)-NRNR196-(C2-6 alkylene)-, (wherein R196 is hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted by phenyl.),

[0069] R38 and R40 are each independently C1-8 alkyl, Cyc 1 or C1-8 alkyl substituted by Cyc 1.)

[0070] Cyc 1 is C3-15 mono-, bi- or tri-(fused or spiro) carbocyclic ring or 3-15 membered mono-, bi- or tri-(fused or spiro) cyclic hetero ring containing 1-4 nitrogen atom(s), 1-3 oxygen atom(s) and/or 1-3 sulfur atom(s).

[0071] With the proviso that, Cyc 1 may be optionally substituted by 1-5 of R51, R5 is

[0072] (1) C1-8 alkyl,

[0073] (2) C2-8 alkenyl,

[0074] (3) C2-8 alkynyl,

[0075] (4) halogen,

[0076] (5) nitro,

[0077] (6) trifluoromethyl,

[0078] (7) trifluoromethoxy,

[0079] (8) nitrile,

[0080] (9) keto,

[0081] (10) Cyc 2

[0082] (11) —OR52,

[0083] (12) —SR53,

[0084] (13) —NR54R55,

[0085] (14) —COOR56,

[0086] (15) —CONR57R56,

[0087] (16) —NR59COR60,

[0088] (17) —SO2NR61R62,

[0089] (18) —OCOR63,

[0090] (19) —NR64SO2R65,

[0091] (20) —NR66COOR67,

[0092] (21) —NR68CONR69R70,

[0093] (22) —B(OR7)2,

[0094] (23) —SO2R72,

[0095] (24) —N(SO2R72)2, or

[0096] (25) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by 1-5 of optionally selected from (a) halogen, (b) Cyc 2, (c) —OR52, (d) —SR53, (e) —NR54R55, (f) —COOR56, (g) —CONR57R58, (h) —NR59COR60, (i) —SO2NR61R62, (j) —OCOR63, (k) —NR64SO2R65, (l) —NR66COOR67, (m) —NR68CON R69R70, (n) —B(OR71)2, (o) —SO2R72 or (p) —N(SO2R72)2.)

[0097] (wherein R52-R62, R64, R66 and R68-R71 are each independently 1) hydrogen, 2) C1-8 alkyl, 3) C2-8 alkenyl, 4) C2-8 alkynyl, 5) Cyc 2 or 6) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by Cyc 2, —OR73, —COOR74 or —NR75R76, or R57 and R58, R61 and R67, R69 and R70, taken together, are 1) C2-6 alkylene, 2) -(C2-6 alkylene)-O-(C2-6 alkylene)-, 3) -(C2-6 alkylene)-S-(C2-6 alkylene)- or 4) -(C2-6 alkylene)-NR197-(C2-6 alkylene)-, (wherein R197 is hydrogen, C1-8 alkyl, phenyl or C1-8alkyl substituted by phenyl.),

[0098] R63, R65, R67 and R72 are each independently 1) C1-8 alkyl, 2) C2-8 alkenyl, 3) C2-8 alkynyl, 4) Cyc 2 or 5) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by Cyc 2, —OR73, —COOR74 or —NR75R76,

[0099] (wherein R73-R76 are independently hydrogen, C1-8 alkyl, Cyc 2 or C1-8 alkyl substituted by Cyc 2.)

[0100] Cyc 2 is the same meaning as Cyc 1.

[0101] With the proviso that, Cyc 2 may be optionally substituted by 1-5 of R77, R77 is

[0102] 1) C1-8alkyl,

[0103] 2) halogen,

[0104] 3) nitro,

[0105] 4) trifluoromethyl,

[0106] 5) trifluoromethoxy,

[0107] 6) nitrile,

[0108] 7) —OR78,

[0109] 8) —NR79R80,

[0110] 9) —COOR81,

[0111] 10) —SR82,

[0112] 11) —CONR83R84,

[0113] 12) C2-8 alkenyl,

[0114] 13) C2-8 alkynyl,

[0115] 14) keto,

[0116] 15) Cyc 6,

[0117] 16) —NR161COR162,

[0118] 17) —SO2NR163R164,

[0119] 18) —OCOR165,

[0120] 19) —NR166SO2R167,

[0121] 20) —NR168COOR169,

[0122] 21) —NR170COR171R172,

[0123] 22) —SO2R173,

[0124] 23) —N(SO2R167)2, or

[0125] 24) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by 1-5 of optionally selected from (a) halogen, (b) —OR78, (c) —NR79R80, (d) —COOR81, (e) —SR82, (f) —CONR83R84, (g) keto, (h) Cyc 6, (i) —NR161COR162, (j) —SO2NR163R164 (k) —OCOR165, (l) —NR166SO2R167, (m) —NR168COOR169, (n) —NR170COR171R172, (o) —SO2R173 or (p) —N(SO2R167)2.)

[0126] (wherein R78-R84, R161-R164, R166, R168 and R170-R172 are each independently (a) hydrogen, (b) C1-8 alkyl, (c) C2-8 alkenyl, (d) C2-8 alkynyl, (e) Cyc 6 or (f) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by Cyc 6, —OR174, —COOR175, —NR176R177 or —CONR178R179, or

[0127] R83 and R84, R163 and R164, R171 and R172, taken together, are 1) C2-6 alkylene, 2) -(C2-6 alkylene)-O-(C2-6 alkylene)-, 3) -(C2-6 alkylene)-S-(C2-6 alkylene)- or 4) -(C2-6 alkylene)-NR198-(C2-6 alkylene)-, (wherein R198 is hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted by phenyl.),

[0128] R165, R167, R169 and R173 are each independently (a) C1-8 alkyl, (b) C2-8 alkenyl, (c) C2-8 alkynyl, (d) Cyc 6 or (e) C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl substituted by Cyc 6, —OR174, —COOR175, —NR176R177 or —CONR178R179.)

[0129] (wherein R174-R177 are each independently 1) hydrogen, 2) C1-8 alkyl, 3) Cyc 6 or 4) C1-8 alkyl substituted by Cyc 6, or

[0130] R178 and R179, taken together, are 1) C2-6 alkylene, 2) -(C2-6 alkylene)-O-(C2-6 alkylene)-, 3) -(C2-6 alkylene)-S-(C2-6 alkylene)- or 4) -(C2-6 alkylene)-NR199-(C2-6 alkylene)-(wherein R199 is hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted by phenyl.),

[0131] Cyc 6 is C3-8 mono-carbocyclic ring or 3-8 membered mono-cyclic hetero ring containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or 1-2 sulfur atom(s).

[0132] With the proviso that, Cyc 6 may be optionally substituted by 1-5 of R180, R180 is,

[0133] (1) C1-8 alkyl,

[0134] (2) halogen,

[0135] (3) nitro,

[0136] (4) trifluoromethyl,

[0137] (5) trifluoromethoxy,

[0138] (6) nitrile,

[0139] (7) —OR181,

[0140] (8) —NR182R183,

[0141] (9) —COOR184,

[0142] (10) —SR185, or

[0143] (11) —CONR186R187,

[0144] (wherein R181-R187 are each independently 1) hydrogen, 2) C1-8 alkyl, 3) phenyl or 4) C1-8 alkyl substituted by phenyl,

[0145] R182 and R183, R186 and R187, taken together, are 1) C2-6 alkylene, 2) —(C2-6 alkylene)-O-(C2-6 alkylene)-, 3) -(C2-6 alkylene)-S-(C2-6 alkylene)- or 4) -(C2-6 alkylene)-NR200-(C2-6 alkylene)-, (wherein R200 is hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted by phenyl.).),

[0146] R2 is

[0147] (1) hydrogen,

[0148] (2) C1-8 alkyl,

[0149] (3) C2-8 alkenyl,

[0150] (4) C2-8 alkynyl,

[0151] (5) —OR90,

[0152] (6) Cyc 3, or

[0153] (7) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by 1-5 of optionally selected from (a) halogen, (b) —OR90, (c) —SR91, (d) —NR92R93, (e) —COOR94, (f) —CONR95R96, (g) —NR97COR98, (h) —SO2NR99R100, (i) —OCOR101, (j) —NR102SO2R103, (k) —NR104COOR105, (l) —NR106CONR107R108, (m) Cyc3, (n) keto or (o) —N(SO2R103)2,

[0154] (wherein R90-R100, R102, R104 and R106-R108 are each independently 1) hydrogen, 2) C1-8 alkyl, 3) C2-8 alkenyl, 4) C2-8 alkynyl, 5) Cyc 3 or 6) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by Cyc 3, or

[0155] R95 and R96, R99 and R100, R107 and R108, taken together, are 1) C2-6 alkylene 2)- (C2-6 alkylene)-O-(C2-6 alkylene)-, 3) -(C2-6 alkylene)-S-(C2-6 alkylene)- or 4) -(C2-6 alkylene)-NR201-(C2-6 alkylene)-, (wherein R201 is hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted by phenyl.),

[0156] R10, R103 and R105 are each independently 1) C1-8 alkyl, 2) C2-8 alkenyl, 3) C2-8 alkynyl or 4) Cyc 3, or C1-8 alkyl, C2-8alkenyl or C2-8alkynyl substituted by Cyc 3,

[0157] Cyc 3 is the same meaning as Cyc 1.

[0158] With the proviso that, Cyc 3 may be optionally substituted by 1-5 of R109, R109 is the same meaning as R51)

[0159] R3 and R4 are each independently

[0160] (1) hydrogen,

[0161] (2) C1-8 alkyl,

[0162] (3) C2-8 alkenyl,

[0163] (4) C2-8 alkynyl,

[0164] (5) —COOR120,

[0165] (6) —CONR21R122,

[0166] (7) Cyc 4, or

[0167] (8) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by 1-5 of optionally selected from (a) halogen, (b) nitrile, (c) Cyc 4, (d) —COOR120, (e) —CONR121R122, (f) —OR123, (g) —SR124, (h) —NR125R126, (i) —NR127COR128, (j) —SO2NR129R130, (k) —OCOR131, (l) —NR132SO2R133, (m) —NR134COOR135, (n) —NR136CONR137R138, (o) —S—SR139, (p) —NHC(═NH)NHR140, (q) keto, (r) —NR145CONR146COR147 or (s) —N(SO2R133)2,

[0168] (wherein R120-R130 R132 R134 R136-R38, R145 and R146 are each independently 1) hydrogen, 2) C1-8 alkyl, 3) C2-8 alkenyl, 4) C2-8 alkynyl, 5) Cyc 4 or 6) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by Cyc 4, halogen, —OR148, —SR149, —COOR150 or —NHCOR141, or

[0169] R121 and R122 R129 and R130, R137 and R138, taken together, are 1) C2-6 alkylene, 2) -(C2-6 alkylene)-O-(C2-6 alkylene)-, 3) -(C2-6 alkylene)-S-(C2-6 alkylene)- or 4) -(C2-6 alkylene)-NR201-(C2-6 alkylene)-, (wherein R201 is hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted by phenyl.),

[0170] R131, R133, R135, R139 and R147 are each independently 1) C1-8 alkyl, 2) C2-8 alkenyl, 3) C2-8 alkynyl, 4) Cyc 4 or 5) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by Cyc 4, halogen, —OR148, —SR149, —COOR150 or —NHCOR141,

[0171] R140 is hydrogen, —COOR142 or —SO2R143,

[0172] (wherein R141-R143 are each independently 1) C1-8 alkyl, 2) C2-8 alkenyl, 3) C2-8 alkynyl, 4) Cyc 4 or 5) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by Cyc 4,

[0173] R148-R150 are each independently 1) hydrogen, 2) C1-8 alkyl, 3) C2-8 alkenyl, 4) C2-8 alkynyl, 5) Cyc 4 or 6) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by Cyc 4,

[0174] Cyc 4 is the same meaning as Cyc 1.

[0175] With the proviso that, Cyc 4 may be optionally substituted by 1-5 of R144, R144 is the same meaning as R51.) or

[0176] R3 and R4, taken together, are

[0177] (wherein R190 and R191 are each independently the same meaning as R3 or R4.),

[0178] R5 is

[0179] (1) hydrogen,

[0180] (2) C1-8 alkyl,

[0181] (3) Cyc 5, or

[0182] (4) C1-8alkyl substituted by Cyc 5.

[0183] (wherein Cyc 5 is the same meaning as Cyc 1.

[0184] With the proviso that, Cyc 5 may be optionally substituted by 1-5 of R150, R150 is the same meaning as R51.)],

[0185] quaternary ammonium salts thereof, N-oxides thereof or non-toxic salts thereof,

[0186] ii) the methods for preparation of compounds of the formula (I), quaternary ammonium salts thereof, N-oxides thereof or non-toxic salts thereof, and

[0187] iii) pharmaceutical compositions comprising compounds of the formula (I), quaternary ammonium salts thereof, N-oxides thereof or non-toxic salts thereof, as an active ingredient.

[0188] In the present invention, C1-18 alkyl means methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl or isomeric groups thereof.

[0189] C2-18 alkenyl means C2-18 alkylene optionally having 1-9 double bond(s) (preferably 1-4 double bond(s)), concretely, vinyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, octadecenyl, butadienyl, pentadienyl, hexadienyl, heptadienyl, octadienyl, nonadienyl, decadienyl, undecadienyl, dodecadienyl, tridecadienyl, tetradecadienyl, pentadecadienyl, hexadecadienyl, heptadecadienyl, octadecadienyl, hexatrienyl, heptatrienyl, octatrienyl, nonatrienyl, decatrienyl, undecatrienyl, dodecatrienyl, tridecatrienyl, tetradecatrienyl, pentadecatrienyl, hexadecatrienyl, heptadecatrienyl, octadecatrienyl or isomeric groups thereof.

[0190] C2-18 alkynyl means C2-18 alkylene optionally having 1-9 triple bond(s) (preferably 1-4 triple bond(s)), concretely, ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl, undecynyl, dodecynyl, tridecynyl, tetradecynyl, pentadecynyl, hexadecynyl, heptadecynyl, octadecynyl, butadiynyl, pentadiynyl, hexadiynyl, heptadiynyl, octadiynyl, nonadiynyl, decadiynyl, undecadiynyl, dodecadiynyl, tridecadiynyl, tetradecadiynyl, pentadecadiynyl, hexadecadiynyl, heptadecadiynyl, octadecadiynyl, hexatriynyl, heptatriynyl, octatriynyl, nonatriynyl, decatriynyl, undecatriynyl, dodecatriynyl, tridecatriynyl, tetradecatriynyl, pentadecatriynyl, hexadecatriynyl, heptadecatriynyl, octadecatriynyl or isomeric groups thereof.

[0191] Halogen is chlorine, bromine, fluorine or iodine.

[0192] C1-8 alkyl means methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl or isomeric groups thereof.

[0193] C2-8 alkenyl means C2-8 alkylene optionally having 1-4 double bond(s), concretely, vinyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, butadienyl, pentadienyl, hexadienyl, heptadienyl, octadienyl, hexatrienyl, heptatrienyl, octatrienyl or isomeric groups thereof.

[0194] C2-8 alkynyl means C2-8 alkylene optionally having 1-4 triple bond(s), concretely, ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, butadiynyl, pentadiynyl, hexadiynyl, heptadiynyl, octadiynyl, hexatriynyl, heptatriynyl, octatriynyl or isomeric groups thereof.

[0195] C2-6 alkylene means methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene or isomeric groups thereof.

[0196] C3-15 mono-, bi- or tri-(fused or spiro)carbocyclic ring means concretely, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, cyclopentene, cyclohexene, cycloheptene, cyclooctene, cyclopentadiene, cyclohexadiene, cycloheptadiene, cyclooctadiene, benzene, indene, naphthalene, indan, tetrahydronaphthalene, bicyclo[3.3.0]octane, bicyclo[4.3.0]nonane, bicyclo[4.4.0]decane, spiro[4.4]nonane, spiro[4.5]decane, spiro[5.5]undecane, bicyclo[3.1.1]heptane, bicyclo[3.3.1]hept-2-ene, fluorene or anthracene etc.

[0197] 3-15 membered mono-, bi- or tri-(fused or spiro)cyclic hetero ring containing 1-4 nitrogen atom(s), 1-3 oxygen atom(s) and/or 1-3 sulfur atom(s) means 3-15 membered mono-, bi- or tri-(fused or spiro)cyclic hetero aryl containing 1-4 nitrogen atom(s), 1-3 oxygen atom(s) and/or 1-3 sulfur atom(s), and partially or fully saturated one.

[0198] 3-15 membered mono-, bi- or tri-(fused or spiro)cyclic hetero aryl containing 1-4 nitrogen atom(s), 1-3 oxygen atom(s) and/or 1-3 sulfur atom(s) is pyrrole, imidazole, triazole, tetrazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, azepine, diazepine, furan, pyran, oxepine, thiophene, thiain (thiopyran), thiepine, oxazole, isoxazole, thiazole, isothiazole, furazan, oxadiazole, oxazine, oxadiazine, oxazepine, oxadiazepine, thiadiazole, thiazine, thiadiazine, thiazepine, thiadiazepine, indole, isoindole, benzofuran, isobenzofuran, benzothiophene, isobenzothiophene, indazole, quinoline, isoquinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, benzoxazole, benzothiazole, benzimidazole, benzoxepine, benzoxazepine, benzoxadiazepine, benzothiepine, benzothiazepine, benzothiadiazepine, benzazepine, benzodiazepine, benzofurazan, benzothiadiazole, benzotriazole, carbazole, acridine, dibenzofuran or dibenzothiophene etc.

[0199] In above 3-15 membered mono-, bi- or tri-(fused or spiro)cyclic hetero ring containing 1-4 nitrogen atom(s), 1-3 oxygen atom(s) and/or 1-3 sulfur atom(s), partially or fully saturated one is pyrroline, pyrrolidine, imidazoline, imidazolidine, pyrazoline, pyrazolidine, triazoline, triazolidine, tetrazoline, tetrazolidine, dihydropyridine, tetrahydropyridine, piperidine, dihydropyrazine, tetrahydropyrazine, piperazine, dihydropyrimidine, tetrahydropyrimidine, perhydropyrimidine, dihydropyridazine, tetrahydropyridazine, perhydropyridazine, dihydroazepine, tetrahydroazepine, perhydroazepine, dihydrodiazepine, tetrahydrodiazepine, perhydrodiazepine, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrothiophene, tetrahydrothiophene, dihydrothiain (dihydrothiopyran), tetrahydrothiain (tetrahydrothiopyran), dihydrooxazole, tetrahydrooxazole, dihydroisoxazole, tetrahydroisoxazole, dihydrothiazole, tetrahydrothiazole, dihydroisothiazole, tetrahydroisothiazole, dihydrooxadiazole, tetrahydrooxadiazole, dihydrothiodiazole, tetrahydrothiodiazole, tetrahydrooxadiazine, tetrahydrothiadiazine, tetrahydrooxazepine, tetrahydrooxadiazepine, perhydrooxazepine, perhydrooxadiazepine, tetrahydrothiazepine, tetrahydrothiadiazepine, perhydrothiazepine, perhydrothiadiazepine, morpholine, thiomorpholine, indoline, isoindoline, dihydrobenzofuran, perhydrobenzofuran, dihydroisobenzofuran, perhydroisobenzofuran, dihydrobenzothiophene, perhydrobenzothiophene, dihydroisobenzothiophene, perhydroisobenzothiophene, dihydroindazole, perhydroindazole, dihydroquinoline, tetrahydroquinoline, perhydroquinoline, dihydroisoquinoline, tetrahydroisoquinoline, perhydroisoquinoline, dihydrophthalazine, tetrahydrophthalazine, perhydrophthalazine, dihydronaphthyridine, tetrahydronaphthyridine, perhydronaphthyridine, dihydroquinoxaline, tetrahydroquinoxaline, perhydroquinoxaline, dihydroquinazoline, tetrahydroquinazoline, perhydroquinazoline, dihydrocinnoline, tetrahydrocinnoline, perhydrocinnoline, dihydrobenzoxazole, perhydrobenzoxazole, dihydrobenzothiazole, perhydrobenzothiazole, dihydrobenzimidazole, perhydrobenzimidazole, dihydrocarbazole, tetrahydrocarbazole, perhydrocarbazole, dihydroacridine, tetrahydroacridine, perhydroacridine, dihydrodibenzofuran, dihydrodibenzothiophene, tetrahydrodibenzofuran, tetrahydrodibenzothiophene, perhydrodibenzofuran, perhydrodibenzothiophene, dioxolane, dioxane, dithiolane, dithiane, benzodioxalane, benzodioxane, benzodithiolane, benzodithiane, 2,4,6-trioxaspiro[bicyclo[3.3.0]octane-3,1′-cyclohexane], 1,3-dioxolano[4,5-g]chromene or 2-oxabicyclo[2.2.1]heptane etc.

[0200] C3-8 mono-carbocyclic ring is concretely, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, cyclopentene, cyclohexene, cycloheptene, cyclooctene, cyclopentadiene, cyclohexadiene, cycloheptadiene, cyclooctadiene or benzene etc.

[0201] 3-8 membered mono-cyclic hetero ring containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or 1-2 sulfur atom(s) means 3-8 membered mono-cyclic hetero aryl containing 1-4 nitrogen atom(s), 1-2 oxygen atom and/or 1-2 sulfur atom(s) and partially or fully saturated one.

[0202] 3-8 membered mono-cyclic hetero aryl containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or 1-2 sulfur atom(s) is pyrrole, imidazole, triazole, tetrazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, azepine, diazepine, furan, pyran, oxepine, thiophene, thiain (thiopyran), thiepine, oxazole, isoxazole, thiazole, isothiazole, furazan, oxadiazole, oxazine, oxadiazine, oxazepine, oxadiazepine, thiadiazole, thiazine, thiadiazine, thiazepine or thiadiazepine etc.

[0203] In above 3-8 membered mono-cyclic hetero ring containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or 1-2 sulfur atom(s), partially or fully saturated one is pyrroline, pyrrolidine, imidazoline, imidazolidine, pyrazoline, pyrazolidine, triazoline, triazolidine, tetrazoline, tetrazolidine, dihydropyridine, tetrahydropyridine, piperidine, dihydropyrazine, tetrahydropyrazine, piperazine, dihydropyrimidine, tetrahydropyrimidine, perhydropyrimidine, dihydropyridazine, tetrahydropyridazine, perhydropyridazine, dihydroazepine, tetrahydroazepine, perhydroazepine, dihydrodiazepine, tetrahydrodiazepine, perhydrodiazepine, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrothiophene, tetrahydrothiophene, dihydrothiain (dihydrothiopyran), tetrahydrothiain (tetrahydrothiopyran), dihydrooxazole, tetrahydrooxazole, dihydroisoxazole, tetrahydroisoxazole, dihydrothiazole, tetrahydrothiazole, dihydroisothiazole, tetrahydroisothiazole, dihydrooxadiazole, tetrahydrooxadiazole, dihydrothiodiazole, tetrahydrothiodiazole, tetrahydrooxadiazine, tetrahydrothiadiazine, tetrahydrooxazepine, tetrahydrooxadiazepine, perhydrooxazepine, perhydrooxadiazepine, tetrahydrothiazepine, tetrahydrothiadiazepine, perhydrothiazepine, perhydrothiadiazepine, morpholine, thiomorpholine, dioxolane, dioxane, dithiolane or dithiane etc.

[0204] In the present invention, each group represented by R1, R2, R3, R4 or R5 is all preferable.

[0205] Preferred R1 is C1-18 alkyl substituted by Cyc 1, C2-18 alkenyl substituted by Cyc 1 or C2-18 alkynyl substituted by Cyc 1, and more preferred R1 is C1-6 alkyl substituted by Cyc 1.

[0206] Preferred Cyc 1 is C3-10 mono- or bi-(fused or spiro) carbocyclic ring or 3-10 membered mono- or bi-(fused or spiro) cyclic hetero ring containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or 1-2 sulfur atom(s), and more preferred Cyc 1 is C5-7 mono-carbocyclic aryl or 5-10 membered mono-cyclic hetero ring containing 1-4 nitrogen atom(s), 2 oxygen atoms and/or 1 sulfur atom.

[0207] Preferred Cyc 1 concretely is benzene, pyrazole, imidazole, furan, thiophene, benzodioxane, thiazole or quinoline.

[0208] Preferred R51 which is a substituent of Cyc 1, is Cyc 2, —OR52, —SR53 or —NR54R55. Preferred R52, R53, R54 and R55 are C1-8 alkyl or Cyc 2, and more preferred R52, R53, R54 and R55 are methyl, ethyl, propyl or phenyl.

[0209] Preferred Cyc 2 is C5-7 mono-carbocyclic aryl or 5-7 membered mono-cyclic hetero aryl containing 1-4 nitrogen atom(s), 1 oxygen atom and/or 1 sulfur atom, and more preferred Cyc 2 is benzene.

[0210] Preferred R77 which is a substituent of Cyc 2 is —CONR83R84, —NR161COR162, —SO2NR163R164, —NR166SO2R167, C1-8 alkyl substituted by —CONR83R84, C1-8 alkyl substituted by —NR161COR162, C1-8 alkyl substituted by —SO2NR163R164 or C1-8 alkyl substituted by —NR166SO2R167. Preferred R83, R84, R161, R162, R163, R164, R166 and R167 are C1-8 alkyl, Cyc 6, C1-8 alkyl substituted by —NR176R177, and more preferred R83, R84, R161, R162, R163, R164, R166 and R167 are methyl, ethyl, propyl, phenyl or dimethylaminoethyl etc.

[0211] Most preferred R1 is phenylethyl, phenylpropyl, phenylbutyl, phenylpentyl, phenylhexyl, 4-methoxyphenylmethyl, 4-propyloxyphenylmethyl, 4-phenyloxyphenylmethyl, 3,5-dimethyl-1-phenylpyrazol-4-ylmethyl, 2-phenylimidazol-4-ylmethyl, 5-ethylfuran-2-ylmethyl, 5-ethylthiophen-2-ylmethyl, 3-chloro-5-methyl-1-phenylpyrazol-4-ylmethyl, 1,4-benzodioxan-6-ylmethyl, 4-(4-methylsulfonylaminophenyloxy)phenylmethyl, 4-(4-(2-dimethylaminoethylsulfonylamino)phenyloxy)phenylmethyl, 4-(4-dimethylaminosulfonylphenyloxy)phenylmethyl, 4-(4-methylcarbonylaminophenyloxy)phenylmethyl, 4-(4-(2-dimethylaminoethylcarbonylamino)phenyloxy)phenylmethyl or 4-(4-dimethylaminocarbonylphenyloxy)phenylmethyl etc.

[0212] Preferred R2 is C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkyl substituted by Cyc 3. Most preferred R2 is C1-4 alkyl, C2-4 alkenyl or C2-4 alkynyl.

[0213] Most preferred R2 is ethyl, propyl, butyl, 2-propenyl, 2-butenyl, 2-propynyl, phenylmethyl, thiophen-2-ylmethyl or 2-butynyl etc.

[0214] Preferred R3 or R4 is hydrogen, C1-8 alkyl, C1-8 alkyl substituted by Cyc4, C1-8alkyl substituted by —OR123, C1-8 alkyl substituted by Cyc4 and —OR123, C1-8 alkyl substituted by —NR127COR128, C1-8 alkyl substituted by —NR132SO2R133, C1-8 alkyl substituted by —NR134COOR135 or C1-8 alkyl substituted by —NR136CONR137R138. More preferred R3 or R4 is C1-4 alkyl, C1-4 alkyl substituted by Cyc4, C1-4 alkyl substituted by —OR23, C1-4 alkyl substituted by Cyc4 and —OR123, C1-4 alkyl substituted by —NR127COR128, C1-4 alkyl substituted by —NR132SO2R133, C1-4 alkyl substituted by —NR134COOR135 or C1-4 alkyl substituted by —NR136CONR137R138.

[0215] Preferred Cyc 4 is benzene or cyclohexane.

[0216] Preferred R123 is hydrogen, C1-4 alkyl, Cyc 4 or C1-4 alkyl substituted by Cyc 4, and more preferred R123 is hydrogen, methyl, ethyl, phenyl or phenylmethyl.

[0217] Preferred R127, R132, R134, R136 and R138 are hydrogen or methyl.

[0218] Preferred R128, R133, R135 and R137 are Cyc 4 or C1-4 alkyl substituted by Cyc 4, and more preferred R128, R133, R135 and R137 are phenyl, phenylmethyl or phenylethyl.

[0219] Preferred R144 which is a substitute of Cyc 4, is C1-4 alkyl, halogen, phenyl or phenyloxy, and more preferred R144 is methyl, fluorine, chlorine, phenyl or phenyloxy.

[0220] Most preferred R3 or R4 is propyl, 1-methylpropyl, 2-methylpropyl, cyclohexylmethyl, 1-hydroxy-2-methylpropyl, 1-hydroxy-1-cyclohexylmethyl, 3-(cyclopentylethylcarbonyl)aminobutyl, 3-(benzyloxycarbonyl) aminopropyl, 3-(phenylcarbonyl)aminobutyl, 3-(phenylmethylcarbonyl)aminobutyl, 3-(phenylethylcarbonyl)aminobutyl, 3-(phenylethenylcarbonyl)aminobutyl, 3-(4-phenylphenylcarbonyl)aminobutyl, 3-(4-phenyloxyphenylaminocarbonyl)aminobutyl, 3-(4-chlorophenylaminocarbonyl)aminobutyl, 3-(4-fluorophenylaminocarbonyl)aminobutyl, 3-(phenylmethylaminocarbonyl)aminobutyl, 3-(4-trifluoromethylsulfonyl)aminobutyl, 4-(cyclopentylethylcarbonyl)aminobutyl, 4-(benzyloxycarbonyl)aminobutyl, 4-(phenylcarbonyl)aminobutyl, 4-(phenylmethylcarbonyl)aminobutyl, 4-(phenylethylcarbonyl)aminobutyl, 4-(phenylethenylcarbonyl)aminobutyl, 4-(4-phenylphenylcarbonyl)aminobutyl, 4-(4-phenyloxyphenylaminocarbonyl)aminobutyl, 4-(4-chlorophenylaminocarbonyl)aminobutyl, 4-(4-fluorophenylaminocarbonyl)aminobutyl, 4-(phenylmethylaminocarbonyl)aminobutyl or 4-(4-trifluoromethylsulfonyl) aminobutyl.

[0221] Preferred R5 is hydrogen or methyl.

[0222] In the compounds of the present invention of the formula (I), the compound of the formula (Ia)

[0223] (wherein R2 is C1-8 alkyl,

[0224] R3 is C1-8 alkyl or C3-7 cycloalkyl(C1-4)alkyl,

[0225] R5 is hydrogen or C1-8alkyl,

[0226] A is a bond or C1-10 alkylene,

[0227] D ring is C3-10 mono- or bi-(fused or spiro) carbocyclic ring or 3-10 membered mono- or bi-(fused or spiro)cyclic hetero ring,

[0228] m is 0 or an integer of 1-4,

[0229] R300 is C1-4 alkyl, C1-4 alkoxy, phenyl, phenoxy or benzyloxy.)

[0230] is preferable.

[0231] Preferred C3-10 carbocyclic ring represented by D ring is C3-10 mono- or bi-carbocyclic ring, and more preferred C3-10 carbocyclic ring is C3-7 mono-carbocyclic ring or C8-10 bi-carbocyclic ring.

[0232] Preferred 3-10 membered cyclic hetero ring represented by D ring is 3-10 membered mono- or bi-cyclic hetero aryl containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or 1 sulfur atom or partially or fully saturated one. More preferred 3-10 membered cyclic hetero ring is 5-7 membered mono- or 8-10 membered bi-cyclic hetero aryl containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or 1 sulfur atom or partially or fully saturated one.

[0233] Unless otherwise specified, all isomers are included in the present invention. For example, alkyl, alkoxy and alkylene groups include straight or branched ones. In addition, isomers on double bond, ring, fused ring (E-, Z-, cis-, trans-isomer), isomers generated from asymmetric carbon atom(s) (R-, S-, α-, β-isomer, enantiomer, diastereomer), optically active isomer (D-, L-, d-, l-isomer), polar compounds generated by chromatographic separation (more polar compound, less polar compound), equilibrium compounds, mixtures thereof at voluntary ratios and racemic mixtures are also included in the present invention.

[0234] [Salts]

[0235] Non-toxic salts of the present invention include all pharmaceutically acceptable salts, for example, general salts, acid addition salts, hydrate salts.

[0236] The compounds of the present invention represented by the formula (I) may be converted into the corresponding salts by conventional means. Water-soluble salts are preferred. Suitable salts, for example, include: salts of alkali metals (e.g. potassium, sodium), salts of alkaline earth metals (e.g. calcium, magnesium), ammonium salts, salts of pharmaceutically acceptable organic amines (e.g. tetramethylammonium, triethylamine, methylamine, dimethylamine, cyclopentylamine, benzylamine, phenethylamine, piperidine, monoethanolamine, diethanolamine, tris(hydroxymethyl)amine, lysine, arginine, N-methyl-D-glucamine).

[0237] The compounds of the present invention represented by the formula (I) may be converted into the corresponding acid addition salts by conventional means. Water-soluble salts are preferred. Suitable salts, for example, include: salts of inorganic acids e.g. hydrochloride, hydrobromide, sulfate, phosphate, nitrate; salts of organic acids e.g. acetate, trifluoroacetate, lactate, tartrate, oxalate, fumarate, maleate, citrate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, toluenesulfonate, isethionate, glucuronate, gluconate.

[0238] The compounds of the present invention of the formula (I) and salts thereof may be converted into the corresponding hydrates by conventional means.

[0239] All of the compounds of the formula (I) or non-toxic salts thereof are preferable, concretely, the compounds described in the example or non-toxic salts thereof.

[0240] Quaternary ammonium salts of the compounds of the formula (I) are the compounds where nitrogen of the compounds represented by the formula (I) is quaternalized by R0.

[0241] R0 is C1-8 alkyl or C1-8 alkyl substituted by phenyl.

[0242] N-oxides of the compounds represented by the formula (I) are the compounds where nitrogen of the compounds represented by the formula (I) is oxidized.

[0243] [Methods for Preparation of the Compounds of the Present Invention]

[0244] The compounds of the present invention of the formula (I) may be prepared by the following methods or the methods described in examples.

[0245] Among the compounds of the present invention of the formula (I), the compounds where nitrogens are not quaternary ammonium salts or N-oxides, i.e., the compounds of the formula (I-1)

[0246] (wherein R1-1, R2-1 R3-1, R4-1 and R5-1 have the same meaning as R1, R2, R3, R4 and R5 respectively, and N1 is nitrogen. With the proviso that, any nitrogen are not quaternary ammonium salts or N-oxides.)

[0247] may be prepared by the following methods.

[0248] Among the compounds of the present invention represented by the formula (I-1), the compounds in which any R1-1, R2-1, R3-1, R4-1 and R5-1 are not a group containing carboxyl, hydroxy, amino or thiol, i.e., the compounds of the formula (I-1A)

[0249] (wherein R1-1A, R2-1A, R3-1A, R4-1A and R5-1A have the same meaning as R1-1, R2-1, R3-1, R4-1 and R5-1 respectively. With the proviso that, all of them are not a group containing carboxyl, hydroxy, amino or thiol, and the other symbol have the same meanings as defined hereinbefore.)

[0250] may be prepared by the following methods.

[0251] Among the compounds of the formula (I-1 A), the compounds in which R1 does not represent hydrogen, i.e., the compounds of the formula (I-1A-1)

[0252] (wherein R1-1A-1 have the same meaning as R1-1A. With the proviso that, R1-1A-1 is not hydrogen and the other symbols have the same meanings as defined hereinbefore.)

[0253] may be prepared by cyclization of the compounds of the formula (II-1)

[0254] (wherein X-L-NH— is an amino terminus of aminated polystyrene resin, and the other symbols have the same meaning as defined hereinbefore.), or the compounds of the formula (II-2)

[0255] (wherein T is C1-8 alkyl, C3-8 mono-carbocyclic ring or C1-8 alkyl substituted by C3-8 mono-carbocyclic ring.).

[0256] The cyclization of compounds of the formula (II-1) is well known. For example, it may be carried out by heating in an organic solvent (toluene etc.) in the presence of acid (acetic acid, trifluoroacetic acid or hydrochloric acid etc.) at 60-120° C. This cyclization reaction is carried out with the cleavage from polystyrene resin.

[0257] If necessary, the conversion to desired non-toxic salts may be carried out by the conventional method in succession to this reaction.

[0258] The cyclization of compounds of the formula (II-2) is well known. For example, it may be carried out by heating in an organic solvent (dichloroethane or toluene etc.), with tertiary amine (triethylamine or diisopropylethylamine etc.) at 60-120° C. This cyclization reaction is carried out with the cleavage of T group.

[0259] Among the compounds of the formula (I-1 A), the compounds in which R1 is hydrogen, i.e., the compounds of the formula (I-1 A)

[0260] (wherein all of the symbols have the same meanings as defined hereinbefore.)

[0261] may be prepared by the removal of an amino-protecting group of the compounds in which R1A-1 is an amino-protecting group, i.e., the compounds of the formula (I-1A-1-1)

[0262] (wherein R1-1A-1-1 is an amino-protecting group, and the other symbols have the same meaning as defined hereinbefore.)

[0263] A protecting group of amino includes, for example, benzyl, benzyloxycarbonyl, allyloxycarbonyl, t-butoxycarbonyl or trifluoroacetyl etc.

[0264] The protecting group of amino includes the above one, in addition, the other protecting group which is removable selectively and easily, for example, one described in T. W. Greene et. al., Protective Groups in Organic Synthesis, Third Edition, Wiley-Interscience, New York, 1999.

[0265] The removal of a protecting group of amino is well known. For example, it is

[0266] (1) the alkaline hydrolysis,

[0267] (2) the removal of a protecting group in an acidic condition,

[0268] (3) the removal of a protecting group by hydrogenolysis, or

[0269] (4) the removal of a protecting group using metal complex etc.

[0270] Concrete descriptions of these methods are as follows:

[0271] (1) The removal of protecting group by alkaline hydrolysis condition (e.g. trifluoroacetyl group) may be carried out, for example, in an organic solvent (methanol, tetrahydrofuran or dioxane etc.) with hydroxide of alkaline metal (sodium hydroxide, potassium hydroxide or lithium hydroxide etc.), hydroxide of alkaline earth metal (barium hydroxide or calcium hydroxide etc.), carbonate (sodium carbonate or potassium carbonate etc.), or an aqueous solution thereof or a mixture thereof at 0-40° C.

[0272] (2) The removal of protecting group in an acidic condition (e.g. t-butoxycarbonyl group) may be carried out, for example, in an organic solvent (dichloromethane, chloroform, dioxane, ethyl acetate or anisole etc.), organic acid (acetic acid, trifluoroacetic acid or methanesulfonic acid etc.) or inorganic acid (hydrochloric acid or sulfuric acid etc.), or a mixture thereof (hydrogen bromide/acetic acid etc.) at 0-100° C.

[0273] (3) The removal of a protecting group by hydrogenolysis (e.g. benzyl, benzyloxycarbonyl or allyloxycarbonyl) may be carried out, for example, in a solvent (ether (tetrahydrofuran, dioxane, dimethoxyethane or diethylether etc.), alcohol(methanol or ethanol etc.), benzene(benzene or toluene etc.), ketone (acetone or methylethylketone etc.), nitrile (acetonitrile etc.), amide (dimethylformamide etc.), water, ethyl acetate, acetic acid or a mixture thereof etc.) in the presence of a catalyst (palladium on carbon, palladium black, palladium hydroxide, platinum oxide, Raney nickel etc.), at atmospheric or positive pressure under an atmosphere of hydrogen or in the presence of ammonium formate at 0-200° C.

[0274] (4) The removal of a protecting group using metal complex may be carried out, for example, in an organic solvent (dichloromethane, dimethylformamide or tetrahydrofuran etc.) in the presence of a trap reagent (tributyltin hydride or dimedone etc.) and/or an organic acid (acetic acid etc.) with metal complex (tetrakis(triphenylphosphine)palladium(0) complex etc.) at 0-40° C.

[0275] Moreover, the compounds of the formula (I-1A-1) may be prepared with the compounds of the formula (I-1A-2) by the following methods of (a)-(g).

[0276] (a) Among the compounds of the formula (I-1A-1), the compounds, in which R1A-1 is C1-18 alkyl, C2-18 alkenyl, C2-18 alkynyl, or C1-18 alkyl, C2-18 alkenyl or C2-18 alkynyl substituted by various substituents, and in which R1A-1 bonds with N1 through —CH2—, i.e., the compounds of the formula (I-1A-1a)

[0277] (wherein R1-1A-1a is C1-17 alkyl, C2-17 alkenyl, C2-17 alkynyl, or C1-17 alkyl, C2-17 alkenyl or C2-17 alkynyl substituted by 1-5 of optionally selected from (a) halogen, (b) —CONR7R8, (c) —COOR9, (d) —OR14, (e) —SR15, (f) —NR16R17, (g) —NR18COR19, (h) —SO2NR20R21, (i) —OCOR22, (j) —NR23SO2R24, (k) —NR25COOR26, (l) —NR27CONR28R29, (m) Cyc 1, (n) keto, (o) —N(SO2R24)2. With the proviso that, R1-1A-1a is not a group containing carboxyl, hydroxy, amino or thiol, and the other symbols have the same meaning as defined hereinbefore.)

[0278] may be prepared by the reductive amination of the compounds of the formula (I-1A-2) with the compounds the formula (III)

R1-1A-1a—CHO (III)

[0279] (wherein all of the symbols have the same meanings as defined hereinbefore.)

[0280] The reductive amination is well known. For example, it may be carried out in an organic solvent (dichloroethane, dichloromethane, dimethylformamide, acetic acid or a mixture thereof etc.) in the presence of a reducing agent (sodium triacetoxyborohydride or sodium cyanoborohydride etc.) at 0-40° C.

[0281] Moreover, the reductive amination may be carried out with the compounds in which nitrogen of R1 is oxidized to N-oxide.

[0282] (b) Among the compounds of the formula (I-1A-1), the compounds, in which R1A-1 is C1-18 alkyl, C2-18 alkenyl, C2-18 alkynyl, or C1-18 alkyl, C2-18 alkenyl or C2-18 alkynyl substituted by various substituents, and in which R1A-1 bonds with N1 through —CHRA-1b— (wherein RA-1b is C1-17 alkyl, C2-17 alkenyl or C2-17 alkynyl.), i.e., the compounds of the formula (I-1A-1b)

[0283] (wherein RA-1b is C1-17 alkyl, C2-17 alkenyl or C2-17 alkynyl, and the other symbols have the same meanings as defined hereinbefore.)

[0284] may be prepared by reductive amination of the compounds of the formula (1-1A-2) with the compounds the formula (IV)

[0285] (wherein all of the symbols have the same meanings as defined hereinbefore.)

[0286] The reductive amination is well known. For example, it may be carried out in an organic solvent (dichloroethane or dichloromethane etc.) in the presence of tertiary amine (triethylamine or diisopropylethylamine etc.) with Lewis acid (titanium tetrachloride etc.), at 0-40° C., and subsequently by the addition of a reducing agent (sodium triacetoxyborohydride or sodium cyanoborohydride etc.) at 0-40° C.

[0287] (c) Among the compounds of the formula (I-1A-1), the compounds in which R1A-1 is COR6, i.e., the compounds of the formula (I-1A-1c)

[0288] (wherein R6-1A-1c has the same meaning as R6. With the proviso that, R6A-1A-1c is not a group containing carboxyl, hydroxy, amino or thiol, and any nitrogen atoms are not quaternary ammonium salt nor N-oxide, and the other symbols have the same meaning as defined hereinbefore.)

[0289] may be prepared by the amidation of the compounds of the formula (I-1A-2) with the compounds of the formula (V)

[0290] (wherein all of the symbols have the same meanings as defined hereinbefore.).

[0291] The amidation is well known. For example, it may be carried out in an organic solvent (chloroform, dichloromethane, diethylether, tetrahydrofuran, dioxane or dimethylformamide etc.) in the presence of tertiary amine (isopropylethylamine, pyridine, triethylamine, dimethylaniline or dimethylaminopyridine etc.) or an aqueous alkali solution (solution of bicarbonate or solution of sodium hydroxide etc.) at 0-40° C.

[0292] (d) Among the compounds of the formula (I-1A-1), the compounds in which R1-1A-1 is SO2R10, i.e., the compounds of the formula (I-1A-1d)

[0293] (wherein R10-1A-1d has the same meaning as R10, With the proviso that, R10-1A-1d is not a group containing carboxyl, hydroxy, amino or thiol, and any nitrogen atoms are not quaternary ammonium salt nor N-oxide, and the other symbols have the same meaning as defined hereinbefore.)

[0294] may be prepared by the sulfonamidation of the compounds of the formula (I-1A-2) with the compounds of the formula (VI)

[0295] (wherein all of the symbols have the same meanings as defined hereinbefore.).

[0296] The sulfonamidation is well known. For example, it may be carried out in an inert organic solvent (chloroform, dichloromethane, dichloroethane, diethylether or tetrahydrofuran etc.) in the presence of tertiary amine (diisopropylethylamine, pyridine, triethylamine, dimethylaniline or dimethylaminopyridine etc.) at 0-40° C.

[0297] (e) Among the compounds of the formula (I-1A-1), the compounds in which RI-1A-1 is CONR7R8, i.e., the compounds of the formula (I-1A-1e)

[0298] (wherein R7-1A-1e and R8-1A-1e have the same meaning as R7 and R8, With the proviso that, R10-1A-1d is not a group containing carboxyl, hydroxy, amino or thiol, and any nitrogen atoms are not quaternary ammonium salt nor N-oxide, and the other symbols have the same meaning as defined hereinbefore.)

[0299] may be prepared by the reaction of the compounds of the formula (I-1A-2) with the compounds of the formula (VII-1)

[0300] (wherein all of the symbols have the same meanings as defined hereinbefore.)

[0301] or with the compounds of the formula (VII-2)

[0302] (wherein all of the symbols have the same meanings as defined hereinbefore.)

[0303] The reaction with the compounds of the formula (VII-1) is well known. For example, it may be carried out in an organic solvent (chloroform, dichloromethane, diethylether or tetrahydrofuran etc.), in the presence of a tertiary amine (isopropylethylamine, pyridine, triethylamine, dimethylaniline or dimethylaminopyridine etc.) at 0-40° C.

[0304] The reaction with the compounds of the formula (VII-2) is well known. For example, it may be carried out in an inert organic solvent (chloroform, dichloromethane, dichloroethane, dimethylformamide, diethylether or tetrahydrofuran etc.) at 0-40° C.

[0305] (f) Among the compounds of the formula (I-1A-1), the compounds in which R1-1A-1 is —CH2—CH(OH)-RA-1f(RA-1f is C1-16 alkyl, C2-16 alkenyl, C2-16 alkynyl, or C1-16 alkyl, C2-16 alkenyl or C2-16 alkynyl substituted by various substituents.), i.e., the compounds of the formula (I-1A-1f)

[0306] (wherein RA-1f is C1-16alkyl, C2-16 alkenyl, C2-16 alkynyl, or C1-16 alkyl, C2-16 alkenyl or C2-16 alkynyl substituted by 1-4 of optionally selected from (a) halogen, (b) —CONR7R8, (c) —COOR9, (d) —OR14, (e) —SR15, (f) —NR16R17, (g) —NR18COR19, (h) —SO2NR20R21, (i) —OCOR22, (j) —NR23SO2R24, (k) —NR25COOR26, (l) —NR27CONR28R29, (m) Cyc 1, (n) keto, (o) —(SO2R24)2, and any nitrogen atoms are not quaternary ammonium salt nor N-oxide and the other symbols have the same meaning as defined hereinbefore.)

[0307] may be prepared by the reaction of the compounds of the formula (1-1A-2) with the compounds the formula (VIII)

[0308] (wherein all of the symbols have the same meanings as defined hereinbefore.).

[0309] The reaction is well known, and it may be carried out in an organic solvent (methanol, ethanol, 2-propanol, tetrahydrofuran or acetonitrile etc.), in the presence or absence of a tertiary amine (triethylamine or N-methylmorpholine etc.) at 40-100° C.

[0310] (g) Among the compounds of the formula (I-1A-1), the compounds in which R1-1A-1 is —CH2—C(═O)-RA-1g (RA-1g has the same meaning as RA-1f), i.e., the compounds of the formula (I-1A-1g)

[0311] (wherein RA-1g has the same meaning as RA-1f, and the other symbols have the same meanings as defined hereinbefore.)

[0312] may be prepared by the reaction of the compounds of the formula (I-1A-2) with the compounds of the formula (IX-1)

[0313] (wherein all of the symbols have the same meanings as defined hereinbefore.)

[0314] or with the compounds of the formula (IX-2)

[0315] (wherein all of the symbols have the same meanings as defined hereinbefore.).

[0316] The reaction is well known, and it may be carried out in an organic solvent (chloroform, dichloromethane, diethylether, tetrahydrofuran, dioxane or dimethylformamide etc.) in the presence of a tertiary amine (isopropylethylamine, pyridine, triethylamine, dimethylaniline or dimethylaminopyridine etc.) at 0-40° C.

[0317] Moreover, the compounds of the formula (I-1A-1) may be prepared by the methods described in (h).

[0318] (h) Among the compounds of the formula (I-1A-1), the compounds in which R1-1A-1 is 2-propenyl (—CH2CH═CH2), i.e., the compounds of the formula (I-1A-1h)

[0319] (wherein all of the symbols have the same meanings as defined hereinbefore.)

[0320] may be prepared by the reaction of the compounds in which R1-1A-1 is 2-propenyloxycarbonyl (—COO—CH2CH═CH2) among the compounds of the formula (I-1A-1) prepared by the above method, i.e., the compounds of the formula (I-1A-1-2)

[0321] (wherein all of the symbols have the same meanings as defined hereinbefore.) with a metal complex.

[0322] The reaction with a metal complex is well known, and it may be carried out, for example, in an organic solvent (tetrahydrofuran or acetic acid etc.), with a metal complex (tetrakis(triphenylphosphine)palladium(0) complex etc.), at 0-40° C.

[0323] Among the compounds of the (I-1), the compounds in which at least one group of R1, R2, R3, R4 and R5 represents a group containing carboxyl, hydroxy, amino or thiol, i.e., the compounds of the formula (I-1B)

[0324] (wherein R1-1B, R2-1B, R3-1B, R4-1B and R5-1B have the same meanings as R1-1, R2-1, R3-1, R4-1 and R5-1, respectively. With the proviso that, at least one group represents a group containing carboxyl, hydroxy, amino or thiol, and the other symbols have the same meanings as defined hereinbefore.)

[0325] may be prepared by the removal of a protecting group of the compounds in which at least one group of R1-1, R2-1, R3-1, R4-1 or R5-1 represents a group containing carboxyl, hydroxy, amino and thiol protected by a protecting group, i.e., the compounds of the formula (I-1A-3)

[0326] (wherein R1-1A-3 R2-1A-3, R3-1A-3, R4-1A-3 and R5-1A-3 have the same meanings of R1-1, R2-1, R3-1, R4-1 and R5-1, respectively. With the proviso that, at least one group represents a group containing carboxyl, hydroxy, amino or thiol protected by a protecting group and the other symbols have the same meanings as defined hereinbefore.)

[0327] A protecting group of carboxyl includes, for example, methyl, ethyl, t-butyl, benzyl or allyl.

[0328] A protecting group of hydroxy includes, for example, methoxymethyl, 2-tetrahydropyranyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, acetyl or benzyl.

[0329] A protecting group of amino includes, for example, benzyloxycarbonyl, allyloxycarbonyl, t-butoxycarbonyl, trifluoroacetyl or 9-fluorenylmethoxycarbonyl.

[0330] A protecting group of thiol includes, for example, benzyl, methoxybenzyl, acetoamidomethyl, triphenylmethyl or acetyl.

[0331] The protecting group of carboxyl, hydroxy, amino or thiol includes the above one, and in addition the other protecting group which is removable selectively and easily, for example, one described in T. W. Greene et. al., Protective Groups in Organic Synthesis, Third Edition, Wiley-Interscience, New York, 1999.

[0332] The removal of a protecting group of amino may be carried out by the method described hereinbefore.

[0333] The removal of a protecting group of carboxyl, hydroxy or thiol is well known. For example, it is

[0334] (1) the alkaline hydrolysis,

[0335] (2) the removal of a protecting group in an acidic condition,

[0336] (3) the removal of a protecting group by hydrogenolysis, or

[0337] (4) the removal of a protecting group containing silyl or

[0338] (5) the removal of a protecting group using metal complex etc.

[0339] Among these methods, (1), (2), (3) and (5) may be carried out by the same methods of the removal of a protecting group of amino.

[0340] Concretely describing (4), the removal of a protecting group containing silyl may be carried out, for example, in an organic solvent (tetrahydrofuran or acetonitrile etc.), with tetrabutylammoniumfluoride at 0-40° C.

[0341] As well known to the person in the art, the aimed compounds of the present invention may be prepared easily by choice of these removal of a protecting group.

[0342] Moreover, the compounds of the formula (I-1A-1) may be prepared by the methods described in (j)-(m) with the compounds of the formula (I-1B-1)

[0343] (wherein R1-1B-1, R2-1B-1, R3-1B-1, R4-1B-1 and R5-1B-1 have the same meanings of R1-1, R2-1, R3-1, R4-1 and R5-1, respectively. With the proviso that, at least one group represents a group containing amino, and the other symbols have the same meanings as defined hereinbefore.)

[0344] (j) Among the compounds of the formula (I-1A-1), the compounds in which at least one group of R1-1A-1, R2-1A, R3-1A, R4-1A and R5-1A represent a group containing amide, i.e., the compounds of the formula (I-1A-1j)

[0345] (wherein R1-1A-1j, R2-1A-1j, R3-1A-1; R4-1A-1j and R5-1A-1j have the same meanings as R1-1, R2-1, R3-1, R4-1 and R5-1, respectively. With the proviso that, at least one group represents a group containing amide and the other symbols have the same meanings as defined hereinbefore.)

[0346] may be prepared by the amidation of the compounds of the formula (I-1B-1).

[0347] The amidation may be carried out by the method described herein before.

[0348] (k) Among the compounds of the formula (I-1A-1), the compounds in which at least one group of R1-1A-1, R2-1A, R3-1A, R4-1A and R5-1A represents a group containing sulfonamide, i.e., the compounds of the formula (I-1A-1k)

[0349] (wherein R1-1A-1k, R2-1A-1k, R3-1A-1k, R4-1A-1k and R5-1A-1k have the same meanings as R1-1, R2-1, R3-1, R4-1 and R5-1, respectively. With the proviso that, at least one group represents a group containing sulfon amide and the other symbols have the same meanings as defined hereinbefore.)

[0350] may be prepared by the sulfonamidation of the compounds of the formula (I-1B-1).

[0351] The sulfonamidation may be carried out the method described hereinbefore.

[0352] (m) Among the compounds of the formula (I-1A-1), the compounds in which at least one group of R1-1A-1, R2-1A, R3-1A, R4-1A and R5-1A represents a group containing urea, i.e., the compounds of the formula (I-1A-1m)

[0353] (wherein R1-1A-1m, R2-1A-1m, R3-1A-1m, R4-1A-1m and R5-1A-1m have the same meanings as R1-1, R2-1, R3-1 R4-1 and R5-1, respectively. With the proviso that, at least one group represents a group containing urea and the other symbols have the same meanings as defined hereinbefore.)

[0354] may be prepared by the urea formation of the compounds of the formula (I-1B-1).

[0355] The urea formation may be carried out the method described hereinbefore.

[0356] Among the compounds of the formula (I-1), the compounds in which at least one group of R1-1, R2-1, R3-1, R4-1 and R5-1 represents a group containing hydroxy, and/or R1 represents a group containing carboxyl, i.e., the compounds of the formula (I-1B-2)

[0357] (wherein R1-1B-2, R2-1B-2, R3-1B-2, R4-1B-2 and R5-1B-2 have the same meanings as R1-1, R2-1, R3-1, R4-1 and R5-1, respectively. With the proviso that, at least one group of R1-B-2, R2-1B-2, R3-1B-2, R4-1B-2 and R5-1B-2 represents a group containing hydroxy and/or R1B-2 includes carboxyl and the other symbols have the same meanings as defined hereinbefore.) may be prepared by the method described in (n).

[0358] (n) Among the compounds of the formula (I-1B-2), the compounds in which R1-1B-2 is C1-18 alkyl, C2-18 alkenyl, C2-18 alkynyl or C1-18 alkyl, C2-18 alkenyl or C2-18 alkynyl substituted by various substituent, and in which that R1-1B-2 bonds to N1 atom through —CH2—, i.e., the compounds of the formula (I-1B-1n)

[0359] (wherein R1-1B-2n is C1-17alkyl, C2-17 alkenyl, C2-17 alkynyl, or C1-17 alkyl, C2-17 alkenyl or C2-17 alkynyl substituted by 1-5 of optionally selected from (a) halogen, (b) —CONR7R8, (c) —COOR9, (d) —OR14, (e) —SR15, (f) —NR16R17, (g) —NR18COR19, (h) —SO2NR20R21, (i) —OCOR22, (j) —NR23SO2R24, (k) —NR25COOR26, (l) —NR27CONR28R29, (m) Cyc 1, (n) keto, (o) —N(SO2R24)2. With the proviso that, at least one group of R1-1B-2n, R2-1B-2, R3-1B-2, R4-1B-2 and R5-1B-2 represents a group containing hydroxy, and/or R1B-2n represents a group containing carboxyl, and any nitrogen atoms are not quaternary ammonium salt nor N-oxide and the other symbols have the same meaning as defined hereinbefore.)

[0360] may be prepared by the reductive amination of the compounds in which R1 is hydrogen, and at least one group of R2-1, R3-1, R4-1 and R5-1 represents a group containing hydroxy among the compounds of the formula (I-1B) prepared by the above method, i.e., the compounds of the formula (I-1B-3)

[0361] (wherein all of the symbols have the same meanings as defined hereinbefore.)

[0362] with the compounds of the formula (X)

R1-1B-2n—CHO (X)

[0363] (wherein all of the symbols have the same meanings as defined hereinbefore.)

[0364] The reductive amination may be carried out by the method described hereinbefore.

[0365] Moreover, the reductive amination may be carried out in the compounds in which nitrogen in R1 represents N-oxide.

[0366] Among the compounds of the present invention of the formula (I), the compounds in which at least one nitrogen is quaternary ammonium salt, i.e., the compounds of the formula (I-2)

[0367] (wherein R1-2, R2-2, R3-2, R4-2 and R5-2 have the same meanings as R1, R2, R3, R4 and R5, respectively, and N2 is nitrogen. With the proviso that, at least one nitrogen is quaternary ammonium salt and Q is halogen.)

[0368] may be prepared by the reaction of the compounds of the formula (I-1) with the compounds of the formula (XI)

R0-Q (XI)

[0369] (wherein R0 is C1-8 alkyl or C1-8 alkyl substituted by phenyl and Q is halogen.)

[0370] The reaction is well known and it may be carried out, for example, in an organic solvent (acetone, dimethylformamide or methyl ethyl ketone etc.) at 0-40° C.

[0371] Among the compounds of the formula (I), the compounds in which at least one nitrogen represents N-oxide, i.e. the compounds of the formula (I-3)

[0372] (wherein R1-3, R2-3, R3-3, R4-3 and R5-3 have the same meanings of R1, R2, R3, R4 and R5, respectively, and N3 is nitrogen. With the proviso that, at least one nitrogen represents N-oxide.)

[0373] may be prepared by the oxidation of the compounds of the formula (I-1).

[0374] The oxidation is well known and it may be carried out, for example, in a suitable organic solvent (dichloromethane, chloroform, benzene, hexane or t-butyl alcohol etc.) in the presence of a excessive oxidizing reagent (hydrogen peroxide, sodium periodate, acyl nitrite, sodium perborate, peroxidized acid (for example, 3-chloroperbenzoic acid, peracetic acid etc.), OXONE (brand name, Potassium peroxymonosulfate is abbreviated as. OXONE.), potassium permanganate or chromic acid etc.) at 20-60° C.

[0375] The compounds of the (II-1) may be prepared according to the following Schemes 1-3.

[0376] In Schemes, X is polystyrene resin, L is bivalent group, and the other symbols have the same meanings as defined hereinbefore.

[0377] Bivalent group represented by L is, though it depends on the type of the used resin, e.g. methylene or Rink. Rink is 4-(2,4-dimethoxybenzyl) phenoxymethyl.

[0378] In the present invention, e.g. aminomethylated polystyrene resin or 9-fluorenylmethyloxycarbonylamino-Rink resin etc. can be used as terminal amino polystyrene resin.

[0379] As shown the following reaction scheme, the resin of the formula (XVI) may be prepared from aminomethylated polystyrene resin or 9-fluorenylmethyloxycarbonylamino-Rink resin.

[0380] In the reaction using polystyrene resin in the present invention, the reaction products may be purified by the conventional methods, for example, washing with a solvent (dimethylformamide, dichloromethane, methanol, tetrahydrofuran, toluene or acetic acid/toluene etc.) at several times. Moreover the obtained products may be purified by conventional techniques. For example, purification may be carried out by distillation at atmospheric or reduced pressure, by high performance liquid chromatography, by thin layer chromatography or by column chromatography using silica gel or magnesium silicate, by washing or by recrystallization.

[0381] The compounds of the formula (II-2) may be prepared according to the following Scheme 5.

[0382] The other starting materials and each test compounds in t he present invention have been known per se or may be prepared by known methods.

[0383] [Pharmacological Activities]

[0384] Efficacy of the compounds of the invention represented by general formula (I) was confirmed, e.g., by the following tests.

[0385] As described in the foregoing, in order to carry out screening of a compound capable of inhibiting binding of HIV to CXCR4 or CCR5 which is a receptor on the CD4-postive cell, it is a more directive method to carry out it in an assay system that uses HIV virus. However, the use of a large amount of HIV virus in the screening is not practical due to a difficulty in handling it. On the other hand, since both the macrophage tropic (R5) HIV-1 and the ligands, that is, RANTES, MIP-1α and MIP-1β, bind to CCR5, it can be presumed that certain common characteristics are present in the CCR5 binding sites of the HIV side and the RANTES, MIP-1α and MIP-1β sides, and in the binding sides of CCR5 to the ligands, that is, RANTES, MIP-1α and MIP-1β, and HIV. Accordingly, in order to find a compound capable of inhibiting adsorption of HIV virus to cells, which has an inhibitory mechanism different from the current anti-AIDS drugs (reverse transcription inhibitors and protease inhibitors), it is possible to use an assay system that uses an endogeneous CCR5 ligand, RANTES, MIP-1α or MIP-1β instead of HIV.

[0386] Specifically, e.g., since CCR5 is a G protein-coupled seven transmembrane type receptor, an assay system in which the effect of RANTES on the transient increase of Ca ion induced via CCR5 is measured can be carried out as an assay system for screening a compound capable of inhibiting binding of RANTES to CCR5. Since both of the T cell tropic (X4) HIV and SDF-1 bind to CXCR4, similar idea can be considered.

[0387] [Test Methods]

[0388] (1) Isolation of Human CCR5 Gene

[0389] Human placental cDNA was prepared using Marathon cDNA amplification kit (Clontech). PCR primers hCCR5XbaI-F1: 5′-AGCTAGTCTAGATCCGTTCCCCTACMGAAACTCTCC-3′ (SEQ ID NO:1) and hCCR5XbaI-R1: 5′-AGCTAGTCTAGAGTGCACAACTCTGACTGGGTCACCA-3′ (SEQ ID NO:2) were designed based on the sequence of GenBank U54994.

[0390] Using the human placental cDNA as the template and using Ex Taq (Takara), PCR reaction (2 minutes at 95° C.→(30 seconds at 95° C., 45 seconds at 60° C., 1 minute at 72° C.)×35 times) was carried out. The thus amplified PCR product was subjected to a 1% agarose gel electrophoresis, purified using QIAquick Gel Extraction Kit (QUIAGEN) and then digested with a restriction enzyme XbaI. The digested fragments were ligated to an expression vector pEF-BOS-bsr using DNA Ligation Kit Ver. 2 (Takara) and transformed into Escherichia coli DH5a. By preparing the resulting plasmid pEF-BOS-bsr/hCCR5, its DNA sequence was verified.

[0391] (2) Culturing of CHO Cell

[0392] CHO-dhfr(−) was cultured using Ham's F-12 (containing fetal bovine serum (10%), penicillin (50 U/ml) and streptomycin (50 mg/ml)). Also, the transduced cell was cultured by adding blasticidin (5 mg/ml) to the above medium.

[0393] (3) Transduction into CHO Cell

[0394] The plasmid pEF-BOS-bsr/hCCR5 was transduced into the CHO-dhfr(−) cell using DMRIE-C reagent (Gibco BRL). After 48 hours, the medium was replaced with a medium containing 5 mg/ml of blasticidin to carry out the selection, thereby establishing a stably over-expressing cell.

[0395] (4) Inhibition Test on the Binding of RANTES to CCR5 (Activity of RANTES to Induce Transient Increase of Ca Ion)

[0396] The thus established human CCR5 stably over-expressing CHO cell (CCR5/CHO cell) was suspended in Ham's F-12 medium containing FBS (10%) and dispensed in 3.0×106 cells/well portions into a 96 well plate. One day after culturing at 37° C., the culture supernatant was discarded, and Ham's F-12 medium (containing Fura-2AM (5 μM), Probenecid (2.5 mM) and HEPES (20 mM; pH 7.4)) was dispensed in 80 μl/well portions to carry out 1 hour of incubation at 37° C. under shaded condition. After washing twice with 1×Hanks/HEPES (20 mM; pH 7.4) solution, the same solution was dispensed in 100 μl/well portions. Each of the test compounds was added to the thus Fura-2AM-incorporated CCR5/CHO cell, and 3 minutes thereafter, a recombinant human RANTES (PeproTach) diluted with 1×Hanks/HEPES (20 mM; pH 7.4) solution was added thereto to a final concentration of 10 nM. Transient increase in the intracellular Ca2+ concentration induced by the human RANTES was measured using a Ca2+ detector for 96 well use (Hamamatsu Photonics), and inhibition ratio (%) of the test compound was calculated by the following calculation formula.

Inhibition ratio=(Ec−Ea)/Ec×100

[0397] Ec: measured value of Ca2+ transient increase by RANTES

[0398] Ea: measured value of Ca2+ transient increase by RANTES when a test compound was added

[0399] As a result, the compounds of the invention showed an inhibition ratio of 50% or more at 10 μM. For example, the compound of Example 2(1) showed an IC50 value of 0.05 μM, and the compound of Example 2(2) an IC50 value of 0.05 μM.

[0400] An assay system for finding a compound having adsorption inhibition effect on CCR5 directional HIV strain was described in the foregoing, and it is possible as a matter of course to find a compound capable of inhibiting the activity of CCR5 or a ligand thereof using this system. In the same manner, it is possible to find a compound capable of inhibiting the activity of other chemokine receptor or a ligand thereof. For example, a system for finding a compound capable of inhibiting the activity of CCR2 or a ligand thereof can be constructed. Since CCR2 is a G protein-coupled seven transmembrane type receptor similar to the case of CCR5, it can be carried out by measuring the effect of a ligand of CCR2, e.g., MCP-1 on the transient increase of Ca ion induced via CCR2.

[0401] (5) Inhibition Test on the Binding of MCP-1 to CCR2 (Activity of MCP-1 to Induce Transient Increase of Ca Ion)

[0402] A human CCR2-expressing cell, e.g., a human monocyte cell strain THP-1 (ATCC No. TIB-202), was suspended in RPMI 1640 medium containing FBS (10%), Fura-2AM (5 μM), Probenecid (2.5 mM) and HEPES (20 mM, pH 7.4) to a density of 5.0×106 cells/ml and incubated at 37° C. for 30 minutes under shaded condition. This was mixed with 4 to 8 volumes of 1×Hanks/HEPES (20 mM, pH 7.4)/Probenecid (2.5 mM) and further incubated at 37° C. for 30 minutes under shaded condition. After washing with 1×Hanks/HEPES (20 mM, pH 7.4)/Probenecid (2.5 mM) solution, the thus washed cells were re-suspended in the same solution to a density of 2.0×106 cells/ml and dispensed in 100 μl/well portions into a 96 well plate. Each of the test compound solutions was added thereto, and 3 minutes thereafter, a recombinant human MCP-1 (PeproTach) diluted with 1×Hanks/HEPES (20 mM, pH 7.4)/Probenecid (2.5 mM)was added thereto to a final concentration of 30 nM. Transient increase in the intracellular Ca 2+concentration induced by the human MCP-1 was measured using a Ca2+ detector for 96 well use (Hamamatsu Photonics), and inhibition ratio (%) of the test compound was calculated by the following calculation formula.

Inhibition ratio=(Ec−Ea)/Ec×100

[0403] Ec: measured value of Ca2+ transient increase by MCP-1

[0404] Ea: measured value of Ca2+ transient increase by MCP-1 when a test compound was added

[0405] As a result, the compounds of the invention showed an inhibition ratio of 50% or more at 10 μM. For example, the compound of Example 5(2) showed an IC50 value of 3 μM.

[0406] [Toxicity]

[0407] The toxicity of the compounds of the present invention is very low and therefore the compounds may be considered safe for pharmaceutical use.

INDUSTRIAL APPLICABILITY

[0408] [Application for Pharmaceuticals]

[0409] The compounds of the present invention of the formula (I) regulate the effect of chemokine/chemokine receptor in animal included human, especially human, so they are used for prevention and/or treatment of various inflammatory diseases, asthma, atopic dermatitis, urticaria, allergic diseases (allergic bronchopulmonary aspergillosis, allergic eosinophilic gastroenteritis est.), nephritis, nephropathy, hepatitis, arthritis, rheumatoid arthritis, psoriasis, rhinitis, conjunctivitis, ischemic reperfusion disorder, multiple sclerosis, ulcerative colitis, adult respiratory distress syndrome, cytotoxic shock, diabetes, autoimmune disease, multiple organ failure, immunosuppression, cancer metastasis and acquired immune deficiency syndrome.

[0410] For the purpose above described, the compounds of formula (I), non-toxic salts thereof, acid addition salts or hydrates thereof may be normally administered systemically or locally, usually by oral or parenteral administration.

[0411] The doses to be administered are determined depending upon, for example, age, body weight, symptom, the desired therapeutic effect, the route of administration, and the duration of the treatment. In the human adult, the doses per person are generally from 1 mg to 1000 mg, by oral administration, up to several times per day, and from 1 mg to 100 mg, by parenteral administration (preferably intravenous administration), up to several times per day, or continuous administration from 1 to 24 hours per day from vein.

[0412] As mentioned above, the doses to be used depend upon various conditions. Therefore, there are cases in which doses lower than or greater than the ranges specified above may be used.

[0413] The compounds of the present invention may be administered in the form of, for example, solid forms for oral administration, liquid forms for oral administration, injections, liniments or suppositories for parenteral administration.

[0414] Solid forms for oral administration include compressed tablets, pills, capsules, dispersible powders, and granules. Capsules include hard capsules and soft capsules.

[0415] In such solid forms, one or more of the active compound(s) may be admixed with vehicles (such as lactose, mannitol, glucose, microcrystalline cellulose, starch), binders (such as hydroxypropyl cellulose, polyvinylpyrrolidone or magnesium metasilicate aluminate), disintegrants (such as cellulose calcium glycolate), lubricants (such as magnesium stearate), stabilizing agents, and solution adjuvants (such as glutamic acid or aspartic acid) and prepared according to methods well known in normal pharmaceutical practice. The solid forms may, if desired, be coated with coating agents (such as sugar, gelatin, hydroxypropyl cellulose or hydroxypropylmethyl cellulose phthalate), or be coated with two or more films. And further, coating may include containment within capsules of absorbable materials such as gelatin.

[0416] Liquid forms for oral administration include pharmaceutically acceptable solutions, suspensions and emulsions, syrups and elixirs. In such forms, one or more of the active compound(s) may be dissolved, suspended or emulized into diluent(s) commonly used in the art (such as purified water, ethanol or a mixture thereof). Besides such liquid forms may also comprise some additives, such as wetting agents, suspending agents, emulsifying agents, sweetening agents, flavoring agents, aroma, preservative or buffering agent.

[0417] Injections for parenteral administration include sterile aqueous, suspensions, emulsions and solid forms which are dissolved or suspended into solvent(s) for injection immediately before use. In injections, one or more of the active compound(s) may be dissolved, suspended or emulized into solvent(s). The solvents may include distilled water for injection, physiological salt solution, vegetable oil, propylene glycol, polyethylene glycol, alcohol, e.g. ethanol, or a mixture thereof. Injections may comprise some additives, such as stabilizing agents, solution adjuvants (such as glutamic acid, aspartic acid or POLYSORBATE80 (registered trade mark)), suspending agents, emulsifying agents, soothing agent, buffering agents, preservative. They may be sterilized at a final step, or may be prepared and compensated according to sterile methods. They may also be manufactured in the form of sterile solid forms such as freeze-dried products, which may be dissolved in sterile water or some other sterile diluent(s) for injection immediately before use.

[0418] Other forms for parenteral administration include liquids for external use, ointments and endermic liniments, inhalations, sprays, suppositories and pessaries for vaginal administration which comprise one or more of the active compound(s) and may be prepared by methods known per se.

[0419] Sprays may comprise additional substances other than diluents, such as stabilizing agents (such as sodium sulfate), isotonic buffers (such as sodium chloride, sodium citrate or citric acid). For preparation of such sprays, for example, the method described in the U.S. Pat. Nos. 2,868,691 or 3,095,355 may be used.

BEST MODE FOR CARRYING OUT THE INVENTION

[0420] The following Reference Examples and Examples are intended to illustrate the present invention, but do not limit them.

[0421] In chromatographic separations and TLC, the solvents in parenthesis show the eluting and developing solvents and the ratios of the solvents used are by volume.

[0422] The solvents in parenthesis in NMR show the solvents used for measurement.

[0423] R* and S* do not represent the absolute position but the relative position.

REFERENCE EXAMPLE 1

Preparation of Resin (2)

[0424]

[0425] Aminomethylpolystyrene resin hydrochloride (Resin (1); X is polystyrene resin.) (30.0 g) (1% divinylbenzene copolymer, Watanabe Kagaku, Catalog No A00062) was washed with dimethylformamide (300 ml), 10% diisopropylethylamine-dimethylformamide solution (300 ml) and dimethylformamide (300 ml) successively, and was suspended in dimethylformamide (200 ml). To the suspension were added formic acid (10.2 ml) and diisopropylcarbodiimide (42.3 ml) under cooling with ice, and it was stirred for 1 hour at room temperature. The resin was collected by filtration from the reaction solution, and was washed with dimethylformamide (250 ml×3), dichloromethane (250 ml×4), methanol (250 ml×2) and dichloromethane (250 ml×4) to give Resin (2).

[0426] IR (KBr): ν 1682 cm−1.

REFERENCE EXAMPLE 2

Preparation of Resin (3)

[0427]

[0428] To a suspension of Resin (2) prepared in Reference Example 1 in dichloromethane (300 ml) were added triethylamine (18.8 ml), carbon tetrachloride (13.0 ml) and triphenylphosphine (35.4 g), and it was refluxed for 1 hour. The reaction solution was cooled to room temperature, and the resin was collected by filtration. The resin was washed with dichloromethane (250 ml×3), methanol (250 ml×1) and dichloromethane (250 ml×2) and dried under reduced pressure to give Resin (3) 28.2 g).

[0429] IR (KBr): ν 2147 cm−1.

REFERENCE EXAMPLE 3

Preparation of Compound (1)

[0430]

[0431] To a suspension of Resin (3) prepared in Reference Example 2 (2.5 g) in tetrahydrofuran/methanol (1:1; 25 ml) were added N-allyloxycarbonyl-4-piperidone (2.15 g), n-propylamine (0.97 ml) and N-(t-butyloxycarbonyl) leucine (2.93 g), and it was stirred for 16 hours at 65° C. The reaction solution was cooled to room temperature, and the resin was collected by filtration. The obtained resin was washed with tetrahydrofuran (25 ml×2), methanol (25 ml×2) and dichloromethane (25 ml×2) to give compound (1).

REFERENCE EXAMPLE 4

Preparation of Compound (2)

[0432]

[0433] To a suspension of the compound (1) prepared in Reference Example 3 in dichloromethane (25 ml) were added acetic acid (0.81 ml), tributyltin hydride (1.90 ml) and tetrakis(triphenylphosphine)palladium (0) complex (270 mg), and it was stirred for 6 hours at room temperature. The resin was collected by filtration from the reaction solution, and was washed with dichloromethane (25 ml×3), methanol (25 ml×2), dichloromethane (25 ml×2) and dimethylformamide (25 ml×3) to give compound (2).

REFERENCE EXAMPLE 5

Preparation of Compound (3)

[0434]

[0435] To a suspension of the compound (2) prepared in Reference Example 4 in dimethylformamide (25 ml) were added 3,5-dimethyl-1-phenyl-4-formylpyrazole (1.41 g), sodium triacetoxyborohydride (1.50 g) and acetic acid (0.2 ml), and it was stirred for 16 hours at room temperature. The resin was collected by filtration from the reaction solution, and was washed with dimethylformamide (20 ml×2), dichloromethane (20 ml×2), methanol (20 ml×2) and dichloromethane (20 ml×4) to give compound (3).

REFERENCE EXAMPLE 6

Preparation of Compound (4)

[0436]

[0437] The compound (3) prepared in Reference Example 5 was suspended in 50% trifluoroacetic acid-dichloromethane solution (25 ml), and the suspension was stirred for 5 minutes at room temperature. The reaction solution was filtrated. The obtained resin was suspended in 50% trifluoroacetic acid-dichloromethane solution (25 ml), and it was stirred for 30 minutes at room temperature. The resin was collected by filtration from the reaction solution and was washed with dichloromethane (25 ml×4), toluene (25 ml×4), and 1.25 M acetic acid-toluene solution (25 ml×1) to give compound (4).

REFERENCE EXAMPLE 7

Preparation of Resin (5)

[0438]

[0439] 9-fluorenylmethyloxycarbonylamino-Rink resin (Resin (4)) (5.0 g) (1% divinylbenzene copolymer, Watanabe Kagaku, Catalog No A00102) was washed with dimethylformamide (50 ml×3), and 20% piperidine-dimethylformamide solution (50 ml×2). The washed resin was suspended in 20% piperidine-dimethylformamide solution (50 ml), and the suspension was stirred for 30 minutes at room temperature. The reaction solution was filtrated. The obtained resin was washed with dimethylformamide (50 ml×5). To a suspension of the washed resin in dimethylformamide (20 ml) was added ethyl formate (30 ml), and it was refluxed for 6 hours. The reaction solution was cooled to room temperature and was filtrated. The filtrated resin was washed with dimethylformamide (50 ml×2), dichloromethane (50 ml×4), methanol (50 ml×4) and dichloromethane (50 ml×4), and dried under reduced pressure to give Resin (5) (4.34 g).

[0440] IR (KBr): ν 1693 cm−1.

REFERENCE EXAMPLE 8

Preparation of Resin (6)

[0441]

[0442] By the same procedure as described in Reference Example 2 using Resin (4) prepared in Reference Example 7 (4.0 g), Resin (6) (3.56 g) was obtained.

[0443] IR (KBr): ν 2136 cm−1.

REFERENCE EXAMPLE 9

Preparation of Compound (5)

[0444]

[0445] By the same procedure as described in Reference Example 3 using Resin (6) prepared in Reference Example 8 (1.0 g), N-(6-phenylhexyl)-4-piperidone (0.44 g), n-propylamine (0.14 ml) and N-(t-butyloxycarbonyl)-L-leucine (0.42 g), compound (5) was obtained.

REFERENCE EXAMPLE 10

Preparation of Compound (6)

[0446]

[0447] To a suspension of the compound (5) prepared in Reference Example 9 in 1.5 M 2,6-lutidine-dichloromethane (4 ml) was added 1 M trimethylsilyl trifluoromethanesulfonate-dichloromethane solution (4 ml), and it was stirred for 30 minutes at room temperature. The resin was collected by filtration from the reaction solution. The obtained resin was again suspended in 1.5 M 2,6-lutidine-dichloromethane solution (4 ml), and 1 M trimethylsilyl trifluoromethanesulfonate-dichloromethane solution (4 ml) was added thereto. It was stirred for 30 minutes at room temperature. The resin was collected by filtration from the reaction solution. The resin was washed with dichloromethane (6 ml×4), methanol (6 ml×4), and toluene (6 ml×5) to give compound (6).

EXAMPLE 1

[0448] 9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-2,5-dioxo-3-(2-methyl-1-propyl)-1-propyl-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

[0449] The compound (4) prepared in Reference Example 6 was suspended in 1.25 M acetic acid-toluene solution (25 ml), and the suspension was stirred for 24 hours at 90° C., and was stirred for 16 hours at room temperature. The reaction solution was filtrated. The obtained resin was washed with chloroform-methanol (1:1; 20 ml×2). The filtrate and the washings were concentrated. The residue was purified by column chromatography on silica gel (Fuji Silysia Chemical Ltd., FL60D; chloroform:methanol=30:1). A solution of the obtained residue in methanol was acidified by adding 1 N hydrochloric acid, and was concentrated to give the title compound (703 mg) having the following physical data.

[0450] TLC: Rf 0.50 (chloroform:methanol=10:1);

[0451] NMR (CD3OD): δ 7.68-7.50 (m, 5H), 4.36 (s, 2H), 4.03 (dd, J=7.8, 5.2 Hz, 1H), 3.83 (m, 2H), 3.64 (m, 2H), 3.47 (m, 2H), 2.64 (m, 2H), 2.49 (s, 3H), 2.44 (s, 3H), 2.20 (m, 2H), 1.81 (m, 1H), 1.68 (m, 2H), 1.60 (m, 2H), 1.05-0.90 (m, 9H);

[0452] IR (KBr): ν 3424, 3215, 2960, 2873, 2492, 1671, 1645, 1554, 1501, 1468, 1418, 1370, 1330, 1297, 1243, 1148, 958, 928, 754, 698 cm1;

[0453] MS (MALDI, Pos., α-CHCA): 488 (M+Na)+, 466 (M+H)+, 185.

[0454] elemental analysis: calculated (C27H39N5O2. 2HCl) C: 60.22%, H: 7.67%, N: 13.00%.

[0455] Found C: 59.89%, H: 7.67%, N: 12.79%.

EXAMPLE 2(1)˜2(3)

[0456] By the same procedure as described in Reference Example 3→Reference Example 4 using Resin (3) prepared in Reference Example 2 and N-allyloxycarbonyl-4-piperidone, using the corresponding compounds respectively instead of n-propylamine and N-(t-butyloxycarbonyl)leucine, and furthermore by the same procedure as described in Reference Example 5→Reference Example 6→Example 1 using the corresponding compound instead of 3,5-dimethyl-1-phenyl-4-formylpyrazole, the following compounds of the present invention were obtained.

EXAMPLE 2(1)

[0457] 9-(1,4-benzodioxan-6-ylmethyl)-1-butyl-3-cyclohexylmethyl-2,5-dioxo-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0458] TLC: Rf 0.63 (chloroform:methanol=10:1);

[0459] NMR (CD3OD): δ 7.08 (d, J=2.2 Hz, 1H), 6.99 (dd, J=8.0, 2.2 Hz, 1H), 6.92 (d, J=8.0 Hz, 1H), 4.27 (s, 4H), 4.23 (s, 2H), 4.04 (dd, J=7.6, 4.8 Hz, 1H), 3.74 (m, 2H), 3.60-3.35 (m, 4H), 2.43 (m, 2H), 2.15 (m, 2H), 1.90-1.60 (m, 7H), 1.60-1.45 (m, 2H), 1.45-1.30 (m, 2H), 1.30-1.10 (m, 4H), 1.10-0.80 (m, 5H);

[0460] IR (KBr): ν 3436, 2926, 2852, 2511, 1675, 1645, 1591, 1511, 1418, 1374, 1294, 1261, 1068, 1050, 930, 888 cm−1;

[0461] MS (MALDI, Pos., α-CHCA): 484 (M+H)+, 149.

[0462] elemental analysis: calculated (C28H41N3O4.HCl) C: 64.66%, H: 8.14%, N: 8.08%.

[0463] Found C: 64.00%, H: 7.94%, N: 7.90%.

EXAMPLE 2(2)

[0464] 1-butyl-3-cyclohexylmethyl-2,5-dioxo-9-(2-phenylimidazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

[0465] TLC: Rf 0.25 (chloroform:methanol=10:1);

[0466] NMR (CD3OD): δ 8.05-7.94 (m, 3H), 7.75-7.60 (m, 3H), 4.59 (s, 2H), 4.05 (dd, J=7.4, 4.8 Hz, 1H), 3.88 (m, 2H), 3.65 (m, 2H), 3.51 (m, 2H), 2.68 (m, 2H), 2.19 (m, 2H), 1.90-1.60 (m, 6H), 1.60-1.45 (m, 3H), 1.45-1.30 (m, 3H), 1.30-1.10 (m, 3H), 1.10-0.80 (m, 5H);

[0467] IR (KBr): ν 3423, 2927, 2854, 2664, 1672, 1644, 1421, 1373, 1177, 775, 709, 688 cm−1;

[0468] MS (MALDI, Pos., α-CHCA): 492 (M+H)+.

[0469] elemental analysis: calculated (C29H41N5O2.2HCl 2.8H2O)C: 56.63%, H: 7.96%, N: 11.39%.

[0470] Found C: 56.90%, H: 7.23%, N: 10.78%.

EXAMPLE 2(3)

[0471] 1-butyl-3-(2-methyl-1-propyl)-2,5-dioxo-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0472] TLC: Rf 0.63 (chloroform:methanol=10:1);

[0473] NMR (CD3OD): δ 7.54 (d, J=8.8 Hz, 2H), 7.40 (m, 2H), 7.18 (m, 1H), 7.11-7.00 (m, 4H), 4.33 (s, 2H), 4.01 (dd, J=7.6, 4.8 Hz, 1H), 3.80 (m, 2H), 3.60-3.35 (m, 4H), 2.46 (m, 2H), 2.18 (m, 2H), 1.80 (m, 1H), 1.70 (m, 1H), 1.54 (m, 2H), 1.37 (m, 3H), 1.00-0.90 (m, 9H);

[0474] IR (KBr): ν 3440, 3221, 3066, 2957, 2871, 2559, 1673, 1590, 1509, 1489, 1419, 1371, 1329, 1242, 1172, 873, 693 cm−1;

[0475] MS (MALDI, Pos., α-CHCA): 478 (M+H)+, 183.

[0476] elemental analysis: calculated (C29H39N3O3.HCl)C: 67.75%, H: 7.84%, N: 8.17%.

[0477] Found C: 67.29%, H: 7.70%, N: 8.06%.

EXAMPLE 2(4)

[0478] (3S)-2,5-dioxo-3-(2-methylpropyl)-9-(6-phenylhexyl)-1-propyl-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0479] By the same procedure as described in Example 1 using the compound (6) prepared in Reference Example 10, the title compound (69 mg) having the following physical data was obtained.

[0480] TLC: Rf 0.46 (chloroform:methanol=10:1);

[0481] NMR (CD3OD): δ 7.18 (m, 5H), 4.02 (dd, J=7.6, 4.8 Hz, 1H), 3.70 (m, 2H), 3.56 (m, 2H), 3.39 (m, 2H), 3.11 (m, 2H), 2.63 (dd, J=7.8, 7.2 Hz, 2H), 2.48 (m, 2H), 2.17 (m, 2H), 1.95-1.50 (m, 9H), 1.42 (m, 4H), 1.00-0.89 (m, 9H);

[0482] IR (KBr): ν 3435, 3205, 3082, 3026, 2935, 2870, 2493, 2361, 1674, 1454, 1417, 1370, 1331, 1155, 1071, 1004, 961, 750, 700 cm−1;

[0483] MS (FAB, Pos., glycerin-m-nitrobenzyl alcohol): 442 (M+H)+, 232, 171, 79 (base peak).

[0484] elemental analysis: calculated (C27H43N3O2.HCl) C: 67.83%, H: 9.28%, N: 8.79%.

[0485] Found C: 67.56%, H: 9.50%, N: 8.71%.

EXAMPLE 2(5)

[0486] (3R)-2,5-dioxo-3-(2-methylpropyl)-9-(6-phenylhexyl)-1-propyl-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0487] By the same procedure as described in Reference Example 9→Reference Example 10→Example 1 using Resin (6) prepared in Reference Example 8 (1.0 g), N-(6-phenylhexyl)-4-piperidone (0.44 g), n-propylamine (0.14 ml) and N-(t-butyloxycarbonyl)-D-leucine (0.42 g), the title compound (63 mg) having the following physical data was obtained.

[0488] TLC: Rf 0.46 (chloroform:methanol=10:1);

[0489] NMR (CD3OD): δ 7.18 (m, 5H), 4.02 (dd, J=7.6, 4.6 Hz, 1H), 3.70 (m, 2H), 3.56 (m, 2H), 3.39 (m, 2H), 3.11 (m, 2H), 2.63 (dd, J=7.8, 7.2 Hz, 2H), 2.48 (m, 2H), 2.17 (m, 2H), 1.95-1.50 (m, 9H), 1.42 (m, 4H), 1.00-0.89 (m, 9H);

[0490] IR (KBr): ν 3441, 3204, 3082, 3026, 2935, 2870, 2660, 2499, 2413, 2361, 1674, 1455, 1417, 1370, 1330, 1267, 1205, 1154, 1070, 1003, 960, 928, 899, 750, 700 cm−1;

[0491] MS (FAB, Pos., glycerin-m-nitrobenzyl alcohol): 442 (M+H)+ (base peak), 294, 232, 202, 171, 79.

[0492] elemental analysis: calculated (C27H43N3O2.HCl) C: 67.83%, H: 9.28%, N: 8.79%.

[0493] Found C: 67.52%, H: 9.51%, N: 8.70%.

EXAMPLE 3(1)-3(4)

[0494] By the same procedure as described in Reference Example 3→Reference Example 4 using Resin (3) prepared in Reference Example 2 and N-allyloxycarbonyl-4-piperidone, using the corresponding compounds respectively instead of n-propylamine and N-(t-butyloxycarbonyl) leucine, and furthermore by the same procedure as described in Reference Example 5→Reference Example 6 Example 1 using the corresponding compound instead of 3,5-dimethyl-1-phenyl-4-formylpyrazole, the following compounds of the present invention were obtained.

EXAMPLE 3(1)

[0495] 1-butyl-9-((3,5-dimethyl-1-phenyl)-4-pyrazolyl) methyl)-2,5-dioxo-3-(2-methyl-1-propyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

[0496] TLC: Rf 0.52 (chloroform:methanol=10:1);

[0497] NMR (CD3OD): δ 7.70-7.48 (m, 5H), 4.35 (s, 2H), 4.03 (dd, J=7.8, 4.8 Hz, 1H), 3.83 (m, 2H), 3.63 (m, 2H), 3.51 (m, 2H), 2.64 (m, 2H), 2.48 (s, 3H), 2.43 (s, 3H), 2.20 (m, 2H), 1.81 (m, 2H), 1.71 (m, 2H), 1.55 (m, 2H), 1.50-1.35 (m, 4H), 1.05-0.90 (m, 6H).

EXAMPLE 3(2)

[0498] 1-butyl-3-cyclohexylmethyl-2,5-dioxo-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0499] TLC: Rf 0.73 (chloroform:methanol=10:1);

[0500] NMR (CD3OD): δ 7.74-7.56 (m, 1H), 7.53 (d, J=8.8 Hz, 2H), 7.40 (m, 2H), 7.18 (m, 1H), 7.10-7.00 (m, 3H), 4.33 (s, 2H), 4.04 (dd, J=7.4, 4.8 Hz, 1H), 3.80 (m, 2H), 3.60-3.35 (m, 4H), 2.43 (m, 2H), 2.17 (m, 2H), 1.90-1.60 (m, 7H), 1.60-1.45 (m, 2H), 1.45-1.30 (m, 2H), 1.30-1.15 (m, 4H), 1.10-0.80 (m, 5H).

EXAMPLE 3(3)

[0501] 9-(1,4-benzodioxan-6-ylmethyl)-1-butyl-3-(2-methyl-1-propyl)-2,5-dioxo-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0502] TLC: Rf 0.53 (chloroform:methanol=10:1);

[0503] NMR (CD3OD): δ 7.08 (d, J=2.2 Hz, 1H), 7.01 (dd, J=8.2, 2.2 Hz, 1H), 6.93 (d, J=8.2 Hz, 1H), 4.27 (s, 4H), 4.23 (s, 2H), 4.01 (dd, J=7.8, 4.8 Hz, 1H), 3.72 (m, 2H), 3.55-3.35 (m, 4H), 2.43 (m, 2H), 2.16 (m, 2H), 1.80 (m, 1H), 1.67 (m, 2H), 1.55 (m, 2H), 1.37 (m, 2H), 1.00-0.90 (m, 9H).

EXAMPLE 3(4)

[0504] 9-(4-benzyl oxyphenylmethyl)-1-butyl-2,5-dioxo-3-(2-methyl-1-propyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0505] TLC: Rf 0.59 (chloroform:methanol=10:1);

[0506] NMR (CD3OD): δ 7.54-7.25 (m, 7H), 7.10 (m, 2H), 5.13 (s, 2H), 4.27 (s, 2H), 4.00 (dd, J=8.2, 4.8 Hz, 1H), 3.72 (m, 2H), 3.55-3.35 (m, 4H), 2.42 (m, 2H), 2.16 (m, 2H), 1.90-1.25 (m, 7H), 1.00-0.90 (m, 9H).

EXAMPLE 4

[0507] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0508] By the same procedure as described in Reference Example 3 Reference Example 6→Example 1 using Resin (3) prepared in Reference Example 2, N-(6-phenylhexyl)-4-piperidone, n-butylamine and N-(t-butyloxycarbonyl)leucine, the compound of the present invention having the following physical data was obtained.

[0509] TLC: Rf 0.62 (chloroform:methanol=10:1);

[0510] NMR (CD3OD): δ 7.30-7.06 (m, 5H), 4.02 (dd, J=7.8, 4.8 Hz, 1H), 3.70 (m, 2H), 3.56 (m, 2H), 3.43 (m, 2H), 3.11 (m, 2H), 2.63 (t, J=7.8 Hz, 2H), 2.46 (m, 2H), 2.18 (m, 2H), 1.95-1.50 (m, 9H), 1.50-1.25 (m, 6H), 0.97 (m, 9H).

EXAMPLE 5(1)˜5(12)

[0511] By the same procedure as described in Reference Example 9→Reference Example 10→Example 1 using the corresponding compounds respectively instead of N-(6-phenylhexyl)-4-piperidone, n-propylamine and N-(t-butyloxycarbonyl)-L-leucine, using Resin (6) prepared in Reference Example 8, the following compounds of the present invention were obtained.

EXAMPLE 5(1)

[0512] (3S)-1-(2-methylpropyl)-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0513] TLC: Rf 0.52 (chloroform:methanol=10:1);

[0514] NMR (CD3OD): δ 7.33 (m, 10H), 5.07 (s, 2H), 4.12 (m, 1H), 3.94 (m, 1H), 3.61 (m, 5H), 3.39 (m, 2H), 3.13 (m, 4H), 2.31 (m, 4H), 1.92 (m, 3H), 1.51 (m, 2H), 1.39 (m, 2H), 0.93 (t, J=6.4 Hz, 6H).

EXAMPLE 5(2)

[0515] (3S)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0516] TLC: Rf 0.41 (chloroform:methanol=10:1);

[0517] NMR (CD3OD): δ 7.33 (m, 10H), 5.06 (m, 2H), 4.07 (m, 1H), 3.86 (m, 1H), 3.76 (m, 1H), 3.63 (m, 2H), 3.37 (m, 4H), 3.12 (m, 4H), 2.43 (m, 2H), 2.21 (m, 2H), 1.86 (m, 2H), 1.55 (m, 4H), 1.37 (m, 2H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 5(3)

[0518] (3R)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl) aminobutyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0519] TLC: Rf 0.41 (chloroform:methanol=10:1);

[0520] NMR (CD3OD): δ 7.33 (m, 10H), 5.06 (s, 2H), 4.07 (m, 1H), 3.86 (m, 1H), 3.76 (m, 1H), 3.63 (m, 2H), 3.37 (m, 4H), 3.12 (m, 4H), 2.43 (m, 2H), 2.21 (m, 2H), 1.86 (m, 2H), 1.55 (m, 4H), 1.37 (m, 2H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 5(4)

[0521] (3S)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(3-phenylpropyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0522] TLC: Rf 0.43 (chloroform:methanol=10:1);

[0523] NMR (CD3OD): δ 7.33 (m, 5H), 7.26 (m, 5H), 5.05 (s, 2H), 4.05(m, 1H), 3.85-3.30 (m, 6H), 3.12 (m, 4H), 2.73 (t, J=7.6 Hz, 2H), 2.44 (m, 2H), 2.13 (m, 4H), 1.85 (m, 2H), 1.54 (m, 4H), 1.38 (m, 2H), 0.94 (t, J=7.2 Hz, 3H).

EXAMPLE 5(5)

[0524] (3R)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(3-phenylpropyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0525] TLC: Rf 0.43 (chloroform:methanol=10:1);

[0526] NMR (CD3OD): δ 7.33 (m, 5H), 7.26 (m, 5H), 5.05 (s, 2H), 4.05(m, 1H), 3.85-3.30 (m, 6H), 3.12 (m, 4H), 2.73 (t, J=7.2 Hz, 2H), 2.44 (m, 2H), 2.13 (m, 4H), 1.85 (m, 2H), 1.54 (m, 4H), 1.38 (m, 2H), 0.94 (t, J=7.2 Hz, 3H).

EXAMPLE 5(6)

[0527] (3S)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0528] TLC: Rf 0.44 (chloroform:methanol=10:1);

[0529] NMR (CD3OD): δ 7.33 (m, 5H), 7.22 (m, 5H), 5.06 (s, 2H), 4.05(m, 1H), 3.85-3.38 (m, 6H), 3.12 (m, 4H), 2.70 (m, 2H), 2.40 (m, 2H), 2.18 (m, 2H), 1.74 (m, 6H), 1.54 (m, 4H), 1.38 (m, 2H), 0.94 (t, J=7.0 Hz, 3H).

EXAMPLE 5(7)

[0530] (3R)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0531] TLC: Rf 0.44 (chloroform:methanol=10:1);

[0532] NMR (CD3OD): δ 7.33 (m, 5H), 7.22 (m, 5H), 5.06 (s, 2H), 4.05(m, 1H), 3.85-3.38 (m, 6H), 3.12 (m, 4H), 2.70 (m, 2H), 2.40 (m, 2H), 2.18 (m, 2H), 1.74 (m, 6H), 1.54 (m, 4H), 1.38 (m, 2H), 0.94 (t, J=7.0 Hz, 3H).

EXAMPLE 5(8)

[0533] (3S)-1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-benzyl-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0534] TLC: Rf 0.57 (chloroform:methanol=10:1);

[0535] NMR (CD3OD): δ 7.48 (m, 5H), 7.23 (m, 5H), 4.82 (m, 2H), 4.31 (s, 2H), 4.17 (dd, J=8.0, 4.6 Hz, 1H), 3.72 (m, 2H), 3.40 (m, 2H), 2.52 (m, 2H), 2.08 (m, 2H), 2.00-1.60 (m, 3H), 0.98 (d, J=6.0 Hz, 6H).

EXAMPLE 5(9)

[0536] (3R)-1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-benzyl-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0537] TLC: Rf 0.57 (chloroform:methanol=10:1);

[0538] NMR (CD3OD): δ 7.48 (m, 5H), 7.23 (m, 5H), 4.82 (m, 2H), 4.31 (s, 2H), 4.17 (dd, J=8.0, 4.6 Hz, 1H), 3.72 (m, 2H), 3.40 (m, 2H), 2.52 (m, 2H), 2.08 (m, 2H), 2.00-1.60 (m, 3H), 0.98 (d, J=6.0 Hz, 6H).

EXAMPLE 5(10)

[0539] (3S)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(2-(2-phenyl-5-methyloxazol-4-yl) ethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0540] TLC: Rf 0.45 (chloroform:methanol=10:1);

[0541] NMR (CD3OD): δ 8.01 (m, 2H), 7.53 (m, 3H), 7.34 (m, 5H), 5.07 (s, 2H), 4.08 (dd, J=5.4, 4.4 Hz, 1H), 4.00-3.60 (m, 4H), 3.47 (m, 4H), 3.13 (m, 4H), 2.56 (m, 2H), 2.46 (s, 3H), 2.25 (m, 2H), 1.87 (m, 2H), 1.75-1.25 (m, 6H), 0.94 (t, J=7.2 Hz, 3H).

EXAMPLE 5(11)

[0542] (3S)-1-propyl-2,5-dioxo-3-(4-(N-(2-chlorophenylmethyl)oxycarbonyl)aminobutyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0543] TLC: Rf 0.33 (chloroform:methanol=10:1);

[0544] NMR (CD3OD): δ 7.33 (m, 9H), 5.17 (s, 2H), 4.08 (dd, J=5.2, 4.8 Hz, 1H), 3.80 (m, 2H), 3.65 (m, 3H), 3.39 (m, 3H), 3.14 (m, 4H), 2.50 (m, 2H), 2.22 (m, 2H), 1.85 (m, 2H), 1.70-1.20 (m, 6H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 5(12)

[0545] (3S)-1-propyl-2,5-dioxo-3-[3-(3-(2,4,6-tri methylphenylsulfonyl)guanidino)propyl]-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0546] TLC: Rf 0.39 (chloroform:methanol=10:1);

[0547] NMR (CD3OD): δ 7.32 (m, 5H), 7.05 (s, 2H), 4.10 (m, 1H), 3.88 (m, 1H), 3.67 (m, 3H), 3.40 (m, 4H), 3.18(m, 4H), 2.66 (s, 6H), 2.51 (m, 2H), 2.31 (s, 3H), 2.21 (m, 2H), 1.82 (m, 2H), 1.60 (m, 4H), 0.96 (t, J=7.2 Hz, 3H).

EXAMPLE 6(1)˜6(32)

[0548] By the same procedure as described in Reference Example 3→-Reference Example 4 using Resin (3) prepared in Reference Example 2, N-allyloxycarbonyl-4-piperidone, the corresponding amine derivatives and the corresponding amino acid derivatives, and furthermore by the same procedure as described in Reference Example 5→Reference Example 6→Example 1 using the corresponding aldehyde derivatives, the following compounds of the present invention were obtained.

EXAMPLE 6(1)

[0549] 1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0550] TLC: Rf 0.61 (chloroform:methanol=10:1);

[0551] NMR (CD3OD): δ 7.55 (m, 2H), 7.40 (m, 2H), 7.18 (m, 1H), 7.05 (m, 4H), 4.33 (s, 2H), 4.01 (dd, J=7.6, 4.8 Hz, 1H), 3.79 (m, 2H), 3.60-3.30 (m, 4H), 2.46 (m, 2H), 2.17 (m, 2H), 1.95-1.40 (m, 5H), 0.94 (m, 9H).

EXAMPLE 6(2)

[0552] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-methoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0553] TLC: Rf 0.63 (chloroform:methanol=10:1);

[0554] NMR (CD3OD): δ 7.47 (d, J=8.8 Hz, 2H), 7.03 (d, J=8.8 Hz, 2H), 4.29 (s, 2H), 4.04 (dd, J=7.6, 4.8 Hz, 1H), 3.83 (s, 3H), 3.74 (m, 2H), 3.55-3.35 (m, 4H), 2.41 (m, 2H), 2.15 (m, 2H), 1.85-1.55 (m, 7H), 1.55-1.42 (m, 3H), 1.42-1.30 (m, 3H), 1.30-1.10 (m, 2H), 1.08-0.80 (m, 5H).

EXAMPLE 6(3)

[0555] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-allyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0556] TLC: Rf 0.57 (chloroform:methanol=10:1);

[0557] NMR (CD3OD): δ 7.46 (d, J=8.4 Hz, 2H), 7.04 (d, J=8.4 Hz, 2H), 6.06 (m, 1H), 5.41 (m, 1H), 5.28 (m, 2H), 4.59 (m, 2H), 4.28 (s, 2H), 4.04 (dd, J=7.2, 4.8 Hz, 1H), 3.77 (m, 2H), 3.55-3.35 (m, 4H), 2.39 (m, 2H), 2.16 (m, 2H), 1.90-1.60 (m, 7H), 1.60-1.45 (m, 2H), 1.45-1.30 (m, 2H), 1.30-1.10 (m, 3H), 1.10-0.80 (m, 5H).

EXAMPLE 6(4)

[0558] (3S)-1-propyl-9-(3,5-dimethyl-1-phenyl pyrazol-4-ylmethyl)-2,5-dioxo-3-(2-methyl-1-propyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

[0559] TLC: Rf 0.50 (chloroform:methanol=10:1);

[0560] NMR (CD3OD): δ 7.65-7.45 (m, 5H), 4.33 (s, 2H), 4.03 (dd, J=7.8, 5.2 Hz, 1H), 3.85 (m, 2H), 3.62 (m, 2H), 3.44 (m, 2H), 2.59 (m, 2H), 2.43 (s, 3H), 2.41 (s, 3H), 2.20 (m, 2H), 1.81 (m, 1H), 1.71 (m, 2H), 1.64 (m, 2H), 1.00-0.90 (m, 9H).

EXAMPLE 6(5)

[0561] (3R)-1-propyl-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-2,5-dioxo-3-(2-methyl-1-propyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

[0562] TLC: Rf 0.50 (chloroform:methanol=10:1);

[0563] NMR (CD3OD): δ 7.65-7.45 (m, 5H), 4.33 (s, 2H), 4.03 (dd, J=7.8, 5.2 Hz, 1H), 3.85 (m, 2H), 3.62 (m, 2H), 3.44 (m, 2H), 2.59 (m, 2H), 2.43 (s, 3H), 2.41 (s, 3H), 2.20 (m, 2H), 1.81 (m, 1H), 1.71 (m, 2H), 1.64 (m, 2H), 1.00-0.90 (m, 9H).

EXAMPLE 6(6)

[0564] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-phenylmethyl-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0565] TLC: Rf 0.54 (chloroform:methanol=10:1);

[0566] NMR (CD3OD): δ 7.64-7.44 (m, 5H), 4.36 (s, 2H), 4.01 (dd, J=7.8, 4.8 Hz, 1H), 3.77 (m, 2H), 3.55-3.35 (m, 4H), 2.60-2.30 (m, 2H), 2.17 (m, 2H), 1.95-1.75 (m, 1H), 1.75-1.60 (m, 2H), 1.60-1.45 (m, 2H), 1.45-1.20 (m, 2H), 1.10-0.80 (m, 9H).

EXAMPLE 6(7)

[0567] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-benzyloxycarbonyl-1,4,9-triazaspiro[5.5]undecane

[0568] TLC: Rf 0.41 (chloroform:methanol=20:1);

[0569] NMR (CDCl3): δ 7.45-7.28 (m, 5H), 6.31 (m, 1H), 5.15 (s, 2H), 4.14 (m, 2H), 3.96 (m, 1H), 3.63 (m, 1H), 3.44 (m, 1H), 3.26 (m, 2H), 1.99-1.14 (m, 11H), 1.02-0.88 (m, 9H).

EXAMPLE 6(8)

[0570] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-benzyloxycarbonyl-1,4,9-triazaspiro[5.5]undecane

[0571] TLC: Rf 0.46 (chloroform:methanol=20:1);

[0572] NMR (CDCl3): δ 7.40-7.29 (m, 5H), 5.98 (m, 1H), 5.15 (s, 2H), 4.14 (m, 2H), 4.00 (m, 1H), 3.65 (m, 1H), 3.43 (m, 1H), 3.26 (m, 2H), 2.03-1.81 (m, 4H), 1.80-1.60 (m, 5H), 1.60-1.10 (m, 10H), 1.10-0.85 (m, 5H).

EXAMPLE 6(9)

[0573] 1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0574] TLC: Rf 0.66 (chloroform:methanol=10:1);

[0575] NMR (CD3OD): δ 7.50 (d, J=8.4 Hz, 2H), 7.45-7.12 (m, 8H), 7.10-6.98 (m, 4H), 4.82 (m, 2H), 4.29 (s, 2H), 4.18 (dd, J=8.0, 4.6 Hz, 1H), 3.73 (m, 2H), 3.42 (m, 2H), 2.65-2.30 (m, 2H), 2.20-2.05 (m, 2H), 2.00-1.60 (m, 3H), 0.98 (d, J=6.2 Hz, 6H).

EXAMPLE 6(10)

[0576] 1-butyl-2,5-dioxo-3-propyl-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0577] TLC: Rf 0.36 (chloroform:methanol=10:1);

[0578] NMR (CD3OD): δ 7.51 (d, J=8.7 Hz, 2H), 7.39 (dd, J=8.7, 7.5 Hz, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.10-7.00 (m, 4H), 4.33 (s, 2H), 4.04 (dd, J=5.7, 4.5 Hz, 1H), 3.93-3.66 (m, 2H), 3.55-3.31 (m, 4H), 2.47-2.09 (m, 4H), 1.92-1.68 (m, 2H), 1.61-1.21 (m, 6H), 1.01-0.90 (m, 6H).

EXAMPLE 6(11)

[0579] 1-butyl-2,5-dioxo-3-methoxymethyl-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0580] TLC: Rf 0.48 (chloroform:methanol=10:1);

[0581] NMR (CD3OD): δ 7.51 (d, J=8.7 Hz, 2H), 7.39 (dd, J=8.7, 7.2 Hz, 2H), 7.17 (t, J=7.2 Hz, 1H), 7.09-6.99 (m, 4H), 4.30 (s, 2H), 4.07 (t, J=3.0 Hz, 1H), 3.91 (m, 1H), 3.77 (dd, J=9.0, 3.0 Hz, 1H), 3.67 (m, 1H), 3.58-3.39 (m, 4H), 3.31 (s, 3H), 3.26 (m, 1H), 2.48-2.13 (m, 4H), 1.65 (m, 1H), 1.53-1.28 (m, 3H), 0.95 (t, J=7.5 Hz, 3H).

EXAMPLE 6(12)

[0582] 1-(1-methylpropyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0583] TLC: Rf 0.43 (chloroform:methanol=10:1);

[0584] NMR (CD3OD): δ 7.46 (d, J=8.4 Hz, 2H), 7.38 (dd, J=8.4, 7.5 Hz, 2H), 7.16 (t, J=7.5 Hz, 1H), 7.08-6.99 (m, 4H), 4.15 (s, 2H), 3.91-3.82 (m, 1H), 3.81-3.65 (m, 1H), 3.64-3.44 (m, 1H), 3.44-3.15 (m, 3H), 2.42-2.00 (m, 4H), 1.88-1.56 (m, 5H), 1.46-1.37 (m, 3H), 0.99-0.85 (m, 9H).

EXAMPLE 6(13)

[0585] 1-(2-methyl butyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0586] TLC: Rf 0.49 (chloroform:methanol=10:1);

[0587] NMR (CD3OD): δ 7.49 (d, J=8.7 Hz, 2H), 7.39 (dd, J=8.7, 7.2 Hz, 2H), 7.17 (t, J=7.2 Hz, 1H), 7.08-6.94 (m, 4H), 4.27 (s, 2H), 4.04 (dd, J=8.4, 4.5 Hz, 1H), 3.83-3.21 (m, 6H), 2.45-2.12 (m, 4H), 1.92-1.56 (m, 4H), 1.42 (m, 1H), 1.14 (m, 1H), 1.00-0.83 (m, 12H).

EXAMPLE 6(14)

[0588] 1-(2-methylpropyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0589] TLC: Rf 0.50 (chloroform:methanol=10:1);

[0590] NMR (CD3OD): δ 7.50 (d, J=8.7 Hz, 2H), 7.39 (dd, J=8.7, 7.5 Hz, 2H), 7.17 (t, J=7.5 Hz, 1H), 7.13-7.04 (m, 4H), 4.28 (s, 2H), 4.04 (dd, J=8.1, 4.2 Hz, 1H), 3.81-3.54 (m, 2H), 3.52-3.21 (m, 4H), 2.46-2.11 (m, 4H), 2.00-1.57 (m, 4H), 0.94 (d, J=6.3 Hz, 6H), 0.90 (d, J=6.3 Hz, 3H), 0.90 (d, J=6.3 Hz, 3H).

EXAMPLE 6(15)

[0591] 1-(2-dimethylaminoethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

[0592] TLC: Rf 0.87 (chloroform:methanol: 28% NH4OH=80:10:1);

[0593] NMR (CD3OD): δ 7.60 (d, J=8.7 Hz, 2H), 7.39 (dd, J=8.7, 7.5 Hz, 2H), 7.17 (t, J=7.5 Hz, 1H), 7.07-6.99 (m, 4H), 4.33 (s, 2H), 4.07 (dd, J=8.4, 4.8 Hz, 1H), 3.99-3.63 (m, 4H), 3.53-3.42 (m, 2H), 3.32-3.21 (m, 2H), 2.99 (s, 3H), 2.96 (s, 3H), 2.70-2.49 (m, 2H), 2.30-2.10 (m, 2H), 1.93-1.56 (m, 3H), 0.94 (d, J=6.6 Hz, 6H).

EXAMPLE 6(16)

[0594] 1-(2-methoxyethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0595] TLC: Rf 0.40 (chloroform:methanol=10:1);

[0596] NMR (CD3OD): δ 7.47 (d, J=8.7 Hz, 2H), 7.39 (dd, J=8.7, 7.5 Hz, 2H), 7.17 (t, J=7.5 Hz, 1H), 7.09-6.99 (m, 4H), 4.25 (s, 2H), 4.03 (dd, J=7.8, 4.8 Hz, 1H), 3.75-3.34 (m, 8H), 3.31 (s, 3H), 2.48-2.28 (m, 2H), 2.25-2.06 (m, 2H), 1.90-1.57 (m, 3H), 0.94 (d, J=6.3 Hz, 3H), 0.93 (d, J=6.3 Hz, 3H).

EXAMPLE 6(17)

[0597] 1-(2-methylthioethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0598] TLC: Rf 0.43 (chloroform:methanol=10:1);

[0599] NMR (CD3OD): δ 7.48 (d, J=8.7 Hz, 2H), 7.39 (dd, J=8.7, 7.8 Hz, 2H), 7.17 (t, J=7.8 Hz, 1H), 7.08-6.99 (m, 4H), 4.25 (s, 2H), 4.02 (dd, J=7.8, 4.5 Hz, 1H), 3.81-3.49 (m, 4H), 3.48-3.33 (m, 2H), 2.74-2.51 (m, 2H), 2.39-2.10 (m, 7H), 1.90-1.56 (m, 3H), 0.94 (d, J=6.6 Hz, 3H), 0.93 (d, J=6.6 Hz, 3H).

EXAMPLE 6(18)

[0600] 1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0601] TLC: Rf 0.55 (chloroform:methanol=10:1);

[0602] NMR (CD3OD): δ 7.40-7.15 (m, 5H), 7.03 (d, J=2.0 Hz, 1H), 6.96 (dd, J=8.2, 2.0 Hz, 1H), 6.90 (d, J=8.2 Hz, 1H), 4.80 (m, 2H), 4.25 (s, 4H), 4.21-4.10 (m, 3H), 3.80-3.55 (m, 2H), 3.50-3.30 (m, 2H), 2.60-2.25 (m, 2H), 2.20-2.00 (m, 2H), 2.00-1.60 (m, 3H), 0.98 (d, J=6.4 Hz, 6H).

EXAMPLE 6(19)

[0603] 1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-benzyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

[0604] TLC: Rf 0.53 (chloroform:methanol=10:1);

[0605] NMR (CD3OD): δ 7.50-7.15 (m, 12H), 7.07 (d, J=8.8 Hz, 2H), 5.12 (s, 2H), 4.81 (m, 2H), 4.24 (s, 2H), 4.17 (dd, J=8.4, 4.8 Hz, 1H), 3.70-3.55 (m, 2H), 3.50-3.35 (m, 2H), 2.60-2.25 (m, 2H), 2.20-2.00 (m, 2H), 2.00-1.60 (m, 3H), 0.98 (d, J=6.0 Hz, 6H).

EXAMPLE 6(20)

[0606] 1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

100

[0607] TLC: Rf 0.50 (chloroform:methanol=10:1);

[0608] NMR (CD3OD): δ 7.70-7.45 (m, 5H), 7.40-7.15 (m, 5H), 4.92 (m, 2H), 4.29 (s, 2H), 4.20 (dd, J=8.4, 4.8 Hz, 1H), 3.90-3.65 (m, 2H), 3.65-3.45 (m, 2H), 2.85-2.50 (m, 2H), 2.44 (s, 3H), 2.39 (s, 3H), 2.20-2.00 (m, 2H), 2.00-1.60 (m, 3H), 1.00 (d, J=5.4 Hz, 6H).

EXAMPLE 6(21)

[0609] 1-(3-methylphenylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

101

[0610] TLC: Rf 0.56 (chloroform:methanol=10:1);

[0611] NMR (CD3OD): δ 7.18 (t, J=7.8 Hz, 1H), 7.10-6.85 (m, 6H), 4.77 (m, 2H), 4.25 (s, 4H), 4.19 (m, 3H), 3.68 (m, 2H), 3.40 (m, 2H), 2.60-,2.30 (m, 2H), 2.29 (s, 3H), 2.20-2.00 (m, 2H), 2.00-1.60 (m, 3H), 0.99 (d, J=6.2 Hz, 6H).

EXAMPLE 6(22)

[0612] 1-(3-methylphenylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

102

[0613] TLC: Rf 0.59 (chloroform:methanol=10:1);

[0614] NMR (CD3OD): δ 7.70-7.45 (m, 5H), 7.18 (t, J=7.4 Hz, 1H), 7.10-7.00 (m, 3H), 4.88 (s, 2H), 4.31 (s, 2H), 4.20 (dd, J=8.2, 4.8 Hz, 1H), 3.76 (m, 2H), 3.60 (m, 2H), 2.90-2.50 (m, 2H), 2.47 (s, 3H), 2.41 (s, 3H), 2.30 (s, 3H), 2.10 (m, 2H), 1.88 (m, 1H), 1.85-1.65 (m, 2H), 1.00 (d, J=5.8 Hz, 6H).

EXAMPLE 6(23)

[0615] 1-(1-methyl butyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

103

[0616] TLC: Rf 0.49, 0.56 (chloroform:methanol=10:1);

[0617] NMR (CD3OD): δ 7.49 (d, J=8.7 Hz, 2H), 7.39 (dd, J=8.7, 7.5 Hz, 2H), 7.17 (t, J=7.5 Hz, 1H), 7.08-6.99 (m, 4H), 4.26 (s, 2H), 3.97-3.79 (m, 2H), 3.78-3.60 (m, 1H), 3.54-3.33 (m, 3H), 2.47-2.29 (m, 2H), 2.26-2.03 (m, 3H), 1.87-1.71 (m, 1H), 1.70-1.53 (m, 3H), 1.48-1.16 (m, 5H), 1.02-0.90 (m, 9H).

EXAMPLE 6(24)

[0618] 1-(3-methylbutyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

104

[0619] TLC: Rf 0.54 (chloroform:methanol=10:1);

[0620] NMR (CD3OD): δ 7.51 (d, J=8.7 Hz, 2H), 7.39 (dd, J=8.7, 7.5 Hz, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.10-7.00 (m, 4H), 4.33 (s, 2H), 4.00 (dd, J=8.1, 4.8 Hz, 1H), 3.90-3.71 (m, 2H), 3.56-3.34 (m, 4H), 2.46-2.29 (m, 2H), 2.28-2.10 (m, 2H), 1.90-1.56 (m, 4H), 1.55-1.32 (m, 2H), 1.04-0.85 (m, 12H).

EXAMPLE 6(25)

[0621] 1-(2-methoxyphenylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-((3,5-dimethyl-1-phenyl)-4-pyrazolyl) methyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

105

[0622] TLC: Rf 0.38 (chloroform:methanol=20:1);

[0623] NMR (CD3OD): δ 7.59-7.41 (m, 5H), 7.26-7.17 (m, 1H), 6.99-6.84 (m, 3H), 4.74 (brs, 2H), 4.27 (s, 2H), 4.19 (dd, J=8.4, 4.5 Hz, 1H), 3.88 (s, 3H), 3.90-3.68 (m, 2H), 3.62-3.45 (m, 2H), 2.60-2.14 (m, 4H), 2.35 (s, 3H), 2.33 (s, 3H), 2.00-1.63 (m, 3H), 0.99 (d, J=6.3 Hz, 6H).

EXAMPLE 6(26)

[0624] 1-(3-methoxyphenylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-((3,5-dimethyl-1-phenyl)-4-pyrazolyl)methyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

106

[0625] TLC: Rf 0.33 (chloroform:methanol=20:1);

[0626] NMR (CD3OD): δ 7.65-7.48 (m, 5H), 7.20 (t, J=8.1 Hz, 1H), 6.85-6.80 (m, 2H), 6.77 (dd, J=7.8, 2.1 Hz, 1H), 4.90 (brs, 2H), 4.31 (s, 2H), 4.20 (dd, J=8.1, 4.8 Hz, 1H), 3.84-3.65 (m, 2H), 3.75 (s, 3H), 3.65-3.48 (m, 2H), 2.84-2.56 (m, 2H), 2.47 (s, 3H), 2.40 (s, 3H), 2.19-2.03 (m, 2H), 2.00-1.65 (m, 3H), 0.99 (d, J=6.3 Hz, 6H).

EXAMPLE 6(27)

[0627] 1-(2-methylphenylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

107

[0628] TLC: Rf 0.35 (chloroform:methanol=20:1);

[0629] NMR (CD3OD): δ 7.63-7.46 (m, 5H), 7.18-7.06 (m, 3H), 6.99-6.91 (m, 1H), 4.81 (brs, 2H), 4.29 (s, 2H), 4.20 (dd, J=8.4, 4.5 Hz, 1H), 3.90-3.66 (m, 2H), 3.63-3.57 (m, 2H), 2.75-2.40 (m, 2H), 2.44 (s, 3H), 2.40 (s, 3H), 2.38 (s, 3H), 2.30-2.10 (m, 2H), 2.00-1.65 (m, 3H), 0.99 (d, J=6.3 Hz, 6H).

EXAMPLE 6(28)

[0630] 1-(3-methylphenylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

108

[0631] TLC: Rf 0.48 (chloroform:methanol=20:1);

[0632] NMR (CD3OD): δ 7.53-7.46 (m, 2H), 7.42-7.36 (m, 2H), 7.22-7.14 (m, 2H), 7.06-6.96 (m, 7H), 4.85-4.65 (m, 2H), 4.28 (s, 2H), 4.18 (dd, J=8.1, 4.5 Hz, 1H), 3.80-3.62 (m, 2H), 3.50-3.30 (m, 2H), 2.58-2.25 (m, 2H), 2.29 (s, 3H), 2.18-2.04 (m, 2H), 1.95-1.62 (m, 3H), 0.98 (d, J=6.3 Hz, 6H).

EXAMPLE 6(29)

[0633] 1-butyl-2,5-dioxo-3-cyclohexyl methyl-9-(5-ethylthiophen-2-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

109

[0634] TLC: Rf 0.62 (chloroform:methanol=20:1);

[0635] NMR (CD3OD): δ 7.17 (d, J=3.6 Hz, 1H), 6.85 (d, J=3.6 Hz, 1H), 4.53 (s, 2H), 4.04 (dd, J=7.8, 4.5 Hz, 1H), 3.88-3.72 (m, 2H), 3.58-3.45 (m, 2H), 3.43-3.33 (m, 2H), 2.87 (q, J=7.5 Hz, 2H), 2.50-2.30 (m, 2H), 2.30-2.08 (m, 2H), 1.83-1.10 (m, 17H), 1.31 (t, J=7.5 Hz, 3H), 1.05-0.85 (m, 2H), 0.95 (t, J=7.5 Hz, 3H).

EXAMPLE 6(30)

[0636] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-ethylfuran-2-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

110

[0637] TLC: Rf 0.62 (chloroform:methanol=20:1);

[0638] NMR (CD3OD): δ 6.63 (d, J=3.0 Hz, 1H), 6.14 (d, J=3.0 Hz, 1H), 4.39 (s, 2H), 4.04 (dd, J=7.5, 4.5 Hz, 1H), 3.90-3.70 (m, 2H), 3.55-3.40 (m, 2H), 3.40-3.35 (m, 2H), 2.69 (q, J=7.5 Hz, 2H), 2.50-2.30 (m, 2H), 2.30-2.10 (m, 2H), 1.85-1.05 (m, 17H), 1.25 (t, J=7.5 Hz, 3H), 1.05-0.85 (m, 2H), 0.96 (t, J=7.5 Hz, 3H).

EXAMPLE 6(31)

[0639] (3S)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

111

[0640] TLC: Rf 0.47 (chloroform:methanol=10:1);

[0641] NMR (CD3OD): δ 7.52 (d, J=9.0 Hz, 2H), 7.44-7.35 (m, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.10-7.00 (m, 4H), 4.33 (s, 2H), 4.16-4.00 (m, 2H), 3.75-3.40 (m, 5H), 3.26-3.09 (m, 1H), 2.56-2.08 (m, 4H), 1.82-1.60 (m, 2H), 1.50-1.30 (m, 3H), 1.05-0.89 (m, 9H).

EXAMPLE 6(32)

[0642] (3R)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

112

[0643] TLC: Rf 0.47 (chloroform:methanol=10:1);

[0644] NMR (CD3OD): δ 7.52 (d, J=9.0 Hz, 2H), 7.44-7.35 (m, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.10-7.00 (m, 4H), 4.33 (s, 2H), 4.16-4.00 (m, 2H), 3.75-3.40 (m, 5H), 3.26-3.09 (m, 1H), 2.56-2.08 (m, 4H), 1.82-1.60 (m, 2H), 1.50-1.30 (m, 3H), 1.05-0.89 (m, 9H).

EXAMPLE 7

[0645] (3S)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-allyloxycarbonyl-1,4,9-triazaspiro[5.5]undecane

113

[0646] By the same procedure as described in Reference Example 9→Reference Example 10→Example 1 using Resin (6) prepared in Reference Example 8, N-allyloxycarbonyl-4-piperidone, n-propylamine and N-(t-butyloxycarbonyl)-N′-(benzyloxycarbonyl)-L-lysine, the compound of the present invention having the following physical data was obtained.

[0647] TLC: Rf 0.24 (ethyl acetate:hexane=4:1);

[0648] NMR (CD3OD): δ 7.35 (m, 5H), 6.40 (m, 1H), 5.96 (ddt, J=17.2, 10.2, 5.6 Hz, 1H), 5.34 (m, 1H), 5.24 (m, 1H), 5.12 (s, 2H), 4.88 (m, 1H), 4.62 (m, 2H), 4.10 (m, 2H), 4.00 (m, 1H), 3.75 (m, 1H), 3.36 (m, 2H), 3.18 (m, 3H), 1.94 (m, 6H), 1.51 (m, 6H), 0.90 (t, J=7.2 Hz, 3H).

EXAMPLE 8

[0649] (3S)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-1,4,9-triazaspiro[5.5]undecane

114

[0650] By the same procedure as described in Reference Example 4 using the compound prepared in Example 7, and furthermore, purification by cation-exchange resin and column chromatography on silica gel, the compound of the present invention having the following physical data was obtained.

[0651] TLC: Rf 0.56 (chloroform:methanol: 28% NH4OH=20:5:1);

[0652] NMR (CD3OD): δ 7.40-7.20 (m, 10H), 5.06 (s, 2H), 4.03 (t, J=5.0 Hz, 1H), 3.55-3.18 (m, 4H), 3.12 (t, J=6.6 Hz, 2H), 3.08-2.98 (m, 2H), 2.20-1.70 (m, 6H), 1.70-1.20 (m, 6H), 0.93 (t, J=7.2 Hz, 3H).

EXAMPLE 8(1)

[0653] 1-propyl-2,5-dioxo-3-(2-methylpropyl)-1,4,9-triazaspiro[5.5]undecane

115

[0654] By the same procedure as described in Example 7→Example 8 using N-(t-butyloxycarbonyl)leucine instead of N-(t-butyloxycarbonyl)-N′-(benzyloxycarbonyl)-L-lysine, the compound of the present invention having the following physical data was obtained.

[0655] TLC: Rf 0.44 (chloroform:methanol: triethylamine=18:2:1);

[0656] NMR (CD3OD): δ 3.99 (d, J=7.8, 4.4 Hz, 1H), 3.50-3.20 (m, 4H), 3.05-2.85 (m, 2H), 2.10-1.75 (m, 5H), 1.75-1.40 (m, 4H), 1.00-0.85 (m, 9H).

EXAMPLE 9

[0657] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-1,4,9-triazaspiro[5.5]undecane

116

[0658] To a solution of the compound prepared in Example 6(7) (202 mg) in methanol (5 ml) was added 5% palladium on carbon (20 mg). Under an atmosphere of hydrogen, the reaction mixture was stirred for 3 hours at room temperature. The reaction mixture was filtrated through Celite (brand name). The filtrate was concentrated to give the compound of the present invention (127 mg) having the following physical data.

[0659] TLC: Rf 0.61 (chloroform:methanol: 28% NH4OH=20:5:1);

[0660] NMR (CD3OD): δ 3.97 (dd, J=7.8 Hz, 4.5 Hz, 1H), 3.48-3.22 (m, 4H), 3.00-2.90 (m, 2H), 2.12-1.60 (m, 11H), 0.95 (t, J=7.2 Hz, 3H), 0.94 (d, J=6.6 Hz, 3H), 0.93 (d, J=6.6 Hz, 3H).

EXAMPLE 9(1)

[0661] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-1,4,9-triazaspiro[5.5]undecane

117

[0662] By the same procedure as described in Example 9 using the compound prepared in Example 6(8) instead of the compound prepared in Example 6(7), the compound of the present invention having the following physical data was obtained.

[0663] TLC: Rf 0.65 (chloroform:methanol: 28% NH4OH=20:5:1);

[0664] NMR (CD3OD): δ 4.00 (dd, J=7.8 Hz, 4.5 Hz, 1H), 3.46-3.24 (m, 4H), 3.03-2.92 (m, 2H), 2.08-1.08 (m, 19H), 1.05-0.84 (m, 5H).

EXAMPLE 10

[0665] (3S)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl) aminobutyl)-9-(4-dihydroxyboranephenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

118

[0666] The compound prepared in Example 8 (70 mg) was dissolved in 1% acetic acid-dimethylformamide solution (2 ml). To this solution were added sodium triacetoxyborohydride (46 mg) and 4-formylphenylboronic acid (30 mg). The reaction mixture was stirred for 46 hours at room temperature. To the reaction mixture was added 10% acetic acid-methanol solution. This solution was loaded on cation-exchange resin (BondElut-SCX, Varian Co. Ltd., 0.6 mmol/g, 500 mg/3 ml), and the resin was washed with methanol, and furthermore, was eluted with 10% triethylamine-methanol solution. Only solution which was eluted with 10% triethylamine-methanol solution, was concentrated. The obtained residue was purified by column chromatography on silica gel (chloroform:methanol=1:0-30:1-10:1) to give the compound of the present invention (45 mg) having the following physical data.

[0667] TLC: Rf 0.24 (chloroform:methanol=10:1);

[0668] NMR (CD3OD): δ 7.73 (br, 2H), 7.52 (br, 2H), 7.32 (m, 5H), 5.03 (s, 2H), 4.36 (s, 2H), 4.05 (t, J=4.8 Hz, 1H), 3.81 (m, 2H), 3.46 (m, 3H), 3.10 (t, J=6.6 Hz, 2H), 2.37 (br, 2H), 2.22 (br, 2H), 1.92-1.66 (m, 2H), 1.60-1.28 (m, 7H), 0.91 (t, J=7.5 Hz, 3H).

EXAMPLE 10(1)

[0669] (3S)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl) aminobutyl)-9-(1,3-benzodioxalan-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

119

[0670] By the same procedure as described in Example 10 using 2,3-(methylenedioxy)benzaldehyde instead of 4-formylphenylboronic acid, the compound of the present invention having the following physical data was obtained.

[0671] TLC: Rf 0.25 (chloroform:methanol=10:1);

[0672] NMR (CD3OD): δ 7.32 (m, 5H), 6.96 (m, 3H), 6.05 (s, 2H), 5.04 (s, 2H), 4.33 (s, 2H), 4.05 (t, J=4.5 Hz, 1H), 3.98-3.54 (m, 2H), 3.53 (m, 2H), 3.38 (m, 3H), 3.11 (t, J=6.6 Hz, 2H), 2.37 (br, 2H), 2.22 (br, 2H), 1.98-1.76 (m, 2H), 1.61-1.28 (m, 5H), 0.92 (t, J=7.2 Hz, 3H).

EXAMPLE 11

[0673] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(1-(1,4-benzodioxan-6-yl)ethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

120

[0674] Under an atmosphere of argon, to a solution of the compound prepared in Example 9 (315 mg) in dichloromethane (5 ml) were added 1,4-benzodioxan-6-yl methyl ketone (285 mg), triethylamine (0.354 ml) and a solution of titanium tetrachloride in dichloromethane (1.0 M, 0.63 ml). The reaction mixture was stirred for 16 hours at room temperature. To the reaction mixture was added a solution of sodium cyanoborohydride (133 mg) in methanol (2 ml). The reaction mixture was stirred for 1 hour at room temperature. To the reaction mixture was added 2N aqueous solution of sodium hydroxide, and was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated. The obtained residue was purified by column chromatography on silica gel (Fuji Silysia Chemical Ltd., BW235; chloroform:methanol=50:1). The obtained residue was dissolved in methanol. The solution was acidified by adding 1 N hydrochloric acid, and was concentrated to give the compound of the present invention (176 mg) having the following physical data.

[0675] TLC: Rf 0.46 (chloroform:methanol=10:1);

[0676] NMR (CD3OD): δ 7.04 (d, J=2.1 Hz, 1H), 6.98 (dd, J=8.4, 2.1 Hz, 1H), 6.92 (d, J=8.4 Hz, 1H), 4.40 (q, J=6.9 Hz, 1H), 4.26 (s, 4H), 3.98 (dd, J=8.1, 4.5 Hz, 1H), 3.82-3.17 (m, 6H), 2.55-2.04 (m, 4H), 1.87-1.28 (m, 10H), 1.04-0.85 (m, 9H).

EXAMPLE 11(1)

[0677] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(1-(4-phenyloxyphenyl)ethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

121

[0678] By the same procedure as described in Example 11 using 4-phenoxyacetophenone instead of 1,4-benzodioxan-6-yl methyl ketone, the compound of the present invention having the following physical data was obtained.

[0679] TLC: Rf 0.58, 0.62 (chloroform:methanol=10:1);

[0680] NMR (CD3OD): δ 7.51 (d, J=8.7 Hz, 2H), 7.39 (dd, J=8.7, 7.5 Hz, 2H), 7.17 (t, J=7.5 Hz, 1H), 7.09-7.01 (m, 4H), 4.48 (m, 1H), 3.98 (dd, J=7.8, 4.8 Hz, 1H), 3.80-3.17 (m, 6H), 2.56-2.28 (m, 2H), 2.28-2.03 (m, 2H), 1.88-1.24 (m, 7H), 1.76 (d, J=6.9 Hz, 3H), 1.04-0.86 (m, 9H).

EXAMPLE 12

[0681] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(1-(1,4-benzodioxan-6-yl)ethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

122

[0682] By the same procedure as described in Example 11 using the compound prepared in Example 9(1) instead of the compound prepared in Example 9, the compound of the present invention having the following physical data was obtained.

[0683] TLC: Rf 0.50 (chloroform:methanol=10:1);

[0684] NMR (CD3OD): δ 7.02 (d, J=1.8 Hz, 1H), 6.96 (dd, J=8.4, 1.8 Hz, 1H), 6.92 (d, J=8.4 Hz, 1H), 4.39 (m, 1H), 4.26 (s, 4H), 4.01 (dd, J=7.5, 4.5 Hz, 1H), 3.80-3.20 (m, 6H), 2.50-2.02 (m, 4H), 1.82-1.13 (m, 18H), 1.04-0.83 (m, 5H).

EXAMPLE 13

[0685] (3S)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl) aminobutyl)-9-allyl-1,4,9-triazaspiro[5.5]undecane.hydrochloride

123

[0686] Under an atmosphere of argon, to a solution of the compound prepared in Example 7 (225 mg) in tetrahydrofuran (5 ml) was added tetrakis(triphenylphosphine)palladium (0) (51 mg) at room temperature. The reaction mixture was stirred for 16 hours at room temperature. The reaction mixture was loaded on cation-exchange resin (BondElut-SCX, Varian Co. Ltd., 0.6 mmol/g, 500 mg/3 ml), and the resin was washed with methanol, and furthermore, was eluted with 10% triethylamine-methanol solution (20 ml). Only solution which was eluted with 10% triethylamine-methanol solution, was concentrated. The obtained residue was purified by column chromatography on silica gel (chloroform:methanol=20:1) to give the compound of the present invention (122 mg) having the following physical data.

[0687] TLC: Rf 0.34 (chloroform:methanol=10:1);

[0688] NMR (CD3OD): δ 7.34 (m, 5H), 6.00 (m, 1H), 5.62 (m, 1H), 5.61 (m, 1H), 5.06 (s, 2H), 4.07 (t, J=5.2 Hz, 1H), 3.77 (m, 4H), 3.44 (m, 4H), 3.12 (t, J=6.6 Hz, 2H), 2.39 (m, 2H), 2.20 (m, 2H), 1.84 (m, 2H), 1.54 (m, 4H), 1.37 (m, 2H), 0.94 (t, J=7.2 Hz, 3H).

EXAMPLE 14

[0689] (3S)-1-propyl-2,5-dioxo-3-(4-aminobutyl)-9-phenylethyl-1,4,9-triazaspiro[5.5]undecane

124

[0690] By the same procedure as described in Example 9 using the compound prepared in Example 5(11) instead of the compound prepared in Example 6(7), the compound of the present invention having the following physical data was obtained.

[0691] TLC: Rf 0.66 (chloroform:methanol: 28% NH4OH=20:5:1);

[0692] NMR (CD3OD): δ 7.23 (m, 5H), 4.05 (t, J=5.2 Hz, 1H), 3.42 (m, 2H), 2.98 (m, 3H), 2.81 (m, 3H), 2.65 (m, 4H), 2.16 (m, 2H), 1.99 (m, 1H), 1.89 (m, 3H), 1.53 (m, 3H), 1.48 (m, 3H), 0.94 (t, J=7.2 Hz, 3H).

EXAMPLE 15

[0693] (3S)-1-propyl-2,5-dioxo-3-(4-(N-(4-phenyl)phenylcarbonyl)aminobutyl)-9-phenylethyl-1,4,9-triazaspiro[5.5]undecane.hydrochloride

125

[0694] To a solution of the compound prepared in Example 14 (42 mg) in dichloroethane (2 ml) were added diisopropylethylamine (35 μl) and 4-phenylbenzoyl chloride (33 mg). The reaction mixture was stirred for 3 hours at room temperature. The reaction mixture was loaded on cation-exchange resin (BondElut-SCX, Varian Co. Ltd., 0.6 mmol/g, 500 mg/3 ml), and the resin was washed with methanol, and furthermore, was eluted with 10% triethylamine-methanol solution (20 ml). Only solution which was eluted with 10% triethylamine-methanol solution, was concentrated. The obtained residue was purified by column chromatography on silica gel (chloroform:methanol=10:0→10:1). To the obtained compound was added 4N hydrogen chloride-ethyl acetate solution to give the compound of the present invention (66 mg) having the following physical data.

[0695] TLC: Rf 0.50 (chloroform:methanol=10:1);

[0696] NMR (CD3OD): δ 7.89 (d, J=8.1 Hz, 2H), 7.72 (d, J=8.1 Hz, 2H), 7.65 (d, J=7.2 Hz, 2H), 7.45 (t, J=7.2 Hz, 2H), 7.39-7.26 (m, 6H), 4.11 (m, 1H), 3.86-3.71 (m, 2H), 3.63-3.53 (m, 2H), 3.45-3.30 (m, 4H), 3.07 (m, 2H), 2.42 (br, 2H), 2.19 (m, 2H), 1.99-1.78 (m, 2H), 1.68-1.28 (m, 7H), 0.86 (t, J=7.5 Hz, 3H).

EXAMPLE 16

[0697] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-methyl-9-(1-(1,4-benzodioxan-6-yl)ethyl)-1,4,-diaza-9-azoniaspiro[5.5]undecane Iodide

126

[0698] To a solution of the compound prepared in Example 2(1) (50 mg) in chloroform (2 ml) was added 1 N aqueous solution of sodium hydroxide (2 ml). The reaction mixture was stirred for 10 minutes at room temperature. The aqueous layer of the reaction mixture was removed. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated. To a solution of the obtained residue in acetone (2 ml) was added methyl iodide (118 μl). The reaction mixture was stirred for 18 hours at room temperature. The reaction mixture was concentrated. The obtained residue was solidified by diethyl ether to give the compound of the present invention (58 mg) having the following physical data.

[0699] TLC: Rf 0.23(ethyl acetate: acetic acid:water=8:1:1);

[0700] NMR (CD3OD): δ 7.10-6.90 (m, 3H), 4.60+4.49 (s+s, 2H), 4.29 (s, 4H), 4.20-4.00 (m, 3H), 3.70-3.35 (m, 4H), 3.11+2.99 (s+s, 3H), 2.80-2.30 (m, 2H), 2.30-2.00 (m, 2H),1.90-1.10 (m, 15H),1.10-0.80 (m, 5H).

EXAMPLE 17

[0701] (3S)-3-(4-(N-benzyloxycarbonyl)aminobutyl)-2,5-dioxo-9-(2-hydroxy-2-phenylethyl)-1-propyl-1,4,9-triazaspiro[5.5]undecane

127

[0702] To a solution of the compound prepared in Example 8 (0.01 g) in 2-propanol (0.4 ml) was added styrene oxide (10 μl). The reaction mixture was refluxed for 4 hours. The reaction mixture was cooled to room temperature, and was loaded on ion exchange resin (OASIS MCX, Waters, 60 mg) washed with methanol (3 ml) prior to use. The resin was washed with methanol (2 ml), and was eluted with 10% triethylamine-methanol solution (2 ml). The elution was concentrated to give the compound of the present invention (13 mg) having the following physical data.

[0703] TLC: Rf 0.34 (chloroform:methanol=10:1);

[0704] NMR (CD3OD): δ 7.40-7.20 (m, 10H), 5.06 (s, 2H), 4.03 (m, 1H), 3.40 (m, 2H), 3.12 (m, 2H), 3.10-2.60 (m, 6H), 2.50 (m, 1H), 2.40-2.00 (m, 2H), 2.00-1.70 (m, 4H), 1.70-1.20 (m, 6H), 0.93 (t, J=7.2 Hz, 3H).

EXAMPLE 18

[0705] (3S)-3-(4-(N-benzyloxycarbonyl) aminobutyl)-2,5-dioxo-9-(2-oxo-2-phenylethyl)-1-propyl-1,4,9-triazaspiro[5.5]undecane

128

[0706] To a solution of the compound prepared in Example 8 (0.01 g) in dimethylformamide (0.4 ml) were added triethylamine (6 III), and phenacyl bromide (9 mg). The reaction mixture was allowed to stand for 24 hours at room temperature. The reaction mixture was acidified by adding acetic acid (0.4 ml). The reaction mixture was loaded on ion exchange resin (OASIS MCX, Waters, 120 mg) washed with methanol (6 ml) prior to use. The resin was washed with methanol (2 ml), and was eluted with 10% triethylamine-methanol solution (4 ml). The elution was concentrated to give the compound of the present invention (12 mg) having the following physical data.

[0707] TLC: Rf 0.33 (chloroform:methanol=10:1);

[0708] NMR (CD3OD): δ 8.01 (m, 2H), 7.54 (m, 3H), 7.33 (m, 5H), 5.05 (s, 2H), 4.02 (m, 1H), 4.00 (s, 2H), 3.44 (m, 2H), 3.12 (t, J=6.6 Hz, 2H), 2.95 (m, 2H), 2.40-2.10 (m, 2H), 2.00-1.70 (m, 5H), 1.68-1.20 (m, 7H), 0.94 (t, J=7.2 Hz, 3H).

EXAMPLE 19

[0709] (3S)-1-(2-methylpropyl)-2,5-dioxo-3-methyl-9-allyloxycarbonyl-1,4,9-triazaspiro[5.5]undecane

129

[0710] To a suspension of Resin (6) prepared in Reference Example 8 (300 mg) in tetrahydrofuran (1.5 ml) and methanol (1.5 ml) were added N-allyloxycarbonyl-4-piperidone (403 mg), isobutylamine (0.22 ml) and N-(t-butyloxycarbonyl)-L-alanine (381 mg) at room temperature. The reaction mixture was stirred for 20 hours at 65° C. The reaction mixture was cooled to room temperature and the resin was collected by filtration. The obtained resin was washed with tetrahydrofuran (3 ml×4) and dichloromethane (3 ml×5), and dried. The resin (384 mg) was obtained. To a suspension of the obtained resin (146 mg) in 1.5 M 2,6-lutidine-dichloromethane (2 ml) was added 1 M trimethylsilyl trifluoromethanesulfonate-dichloromethane solution (2 ml). It was stirred for 30 minutes at room temperature. The reaction mixture was filtrated, and the resin was washed with dichloromethane (2 ml×3). The obtained resin was suspended in 1.5 M 2,6-lutidine-dichloromethane solution (2 ml) and 1 M trimethylsilyl trifluoromethanesulfonate-dichloromethane solution (2 ml) was added thereto. The reaction mixture was stirred for 30 minutes at room temperature. The resin was collected by filtration from the reaction solution, and was washed with dichloromethane (2 ml×4), methanol (2 ml×4) and dichloromethane (2 ml×4), dried and the resin was obtained. The obtained resin was suspended in 1.25M acetic acid-toluene solution (2 ml). The reaction mixture was stirred for 20 hours at 90° C. The reaction mixture was filtrated, and the resin was washed with toluene (2 ml×3) and methanol (2 ml×4). The filtrate was concentrated to give the compound of the present invention (19 mg) having the following physical data.

[0711] TLC: Rf 0.39 (chloroform:methanol=10:1);

[0712] MS (ESI, Pos., 20 V): 388 (M+H)+;

[0713] HPLC condition: F;

[0714] HPLC retention time: 3.40 min;

[0715] NMR (CD3OD): δ 5.98 (ddt, J=15.8, 10.4, 5.4 Hz, 1H), 5.30 (m, 1H), 5.21 (m, 1H), 4.59 (m, 2H), 4.20-4.00 (m, 3H), 3.85-3.60 (m, 2H), 3.41 (dd, J=14.2, 8.0 Hz, 1H), 3.18 (dd, J=14.2, 7.2 Hz, 1H), 2.10-1.70 (m, 5H), 1.43 (d, J=6.8 Hz, 3H), 0.89 (t, J=6.2 Hz, 6H).

EXAMPLE 19(1)

[0716] (3S)-1-(2-methylpropyl)-2,5-dioxo-3-methyl-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane.acetate

130

[0717] By the same procedure as described in Example 19 using Resin (6) prepared in Reference Example 8 (200 mg), N-(2-phenylethyl)-4-piperidone (252 mg), isobutylamine (0.123 ml) and N-(t-butyloxycarbonyl)-L-alanine (235 mg), the compound of the present invention (50 mg) having the following physical data was obtained.

[0718] TLC: Rf 0.46 (chloroform:methanol=10:1);

[0719] MS (ESI, Pos., 20 V): 358 (M+H)+;

[0720] HPLC condition: F;

[0721] HPLC retention time: 3.14 min;

[0722] NMR (CD3OD): δ 7.40-7.20 (m, 5H), 4.15 (q, J=6.8 Hz, 1H), 3.65 (m, 1H), 3.55-3.35 (m, 3H), 3.25-3.05 (m, 3H), 3.05-2.90 (m, 3H), 2.50-2.05 (m, 4H), 1.98 (s, 3H), 1.92 (m, 1H), 1.43 (d, J=6.8 Hz, 3H), 0.92 (t, J=6.4 Hz, 6H).

EXAMPLE 19(2)

[0723] (3S)-1-(2-methylpropyl)-2,5-dioxo-3-(4-(N-benzyloxycarbonyl) aminobutyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane.acetate

131

[0724] By the same procedure as described in Example 19 using Resin (6) prepared in Reference Example 8 (200 mg), N-(2-phenylethyl)-4-piperidone (252 mg), isobutylamine (0.123 ml) and N-(t-butyloxycarbonyl)-N′-(benzyloxycarbonyl)-L-lysine (472 mg), the compound of the present invention (71 mg) having the following physical data was obtained.

[0725] TLC: Rf 0.44 (chloroform:methanol=10:1);

[0726] MS (ESI, Pos., 20 V): 549 (M+H)+;

[0727] HPLC condition: F;

[0728] HPLC retention time: 3.49 min;

[0729] NMR (CD3OD): b 7.40-7.20 (m, 10H), 5.06 (s, 2H), 4.10 (m, 1H), 3.67 (m, 1H), 3.60-3.40 (m, 3H), 3.28-3.05 (m, 5H), 3.05-2.90 (m, 3H), 2.50-2.10 (m, 4H), 1.98 (s, 3H), 2.05-1.70 (m, 3H), 1.65-1.20 (m, 4H), 0.92 (t, J=6.2 Hz, 6H).

EXAMPLE 19(3)

[0730] (3S)-1-(1-benzyl piperidin-4-yl)-2,5-dioxo-3-methyl-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane.2 acetate

132

[0731] By the same procedure as described in Example 19 using Resin (6) prepared in Reference Example 8 (200 mg), N-(2-phenylethyl)-4-piperidone (252 mg), 4-amino-1-benzylpiperidine (0.253 ml) and N-(t-butyloxycarbonyl)-L-alanine (235 mg), the compound of the present invention (41 mg) having the following physical data was obtained.

[0732] TLC: Rf 0.10 (chloroform:methanol=10:1);

[0733] MS (ESI, Pos., 20 V): 475 (M+H)+;

[0734] HPLC condition: F;

[0735] HPLC retention time: 3.09 min;

[0736] NMR (CD3OD): δ 7.47 (m, 5H), 7.40-7.20 (m, 5H), 4.19 (s, 2H), 4.00 (q, J=6.8 Hz, 1H), 3.80-3.53 (m, 4H), 3.53-3,35 (m, 4H), 3.30-3.15 (m, 2H), 3.15-2.90 (m, 3H), 2,55-2.30 (m, 3H), 2.30-2.00 (m, 2H), 1.98 (s, 6H), 1.85-1.70 (m, 3H), 1.42 (d, J=7.0 Hz, 3H).

EXAMPLE 19(4)

[0737] (3S)-1-(1-benzylpiperidin-4-yl)-2,5-dioxo-3-(4-(N-benzyloxycarbonyl) aminobutyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane.2 acetate

133

[0738] By the same procedure as described in Example 19 using Resin (6) prepared in Reference Example 8 (200 mg), N-(2-phenylethyl)-4-piperidone (252 mg), 4-amino-1-benzylpiperidine (0.253 ml) and N-(t-butyloxycarbonyl)-N′-(benzyloxycarbonyl)-L-lysine (472 mg), the compound of the present invention (33 mg) having the following physical data was obtained.

[0739] TLC: Rf 0.12 (chloroform:methanol=10:1);

[0740] MS (ESI, Pos., 20 V): 666 (M+H)+;

[0741] HPLC condition: F;

[0742] HPLC retention time: 3.36 min;

[0743] NMR (CD3OD): b 7.46 (m, 5H), 7.40-7.20 (m, 10H), 5.03 (s, 2H), 4.19 (s, 2H), 3.99 (m, 1H), 3.80-3.40 (m, 6H), 3.30-2.85 (m, 9H), 2.50-2.10 (m, 6H), 1.98 (s, 6H), 1.95-1.60 (m, 4H), 1.60-1.40 (m, 4H).

EXAMPLE 19(5)

[0744] (3S)—-(2,2-diphenylpropyl)-2,5-dioxo-3-methyl-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane.acetate

134

[0745] By the same procedure as described in Example 19 using Resin (6) prepared in Reference Example 8 (200 mg), N-(2-phenylethyl)-4-piperidone (252 mg), 2,2-diphenylpropylamine (307 mg) and N-(t-butyloxycarbonyl)-L-alanine (235 mg), the compound of the present invention (22 mg) having the following physical data was obtained.

[0746] TLC: Rf 0.42 (chloroform:methanol=10:1);

[0747] MS (ESI, Pos., 20 V): 496 (M+H)+;

[0748] HPLC condition: F;

[0749] HPLC retention time: 3.58 min;

[0750] NMR (CD3OD): δ 7.40-7.10 (m, 15H), 4.79 (m, 1H), 4.16 (m, 1H), 3.93 (m, 1H), 3.71 (s, 2H), 3.23 (m, 1H), 3.10-2.80 (m, 5H), 1.98 (s, 3H), 1.95-1.82 (m, 2H), 1.70-1.15 (m, 1H), 1.58 (s, 3H), 1.49 (d, J=6.8 Hz, 3H), 0.70 (m, 1H).

EXAMPLE 19(6)

[0751] (3S)-1-(2,2-diphenylpropyl)-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane.acetate

135

[0752] By the same procedure as described in Example 19 using Resin (6) prepared in Reference Example 8 (200 mg), N-(2-phenylethyl)-4-piperidone (252 mg), 2,2-diphenylpropylamine (307 mg) and N-(t-butyloxycarbonyl)-N′-(benzyloxycarbonyl)-L-lysine (472 mg), the compound of the present invention (18 mg) having the following physical data was obtained. MS (ESI, Pos., 20 V): 687 (M+H)+;

[0753] HPLC condition: F;

[0754] HPLC retention time: 3.80 min;

[0755] TLC: Rf 0.46 (chloroform:methanol=10:1);

[0756] NMR (CD3OD): δ 7.40-7.00 (m, 20H), 5.06 (s, 2H), 4.16 (m, 1H), 3.93 (m, 1H), 3.70 (s, 2H), 3.55 (m, 1H), 3.30-3.10 (m, 2H), 3.10-2.80 (m, 6H), 1.98 (s, 3H), 1.95-1.85 (m, 2H), 1.80 (s, 3H), 1.70-1.30 (m, 8H).

EXAMPLE 19(7)

[0757] (3S)-1-propyl-2,5-dioxo-3-(4-benzyloxyphenylmethyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane.acetate

136

[0758] By the same procedure as described in Example 19 using Resin (6) prepared in Reference Example 8 (0.5 g), N-(2-phenylethyl)-4-piperidone (0.32 g), n-propylamine (0.13 ml) and N-(t-butyloxycarbonyl)-O-benzyl-L-tyrosine (0.58 g), the compound of the present invention (68 mg) having the following physical data was obtained.

[0759] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0760] NMR (CD3OD): δ 7.50-7.10 (m, 10H), 7.06 (d, J=8.8 Hz, 2H), 6.92 (d, J=8.8 Hz, 2H), 5.07 (s, 2H), 4.31 (m, 1H), 3.68 (m, 1H), 3.40 (m, 1H), 3.28-3.13 (m, 4H), 3.13-2.80 (m, 6H), 2.30-2.00 (m, 2H), 1.80-1.35 (m, 4H), 0.91 (t, J=7.2 Hz, 3H).

Example 19(H1-1)˜19(H13-62)

[0761] By the same procedure as described in Example 19 using Resin (6) prepared in Reference Example 8, the corresponding 4-piperidone derivatives, the corresponding amine derivatives and the corresponding amino acid derivatives, the compounds of the present invention, whose names were shown in the following Table 1A-1˜13A-9, and whose structures were shown in the following Table 1B-1˜13B-7, were obtained. Also, physical data of the above compounds were shown in the following Table 1C-1˜13C-3.

[0762] In Tables in the present specification,

[0763] X1 is binding site of R1,

[0764] X2 is binding site of R2,

[0765] X3 is binding site of R3,

[0766] X4 is binding site of R4,

[0767] X5 is binding site of R5.

[0768] For example, the structure of Example 19(H1-1) is shown as follows:

137

[0769] Furthermore, the conditions of high performance liquid chromatography (HPLC) in Tables in the present specification, were shown below:

[0770] Condition A

[0771] Column: YMC-Pack FL-ODS, 50×4.6 mm I.D., S-5 um, 120A

[0772] Flow rate: 1 mL/min

[0773] Eluent

[0774] Component A: 0.1% trifluoroacetic acid aqueous solution

[0775] Component B: methanol

[0776] The mixture ratio of A and B was fixed in 90/10 for 2 minutes from starting of measurement. The mixture ratio of A and B was linearly changed to 20/80 for 20 minutes. The mixture ratio of A and B was fixed in 20/80 for 5 minutes. The mixture ratio of A and B was linearly changed to 90/10 for 1 minute.

[0777] Condition B

[0778] Column: YMC-Pack FL-ODS, 50×4.6 mm I.D., S-5 um, 120A

[0779] Flow rate: 1 mL/min

[0780] Eluent

[0781] Component A: 0.1% trifluoroacetic acid aqueous solution

[0782] Component B: methanol

[0783] The mixture ratio of A and B was fixed in 80/20 for 2 minutes from starting of measurement. The mixture ratio of A and B was linearly changed to 20/80 for 20 minutes. The mixture ratio of A and B was fixed in 20/80 for 5 minutes. The mixture ratio of A and B was linearly changed to 80/20 for 1 minute.

[0784] Condition C

[0785] Column: YMC-Pack FL-ODS, 50×4.6 mm I.D., S-5 um, 120A

[0786] Flow rate: 1 mL/min

[0787] Eluent

[0788] Component A: 0.1% trifluoroacetic acid aqueous solution

[0789] Component B: methanol

[0790] The mixture ratio of A and B was fixed in 90/10 for 1 minute from starting of measurement. The mixture ratio of A and B was linearly changed to 10/90 for 16 minutes. The mixture ratio of A and B was fixed in 10/90 for 1 minute. The mixture ratio of A and B was linearly changed to 90/10 for 1 minute.

[0791] Condition D

[0792] Column: YMC-Pack FL-ODS, 50×4.6 mm I.D., S-5 um, 120A

[0793] Flow rate: 1 mL/min

[0794] Eluent

[0795] Component A: 0.1% trifluoroacetic acid aqueous solution

[0796] Component B: methanol

[0797] The mixture ratio of A and B was fixed in 90/10 at starting of measurement. The mixture ratio of A and B was linearly changed to 10/90 for 16 minutes. The mixture ratio of A and B was fixed in 10/90 for 0.5 minute. The mixture ratio of A and B was linearly changed to 90/10 for 0.5 minute.

[0798] Condition E

[0799] Column: YMC-Pack FL-ODS, 50×4.6 mm I.D., S-5 um, 120A

[0800] Flow rate: 3 mL/min

[0801] Eluent

[0802] Component A: 0.1% trifluoroacetic acid aqueous solution

[0803] Component B: methanol

[0804] The mixture ratio of A and B was fixed in 90/10 at starting of measurement. The mixture ratio of A and B was linearly changed to 10/90 for 5 minutes. The mixture ratio of A and B was fixed in 10/90 for 0.5 minute. The mixture ratio of A and B was linearly changed to 90/10 for 0.1 minute.

[0805] Condition F

[0806] Column: Xterraem MS C18 5 um, 4.6×50 mm I.D.

[0807] Flow rate: 3 mL/min

[0808] Eluent

[0809] Component A: 0.1% trifluoroacetic acid aqueous solution

[0810] Component B: 0.1% trifluoroacetic acid-acetonitrile solution

[0811] The mixture ratio of A and B was fixed in 95/5 for 0.5 minute from starting of measurement. The mixture ratio of A and B was linearly changed to 0/100 for 2.5 minute. The mixture ratio of A and B was fixed in 0/100 for 0.5 minute. The mixture ratio of A and B was linearly changed to 95/5 for 0.01 minute.

1TABLE 1A-1Example NoCompound Name19(H1-1)1-(furan-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-benzyl-1,4,9-triazaspiro[5.5]undecane19(H1-2)1-(furan-2-ylmethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-benzyl-1,4,9-triazaspiro[5.5]undecane19(H1-3)1-(furan-2-ylmethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-9-benzyl-1,4,9-triazaspiro[5.5]undecane19(H1-4)1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-9-benzyl-1,4,9-triazaspiro[5.5]undecane19(H1-5)1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-benzyl-1,4,9-triazaspiro[5.5]undecane19(H1-6)1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-phenylmethyl-9-benzyl-1,4,9-triazaspiro[5.5]undecane19(H1-7)1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-benzyl-1,4,9-triazaspiro[5.5]undecane19(H1-8)1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-benzyloxymethyl-9-benzyl-1,4,9-triazaspiro[5.5]undecane19(H1-9)1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-9-benzyl-1,4,9-triazaspiro[5.5]undecane

[0812]

2

TABLE 1A-2

Example No
Compound Name

19(H1-10)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

19(H1-11)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(2-methylpropyl)-9-benzyl-

1,4,9-triazaspiro[5.5]undecane

19(H1-12)
1(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-benzyl-

1,4,9-triazaspiro[5.5]undecane

19(H1-13)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-benzyloxymethyl-9-benzyl-

1,4,9-triazaspiro[5.5]undecane

19(H1-14)
1-benzyl-2,5-dioxo-9-benzyl-1,4,9-triazaspiro[5.5]undecane

19(H1-15)
1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

19(H1-16)
1-benzyl-2,5-dioxo-3-phenylmethyl-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

19(H1-17)
1-benzyl-2,5-dioxo-3-(indol-3-ylmethyl)-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

19(H1-18)
1-benzyl-2,5-dioxo-3-benzyloxymethyl-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

[0813]

3

TABLE 1A-3

Example No
Compound Name

19(H1-19)
1-benzyl-2,5-dioxo-3-benzyloxycarbonylmethyl-9-benzyl-

1,4,9-triazaspiro[5.5]undecane

19(H1-20)
1-benzyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)butyl)-9-

benzyl-1,4,9-triazaspiro[5.5]undecane

19(H1-21)
1-(2,2-diphenylethyl)-2,5-dioxo-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

19(H1-22)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-benzyl-

1,4,9-triazaspiro[5.5]undecane

19(H1-23)
1-(2,2-diphenylethyl)-2,5-dioxo-3-phenylmethyl-9-benzyl-

1,4,9-triazaspiro[5.5]undecane

19(H1-24)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-benzyl-

1,4,9-triazaspiro[5.5]undecane

19(H1-25)
1-(2,2-diphenylethyl)-2,5-dioxo-3-benzyloxymethyl-9-benzyl-

1,4,9-triazaspiro[5.5]undecane

19(H1-26)
1-(2,2-diphenylethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-

9-benzyl-1,4,9-triazaspiro[5.5]undecane

19(H1-27)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

[0814]

4

TABLE

Example No
Compound Name

19(H1-28)
1-(2-phenylethyl)-2,5-dioxo-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

19(H1-29)
1-(2-phenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-benzyl-

1,4,9-triazaspiro[5.5]undecane

19(H1-30)
1-(2-phenylethyl)-2,5-dioxo-3-phenylmethyl-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

19(H1-31)
1-(2-phenylethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-benzyl-

1,4,9-triazaspiro[5.5 ]undecane

19(H1-32)
1-(2-phenylethyl)-2,5-dioxo-3-benzyloxymethyl-9-benzyl-

1,4,9-triazaspiro[5.5]undecane

19(H1-33)
1-(2-phenylethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-9-

benzyl-1,4,9-triazaspiro[5.5]undecane

19(H1-34)
1-(2-phenylethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

19(H1-35)
1-propyl-2,5-dioxo-9-benzyl-1,4,9-triazaspiro[5.5]undecane

19(H1-36)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

19(H1-37)
1-propyl-2,5-dioxo-3-phenylmethyl-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

[0815]

5

TABLE 1A-5

Example No
Compound Name

19(H1-38)
1-propyl-2,5-dioxo-3-(indol-3-ylmethyl)-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

19(H1-39)
1-propyl-2,5-dioxo-3-benzyloxymethyl-9-benzyl-1,4,9-

triazaspiro[5.5[undecane

19(H1-40)
1-propyl-2,5-dioxo-3-benzyloxycarbonylmethyl-9-benzyl-

1,4,9-triazaspiro[5.5]undecane

19(H1-41)
1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)butyl)-9-

benzyl-1,4,9-triazaspiro[5.5]undecane

19(H1-42)
1-(2-(t-butyloxycarbonyl)ethyl) -2,5-dioxo-9-benzyl-1 ,4,9-

triazaspiro[5.5]undecane

19(H1-43)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-benzyl-1,4,9-triazaspiro[5.5]undecane

19(H1-44)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-phenylmethyl-9-

benzyl-1,4,9-triazaspiro[5.5]undecane

19(H1-45)
1-(2-(t-butyloxycarbonyl)ethyl)-2,-dioxo-3-(indol-3-ylmethyl)-

9-benzyl-1,4,9-triazaspiro[5.5 ]undecane

19(H1-46)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-benzyloxymethyl-

9-benzyl-1,4,9-triazaspiro[5.5]undecane

[0816]

6

TABLE 1A-6

Example

No
Compound Name

19(H1-47)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

19(H1-48)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

19(H1-49)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

19(H1-50)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(2-methylpropyl)-9-

benzyl-1,4,9-triazaspiro[5.5]undecane

19(H1-51)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-phenylmethyl-9-

benzyl-1,4,9-triazaspiro[5.5]undecane

19(H1-52)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-

benzyl-1,4,9-triazaspiro[5.5]undecane

19(H1-53)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-benzyloxymethyl-9-

benzyl-1,4,9-triazaspiro[5.5]undecane

19(H1-54)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

[0817]

7

TABLE 1A-7

Example

No
Compound Name

19(H1-55)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(4-

benzyloxycarbonylamino)butyl)-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

[0818]

8

TABLE 2A-1

Example

No
Compound Name

19(H2-1)
1-(furan-2-ylmethyl)-2,5-dioxo-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H2-2)
1-(furan-2-ylmethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-3)
1-(furan-2-ylmethyl)-2,5-dioxo-3-benzyloxymethyl-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-4)
1-(furan-2-ylmethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-9-

(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-5)
1-(furan-2-ylmethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H2-6)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

19(H2-7)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-8)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-phenylmethyl-9-

(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

[0819]

9

TABLE 2A-2

Example

No
Compound Name

19(H2-9)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(indol-3-

ylmethyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]

undecane

19(H2-10)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-benzyloxymethyl-

9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-11)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H2-12)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H2-13)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H2-14)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-15)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-phenylmethyl-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-16)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

[0820]

10

TABLE 2A-3

Example

No
Compound Name

19(H2-17)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-benzyloxymethyl-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-18)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-

9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-19)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H2-20)
1-benzyl-2,5-dioxo-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H2-21)
1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

19(H2-22)
1-benzyl-2,5-dioxo-3-phenylmethyl-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H2-23)
1-benzyl-2,5-dioxo-3-(indol-3-ylmethyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

19(H2-24)
1-benzyl-2,5-dioxo-3-benzyloxymethyl-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

19(H2-25)
1-benzyl-2,5-dioxo-3-benzyloxycarbonylmethyl-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

[0821]

11

TABLE 2A-4

Example

No
Compound Name

19(H2-26)
1-benzyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-27)
1-(2,2-diphenylethyl)-2,5-dioxo-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H2-28)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-29)
1-(2,2-diphenylethyl)-2,5-dioxo-3-phenylmethyl-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-30)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-31)
1-(2,2-diphenylethyl)-2,5-dioxo-3-benzyloxymethyl-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-32)
1-(2,2-diphenylethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-

9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-33)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H2-34)
1-(2-phenylethyl)-2,5-dioxo-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0822]

12

TABLE 2A-5

Example

No
Compound Name

19(H2-35)
1-(2-phenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-36)
1-(2-phenylethyl)-2,5-dioxo-3-phenylmethyl-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-37)
1-(2-phenylethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-38)
1-(2-phenylethyl)-2,5-dioxo-3-benzyloxymethyl-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-39)
1-(2-phenylethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-40)
1-(2-phenylethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H2-41)
1-propyl-2,5-dioxo-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H2-42)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

19(H2-43)
1-propyl-2,5-dioxo-3-phenylmethyl-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0823]

13

TABLE 2A-6

Example

No
Compound Name

19(H2-44)
1-propyl-2,5-dioxo-3-(indol-3-ylmethyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

19(H2-45)
1-propyl-2,5-dioxo-3-benzyloxymethyl-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

19(H2-46)
1-propyl-2,5-dioxo-3-benzyloxycarbonylmethyl-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-47)
1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-48)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

19(H2-49)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-50)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-phenylmethyl-9-

(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-51)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(indol-3-

ylmethyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]

undecane

[0824]

14

TABLE 2A-7

Example

No
Compound Name

19(H2-52)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-benzyloxymethyl-

9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-53)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H2-54)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H2-55)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H2-56)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(2-methylpropyl)-9-

(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-57)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-phenylmethyl-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-58)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-

(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H2-59)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-benzyloxymethyl-9-

(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

[0825]

15

TABLE 2A-8

Example No
Compound Name

19(H2-60)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H2-61)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0826]

16

TABLE 3A-1

Example

No
Compound Name

19(H3-1)
1-(furan-2-ylmethyl)-2,5-dioxo-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

19(H3-2)
1-(furan-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-3)
1-(furan-2-ylmethyl)-2,5-dioxo-3-benzyl-9-(3-phenylpropyl)-

1,4,9-triazaspiro[5.5]undecane

19(H3-4)
1-(furan-2-ylmethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-5)
1-(furan-2-ylmethyl)-2,5-dioxo-3-benzyloxymethyl-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-6)
1-(furan-2-ylmethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-9-

(3-phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-7)
1-(furan-2-ylmethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

19(H3-8)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-9-(3-phenylpropyl)-

1,4,9-triazaspiro[5.5]undecane

19(H3-9)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(3-phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

[0827]

17

TABLE 3A-2

Example

No
Compound Name

19(H3-10)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-phenylmethyl-9-

(3-phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-11)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(indol-3-

ylmethyl)-9-(3-phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-12)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-benzyloxymethyl-

9-(3-phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-13)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

19(H3-14)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

19(H3-15)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

19(H3-16)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-17)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-phenylmethyl-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

[0828]

18

TABLE 3A-3

Example

No
Compound Name

19(H3-18)
1-(2-indol-3-yl)ethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-19)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-benzyloxymethyl-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-20)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-

9-(3-phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-21)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

19(H3-22)
1-benzyl-2,5-dioxo-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

19(H3-23)
1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-phenylpropyl)-

1,4,9-triazaspiro[5.5]undecane

19(H3-24)
1-benzyl-2,5-dioxo-3-phenylmethyl-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

19(H3-25)
1-benzyl-2,5-dioxo-3-(indol-3-ylmethyl)-9-(3-phenylpropyl)-

1,4,9-triazaspiro[5.5]undecane

[0829]

19

TABLE 3A-4

Example

No
Compound Name

19(H3-26)
1-benzyl-2,5-dioxo-3-benzyloxymethyl-9-(3-phenylpropyl)-

1,4,9-triazaspiro[5.5]undecane

19(H3-27)
1-benzyl-2,5-dioxo-3-benzyloxycarbonylmethyl-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-28)
1-benzyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)butyl)-9-

(3-phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-29)
1-(2,2-diphenylethyl)-2,5-dioxo-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

19(H3-30)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-31)
1-(2,2-diphenylethl)-2,5-dioxo-3-phenylmethyl-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-32)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-33)
1-(2,2-diphenylethyl)-2,5-dioxo-3-benzyloxymethyl-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-34)
1-(2,2-diphenylethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-

9-(3-phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

[0830]

20

TABLE 3A-5

Example

No
Compound Name

19(H3-35)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

19(H3-36)
1-(2-phenylethyl)-2,5-dioxo-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

19(H3-37)
1-(2-phenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-38)
1-(2-phenylethyl)-2,5-dioxo-3-phenylmethyl-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-39)
1-(2-phenylethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-40)
1-(2-phenylethyl)-2,5-dioxo-3-benzyloxymethyl-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-41)
1-(2-phenylethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-42)
1-(2-phenylethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

19(H3-43)
1-propyl-2,5-dioxo-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

[0831]

21

TABLE 3A-6

Example

No
Compound Name

19(H3-44)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-phenylpropyl)-

1,4,9-triazaspiro[5.5]undecane

19(H3-45)
1-propyl-2,5-dioxo-3-phenylmethyl-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

19(H3-46)
1-propyl-2,5-dioxo-3-(indol-3-ylmethyl)-9-(3-phenylpropyl)-

1,4,9-triazaspiro[5.5]undecane

19(H3-47)
1-propyl-2,5-dioxo-3-benzyloxymethyl-9-(3-phenylpropyl)-

1,4,9-triazaspiro[5.5]undecane

19(H3-48)
1-propyl-2,5-dioxo-3-benzyloxycarbonylmethyl-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-49)
1-propyl-2,5-dioxo-3-(4-benzyloxycarbonylamino)butyl)-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-50)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-9-(3-phenylpropyl)-

1,4,9-triazaspiro[5.5]undecane

19(H3-51)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(3-phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-52)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-phenylmethyl-9-

(3-phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

[0832]

22

TABLE 3A-7

Example

No
Compound Name

19(H3-53)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(indol-3-

ylmethyl)-9-(3-phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-54)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-

benzyloxymethyl-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

19(H3-55)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

19(H3-56)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

19(H3-57)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-58)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(2-

methylpropyl)-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

19(H3-59)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-phenylmethyl-9-(3-

phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-60)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(indol-3-

ylmethyl)-9-(3-phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

[0833]

23

TABLE 3A-8

Example

No
Compound Name

19(H3-61)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-benzyloxymethyl-

9-(3-phenylpropyl)-1,4,9-triazaspiro[5.5]undecane

19(H3-62)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

19(H3-63)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(3-phenylpropyl)-1,4,9-

triazaspiro[5.5]undecane

[0834]

24

TABLE 4A-1

Example

No
Compound Name

19(H4-1)
1-(furan-2-ylmethyl)-2,5-dioxo-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H4-2)
1-(furan-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-3)
1-(furan-2-ylmethyl)-2,5-dioxo-3-benzyl-9-(4-phenylbutyl)-

1,4,9-triazaspiro[5.5]undecane

19(H4-4)
1-(furan-2-ylmethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-5)
1-(furan-2-ylmethyl)-2,5-dioxo-3-benzyloxymethyl-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-6)
1-(furan-2-ylmethyl)-2,5-

dioxo-3-benzyloxycarbonylmethyl-

9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-7)
1-(furan-2-ylmethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H4-8)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-9)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

[0835]

25

TABLE 4A-2

Example

No
Compound Name

19(H4-10)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-phenylmethyl-9-

(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-11)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(indol-3-

ylmethyl)-9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-12)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-benzyloxymethyl-

9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-13)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H4-14)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H4-15)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H4-16)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-17)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-phenylmethyl-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

[0836]

26

TABLE 4A-3

Example

No
Compound Name

19(H4-18)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-19)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-benzyloxymethyl-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-20)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-

9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-21)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H4-22)
1-benzyl-2,5-dioxo-9-(4-phenylbutyl)-1,4, 9-

triazaspiro[5.5]undecane

19(H4-23)
1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenylbutyl)-

1,4,9-triazaspiro[5.5]undecane

19(H4-24)
1-benzyl-2,5-dioxo-3-phenylmethyl-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H4-25)
1-benzyl-2,5-dioxo-3-(indol-3-ylmethyl)-9-(4-phenylbutyl)-

1,4,9-triazaspiro[5.5]undecane

19(H4-26)
1-benzyl-2,5-dioxo-3-benzyloxymethyl-9-(4-phenylbutyl)-

1,4,9-triazaspiro[5.5]undecane

[0837]

27

TABLE 4A-4

Example

No
Compound Name

19(H4-27)
1-benzyl-2,5-dioxo-3-benzyloxycarbonylmethyl-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-28)
1-benzyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)butyl)-9-

(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-29)
1-(2,2-diphenylethyl)-2,5-dioxo-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H4-30)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-31)
1-(2,2-diphenylethyl)-2,5-dioxo-3-phenylmethyl-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-32)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-33)
1-(2,2-diphenylethyl)-2,5-dioxo-3-benzyloxymethyl-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-34)
1-(2,2-diphenylethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-

9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-35)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

[0838]

28

TABLE 4A-5

Example

No
Compound Name

19(H4-36)
1-(2-phenylethyl)-2,5-dioxo-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H4-37)
1-(2-phenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-38)
1-(2-phenylethyl)-2,5-dioxo-3-phenylmethyl-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-39)
1-(2-phenylethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-40)
1-(2-phenylethyl)-2,5-dioxo-3-benzyloxymethyl-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-41)
1-(2-phenylethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-42)
1-(2-phenylethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H4-43)
1-propyl-2,5-dioxo-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H4-44)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenylbutyl)-

1,4,9-triazaspiro[5.5]undecane

[0839]

29

TABLE 4A-6

Example

No
Compound Name

19(H4-45)
1-propyl-2,5-dioxo-3-phenylmethyl-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H4-46)
1-propyl-2,5-dioxo-3-(indol-3-ylmethyl)-9-(4-phenylbutyl)-

1,4,9-triazaspiro[5.5]undecane

19(H4-47)
1-propyl-2,5-dioxo-3-benzyloxymethyl-9-(4-phenylbutyl)-

1,4,9-triazaspiro[5.5]undecane

19(H4-48)
1-propyl-2,5-dioxo-3-benzyloxycarbonylmethyl-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-49)
1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)butyl)-9-

(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-50)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-9-(4-phenylbutyl)-

1,4,9-triazaspiro[5.5]undecane

19(H4-51)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-52)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-phenylmethyl-9-

(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-53)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(indol-3-

ylmethyl)-9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

[0840]

30

TABLE 4A-7

Example

No
Compound Name

19(H4-54)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-benzyloxymethyl-

9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-55)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H4-56)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H4-57)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H4-58)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(2-methylpropyl)-9-

(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-59)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-phenylmethyl-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-60)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-

(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H4-61)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-benzyloxymethyl-

9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

[0841]

31

TABLE 4A-8

Example

No
Compound Name

19(H4-62)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H4-63)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

[0842]

32

TABLE 5A-1

Example

No
Compound Name

19(H5-1)
1-(furan-2-ylmethyl)-2,5-dioxo-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-2)
1-(furan-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-phenyl-

1,4,9-triazaspiro[5.5]undecane

19(H5-3)
1-(furan-2-ylmethyl)-2,5-dioxo-3-benzyl-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-4)
1-(furan-2-ylmethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-phenyl-

1,4,9-triazaspiro[5.5]undecane

19(H5-5)
1-(furan-2-ylmethyl)-2,5-dioxo-3-benzyloxymethyl-9-phenyl-

1,4,9-triazaspiro[5.5]undecane

19(H5-6)
1-(furan-2-ylmethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-9-

phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-7)
1-(furan-2-ylmethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-8)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-9)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-phenyl-1,4,9-triazaspiro[5.5]undecane

[0843]

33

TABLE 5A-2

Example

No
Compound Name

19(H5-10)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-phenylmethyl-9-

phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-11)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(indol-3-

ylmethyl)-9-phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-12)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-benzyloxymethyl-

9-phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-13)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-14)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-15)
1-(2-(indol-3-yl) ethyl)-2,5-dioxo-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-16)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(2-methylpropyl)-9-

phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-17)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-phenylmethyl-9-phenyl-

1,4,9-triazaspiro[5.5]undecane

19(H5-18)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-

phenyl-1,4,9-triazaspiro[5.5]undecane

[0844]

34

TABLE 5A-3

Example

No
Compound Name

19(H5-19)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-benzyloxymethyl-9-

phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-20)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-

9-phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-21)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-22)
1-benzyl-2,5-dioxo-9-phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-23)
1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-24)
1-benzyl-2,5-dioxo-3-phenylmethyl-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-25)
1-benzyl-2,5-dioxo-3-(indol-3-ylmethyl)-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-26)
1-benzyl-2,5-dioxo-3-benzyloxymethyl-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-27)
1-benzyl-2,5-dioxo-3-benzyloxycarbonylmethyl-9-phenyl-

1,4,9-triazaspiro[5.5]undecane

[0845]

35

TABLE 5A-4

Example

No
Compound Name

19(H5-28)
1-benzyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)butyl)-9-

phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-29)
1-(2,2-diphenylethyl)-2,5-dioxo-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-30)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-phenyl-

1,4,9-triazaspiro[5.5]undecane

19(H5-31)
1-(2,2-diphenylethyl)-2,5-dioxo-3-phenylmethyl-9-phenyl-

1,4,9-triazaspiro[5.5]undecane

19(H5-32)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-

phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-33)
1-(2,2-diphenylethyl)-2,5-dioxo-3-benzyloxymethyl-9-phenyl-

1,4,9-triazaspiro[5.5]undecane

19(H5-34)
1-(2,2-diphenylethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-

9-phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-35)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-36)
1-(2-phenylethyl)-2,5-dioxo-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

[0846]

36

TABLE 5A-5

Example

No
Compound Name

19(H5-37)
1-(2-phenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-phenyl-

1,4,9-triazaspiro[5.5]undecane

19(H5-38)
1-(2-phenylethyl)-2,5-dioxo-3-phenylmethyl-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-39)
1-(2-phenylethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-phenyl-

1,4,9-triazaspiro[5.5]undecane

19(H5-40)
1-(2-phenylethyl)-2,5-dioxo-3-benzyloxymethyl-9-phenyl-

1,4,9-triazaspiro[5.5]undecane

19(H5-41)
1-(2-phenylethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-9-

phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-42)
1-(2-phenylethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-43)
1-propyl-2,5-dioxo-9-phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-44)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-45)
1-propyl-2,5-dioxo-3-phenylmethyl-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

[0847]

37

TABLE 5A-6

Example

No
Compound Name

19(H5-46)
1-propyl-2,5-dioxo-3-(indol-3-ylmethyl)-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-47)
1-propyl-2,5-dioxo-3-benzyloxymethyl-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-48)
1-propyl-2,5-dioxo-3-benzyloxycarbonylmethyl-9-phenyl-

1,4,9-triazaspiro[5.5]undecane

19(H5-49)
1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)butyl)-9-

phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-50)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-51)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-52)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-phenylmethyl-9-

phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-53)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-

(indol-3-ylmethyl)-9-phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-54)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-benzyloxymethyl-

9-phenyl-1,4,9-triazaspiro[5.5]undecane

[0848]

38

TABLE 5A-7

Example

No
Compound Name

19(H5-55)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-56)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-57)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(2-methylpropyl)-9-

phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-58)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-phenylmethyl-9-

phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-59)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-

phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-60)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-benzyloxymethyl-9-

phenyl-1,4,9-triazaspiro[5.5]undecane

19(H5-61)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

19(H5-62)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-phenyl-1,4,9-

triazaspiro[5.5]undecane

[0849]

39

TABLE 6A-1

Example

No
Compound Name

19(H6-1)
1-(furan-2-ylmethyl)-2,5-dioxo-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H6-2)
1-(furan-2-ylmethyl)-2,5-dioxo-3-benzyloxymethyl-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-3)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-9-(5-phenylpentyl)-

1,4,9-triazaspiro[5.5]undecane

19(H6-4)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-5)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-phenylmethyl-9-

(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-6)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(indol-3-

ylmethyl)-9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-7)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-benzyloxymethyl-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-8)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

[0850]

40

TABLE 6A-2

Example

No
Compound Name

19(H6-9)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H6-10)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H6-11)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-12)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-phenylmethyl-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-13)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-14)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-benzyloxymethyl-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-15)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-16)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

[0851]

41

TABLE 6A-3

Example

No
Compound Name

19(H6-17)
1-benzyl-2,5-dioxo-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H6-18)
1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-phenylpentyl)-

1,4,9-triazaspiro[5.5]undecane

19(H6-19)
1-benzyl-2,5-dioxo-3-phenylmethyl-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H6-20)
1-benzyl-2,5-dioxo-3-indol-3-ylmethyl)-9-(5-phenylpentyl)-

1,4,9-triazaspiro[5.5]undecane

19(H6-21)
1-benzyl-2,5-dioxo-3-benzyloxymethyl-9-(5-phenylpentyl)-

1,4,9-triazaspiro[5.5]undecane

19(H6-22)
1-benzyl-2,5-dioxo-3-benzyloxycarbonylmethyl-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-23)
1-benzyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)butyl)-9-

(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-24)
1-(2,2-diphenylethyl)-2,5-dioxo-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H6-25)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

[0852]

42

TABLE 6A-4

Example

No
Compound Name

19(H6-26)
1-(2,2-diphenylethyl)-2,5-dioxo-3-phenylmethyl-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-27)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-28)
1-(2,2-diphenylethyl)-2,5-dioxo-3-benzyloxymethyl-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-29)
1-(2,2-diphenylethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-30)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H6-31)
1-(2-phenylethyl)-2,5-dioxo-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H6-32)
(1-(2-phenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-33)
1-(2-phenylethyl)-2,5-dioxo-3-phenylmethyl-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

[0853]

43

TABLE 6A-5

Example

No
Compound Name

19(H6-34)
1-(2-phenylethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-35)
1-(2-phenylethyl)-2,5-dioxo-3-benzyloxymethyl-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-36)
1-(2-phenylethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-37)
1-(2-phenylethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H6-38)
1-propyl-2,5-dioxo-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H6-39)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-phenylpentyl)-

1,4,9-triazaspiro[5.5]undecane

19(H6-40)
1-propyl-2,5-dioxo-3-phenylmethyl-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H6-41)
1-propyl-2,5-dioxo-3-(indol-3-ylmethyl)-9-(5-phenylpentyl)-

1,4,9-triazaspiro[5.5]undecane

19(H6-42)
1-propyl-2,5-dioxo-3-benzyloxymethyl-9-(5-phenylpentyl)-

1,4,9-triazaspiro[5.5]undecane

[0854]

44

TABLE 6A-6

Example

No
Compound Name

19(H6-43)
1-propyl-2,5-dioxo-3-benzyloxycarbonylmethyl-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-44)
1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)butyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-45)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-9-(5-phenylpentyl)-

1,4,9-triazaspiro[5.5]undecane

19(H6-46)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-47)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-phenylmethyl-9-

(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-48)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(indol-3-

ylmethyl)-9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-49)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-benzyloxymethyl-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-50)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

[0855]

45

TABLE 6A-7

Example

No
Compound Name

19(H6-51)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H6-52)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-9-(5-phenylpentyl)-

1,4,9-triazaspiro[5.5]undecane

19(H6-53)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(2-methylpropyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-54)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-phenylmethyl-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-55)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(indol-3-ylmethyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-56)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-benzyloxymethyl-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H6-57)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H6-58)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

[0856]

46

TABLE 7A-1

Example

No
Compound Name

19(H7-1)
1-(furan-2-ylmethyl)-2,5-dioxo-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H7-2)
1-(furan-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-3)
1-(furan-2-ylmethyl)-2,5-dioxo-3-benzyl-9-(6-phenylhexyl)-

1,4,9-triazaspiro[5.5]undecane

19(H7-4)
1-(furan-2-ylmethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-5)
1-(furan-2-ylmethyl)-2,5-dioxo-3-benzyloxymethyl-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-6)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-9-(6-phenylhexyl)-

1,4,9-triazaspiro[5.5]undecane

19(H7-7)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-8)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-phenylmethyl-9-

(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-9)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(indol-3-

ylmethyl)-9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

[0857]

47

TABLE 7A-2

Example

No
Compound Name

19(H7-10)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-benzyloxymethyl-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-11)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H7-12)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H7-13)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H7-14)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-15)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-phenylmethyl-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-16)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-17)
1-(2-(indol-3-yl) ethyl)-2,5-dioxo-3-benzyloxymethyl-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

[0858]

48

TABLE 7A-3

Example

No
Compound Name

19(H7-18)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-19)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H7-20)
1-benzyl-2,5-dioxo-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H7-21)
1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-phenylhexyl)-

1,4,9-triazaspiro[5.5]undecane

19(H7-22)
1-benzyl-2,5-dioxo-3-phenylmethyl-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H7-23)
1-benzyl-2,5-dioxo-3-(indol-3-ylmethyl)-9-(6-phenylhexyl)-

1,4,9-triazaspiro[5.5]undecane

19(H7-24)
1-benzyl-2,5-dioxo-3-benzyloxymethyl-9-(6-phenylhexyl)-

1,4,9-triazaspiro[5.5]undecane

19(H7-25)
1-benzyl-2,5-dioxo-3-benzyloxycarbonylmethyl-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-26)
1-benzyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)butyl)-9-

(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

[0859]

49

TABLE 7A-4

Example

No
Compound Name

19(H7-27)
1-(2,2-diphenylethyl)-2,5-dioxo-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H7-28)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-29)
1-(2,2-diphenylethyl)-2,5-dioxo-3-phenylmethyl-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-30)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-31)
1-(2,2-diphenylethyl)-2,5-dioxo-3-benzyloxymethyl-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-32)
1-(2,2-diphenylethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-33)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H7-34)
1-(2-phenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

[0860]

50

TABLE 7A-5

Example

No
Compound Name

19(H7-35)
1-(2-phenylethyl)-2,5-dioxo-3-phenylmethyl-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-36)
1-(2-phenylethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-37)
1-(2-phenylethyl)-2,5-dioxo-3-benzyloxymethyl-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-38)
1-(2-phenylethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-39)
1-(2-phenylethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H7-40)
1-propyl-2,5-dioxo-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H7-41)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-phenylhexyl)-

1,4,9-triazaspiro[5.5]undecane

19(H7-42)
1-propyl-2,5-dioxo-3-phenylmethyl-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H7-43)
1-propyl-2,5-dioxo-3-(indol-3-ylmethyl)-9-(6-phenylhexyl)-

1,4,9-triazaspiro[5.5]undecane

[0861]

51

TABLE 7A-6

Example

No
Compound Name

19(H7-44)
1-propyl-2,5-dioxo-3-benzyloxymethyl-9-(6-phenylhexyl)-

1,4,9-triazaspiro[5.5]undecane

19(H7-45)
1-propyl-2,5-dioxo-3-benzyloxycarbonylmethyl-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-46)
1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)butyl)-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-47)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-9-(6-phenylhexyl)-

1,4,9-triazaspiro[5.5]undecane

19(H7-48)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-49)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-phenylmethyl-9-

(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-50)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(indol-3-

ylmethyl)-9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-51)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-benzyloxymethyl-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

[0862]

52

TABLE 7A-7

Example

No
Compound Name

19(H7-52)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H7-53)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H7-54)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-9-(6-phenylhexyl)-

1,4,9-triazaspiro[5.5]undecane

19(H7-55)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(2-methylpropyl)-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-56)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-phenylmethyl-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-57)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(indol-3-ylmethyl)-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-58)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-benzyloxymethyl-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H7-59)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

[0863]

53

TABLE 7A-8

Example

No
Compound Name

19(H7-60)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

[0864]

54

TABLE 8A-1

Example

No
Compound Name

19(H8-1)
1-(furan-2-ylmethyl)-2,5-dioxo-3-benzyl-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-2)
1-(furan-2-ylmethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-

methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-3)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-4)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-5)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-phenylmethyl-9-

methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-6)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(indol-3-

ylmethyl)-9-methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-7)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-benzyloxymethyl-

9-methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-8)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-9)
1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-methyl-1,4,9-

triazaspiro[5.5]undecane

[0865]

55

TABLE 8A-2

Example

No
Compound Name

19(H8-10)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-11)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(2-methylpropyl)-9-

methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-12)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-phenylmethyl-9-methyl-

1,4,9-triazaspiro[5.5]undecane

19(H8-13)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-

methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-14)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-benzyloxymethyl-9-

methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-15)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-

9-methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-16)
1-(2-(indol-3-yl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-17)
1-benzyl-2,5-dioxo-9-methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-18)
1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-methyl-1,4,9-

triazaspiro[5.5]undecane

[0866]

56

TABLE 8A-3

Example

No
Compound Name

19(H8-19)
1-benzyl-2,5-dioxo-3-phenylmethyl-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-20)
1-benzyl-2,5-dioxo-3-(indol-3-ylmethyl)-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-21)
1-benzyl-2,5-dioxo-3-benzyloxymethyl-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-22)
1-benzyl-2,5-dioxo-3-benzyloxycarbonylmethyl-9-methyl-

1,4,9-triazaspiro[5.5]undecane

19(H8-23)
1-benzyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)butyl)-9-

methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-24)
1-(2,2-diphenylethyl)-2,5-dioxo-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-25)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-methyl-

1,4,9-triazaspiro[5.5]undecane

19(H8-26)
1-(2,2-diphenylethyl)-2,5-dioxo-3-phenylmethyl-9-methyl-

1,4,9-triazaspiro[5.5]undecane

19(H8-27)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-

methyl-1,4,9-triazaspiro[5.5]undecane

[0867]

57

TABLE 8A-4

Example

No
Compound Name

19(H8-28)
1-(2,2-diphenylethyl)-2,5-dioxo-3-benzyloxymethyl-9-methyl-

1,4,9-triazaspiro[5.5]undecane

19(H8-29)
1-(2,2-diphenylethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-

9-methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-30)
1-(2,2-diphenylethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-31)
1-(2-phenylethyl)-2,5-dioxo-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-32)
1-(2-phenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-methyl-

1,4,9-triazaspiro[5.5]undecane

19(H8-33)
1-(2-phenylethyl)-2,5-dioxo-3-phenylmethyl-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-34)
1-(2-phenylethyl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-methyl-

1,4,9-triazaspiro[5.5]undecane

19(H8-35)
1-(2-phenylethyl)-2,5-dioxo-3-benzyloxymethyl-9-methyl-

1,4,9-triazaspiro[5.5]undecane

19(H8-36)
1-(2-phenylethyl)-2,5-dioxo-3-benzyloxycarbonylmethyl-9-

methyl-1,4,9-triazaspiro[5.5]undecane

[0868]

58

TABLE 8A-5

Example

No
Compound Name

19(H8-37)
1-(2-phenylethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-38)
1-propyl-2,5-dioxo-9-methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-39)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-40)
1-propyl-2,5-dioxo-3-phenylmethyl-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-41)
1-propyl-2,5-dioxo-3-(indol-3-ylmethyl)-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-42)
1-propyl-2,5-dioxo-3-benzyloxymethyl-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-43)
1-propyl-2,5-dioxo-3-benzyloxycarbonylmethyl-9-methyl-

1,4,9-triazaspiro[5.5]undecane

19(H8-44)
1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)butyl)-9-

methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-45)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-9-methyl-1,4,9-

triazaspiro[5.5]undecane

[0869]

59

TABLE 8A-6

Example

No
Compound Name

19(H8-46)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-phenylmethyl-9-

methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-47)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(indol-3-

ylmethyl)-9-methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-48)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-benzyloxymethyl-

9-methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-49)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-50)
1-(2-(t-butyloxycarbonyl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-51)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-52)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(2-methylpropyl)-9-

methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-53)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-phenylmethyl-9-

methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-54)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(indol-3-ylmethyl)-9-

methyl-1,4,9-triazaspiro[5.5]undecane

[0870]

60

TABLE 8A-7

Example

No
Compound Name

19(H8-55)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-benzyloxymethyl-9-

methyl-1,4,9-triazaspiro[5.5]undecane

19(H8-56)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-

benzyloxycarbonylmethyl-9-methyl-1,4,9-

triazaspiro[5.5]undecane

19(H8-57)
1-(1-benzylpyrrolidin-3-yl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-methyl-1,4,9-

triazaspiro[5.5]undecane

[0871]

61

TABLE 9A-1

Example

No
Compound Name

19(H9-1)
(3S)-1-cyclopropyl-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-2)
(3S)-1-cyclobutyl-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-3)
(3S)-1-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-

ylmethyl)-2,5-dioxo-3-(4-(benzyloxycarbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H9-4)
(3S)-1-cyclopentyl-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-5)
(3S)-1-cyclohexyl-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-6)
(3S)-1-(cyclohexylmethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-7)
(3S)-1-(2-(1-methylpyrrolidin-2-yl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0872]

62

TABLE 9A-2

Example

No
Compound Name

19(H9-8)
(3S)-1-((1-ethylpyrrolidin-2-yl)methyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-9)
(3S)-1-(indan-5-yl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-10)
(3S)-1-cycloheptyl-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-11)
(3S)-1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-12)
(3S)-1-(2-(morpholin-4-yl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-13)
(3S)-1-(3-(morpholin-4-yl)propyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-14)
(3S)-1-(2-(pyridin-2-yl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0873]

63

TABLE 9A-3

Example

No
Compound Name

19(H9-15)
(3S)-1-(pyridin-3-ylmethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-16)
(3S)-1-(pyridin-4-ylmethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-17)
(3S)-1-(1-(ethoxycarbonyl)piperidin-4-yl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-18)
(3S)-1-(2-(piperidin-1-yl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-19)
(3S)-1-(1-phenylethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-20)
(3S)-1-(1-methylethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-21)
(3S)-1-(1,3-dimethylbutyl)-2,5-dioxo-3-(4

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0874]

64

TABLE 9A-4

Example

No
Compound Name

19(H9-22)
(3S)-1-(1-methyl-3-phenylpropyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-23)
(3S)-1-(1-methylpropyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-24)
(3S)-1-(1-methylbutyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-25)
(3S)-1-((2-fluorophenyl)methyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-26)
(3S)-1-((2-methoxyphenyl)methyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-27)
(3S)-1-((3-fluorophenyl)methyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-28)
(3S)-1-((3-methoxyphenyl)methyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0875]

65

TABLE 9A-5

Example

No
Compound Name

19(H9-29)
(3S)-1-((4-fluorophenyl)methyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-30)
(3S)-1-((4-methoxyphenyl)methyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-31)
(3S)-1-((4-methylphenyl)methyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-32)
(3S)-1-(2,2-dimethylpropyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-33)
(3S)-1-(2-phenylpropyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-34)
(3S)-1-(2-methylpropyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-35)
(3S)-1-(2-methylbutyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0876]

66

TABLE 9A-6

Example

No
Compound Name

19(H9-36)
(3S)-1-benzyl-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-37)
(3S)-1-(2-(N,N-dimethylamino)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-38)
(3S)-1-(2-methoxyethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-39)
(3S)-1-(2-propynyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-40)
(3S)-1-(2-propenyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-41)
(3S)-1-(3-hydroxypropyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-42)
(3S)-1-(3-methylbutyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0877]

67

TABLE 9A-7

Example

No
Compound Name

19(H9-43)
(3S)-1-propyl-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H9-44)
(3S)-1-(3-(N,N-dimethylamino)propyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-45)
(3S)-1-(3-ethoxypropyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-46)
(3S)-1-(3-phenylpropyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-47)
(3S)-1-(4-phenylbutyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-48)
(3S)-1-pentyl-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H9-49)
(3S)-1-(3-(imidazol-1-yl)propyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0878]

68

TABLE 9A-8

Example

No
Compound Name

19(H9-50)
(3S)-1-butyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H9-51)
(3S)-1-(2-(1-cyclohexenyl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-52)
(3S)-1-(cyclopropylmethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-53)
(3S)-1-ethyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H9-54)
(3S)-1-(3-methoxypropyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-55)
(3S)-1-(2-(pyridin-4-yl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-56)
(3S)-1-((3-chlorophenyl)methyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0879]

69

TABLE 9A-9

Example

No
Compound Name

19(H9-57)
(3S)-1-(3-methylthiopropyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-58)
(3S)-1-(2-(thiophen-2-yl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-59)
(3S)-1-(2-(1,1-dimethylethylthio)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-60)
(3S)-1-((t-butoxycarbonyl)methyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-61)
(3S)-1-((5-methylfuran-2-yl)methyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H9-62)
(3S)-1-(2-(pyridin-3-yl)ethyl)-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0880]

70

TABLE 10A-1

Example

No
Compound Name

19(H10-1)
(3S)-1-cyclopropyl-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-2)
(3S)-1-cyclobutyl-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-3)
(3S)-1-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-

ylmethyl)-2,5-dioxo-3-(3-(benzyloxycarbonylamino)propyl)-9-

(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H10-4)
(3S)-1-cyclopentyl-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-5)
(3S)-1-cyclohexyl-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-6)
(3S)-1-(cyclohexylmethyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-7)
(3S)-1-cyclooctyl-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0881]

71

TABLE 10A-2

Example

No
Compound Name

19(H10-8)
(3S)-1-(2-(1-methylpyrrolidin-2-yl)ethyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-9)
(3S)-1-((1-ethylpyrrolidin-2-yl)methyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-10)
(3S)-1-(indan-5-yl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-11)
(3S)-1-cycloheptyl-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-12)
(3S)-1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-13)
(3S)-1-(2-(morpholin-4-yl)ethyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-14)
(3S)-1-(3-(morpholin-4-yl)propyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0882]

72

TABLE 10A-3

Example

No
Compound Name

19(H10-15)
(3S)-1-(2-(pyridin-2-yl)ethyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-16)
(3S)-1-(pyridin-3-ylmethyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-17)
(3S)-1-(pyridin-4-ylmethyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-18)
(3S)-1-(1-(ethoxycarbonyl)piperidin-4-yl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-19)
(3S)-1-(2-(piperidin-1-yl)ethyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-20)
(3S)-1-phenyl-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-21)
(3S)-1-(1-phenylethyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0883]

73

TABLE 10A-4

Example

No
Compound Name

19(H10-22)
(3S)-1-(1-methylethyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-23)
(3S)-1-(1,3-dimethylbutyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-24)
(3S)-1-(1-methyl-3-phenylpropyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamnio)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-25)
(3S)-1-(1-methylpropyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-26)
(3S)-1-(1-ethylpropyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-27)
(3S)-1-(1-methylbutyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-28)
(3S)-1-((2-fluorophenyl)methyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0884]

74

TABLE 10A-5

Example

No
Compound Name

19(H10-29)
(3S)-1-((2-methoxyphenyl)methyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-30)
(3S)-1-((3-fluorophenyl)methyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-31)
(3S)-1-((3-methoxyphenyl)methyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-32)
(3S)-1-((4-fluorophenyl)methyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-33)
(3S)-1-((4-methoxyphenyl)methyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-34)
(3S)-1-((4-methylphenyl)methyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-35)
(3S)-1-(2,2-dimethylpropyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0885]

75

TABLE 10A-6

Example

No
Compound Name

19(H10-36)
(3S)-1-(2-phenylpropyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-37)
(3S)-1-(2-methylpropyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-38)
(3S)-1-(2-methylbutyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-39)
(3S)-1-benzyl-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-40)
(3S)-1-(2-(N,N-dimethylamino)ethyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-41)
(3S)-1-(2-methoxyethyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-42)
(3S)-1-(2-propynyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0886]

76

TABLE 10A-7

Example

No
Compound Name

19(H10-43)
(3S)-1-(2-propenyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-44)
(3S)-1-(3-hydroxypropyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-45)
(3S)-1-(3-methylbutyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-46)
(3S)-1-propyl-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-47)
(3S)-1-(3-(N,N-dimethylamino)propyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-48)
(3S)-1-(3-ethoxypropyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-49)
(3S)-1-(3-phenylpropyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0887]

77

TABLE 10A-8

Example

No
Compound Name

19(H10-50)
(3S)-1-(4-phenylbutyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

19(H10-51)
(3S)-1-pentyl-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

19(H10-52)
(3S)-1-(3-(imidazol-1-yl)propyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

19(H10-53)
(3S)-1-butyl-2,5-dioxo-3-(3-(benzyloxycarbonylamino)

propyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H10-54)
(3S)-1-(2-(1-cyclohexenyl)ethyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

19(H10-55)
(3S)-1-(cyclopropylmethyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

19(H10-56)
(3S)-1-ethyl-2,5-dioxo-3-(3-(benzyloxycarbonylamino)

propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0888]

78

TABLE 10A-9

Example

No
Compound Name

19(H10-57)
(3S)-1-(3-methoxypropyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-58)
(3S)-1-(2-N-ethyl-N-(3-methylphenyl)amino)ethyl)-

2,5-dioxo-3-(3-benzyloxycarbonylamino)propyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

19(H10-59)
(3S)-1-(2-(pyridin-4-yl)ethyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-60)
(3S)-1-((3-chlorophenyl)methyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-61)
(3S)-1-(3-methylthiopropyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-62)
(3S)-1-(2-thiophen-2-yl)ethyl-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-63)
(3S)-1-(2-(1,1-dimethylethylthio)ethyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0889]

79

TABLE 10A-10

Example

No
Compound Name

19(H10-64)
(3S)-1-((t-butoxycarbonyl)methyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-65)
(3S)-1-((2S)-2-hydroxypropyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-66)
(3S)-1-((5-methylfuran-2-yl)methyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-67)
(3S)-1-((1R)-1-(4-methylphenyl)ethyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

19(H10-68)
(3S)-1-(2-(pyridin-3-yl)ethyl)-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[0890]

80

TABLE 11A-1

Example

No
Compound Name

19(H11-1)
(3S)-1-cyclopropyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-2)
(3S)-1-cyclobutyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-3)
(3S)-1-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-

ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenylbutyl)-

1,4,9-triazaspiro[5.5]undecane

19(H11-4)
(3S)-1-cyclopentyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-5)
(3S)-1-cyclohexyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-6)
(3S)-1-(cyclohexylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-7)
(3S)-1-(2-(1-methylpyrrolidin-2-yl)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-8)
(3S)-1-((1-ethylpyrrolidin-2-yl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

[0891]

81

TABLE 11A-2

Example

No
Compound Name

19(H11-9)
(3S)-1-(indan-5-yl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-10)
(3S)-1-cycloheptyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-11)
(3S)-1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-12)
(3S)-1-(2-(morpholin-4-yl)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-13)
(3S)-1-(3-(morpholin-4-yl)propyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-14)
(3S)-1-(2-(pyridin-2-yl)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-15)
(3S)-1-(pyridin-3-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

[0892]

82

TABLE 11A-3

Example

No
Compound Name

19(H11-16)
(3S)-1-(pyridin-4-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-17)
(3S)-1-(1-(ethoxycarbonyl)piperidin-4-yl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-18)
(3S)-1-(2-(piperidin-1-yl)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-19)
(3S)-1-(1-phenylethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-20)
(3S)-1-(1-methylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-21)
(3S)-1-((2-fluorophenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-22)
(3S)-1-((2-methoxyphenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

[0893]

83

TABLE 11A-4

Example

No
Compound Name

19(H11-23)
(3S)-1-((3-fluorophenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-24)
(3S)-1-((3-methoxyphenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-25)
(3S)-1-((4-fluorophenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-26)
(3S)-1-((4-methoxyphenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-27)
(3S)-1-((4-methylphenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-28)
(3S)-1-(2,2-dimethylpropyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-29)
(3S)-1-(2-phenylpropyl)-2,5-dioxo-3-(2-methylpropyl)-9-

(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

[0894]

84

TABLE 11A-5

Example

No
Compound Name

19(H11-30)
(3S)-1-(2-methylpropyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-31)
(3S)-1-(2-methylbutyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-32)
(3S)-1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-33)
(3S)-1-(2-(N,N-dimethylamino)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-34)
(3S)-1-(2-methoxyethyl)-2,5-dioxo-3-(2-methylpropyl)-9-

(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-35)
(3S)-1-(2-propynyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-36)
(3S)-1-(2-propenyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-37)
(3S)-1-(3-hydroxypropyl)-2,5-dioxo-3-(2-methylpropyl)-9-

(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

[0895]

85

TABLE 11A-6

Example

No
Compound Name

19(H11-38)
(3S)-1-(3-methylbutyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-39)
(3S)-1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-40)
(3S)-1-(3-(N,N-dimethylamino)propyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-41)
(3S)-1-(3-ethoxypropyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-42)
(3S)-1-(3-phenylpropyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-43)
(3S)-1-(4-phenylbutyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-44)
(3S)-1-pentyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-45)
(3S)-1-(3-(imidazol-1-yl)propyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

[0896]

86

TABLE 11A-7

Example

No
Compound Name

19(H11-46)
(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-47)
(3S)-1-(2-(1-cyclohexenyl)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-48)
(3S)-1-(cyclopropylmethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-49)
(3S)-1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-50)
(3S)-1-(3-methoxypropyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

19(H11-51)
(3S)-1-(2-(pyridin-4-yl)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-52)
(3S)-1-((3-chlorophenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-53)
(3S)-1-(3-methylthiopropyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane

[0897]

87

TABLE 11A-8

Example

No
Compound Name

19(H11-54)
(3S)-1-(2-(thiophen-2-yl)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-55)
(3S)-1-(2-(1,1-dimethylethylthio)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-56)
(3S)-1-((t-butoxycarbonyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenlybutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-57)
(3S)-1-((5-methylfuran-2-yl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

19(H11-58)
(3S)-1-(2-(pyridin-3-yl)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenylbutyl)-1,4,9-

triazaspiro[5.5]undecane

[0898]

88

TABLE 12A-1

Example

No
Compound Name

19(H12-1)
(3S)-1-cyclopropyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-2)
(3S)-1-cyclobutyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-3)
(3S)-1-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-

ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(5-phenylpentyl)-

1,4,9-triazaspiro[5.5]undecane

19(H12-4)
(3S)-1-cyclopentyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-5)
(3S)-1-cyclohexyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-6)
(3S)-1-(cyclohexylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-7)
(3S)-1-(1,2,3,4-tetrahydronaphthyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-8)
(3S)-1-cyclooctyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

[0899]

89

TABLE 12A-2

Example

No
Compound Name

19(H12-9)
(3S)-1-(2-(1-methylpyrrolidin-2-yl)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-10)
(3S)-1-((1-ethylpyrrolidin-2-yl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-11)
(3S)-1-(indan-5-yl)-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-12)
(3S)-1-cycloheptyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-13)
(3S)-1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-14)
(3S)-1-(2-(morpholin-4-yl)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-15)
(3S)-1-(3-(morpholin-4-yl)propyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

[0900]

90

TABLE 12A-3

Example

No
Compound Name

19(H12-16)
(3S)-1-(2-(pyridin-2-yl)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-17)
(3S)-1-(pyridin-3-ylmethyl)-2,5-dioxo-3-(2-methyipropyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-18)
(3S)-1-(pyridin-4-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-19)
(3S)-1-(2-(piperidin-1-yl)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-20)
(3S)-1-phenyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-21)
(3S)-1-(1-phenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-22)
(3S)-1-(1-methylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

[0901]

91

TABLE 12A-4

Example

No
Compound Name

19(H12-23)
(3S)-1-(1,3-dimethylbutyl)-2,5-dioxo-3-(2-methylpropyl)-9-

(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-24)
(3S)-1-(1-methyl-3-phenylpropyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-25)
(3S)-1-(1-methylpropyl)-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-26)
(3S)-1-(1-ethylpropyl)-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-27)
(3S)-1-(1-methylbutyl)-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-28)
(3S)-1-((2-fluorophenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-29)
(3S)-1-((2-methoxyphenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

[0902]

92

TABLE 12A-5

Example

No
Compound Name

19(H12-30)
(3S)-1-((3-fluorophenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-31)
(3S)-1-((3-methoxyphenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-32)
(3S)-1-((4-fluorophenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-33)
(3S)-1-((4-methoxyphenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-34)
(3S)-1-((4-methylphenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-35)
(3S)-1-(2,2-dimethylpropyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-36)
(3S)-1-(2-phenylpropyl)-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

[0903]

93

TABLE 12A-6

Example

No
Compound Name

19(H12-37)
(3S)-1-(2-methylpropyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-38)
(3S)-1-(2-methylbutyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(5-phenylpentyl-1,4,9-triazaspiro[5.5]undecane

19(H12-39)
(3S)-1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-40)
(3S)-1-(2-(N,N-dimethylamino)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-41)
(3S)-1-(2-methoxyethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-42)
(3S)-1-(2-propynyl)-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-43)
(3S)-1-(2-propenyl)-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl-1,4,9-triazaspiro[5.5]undecane

19(H12-44)
(3S)-1-(3-hydroxypropyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(5-penylpentyl)-1,4,9-triazaspiro[5.5]undecane

[0904]

94

TABLE 12A-7

Example

No
Compound Name

19(H12-45)
(3S)-1-(3-methylbutyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-46)
(3S)-1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-47)
(3S)-1-(3-(N,N-dimethylamino)propyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-48)
(3S)-1-(3-ethoxypropyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-49)
(3S)-1-(3-phenylpropyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-50)
(3S)-1-(4-phenylbutyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-51)
(3S)-1-pentyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-

phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-52)
(3S)-1-(3-(imidazol-1-yl)propyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

[0905]

95

TABLE 12A-8

Example

No
Compound Name

19(H12-53)
(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-54)
(3S)-1-(2-(1-cyclohexenyl)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-55)
(3S)-1-(cyclopropylmethyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-56)
(3S)-1-ethyl-2,5-dioxo-3-(2-methylpropyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-57)
(3S)-1-(1-propylbutyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-58)
(3S)-1-(3-methoxypropyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(5-phenylpentyl)-1,4,9-triazaspiro[5.5]undecane

19(H12-59)
(3S)-1-(2-(pyridin-4-yl)ethyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-60)
(3S)-1-((3-chlorophenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

[0906]

96

TABLE 12A-9

Example

No
Compound Name

19(H12-61)
(3S)-1-(3-methylthiopropyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-62)
(3S)-1-(2-(thiophen-2-yl)ethyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-63)
(3S)-1-(2-(1,1-dimethylethylthio)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-64)
(3S)-1-((t-butoxycarbonyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-65)
(3S)-1-((2R)-2-hydroxypropyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-66)
(3S)-1-((2S)-2-hydroxypropyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-67)
(3S)-1-((5-methylfuran-2-yl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

[0907]

97

TABLE 12A-10

Example

No
Compound Name

19(H12-68)
(3S)-1-((1R)-1-(4-methylphenyl)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro[5.5]undecane

19(H12-69)
(3S)-1-(2-(pyridin-3-yl)ethyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(5-phenylpentyl)-1,4,9-

triazaspiro-[5.5]undecane

[0908]

98

TABLE 13A-1

Example

No
Compound Name

19(H13-1)
(3S)-1-cyclopropyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-2)
(3S)-1-cyclobutyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-3)
(3S)-1-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-

ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-

(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-4)
(3S)-1-cyclopentyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-5)
(3S)-1-cyclohexyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-6)
(3S)-1-(cyclohexylmethyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-7)
(3S)-1-(1,2,3,4-tetrahydronaphthyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-8)
(3S)-1-cyclooctyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

[0909]

99

TABLE 13A-2

Example

No
Compound Name

19(H13-9)
(3S)-1-(2-(1-methylpyrrolidin-2-yl)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-10)
(3S)-1-((1-ethylpyrrolidin-2-yl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-11)
(3S)-1-(indan-5-yl)-2,5-dioxo-3-(2-methylpropyl)-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-12)
(3S)-1-cycloheptyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-13)
(3S)-1-(thiophen-2-ylmethyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-14)
(3S)-1-(2-(morpholin-4-yl)ethyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-15)
(3S)-1-(3-(morpholin-4-yl)propyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

[0910]

100

TABLE 13A-3

Example

No
Compound Name

19(H13-16)
(3S)-1-(2-(pyridin-2-yl)ethyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-17)
(3S)-1-(pyridin-3-ylmethyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-18)
(3S)-1-(1-(ethoxycarbonyl)piperidin-4-yl)-2,5-dioxo-3-(2-

methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-19)
(3S)-1-(2-(piperidin-1-yl)ethyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-20)
(3S)-1-(1-phenylethyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-21)
(3S)-1-(1,2-dimethylpropyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-22)
(3S)-1-(1,3-dimethylbutyl)-2,5-dioxo-3-(2-methylpropyl)

-9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

[0911]

101

TABLE 13A-4

Example

No
Compound Name

19(H13-23)
(3S)-1-(1-ethylpropyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-24)
(3S)-1-((2-fluorophenyl)methyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-25)
(3S)-1-((2-methoxyphenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-26)
(3S)-1-((3-fluorophenyl)methyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-27)
(3S)-1-((3-methoxyphenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-28)
(3S)-1-((4-fluorophenyl)methyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-29)
(3S)-1-((4-methoxyphenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

[0912]

102

TABLE 13A-5

Example

No
Compound Name

19(H13-30)
(3S)-1-((4-methylphenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-31)
(3S)-1-(2,2-dimethylpropyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-32)
(3S)-1-(2-phenylpropyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-33)
(3S)-1-(2-methylpropyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-34)
(3S)-1-(2-methylbutyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-35)
(3S)-1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-36)
(3S)-1-(2-(N,N-dimethylamino)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-37)
(3S)-1-(2-methoxyethyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

[0913]

103

TABLE 13A-6

Example

No
Compound Name

19(H13-38)
(3S)-1-(2-propynyl)-2,5-dioxo-3-(2-methylpropyl)-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-39)
(3S)-1-(2-propenyl)-2,5-dioxo-3-(2-methylpropyl)-9-(6-

phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-40)
(3S)-1-(3-hydroxypropyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-41)
(3S)-1-(3-methylbutyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-42)
(3S)-1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-43)
(3S)-1-(3-(N,N-dimethylamino)propyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-44)
(3S)-1-(3-ethoxypropyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-45)
(3S)-1-(3-phenylpropyl)-2,5-dioxo-3-(2-methylpropyl)-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

[0914]

104

TABLE 13A-7

Example

No
Compound Name

19(H13-46)
(3S)-1-(4-phenylbutyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-47)
(3S)-1-pentyl-2,5-dioxo-3-(2-methylpropyl)-9-

(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-48)
(3S)-1-(3-(imidazol-1-yl)propyl)-2,5-dioxo-

3-(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-49)
(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-50)
(3S)-1-(2-(1-cyclohexenyl)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-51)
(3S)-1-(cyclopropylmethyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-52)
(3S)-1-ethyl-2,5-dioxo-3-(2-methylpropyl)-

9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

19(H13-53)
(3S)-1-(1-propylbutyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

[0915]

105

TABLE 13A-8

Example

No
Compound Name

19(H13-54)
(3S)-1-(3-methoxypropyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-55)
(3S)-1-(2-(pyridin-4-yl)ethyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-56)
(3S)-1-((3-chlorophenyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-57)
(3S)-1-(3-methylthiopropyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]-undecane

19(H13-58)
(3S)-1-(2-(thiophen-2-yl)ethyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-59)
(3S)-1-(2-(1,1-dimethylethylthio)ethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-6O)
(3S)-1-((t-butoxycarbonyl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

[0916]

106

TABLE 13A-9

Example

No
Compound Name

19(H13-61)
(3S)-1-((5-methylfuran-2-yl)methyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

19(H13-62)
(3S)-1-(2-(pyridin-3-yl)ethyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

[0917]

107

TABLE 1B-1

138

Example No
R2
R3
R4
R5

19(H1-1)

139

140

H

19(H1-2)

141

142

H

19(H1-3)

143

144

H

19(H1-4)

145

H
H
H

19(H1-5)

146

147

H

19(H1-6)

148

149

H

19(H1-7)

150

151

H

19(H1-8)

152

153

[0918]

108

TABLE 1B-2

154

Example No
R2
R3
R4
R5

19(H1-9)

155

156

H

19(H1-10)

157

158

H

19(H1-11)

159

160

H

19(H1-12)

161

162

H

19(H1-13)

163

164

H

19(H1-14)

165

H
H
H

19(H1-15)

166

167

H

19(H1-16)

168

169

[0919]

109

TABLE 1B-3

170

Example No
R2
R3
R4
R5

19(H1-17)

171

172

H

19(H1-18)

173

174

H

19(H1-19)

175

176

H

19(H1-20)

177

178

H

19(H1-21)

179

H
H
H

19(H1-22)

180

181

H

19(H1-23)

182

183

[0920]

110

TABLE 1B-4

184

Example No
R2
R3
R4
R5

19(H1-24)

185

186

H

19(H1-25)

187

188

H

19(H1-26)

189

190

H

19(H1-27)

191

192

H

19(H1-28)

193

H
H
H

19(H1-29)

194

195

H

19(H1-30)

196

197

H

19(H1-31)

198

199

[0921]

111

TABLE 1B-5

200

Example No
R2
R3
R4
R5

19(H1-32)

201

202

H

19(H1-33)

203

204

H

19(H1-34)

205

206

H

19(H1-35)

207

H
H
H

19(H1-36)

208

209

H

19(H1-37)

210

211

H

19(H1-38)

212

213

H

19(H1-39)

214

215

H

19(H1-40)

216

217

[0922]

112

TABLE 1B-6

218

Example No
R2
R3
R4
R5

19(H1-41)

219

220

H

19(H1-42)

221

H
H
H

19(H1-43)

222

223

H

19(H1-44)

224

225

H

19(H1-45)

226

227

H

19(H1-46)

228

229

H

19(H1-47)

230

231

H

19(H1-48)

232

233

[0923]

113

TABLE 1B-7

234

Example No
R2
R3
R4
R5

19(H1-49)

235

H
H
H

19(H1-50)

236

237

H

19(H1-51)

238

239

H

19(H1-52)

240

241

H

19(H1-53)

242

243

H

19(H1-54)

244

245

H

19(H1-55)

246

247

[0924]

114

TABLE 2B-1

248

Example No
R2
R3
R4
R5

19(H2-1)

249

H
H
H

19(H2-2)

250

251

H

19(H2-3)

252

253

H

19(H2-4)

254

255

H

19(H2-5)

256

257

H

19(H2-6)

258

H
H
H

19(H2-7)

259

260

H

19(H2-8)

261

262

[0925]

115

TABLE 2B-2

263

Example No
R2
R3
R4
R5

19(H2-9)

264

265

H

19(H2-10)

266

267

H

19(H2-11)

268

269

H

19(H2-12)

270

271

H

19(H2-13)

272

H
H
H

19(H2-14)

273

274

H

19(H2-15)

275

276

[0926]

116

TABLE 2B-3

277

Example No
R2
R3
R4
R5

19(H2-16)

278

279

H

19(H2-17)

280

281

H

19(H2-18)

282

283

H

19(H2-19)

284

285

H

19(H2-20)

286

H
H
H

19(H2-21)

287

288

H

19(H2-22)

289

290

H

19(H2-23)

291

292

[0927]

117

TABLE 2B-4

293

Example No
R2
R3
R4
R5

19(H2-24)

294

295

H

19(H2-25)

296

297

H

19(H2-26)

298

299

H

19(H2-27)

300

H
H
H

19(H2-28)

301

302

H

19(H2-29)

303

304

H

19(H2-30)

305

306

H

19(H2-31)

307

308

[0928]

118

TABLE 2B-5

309

Example No
R2
R3
R4
R5

19(H2-32)

310

311

H

19(H2-33)

312

313

H

19(H2-34)

314

H
H
H

19(H2-35)

315

316

H

19(H2-36)

317

318

H

19(H2-37)

319

320

H

19(H2-38)

321

322

H

19(H2-39)

323

324

[0929]

119

TABLE 2B-6

325

Example No
R2
R3
R4
R5

19(H2-40)

326

327

H

19(H2-41)

328

H
H
H

19(H2-42)

329

330

H

19(H2-43)

331

332

H

19(H2-44)

333

334

H

19(H2-45)

335

336

H

19(H2-46)

337

338

H

19(H2-47)

339

340

H

19(H2-48)

341

H
H
H

[0930]

120

TABLE 2B-7

342

Example No
R2
R3
R4
R5

19(H2-49)

343

344

H

19(H2-50)

345

346

H

19(H2-51)

347

348

H

19(H2-52)

349

350

H

19(H2-53)

351

352

H

19(H2-54)

353

354

H

19(H2-55)

355

H
H
H

19(H2-56)

356

357

[0931]

121

TABLE 2B-8

358

Example No
R2
R3
R4
R5

19(H2-57)

359

360

H

19(H2-58)

361

362

H

19(H2-59)

363

364

H

19(H2-60)

365

366

H

19(H2-61)

367

368

[0932]

122

TABLE 3B-1

369

Example No
R2
R3
R4
R5

19(H3-1)

370

H
H
H

19(H3-2)

371

372

H

19(H3-3)

373

374

H

19(H3-4)

375

376

H

19(H3-5)

377

378

H

19(H3-6)

379

380

H

19(H3-7)

381

382

H

19(H3-8)

383

H
H
H

[0933]

123

TABLE 3B-2

384

Example No
R2
R3
R4
R5

19(H3-9)

385

386

H

19(H3-10)

387

388

H

19(H3-11)

389

390

H

19(H3-12)

391

392

H

19(H3-13)

393

394

H

19(H3-14)

395

396

H

19(H3-15)

397

H
H
H

19(H3-16)

398

399

[0934]

124

TABLE 3B-3

400

Example No
R2
R3
R4
R5

19(H3-17)

401

402

H

19(H3-18)

403

404

H

19(H3-19)

405

406

H

19(H3-20)

407

408

H

19(H3-21)

409

410

H

19(H3-22)

411

H
H
H

19(H3-23)

412

413

H

19(H3-24)

414

415

[0935]

125

TABLE 3B-4

416

Example No
R2
R3
R4
R5

19(H3-25)

417

418

H

19(H3-26)

419

420

H

19(H3-27)

421

422

H

19(H3-28)

423

424

H

19(H3-29)

425

H
H
H

19(H3-30)

426

427

H

19(H3-31)

428

429

[0936]

126

TABLE 3B-5

430

Example No
R2
R3
R4
R5

19(H3-32)

431

432

H

19(H3-33)

433

434

H

19(H3-34)

435

436

H

19(H3-35)

437

438

H

19(H3-36)

439

H
H
H

19(H3-37)

440

441

H

19(H3-38)

442

443

H

19(H3-39)

444

445

[0937]

127

TABLE 3B-6

446

Example No
R2
R3
R4
R5

19(H3-40)

447

448

H

19(H3-41)

449

450

H

19(H3-42)

451

452

H

19(H3-43)

453

H
H
H

19(H3-44)

454

455

H

19(H3-45)

456

457

H

19(H3-46)

458

459

H

19(H3-47)

460

461

H

19(H3-48)

462

463

[0938]

128

TABLE 3B-7

464

Example No
R2
R3
R4
R5

19(H3-49)

465

466

H

19(H3-50)

467

H
H
H

19(H3-51)

468

469

H

19(H3-52)

470

471

H

19(H3-53)

472

473

H

19(H3-54)

474

475

H

19(H3-55)

476

477

H

19(H3-56)

478

479

[0939]

129

TABLE 3B-8

480

Example No
R2
R3
R4
R5

19(H3-57)

481

H
H
H

19(H3-58)

482

483

H

19(H3-59)

484

485

H

19(H3-60)

486

487

H

19(H3-61)

488

489

H

19(H3-62)

490

491

H

19(H3-63)

492

493

[0940]

130

TABLE 4B-1

494

Example No
R2
R3
R4
R5

19(H4-1)

495

H
H
H

19(H4-2)

496

497

H

19(H4-3)

498

499

H

19(H4-4)

500

501

H

19(H4-5)

502

503

H

19(H4-6)

504

505

H

19(H4-7)

506

507

H

19(H4-8)

508

H
H
H

[0941]

131

TABLE 4B-2

509

Example No
R2
R3
R4
R5

19(H4-9)

510

511

H

19(H4-10)

512

513

H

19(H4-11)

514

515

H

19(H4-12)

516

517

H

19(H4-13)

518

519

H

19(H4-14)

520

521

H

19(H4-15)

522

H
H
H

19(H4-16)

523

524

[0942]

132

TABLE 4B-3

525

Example No
R2
R3
R4
R5

19(H4-17)

526

527

H

19(H4-18)

528

529

H

19(H4-19)

530

531

H

19(H4-20)

532

533

H

19(H4-21)

534

535

H

19(H4-22)

536

H
H
H

19(H4-23)

537

538

H

19(H4-24)

539

540

[0943]

133

TABLE 4B-4

541

Example No
R2
R3
R4
R5

19(H4-25)

542

543

H

19(H4-26)

544

545

H

19(H4-27)

546

547

H

19(H4-28)

548

549

H

19(H4-29)

550

H
H
H

19(H4-30)

551

552

H

19(H4-31)

553

554

[0944]

134

TABLE 4B-5

555

Example No
R2
R3
R4
R5

19(H4-32)

556

557

H

19(H4-33)

558

559

H

19(H4-34)

560

561

H

19(H4-35)

562

563

H

19(H4-36)

564

H
H
H

19(H4-37)

565

566

H

19(H4-38)

567

568

H

19(H4-39)

569

570

[0945]

135

TABLE 4B-6

571

Example No
R2
R3
R4
R5

19(H4-40)

572

573

H

19(H4-41)

574

575

H

19(H4-42)

576

577

H

19(H4-43)

578

H
H
H

19(H4-44)

579

580

H

19(H4-45)

581

582

H

19(H4-46)

583

584

H

19(H4-47)

585

586

H

19(H4-48)

587

588

[0946]

136

TABLE 4B-7

589

Example No
R2
R3
R4
R5

19(H4-49)

590

591

H

19(H4-50)

592

H
H
H

19(H4-51)

593

594

H

19(H4-52)

595

596

H

19(H4-53)

597

598

H

19(H4-54)

599

600

H

19(H4-55)

601

602

H

19(H4-56)

603

604

[0947]

137

TABLE 4B-8

605

Example No
R2
R3
R4
R5

19(H4-57)

606

H
H
H

19(H4-58)

607

608

H

19(H4-59)

609

610

H

19(H4-60)

611

612

H

19(H4-61)

613

614

H

19(H4-62)

615

616

H

19(H4-63)

617

618

[0948]

138

TABLE 5B-1

619

Example No
R2
R3
R4
R5

19(H5-1)

620

H
H
H

19(H5-2)

621

622

H

19(H5-3)

623

624

H

19(H5-4)

625

626

H

19(H5-5)

627

628

H

19(H5-6)

629

630

H

19(H5-7)

631

632

H

19(H5-8)

633

H
H
H

[0949]

139

TABLE 5B-2

634

Example No
R2
R3
R4
R5

19(H5-9)

635

636

H

19(H5-10)

637

638

H

19(H5-11)

639

640

H

19(H5-12)

641

642

H

19(H5-13)

643

644

H

19(H5-14)

645

646

H

19(H5-15)

647

H
H
H

19(H5-16)

648

649

[0950]

140

TABLE 5B-3

650

Example No
R2
R3
R4
R5

19(H5-17)

651

652

H

19(H5-18)

653

654

H

19(H5-19)

655

656

H

19(H5-20)

657

658

H

19(H5-21)

659

660

H

19(H5-22)

661

H
H
H

19(H5-23)

662

663

H

19(H5-24)

664

665

[0951]

141

TABLE 5B-4

666

Example No
R2
R3
R4
R5

19(H5-25)

667

668

H

19(H5-26)

669

670

H

19(H5-27)

671

672

H

19(H5-28)

673

674

H

19(H5-29)

675

H
H
H

19(H5-30)

676

677

H

19(H5-31)

678

679

[0952]

142

TABLE 5B-5

680

Example No
R2
R3
R4
R5

19(H5-32)

681

682

H

19(H5-33)

683

684

H

19(H5-34)

685

686

H

19(H5-35)

687

688

H

19(H5-36)

689

H
H
H

19(H5-37)

690

691

H

19(H5-38)

692

693

H

19(H5-39)

694

695

[0953]

143

TABLE 5B-6

696

Example No
R2
R3
R4
R5

19(H5-40)

697

698

H

19(H5-41)

699

700

H

19(H5-42)

701

702

H

19(H5-43)

703

H
H
H

19(H5-44)

704

705

H

19(H5-45)

706

707

H

19(H5-46)

708

709

H

19(H5-47)

710

711

H

19(H5-48)

712

713

[0954]

144

TABLE 5B-7

714

Example No
R2
R3
R4
R5

19(H5-49)

715

716

H

19(H5-50)

717

H
H
H

19(H5-51)

718

719

H

19(H5-52)

720

721

H

19(H5-53)

722

723

H

19(H5-54)

724

725

H

19(H5-55)

726

727

H

19(H5-56)

728

729

[0955]

145

TABLE 5B-8

730

Example No
R2
R3
R4
R5

19(H5-57)

731

732

H

19(H5-58)

733

734

H

19(H5-59)

735

736

H

19(H5-60)

737

738

H

19(H5-61)

739

740

H

19(H5-62)

741

742

[0956]

146

TABLE 6B-1

743

Example No
R2
R3
R4
R5

19(H6-1)

744

H
H
H

19(H6-2)

745

746

H

19(H6-3)

747

H
H
H

19(H6-4)

748

749

H

19(H6-5)

750

751

H

19(H6-6)

752

753

H

19(H6-7)

754

755

H

19(H6-8)

756

757

[0957]

147

TABLE 6B-2

758

Example No
R2
R3
R4
R5

19(H6-9)

759

760

H

19(H6-10)

761

H
H
H

19(H6-11)

762

763

H

19(H6-12)

764

765

H

19(H6-13)

766

767

H

19(H6-14)

768

769

H

19(H6-15)

770

771

H

19(H6-16)

772

773

[0958]

148

TABLE 6B-3

774

Example No
R2
R3
R4
R5

19(H6-17)

775

H
H
H

19(H6-18)

776

777

H

19(H6-19)

778

779

H

19(H6-20)

780

781

H

19(H6-21)

782

783

H

19(H6-22)

784

785

H

19(H6-23)

786

787

H

19(H6-24)

788

H
H
H

[0959]

149

TABLE 6B-4

789

Example No
R2
R3
R4
R5

19(H6-25)

790

791

H

19(H6-26)

792

793

H

19(H6-27)

794

795

H

19(H6-28)

796

797

H

19(H6-29)

798

799

H

19(H6-30)

800

801

H

19(H6-31)

802

H
H
H

19(H6-32)

803

804

[0960]

150

TABLE 6B-5

805

Example No
R2
R3
R4
R5

19(H6-33)

806

807

H

19(H6-34)

808

809

H

19(H6-35)

810

811

H

19(H6-36)

812

813

H

19(H6-37)

814

815

H

19(H6-38)

816

H
H
H

19(H6-39)

817

818

H

19(H6-40)

819

820

[0961]

151

TABLE 6B-6

821

Example No
R2
R3
R4
R5

19(H6-41)

822

823

H

19(H6-42)

824

825

H

19(H6-43)

826

827

H

19(H6-44)

828

829

H

19(H6-45)

830

H
H
H

19(H6-46)

831

832

H

19(H6-47)

833

834

H

19(H6-48)

835

836

[0962]

152

TABLE 6B-7

837

Example No
R2
R3
R4
R5

19(H6-49)

838

839

H

19(H6-50)

840

841

H

19(H6-51)

842

843

H

19(H6-52)

844

H
H
H

19(H6-53)

845

846

H

19(H6-54)

847

848

H

19(H6-55)

849

850

H

19(H6-56)

851

852

[0963]

153

TABLE 6B-8

853

Example No
R2
R3
R4
R5

19(H6-57)

854

855

H

19(H6-58)

856

857

[0964]

154

TABLE 7B-1

858

Example

No
R2
R3
R4
R5

19(H7-1)

859

H
H
H

19(H7-2)

860

861

H

19(H7-3)

862

863

H

19(H7-4)

864

865

H

19(H7-5)

866

867

H

19(H7-6)

868

H
H
H

19(H7-7)

869

870

H

19(H7-8)

871

872

[0965]

155

TABLE 7B-2

873

Example No
R2
R3
R4
R5

19(H7-9)

874

875

H

19(H7-10)

876

877

H

19(H7-11)

878

879

H

19(H7-12)

880

881

H

19(H7-13)

882

H
H
H

19(H7-14)

883

884

H

19(H7-15)

885

886

[0966]

156

TABLE 7B-3

887

Example No
R2
R3
R4
R5

19(H7-16)

888

889

H

19(H7-17)

890

891

H

19(H7-18)

892

893

H

19(H7-19)

894

895

H

19(H7-20)

896

H
H
H

19(H7-21)

897

898

H

19(H7-22)

899

900

H

19(H7-23)

901

902

[0967]

157

TABLE 7B-4

903

Example No
R2
R3
R4
R5

19(H7-24)

904

905

H

19(H7-25)

906

907

H

19(H7-26)

908

909

H

19(H7-27)

910

H
H
H

19(H7-28)

911

912

H

19(H7-29)

913

914

H

19(H7-30)

915

916

H

19(H7-31)

917

918

[0968]

158

TABLE 7B-5

919

Example No
R2
R3
R4
R5

19(H7-32)

920

921

H

19(H7-33)

922

923

H

19(H7-34)

924

925

H

19(H7-35)

926

927

H

19(H7-36)

928

929

H

19(H7-37)

930

931

H

19(H7-38)

932

933

H

19(H7-39)

934

935

[0969]

159

TABLE 7B-6

936

Example No
R2
R3
R4
R5

19(H7-40)

937

H
H
H

19(H7-41)

938

939

H

19(H7-42)

940

941

H

19(H7-43)

942

943

H

19(H7-44)

944

945

H

19(H7-45)

946

947

H

19(H7-46)

948

949

H

19(H7-47)

950

H
H
H

19(H7-48)

951

952

[0970]

160

TABLE 7B-7

953

Example No
R2
R3
R4
R5

19(H7-49)

954

955

H

19(H7-50)

956

957

H

19(H7-51)

958

959

H

19(H7-52)

960

961

H

19(H7-53)

962

963

H

19(H7-54)

964

H
H
H

19(H7-55)

965

966

H

19(H7-56)

967

968

[0971]

161

TABLE 7B-8

969

Example No
R2
R3
R4
R5

19(H7-57)

970

971

H

19(H7-58)

972

973

H

19(H7-59)

974

975

H

19(H7-60)

976

977

[0972]

162

TABLE 8B-1

978

Example No
R2
R3
R4
R5

19(H8-1)

979

980

H

19(H8-2)

981

982

H

19(H8-3)

983

H
H
H

19(H8-4)

984

985

H

19(H8-5)

986

987

H

19(H8-6)

988

989

H

19(H8-7)

990

991

H

19(H8-8)

992

993

[0973]

163

TABLE 8B-2

994

Example No
R2
R3
R4
R5

19(H8-9)

995

996

H

19(H8-10)

997

H
H
H

19(H8-11)

998

999

H

19(H8-12)

1000

1001

H

19(H8-13)

1002

1003

H

19(H8-14)

1004

1005

H

19(H8-15)

1006

1007

H

19(H8-16)

1008

1009

[0974]

164

TABLE 8B-3

1010

Example No
R2
R3
R4
R5

19(H8-17)

1011

H
H
H

19(H8-18)

1012

1013

H

19(H8-19)

1014

1015

H

19(H8-20)

1016

1017

H

19(H8-21)

1018

1019

H

19(H8-22)

1020

1021

H

19(H8-23)

1022

1023

H

19(H8-24)

1024

H
H
H

[0975]

165

TABLE 8B-4

1025

Example No
R2
R3
R4
R5

19(H8-25)

1026

1027

H

19(H8-26)

1028

1029

H

19(H8-27)

1030

1031

H

19(H8-28)

1032

1033

H

19(H8-29)

1034

1035

H

19(H8-30)

1036

1037

H

19(H8-31)

1038

H
H
H

19(H8-32)

1039

1040

[0976]

166

TABLE 8B-5

1041

Example No
R2
R3
R4
R5

19(H8-33)

1042

1043

H

19(H8-34)

1044

1045

H

19(H8-35)

1046

1047

H

19(H8-36)

1048

1049

H

19(H8-37)

1050

1051

H

19(H8-38)

1052

H
H
H

19(H8-39)

1053

1054

H

19(H8-40)

1055

1056

[0977]

167

TABLE 8B-6

1057

Example No
R2
R3
R4
R5

19(H8-41)

1058

1059

H

19(H8-42)

1060

1061

H

19(H8-43)

1062

1063

H

19(H8-44)

1064

1065

H

19(H8-45)

1066

H
H
H

19(H8-46)

1067

1068

H

19(H8-47)

1069

1070

H

19(H8-48)

1071

1072

[0978]

168

TABLE 8B-7

1073

Example No
R2
R3
R4
R5

19(H8-49)

1074

1075

H

19(H8-50)

1076

1077

H

19(H8-51)

1078

H
H
H

19(H8-52)

1079

1080

H

19(H8-53)

1081

1082

H

19(H8-54)

1083

1084

H

19(H8-55)

1085

1086

H

19(H8-56)

1087

1088

[0979]

169

TABLE 8B-8

1089

Example No
R2
R3
R4
R5

19(H8-57)

1090

1091

[0980]

170

TABLE 9B-1

1092

Example No
R2

19(H9-1)

1093

19(H9-2)

1094

19(H9-3)

1095

19(H9-4)

1096

19(H9-5)

1097

19(H9-6)

1098

19(H9-7)

1099

19(H9-8)

1100

[0981]

171

TABLE 9B-2

1101

Example No
R2

19(H9-9)

1102

19(H9-10)

1103

19(H9-11)

1104

19(H9-12)

1105

19(H9-13)

1106

19(H9-14)

1107

19(H9-15)

1108

19(H9-16)

1109

[0982]

172

TABLE 9B-3

1110

Example No
R2

19(H9-17)

1111

19(H9-18)

1112

19(H9-19)

1113

19(H9-20)

1114

19(H9-21)

1115

19(H9-22)

1116

19(H9-23)

1117

19(H9-24)

1118

[0983]

173

TABLE 9B-4

1119

Example No
R2

19(H9-25)

1120

19(H9-26)

1121

19(H9-27)

1122

19(H9-28)

1123

19(H9-29)

1124

19(H9-30)

1125

19(H9-31)

1126

19(H9-32)

1127

[0984]

174

TABLE 9B-5

1128

Example No
R2

19(H9-33)

1129

19(H9-34)

1130

19(H9-35)

1131

19(H9-36)

1132

19(H9-37)

1133

19(H9-38)

1134

19(H9-39)

1135

19(H9-40)

1136

19(H9-41)

1137

19(H9-42)

1138

19(H9-43)

1139

[0985]

175

TABLE 9B-6

1140

Example No
R2

19(H9-44)

1141

19(H9-45)

1142

19(H9-46)

1143

19(H9-47)

1144

19(H9-48)

1145

19(H9-49)

1146

19(H9-50)

1147

19(H9-51)

1148

19(H9-52)

1149

19(H9-53)

1150

19(H9-54)

1151

[0986]

176

TABLE 9B-7

1152

Example No
R2

19(H9-55)

1153

19(H9-56)

1154

19(H9-57)

1155

19(H9-58)

1156

19(H9-59)

1157

19(H9-60)

1158

19(H9-61)

1159

19(H9-62)

1160

[0987]

177

TABLE 10B-1

1161

Example No
R2

19(H10-1)

1162

19(H10-2)

1163

19(H10-3)

1164

19(H10-4)

1165

19(H10-5)

1166

19(H10-6)

1167

19(H10-7)

1168

19(H10-8)

1169

[0988]

178

TABLE 10B-2

1170

Example No
R2

19(H10-9)

1171

19(H10-10)

1172

19(H10-11)

1173

19(H10-12)

1174

19(H10-13)

1175

19(H10-14)

1176

19(H10-15)

1177

19(H10-16)

1178

[0989]

179

TABLE 10B-3

1179

Example No
R2

19(H10-17)

1180

19(H10-18)

1181

19(H10-19)

1182

19(H10-20)

1183

19(H10-21)

1184

19(H10-22)

1185

19(H10-23)

1186

19(H10-24)

1187

[0990]

180

TABLE 10B-4

1188

Example No
R2

19(H10-25)

1189

19(H10-26)

1190

19(H10-27)

1191

19(H10-28)

1192

19(H10-29)

1193

19(H10-30)

1194

19(H10-31)

1195

19(H10-32)

1196

[0991]

181

TABLE 10B-5

1197

Example No
R2

19(H10-33)

1198

19(H10-34)

1199

19(H10-35)

1200

19(H10-36)

1201

19(H10-37)

1202

19(H10-38)

1203

19(H10-39)

1204

19(H10-40)

1205

19(H10-41)

1206

[0992]

182

TABLE 10B-6

1207

Example No
R2

19(H10-42)

1208

19(H10-43)

1209

19(H10-44)

1210

19(H10-45)

1211

19(H10-46)

1212

19(H10-47)

1213

19(H10-48)

1214

19(H10-49)

1215

19(H10-50)

1216

19(H10-51)

1217

19(H10-52)

1218

19(H10-53)

1219

[0993]

183

TABLE 10B-7

1220

Example No
R2

19(H10-54)

1221

19(H10-55)

1222

19(H10-56)

1223

19(H10-57)

1224

19(H10-58)

1225

19(H10-59)

1226

19(H10-60)

1227

19(H10-61)

1228

19(H10-62)

1229

[0994]

184

TABLE 10B-8

1230

Example No
R2

19(H10-63)

1231

19(H10-64)

1232

19(H10-65)

1233

19(H10-66)

1234

19(H10-67)

1235

19(H10-68)

1236

[0995]

185

TABLE 11B-1

1237

Example No
R2

19(H11-1)

1238

19(H11-2)

1239

19(H11-3)

1240

19(H11-4)

1241

19(H11-5)

1242

19(H11-6)

1243

19(H11-7)

1244

19(H11-8)

1245

[0996]

186

TABLE 11B-2

1246

Example No
R2

19(H11-9)

1247

19(H11-10)

1248

19(H11-11)

1249

19(H11-12)

1250

19(H11-13)

1251

19(H11-14)

1252

19(H11-15)

1253

19(H11-16)

1254

[0997]

187

TABLE 11B-3

1255

Example No
R2

19(H11-17)

1256

19(H11-18)

1257

19(H11-19)

1258

19(H11-20)

1259

19(H11-21)

1260

19(H11-22)

1261

19(H11-23)

1262

19(H11-24)

1263

[0998]

188

TABLE 11B-4

1264

Example No
R2

19(H11-25)

1265

19(H11-26)

1266

19(H11-27)

1267

19(H11-28)

1268

19(H11-29)

1269

19(H11-30)

1270

19(H11-31)

1271

19(H11-32)

1272

19(H11-33)

1273

[0999]

189

TABLE 11B-5

1274

Example No
R2

19(H11-34)

1275

19(H11-35)

1276

19(H11-36)

1277

19(H11-37)

1278

19(H11-38)

1279

19(H11-39)

1280

19(H11-40)

1281

19(H11-41)

1282

19(H11-42)

1283

19(H11-43)

1284

19(H11-44)

1285

19(H11-45)

1286

[1000]

190

TABLE 11B-6

1287

Example No
R2

19(H11-46)

1288

19(H11-47)

1289

19(H11-48)

1290

19(H11-49)

1291

19(H11-50)

1292

19(H11-51)

1293

19(H11-52)

1294

19(H11-53)

1295

19(H11-54)

1296

19(H11-55)

1297

[1001]

191

TABLE 11B-7

1298

Example No
R2

19(H11-56)

1299

19(H11-57)

1300

19(H11-58)

1301

[1002]

192

TABLE 12B-1

1302

Example No
R2

19(H12-1)

1303

19(H12-2)

1304

19(H12-3)

1305

19(H12-4)

1306

19(H12-5)

1307

19(H12-6)

1308

19(H12-7)

1309

19(H12-8)

1310

[1003]

193

TABLE 12B-2

1311

Example No
R2

19(H12-9)

1312

19(H12-9)

1313

19(H12-9)

1314

19(H12-9)

1315

19(H12-9)

1316

19(H12-9)

1317

19(H12-9)

1318

19(H12-9)

1319

[1004]

194

TABLE 12B-3

1320

Example No
R2

19(H12-17)

1321

19(H12-18)

1322

19(H12-19)

1323

19(H12-20)

1324

19(H12-21)

1325

19(H12-22)

1326

19(H12-23)

1327

19(H12-24)

1328

[1005]

195

TABLE 12B-4

1329

Example No
R2

19(H12-25)

1330

19(H12-26)

1331

19(H12-27)

1332

19(H12-28)

1333

19(H12-29)

1334

19(H12-30)

1335

19(H12-31)

1336

19(H12-32)

1337

[1006]

196

TABLE 12B-5

1338

Example No
R2

19(H12-33)

1339

19(H12-34)

1340

19(H12-35)

1341

19(H12-36)

1342

19(H12-37)

1343

19(H12-38)

1344

19(H12-39)

1345

19(H12-40)

1346

19(H12-41)

1347

[1007]

197

TABLE 12B-6

1348

Example No
R2

19(H12-42)

1349

19(H12-43)

1350

19(H12-44)

1351

19(H12-45)

1352

19(H12-46)

1353

19(H12-47)

1354

19(H12-48)

1355

19(H12-49)

1356

19(H12-50)

1357

19(H12-51)

1358

19(H12-52)

1359

19(H12-53)

1360

[1008]

198

TABLE 12B-7

1361

Example No
R2

19(H12-54)

1362

19(H12-54)

1363

19(H12-54)

1364

19(H12-54)

1365

19(H12-54)

1366

19(H12-54)

1367

19(H12-54)

1368

19(H12-54)

1369

19(H12-54)

1370

19(H12-54)

1371

[1009]

199

TABLE 12B-8

1372

Example No
R2

19(H12-64)

1373

19(H12-65)

1374

19(H12-66)

1375

19(H12-67)

1376

19(H12-68

1377

19(H12-69)

1378

[1010]

200

TABLE 13B-1

1379

Example No
R2

19(H13-1)

1380

19(H13-2)

1381

19(H13-3)

1382

19(H13-4)

1383

19(H13-5)

1384

19(H13-6)

1385

19(H13-7)

1386

19(H13-8)

1387

[1011]

201

TABLE 13B-2

1388

Example No
R2

19(H13-9)

1389

19(H13-10)

1390

19(H13-11)

1391

19(H13-12)

1392

19(H13-13)

1393

19(H13-14)

1394

19(H13-15)

1395

19(H13-16)

1396

[1012]

202

TABLE 13B-3

1397

Example No
R2

19(H13-17)

1398

19(H13-18)

1399

19(H13-19)

1400

19(H13-20)

1401

19(H13-21)

1402

19(H13-22)

1403

19(H13-23)

1404

19(H13-24)

1405

[1013]

203

TABLE 13B-4

1406

Example No
R2

19(H13-25)

1407

19(H13-26)

1408

19(H13-27)

1409

19(H13-28)

1410

19(H13-29)

1411

19(H13-31)

1412

19(H13-32)

1413

[1014]

204

TABLE 13B-5

1414

Example No
R2

19(H13-33)

1415

19(H13-34)

1416

19(H13-35)

1417

19(H13-36)

1418

19(H13-37)

1419

19(H13-38)

1420

19(H13-39)

1421

19(H13-40)

1422

19(H13-41)

1423

19(H13-42)

1424

19(H13-43)

1425

19(H13-44)

1426

[1015]

205

TABLE 13B-6

1427

Example No
R2

19(H13-45)

1428

19(H13-46)

1429

19(H13-47)

1430

19(H13-48)

1431

19(H13-49)

1432

19(H13-50)

1433

19(H13-51)

1434

19(H13-52)

1435

19(H13-53)

1436

19(H13-54)

1437

[1016]

206

TABLE 13B-7

1438

Example No
R2

19(H13-55)

1439

19(H13-56)

1440

19(H13-57)

1441

19(H13-58)

1442

19(H13-59)

1443

19(H13-60)

1444

19(H13-61)

1445

19(H13-62)

1446

[1017]

207

TABLE 1C-1

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

19(H1-1)
F
3.16
410 (M + H)+.
ESI (Pos., 20 V)

19(H1-2)
F
3.17
483 (M + H)+.
ESI (Pos., 20 V)

19(H1-3)
F
4.24
502 (M + H)+.
ESI (Pos., 20 V)

19(H1-4)
F
2.83
358 (M + H)+.
ESI (Pos., 20 V)

19(H1-5)
F
3.09
415 (M + H)+.
ESI (Pos., 20 V)

19(H1-6)
F
3.11
448 (M + H)+.
ESI (Pos., 20 V)

19(H1-7)
F
3.11
487 (M + H)+.
ESI (Pos., 20 V)

19(H1-8)
F
3.17
478 (M + H)+.
ESI (Pos., 20 V)

19(H1-9)
F
3.23
506 (M + H)+.
ESI (Pos., 20 V)

19(H1-10)
F
3.25
563 (M + H)+.
ESI (Pos., 20 V)

19(H1-11)
F
3.35
473 (M + H)+.
ESI (Pos., 20 V)

19(H1-12)
F
3.32
546 (M + H)+.
ESI (Pos., 20 V)

19(H1-13)
F
3.37
537 (M + H)+.
ESI (Pos., 20 V)

19(H1-14)
F
3.01
364 (M + H)+.
ESI (Pos., 20 V)

19(H1-15)
F
3.25
420 (M + H)+.
ESI (Pos., 20 V)

19(H1-16)
F
3.24
454 (M + H)+.
ESI (Pos., 20 V)

19(H1-17)
F
3.23
493 (M + H)+.
ESI (Pos., 20 V)

19(H1-18)
F
3.29
484 (M + H)+.
ESI (Pos., 20 V)

19(H1-19)
F
3.36
512 (M + H)+.
ESI (Pos., 20 V)

19(H1-20)
F
3.38
569 (M + H)+.
ESI (Pos., 20 V)

19(H1-21)
F
3.26
454 (M + H)+.
ESI (Pos., 20 V)

19(H1-22)
F
3.52
510 (M + H)+.
ESI (Pos., 20 V)

19(H1-23)
F
3.51
544 (M + H)+.
ESI (Pos., 20 V)

19(H1-24)
F
3.48
583 (M + H)+.
ESI (Pos., 20 V)

19(H1-25)
F
3.53
574 (M + H)+.
ESI (Pos., 20 V)

19(H1-26)
F
3.59
602 (M + H)+.
ESI (Pos., 20 V)

[1018]

208

TABLE 1C-2

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

19(H1-27)
F
3.56
659 (M + H)+.
ESI (Pos., 20 V)

19(H1-28)
F
3.07
378 (M + H)+.
ESI (Pos., 20 V)

19(H1-29)
F
3.31
434 (M + H)+.
ESI (Pos., 20 V)

19(H1-30)
F
3.30
468 (M + H)+.
ESI (Pos., 20 V)

19(H1-31)
F
3.29
507 (M + H)+.
ESI (Pos., 20 V)

19(H1-32)
F
3.35
498 (M + H)+.
ESI (Pos., 20 V)

19(H1-33)
F
3.40
526 (M + H)+.
ESI (Pos., 20 V)

19(H1-34)
F
3.41
583 (M + H)+.
ESI (Pos., 20 V)

19(H1-35)
F
2.84
316 (M + H)+.
ESI (Pos., 20 V)

19(H1-36)
F
3.11
372 (M + H)+.
ESI (Pos., 20 V)

19(H1-37)
F
3.11
406 (M + H)+.
ESI (Pos., 20 V)

19(H1-38)
F
3.09
445 (M + H)+.
ESI (Pos., 20 V)

19(H1-39)
F
3.18
436 (M + H)+.
ESI (Pos., 20 V)

19(H1-40)
F
3.22
464 (M + H)+.
ESI (Pos., 20 V)

19(H1-41)
F
3.26
521 (M + H)+.
ESI (Pos., 20 V)

19(H1-42)
F
3.04
402 (M + H)+.
ESI (Pos., 20 V)

19(H1-43)
F
3.34
458 (M + H)+.
ESI (Pos., 20 V)

19(H1-44)
F
3.36
492 (M + H)+.
ESI (Pos., 20 V)

19(H1-45)
F
3.30
531 (M + H)+.
ESI (Pos., 20 V)

19(H1-46)
F
3.35
522 (M + H)+.
ESI (Pos., 20 V)

19(H1-47)
F
3.39
550 (M + H)+.
ESI (Pos., 20 V)

19(H1-48)
F
3.40
607 (M + H)+.
ESI (Pos., 20 V)

19(H1-49)
F
2.85
433 (M + H)+.
ESI (Pos., 20 V)

19(H1-50)
F
3.03
489 (M + H)+.
ESI (Pos., 20 V)

19(H1-51)
F
3.05
523 (M + H)+.
ESI (Pos., 20 V)

19(H1-52)
F
3.06
562 (M + H)+.
ESI (Pos., 20 V)

[1019]

209

TABLE 1C-3

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

19(H1-53)
F
3.11
553 (M + H)+.
ESI (Pos., 20 V)

19(H1-54)
F
3.14
581 (M + H)+.
ESI (Pos., 20 V)

19(H1-55)
F
3.16
638 (M + H)+.
ESI (Pos., 20 V)

[1020]

210

TABLE 2C-1

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

19(H2-1)
B
10.20
368 (M + H)+.
APCI (Pos., 40 V)

19(H2-2)
F
3.23
497 (M + H)+.
ESI (Pos., 20 V)

19(H2-3)
F
3.73
488 (M + H)+.
ESI (Pos., 20 V)

19(H2-4)
F
3.72
516 (M + H)+.
ESI (Pos., 20 V)

19(H2-5)
C
14.80
573 (M + H)+,
APCI (Pos., 40 V)

465.

19(H2-6)
F
2.91
372 (M + H)+.
ESI (Pos., 20 V)

19(H2-7)
F
3.15
428 (M + H)+.
ESI (Pos., 20 V)

19(H2-8)
F
3.17
462 (M + H)+.
ESI (Pos., 20 V)

19(H2-9)
F
3.17
501 (M + H)+.
ESI (Pos., 20 V)

19(H2-10)
F
3.24
492 (M + H)+.
ESI (Pos., 20 V)

19(H2-11)
F
3.26
520 (M + H)+.
ESI (Pos., 20 V)

19(H2-12)
F
3.30
577 (M + H)+.
ESI (Pos., 20 V)

19(H2-13)
F
3.16
431 (M + H)+.
ESI (Pos., 20 V)

19(H2-14)
F
3.37
487 (M + H)+.
ESI (Pos., 20 V)

19(H2-15)
B
17.50
521 (M + H)+,
APCI (Pos., 40 V)

144.

19(H2-16)
F
3.34
560 (M + H)+.
ESI (Pos., 20 V)

19(H2-17)
F
3.41
551 (M + H)+.
ESI (Pos., 20 V)

19(H2-18)
F
3.44
579 (M + H)+.
ESI (Pos., 20 V)

19(H2-19)
C
15.70
636 (M + H)+,
APCI (Pos., 40 V)

528, 279.

19(H2-20)
F
3.07
378 (M + H)+.
ESI (Pos., 20 V)

19(H2-21)
F
3.30
434 (M + H)+.
ESI (Pos., 20 V)

19(H2-22)
F
3.31
468 (M + H)+.
ESI (Pos., 20 V)

19(H2-23)
F
3.30
507 (M + H)+.
ESI (Pos., 20 V)

19(H2-24)
F
3.36
498 (M + H)+.
ESI (Pos., 20 V)

19(H2-25)
F
3.41
526 (M + H)+.
ESI (Pos., 20 V)

19(H2-26)
F
3.42
583 (M + H)+.
ESI (Pos.. 20 V)

[1021]

211

TABLE 2C-2

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

19(H2-27)
F
3.33
468 (M + H)+.
ESI (Pos., 20 V)

19(H2-28)
F
3.57
524 (M + H)+.
ESI (Pos., 20 V)

19(H2-29)
F
3.55
558 (M + H)+.
ESI (Pos., 20 V)

19(H2-30)
F
3.54
597 (M + H)+.
ESI (Pos., 20 V)

19(H2-31)
F
3.60
588 (M + H)+.
ESI (Pos., 20 V)

19(H2-32)
F
3.65
616 (M + H)+.
ESI (Pos., 20 V)

19(H2-33)
F
3.60
673 (M + H)+.
ESI (Pos., 20 V)

19(H2-34)
F
3.13
392 (M + H)+.
ESI (Pos., 20 V)

19(H2-35)
F
3.37
448 (M + H)+.
ESI (Pos., 20 V)

19(H2-36)
F
3.37
482 (M + H)+.
ESI (Pos., 20 V)

19(H2-37)
F
3.35
521 (M + H)+.
ESI (Pos., 20 V)

19(H2-38)
F
3.42
512 (M + H)+.
ESI (Pos., 20 V)

19(H2-39)
F
3.46
540 (M + H)+.
ESI (Pos., 20 V)

19(H2-40)
F
3.50
597 (M + H)+.
ESI (Pos., 20 V)

19(H2-41)
F
2.92
330 (M + H)+.
ESI (Pos., 20 V)

19(H2-42)
F
3.20
386 (M + H)+.
ESI (Pos., 20 V)

19(H2-43)
F
3.17
420 (M + H)+.
ESI (Pos., 20 V)

19(H2-44)
F
3.17
459 (M + H)+.
ESI (Pos., 20 V)

19(H2-45)
F
3.26
450 (M + H)+.
ESI (Pos., 20 V)

19(H2-46)
F
3.30
478 (M + H)+.
ESI (Pos., 20 V)

19(H2-47)
F
3.32
535 (M + H)+.
ESI (Pos., 20 V)

19(H2-48)
F
3.11
416 (M + H)+.
ESI (Pos., 20 V)

19(H2-49)
F
3.36
472 (M + H)+.
ESI (Pos., 20 V)

19(H2-50)
F
3.34
506 (M + H)+.
ESI (Pos., 20 V)

19(H2-51)
F
3.33
545 (M + H)+.
ESI (Pos., 20 V)

19(H2-52)
F
3.41
536 (M + H)+.
ESI (Pos., 20 V)

[1022]

212

TABLE 2C-3

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

19(H2-53)
F
3.50
564 (M + H)+.
ESI (Pos., 20 V)

19(H2-54)
F
3.50
621 (M + H)+.
ESI (Pos., 20 V)

19(H2-55)
F
2.92
447 (M + H)+.
ESI (Pos., 20 V)

19(H2-56)
F
3.09
503 (M + H)+.
ESI (Pos., 20 V)

19(H2-57)
F
3.09
537 (M + H)+.
ESI (Pos., 20 V)

19(H2-58)
F
3.11
576 (M + H)+.
ESI (Pos., 20 V)

19(H2-59)
F
3.18
567 (M + H)+.
ESI (Pos., 20 V)

19(H2-60)
F
3.20
595 (M + H)+.
ESI (Pos., 20 V)

19(H2-61)
F
3.24
652 (M + H)+.
ESI (Pos., 20 V)

[1023]

213

TABLE 3C-1

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

19(H3-1)
B
10.80
382 (M + H)+.
APCI (Pos., 40 V)

19(H3-2)
F
3.27
438 (M + H)+.
ESI (Pos., 20 V)

19(H3-3)
F
3.28
472 (M + H)+.
ESI (Pos., 20 V)

19(H3-4)
F
3.27
511 (M + H)+.
ESI (Pos., 20 V)

19(H3-5)
F
3.35
502 (M + H)+.
ESI (Pos., 20 V)

19(H3-6)
F
3.37
530 (M + H)+.
ESI (Pos., 20 V)

19(H3-7)
F
2.98
386 (M + H)+.
ESI (Pos., 20 V)

19(H3-8)
F
3.22
442 (M + H)+.
ESI (Pos., 20 V)

19(H3-9)
F
3.23
476 (M + H)+.
ESI (Pos., 20 V)

19(H3-10)
F
3.23
476 (M + H)+.
ESI (Pos., 20 V)

19(H3-11)
F
3.22
515 (M + H)+.
ESI (Pos., 20 V)

19(H3-12)
F
3.29
506 (M + H)+.
ESI (Pos., 20 V)

19(H3-13)
F
3.31
534 (M + H)+.
ESI (Pos., 20 V)

19(H3-14)
F
3.34
591 (M + H)+.
ESI (Pos., 20 V)

19(H3-15)
F
3.20
445 (M + H)+.
ESI (Pos., 20 V)

19(H3-16)
F
3.43
501 (M + H)+.
ESI (Pos., 20 V)

19(H3-17)
F
3.40
535 (M + H)+.
ESI (Pos., 20 V)

19(H3-18)
F
3.39
571 (M + H)+.
ESI (Pos., 20 V)

19(H3-19)
F
3.45
565 (M + H)+.
ESI (Pos., 20 V)

19(H3-20)
F
3.49
593 (M + H)+.
ESI (Pos., 20 V)

19(H3-21)
F
3.49
650 (M + H)+.
ESI (Pos., 20 V)

19(H3-22)
F
3.13
392 (M + H)+.
ESI (Pos., 20 V)

19(H3-23)
F
3.35
448 (M + H)+.
ESI (Pos., 20 V)

19(H3-24)
F
3.34
482 (M + H)+.
ESI (Pos., 20 V)

19(H3-25)
F
3.34
521 (M + H)+.
ESI (Pos., 20 V)

19(H3-26)
F
3.42
512 (M + H)+.
ESI (Pos., 20 V)

[1024]

214

TABLE 3C-2

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

19(H3-27)
F
3.45
540 (M + H)+.
ESI (Pos., 20 V)

19(H3-28)
F
3.46
597 (M + H)+.
ESI (Pos., 20 V)

19(H3-29)
F
3.37
482 (M + H)+.
ESI (Pos., 20 V)

19(H3-30)
F
3.61
538 (M + H)+.
ESI (Pos., 20 V)

19(H3-31)
F
3.61
572 (M + H)+.
ESI (Pos., 20 V)

19(H3-32)
F
3.57
611 (M + H)+.
ESI (Pos., 20 V)

19(H3-33)
F
3.64
602 (M + H)+.
ESI (Pos., 20 V)

19(H3-34)
F
3.68
630 (M + H)+.
ESI (Pos., 20 V)

19(H3-35)
F
3.66
687 (M + H)+.
ESI (Pos., 20 V)

19(H3-36)
F
3.20
406 (M + H)+.
ESI (Pos., 20 V)

19(H3-37)
F
3.43
462 (M + H)+.
ESI (Pos., 20 V)

19(H3-38)
F
3.42
496 (M + H)+.
ESI (Pos., 20 V)

19(H3-39)
F
3.40
535 (M + H)+.
ESI (Pos., 20 V)

19(H3-40)
F
3.48
526 (M + H)+.
ESI (Pos., 20 V)

19(H3-41)
F
3.50
554 (M + H)+.
ESI (Pos., 20 V)

19(H3-42)
F
3.51
611 (M + H)+.
ESI (Pos., 20 V)

19(H3-43)
F
3.01
344 (M + H)+.
ESI (Pos., 20 V)

19(H3-44)
F
3.23
400 (M + H)+.
ESI (Pos., 20 V)

19(H3-45)
F
3.24
434 (M + H)+.
ESI (Pos., 20 V)

19(H3-46)
F
3.25
473 (M + H)+.
ESI (Pos., 20 V)

19(H3-47)
F
3.30
464 (M + H)+.
ESI (Pos., 20 V)

19(H3-48)
F
3.33
492 (M + H)+.
ESI (Pos., 20 V)

19(H3-49)
F
3.37
549 (M + H)+.
ESI (Pos., 20 V)

19(H3-50)
F
3.18
430 (M + H)+.
ESI (Pos., 20 V)

19(H3-51)
F
3.40
486 (M + H)+.
ESI (Pos., 20 V)

19(H3-52)
F
3.40
520 (M + H)+.
ESI (Pos., 20 V)

[1025]

215

TABLE 3C-3

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

19(H3-53)
F
3.40
559 (M + H)+.
ESI (Pos., 20 V)

19(H3-54)
F
3.45
550 (M + H)+.
ESI (Pos., 20 V)

19(H3-55)
F
3.49
578 (M + H)+.
ESI (Pos., 20 V)

19(H3-56)
F
3.51
635 (M + H)+.
ESI (Pos., 20 V)

19(H3-57)
F
2.98
461 (M + H)+.
ESI (Pos., 20 V)

19(H3-58)
F
3.14
517 (M + H)+.
ESI (Pos., 20 V)

19(H3-59)
F
3.14
551 (M + H)+.
ESI (Pos., 20 V)

19(H3-60)
F
3.15
590 (M + H)+.
ESI (Pos., 20 V)

19(H3-61)
F
3.21
581 (M + H)+.
ESI (Pos., 20 V)

19(H3-62)
F
3.24
609 (M + H)+.
ESI (Pos., 20 V)

19(H3-63)
F
3.27
666 (M + H)+.
ESI (Pos., 20 V)

[1026]

216

TABLE 4C-1

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

19(H4-1)
F
3.14
396 (M + H)+.
ESI (Pos., 20 V)

19(H4-2)
F
3.36
453 (M + H)+.
ESI (Pos., 20 V)

19(H4-3)
F
3.35
486 (M + H)+.
ESI (Pos., 20 V)

19(H4-4)
F
3.36
525 (M + H)+.
ESI (Pos., 20 V)

19(H4-5)
F
3.41
516 (M + H)+.
ESI (Pos., 20 V)

19(H4-6)
F
3.45
544 (M + H)+.
ESI (Pos., 20 V)

19(H4-7)
F
3.45
601 (M + H)+.
ESI (Pos., 20 V)

19(H4-8)
F
3.05
400 (M + H)+.
ESI (Pos., 20 V)

19(H4-9)
F
3.29
456 (M + H)+.
ESI (Pos., 20 V)

19(H4-10)
F
3.29
490 (M + H)+.
ESI (Pos., 20 V)

19(H4-11)
F
3.29
529 (M + H)+.
ESI (Pos., 20 V)

19(H4-12)
F
3.36
520 (M + H)+.
ESI (Pos., 20 V)

19(H4-13)
F
3.38
548 (M + H)+.
ESI (Pos., 20 V)

19(H4-14)
F
3.42
605 (M + H)+.
ESI (Pos., 20 V)

19(H4-15)
F
3.26
459 (M + H)+.
ESI (Pos., 20 V)

19(H4-16)
F
3.47
515 (M + H)+.
ESI (Pos., 20 V)

19(H4-17)
F
3.47
549 (M + H)+.
ESI (Pos., 20 V)

19(H4-18)
F
3.44
588 (M + H)+.
ESI (Pos., 20 V)

19(H4-19)
F
3.51
579 (M + H)+.
ESI (Pos., 20 V)

19(H4-20)
F
3.54
607 (M + H)+.
ESI (Pos., 20 V)

19(H4-21)
F
3.55
664 (M + H)+.
ESI (Pos., 20 V)

19(H4-22)
F
3.20
406 (M + H)+.
ESI (Pos., 20 V)

19(H4-23)
F
3.44
462 (M + H)+.
ESI (Pos., 20 V)

19(H4-24)
F
3.42
496 (M + H)+.
ESI (Pos., 20 V)

19(H4-25)
F
3.42
535 (M + H)+.
ESI (Pos., 20 V)

19(H4-26)
F
3.47
526 (M + H)+.
ESI (Pos., 20 V)

[1027]

217

TABLE 4C-2

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

19(H4-27)
F
3.51
554 (M + H)+.
ESI (Pos., 20 V)

19(H4-28)
F
3.52
611 (M + H)+.
ESI (Pos., 20 V)

19(H4-29)
F
3.42
496 (M + H)+.
ESI (Pos., 20 V)

19(H4-30)
F
3.66
552 (M + H)+.
ESI (Pos., 20 V)

19(H4-31)
F
3.66
586 (M + H)+.
ESI (Pos., 20 V)

19(H4-32)
F
3.62
625 (M + H)+.
ESI (Pos., 20 V)

19(H4-33)
F
3.68
616 (M + H)+.
ESI (Pos., 20 V)

19(H4-34)
F
3.72
644 (M + H)+.
ESI (Pos., 20 V)

19(H4-35)
F
3.69
701 (M + H)+.
ESI (Pos., 20 V)

19(H4-36)
F
3.26
420 (M + H)+.
ESI (Pos., 20 V)

19(H4-37)
F
3.48
476 (M + H)+.
ESI (Pos., 20 V)

19(H4-38)
F
3.46
510 (M + H)+.
ESI (Pos., 20 V)

19(H4-39)
F
3.46
549 (M + H)+.
ESI (Pos., 20 V)

19(H4-40)
F
3.55
540 (M + H)+.
ESI (Pos., 20 V)

19(H4-41)
F
3.56
568 (M + H)+.
ESI (Pos., 20 V)

19(H4-42)
F
3.57
625 (M + H)+.
ESI (Pos., 20 V)

19(H4-43)
F
3.09
358 (M + H)+.
ESI (Pos., 20 V)

19(H4-44)
F
3.31
414 (M + H)+.
ESI (Pos., 20 V)

19(H4-45)
F
3.31
448 (M + H)+.
ESI (Pos., 20 V)

19(H4-46)
F
3.31
487 (M + H)+.
ESI (Pos., 20 V)

19(H4-47)
F
3.38
478 (M + H)+.
ESI (Pos., 20 V)

19(H4-48)
F
3.40
506 (M + H)+.
ESI (Pos., 20 V)

19(H4-49)
F
3.43
563 (M + H)+.
ESI (Pos., 20 V)

19(H4-50)
F
3.25
444 (M + H)+.
ESI (Pos., 20 V)

19(H4-51)
F
3.50
500 (M + H)+.
ESI (Pos., 20 V)

19(H4-52)
F
3.47
534 (M + H)+.
ESI (Pos., 20 V)

[1028]

218

TABLE 4C-3

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

19(H4-53)
F
3.46
573 (M + H)+.
ESI (Pos., 20 V)

19(H4-54)
F
3.53
564 (M + H)+.
ESI (Pos., 20 V)

19(H4-55)
F
3.55
592 (M + H)+.
ESI (Pos., 20 V)

19(H4-56)
F
3.56
649 (M + H)+.
ESI (Pos., 20 V)

19(H4-57)
F
3.05
475 (M + H)+.
ESI (Pos., 20 V)

19(H4-58)
F
3.19
531 (M + H)+.
ESI (Pos., 20 V)

19(H4-59)
F
3.20
565 (M + H)+.
ESI (Pos., 20 V)

19(H4-60)
F
3.22
604 (M + H)+.
ESI (Pos., 20 V)

19(H4-61)
F
3.27
595 (M + H)+.
ESI (Pos., 20 V)

19(H4-62)
F
3.30
623 (M + H)+.
ESI (Pos., 20 V)

19(H4-63)
F
3.33
680 (M + H)+.
ESI (Pos., 20 V)

[1029]

219

TABLE 5C-1

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

19(H5-1)
F
2.89
340 (M + H)+.
ESI (Pos., 20 V)

19(H5-2)
F
3.17
396 (M + H)+.
ESI (Pos., 20 V)

19(H5-3)
F
3.16
430 (M + H)+.
ESI (Pos., 20 V)

19(H5-4)
F
3.14
469 (M + H)+.
ESI (Pos., 20 V)

19(H5-5)
F
3.23
460 (M + H)+.
ESI (Pos., 20 V)

19(H5-6)
F
3.29
488 (M + H)+.
ESI (Pos., 20 V)

19(H5-7)
F
3.31
545 (M + H)+.
ESI (Pos., 20 V)

19(H5-8)
F
2.79
344 (M + H)+.
ESI (Pos., 20 V)

19(H5-9)
F
3.07
400 (M + H)+.
ESI (Pos., 20 V)

19(H5-10)
F
3.09
434 (M + H)+.
ESI (Pos., 20 V)

19(H5-11)
F
3.07
473 (M + H)+.
ESI (Pos., 20 V)

19(H5-12)
F
3.16
464 (M + H)+.
ESI (Pos., 20 V)

19(H5-13)
F
3.20
492 (M + H)+.
ESI (Pos., 20 V)

19(H5-14)
F
3.22
549 (M + H)+.
ESI (Pos., 20 V)

19(H5-15)
F
3.08
403 (M + H)+.
ESI (Pos., 20 V)

19(H5-16)
F
3.34
459 (M + H)+.
ESI (Pos., 20 V)

19(H5-17)
F
3.31
493 (M + H)+.
ESI (Pos., 20 V)

19(H5-18)
F
3.29
532 (M + H)+.
ESI (Pos., 20 V)

19(H5-19)
F
3.36
523 (M + H)+.
ESI (Pos., 20 V)

19(H5-20)
F
3.42
551 (M + H)+.
ESI (Pos., 20 V)

19(H5-21)
F
3.42
608 (M + H)+.
ESI (Pos., 20 V)

19(H5-22)
F
3.00
350 (M + H)+.
ESI (Pos., 20 V)

19(H5-23)
F
3.27
406 (M + H)+.
ESI (Pos., 20 V)

19(H5-24)
F
3.25
440 (M + H)+.
ESI (Pos., 20 V)

19(H5-25)
F
3.23
479 (M + H)+.
ESI (Pos., 20 V)

19(H5-26)
F
3.31
470 (M + H)+.
ESI (Pos., 20 V)

[1030]

220

TABLE 5C-2

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

19(H5-27)
F
3.38
498 (M + H)+.
ESI (Pos., 20 V)

19(H5-28)
F
3.38
555 (M + H)+.
ESI (Pos., 20 V)

19(H5-29)
F
3.31
440 (M + H)+.
ESI (Pos., 20 V)

19(H5-30)
F
3.61
496 (M + H)+.
ESI (Pos., 20 V)

19(H5-31)
F
3.57
530 (M + H)+.
ESI (Pos., 20 V)

19(H5-32)
F
3.51
569 (M + H)+.
ESI (Pos., 20 V)

19(H5-33)
F
3.61
560 (M + H)+.
ESI (Pos., 20 V)

19(HS-34)
F
3.66
588 (M + H)+.
ESI (Pos., 20 V)

19(H5-35)
F
3.62
645 (M + H)+.
ESI (Pos., 20 V)

19(H5-36)
F
3.07
364 (M + H)+.
ESI (Pos., 20 V)

19(H5-37)
F
3.36
420 (M + H)+.
ESI (Pos., 20 V)

19(H5-38)
F
3.33
454 (M + H)+.
ESI (Pos., 20 V)

19(H5-39)
F
3.29
493 (M + H)+.
ESI (Pos., 20 V)

19(H5-40)
F
3.38
484 (M + H)+.
ESI (Pos., 20 V)

19(H5-41)
F
3.44
512 (M + H)+.
ESI (Pos., 20 V)

19(H5-42)
F
3.44
569 (M + H)+.
ESI (Pos., 20 V)

19(H5-43)
F
2.81
302 (M + H)+.
ESI (Pos., 20 V)

19(H5-44)
F
3.11
358 (M + H)+.
ESI (Pos., 20 V)

19(H5-45)
F
3.09
392 (M + H)+.
ESI (Pos., 20 V)

19(H5-46)
F
3.09
431 (M + H)+.
ESI (Pos., 20 V)

19(H5-47)
F
3.18
422 (M + H)+.
ESI (Pos., 20 V)

19(H5-48)
F
3.22
450 (M + H)+.
ESI (Pos., 20 V)

19(H5-49)
F
3.25
507 (M + H)+.
ESI (Pos., 20 V)

19(H5-50)
F
3.03
388 (M + H)+.
ESI (Pos., 20 V)

19(H5-51)
F
3.33
444 (M + H)+.
ESI (Pos., 20 V)

19(H5-52)
F
3.29
478 (M + H)+.
ESI (Pos., 20 V)

[1031]

221

TABLE 5C-3

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

19(H5-53)
F
3.27
517 (M + H)+.
ESI (Pos., 20 V)

19(H5-54)
F
3.36
508 (M + H)+.
ESI (Pos., 20 V)

19(H5-55)
F
3.42
536 (M + H)+.
ESI (Pos., 20 V)

19(H5-56)
F
3.42
593 (M + H)+.
ESI (Pos., 20 V)

19(H5-57)
F
3.05
475 (M + H)+.
ESI (Pos., 20 V)

19(H5-58)
A
3.07
509 (M + H)+.
APCI (Pos., 40 V)

19(H5-59)
F
3.11
548 (M + H)+.
ESI (Pos., 20 V)

19(H5-60)
F
3.11
539 (M + H)+.
ESI (Pos., 20 V)

19(H5-61)
F
3.18
566 (M + H)+.
ESI (Pos., 20 V)

19(H5-62)
F
3.46
624 (M + H)+.
ESI (Pos., 20 V)

[1032]

222

TABLE 6C-1

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

19(H6-1)
C
14.10
410 (M + H)+.
APCI (Pos., 40 V)

19(H6-2)
D
15.20
530 (M + H)+,
APCI (Pos., 40 V)

279.

19(H6-3)
D
12.60
414 (M + H)+,
ARCI (Pos., 40 V)

264.

19(H6-4)
C
15.40
470 (M + H)+,
APCI (Pos., 40 V)

215.

19(H6-5)
D
15.00
504 (M + H)+,
APCI (Pos., 40 V)

354.

19(H6-6)
D
14.60
543 (M + H)+,
APCI (Pos., 40 V)

279.

19(H6-7)
D
15.30
534 (M + H)+,
APCI (Pos., 40 V)

426, 279.

19(H6-8)
D
15.30
562 (M + H)+,
APCI (Pos., 40 V)

244.

19(H6-9)
D
15.50
619 (M + H)+,
APCI (Pos., 40 V)

511, 281.

19(H6-10)
F
3.38
473 (M + H)+.
ESI (Pos., 20 V)

19(H6-11)
F
3.59
529 (M + H)+.
ESI (Pos., 20 V)

19(H6-12)
C
16.50
563 (M + H)+,
APCI (Pos., 40 V)

144.

19(H6-13)
F
3.55
602 (M + H)+.
ESI (Pos., 20 V)

19(H6-14)
D
15.80
593 (M + H)+.
APCI (Pos., 40 V)

19(H6-15)
F
3.64
621 (M + H)+.
ESI (Pos., 20 V)

19(H6-16)
F
3.65
678 (M + H)+.
ESI (Pos., 20 V)

19(H6-17)
C
14.90
420 (M + H)+,
APCI (Pos., 40 V)

270.

19(H6-18)
F
3.55
476 (M + H)+.
ESI (Pos., 20 V)

19(H6-19)
F
3.55
510 (M + H)+.
ESI (Pos., 20 V)

19(H6-20)
C
15.80
549 (M + H)+,
APCI (Pos., 40 V)

279.

19(H6-21)
D
15.70
540 (M + H)+.
ARCI (Pos., 40 V)

19(H6-22)
F
3.62
568 (M + H)+.
ESI (Pos., 20 V)

19(H6-23)
F
3.62
625 (M + H)+.
ESI (Pos., 20 V)

19(H6-24)
F
3.55
510 (M + H)+.
ESI (Pos., 20 V)

19(H6-25)
F
3.79
566 (M + H)+.
ESI (Pos., 20 V)

19(H6-26)
F
3.78
600 (M + H)+.
ESI (Pos., 20 V)

[1033]

223

TABLE 6C-2

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H6-27)
F
3.74
639 (M + H)+.
ESI (Pos., 20 V)

19(H6-28)
D
17.20
630 (M + H)+,
APCI (Pos., 40 V)

480, 279.

19(H6-29)
F
3.84
658 (M + H)+.
ESI (Pos., 20 V)

19(H6-30)
F
3.80
715 (M + H)+.
ESI (Pos., 20 V)

19(H6-31)
C
15.50
434 (M + H)+,
APCI (Pos., 40 V)

284.

19(H6-32)
F
3.60
490 (M + H)+.
ESI (Pos., 20 V)

19(H6-33)
F
3.60
524 (M + H)+.
ESI (Pos., 20 V)

19(H6-34)
F
3.56
563 (M + H)+.
ESI (Pos., 20 V)

19(H6-35)
C
17.20
554 (M + H)+,
APCI (Pos., 40 V)

446.

19(H6-36)
F
3.67
582 (M + H)+.
ESI (Pos., 20 V)

19(H6-37)
F
3.67
639 (M + H)+.
ESI (Pos., 20 V)

19(H6-38)
F
3.22
372 (M + H)+.
ESI (Pos., 20 V)

19(H6-39)
D
14.30
428 (M + H)+,
APCI (Pos., 40 V)

279.

19(H6-40)
F
3.44
462 (M + H)+.
ESI (Pos., 20 V)

19(H6-41)
F
3.42
501 (M + H)+.
ESI (Pos., 20 V)

19(H6-42)
D
15.20
492 (M + H)+,
APCI (Pos., 40 V)

384, 279

19(H6-43)
C
16.20
520 (M + H)+,
APCI (Pos., 40 V)

224.

19(H6-44)
C
16.40
577 (M + H)+,
APCI (Pos., 40 V)

469, 281.

19(H6-45)
F
3.36
458 (M + H)+.
ESI (Pos., 20 V)

19(H6-46)
F
3.60
514 (M + H)+.
ESI (Pos., 20 V)

19(H6-47)
F
3.59
548 (M + H)+.
ESI (Pos., 20 V)

19(H6-48)
F
3.57
587 (M + H)+.
ESI (Pos., 20 V)

19(H6-49)
D
16.20
578 (M + H)+,
APCI (Pos., 40 V)

522.

19(H6-50)
C
17.20
606 (M + H)+,
APCI (Pos., 40 V)

550.

19(H6-51)
F
3.66
663 (M + H)+.
ESI (Pos., 20 V)

19(H6-52)
F
3.16
489 (M + H)+.
ESI (Pos., 20 V)

[1034]

224

TABLE 6C-3

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H6-53)
F
3.33
545 (M + H)+.
ESI (Pos., 20 V)

19(H6-54)
C
15.20
579 (M + H)+,
APCI (Pos., 40 V)

15.70
420, 158.

19(H6-55)
F
3.33
618 (M + H)+.
ESI (Pos., 20 V)

19(H6-56)
C
15.60
609 (M + H)+,
APCI (Pos., 40 V)

16.00
501, 279, 158.

19(H6-57)
F
3.40
637 (M + H)+.
ESI (Pos., 20 V)

19(H6-58)
F
3.44
694 (M + H)+.
ESI (Pos., 20 V)

[1035]

225

TABLE 7C-1

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

19(H7-1)
C
15.20
424 (M + H)+.
APCI (Pos., 40 V)

19(H7-2)
D
14.90
480 (M + H)+.
APCI (Pos., 40 V)

19(H7-3)
F
3.57
514 (M + H)+.
ESI (Pos., 20 V)

19(H7-4)
F
3.55
553 (M + H)+.
ESI (Pos., 20 V)

19(H7-5)
C
17.10
544 (M + H)+.
APCI (Pos., 40 V)

19(H7-6)
C
15.20
428 (M + H)+,
APCI (Pos., 40 V)

264.

19(H7-7)
D
15.00
484 (M + H)+.
APCI (Pos., 40 V)

19(H7-8)
F
3.51
518 (M + H)+.
ESI (Pos., 20 V)

19(H7-9)
F
3.49
557 (M + H)+.
ESI (Pos., 20 V)

19(H7-10)
F
3.56
548 (M + H)+.
ESI (Pos., 20 V)

19(H7-11)
C
17.20
576 (M + H)+,
APCI (Pos., 40 V)

197.

19(H7-12)
F
3.59
633 (M + H)+.
ESI (Pos., 20 V)

19(H7-13)
C
16.20
487 (M + H)+,
APCI (Pos., 40 V)

279.

19(H7-14)
D
15.70
543 (M + H)+,
APCI (Pos., 40 V)

274.

19(H7-15)
F
3.64
577 (M + H)+.
ESI (Pos., 20 V)

19(H7-16)
F
3.62
616 (M + H)+.
ESI (Pos., 20 V)

19(H7-17)
F
3.68
607 (M + H)+.
ESI (Pos., 20 V)

19(H7-18)
F
3.72
635 (M + H)+.
ESI (Pos., 20 V)

19(H7-19)
C
17.70
692 (M + H)+,
APCI (Pos., 40 V)

584.

19(H7-20)
C
15.60
434 (M + H)+,
APCI (Pos., 40 V)

270.

19(H7-21)
C
17.20
490 (M + H)+,
APCI (Pos., 40 V)

326, 221.

19(H7-22)
C
17.20
524 (M + H)+,
APCI (Pos., 40 V)

360, 255.

19(H7-23)
C
16.90
563 (M + H)+.
APCI (Pos., 40 V)

19(H7-24)
C
17.50
554 (M + H)+,
APCI (Pos., 40 V)

285.

19(H7-25)
C
17.70
582 (M + H)+,
APCI (Pos., 40 V)

313, 149.

19(H7-26)
C
17.70
639 (M + H)+,
APCI (Pos., 40 V)

531, 370, 213.

[1036]

226

TABLE 7C-2

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H7-27)
C
17.70
524 (M + H)+,
APCI (Pos., 40 V)

360, 255, 181.

19(H7-28)
D
17.10
580 (M + H)+,
APCI (Pos., 40 V)

416, 181.

19(H7-29)
F
3.86
614 (M + H)+.
ESI (Pos., 20 V)

19(H7-30)
F
3.80
653 (M + H)+.
ESI (Pos., 20 V)

19(H7-31)
C
19.00
644 (M + H)+,
APCI (Pos., 40 V)

149.

19(H7-32)
F
3.91
672 (M + H)+.
ESI (Pos., 20 V)

19(H7-33)
F
3.87
729 (M + H)+.
ESI (Pos., 20 V)

19(H7-34)
D
16.10
504 (M + H)+,
APCI (Pos., 40 V)

235.

19(H7-35)
F
3.67
538 (M + H)+.
ESI (Pos., 20 V)

19(H7-36)
F
3.66
577 (M + H)+.
ESI (Pos., 20 V)

19(H7-37)
F
3.73
568 (M + H)+.
ESI (Pos., 20 V)

19(H7-38)
F
3.76
596 (M + H)+.
ESI (Pos., 20 V)

19(H7-39)
F
3.72
653 (M + H)+.
ESI (Pos., 20 V)

19(H7-40)
C
15.20
386 (M + H)+,
APCI (Pos., 40 V)

222.

19(H7-41)
D
14.90
442 (M + H)+,
APCI (Pos., 40 V)

278.

19(H7-42)
D
15.20
476 (M + H)+,
APCI (Pos., 40 V)

312.

19(H7-43)
C
16.40
515 (M + H)+,
APCI (Pos., 40 V)

488, 404, 351,

256, 220, 146,

130.

19(H7-44)
D
15.50
506 (M + H)+,
APCI (Pos., 40 V)

398.

19(H7-45)
D
15.50
534 (M + H)+.
APCI (Pos., 40 V)

19(H7-46)
D
15.80
591 (M + H)+,
APCI (Pos., 40 V)

483.

19(H7-47)
C
16.60
472 (M + H)+,
APCI (Pos., 40 V)

416, 279

19(H7-48)
C
17.40
528 (M + H)+,
APCI (Pos., 40 V)

499, 473, 452,

415, 247, 203,

149.

19(H7-49)
F
3.69
562 (M + H)+.
ESI (Pos., 20 V)

19(H7-50)
F
3.66
601 (M + H)+.
ESI (Pos., 20 V)

19(H7-51)
F
3.71
592 (M + H)+.
ESI (Pos., 20 V)

[1037]

227

TABLE 7C-3

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H7-52)
F
3.74
620 (M + H)+.
ESI (Pos., 20 V)

19(H7-53)
F
3.75
677 (M + H)+.
ESI (Pos., 20 V)

19(H7-54)
C
14.70
503 (M + H)+,
APCI (Pos., 40 V)

344.

19(H7-55)
D
14.20
559 (M + H)+,
APCI (Pos., 40 V)

400, 279, 158.

19(H7-56)
F
3.39
593 (M + H)+.
ESI (Pos., 20 V)

19(H7-57)
F
3.39
632 (M + H)+.
ESI (Pos., 20 V)

19(H7-58)
F
3.46
623 (M + H)+.
ESI (Pos., 20 V)

19(H7-59)
F
3.48
651 (M + H)+.
ESI (Pos., 20 V)

19(H7-60)
F
3.51
708 (M + H)+.
ESI (Pos., 20 V)

[1038]

228

TABLE 8C-1

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H8-1)
C
10.70
368 (M + H)+,
APCI (Pos., 40 V)

250.

19(H8-2)
F
2.98
407 (M + H)+.
ESI (Pos., 20 V)

19(H8-3)
F
0.67
282 (M + H)+.
ESI (Pos., 20 V)

19(H8-4)
C
9.60
338 (M + H)+.
APCI (Pos., 40 V)

10.30

19(H8-5)
F
2.90
372 (M + H)+.
ESI (Pos., 20 V)

19(H8-6)
F
2.92
411 (M + H)+.
ESI (Pos., 20 V)

19(H8-7)
F
2.98
402 (M + H)+.
ESI (Pos., 20 V)

19(H8-8)
F
3.03
452 (M + Na)+,
ESI (Pos., 20 V)

430 (M + H)+.

19(H8-9)
F
3.09
509 (M + Na)+,
ESI (Pos., 20 V)

487 (M + H)+.

19(H8-10)
C
9.20
341 (M + H)+.
APCI (Pos., 40 V)

19(H8-11)
F
3.14
397 (M + H)+.
ESI (Pos., 20 V)

19(H8-12)
F
3.12
431 (M + H)+.
ESI (Pos., 20 V)

19(H8-13)
F
3.12
470 (M + H)+.
ESI (Pos., 20 V)

19(H8-14)
F
3.18
461 (M + H)+.
ESI (Pos., 20 V)

19(H8-15)
F
3.23
489 (M + H)+.
ESI (Pos., 20 V)

19(H8-16)
F
3.27
546 (M + H)+.
ESI (Pos., 20 V)

19(H8-17)
F
2.63
288 (M + H)+.
ESI (Pos., 20 V)

19(H8-18)
C
12.00
344 (M + H)+,
APCI (Pos., 40 V)

215, 124.

19(H8-19)
F
3.01
378 (M + H)+.
ESI (Pos., 20 V)

19(H8-20)
F
3.03
417 (M + H)+.
ESI (Pos., 20 V)

19(H8-21)
F
3.10
408 (M + H)+.
ESI (Pos., 20 V)

19(H8-22)
F
3.16
436 (M + H)+.
ESI (Pos., 20 V)

19(H8-23)
F
3.20
493 (M + H)+.
ESI (Pos., 20 V)

19(H8-24)
F
3.07
378 (M + H)+.
ESI (Pos., 20 V)

19(H8-25)
F
3.34
434 (M + H)+.
ESI (Pos., 20 V)

[1039]

229

TABLE 8C-2

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H8-26)
C
16.00
468 (M + H)+.
APCI (Pos., 40 V)

19(H8-27)
F
3.33
507 (M + H)+.
ESI (Pos., 20 V)

19(H8-28)
F
3.38
498 (M + H)+.
ESI (Pos., 20 V)

19(H8-29)
F
3.44
526 (M + H)+.
ESI (Pos., 20 V)

19(H8-30)
F
3.42
583 (M + H)+.
ESI (Pos., 20 V)

19(H8-31)
C
8.90
302 (M + H)+,
APCI (Pos., 40 V)

123.

19(H8-32)
F
3.12
358 (M + H)+.
ESI (Pos., 20 V)

19(H8-33)
F
3.11
392 (M + H)+.
ESI (Pos., 20 V)

19(H8-34)
C
13.40
431 (M + H)+.
APCI (Pos., 40 V)

19(H8-35)
F
3.18
422 (M + H)+.
ESI (Pos., 20 V)

19(H8-36)
F
3.23
450 (M + H)+.
ESI (Pos., 20 V)

19(H8-37)
F
3.23
507 (M + H)+.
ESI (Pos., 20V)

19(H8-38)
F
0.65
240 (M + H)+.
ESI (Pos., 20 V)

19(H8-39)
D
8.60
296 (M + H)+.
APCI (Pos., 40 V)

19(H8-40)
F
2.87
330 (M + H)+.
ESI (Pos., 20 V)

19(H8-41)
F
2.89
369 (M + H)+.
ESI (Pos., 20 V)

19(H8-42)
F
2.94
360 (M + H)+.
ESI (Pos., 20V)

19(H8-43)
F
3.01
388 (M + H)+.
ESI (Pos., 20V)

19(H8-44)
F
3.07
445 (M + H)+.
ESI (Pos., 20V)

19(H8-45)
F
2.79
326 (M + H)+.
ESI (Pos., 20 V)

19(H8-46)
F
3.09
416 (M + H)+.
ESI (Pos., 20 V)

19(H8-47)
F
3.11
455 (M + H)+.
ESI (Pos., 20 V)

19(H8-48)
F
3.16
446 (M + H)+.
ESI (Pos., 20 V)

19(H8-49)
C
14.60
474 (M + H)+,
APCI (Pos., 40 V)

418.

19(H8-50)
F
3.23
531 (M + H)+.
ESI (Pos., 20 V)

19(H8-51)
F
1.95
357 (M + H)+.
ESI (Pos., 20 V)

[1040]

230

TABLE 8C-3

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H8-52)
F
3.01
413 (M + H)+.
ESI (Pos., 20 V)

19(H8-53)
F
3.00
447 (M + H)+.
ESI (Pos., 20 V)

19(H8-54)
F
3.03
486 (M + H)+.
ESI (Pos., 20 V)

19(H8-55)
F
3.07
477 (M + H)+.
ESI (Pos., 20 V)

19(H8-56)
F
3.12
505 (M + H)+.
ESI (Pos., 20 V)

19(H8-57)
C
12.50
562 (M + H)+,
APCI (Pos., 40 V)

454.

[1041]

231

TABLE 9C-1

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H9-1)
D
12.30
533 (M + H)+,
APCI(Pos., 40 V)

388.

19(H9-2)
D
13.36
547 (M + H)+,
APCI (Pos., 40 V)

439, 181.

19(H9-3)
D
16.15
629 (M + H)+,
APCI (Pos., 40 V)

521.

19(H9-4)
D
13.78
561 (M + H)+,
APCI (Pos., 40 V)

19(H9-5)
D
14.20
575 (M + H)+,
APCI (Pos., 40 V)

460.

19(H9-6)
D
14.90
589 (M + H)+.
APCI (Pos., 40 V)

19(H9-7)
D
11.36
604 (M + H)+.
APCI (Pos., 40 V)

19(H9-8)
D
11.26
604 (M + H)+,
APCI (Pos., 40 V)

496.

19(H9-9)
D
13.90
609 (M + H)+.
APCI (Pos., 40 V)

19(H9-10)
D
14.40
589 (M + H)+,
APCI (Pos., 40 V)

474.

19(H9-11)
D
13.52
589 (M + H)+,
APCI (Pos., 40 V)

481.

19(H9-12)
D
11.05
606 (M + H)+,
APCI (Pos., 40 V)

498.

19(H9-13)
D
11.06
620 (M + H)+,
APCI (Pos., 40 V)

512.

19(H9-14)
D
11.31
598 (M + H)+,
APCI (Pos., 40 V)

490.

19(H9-15)
D
11.05
584 (M + H)+,
APCI (Pos., 40 V)

476.

19(H9-16)
D
10.99
584 (M + H)+.
APCI (Pos., 40 V)

19(H9-17)
D
13.62
648 (M + H)+.
APCI (Pos., 40 V)

19(H9-18)
D
11.68
604 (M + H)+,
APCI (Pos., 40 V)

496.

19(H9-19)
D
14.41
597 (M + H)+.
APCI (Pos., 40 V)

19(H9-20)
D
12.89
535 (M + H)+.
APCI (Pos., 40 V)

19(H9-21)
D
14.41
577 (M + H)+.
APCI (Pos., 40 V)

19(H9-22)
D
14.05
625 (M + H)+.
APCI (Pos., 40 V)

19(H9-23)
D
13.68
549 (M + H)+.
APCI (Pos., 40 V)

19(H9-24)
D
14.05
563 (M + H)+.
APCI (Pos., 40 V)

19(H9-25)
D
13.73
601 (M + H)+,
APCI (Pos., 40 V)

493.

19(H9-26)
D
13.89
613 (M + H)+,
APCI (Pos., 40 V)

505.

[1042]

232

TABLE 9C-2

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H9-27)
D
13.99
601 (M + H)+,
APCI (Pos., 40 V)

493.

19(H9-28)
D
13.89
613 (M + H)+,
APCI (Pos., 40 V)

505.

19(H9-29)
D
14.05
601 (M + H)+,
APCI (Pos., 40 V)

493.

19(H9-30)
D
13.73
613 (M + H)+,
APCI (Pos., 40 V)

505.

19(H9-31)
D
14.41
597 (M + H)+,
APCI (Pos., 40 V)

489.

19(H9-32)
D
14.31
563 (M + H)+,
APCI (Pos., 40 V)

455.

19(H9-33)
D
14.68
611 (M + H)+,
APCI (Pos., 40 V)

14.95
503.

19(H9-34)
D
13.57
549 (M + H)+,
APCI (Pos., 40 V)

441.

19(H9-35)
D
14.20
563 (M + H)+,
APCI (Pos., 40 V)

455.

19(H9-36)
D
13.84
583 (M + H)+,
APCI (Pos., 40 V)

475.

19(H9-37)
D
11.10
564 (M + H)+,
APCI (Pos., 40 V)

456.

19(H9-38)
D
12.35
551 (M + H)+,
APCI (Pos., 40 V)

443.

19(H9-39)
D
12.04
531 (M + H)+,
APCI (Pos., 40 V)

423.

19(H9-40)
D
12.56
533 (M + H)+,
APCI (Pos., 40 V)

425.

19(H9-41)
D
11.78
551 (M + H)+,
APCI (Pos., 40 V)

443.

19(H9-42)
D
14.20
563 (M + H)+,
APCI (Pos., 40 V)

455.

19(H9-43)
D
12.99
535 (M + H)+,
APCI (Pos., 40 V)

427.

19(H9-44)
D
11.21
578 (M + H)+,
APCI (Pos., 40 V)

470.

19(H9-45)
D
13.20
579 (M + H)+,
APCI (Pos., 40 V)

471.

19(H9-46)
D
14.83
611 (M + H)+,
APCI (Pos., 40 V)

503.

19(H9-47)
D
15.31
625 (M + H)+,
APCI (Pos., 40 V)

517.

19(H9-48)
D
14.36
563 (M + H)+,
APCI (Pos., 40 V)

563.

19(H9-49)
D
11.04
601 (M + H)+,
APCI (Pos., 40 V)

493.

19(H9-50)
D
13.56
549 (M + H)+,
APCI (Pos., 40 V)

441.

19(H9-51)
D
15.26
601 (M + H)+,
APCI (Pos., 40 V)

493.

[1043]

233

TABLE 9C-3

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H9-52)
D
13.15
547 (M + H)+,
APCI (Pos., 40 V)

439.

19(H9-53)
D
12.19
521 (M + H)+,
APCI (Pos., 40 V)

413.

19(H9-54)
D
12.63
565 (M + H)+,
APCI (Pos., 40 V)

457.

19(H9-55)
D
11.00
598 (M + H)+,
APCI (Pos., 40 V)

493.

19(H9-56)
D
14.57
617 (M + H)+,
APCI (Pos., 40 V)

509.

19(H9-57)
D
13.36
581 (M + H)+,
APCI (Pos., 40 V)

473.

19(H9-58)
D
13.98
603 (M + H)+,
APCI (Pos., 40 V)

495.

19(H9-59)
D
14.57
609 (M + H)+,
APCI (Pos., 40 V)

501.

19(H9-60)
D
14.05
607 (M + H)+.
APCI (Pos., 40 V)

19(H9-61)
D
13.68
587 (M + H)+.
APCI (Pos., 40 V)

19(H9-62)
D
11.21
598 (M + H)+,
APCI (Pos., 40 V)

490.

[1044]

234

TABLE 10C-1

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H10-1)
F
3.39
519 (M + H)+.
ESI (Pos., 20 V)

19(H10-2)
F
3.47
532 (M + H)+.
ESI (Pos., 20 V)

19(H10-3)
F
3.79
615 (M + H)+.
ESI (Pos., 20 V)

19(H10-4)
F
3.49
547 (M + H)+.
ESI (Pos., 20 V)

19(H10-5)
F
3.55
561 (M + H)+.
ESI (Pos., 20 V)

19(H10-6)
F
3.62
575 (M + H)+.
ESI (Pos., 20 V)

19(H10-7)
F
3.64
589 (M + H)+.
ESI (Pos., 20 V)

19(H10-8)
F
3.22
590 (M + H)+.
ESI (Pos., 20 V)

19(H10-9)
F
3.22
590 (M + H)+.
ESI (Pos., 20 V)

19(H10-10)
F
3.58
595 (M + H)+.
ESI (Pos., 20 V)

19(H10-11)
F
3.58
575 (M + H)+.
ESI (Pos., 20 V)

19(H10-12)
F
3.49
575 (M + H)+.
ESI (Pos., 20 V)

19(H10-13)
F
3.20
592 (M + H)+.
ESI (Pos., 20 V)

19(H10-14)
F
3.20
606 (M + H)+.
ESI (Pos., 20 V)

19(H10-15)
F
3.20
584 (M + H)+.
ESI (Pos., 20 V)

19(H10-16)
F
3.18
570 (M + H)+.
ESI (Pos., 20 V)

19(H10-17)
F
3.18
570 (M + H)+.
ESI (Pos., 20 V)

19(H10-18)
F
3.45
634 (M + H)+.
ESI (Pos., 20 V)

19(H10-19)
F
3.23
590 (M + H)+.
ESI (Pos., 20 V)

19(H10-20)
F
3.44
555 (M + H)+.
ESI (Pos., 20 V)

19(H10-21)
F
3.57
583 (M + H)+.
ESI (Pos., 20 V)

19(H10-22)
F
3.40
521 (M + H)+.
ESI (Pos., 20 V)

19(H10-23)
F
3.58
563 (M + H)+.
ESI (Pos., 20 V)

19(H10-24)
F
3.66
611 (M + H)+.
ESI (Pos., 20 V)

19(H10-25)
F
3.47
535 (M + H)+.
ESI (Pos., 20 V)

19(H10-26)
D
13.62
549 (M + H)+.
APCI (Pos., 40 V)

[1045]

235

TABLE 10C-2

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H10-27)
F
3.55
549 (M + H)+.
ESI (Pos., 20 V)

19(H10-28)
F
3.53
587 (M + H)+.
ESI (Pos., 20 V)

19(H10-29)
F
3.53
599 (M + H)+.
ESI (Pos., 20 V)

19(H10-30)
F
3.55
587 (M + H)+.
ESI (Pos., 20 V)

19(H10-31)
F
3.53
599 (M + H)+.
ESI (Pos., 20 V)

19(H10-32)
F
3.55
587 (M + H)+.
ESI (Pos., 20 V)

19(H10-33)
F
3.53
599 (M + H)+.
ESI (Pos., 20 V)

19(H10-34)
F
3.58
583 (M + H)+.
ESI (Pos., 20 V)

19(H10-35)
F
3.56
549 (M + H)+.
ESI (Pos., 20 V)

19(H10-36)
F
3.60
597 (M + H)+.
ESI (Pos., 20 V)

19(H10-37)
F
3.45
535 (M + H)+.
ESI (Pos., 20 V)

19(H10-38)
F
3.53
549 (M + H)+.
ESI (Pos., 20 V)

19(H10-39)
F
3.51
569 (M + H)+.
ESI (Pos., 20 V)

19(H10-40)
F
3.18
550 (M + H)+.
ESI (Pos., 20 V)

19(H10-41)
F
3.34
537 (M + H)+.
ESI (Pos., 20 V)

19(H10-42)
F
3.36
517 (M + H)+.
ESI (Pos., 20 V)

19(H10-43)
F
3.40
519 (M + H)+.
ESI (Pos., 20 V)

19(H10-44)
F
3.27
537 (M + H)+.
ESI (Pos., 20 V)

19(H10-45)
F
3.53
549 (M + H)+.
ESI (Pos., 20 V)

19(H10-46)
F
3.40
521 (M + H)+.
ESI (Pos., 20 V)

19(H10-47)
F
3.18
564 (M + H)+.
ESI (Pos., 20 V)

19(H10-48)
F
3.40
565 (M + H)+.
ESI (Pos., 20 V)

19(H10-49)
F
3.60
597 (M + H)+.
ESI (Pos., 20 V)

19(H10-50)
F
3.67
611 (M + H)+.
ESI (Pos., 20 V)

19(H10-51)
F
3.53
549 (M + H)+.
ESI (Pos., 20 V)

19(H10-52)
F
3.18
587 (M + H)+.
ESI (Pos., 20 V)

[1046]

236

TABLE 10C-3

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H10-53)
F
3.47
535 (M + H)+.
ESI (Pos., 20 V)

19(H10-54)
F
3.64
587 (M + H)+.
ESI (Pos., 20 V)

19(H10-55)
F
3.44
533 (M + H)+.
ESI (Pos., 20 V)

19(H10-56)
F
3.34
507 (M + H)+.
ESI (Pos., 20 V)

19(H10-57)
F
3.36
551 (M + H)+.
ESI (Pos., 20 V)

19(H10-58)
F
3.45
640 (M + H)+.
ESI (Pos., 20 V)

19(H10-59)
F
3.18
584 (M + H)+.
ESI (Pos., 20 V)

19(H10-60)
F
3.60
603 (M + H)+.
ESI (Pos., 20 V)

19(H10-61)
F
3.45
567 (M + H)+.
ESI (Pos., 20 V)

19(H10-62)
F
3.53
589 (M + H)+.
ESI (Pos., 20 V)

19(H10-63)
F
3.60
595 (M + H)+.
ESI (Pos., 20 V)

19(H10-64)
F
3.53
593 (M + H)+.
ESI (Pos., 20 V)

19(H10-65)
F
3.29
537 (M + H)+.
ESI (Pos., 20 V)

19(H10-66)
F
3.49
573 (M + H)+.
ESI (Pos., 20 V)

19(H10-67)
F
3.60
597 (M + H)+.
ESI (Pos., 20 V)

19(H10-68)
F
3.20
584 (M + H)+.
ESI (Pos., 20 V)

[1047]

237

TABLE 11C-1

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H11-1)
D
12.10
412 (M + H)+.
APCI (Pos., 40 V)

19(H11-2)
D
13.52
426 (M + H)+.
APCI (Pos., 40 V)

19(H11-3)
D
16.47
508 (M + H)+.
APCI (Pos., 40 V)

19(H11-4)
D
14.03
440 (M + H)+.
APCI (Pos., 40 V)

19(H11-5)
D
14.36
454 (M + H)+.
APCI (Pos., 40 V)

19(H11-6)
D
15.15
468 (M + H)+.
APCI (Pos., 40 V)

19(H11-7)
D
10.66
483 (M + H)+.
APCI (Pos., 40 V)

19(H11-8)
D
10.52
483 (M + H)+.
APCI (Pos., 40 V)

19(H11-9)
D
13.94
488 (M + H)+.
APCI (Pos., 40 V)

19(H11-10)
D
15.02
468 (M + H)+.
APCI (Pos., 40 V)

19(H11-11)
D
13.36
468 (M + H)+.
APCI (Pos., 40 V)

19(H11-12)
D
10.31
485 (M + H)+.
APCI (Pos., 40 V)

19(H11-13)
D
10.52
499 (M + H)+.
APCI (Pos., 40 V)

19(H11-14)
D
10.73
477 (M + H)+.
APCI (Pos., 40 V)

19(H11-15)
D
10.36
463 (M + H)+.
APCI (Pos., 40 V)

19(H11-16)
D
10.26
463 (M + H)+.
APCI (Pos., 40 V)

19(H11-17)
D
13.76
527 (M + H)+.
APCI (Pos., 40 V)

19(H11-18)
D
10.89
483 (M + H)+.
APCI (Pos., 40 V)

19(H11-19)
D
13.92
476 (M + H)+.
APCI (Pos., 40 V)

19(H11-20)
D
12.78
414 (M + H)+.
APCI (Pos., 40 V)

19(H11-21)
D
13.47
480 (M + H)+.
APCI (Pos., 40 V)

19(H11-22)
D
13.84
492 (M + H)+.
APCI (Pos., 40 V)

19(H11-23)
D
13.84
480 (M + H)+.
APCI (Pos., 40 V)

19(H11-24)
D
13.84
492 (M + H)+.
APCI (Pos., 40 V)

19(H11-25)
D
14.05
480 (M + H)+.
APCI (Pos., 40 V)

19(H11-26)
D
13.57
492 (M + H)+.
APCI (Pos., 40 V)

[1048]

238

TABLE 11C-2

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H11-27)
D
14.52
476 (M + H)+.
APCI (Pos., 40 V)

19(H11-28)
D
14.41
442 (M + H)+.
APCI (Pos., 40 V)

19(H11-29)
D
14.92
490 (M + H)+.
APCI (Pos., 40 V)

15.50

19(H11-30)
D
13.62
428 (M + H)+.
APCI (Pos., 40 V)

19(H11-31)
D
14.36
442 (M + H)+.
APCI (Pos., 40 V)

19(H11-32)
D
13.78
462 (M + H)+.
APCI (Pos., 40 V)

19(H11-33)
D
10.31
443 (M + H)+.
APCI (Pos., 40 V)

19(H11-34)
D
12.10
430 (M + H)+.
APCI (Pos., 40 V)

19(H11-35)
D
11.63
410 (M + H)+.
APCI (Pos., 40 V)

19(H11-36)
D
12.42
412 (M + H)+.
APCI (Pos., 40 V)

19(H11-37)
D
11.31
430 (M + H)+.
APCI (Pos., 40 V)

19(H11-38)
D
14.26
442 (M + H)+.
APCI (Pos., 40 V)

19(H11-39)
D
12.89
414 (M + H)+.
APCI (Pos., 40 V)

19(H11-40)
D
10.52
457 (M + H)+.
APCI (Pos., 40 V)

19(H11-41)
D
13.10
458 (M + H)+.
APCI (Pos., 40 V)

19(H11-42)
D
15.04
490 (M + H)+.
APCI (Pos., 40 V)

19(H11-43)
D
15.57
504 (M + H)+.
APCI (Pos., 40 V)

19(H11-44)
D
14.57
442 (M + H)+.
APCI (Pos., 40 V)

19(H11-45)
D
10.52
480 (M + H)+.
APCI (Pos., 40 V)

19(H11-46)
D
13.73
428 (M + H)+.
APCI (Pos., 40 V)

19(H11-47)
D
15.47
480 (M + H)+.
APCI (Pos., 40 V)

19(H11-48)
D
13.10
426 (M + H)+.
APCI (Pos., 40 V)

19(H11-49)
D
11.94
400 (M + H)+.
APCI (Pos., 40 V)

19(H11-50)
D
12.36
444 (M + H)+.
APCI (Pos., 40 V)

19(H11-51)
D
10.63
477 (M + H)+.
APCI (Pos., 40 V)

[1049]

239

TABLE 11C-3

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H11-52)
D
14.57
496 (M + H)+.
APCI (Pos., 40 V)

19(H11-53)
D
13.15
460 (M + H)+.
APCI (Pos., 40 V)

19(H11-54)
D
13.99
482 (M + H)+.
APCI (Pos., 40 V)

19(H11-55)
D
14.73
488 (M + H)+.
APCI (Pos., 40 V)

19(H11-56)
D
14.05
486 (M + H)+.
APCI (Pos., 40 V)

19(H11-57)
D
13.68
466 (M + H)+.
APCI (Pos., 40 V)

19(H11-58)
D
10.73
477 (M + H)+.
APCI (Pos., 40 V)

[1050]

240

TABLE 12C-1

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H12-1)
F
3.45
426 (M + H)+.
ESI (Pos., 20 V)

19(H12-2)
F
3.56
440 (M + H)+.
ESI (Pos., 20 V)

19(H12-3)
F
3.93
522 (M + H)+.
ESI (Pos., 20 V)

19(H12-4)
F
3.60
454 (M + H)+.
ESI (Pos., 20 V)

19(H12-5)
F
3.66
468 (M + H)+.
ESI (Pos., 20 V)

19(H12-6)
F
3.75
482 (M + H)+.
ESI (Pos., 20 V)

19(H12-7)
F
3.71
516 (M + H)+.
ESI (Pos., 20 V)

19(H12-8)
F
3.77
496 (M + H)+.
ESI (Pos., 20 V)

19(H12-9)
F
3.25
497 (M + H)+.
ESI (Pos., 20 V)

19(H12-10)
F
3.27
497 (M + H)+.
ESI (Pos., 20 V)

19(H12-11)
F
3.67
502 (M + H)+.
ESI (Pos., 20 V)

19(H12-12)
F
3.69
482 (M + H)+.
ESI (Pos., 20 V)

19(H12-13)
F
3.60
482 (M + H)+.
ESI (Pos., 20 V)

19(H12-14)
F
3.23
499 (M + H)+.
ESI (Pos., 20 V)

19(H12-15)
F
3.23
513 (M + H)+.
ESI (Pos., 20 V)

19(H12-16)
F
3.23
491 (M + H)+.
ESI (Pos., 20 V)

19(H12-17)
F
3.22
477 (M + H)+.
ESI (Pos., 20 V)

19(H12-18)
F
3.22
477 (M + H)+.
ESI (Pos., 20 V)

19(H12-19)
F
3.27
497 (M + H)+.
ESI (Pos., 20 V)

19(H12-20)
F
3.49
462 (M + H)+.
ESI (Pos., 20 V)

19(H12-21)
F
3.64
490 (M + H)+.
ESI (Pos., 20 V)

19(H12-22)
F
3.49
428 (M + H)+.
ESI (Pos., 20 V)

19(H12-23)
F
3.69
470 (M + H)+.
ESI (Pos., 20 V)

19(H12-24)
F
3.77
518 (M + H)+.
ESI (Pos., 20 V)

19(H12-25)
F
3.54
442 (M + H)+.
ESI (Pos., 20 V)

19(H12-26)
F
3.62
456 (M + H)+.
ESI (Pos., 20 V)

[1051]

241

TABLE 12C-2

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H12-27)
F
3.64
456 (M + H)+.
ESI (Pos., 20 V)

19(H12-28)
F
3.62
494 (M + H)+.
ESI (Pos., 20 V)

19(H12-29)
F
3.62
506 (M + H)+.
ESI (Pos., 20 V)

19(H12-30)
F
3.62
494 (M + H)+.
ESI (Pos., 20 V)

19(H12-31)
F
3.61
506 (M + H)+.
ESI (Pos., 20 V)

19(H12-32)
F
3.64
494 (M + H)+.
ESI (Pos., 20 V)

19(H12-33)
F
3.60
506 (M + H)+.
ESI (Pos., 20 V)

19(H12-34)
F
3.66
490 (M + H)+.
ESI (Pos., 20 V)

19(H12-35)
F
3.64
456 (M + H)+.
ESI (Pos., 20 V)

19(H12-36)
F
3.71
504 (M + H)+.
ESI (Pos., 20 V)

19(H12-37)
F
3.57
442 (M + H)+.
ESI (Pos., 20 V)

19(H12-38)
F
3.63
456 (M + H)+.
ESI (Pos., 20 V)

19(H12-39)
F
3.60
476 (M + H)+.
ESI (Pos., 20 V)

19(H12-40)
F
3.19
457 (M + H)+.
ESI (Pos., 20 V)

19(H12-41)
F
3.42
444 (M + H)+.
ESI (Pos., 20 V)

19(H12-42)
F
3.43
424 (M + H)+.
ESI (Pos., 20 V)

19(H12-43)
F
3.45
426 (M + H)+.
ESI (Pos., 20 V)

19(H12-44)
F
3.32
444 (M + H)+.
ESI (Pos., 20 V)

19(H12-45)
F
3.62
456 (M + H)+.
ESI (Pos., 20 V)

19(H12-46)
F
3.49
428 (M + H)+.
ESI (Pos., 20 V)

19(H12-47)
F
3.20
471 (M + H)+.
ESI (Pos., 20 V)

19(H12-48)
F
3.49
472 (M + H)+.
ESI (Pos., 20 V)

19(H12-49)
F
3.70
504 (M + H)+.
ESI (Pos., 20 V)

19(H12-50)
F
3.77
518 (M + H)+.
ESI (Pos., 20 V)

19(H12-51)
F
3.62
456 (M + H)+.
ESI (Pos., 20 V)

19(H12-52)
F
3.21
494 (M + H)+.
ESI (Pos., 20 V)

[1052]

242

TABLE 12C-4

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H12-53)
F
3.56
442 (M + H)+.
ESI (Pos., 20 V)

19(H12-54)
F
3.75
494 (M + H)+.
ESI (Pos., 20 V)

19(H12-55)
F
3.51
440 (M + H)+.
ESI (Pos., 20 V)

19(H12-56)
F
3.40
414 (M + H)+.
ESI (Pos., 20 V)

19(H12-57)
F
3.75
484 (M + H)+.
ESI (Pos., 20 V)

19(H12-58)
F
3.42
458 (M + H)+.
ESI (Pos., 20 V)

19(H12-59)
F
3.20
491 (M + H)+.
ESI (Pos., 20 V)

19(H12-60)
F
3.68
510 (M + H)+.
ESI (Pos., 20 V)

19(H12-61)
F
3.52
474 (M + H)+.
ESI (Pos., 20 V)

19(H12-62)
F
3.62
496 (M + H)+.
ESI (Pos., 20 V)

19(H12-63)
F
3.67
502 (M + H)+.
ESI (Pos., 20 V)

19(H12-64)
F
3.60
500 (M + H)+.
ESI (Pos., 20 V)

19(H12-65)
F
3.33
444 (M + H)+.
ESI (Pos., 20 V)

19(H12-66)
F
3.33
444 (M + H)+.
ESI (Pos., 20 V)

19(H12-67)
F
3.57
480 (M + H)+.
ESI (Pos., 20 V)

19(H12-68)
F
3.68
504 (M + H)+.
ESI (Pos., 20 V)

19(H12-69)
F
3.20
491 (M + H)+.
ESI (Pos., 20 V)

[1053]

243

TABLE 13C-1

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H13-1)
F
3.48
440 (M + H)+.
ESI (Pos., 20 V)

19(H13-2)
F
3.60
454 (M + H)+.
ESI (Pos., 20 V)

19(H13-3)
F
3.94
536 (M + H)+.
ESI (Pos., 20 V)

19(H13-4)
F
3.64
468 (M + H)+.
ESI (Pos., 20 V)

19(H13-5)
F
3.69
482 (M + H)+.
ESI (Pos., 20 V)

19(H13-6)
F
3.78
496 (M + H)+.
ESI (Pos., 20 V)

19(H13-7)
F
3.74
530 (M + H)+.
ESI (Pos., 20 V)

19(H13-8)
F
3.79
510 (M + H)+.
ESI (Pos., 20 V)

19(H13-9)
F
3.29
511 (M + H)+.
ESI (Pos., 20 V)

19(H13-10)
F
3.32
511 (M + H)+.
ESI (Pos., 20 V)

19(H13-11)
F
3.72
516 (M + H)+.
ESI (Pos., 20 V)

19(H13-12)
F
3.73
496 (M + H)+.
ESI (Pos., 20 V)

19(H13-13)
F
3.64
496 (M + H)+.
ESI (Pos., 20 V)

19(H13-14)
F
3.26
513 (M + H)+.
ESI (Pos., 20 V)

19(H13-15)
F
3.28
527 (M + H)+.
ESI (Pos., 20 V)

19(H13-16)
F
3.28
505 (M + H)+.
ESI (Pos., 20 V)

19(H13-17)
F
3.27
491 (M + H)+.
ESI (Pos., 20 V)

19(H13-18)
F
3.58
555 (M + H)+.
ESI (Pos., 20 V)

19(H13-19)
F
3.32
511 (M + H)+.
ESI (Pos., 20 V)

19(H13-20)
F
3.66
504 (M + H)+.
ESI (Pos., 20 V)

19(H13-21)
F
3.66
470 (M + H)+.
ESI (Pos., 20 V)

19(H13-22)
F
3.74
484 (M + H)+.
ESI (Pos., 20 V)

19(H13-23)
F
3.67
470 (M + H)+.
ESI (Pos., 20 V)

19(H13-24)
F
3.66
508 (M + H)+.
ESI (Pos., 20 V)

19(H13-25)
F
3.67
520 (M + H)+.
ESI (Pos., 20 V)

19(H13-26)
F
3.69
508 (M + H)+.
ESI (Pos., 20 V)

[1054]

244

TABLE 13C-2

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H13-27)
F
3.64
520 (M + H)+.
ESI (Pos., 20 V)

19(H13-28)
F
3.68
508 (M + H)+.
ESI (Pos., 20 V)

19(H13-29)
F
3.64
520 (M + H)+.
ESI (Pos., 20 V)

19(H13-30)
F
3.72
504 (M + H)+.
ESI (Pos., 20 V)

19(H13-31)
F
3.70
470 (M + H)+.
ESI (Pos., 20 V)

19(H13-32)
F
3.76
518 (M + H)+.
ESI (Pos,, 20 V)

19(H13-33)
F
3.61
456 (M + H)+.
ESI (Pos., 20 V)

19(H13-34)
F
3.68
470 (M + H)+.
ESI (Pos., 20 V)

19(H13-35)
F
3.65
490 (M + H)+.
ESI (Pos., 20 V)

19(H13-36)
F
3.24
471 (M + H)+.
ESI (Pos., 20 V)

19(H13-37)
F
3.47
458 (M + H)+.
ESI (Pos., 20 V)

19(H13-38)
F
3.51
438 (M + H)+.
ESI (Pos., 20 V)

19(H13-39)
F
3.51
440 (M + H)+.
ESI (Pos., 20 V)

19(H13-40)
F
3.39
458 (M + H)+.
ESI (Pos., 20 V)

19(H13-41)
F
3.67
470 (M + H)+.
ESI (Pos., 20 V)

19(H13-42)
F
3.54
442 (M + H)+.
ESI (Pos., 20 V)

19(H13-43)
F
3.25
485 (M + H)+.
ESI (Pos., 20 V)

19(H13-44)
F
3.55
486 (M + H)+.
ESI (Pos., 20 V)

19(H13-45)
F
3.75
518 (M + H)+.
ESI (Pos., 20 V)

19(H13-46)
F
3.80
532 (M + H)+.
ESI (Pos., 20 V)

19(H13-47)
F
3.69
470 (M + H)+.
ESI (Pos., 20 V)

19(H13-48)
F
3.25
508 (M + H)+.
ESI (Pos., 20 V)

19(H13-49)
F
3.62
456 (M + H)+.
ESI (Pos., 20 V)

19(H13-50)
F
3.80
508 (M + H)+.
ESI (Pos., 20 V)

19(H13-51)
F
3.58
454 (M + H)+.
ESI (Pos., 20 V)

19(H13-52)
F
3.46
428 (M + H)+.
ESI (Pos., 20 V)

[1055]

245

TABLE 13C-3

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

19(H13-53)
F
3.80
498 (M + H)+.
ESI (Pos., 20 V)

19(H13-54)
F
3.47
472 (M + H)+.
ESI (Pos., 20 V)

19(H13-55)
F
3.26
505 (M + H)+.
ESI (Pos., 20 V)

19(H13-56)
F
3.73
524 (M + H)+.
ESI (Pos., 20 V)

19(H13-57)
F
3.58
488 (M + H)+.
ESI (Pos., 20 V)

19(H13-58)
F
3.67
510 (M + H)+.
ESI (Pos., 20 V)

19(H13-59)
F
3.73
516 (M + H)+.
ESI (Pos., 20 V)

19(H13-60)
F
3.64
514 (M + H)+.
ESI (Pos., 20 V)

19(H13-61)
F
3.62
494 (M + H)+.
ESI (Pos., 20 V)

19(H13-62)
F
3.25
505 (M + H)+.
ESI (Pos., 20 V)

EXAMPLE 20

[1056] (3S)-1-propyl-2,5-dioxo-3-(4-(benzylcarbonylamino)butyl)-9-(2,4,6-trimethoxybenzyl)-1,4,9-triazaspiro[5.5]undecane

1447

[1057] To a solution of the compound prepared in Example 8 (0.01 g) in dichloroethane (0.2 ml) were added 2,4,6-trimethoxybenzaldehyde (0.013 g), sodium triacetoxyborohydride (0.015 g) and dimethylformamide (0.2 ml). The reaction mixture was stirred for 50 hours at room temperature. The reaction mixture was loaded on ion exchange resin (OASIS MCX, Waters, 60 mg) washed with methanol (3 ml) prior to use. The resin was washed with methanol (2 ml), and was eluted with 10% triethylamine-methanol solution (2 ml). The elution was concentrated to give the compound of the present invention (4.4 mg) having the following physical data.

[1058] TLC: Rf 0.33 (chloroform:methanol=10:1);

[1059] NMR (CD3OD): δ 7.33 (m, 5H), 6.21 (s, 2H), 5.05 (s, 2H), 4.00 (m, 1H), 3.80 (s, 9H), 3.59 (s, 2H), 3.40 (m, 2H), 3.11 (t, J=6.6 Hz, 2H), 3.05-2.75 (m, 4H), 2.40-2.00 (m, 2H), 2.00-1.70 (m, 4H), 1.65-1.25 (m, 6H), 0.90 (t, J=7.2 Hz, 3H).

EXAMPLE 20(1)

[1060] (3S)-1-propyl-2,5-dioxo-3-(4-(benzylcarbonylamino) butyl)-9-(2,2-dimethylpropyl)-1,4,9-triazaspiro[5.5]undecane

1448

[1061] By the same procedure as described in Example 20 using the compound prepared in Example 8 (0.01 g) and pivalaldehyde (8 μl), the compound of the present invention (2.5 mg) having the following physical data was obtained.

[1062] TLC: Rf 0.53 (chloroform:methanol=10:1);

[1063] NMR (CD3OD): δ 7.33 (m, 5H), 5.06 (s, 2H), 4.02 (m, 1H), 3.50-3.30 (m, 2H), 3.20-3.00 (m, 4H), 3.00-2.60 (m, 4H), 2.20-2.00 (m, 2H), 1.90-1.70 (m, 3H), 1.70-1.20 (m, 7H), 0.92 (t, J=7.4 Hz, 3H), 0.90 (s, 9H).

EXAMPLE 20(H14-1)˜20(H15-77)

[1064] By the same procedure as described in Example 20 using the compound prepared in Example 8 or 8(1) and the corresponding aldehyde derivatives, the compounds of the present invention, whose names were shown in the following Table 14A-1˜15A-10, and whose structures were shown in the following Table 14B-1˜15B-12, were obtained. Also, physical data of the above compounds were shown in the following Table 14C-1˜15C-3.

246TABLE 14A-1ExampleNoCompound Name20(H14-1)(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-butyl)-9-(2,4,6-trimethoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane20(H14-2)(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-butyl)-9-(3-cyanophenylmethyl)-1,4,9-triazaspiro-[5.5]undecane20(H14-3)(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-butyl)-9-(3-methylbutyl)-1,4,9-triazaspiro-[5.5]undecane20(H14-4)(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-butyl)-9-(2-(1-carboxymethyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane20(H14-5)(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-butyl)-9-(4-dimethylaminophenylmethyl)-1,4,9-triazaspiro[5.5]undecane20(H14-6)(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-butyl)-9-(3-phenoxyphenylmethyl)-1,4,9-triazaspiro-[5.5]undecane20(H14-7)(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-butyl)-9-((2E)-2-methylbutenyl)-1,4,9-triazaspiro-[5.5]undecane

[1065]

247

TABLE 14A-2

Example

No
Compound Name

20(H14-8)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((1S,5S)-6,6-dimethylbicyclo[3.3.1]-

2-hepten-2-ylmethyl)-1,4,9-triazaspiro[5.5]-

undecane

20(H14-9)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(1-carboxymethyl)-1,4,9-triazaspiro[5.5]-

undecane

20(H14-10)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-cyclopropylmethyl-1,4,9-triazaspiro[5.5]-

undecane

20(H14-11)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3-methylthiopropyl)-1,4,9-triazaspiro[5.5]-

undecane

20(H14-12)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3-carboxypropyl)-1,4,9-triazaspiro[5.5]-

undecane

20(H14-13)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2,6-dimethyl-5-heptenyl)-1,4,9-triazaspiro-

[5.5]undecane

20(H14-14)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(quinolin-2-yl)-1,4,9-triazaspiro[5.5]-

undecane

[1066]

248

TABLE 14A-3

Example

No
Compound Name

20(H14-15)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2S,3R,4R,5R)-2-acetylamino-3,4,5,6-

tetrahydroxyhexanyl)-1,4,9-triazaspiro[5.5]-

undecane

20(H14-16)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2,2-dimethylpropyl)-1,4,9-triazaspiro[5.5]-

undecane

20(H14-17)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4Z)-decenyl)-1,4,9-triazaspiro[5.5]-

undecane

20(H14-18)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3-phenylpropyl)-1,4,9-triazaspiro[5.5]-

undecane

20(H14-19)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-butyl-1,4,9-triazaspiro[5.5]undecane

20(H14-20)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-benzyl-1,4,9-triazaspiro[5.5]undecane

20(H14-21)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2E)-3-(4-dimethylaminophenyl)propenyl)-1,4,9-

triazaspiro[5.5]undecane

[1067]

249

TABLE 14A-4

Example

No
Compound Name

20(H14-22)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)9-((2E)-3-(furan-2-yl)propenyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-23)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3-hydroxyphenylmethyl)-1,4,9-triazaspiro-

[5.5]undecane

20(H14-24)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-hydroxyphenylmethyl)-1,4,9-triazaspiro-

[5.5]undecane

20(H14-25)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-dihydroxyboranephenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-26)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-heptyloxyphenylmethyl)-1,4,9-triazaspiro-

[5.5]undecane

20(H14-27)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(benzofuran-2-ylmethyl)-1,4,9-triazaspiro-

[5.5]undecane

20(H14-28)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3-methylbenzothiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1068]

250

TABLE 14A-5

Example

No
Compound Name

20(H14-29)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-(4-chlorophenylthio)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-30)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3,7-dimethyl-6-octenyl)-1,4,9-triazaspiro-

[5.5]undecane

20(H14-31)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-(pyrrolidin-1-yl)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-32)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-methyl-3-(4-(2,2-dimethylpropyl)phenyl)-

propyl)-1,4,9-triazaspiro[5.5]undecane

20(H14-33)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-benzyloxyphenylmethyl)-1,4,9-triazaspiro-

[5.5]undecane

20(H14-34)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-hydroxy-3,5-bis(1,1-dimethylethyl)-

phenylmethyl)-1,4,9-triazaspiro[5.5]undecane

[1069]

251

TABLE 14A-6

Example

No
Compound Name

20(H14-35)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-methyl-3-(4-(1-methylethyl)phenyl)propyl)-

1,4,9-triazaspiro[5.5]undecane

20(H14-36)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3,4-di-(benzyloxy)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-37)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-octyloxyphenylmethyl)-1,4,9-triazaspiro-

[5.5]undecane

20(H14-38)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3,5,5-trimethylhexyl)-1,4,9-triazaspiro-

[5.5]undecane

20(H14-39)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-butyloxycarbonylmethyl-1,4,9-triazaspiro-

[5.5]undecane

20(H14-40)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-(4-hydroxy-4-methylpentyl)-3-cyclohexenyl-

methyl)-1,4,9-triazaspiro[5.5]undecane

20(H14-41)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(5-hydroxypentyl)-1,4,9-triazaspiro[5.5]-

undecane

[1070]

252

TABLE 14A-7

Example

No
Compound Name

20(H14-42)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-((1R,2S,3R,5R)-2-hydroxy-4,6,8-trioxaspiro-

[bicyclo[3.3.0]octan-7,1′-cyclohexan]-

3-ylmethyl)-1,4,9-triazaspiro[5.5]undecane

20(H14-43)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3-phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-44)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-(1,1-dimethylethyl)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-45)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-46)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-(2,2,6-trimethyl-1-cyclohexenyl)ethyl)-

1,4,9-triazaspiro[5.5]undecane

20(H14-47)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-(3-dimethylaminopropyloxy)phenylmethyl)-

1,4,9-triazaspiro[5.5]undecane

[1071]

253

TABLE 14A-8

Example

No
Compound Name

20(H14-48)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(furan-2-ylmethyl)-1,4,9-triazaspiro[5.5]-

undecane

20(H14-49)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-methylpropyl)-1,4,9-triazaspiro[5.5]undecane

20(H14-50)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-cyclohexylmethyl-1,4,9-triazaspiro[5.5]undecane

20(H14-51)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(thiazol-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-52)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-acetylaminophenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-53)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-methoxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-54)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-methoxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1072]

254

TABLE 14A-9

Example

No
Compound Name

20(H14-55)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-biphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-56)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2E,6E)-3,7-dimethyl-2,6-octadienyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-57)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-dimethylaminophenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-58)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-ethylhexyl)-1,4,9-triazaspiro[5.5]undecane

20(H14-59)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3-fluorophenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-60)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-hydroxyethyl)-1,4,9-triazaspiro[5.5]undecane

20(H14-61)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(naphthalen-1-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1073]

255

TABLE 14A-10

Example

No
Compound Name

20(H14-62)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-propyl-1,4,9-triazaspiro[5.5]undecane

20(H14-63)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2S,3S,4R)-2,3,4,5-tetrahydroxypentyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-64)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(thiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-65)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2E)-decenyl)-1,4,9-triazaspiro[5.5]undecane

20(H14-66)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-chlorophenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-67)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(1,3-benzodioxolen-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-68)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((3S,4R)-3,4,5-trihydroxypentyl)-1,4,9-

triazaspiro[5.5]undecane

[1074]

256

TABLE 14A-11

Example

No
Compound Name

20(H14-69)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2,3-dimethyl-5-oxo-1-phenyl-3-pyrazolin-4-

ylmethyl)-1,4,9-triazaspiro[5.5]undecane

20(H14-70)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-((2E)-4-methylpentenyl)-3-cyclohexenyl-

methyl)-1,4,9-triazaspiro[5.5]undecane

20(H14-71)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3-methoxy-4-hexyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-72)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-fluorophenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-73)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3,5,6-trimethyl-3-cyclohexenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-74)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

20(H14-75)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-benzyloxyethyl)-1,4,9-triazaspiro[5.5]-

undecane

[1075]

257

TABLE 14A-12

Example

No
Compound Name

20(H14-76)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3-methoxy-4-benzyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-77)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3-benzyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-78)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-benzyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-79)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H14-80)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-allyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1076]

258

TABLE 15A-1

Example

No
Compound Name

20(H15-1)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2,4,6-

trimethoxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-2)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-

cyanophenylmethyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-3)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-

methylbutyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-4)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-(1-

carboxymethyloxy)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-5)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

dimethylaminophenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-6)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-

phenoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-7)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2E)-2-

methylbutenyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-8)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((1S,5S)-

6,6-dimethylbicyclo[3.3.1]-2-hepten-2-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

[1077]

259

TABLE 15A-2

Example

No
Compound Name

20(H15-9)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(1-

carboxymethyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-10)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

cyclopropylmethyl-1,4,9-triazaspiro[5.5]undecane

20(H15-11)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-

methylthiopropyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-12)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-

carboxypropyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-13)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2,6-

dimethyl-5-heptenyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-14)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(quinolin-

2-yl)-1,4,9-triazaspiro[5.5]undecane

20(H15-15)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2S,3R,4R,5R)-

2-acetylamino-3,4,5,6-tetrahydroxyhexanyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-16)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2,2-

dimethylpropyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-17)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4Z)-decenyl)-

1,4,9-triazaspiro[5.5]undecane

[1078]

260

TABLE 15A-3

Example

No
Compound Name

20(H15-18)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-phenylpropyl)-

1,4,9-triazaspiro[5.5]undecane

20(H15-19)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-butyl-1,4,9-

triazaspiro[5.5]undecane

20(H15-20)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

20(H15-21)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2E)-3-(furan-2-

yl)propenyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-22)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-

hydroxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-23)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-

hydroxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-24)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

dihydroxyboranephenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-25)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

heptyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-26)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(benzofuran-2-

ylmethyl)-1,4,9-triazaspiro[5.5]undecane

[1079]

261

TABLE 15A-4

Example

No
Compound Name

20(H15-27)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-

methylbenzothiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-28)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-(4-

chlorophenylthio)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-29)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,7-dimethyl-

6-octenyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-30)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(pyrrolidin-

1-yl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-31)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-methyl-3-

(4-(2,2-dimethylpropyl)phenyl)propyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-32)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-

benzyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-33)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-hydroxy-

3,5-di-(1,1-dimethylethyl)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-34)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-methyl-3-(4-

(1-methylethyl)phenyl)propyl)-1,4,9-

triazaspiro[5.5]undecane

[1080]

262

TABLE 15A-5

Example

No
Compound Name

20(H15-35)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,4-di-

(benzyloxy)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-36)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

octyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-37)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5,5-

trimethylhexyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-38)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

butyloxycarbonylmethyl-1,4,9-

triazaspiro[5.5]undecane

20(H15-39)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-

hydroxy-4-methylpentyl)-3-cyclohexenylmethyl)-

1,4,9-triazaspiro[5.5]undecane

20(H15-40)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-

hydroxypentyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-41)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-

((1R,2S,3R,5R)-2-hydroxy-4,6,8-

trioxaspiro[bicyclo[3.3.0]octan-7,1′-

cyclohexan]-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-42)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-

phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1081]

263

TABLE 15A-6

Example

No
Compound Name

20(H15-43)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(1,1-

dimethylethyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-44)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(1,4-benzodioxan-

6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-45)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-(2,2,6-

trimethyl-1-cyclohexenyl)ethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-46)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(3-

dimethylaminopropyloxy)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-47)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(furan-2-

ylmethyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-48)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-

methylpropyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-49)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

cyclohexylmethyl-1,4,9-triazaspiro[5.5]undecane

20(H15-50)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(thiazol-2-

ylmethyl)-1,4,9-triazaspiro[5.5]undecane

[1082]

264

TABLE 15A-7

Example

No
Compound Name

20(H15-51)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

acetylaminophenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-52)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-

methoxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-53)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

methoxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-54)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

biphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-55)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-

ethylhexyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-56)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-

fluorophenylmethyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-57)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-

hydroxyethyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-58)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(naphthalen-1-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-59)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

propyl-1,4,9-triazaspiro[5.5]undecane

[1083]

265

TABLE 15A-8

Example

No
Compound Name

20(H15-60)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2S,3S,4R)-

2,3,4,5-tetrahydroxypentyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-61)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(thiophen-2-

ylmethyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-62)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2E)-decenyl)-

1,4,9-triazaspiro[5.5]undecane

20(H15-63)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

chlorophenylmethyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-64)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(1,3-

benzodioxolen-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-65)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((3S,4R)-3,4,5-

trihydroxypentyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-66)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2,3-dimethyl-

5-oxo-1-phenyl-3-pyrazolin-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-67)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-((2E)-4-

methylpentenyl)-3-cyclohexenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1084]

266

TABLE 15A-9

Example

No
Compound Name

20(H15-68)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-methoxy-

4-hexyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-69)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

fluorophenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-70)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5,6-

trimethyl-3-cyclohexenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-71)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-

dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-72)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-benzyl-

oxyethyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-73)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-methoxy-

4-benzyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-74)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-

benzyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

20(H15-75)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

benzyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1085]

267

TABLE 15A-10

Example

No
Compound Name

20(H15-76)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

20(H15-77)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

allyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

[1086]

268

TABLE 14B-1

1449

Example No
R1

20(H14-1)

1450

20(H14-2)

1451

20(H14-3)

1452

20(H14-4)

1453

20(H14-5)

1454

20(H14-6)

1455

[1087]

269

TABLE 14B-2

1456

Example No
R1

20(H14-7)

1457

20(H14-8)

1458

20(H14-9)

1459

20(H14-10)

1460

20(H14-11)

1461

20(H14-12)

1462

20(H14-13)

1463

20(H14-14)

1464

[1088]

270

TABLE 14B-3

1465

Example No
R1

20(H14-15)

1466

20(H14-16)

1467

20(H14-17)

1468

20(H14-18)

1469

20(H14-19)

1470

20(H14-20)

1471

20(H14-21)

1472

20(H14-22)

1473

[1089]

271

TABLE 14B-4

1474

Example No
R1

20(H14-23)

1475

20(H14-24)

1476

20(H14-25)

1477

20(H14-26)

1478

20(H14-27)

1479

20(H14-28)

1480

20(H14-29)

1481

[1090]

272

TABLE 14B-5

1482

Example No
R1

20(H14-30)

1483

20(H14-31)

1484

20(H14-32)

1485

20(H14-33)

1486

20(H14-34)

1487

20(H14-35)

1488

[1091]

273

TABLE 14B-6

1489

Example No
R1

20(H14-36)

1490

20(H14-37)

1491

20(H14-38)

1492

20(H14-39)

1493

20(H14-40)

1494

20(H14-41)

1495

20(H14-42)

1496

[1092]

274

TABLE 14B-7

1497

Example No
R1

20(H14-43)

1498

20(H14-44)

1499

20(H14-45)

1500

20(H14-46)

1501

20(H14-48)

1502

20(H14-49)

1503

[1093]

275

TABLE 14B-8

1504

Example No
R1

20(H14-50)

1505

20(H14-51)

1506

20(H14-52)

1507

20(H14-53)

1508

20(H14-54)

1509

20(H14-55)

1510

20(H14-56)

1511

20(H14-57)

1512

[1094]

276

TABLE 14B-9

1513

Example No
R1

20(H14-58)

1514

20(H14-59)

1515

20(H14-60)

1516

20(H14-61)

1517

20(H14-62)

1518

20(H14-63)

1519

20(H14-64)

1520

20(H14-65)

1521

20(H14-66)

1522

[1095]

277

TABLE 14B-10

1523

Example No
R1

20(H14-67)

1524

20(H14-68)

1525

20(H14-69)

1526

20(H14-70)

1527

20(H14-71)

1528

20(H14-72)

1529

20(H14-73)

1530

[1096]

278

TABLE 14B-11

1531

Example No
R1

20(H14-74)

1532

20(H14-75)

1533

20(H14-76)

1534

20(H14-77)

1535

20(H14-78)

1536

20(H14-79)

1537

20(H14-80)

1538

[1097]

279

TABLE 15B-1

1539

Example No
R1

20(H15-1)

1540

20(H15-2)

1541

20(H15-3)

1542

20(H15-4)

1543

20(H15-5)

1544

20(H15-6)

1545

[1098]

280

TABLE 15B-2

1546

Example No
R1

20(H15-7)

1547

20(H15-8)

1548

20(H15-9)

1549

20(H15-10)

1550

20(H15-11)

1551

20(H15-12)

1552

20(H15-13)

1553

20(H15-14)

1554

[1099]

281

TABLE 15B-3

1555

Example No
R1

20(H15-15)

1556

20(H15-16)

1557

20(H15-17)

1558

20(H15-18)

1559

20(H15-19)

1560

20(H15-20)

1561

20(H15-21)

1562

20(H15-22)

1563

[1100]

282

TABLE 15B-4

1564

Example No
R1

20(H15-23)

1565

20(H15-24)

1566

20(H15-25)

1567

20(H15-26)

1568

20(H15-27)

1569

20(H15-28)

1570

20(H15-29)

1571

[1101]

283

TABLE 15B-5

1572

Example No
R1

20(H15-30)

1573

20(H15-31)

1574

20(H15-32)

1575

20(H15-33)

1576

20(H15-34)

1577

[1102]

284

TABLE 15B-6

1578

Example No
R1

20(H15-35)

1579

20(H15-36)

1580

20(H15-37)

1581

20(H15-38)

1582

20(H15-39)

1583

20(H15-40)

1584

20(H15-41)

1585

[1103]

285

TABLE 15B-7

1586

Example No
R1

20(H15-42)

1587

20(H15-43)

1588

20(H15-44)

1589

20(H15-45)

1590

20(H15-46)

1591

20(H15-47)

1592

20(H15-48)

1593

[1104]

286

TABLE 15B-8

1594

Example No
R1

20(H15-49)

1595

20(H15-50)

1596

20(H15-51)

1597

20(H15-52)

1598

20(H15-53)

1599

20(H15-54)

1600

20(H15-55)

1601

[1105]

287

TABLE 15B-9

1602

Example No
R1

20(H15-56)

1603

20(H15-57)

1604

20(H15-58)

1605

20(H15-59)

1606

20(H15-60)

1607

20(H15-61)

1608

20(H15-62)

1609

20(H15-63)

1610

20(H15-64)

1611

[1106]

288

TABLE 15B-10

1612

Example No
R1

20(H15-65)

1613

20(H15-66)

1614

20(H15-67)

1615

20(H15-68)

1616

20(H15-69)

1617

20(H15-70)

1618

[1107]

289

TABLE 15B-11

1619

Example No
R1

20(H15-71)

1620

20(H15-72)

1621

20(H15-73)

1622

20(H15-74)

1623

20(H15-75)

1624

20(H15-76)

1625

[1108]

290

TABLE 15B-12

1626

Example No
R1

20(H15-77)

1627

[1109]

291

TABLE 14C-1

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

20(H14-1)
F
3.40
611 (M + H)+.
ESI (Pos., 20 V)

20(H14-2)
F
3.27
546 (M + H)+.
ESI (Pos., 20 V)

20(H14-3)
F
3.29
501 (M + H)+.
ESI (Pos., 20 V)

20(H14-4)
F
3.25
595 (M + H)+.
ESI (Pos., 20 V)

20(H14-5)
F
3.12
564 (M + H)+.
ESI (Pos., 20 V)

20(H14-6)
F
3.52
613 (M + H)+.
ESI (Pos., 20 V)

20(H14-7)
F
3.25
499 (M + H)+.
ESI (Pos., 20 V)

20(H14-8)
F
3.49
565 (M + H)+.
ESI (Pos., 20 V)

20(H14-9)
F
3.09
489 (M + H)+.
ESI (Pos., 20 V)

20(H14-10)
F
3.18
485 (M + H)+.
ESI (Pos., 20 V)

20(H14-11)
F
3.23
519 (M + H)+.
ESI (Pos., 20 V)

20(H14-12)
F
3.12
517 (M + H)+.
ESI (Pos., 20 V)

20(H14-13)
F
3.53
555 (M + H)+.
ESI (Pos., 20 V)

20(H14-14)
F
3.33
572 (M + H)+.
ESI (Pos., 20 V)

20(H14-15)
F
3.03
636 (M + H)+.
ESI (Pos., 20 V)

20(H14-16)
F
3.25
501 (M + H)+.
ESI (Pos., 20 V)

20(H14-17)
F
3.66
569 (M + H)+.
ESI (Pos., 20 V)

20(H14-18)
F
3.38
549 (M + H)+.
ESI (Pos., 20 V)

20(H14-19)
F
3.22
487 (M + H)+.
ESI (Pos., 20 V)

20(H14-20)
F
3.29
521 (M + H)+.
ESI (Pos., 20 V)

20(H14-21)
F
3.11
590 (M + H)+.
ESI (Pos., 20 V)

20(H14-22)
F
3.31
537 (M + H)+.
ESI (Pos., 20 V)

20(H14-23)
F
3.20
537 (M + H)+.
ESI (Pos., 20 V)

20(H14-24)
F
3.23
537 (M + H)+.
ESI (Pos., 20 V)

20(H14-25)
F
3.16
565 (M + H)+.
ESI (Pos., 20 V)

20(H14-26)
F
3.82
635 (M + H)+.
ESI (Pos., 20 V)

[1110]

292

TABLE 14C-2

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

20(H14-27)
F
3.36
561 (M + H)+.
ESI (Pos., 20 V)

20(H14-28)
F
3.44
591 (M + H)+.
ESI (Pos., 20 V)

20(H14-29)
F
3.62
663 (M + H)+.
ESI (Pos., 20 V)

20(H14-30)
F
3.60
569 (M + H)+.
ESI (Pos., 20 V)

20(H14-31)
F
3.40
590 (M + H)+.
ESI (Pos., 20 V)

20(H14-32)
F
3.67
619 (M + H)+.
ESI (Pos., 20 V)

20(H14-33)
F
3.51
627 (M + H)+.
ESI (Pos., 20 V)

20(H14-34)
F
3.66
649 (M + H)+.
ESI (Pos., 20 V)

20(H14-35)
F
3.64
605 (M + H)+.
ESI (Pos., 20 V)

20(H14-36)
F
3.71
733 (M + H)+.
ESI (Pos., 20 V)

20(H14-37)
F
3.91
649 (M + H)+.
ESI (Pos., 20 V)

20(H14-38)
F
3.56
557 (M + H)+.
ESI (Pos., 20 V)

20(H14-39)
F
3.33
545 (M + H)+.
ESI (Pos., 20 V)

20(H14-40)
F
3.38
625 (M + H)+.
ESI (Pos., 20 V)

20(H14-41)
F
3.12
517 (M + H)+.
ESI (Pos., 20 V)

20(H14-42)
F
3.34
643 (M + H)+.
ESI (Pos., 20 V)

20(H14-43)
F
3.23
587 (M + H)+.
ESI (Pos., 20 V)

20(H14-44)
F
3.53
577 (M + H)+.
ESI (Pos., 20 V)

20(H14-45)
F
3.31
579 (M + H)+.
ESI (Pos., 20 V)

20(H14-46)
F
3.60
581 (M + H)+.
ESI (Pos., 20 V)

20(H14-47)
F
3.09
622 (M + H)+.
ESI (Pos., 20 V)

20(H14-48)
F
3.22
511 (M + H)+.
ESI (Pos., 20 V)

20(H14-49)
F
3.20
487 (M + H)+.
ESI (Pos., 20 V)

20(H14-50)
F
3.36
527 (M + H)+.
ESI (Pos., 20 V)

20(H14-51)
F
3.14
528 (M + H)+.
ESI (Pos., 20 V)

20(H14-52)
F
3.16
578 (M + H)+.
ESI (Pos., 20 V)

[1111]

293

TABLE 14C-3

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

20(H14-53)
F
3.31
551 (M + H)+.
ESI (Pos., 20 V)

20(H14-54)
F
3.31
551 (M + H)+.
ESI (Pos., 20 V)

20(H14-55)
F
3.51
597 (M + H)+.
ESI (Pos., 20 V)

20(H14-56)
F
3.55
567 (M + H)+.
ESI (Pos., 20 V)

20(H14-57)
F
3.09
592 (M + H)+.
ESI (Pos., 20 V)

20(H14-58)
F
3.51
543 (M + H)+.
ESI (Pos., 20 V)

20(H14-59)
F
3.31
539 (M + H)+.
ESI (Pos., 20 V)

20(H14-60)
F
3.07
475 (M + H)+.
ESI (Pos., 20 V)

20(H14-61)
F
3.40
571 (M + H)+.
ESI (Pos., 20 V)

20(H14-62)
F
3.15
473 (M + H)+.
ESI (Pos., 20 V)

20(H14-63)
F
3.04
565 (M + H)+.
ESI (Pos., 20 V)

20(H14-64)
F
3.25
527 (M + H)+.
ESI (Pos., 20 V)

20(H14-65)
F
3.69
569 (M + H)+.
ESI (Pos., 20 V)

20(H14-66)
F
3.38
555 (M + H)+.
ESI (Pos., 20 V)

20(H14-67)
F
3.29
565 (M + H)+.
ESI (Pos., 20 V)

20(H14-68)
F
3.03
549 (M + H)+.
ESI (Pos., 20 V)

20(H14-69)
F
3.22
631 (M + H)+.
ESI (Pos., 20 V)

20(H14-70)
F
3.69
607 (M + H)+.
ESI (Pos., 20 V)

20(H14-71)
F
3.66
651 (M + H)+.
ESI (Pos., 20 V)

20(H14-72)
F
3.31
539 (M + H)+.
ESI (Pos., 20 V)

20(H14-73)
F
3.50
567 (M + H)+.
ESI (Pos., 20 V)

20(H14-74)
F
3.31
615 (M + H)+.
ESI (Pos., 20 V)

20(H14-75)
F
3.35
565 (M + H)+.
ESI (Pos., 20 V)

20(H14-76)
F
3.51
657 (M + H)+.
ESI (Pos., 20 V)

20(H14-77)
F
3.55
627 (M + H)+.
ESI (Pos., 20 V)

20(H14-78)
F
3.55
627 (M + H)+.
ESI (Pos., 20 V)

[1112]

294

TABLE 14C-4

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

20(H14-79)
F
3.53
613 (M + H)+.
ESI (Pos., 20 V)

20(H14-80)
F
3.42
577 (M + H)+.
ESI (Pos., 20 V)

[1113]

295

TABLE 15C-1

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

20(H15-1)
D
12.20
462 (M + H)+,
APCI (Pos., 40 V)

282, 181.

20(H15-2)
D
10.20
397 (M + H)+.
APCI (Pos., 40 V)

20(H15-3)
D
10.50
352 (M + H)+.
APCI (Pos., 40 V)

20(H15-4)
D
10.90
446 (M + H)+.
APCI (Pos., 40 V)

20(H15-5)
D
9.47
415 (M + H)+,
APCI (Pos., 40 V)

282, 150.

20(H15-6)
D
13.90
464 (M + H)+.
APCI (Pos., 40 V)

20(H15-7)
D
10.50
350 (M + H)+.
APCI (Pos., 40 V)

20(H15-8)
D
13.70
416 (M + H)+.
APCI (Pos., 40 V)

20(H15-9)
D
8.05
340 (M + H)+,
APCI (Pos., 40 V)

282.

20(H15-10)
D
9.26
336 (M + H)+.
APCI (Pos., 40 V)

20(H15-11)
D
9.73
370 (M + H)+,
APCI (Pos., 40 V)

282.

20(H15-12)
D
8.36
368 (M + H)+,
APCI (Pos., 40 V)

310, 282.

20(H15-13)
D
13.70
406 (M + H)+.
APCI (Pos., 40 V)

20(H15-14)
D
12.40
423 (M + H)+,
APCI (Pos., 40 V)

158.

20(H15-15)
D
7.94
487 (M + H)+,
APCI (Pos., 40 V)

310, 282.

20(H15-16)
D
9.94
352 (M + H)+,
APCI (Pos., 40 V)

310.

20(H15-17)
D
15.10
420 (M + H)+.
APCI (Pos., 40 V)

20(H15-18)
D
11.80
400 (M + H)+.
APCI (Pos., 40 V)

20(H15-19)
D
9.80
338 (M + H)+.
APCI (Pos., 40 V)

20(H15-20)
D
10.80
372 (M + H)+.
APCI (Pos., 40 V)

20(H15-21)
D
11.20
388 (M + H)+.
APCI (Pos., 40 V)

20(H15-22)
D
10.10
388 (M + H)+.
APCI (Pos., 40 V)

20(H15-23)
D
10.70
388 (M + H)+,
APCI (Pos., 40 V)

282.

20(H15-24)
D
9.80
416 (M + H)+,
APCI (Pos., 40 V)

372, 310, 282.

20(H15-25)
D
16.40
486 (M + H)+.
APCI (Pos., 40 V)

20(H15-26)
D
12.30
412 (M + H)+.
APCI (Pos., 40 V)

[1114]

296

TABLE 15C-2

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

20(H15-27)
D
13.20
442 (M + H)+.
APCI (Pos., 40 V)

20(H15-28)
D
14.90
514 (M + H)+.
APCI (Pos., 40 V)

20(H15-29)
D
14.40
420 (M + H)+.
APCI (Pos., 40 V)

20(H15-30)
D
13.20
441 (M + H)+,
APCI (Pos., 40 V)

282, 160.

20(H15-31)
D
15.40
470 (M + H)+.
APCI (Pos., 40 V)

20(H15-32)
D
13.80
478 (M + H)+.
APCI (Pos., 40 V)

20(H15-33)
D
15.10
500 (M + H)+,
APCI (Pos., 40 V)

282, 219.

20(H15-34)
D
14.90
456 (M + H)+.
APCI (Pos., 40 V)

20(H15-35)
D
15.60
584 (M + H)+.
APCI (Pos., 40 V)

20(H15-36)
D
17.10
500 (M + H)+.
APCI (Pos., 40 V)

20(H15-37)
D
14.30
408 (M + H)+.
APCI (Pos., 40 V)

20(H15-38)
D
11.60
396 (M + H)+.
APCI (Pos., 40 V)

20(H15-39)
D
13.30
476 (M + H)+,
APCI (Pos., 40 V)

458.

20(H15-40)
D
8.94
368 (M + H)+,
APCI (Pos., 40 V)

310, 282.

20(H15-41)
D
13.30
516 (M + Na)+,
APCI (Pos., 40 V)

494 (M + H)+.

20(H15-42)
D
11.10
438 (M + H)+,
APCI (Pos., 40 V)

282, 189, 173.

20(H15-43)
D
14.40
428 (M + H)+.
APCI (Pos., 40 V)

20(H15-44)
D
11.10
430 (M + H)+.
APCI (Pos., 40 V)

20(H15-45)
D
14.50
432 (M + H)+.
APCI (Pos., 40 V)

20(H15-46)
D
9.21
473 (M + H)+.
APCI (Pos., 40 V)

20(H15-47)
D
9.84
362 (M + H)+.
APCI (Pos., 40 V)

20(H15-48)
D
9.57
338 (M + H)+.
APCI (Pos., 40 V)

20(H15-49)
D
11.70
378 (M + H)+.
APCI (Pos., 40 V)

20(H15-50)
D
9.42
379 (M + H)+.
APCI (Pos., 40 V)

20(H15-51)
D
10.00
429 (M + H)+.
APCI (Pos., 40 V)

20(H15-52)
D
11.40
402 (M + H)+.
APCI (Pos., 40 V)

[1115]

297

TABLE 15C-3

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

20(H15-53)
D
11.30
402 (M + H)+.
APCI (Pos., 40 V)

20(H15-54)
D
14.00
448 (M + H)+.
APCI (Pos., 40 V)

20(H15-55)
D
13.50
394 (M + H)+.
APCI (Pos., 40 V)

20(H15-56)
D
11.10
390 (M + H)+.
APCI (Pos., 40 V)

20(H15-57)
D
8.00
326 (M + H)+,
APCI (Pos., 40 V)

296.

20(H15-58)
D
12.90
422 (M + H)+.
APCI (Pos., 40 V)

20(H15-59)
D
9.05
324 (M + H)+.
APCI (Pos., 40 V)

20(H15-60)
D
8.00
414 (M + H)+,
APCI (Pos., 40 V)

340, 310, 282.

20(H15-61)
D
10.40
378 (M + H)+,
APCI (Pos., 40 V)

310.

20(H15-62)
D
15.70
420 (M + H)+.
APCI (Pos., 40 V)

20(H15-63)
D
12.30
406 (M + H)+.
APCI (Pos., 40 V)

20(H15-64)
D
11.10
416 (M + H)+.
APCI (Pos., 40 V)

20(H15-65)
D
7.79
400 (M + H)+,
APCI (Pos., 40 V)

310, 282.

20(H15-66)
D
10.60
482 (M + H)+,
APCI (Pos., 40 V)

282.

20(H15-67)
D
15.60
458 (M + H)+.
APCI (Pos., 40 V)

20(H15-68)
D
15.40
502 (M + H)+,
APCI (Pos., 40 V)

137.

20(H15-69)
D
11.20
390 (M + H)+.
APCI (Pos., 40 V)

20(H15-70)
D
13.60
418 (M + H)+.
APCI (Pos., 40 V)

20(H15-71)
D
11.40
466 (M + H)+,
APCI (Pos., 40 V)

217.

20(H15-72)
D
12.40
416 (M + H)+.
APCI (Pos., 40 V)

20(H15-73)
D
13.70
508 (M + H)+.
APCI (Pos., 40 V)

20(H15-74)
D
14.20
478 (M + H)+.
APCI (Pos., 40 V)

20(H15-75)
D
14.20
478 (M + H)+.
APCI (Pos., 40 V)

20(H15-76)
D
13.70
464 (M + H)+,
APCI (Pos., 40 V)

205.

20(H15-77)
D
12.60
428 (M + H)+.
APCI (Pos., 40 V)

EXAMPLE 21

[1116] (3S)-1-propyl-2,5-dioxo-3-(4-(benzylcarbonylamino) butyl)-9-(3-phenylpropanoyl)-1,4,9-triazaspiro[5.5]undecane

1628

[1117] To a solution of the compound prepared in Example 8 (0.01 g) in dichloroethane (0.2 ml) were added diisopropylethylamine (6 μl), 3-phenylpropanoyl chloride (5 μl). The reaction mixture was stirred for 1 hour at room temperature. The reaction mixture was passed through the column with aminomethylated polystyrene-2% divinylbenzene copolymer resin (NovaBiochem, AM Resin, 50 mg). The resin was washed with dichloroethane and filtrated. The filtrate was concentrated to give the compound of the present invention (14 mg) having the following physical data.

[1118] TLC: Rf 0.55 (chloroform:methanol=10:1);

[1119] NMR (CD3OD): δ 7.40-7.10 (m, 10H), 5.06 (s, 2H), 4.03 (m, 1H), 3.70-3.55 (m, 2H), 3.28-3.00 (m, 5H), 3.00-2.80 (m, 3H), 2.80-2.60 (m, 2H), 2.00-1.65 (m, 6H), 1.65-1.40 (m, 6H), 0.90 (t, J=7.2 Hz, 3H).

EXAMPLE 21(1)

[1120] (3S)-1-propyl-2,5-dioxo-3-(4-(benzylcarbonylamino) butyl)-9-benzenesulfonyl-1,4,9-triazaspiro[5.5]undecane

1629

[1121] By the same procedure as described in Example 21 using the compound prepared in Example 8 (0.01 g), diisopropylethylamine (6 μl) and benzenesulfonyl chloride (4.5 μl), the compound of the present invention (16 mg) having the following physical data was obtained.

[1122] TLC: Rf 0.58 (chloroform:methanol=10:1);

[1123] NMR (CD3OD): δ 7.80 (m, 2H), 7.63 (m, 3H), 7.33 (m, 5H), 5.04 (s, 2H), 3.98 (t, J=4.8 Hz, 1H), 3.60-3.35 (m, 2H), 3.28-2.90 (m, 6H), 2.20-1.65 (m, 6H), 1.65-1.20 (m, 6H), 0.89 (t, J=7.2 Hz, 3H).

EXAMPLE 21(2)

[1124] (3S)-1-propyl-2,5-dioxo-3-(4-(benzylcarbonylamino) butyl)-9-benzylaminocarbonyl-1,4,9-triazaspiro[5.5]undecane

1630

[1125] By the same procedure as described in Example 21 using the compound prepared in Example 8 (0.01 g) and benzyl isocyanate (4 μl), the compound of the present invention (16 mg) having the following physical data was obtained.

[1126] TLC: Rf 0.45 (chloroform:methanol=10:1);

[1127] NMR (CD3OD): b 7.40-7.10 (m, 10H), 5.05 (s, 2H), 4.37 (s, 2H), 4.10-3.90 (m, 3H), 3.60-3.45 (m, 2H), 3.30-3.00 (m, 4H), 2.10-1.70 (m, 6H), 1.65-1.20 (m, 6H), 0.87 (t, J=7.4 Hz, 3H).

EXAMPLE 21 (H16-1)˜21 (H19-71)

[1128] By the same procedure as described in Example 21, 21(1) or 21(2), using the compound prepared in Example 8 or 8(1) and the corresponding acid chloride derivatives, sulfonyl chloride derivatives or isocyanate derivatives, the compounds of the present invention, whose names were shown in the following Table 16A-1˜19A-9, and whose structures were shown in the following Table 16B-1˜19B-11, were obtained. Also, physical data of the above compounds were shown in the following Table 16C-1˜19C-3.

298TABLE 16A-1ExampleNoCompound Name21(H16-1)(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-butyl)-9-((4-phenylphenyl)carbonyl)-1,4,9-triazaspiro[5.5]undecane21(H16-2)(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-butyl)-9-((4-dimethylaminophenyl)carbonyl)-1,4,9-triazaspiro[5.5]undecane21(H16-3)(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-butyl)-9-((3-(2-chlorophenyl)-5-methylisooxazol-4-yl)carbonyl)-1,4,9-triazaspiro[5.5]undecane21(H16-4)(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-butyl)-9-((4-fluorophenyl)carbonyl)-1,4,9-triazaspiro[5.5]undecane21(H16-5)(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-butyl)-9-((3-fluorophenyl)carbonyl)-1,4,9-triazaspiro[5.5]undecane21(H16-6)(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-butyl)-9-((2-fluorophenyl)carbonyl)-1,4,9-triazaspiro[5.5]undecane21(H16-7)(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-butyl)-9-(cyclopentylcarbonyl)-1,4,9-triazaspiro[5.5]undecane

[1129]

299

TABLE 16A-2

Example

No
Compound Name

21(H16-8)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((3-methylphenyl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-9)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((3-methoxyphenyl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-10)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2,2-dimethylpropanoyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-11)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(pyridin-3-ylcarbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-12)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(pyridin-4-ylcarbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-13)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(pyridin-2-ylcarbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-14)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-phenylacetyl)-1,4,9-

triazaspiro[5.5]undecane

[1130]

300

TABLE 16A-3

Example

No
Compound Name

21(H16-15)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-phenyloxyacetyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-16)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-ethyl-2,3-dioxopiperazinyl)carbonyl)-

1,4,9-triazaspiro[5.5]undecane

21(H16-17)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2-phenylthiopyridin-3-yl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-18)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2-phenyloxypyridin-3-yl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-19)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2-methoxyphenyl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-20)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-(thiophen-2-yl)acetyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-21)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-hexanoyl-1,4,9-triazaspiro[5.5]undecane

[1131]

301

TABLE 16A-4

Example

No
Compound Name

21(H16-22)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-methylphenyl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-23)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-methylpropanoyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-24)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3-cyclopentylpropanoyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-25)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2E)3-phenyl-2-propenoyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-26)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2-methylphenyl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-27)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3,3-dimethylbutenoyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-28)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(cyclohexylcarbonyl)-1,4,9-

triazaspiro[5.5]undecane

[1132]

302

TABLE 16A-5

Example

No
Compound Name

21(H16-29)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(phenylcarbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-30)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(thiophen-2-ylcarbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-31)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2,6,6-trimethyl-1-cyclohexenyl)carbonyl)-

1,4,9-triazaspiro[5.5]undecane

21(H16-32)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(ethoxyoxalyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-33)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((3-phenyl-5-methylisooxazol-4-yl)carbonyl)-

1,4,9-triazaspiro[5.5]undecane

21(H16-34)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((5-methyl-2-phenyl-1,2,3-triazol-4-

yl)carbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H16-35)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-(3-methoxyphenyl)acetyl)-1,4,9-

triazaspiro[5.5]undecane

[1133]

303

TABLE 16A-6

Example

No
Compound Name

21(H16-36)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-methoxyphenylcarbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-37)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((furan-2-yl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-38)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-benzyloxyacetyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-39)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(cyclobutylcarbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-40)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-(4-methoxyphenyl)acetyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-41)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-acetyl-1,4,9-triazaspiro[5.5]undecane

21(H16-42)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(4-methylpentanoyl)-1,4,9-

triazaspiro[5.5]undecane

[1134]

304

TABLE 16A-7

Example

No
Compound Name

21(H16-43)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-methoxyacetyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-44)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3-methylthiopropanoyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-45)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((isooxazol-5-yl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-46)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-cyclopentylacetyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-47)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-pentanoyl-1,4,9-

triazaspiro[5.5]undecane

21(H16-48)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(3-methylbutanoyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-49)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-phenylthioacetyl)-1,4,9-

triazaspiro[5.5]undecane

[1135]

305

TABLE 16A-8

Example

No
Compound Name

21(H16-50)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-methyl-1,2,3-thiadiazol-5-yl)carbonyl)-

1,4,9-triazaspiro[5.5]undecane

21(H16-51)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((3-cyanophenyl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-52)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-butanoyl-1,4,9-triazaspiro[5.5]undecane

21(H16-53)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-propanoyl-1,4,9-triazaspiro[5.5]undecane

21(H16-54)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(cyclopropylcarbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-55)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2H-benzo[3,4-d]1,3-dioxolan-5-

ylcarbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H16-56)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((1-phenyl-5-propylpyrazol-4-yl)carbonyl)-

1,4,9-triazaspiro[5.5]undecane

[1136]

306

TABLE 16A-9

Example

No
Compound Name

21(H16-57)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((5-(1,1-dimethylethyl)-2-methylfuran-3-yl)-

carbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H16-58)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((1-(1,1-dimethylethyl)-3-methylpyrazol-5-yl)-

carbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H16-59)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-methylsulfonyl-1,4,9-triazaspiro[5.5]undecane

21(H16-60)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-pentylsulfonyl-1,4,9-triazaspiro[5.5]undecane

21(H16-61)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((1-methylethyl)sulfonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H16-62)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-chlorophenyl)sulfonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H16-63)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2-iodophenyl)sulfonyl)-1,4,9-triazaspiro[5.5]-

undecane

[1137]

307

TABLE 16A-10

Example

No
Compound Name

21(H16-64)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-nitrophenyl)sulfonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H16-65)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-methylsulfonylphenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-66)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-trifluoromethylphenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-67)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-biphenyl)sulfonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H16-68)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2-biphenyl)sulfonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H16-69)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2-methoxycarbonylphenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-70)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((3,4-difluorophenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

[1138]

308

TABLE 16A-11

Example

No
Compound Name

21(H16-71)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2,6-difluorophenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-72)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2,5-difluorophenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-73)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2,5-dimethoxyphenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-74)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2-chloro-4-trifluoromethylphenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-75)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(2-naphthylsulfonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H16-76)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(((1E)-2-phenylvinyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H16-77)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((furan-2-yl)sulfonyl)-1,4,9-triazaspiro[5.5]-

undecane

[1139]

309

TABLE 16A-12

Example

No
Compound Name

21(H16-78)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((thiophen-2-yl)sulfonyl)-1,4,9-triazaspiro[5.5]-

undecane

[1140]

310

TABLE 17A-1

Example

No
Compound Name

21(H17-1)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-bromo-2,5-dichlorothiophen-3-yl)sulfonyl)-

1,4,9-triazaspiro[5.5]undecane

21(H17-2)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((5-phenylsulfonylthiophen-2-yl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-3)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((7-chlorobenzofurazan-4-yl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-4)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-methyl-2-acetylaminothiazol-5-yl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-5)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2-methoxy-dibenzofuran-3-yl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-6)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((3,4-dichlorophenyl)sulfonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H17-7)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-methoxyphenyl)sulfonyl)-1,4,9-triazaspiro[5.5]-

undecane

[1141]

311

TABLE 17A-2

Example

No
Compound Name

21(H17-8)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-benzylsulfonyl-1,4,9-triazaspiro[5.5]undecane

21(H17-9)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((ethylamino)carbonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H17-10)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((propylamino)carbonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H17-11)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((1-methylethylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-12)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((ethoxycarbonylmethylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-13)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((butylamino)carbonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H17-14)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-chlorophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

[1142]

312

TABLE 17A-3

Example

No
Compound Name

21(H17-15)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((phenylamino)carbonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H17-16)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-methylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-17)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((hexylamino)carbonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H17-18)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-fluorophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-19)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((benzylamino)carbonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H17-20)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((cyclohexylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-21)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((3-methylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

[1143]

313

TABLE 17A-4

Example

No
Compound Name

21(H17-22)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((octylamino)carbonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H17-23)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-bromophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-24)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2-(thiophen-2-yl)ethylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-25)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-(1-methylethyl)phenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-26)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((3-chlorophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-27)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2,4,5-trimethylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-28)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2,4,6-trimethylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

[1144]

314

TABLE 17A-5

Example

No
Compound Name

21(H17-29)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-phenyloxyphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-30)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-butyloxyphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-31)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-phenylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-32)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2-phenylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-33)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-trifluoromethylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-34)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((3,4-dichlorophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-35)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-butyloxycarbonylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

[1145]

315

TABLE 17A-6

Example

No
Compound Name

21(H17-36)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2,6-di(1-methylethyl)phenylamino)carbonyl)-

1,4,9-triazaspiro[5.5]undecane

21(H17-37)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2,5-dimethylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-38)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2-ethyl-6-(1-methylethyl)phenylamino)carbonyl)-

1,4,9-triazaspiro[5.5]undecane

21(H17-39)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2,4,6-trichlorophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-40)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((3,4-dimethylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-41)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2-methylthiophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-42)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-methylthiophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

[1146]

316

TABLE 17A-7

Example

No
Compound Name

21(H17-43)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((4-butylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-44)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2-chloro-5-trifluoromethylphenylamino)carbon-

yl)-1,4,9-triazaspiro[5.5]undecane

21(H17-45)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2,6-dibromo-4-ethylphenylamino)carbonyl)-

1,4,9-triazaspiro[5.5]undecane

21(H17-46)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((1-ethoxycarbonyl-2-methylpropylamino)carbon-

yl)-1,4,9-triazaspiro[5.5]undecane

21(H17-47)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((phenylcarbonylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-48)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2,4,6-tribromophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-49)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2,5-difluorophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

[1147]

317

TABLE 17A-8

Example

No
Compound Name

21(H17-50)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((3,5-bis(methoxycarbonyl)phenylamino)carbonyl)-

1,4,9-triazaspiro[5.5]undecane

21(H17-51)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((6,7-methylenedioxycoumarin-4-ylmethylamino)-

carbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H17-52)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2,6-dimethylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-53)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2-methylpropyloxy)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-54)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2-ethylhexyloxy)carbonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H17-55)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(ethoxycarbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H17-56)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(allyloxycarbonyl)-1,4,9-triazaspiro[5.5]undecane

[1148]

318

TABLE 17A-9

Example

No
Compound Name

21(H17-57)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(propyloxycarbonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H17-58)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(butyloxycarbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H17-59)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(hexyloxycarbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H17-60)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2,2,2-trichloroethyloxy)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-61)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((fluoren-9-ylmethyloxy)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-62)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((1R,5R,2S)-5-methyl-2-(1-methylethyl)cyclohex-

yloxycarbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H17-63)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2-methoxyethoxy)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

[1149]

319

TABLE 17A-10

Example

No
Compound Name

21(H17-64)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(pentyloxycarbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H17-65)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((1-methylethyloxy)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-66)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((3-butenyloxy)carbonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H17-67)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((2R,1S,5S)-methyl-2-(1-methylethyl)cyclohexyl-

oxycarbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H17-68)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(cyclopentyloxycarbonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H17-69)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((1,1-dimethylethyloxy)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-70)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(benzyloxycarbonyl)-1,4,9-triazaspiro[5.5]-

undecane

[1150]

320

TABLE 17A-11

Example

No
Compound Name

21(H17-71)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((N,N-diphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-72)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((N-phenyl-N-methylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-73)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((N,N-dimethylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-74)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((N,N-diethylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-75)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-((N,N-bis(1-methylethyl)amino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H17-76)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(morpholin-4-ylcarbonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H17-77)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(carbazol-9-ylcarbonyl)-1,4,9-triazaspiro[5.5]-

undecane

[1151]

321

TABLE 17A-12

Example

No
Compound Name

21(H17-78)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzyloxycarbonylamino)-

butyl)-9-(pyrrolidin-1-ylcarbonyl)-1,4,9-

triazaspiro[5.5]undecane

[1152]

322

TABLE 18A-1

Example

No
Compound Name

21(H18-1)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

biphenyl)carbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-2)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4,7,7-

trimethyl-2-oxa-3-oxobicyclo[2.2.1]heptan-1-yl)-

carbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-3)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

dimethylaminophenyl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-4)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((3-(2-

chlorophenyl)-5-methylisooxazol-4-yl)carbonyl)-

1,4,9-triazaspiro[5.5]undecane

21(H18-5)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

fluorophenyl)carbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-6)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((3-

fluorophenyl)carbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-7)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2-

fluorophenyl)carbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-8)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(cyclopentylcarbonyl)-1,4,9-triazaspiro[5.5]undecane

[1153]

323

TABLE 18A-2

Example

No
Compound Name

21(H18-9)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((3-

methylphenyl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-10)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((3-

methoxyphenyl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-11)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2,2-

dimethylpropanoyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-12)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(pyridin-3-

ylcarbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-13)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(pyridin-2-

ylcarbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-14)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-phenylacetyl)-

1,4,9-triazaspiro[5.5]undecane

21(H18-15)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-

phenyloxyacetyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-16)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-ethyl-

2,3-dioxopiperazinyl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-17)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2-

phenylthiopyridin-3-yl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

[1154]

324

TABLE 18A-3

Example

No
Compound Name

21(H18-18)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2-

phenyloxypyridin-3-yl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-19)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2-

methoxyphenyl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-20)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-(thiophen-2-

yl)acetyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-21)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-hexanoyl-1,4,9-

triazaspiro[5.5]undecane

21(H18-22)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

methylphenyl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-23)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-

methylpropanoyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-24)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-

cyclopentylpropanoyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-25)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2E)-3-

phenyl-2-propenoyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-26)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2-

methylphenyl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

[1155]

325

TABLE 18A-4

Example

No
Compound Name

21(H18-27)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,3-

dimethylbutanoyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-28)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

cyclohexylcarbonyl-1,4,9-triazaspiro[5.5]undecane

21(H18-29)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

phenylcarbonyl-1,4,9-triazaspiro[5.5]undecane

21(H18-30)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(thiophen-

2-ylcarbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-31)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2,6,6-

trimethyl-1-cyclohexenyl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-32)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

((ethoxycarbonyl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-33)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((3-phenyl-

5-methylisooxazol-4-yl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-34)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((5-methyl-

2-phenyl-1,2,3-triazol-4-yl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

[1156]

326

TABLE 18A-5

Example

No
Compound Name

21(H18-35)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-(3-

methoxyphenyl)acetyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-36)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

methoxyphenylcarbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-37)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((furan-2-

yl)carbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-38)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-

benzyloxyacetyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-39)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(cyclobutylcarbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-40)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-(4-

methoxyphenyl)acetyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-41)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-acetyl-1,4,9-

triazaspiro[5.5]undecane

21(H18-42)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

methylpentanoyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-43)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-

methoxyacetyl)-1,4,9-triazaspiro[5.5]undecane

[1157]

327

TABLE 18A-6

Example

No
Compound Name

2l(H18-44)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-

methylthiopropanoyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-45)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((isooxazol-

5-yl)carbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-46)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-

cyclopentylacetyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H18-47)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-pentanoyl-

1,4,9-triazaspiro[5.5]undecane

21(H18-48)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-

methylpropanoyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-49)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-

phenylthioacetyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-50)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-methyl-

1,2,3-thiadiazol-5-yl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-51)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((3-

cyanophenyl)carbonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H18-52)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-butanoyl-

1,4,9-triazaspiro[5.5]undecane

[1158]

328

TABLE 18A-7

Example

No
Compound Name

21(H18-53)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-propanoyl-

1,4,9-triazaspiro[5.5]undecane

21(H18-54)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

cyclopropylcarbonyl-1,4,9-triazaspiro[5.5]undecane

21(H18-55)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2H-benzo[3,4-

d]1,3-dioxolan-5-ylcarbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-56)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((1-phenyl-

5-propylpyrazol-4-yl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-57)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((5-(1,1-

dimethylethyl)-2-methylfuran-3-yl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-58)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((1-(1,1-

dimethylethyl)-3-methylpyrazol-5-yl)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-59)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

methylsulfonyl-1,4,9-triazaspiro[5.5]undecane

21(H18-60)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

pentylsulfonyl-1,4,9-triazaspiro[5.5]undecane

[1159]

329

TABLE 18A-8

Example

No
Compound Name

21(H18-61)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((1-

methylethyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-62)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2-

iodophenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-63)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

methylsulfonylphenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-64)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

trifluoromethylphenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-65)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

phenylphenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-66)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2-

phenylphenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-67)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2-

methoxycarbonylphenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-68)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((3,4-

difluorophenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-69)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2,6-

difluorophenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

[1160]

330

TABLE 18A-9

Example

No
Compound Name

21(H18-70)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2,5-

difluorophenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-71)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2,5-

dimethoxyphenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-72)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-

naphthylsulfonyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-73)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(((1E)-2-

phenylvinyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H18-74)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((furan-2-yl)-

sulfonyl)-1,4,9-triazaspiro[5.5]undecane

21(H18-75)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((thiophen-2-

yl)sulfonyl)-1,4,9-triazaspiro[5.5]undecane

[1161]

331

TABLE 19A-1

Example

No
Compound Name

21(H19-1)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-methyl-2-

acetylaminothiazol-5-yl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-2)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2-methoxy-

dibenzofuran-3-yl)sulfonyl)-1,4,9-triazaspiro[5.5]-

undecane

21(H19-3)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

methoxyphenyl)sulfonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-4)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-benzylsulfonyl-

1,4,9-triazaspiro[5.5]undecane

21(H19-5)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

((ethylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-6)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

((propylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-7)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((1-

methylethylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-8)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

((ethoxycarbonylmethylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

[1162]

332

TABLE 19A-2

Example

No
Compound Name

21(H19-9)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

((butylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-10)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

chlorophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-11)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

((phenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-12)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

methylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-13)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

((hexylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-14)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

fluorophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-15)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

((benzylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-16)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

((cyclohexylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-17)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((3-

methylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

[1163]

333

TABLE 19A-3

Example

No
Compound Name

21(H19-18)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

((octylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-19)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

bromophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-20)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2-(thiophen-

2-yl)ethylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-21)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-(1-

methylethyl)phenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-22)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((3-

chlorophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-23)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2,4,5-

trimethylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-24)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2,4,6-

trimethylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-25)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

phenyloxyphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

[1164]

334

TABLE 19A-4

Example

No
Compound Name

21(H19-26)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

butyloxyphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-27)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

phenylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-28)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2-

phenylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-29)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

trifluoromethylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-30)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((3,4-

dichlorophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-31)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

butyloxycarbonylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-32)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2,6-

bis(1-methylethyl)phenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-33)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2,5-

dimethylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

[1165]

335

TABLE 19A-5

Example

No
Compound Name

21(H19-34)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2-ethyl-

6-(1-methylethyl)phenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-35)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2,4,6-

trichlorophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-36)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((3,4-

dimethylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-37)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2-

methylthiophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-38)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

methylthiophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-39)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

butylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-40)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2,6-

dibromo-4-ethylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-41)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((1-

ethoxycarbonyl-2-methylpropylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

[1166]

336

TABLE 19A-6

Example

No
Compound Name

21(H19-42)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

((phenylcarbonylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-43)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2,4,6-

tribromophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-44)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2,5-

difluorophenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-45)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((3,5-

bis(methoxycarbonyl)phenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-46)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((6,7-

methylenedioxycoumarin-4-ylmethylamino)carbonyl)-

1,4,9-triazaspiro[5.5]undecane

21(H19-47)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2,6-

dimethylphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-48)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2-

methylpropyloxy)carbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H19-49)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2-

ethylhexyloxy)carbonyl)-1,4,9-triazaspiro[5.5]undecane

[1167]

337

TABLE 19A-7

Example

No
Compound Name

21(H19-50)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-ethoxy-

carbonyl-1,4,9-triazaspiro[5.5]undecane

21(H19-51)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-allyloxy-

carbonyl-1,4,9-triazaspiro[5.5]undecane

21(H19-52)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-propyloxy-

carbonyl-1,4,9-triazaspiro[5.5]undecane

21(H19-53)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-butyloxy-

carbonyl-1,4,9-triazaspiro[5.5]undecane

21(H19-54)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-hexyloxy-

carbonyl-1,4,9-triazaspiro[5.5]undecane

21(H19-55)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((fluoren-

9-ylmethyloxy)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-56)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((1R,5R,2S)-

5-methyl-2-(1-methylethyl)cyclohexyloxycarbonyl)-

1,4,9-triazaspiro[5.5]undecane

21(H19-57)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2-

methoxyethoxy)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-58)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-pentyloxy-

carbonyl-1,4,9-triazaspiro[5.5]undecane

[1168]

338

TABLE 19A-8

Example

No
Compound Name

21(H19-59)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((1-

methylethyloxy)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-60)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((3-

butenyloxy)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-61)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((2R,1S,5S)-

methyl-2-(1-methylethyl)cyclohexyloxycarbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-62)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

cyclopentyloxycarbonyl-1,4,9-

triazaspiro[5.5]undecane

21(H19-63)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-benzyloxy-

carbonyl-1,4,9-triazaspiro[5.5]undecane

21(H19-64)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((N,N-

diphenylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-65)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((N-phenyl-

N-methylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-66)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((N,N-

dimethylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-67)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((N,N-

diethylamino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

[1169]

339

TABLE 19A-9

Example

No
Compound Name

21(H19-68)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-((N,N-bis(1-

methylethyl)amino)carbonyl)-1,4,9-

triazaspiro[5.5]undecane

21(H19-69)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(morpholin-4-

ylcarbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H19-70)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(carbazol-9-

ylcarbonyl)-1,4,9-triazaspiro[5.5]undecane

21(H19-71)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(pyrrolidin-

1-ylcarbonyl)-1,4,9-triazaspiro[5.5]undecane

[1170]

340

TABLE 16B-1

1631

Example No
R1

21(H16-1)

1632

21(H16-2)

1633

21(H16-3)

1634

21(H16-4)

1635

21(H16-5)

1636

[1171]

341

TABLE 16B-2

1637

Example No
R1

21(H16-6)

1638

21(H16-7)

1639

21(H16-8)

1640

21(H16-9)

1641

21(H16-10)

1642

21(H16-11)

1643

[1172]

342

TABLE 16B-3

1644

Example No
R1

21(H16-12)

1645

21(H16-13)

1646

21(H16-14)

1647

21(H16-15)

1648

21(H16-16)

1649

21(H16-17)

1650

[1173]

343

TABLE 16B-4

1651

Example No
R1

21(H16-18)

1652

21(H16-19)

1653

21(H16-20)

1654

21(H16-21)

1655

21(H16-22)

1656

21(H16-23)

1657

21(H16-24)

1658

[1174]

344

TABLE 16B-5

1659

Example No
R1

21(H16-25)

1660

21(H16-26)

1661

21(H16-27)

1662

21(H16-28)

1663

21(H16-29)

1664

21(H16-30)

1665

21(H16-31)

1666

[1175]

345

TABLE 16B-6

1667

Example No
R1

21(H16-32)

1668

21(H16-33)

1669

21(H16-34)

1670

21(H16-35)

1671

21(H16-36)

1672

21(H16-37)

1673

21(H16-38)

1674

[1176]

346

TABLE 16B-7

1675

Example No
R1

21(H16-39)

1676

21(H16-40)

1677

21(H16-41)

1678

21(H16-42)

1679

21(H16-43)

1680

21(H16-44)

1681

21(H16-45)

1682

21(H16-46)

1683

[1177]

347

TABLE 16B-8

1684

Example No
R1

21(H16-47)

1685

21(H16-48)

1686

21(H16-49)

1687

21(H16-50)

1688

21(H16-51)

1689

21(H16-52)

1690

21(H16-53)

1691

21(H16-54)

1692

[1178]

348

TABLE 16B-9

1693

Example No
R1

21(H16-55)

1694

21(H16-56)

1695

21(H16-57)

1696

21(H16-58)

1697

21(H16-59)

1698

21(H16-60)

1699

[1179]

349

TABLE 16B-10

1700

Example No
R1

21(H16-61)

1701

21(H16-62)

1702

21(H16-63)

1703

21(H16-64)

1704

21(H16-65)

1705

21(H16-66)

1706

21(H16-67)

1707

21(H16-68)

1708

[1180]

350

TABLE 16B-11

1709

Example No
R1

21(H16-69)

1710

21(H16-70)

1711

21(H16-71)

1712

21(H16-72)

1713

21(H16-73)

1714

21(H16-74)

1715

[1181]

351

TABLE 16B-12

1716

Example No
R1

21(H16-75)

1717

21(H16-76)

1718

21(H16-77)

1719

21(H16-78)

1720

[1182]

352

TABLE 17B-1

1721

Example No
R1

21(H17-1)

1722

21(H17-2)

1723

21(H17-3)

1724

21(H17-4)

1725

21(H17-5)

1726

21(H17-6)

1727

[1183]

353

TABLE 17B-2

1728

Example No
R1

21(H17-7)

1729

21(H17-8)

1730

21(H17-9)

1731

21(H17-10)

1732

21(H17-11)

1733

21(H17-12)

1734

21(H17-13)

1735

21(H17-14)

1736

[1184]

354

TABLE 17B-3

1737

Example No
R1

21(H17-15)

1738

21(H17-16)

1739

21(H17-17)

1740

21(H17-18)

1741

21(H17-19)

1742

21(H17-20)

1743

21(H17-21)

1744

[1185]

355

TABLE 17B-4

1745

Example No
R1

21(H17-22)

1746

21(H17-23)

1747

21(H17-24)

1748

21(H17-25)

1749

21(H17-26)

1750

21(H17-27)

1751

21(H17-28)

1752

[1186]

356

TABLE 17B-5

1753

Example No
R1

21(H17-29)

1754

21(H17-30)

1755

21(H17-31)

1756

21(H17-32)

1757

21(H17-33)

1758

21(H17-34)

1759

[1187]

357

TABLE 17B-6

1760

Example No
R1

21(H17-35)

1761

21(H17-36)

1762

21(H17-37)

1763

21(H17-38)

1764

21(H17-39)

1765

[1188]

358

TABLE 17B-7

1766

Example No
R1

21(H17-40)

1767

21(H17-41)

1768

21(H17-42)

1769

21(H17-43)

1770

21(H17-44)

1771

21(H17-45)

1772

[1189]

359

TABLE 17B-8

1773

Example No
R1

21(H17-46)

1774

21(H17-47)

1775

21(H17-48)

1776

21(H17-49)

1777

21(H17-50)

1778

21(H17-51)

1779

[1190]

360

TABLE 17B-9

1780

Example No
R1

21(H17-52)

1781

21(H17-53)

1782

21(H17-54)

1783

21(H17-55)

1784

21(H17-56)

1785

21(H17-57)

1786

21(H17-58)

1787

21(H17-59)

1788

[1191]

361

TABLE 17B-10

1789

Example No
R1

21(H17-60)

1790

21(H17-61)

1791

21(H17-62)

1792

21(H17-63)

1793

21(H17-64)

1794

21(H17-65)

1795

21(H17-66)

1796

[1192]

362

TABLE 17B-11

1797

Example No
R1

21(H17-67)

1798

21(H17-68)

1799

21(H17-69)

1800

21(H17-70)

1801

21(H17-71)

1802

21(H17-72)

1803

[1193]

363

TABLE 17B-12

1804

Example No
R1

21(H17-73)

1805

21(H17-74)

1806

21(H17-75)

1807

21(H17-76)

1808

21(H17-77)

1809

21(H17-78)

1810

[1194]

364

TABLE 18B-1

1811

Example No
R1

21(H18-1)

1812

21(H18-2)

1813

21(H18-3)

1814

21(H18-4)

1815

21(H18-5)

1816

[1195]

365

TABLE 18B-2

1817

Example No
R1

21(H18-6)

1818

21(H18-7)

1819

21(H18-8)

1820

21(H18-9)

1821

21(H18-10)

1822

21(H18-11)

1823

21(H18-12)

1824

[1196]

366

TABLE 18B-3

1825

Example No
R1

21(H18-13)

1826

21(H18-14)

1827

21(H18-15)

1828

21(H18-16)

1829

21(H18-17)

1830

21(H18-18)

1831

[1197]

367

TABLE18B-4

1832

Example No
R1

21(H18-19)

1833

21(H18-20)

1834

21(H18-21)

1835

21(H18-22)

1836

21(H18-23)

1837

21(H18-24)

1838

21(H18-25)

1839

[1198]

368

TABLE 18B-5

1840

Example No
R1

21(H18-26)

1841

21(H18-27)

1842

21(H18-28)

1843

21(H18-29)

1844

21(H18-30)

1845

21(H18-31)

1846

21(H18-32)

1847

[1199]

369

TABLE 18B-6

1848

Example No
R1

21(H18-33)

1849

21(H18-34)

1850

21(H18-35)

1851

21(H18-36)

1852

21(H18-37)

1853

21(H18-38)

1854

21(H18-39)

1855

[1200]

370

TABLE 18B-7

1856

Example No
c R1

21(H18-40)

1857

21(H18-41)

1858

21(H18-42)

1859

21(H18-43)

1860

21(H18-44)

1861

21(H18-45)

1862

21(H18-46)

1863

21(H18-47)

1864

21(H18-48)

1865

[1201]

371

TABLE 18B-8

1866

Example No
R1

21(H18-49)

1867

21(H18-50)

1868

21(H18-51)

1869

21(H18-52)

1870

21(H18-53)

1871

21(H18-54)

1872

21(H18-55)

1873

[1202]

372

TABLE 18B-9

1874

Example No
R1

21(H18-56)

1875

21(H18-57)

1876

21(H18-58)

1877

21(H18-59)

1878

21(H18-60)

1879

21(H18-61)

1880

21(H18-62)

1881

[1203]

373

TABLE 18D-10

1882

Example No
R1

21(H18-63)

1883

21(H18-64)

1884

21(H18-65)

1885

21(H18-66)

1886

21(H18-67)

1887

21(H18-68)

1888

21(H18-69)

1889

[1204]

374

TABLE 18B-11

1890

Example No
R1

21(H18-70)

1891

21(H18-71)

1892

21(H18-72)

1893

21(H18-73)

1894

21(H18-74)

1895

21(H18-75)

1896

[1205]

375

TABLE 19B-1

1897

Example No
R1

21(H19-1)

1898

21(H19-2)

1899

21(H19-3)

1900

21(H19-4)

1901

21(H19-5)

1902

21(H19-6)

1903

21(H19-7)

1904

21(H19-8)

1905

[1206]

376

TABLE 19B-2

1906

Example No
R1

21(H19-9)

1907

21(H19-10)

1908

21(H19-11)

1909

21(H19-12)

1910

21(H19-13)

1911

21(H19-14)

1912

21(H19-15)

1913

[1207]

377

TABLE 19B-3

1914

Example No
R1

21(H19-16)

1915

21(H19-17)

1916

21(H19-18)

1917

21(H19-19)

1918

21(H19-20)

1919

21(H19-21)

1920

21(H19-22)

1921

[1208]

378

TABLE 19B-4

1922

Example No
R1

21(H19-23)

1923

21(H19-24)

1924

21(H19-25)

1925

21(H19-26)

1926

21(H19-27)

1927

21(H19-28)

1928

[1209]

379

TABLE 19B-5

1929

Example No
R1

21(H19-29)

1930

21(H19-30)

1931

21(H19-31)

1932

21(H19-32)

1933

21(H19-33)

1934

[1210]

380

TABLE 19B-6

1935

Example No
R1

21(H19-34)

1936

21(H19-35)

1937

21(H19-36)

1938

21(H19-37)

1939

21(H19-38)

1940

21(H19-39)

1941

[1211]

381

TABLE 19B-7

1942

Example No
R1

21(H19-40)

1943

21(H19-41)

1944

21(H19-42)

1945

21(H19-43)

1946

21(H19-44)

1947

21(H19-45)

1948

[1212]

382

TABLE 19B-8

1949

Example No
R1

21(H19-46)

1950

21(H19-47)

1951

21(H19-48)

1952

21(H19-49)

1953

21(H19-50)

1954

21(H19-51)

1955

21(H19-52)

1956

21(H19-53)

1957

[1213]

383

TABLE 19B-9

1958

Example No
R1

21(H19-54)

1959

21(H19-55)

1960

21(H19-56)

1961

21(H19-57)

1962

21(H19-58)

1963

21(H19-59)

1964

21(H19-60)

1965

[1214]

384

TABLE 19B-10

1966

Example No
R1

21(H19-61)

1967

21(H19-62)

1968

21(H19-63)

1969

21(H19-64)

1970

21(H19-65)

1971

21(H19-66)

1972

[1215]

385

TABLE 19B-11

1973

Example No
R1

21(H19-67)

1974

21(H19-68)

1975

21(H19-69)

1976

21(H19-70)

1977

21(H19-71)

1978

[1216]

386

TABLE 16C-1

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

21(H16-1)
F
3.84
611 (M + H)+.
ESI (Pos., 20 V)

21(H16-2)
F
3.28
578 (M + H)+.
ESI (Pos., 20 V)

21(H16-3)
F
3.70
651 (M + H)+.
ESI (Pos., 20 V)

21(H16-4)
F
3.59
553 (M + H)+.
ESI (Pos., 20 V)

21(H16-5)
F
3.59
553 (M + H)+.
ESI (Pos., 20 V)

21(H16-6)
F
3.57
553 (M + H)+.
ESI (Pos., 20 V)

21(H16-7)
F
3.60
527 (M + H)+.
ESI (Pos., 20 V)

21(H16-8)
F
3.63
549 (M + H)+.
ESI (Pos., 20 V)

21(H16-9)
F
3.56
565 (M + H)+.
ESI (Pos., 20 V)

21(H16-10)
F
3.59
515 (M + H)+.
ESI (Pos., 20 V)

21(H16-11)
F
3.16
536 (M + H)+,
ESI (Pos., 20 V)

431.

21(H16-12)
F
3.15
536 (M + H)+,
ESI (Pos., 20 V)

431.

21(H16-13)
F
3.32
536 (M + H)+.
ESI (Pos., 20 V)

21(H16-14)
F
3.60
549 (M + H)+.
ESI (Pos., 20 V)

21(H16-15)
F
3.62
565 (M + H)+.
ESI (Pos., 20 V)

21(H16-16)
F
3.29
599 (M + H)+.
ESI (Pos., 20 V)

21(H16-17)
F
3.63
644 (M + H)+.
ESI (Pos., 20 V)

21(H16-18)
F
3.59
628 (M + H)+.
ESI (Pos., 20 V)

21(H16-19)
F
3.53
565 (M + H)+.
ESI (Pos., 20 V)

21(H16-20)
F
3.56
555 (M + H)+.
ESI (Pos., 20 V)

21(H16-21)
F
3.68
529 (M + H)+.
ESI (Pos., 20 V)

21(H16-22)
F
3.64
549 (M + H)+.
ESI (Pos., 20 V)

21(H16-23)
F
3.47
501 (M + H)+.
ESI (Pos., 20 V)

21(H16-24)
F
3.81
555 (M + H)+.
ESI (Pos., 20 V)

21(H16-25)
F
3.67
561 (M + H)+.
ESI (Pos., 20 V)

21(H16-26)
F
3.59
549 (M + H)+.
ESI (Pos., 20 V)

[1217]

387

TABLE 16C-2

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

21(H16-27)
F
3.64
529 (M + H)+.
ESI (Pos., 20 V)

21(H16-28)
F
3.68
541 (M + H)+.
ESI (Pos., 20 V)

21(H16-29)
F
3.53
535 (M + H)+.
ESI (Pos., 20 V)

21(H16-30)
F
3.54
541 (M + H)+.
ESI (Pos., 20 V)

21(H16-31)
F
3.84
581 (M + H)+.
ESI (Pos., 20 V)

21(H16-32)
F
3.52
531 (M + H)+.
ESI (Pos., 20 V)

21(H16-33)
F
3.67
616 (M + H)+.
ESI (Pos., 20 V)

21(H16-34)
F
3.84
616 (M + H)+.
ESI (Pos., 20 V)

21(H16-35)
F
3.59
579 (M + H)+.
ESI (Pos., 20 V)

21(H16-36)
F
3.55
565 (M + H)+.
ESI (Pos., 20 V)

21(H16-37)
F
3.45
525 (M + H)+.
ESI (Pos., 20 V)

21(H16-38)
F
3.63
579 (M + H)+.
ESI (Pos., 20 V)

21(H16-39)
F
3.52
513 (M + H)+.
ESI (Pos., 20 V)

21(H16-40)
F
3.57
579 (M + H)+.
ESI (Pos., 20 V)

21(H16-41)
F
3.30
473 (M + H)+.
ESI (Pos., 20 V)

21(H16-42)
F
3.65
529 (M + H)+.
ESI (Pos., 20 V)

21(H16-43)
F
3.28
503 (M + H)+.
ESI (Pos., 20 V)

21(H16-44)
F
3.49
533 (M + H)+.
ESI (Pos., 20 V)

21(H16-45)
F
3.43
526 (M + H)+.
ESI (Pos., 20 V)

21(H16-46)
F
3.70
541 (M + H)+.
ESI (Pos., 20 V)

21(H16-47)
F
3.58
515 (M + H)+.
ESI (Pos., 20 V)

21(H16-48)
F
3.55
515 (M + H)+.
ESI (Pos., 20 V)

21(H16-49)
F
3.69
581 (M + H)+.
ESI (Pos., 20 V)

21(H16-50)
F
3.47
557 (M + H)+.
ESI (Pos., 20 V)

21(H16-51)
F
3.53
560 (M + H)+.
ESI (Pos., 20 V)

21(H16-52)
F
3.46
501 (M + H)+.
ESI (Pos., 20 V)

[1218]

388

TABLE 16C-3

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

21(H16-53)
F
3.37
487 (M + H)+.
ESI (Pos., 20 V)

21(H16-54)
F
3.42
499 (M + H)+.
ESI (Pos., 20 V)

21(H16-55)
F
3.54
579 (M + H)+.
ESI (Pos., 20 V)

21(H16-56)
F
3.71
643 (M + H)+.
ESI (Pos., 20 V)

21(H16-57)
F
3.89
595 (M + H)+.
ESI (Pos., 20 V)

21(H16-58)
F
3.60
595 (M + H)+.
ESI (Pos., 20 V)

21(H16-59)
F
3.45
509 (M + H)+.
ESI (Pos., 20 V)

21(H16-60)
F
3.81
565 (M + H)+.
ESI (Pos., 20 V)

21(H16-61)
F
3.56
537 (M + H)+.
ESI (Pos., 20 V)

21(H16-62)
F
3.87
605 (M + H)+.
ESI (Pos., 20 V)

21(H16-63)
F
3.86
697 (M + H)+.
ESI (Pos., 20 V)

21(H16-64)
F
3.79
616 (M + H)+.
ESI (Pos., 20 V)

21(H16-65)
F
3.63
649 (M + H)+.
ESI (Pos., 20 V)

21(H16-66)
F
3.93
639 (M + H)+.
ESI (Pos., 20 V)

21(H16-67)
F
4.00
647 (M + H)+.
ESI (Pos., 20 V)

21(H16-68)
F
3.97
647 (M + H)+.
ESI (Pos., 20 V)

21(H16-69)
F
3.71
629 (M + H)+.
ESI (Pos., 20 V)

21(H16-70)
F
3.82
607 (M + H)+.
ESI (Pos., 20 V)

21(H16-71)
F
3.76
607 (M + H)+.
ESI (Pos., 20 V)

21(H16-72)
F
3.81
607 (M + H)+.
ESI (Pos., 20 V)

21(H16-73)
F
3.71
631 (M + H)+.
ESI (Pos., 20 V)

21(H16-74)
F
4.01
673 (M + H)+.
ESI (Pos., 20 V)

21(H16-75)
F
3.91
621 (M + H)+.
ESI (Pos., 20 V)

21(H16-76)
F
3.82
597 (M + H)+.
ESI (Pos., 20 V)

21(H16-77)
F
3.67
561 (M + H)+.
ESI (Pos., 20 V)

21(H16-78)
F
3.73
577 (M + H)+.
ESI (Pos., 20 V)

[1219]

389

TABLE 17C-1

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

21(H17-1)
F
4.08
724 (M + H)+.
ESI (Pos., 20 V)

21(H17-2)
F
3.90
717 (M + H)+.
ESI (Pos., 20 V)

21(H17-3)
F
3.87
647 (M + H)+.
ESI (Pos., 20 V)

21(H17-4)
F
3.59
649 (M + H)+.
ESI (Pos., 20 V)

21(H17-5)
F
3.98
691 (M + H)+.
ESI (Pos., 20 V)

21(H17-6)
F
4.01
639 (M + H)+.
ESI (Pos., 20 V)

21(H17-7)
F
3.76
601 (M + H)+.
ESI (Pos., 20 V)

21(H17-8)
F
3.72
585 (M + H)+.
ESI (Pos., 20 V)

21(H17-9)
F
3.33
502 (M + H)+.
ESI (Pos., 20 V)

21(H17-10)
F
3.42
516 (M + H)+.
ESI (Pos., 20 V)

21(H17-11)
F
3.43
516 (M + H)+.
ESI (Pos., 20 V)

21(H17-12)
F
3.40
560 (M + H)+.
ESI (Pos., 20 V)

21(H17-13)
F
3.54
530 (M + H)+.
ESI (Pos., 20 V)

21(H17-14)
F
3.72
584 (M + H)+.
ESI (Pos., 20 V)

21(H17-15)
F
3.59
550 (M + H)+.
ESI (Pos., 20 V)

21(H17-16)
F
3.66
564 (M + H)+.
ESI (Pos., 20 V)

21(H17-17)
F
3.73
558 (M + H)+.
ESI (Pos., 20 V)

21(H17-18)
F
3.60
568 (M + H)+.
ESI (Pos., 20 V)

21(H17-19)
F
3.57
564 (M + H)+.
ESI (Pos., 20 V)

21(H17-20)
F
3.62
556 (M + H)+.
ESI (Pos., 20 V)

21(H17-21)
F
3.66
564 (M + H)+.
ESI (Pos., 20 V)

21(H17-22)
F
3.96
586 (M + H)+.
ESI (Pos., 20 V)

21(H17-23)
F
3.76
628 (M + H)+.
ESI (Pos., 20 V)

21(H17-24)
F
3.59
584 (M + H)+.
ESI (Pos., 20 V)

21(H17-25)
F
3.85
592 (M + H)+.
ESI (Pos., 20 V)

21(H17-26)
F
3.75
584 (M + H)+.
ESI (Pos., 20 V)

[1220]

390

TABLE 17C-2

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

21(H17-27)
F
3.74
592 (M + H)+.
ESI (Pos., 20 V)

21(H17-28)
F
3.69
592 (M + H)+.
ESI (Pos., 20 V)

21(H17-29)
F
3.85
642 (M + H)+.
ESI (Pos., 20 V)

21(H17-30)
F
3.86
622 (M + H)+.
ESI (Pos., 20 V)

21(H17-31)
F
3.86
626 (M + H)+.
ESI (Pos., 20 V)

21(H17-32)
F
3.78
626 (M + H)+.
ESI (Pos., 20 V)

21(H17-33)
F
3.82
618 (M + H)+.
ESI (Pos., 20 V)

21(H17-34)
F
3.86
618 (M + H)+.
ESI (Pos., 20 V)

21(H17-35)
F
3.90
650 (M + H)+.
ESI (Pos., 20 V)

21(H17-36)
F
3.89
634 (M + H)+.
ESI (Pos., 20 V)

21(H17-37)
F
3.66
578 (M + H)+.
ESI (Pos., 20 V)

21(H17-38)
F
3.80
620 (M + H)+.
ESI (Pos., 20 V)

21(H17-39)
F
3.76
652 (M + H)+.
ESI (Pos., 20 V)

21(H17-40)
F
3.72
578 (M + H)+.
ESI (Pos., 20 V)

21(H17-41)
F
3.64
596 (M + H)+.
ESI (Pos., 20 V)

21(H17-42)
F
3.68
596 (M + H)+.
ESI (Pos., 20 V)

21(H17-43)
F
3.97
606 (M + H)+.
ESI (Pos., 20 V)

21(H17-44)
F
3.90
652 (M + H)+.
ESI (Pos., 20 V)

21(H17-45)
F
3.83
736 (M + H)+.
ESI (Pos., 20 V)

21(H17-46)
F
3.65
602 (M + H)+.
ESI (Pos., 20 V)

21(H17-47)
F
3.48
578 (M + H)+.
ESI (Pos., 20 V)

21(H17-48)
F
3.80
785 (M + H)+.
ESI (Pos., 20 V)

21(H17-49)
F
3.64
586 (M + H)+.
ESI (Pos., 20 V)

21(H17-50)
F
3.68
666 (M + H)+.
ESI (Pos., 20 V)

21(H17-51)
F
3.51
676 (M + H)+.
ESI (Pos., 20 V)

21(H17-52)
F
3.61
578 (M + H)+.
ESI (Pos., 20 V)

[1221]

391

TABLE 17C-3

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

21(H17-53)
F
3.79
531 (M + H)+.
ESI (Pos., 20 V)

21(H17-54)
F
4.24
587 (M + H)+.
ESI (Pos., 20 V)

21(H17-55)
F
3.57
503 (M + H)+.
ESI (Pos., 20 V)

21(H17-56)
F
3.62
515 (M + H)+.
ESI (Pos., 20 V)

21(H17-57)
F
3.67
517 (M + H)+.
ESI (Pos., 20 V)

21(H17-58)
F
3.79
531 (M + H)+.
ESI (Pos., 20 V)

21(H17-59)
F
4.03
559 (M + H)+.
ESI (Pos., 20 V)

21(H17-60)
F
3.89
605 (M + H)+.
ESI (Pos., 20 V)

21(H17-61)
F
4.06
653 (M + H)+.
ESI (Pos., 20 V)

21(H17-62)
F
4.35
613 (M + H)+.
ESI (Pos., 20 V)

21(H17-63)
F
3.44
533 (M + H)+.
ESI (Pos., 20 V)

21(H17-64)
F
3.90
545 (M + H)+.
ESI (Pos., 20 V)

21(H17-65)
F
3.67
517 (M + H)+.
ESI (Pos., 20 V)

21(H17-66)
F
3.72
529 (M + H)+.
ESI (Pos., 20 V)

21(H17-67)
F
4.35
613 (M + H)+.
ESI (Pos., 20 V)

21(H17-68)
F
3.78
543 (M + H)+.
ESI (Pos., 20 V)

21(H17-69)
F
3.79
531 (M + H)+.
ESI (Pos., 20 V)

21(H17-70)
F
3.81
565 (M + H)+.
ESI (Pos., 20 V)

21(H17-71)
F
3.86
626 (M + H)+.
ESI (Pos., 20 V)

21(H17-72)
F
3.65
564 (M + H)+.
ESI (Pos., 20 V)

21(H17-73)
F
3.39
502 (M + H)+.
ESI (Pos., 20 V)

21(H17-74)
F
3.58
530 (M + H)+.
ESI (Pos., 20 V)

21(H17-75)
F
3.79
558 (M + H)+.
ESI (Pos., 20 V)

21(H17-76)
F
3.34
544 (M + H)+.
ESI (Pos., 20 V)

21(H17-77)
F
4.03
624 (M + H)+.
ESI (Pos., 20 V)

21(H17-78)
F
3.49
528 (M + H)+.
ESI (Pos., 20 V)

[1222]

392

TABLE 18C-1

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

21(H18-1)
F
3.82
923 (2M + H)+,
ESI (Pos., 20 V)

462 (M + H)+.

21(H18-2)
F
3.81
462 (M + H)+.
ESI (Pos., 20 V)

21(H18-3)
F
3.12
857 (2M + H)+,
ESI (Pos., 20 V)

429 (M + H)+.

21(H18-4)
F
3.62
501 (M + H)+.
ESI (Pos., 20 V)

21(H18-5)
F
3.49
807 (2M + H)+,
ESI (Pos., 20 V)

404 (M + H)+.

21(H18-6)
F
3.51
807 (2M + H)+,
ESI (Pos., 20 V)

404 (M + H)+.

21(H18-7)
F
3.49
807 (2M + H)+,
ESI (Pos., 20 V)

404 (M + H)+.

21(H18-8)
F
3.51
755 (2M + H)+,
ESI (Pos., 20 V)

378 (M + H)+.

21(H18-9)
F
3.56
799 (2M + H)+,
ESI (Pos., 20 V)

400 (M + H)+.

21(H18-10)
F
3.49
831 (2M + H)+,
ESI (Pos., 20 V)

416 (M + H)+.

21(H18-11)
F
3.49
753 (2M + H)+,
ESI (Pos., 20 V)

366 (M + H)+.

21(H18-12)
F
3.00
773 (2M + H)+,
ESI (Pos., 20 V)

387 (M + H)+.

21(H18-13)
F
3.16
387 (M + H)+.
ESI (Pos., 20 V)

21(H18-14)
F
3.50
799 (2M + H)+,
ESI (Pos., 20 V)

400 (M + H)+.

21(H18-15)
F
3.53
831 (2M + H)+,
ESI (Pos., 20 V)

416 (M + H)+.

21(H18-16)
F
3.13
450 (M + H)+.
ESI (Pos., 20 V)

21(H18-17)
F
3.57
989 (2M + H)+,
ESI (Pos., 20 V)

495 (M + H)+.

21(H18-18)
F
3.53
957 (2M + H)+,
ESI (Pos., 20 V)

479 (M + H)+.

21(H18-19)
F
3.44
831 (2M + H)+,
ESI (Pos., 20 V)

416 (M + H)+.

21(H18-20)
F
3.45
811 (2M + H)+,
ESI (Pos., 20 V)

406 (M + H)+.

21(H18-21)
F
3.61
759 (2M + H)+,
ESI (Pos., 20 V)

380 (M + H)+.

21(H18-22)
F
3.56
799 (2M + H)+,
ESI (Pos., 20 V)

400 (M + H)+.

21(H18-23)
F
3.32
703 (2M + H)+,
ESI (Pos., 20 V)

352 (M + H)+.

21(H18-24)
F
3.75
811 (2M + H)+,
ESI (Pos., 20 V)

406 (M + H)+.

21(H18-25)
F
3.60
823 (2M + H)+,
ESI (Pos., 20 V)

412 (M + H)+.

21(H18-26)
F
3.51
799 (2M + H)+,
ESI (Pos., 20 V)

400 (M + H)+.

[1223]

393

TABLE 18C-2

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

21(H18-27)
F
3.55
759 (2M + H)+,
ESI (Pos., 20 V)

380 (M + H)+.

21(H18-28)
F
3.58
783 (2M + H)+,
ESI (Pos., 20 V)

392 (M + H)+.

21(H18-29)
F
3.45
771 (2M + H)+,
ESI (Pos., 20 V)

386 (M + H)+.

21(H18-30)
F
3.44
783 (2M + H)+,
ESI (Pos., 20 V)

392 (M + H)+.

21(H18-31)
F
3.79
432 (M + H)+.
ESI (Pos., 20 V)

21(H18-32)
F
3.41
382 (M + H)+.
ESI (Pos., 20 V)

21(H18-33)
F
3.61
933 (2M + H)+,
ESI (Pos., 20 V)

467 (M + H)+.

21(H18-34)
F
3.80
933 (2M + H)+,
ESI (Pos., 20 V)

467 (M + H)+.

21(H18-35)
F
3.48
859 (2M + H)+,
ESI (Pos., 20 V)

430 (M + H)+.

21(H18-36)
F
3.46
831 (2M + H)+,
ESI (Pos., 20 V)

416 (M + H)+.

21(H18-37)
F
3.35
751 (2M + H)+,
ESI (Pos., 20 V)

376 (M + H)+.

21(H18-38)
F
3.53
430 (M + H)+.
ESI (Pos., 20 V)

21(H18-39)
F
3.40
727 (2M + H)+,
ESI (Pos., 20 V)

364 (M + H)+.

21(H18-40)
F
3.48
859 (2M + H)+,
ESI (Pos., 20 V)

430 (M + H)+.

21(H18-41)
F
3.11
647 (2M + H)+,
ESI (Pos., 20 V)

324 (M + H)+.

21(H18-42)
F
3.60
759 (2M + H)+,
ESI (Pos., 20 V)

380 (M + H)+.

21(H18-43)
F
3.13
354 (M + H)+.
ESI (Pos., 20 V)

21(H18-44)
F
3.35
767 (2M + H)+,
ESI (Pos., 20 V)

384 (M + H)+.

21(H18-45)
F
3.28
753 (2M + H)+,
ESI (Pos., 20 V)

377 (M + H)+.

21(H18-46)
F
3.60
783 (2M + H)+,
ESI (Pos., 20 V)

392 (M + H)+.

21(H18-47)
F
3.47
731 (2M + H)+,
ESI (Pos., 20 V)

366 (M + H)+.

21(H18-48)
F
3.44
731 (2M + H)+,
ESI (Pos., 20 V)

366 (M + H)+.

21(H18-49)
F
3.62
863 (2M + H)+,
ESI (Pos., 20 V)

432 (M + H)+.

21(H18-50)
F
3.34
815 (2M + H)+,
ESI (Pos., 20 V)

408 (M + H)+.

21(H18-51)
F
3.42
821 (2M + H)+,
ESI (Pos., 20 V)

411 (M + H)+.

21(H18-52)
F
3.33
703 (2M + H)+,
ESI (Pos., 20 V)

352 (M + H)+.

[1224]

394

TABLE 18C-3

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

21(H18-53)
F
3.22
675 (2M + H)+,
ESI (Pos., 20 V)

338 (M + H)+.

21(H18-54)
F
3.27
699 (2M + H)+,
ESI (Pos., 20 V)

350 (M + H)+.

21(H18-55)
F
3.45
859 (2M + H)+,
ESI (Pos., 20 V)

430 (M + H)+.

21(H18-56)
F
3.64
987 (2M + H)+,
ESI (Pos., 20 V)

494 (M + H)+.

21(H18-57)
F
3.86
891 (2M + H)+,
ESI (Pos., 20 V)

446 (M + H)+.

21(H18-58)
F
3.51
446 (M + H)+.
ESI (Pos., 20 V)

21(H18-59)
F
3.29
360 (M + H)+.
ESI (Pos., 20 V)

21(H18-60)
F
3.76
416 (M + H)+.
ESI (Pos., 20 V)

21(H18-61)
F
3.45
797 (2M + Na)+,
ESI (Pos., 20 V)

388 (M + H)+.

21(H18-62)
F
3.82
548 (M + H)+.
ESI (Pos., 20 V)

21(H18-63)
F
3.55
500 (M + H)+.
ESI (Pos., 20 V)

21(H18-64)
F
3.90
490 (M + H)+.
ESI (Pos., 20 V)

21(H18-65)
F
3.99
498 (M + H)+.
ESI (Pos., 20 V)

21(H18-66)
F
3.97
498 (M + H)+.
ESI (Pos., 20 V)

21(H18-67)
F
3.62
480 (M + H)+.
ESI (Pos., 20 V)

21(H18-68)
F
3.77
458 (M + H)+.
ESI (Pos., 20 V)

21(H18-69)
F
3.70
458 (M + H)+.
ESI (Pos., 20 V)

21(H18-70)
F
3.76
458 (M + H)+.
ESI (Pos., 20 V)

21(H18-71)
F
3.62
985 (2M + Na)+,
ESI (Pos., 20 V)

482 (M + H)+.

21(H18-72)
F
3.89
472 (M + H)+.
ESI (Pos., 20 V)

21(H18-73)
F
3.79
448 (M + H)+.
ESI (Pos., 20 V)

21(H18-74)
F
3.58
412 (M + H)+.
ESI (Pos., 20 V)

21(H18-75)
F
3.65
428 (M + H)+.
ESI (Pos., 20 V)

[1225]

395

TABLE 19C-1

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

21(H19-1)
F
3.48
500 (M + H)+.
ESI (Pos., 20 V)

21(H19-2)
F
3.96
542 (M + H)+.
ESI (Pos., 20 V)

21(H19-3)
F
3.68
452 (M + H)+.
ESI (Pos., 20 V)

21(H19-4)
F
3.64
436 (M + H)+.
ESI (Pos., 20 V)

21(H19-5)
F
3.13
353 (M + H)+.
ESI (Pos., 20 V)

21(H19-6)
F
3.25
367 (M + H)+.
ESI (Pos., 20 V)

21(H19-7)
F
3.26
367 (M + H)+.
ESI (Pos., 20 V)

21(H19-8)
F
3.21
411 (M + H)+.
ESI (Pos., 20 V)

21(H19-9)
F
3.37
381 (M + H)+.
ESI (Pos., 20 V)

21(H19-10)
F
3.63
435 (M + H)+.
ESI (Pos., 20 V)

21(H19-11)
F
3.45
401 (M + H)+.
ESI (Pos., 20 V)

21(H19-12)
F
3.55
415 (M + H)+.
ESI (Pos., 20 V)

21(H19-13)
F
3.65
409 (M + H)+.
ESI (Pos., 20 V)

21(H19-14)
F
3.49
419 (M + H)+.
ESI (Pos., 20 V)

21(H19-15)
F
3.43
415 (M + H)+.
ESI (Pos., 20 V)

21(H19-16)
F
3.50
407 (M + H)+.
ESI (Pos., 20 V)

21(H19-17)
F
3.54
415 (M + H)+.
ESI (Pos., 20 V)

21(H19-18)
F
3.90
437 (M + H)+.
ESI (Pos., 20 V)

21(H19-19)
F
3.67
481 (M + H)+.
ESI (Pos., 20 V)

21(H19-20)
F
3.46
435 (M + H)+.
ESI (Pos., 20 V)

21(H19-21)
F
3.77
443 (M + H)+.
ESI (Pos., 20 V)

21(H19-22)
F
3.64
435 (M + H)+.
ESI (Pos., 20 V)

21(H19-23)
F
3.64
443 (M + H)+.
ESI (Pos., 20 V)

21(H19-24)
F
3.58
443 (M + H)+.
ESI (Pos., 20 V)

21(H19-25)
F
3.79
493 (M + H)+.
ESI (Pos., 20 V)

21(H19-26)
F
3.78
473 (M + H)+.
ESI (Pos., 20 V)

[1226]

396

TABLE 19C-2

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

21(H19-27)
F
3.80
477 (M + H)+.
ESI (Pos., 20 V)

21(H19-28)
F
3.70
477 (M + H)+.
ESI (Pos., 20 V)

21(H19-29)
F
3.74
469 (M + H)+.
ESI (Pos., 20 V)

21(H19-30)
F
3.79
469 (M + H)+.
ESI (Pos., 20 V)

21(H19-31)
F
3.85
501 (M + H)+.
ESI (Pos., 20 V)

21(H19-32)
F
3.81
485 (M + H)+.
ESI (Pos., 20 V)

21(H19-33)
F
3.56
429 (M + H)+.
ESI (Pos., 20 V)

21(H19-34)
F
3.72
471 (M + H)+.
ESI (Pos., 20 V)

21(H19-35)
F
3.67
505 (M + H)+.
ESI (Pos., 20 V)

21(H19-36)
F
3.63
429 (M + H)+.
ESI (Pos., 20 V)

21(H19-37)
F
3.57
447 (M + H)+.
ESI (Pos., 20 V)

21(H19-38)
F
3.59
447 (M + H)+.
ESI (Pos., 20 V)

21(H19-39)
F
3.91
457 (M + H)+.
ESI (Pos., 20 V)

21(H19-40)
F
3.77
587 (M + H)+.
ESI (Pos., 20 V)

21(H19-41)
F
3.50
453 (M + H)+.
ESI (Pos., 20 V)

21(H19-42)
F
3.34
429 (M + H)+.
ESI (Pos., 20 V)

21(H19-43)
F
3.75
638 (M + H)+.
ESI (Pos., 20 V)

21(H19-44)
F
3.54
437 (M + H)+.
ESI (Pos., 20 V)

21(H19-45)
F
3.58
517 (M + H)+.
ESI (Pos., 20 V)

21(H19-46)
F
3.35
527 (M + H)+.
ESI (Pos., 20 V)

21(H19-47)
F
3.47
429 (M + H)+.
ESI (Pos., 20 V)

21(H19-48)
F
3.70
382 (M + H)+.
ESI (Pos., 20 V)

21(H19-49)
F
4.22
438 (M + H)+.
ESI (Pos., 20 V)

21(H19-50)
F
3.43
354 (M + H)+.
ESI (Pos., 20 V)

21(H19-51)
F
3.50
366 (M + H)+.
ESI (Pos., 20 V)

21(H19-52)
F
3.57
368 (M + H)+.
ESI (Pos., 20 V)

[1227]

397

TABLE 19C-3

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

21(H19-53)
F
3.72
382 (M + H)+.
ESI (Pos., 20 V)

21(H19-54)
F
3.99
410 (M + H)+.
ESI (Pos., 20 V)

21(H19-55)
F
4.03
504 (M + H)+.
ESI (Pos., 20 V)

21(H19-56)
F
4.37
464 (M + H)+.
ESI (Pos., 20 V)

21(H19-57)
F
3.28
384 (M + H)+.
ESI (Pos., 20 V)

21(H19-58)
F
3.86
396 (M + H)+.
ESI (Pos., 20 V)

21(H19-59)
F
3.56
368 (M + H)+.
ESI (Pos., 20 V)

21(H19-60)
F
3.60
380 (M + H)+.
ESI (Pos., 20 V)

21(H19-61)
F
4.39
464 (M + H)+.
ESI (Pos., 20 V)

21(H19-62)
F
3.71
394 (M + H)+.
ESI (Pos., 20 V)

21(H19-63)
F
3.74
416 (M + H)+.
ESI (Pos., 20 V)

21(H19-64)
F
3.81
477 (M + H)+.
ESI (Pos., 20 V)

21(H19-65)
F
3.55
415 (M + H)+.
ESI (Pos., 20 V)

21(H19-66)
F
3.22
353 (M + H)+.
ESI (Pos., 20 V)

21(H19-67)
F
3.46
381 (M + H)+.
ESI (Pos., 20 V)

21(H19-68)
F
3.71
409 (M + H)+.
ESI (Pos., 20 V)

21(H19-69)
F
3.17
395 (M + H)+.
ESI (Pos., 20 V)

21(H19-70)
F
3.97
475 (M + H)+.
ESI (Pos., 20 V)

21(H19-71)
F
3.34
379 (M + H)+.
ESI (Pos., 20 V)

EXAMPLE 22

[1228] (3S)-1-propyl-2,5-dioxo-3-(4-(3-phenylpropanoyl)aminobutyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

1979

[1229] To a solution of the compound prepared in Example 14 (5 mg) in dichloroethane (0.5 ml) were added pyridine (2 μl), 3-phenylpropanoyl chloride (4 μl). The reaction mixture was stirred for 3 hours at room temperature. To the reaction mixture was added methanol, and it was loaded on ion exchange resin (OASIS MCX, Waters, 60 mg) washed with methanol (3 ml) prior to use. The resin was washed with methanol (2 ml), and was eluted with 10% triethylamine-methanol solution (2 ml). The elution was concentrated to give the compound of the present invention (1.6 mg) having the following physical data.

[1230] TLC: Rf 0.49 (chloroform:methanol=10:1);

[1231] NMR (CD3OD): 67.40-7.10 (m, 10H), 4.03 (m, 1H), 3.60-3.30 (m, 2H), 3.14 (m, 2H), 3.06-2.90 (m, 3H), 2.90-2.75 (m, 4H), 2.75-2.60 (m, 3H), 2.45 (t, J=7.4 Hz, 2H), 2.30-2.00 (m, 2H), 2.00-1.70 (m, 4H), 1.70-1.20 (m, 6H), 0.93 (t, J=7.2 Hz, 3H).

EXAMPLE 22(1)

[1232] (3S)-1-propyl-2,5-dioxo-3-(4-benzenesulfonylaminobutyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

1980

[1233] By the same procedure as described in Example 22 using the compound prepared in Example 14 (5 mg), pyridine (2 μl), benzenesulfonyl chloride (3 μl), the compound of the present invention (4.4 mg) having the following physical data was obtained.

[1234] TLC: Rf 0.49 (chloroform:methanol=10:1);

[1235] NMR (CD3OD): δ 7.84 (m, 2H), 7.59 (m, 3H), 7.34-7.10 (m, 5H), 4.01 (t, J=5.0 Hz, 1H), 3.55-3.30 (m, 2H), 3.05-2.90 (m, 3H), 2.90-2.75 (m, 4H), 2.75-2.60 (m, 3H), 2.30-2.00 (m, 2H), 1.96 (m, 2H), 1.88-1.70 (m, 2H), 1.70-1.20 (m, 6H), 0.94 (t, J=7.4 Hz, 3H).

EXAMPLE 22(2)

[1236] (3S)-1-propyl-2,5-dioxo-3-(4-(N-benzylcarbamoyl)aminobutyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

1981

[1237] By the same procedure as described in Example 22 using the compound prepared in Example 14 (5 mg), and benzyl isocyanate (3 μl), the compound of the present invention (7 mg) having the following physical data was obtained.

[1238] TLC: Rf 0.46 (chloroform:methanol=10:1);

[1239] NMR (CD3OD): δ 7.40-7.10 (m, 10H), 4.30 (s, 2H), 4.04 (t, J=5.0 Hz, 1H), 3.55-3.30 (m, 2H), 3.15 (t, J=6.6 Hz, 3H), 3.05-2.90 (m, 3H), 2.90-2.75 (m, 3H), 2.75-2.60 (m, 2H), 2.35-2.05 (m, 2H), 2.02-1.70 (m, 4H), 1.70-1.20 (m, 6H), 0.93 (t, J=7.4 Hz, 3H).

EXAMPLE 22(H20-1)˜22(H21-77)

[1240] By the same procedure as described in Example 22, 22(1) or 22(2) using the compound prepared in Example 14 and the corresponding acid chloride derivatives, sulfonyl chloride derivatives or isocyanate derivatives, the compounds of the present invention, whose names were shown in the following Table 20A-1˜21A-11, and whose structures were shown in the following Table 20B-1˜21B-12, were obtained. Also, physical data of the above compounds were shown in the following Table 20C-1˜21C-3.

398TABLE 20A-1ExampleNoCompound Name22(H20-1)(3S)-1-propyl-2,5-dioxo-3-(4-((4-biphenyl)carbon-ylamino)butyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane22(H20-2)(3S)-1-propyl-2,5-dioxo-3-(4-((4,7,7-trimethyl-2-oxa-3-oxobicyclo[2.2.1]heptan-1-yl)carbonyl-amino)butyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane22(H20-3)(3S)-1-propyl-2,5-dioxo-3-(4-((4-dimethylamino-phenyl)carbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane22(H20-4)(3S)-1-propyl-2,5-dioxo-3-(4-((3-(2-chlorophenyl)-5-methylisooxazol-4-yl)carbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane22(H20-5)(3S)-1-propyl-2,5-dioxo-3-(4-((4-fluorophenyl)carbon-ylamino)butyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane22(H20-6)(3S)-1-propyl-2,5-dioxo-3-(4-((3-fluorophenyl)carbon-ylamino)butyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane22(H20-7)(3S)-1-propyl-2,5-dioxo-3-(4-((2-fluorophenyl)carbon-ylamino)butyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

[1241]

399

TABLE 20A-2

Example

No
Compound Name

22(H20-8)
(3S)-1-propyl-2,5-dioxo-3-(4-(cyclopentylcarbon-

ylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-9)
(3S)-1-propyl-2,5-dioxo-3-(4-((3-methylphenyl)carbon-

ylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-10)
(3S)-1-propyl-2,5-dioxo-3-(4-((3-methoxyphenyl)carbon-

ylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-11)
(3S)-1-propyl-2,5-dioxo-3-(4-(2,2-dimethylpro-

panoylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-12)
(3S)-1-propyl-2,5-dioxo-3-(4-(pyridin-3-ylcarbonyl-

amino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-13)
(3S)-1-propyl-2,5-dioxo-3-(4-(pyridin-2-

ylcarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-14)
(3S)-1-propyl-2,5-dioxo-3-(4-(2-phenylacetyl-

amino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[1242]

400

TABLE 20A-3

Example

No
Compound Name

22(H20-15)
(3S)-1-propyl-2,5-dioxo-3-(4-(2-phenyloxyacetyl-

amino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-16)
(3S)-1-propyl-2,5-dioxo-3-(4-((4-ethyl-2,3-

dioxopiperazinyl)carbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H20-17)
(3S)-1-propyl-2,5-dioxo-3-(4-((2-phenylthiopyridin-3-

yl)carbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-18)
(3S)-1-propyl-2,5-dioxo-3-(4-((2-phenyloxypyridin-3-

yl)carbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-19)
(3S)-1-propyl-2,5-dioxo-3-(4-((2-methoxyphenyl)carbon-

ylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-20)
(3S)-1-propyl-2,5-dioxo-3-(4-(2-(thiophen-2-

yl)acetylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-21)
(3S)-1-propyl-2,5-dioxo-3-(4-(hexanoylamino)butyl)-9-

(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

[1243]

401

TABLE 20A-4

Example

No
Compound Name

22(H20-22)
(3S)-1-propyl-2,5-dioxo-3-(4-((4-methylphenyl)carbon-

ylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-23)
(3S)-1-propyl-2,5-dioxo-3-(4-(2-methylpropanoyl-

amino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-24)
(3S)-1-propyl-2,5-dioxo-3-(4-(3-cyclopentylpropanoyl-

amino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-25)
(3S)-1-propyl-2,5-dioxo-3-(4-((2E)-3-phenyl-2-

propenoylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-26)
(3S)-1-propyl-2,5-dioxo-3-(4-((2-

methylphenyl)carbonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H20-27)
(3S)-1-propyl-2,5-dioxo-3-(4-(3,3-

dimethylbutanoylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H20-28)
(3S)-1-propyl-2,5-dioxo-3-(4-

(cyclohexylcarbonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

[1244]

402

TABLE 20A-5

Example

No
Compound Name

22(H20-29)
(3S)-1-propyl-2,5-dioxo-3-(4-(phenylcarbonyl-

amino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-30)
(3S)-1-propyl-2,5-dioxo-3-(4-(thiophen-2-

ylcarbonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H20-31)
(3S)-1-propyl-2,5-dioxo-3-(4-((2,6,6-trimethyl-

1-cyclohexenyl)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H20-32)
(3S)-1-propyl-2,5-dioxo-3-(4-((3-phenyl-5-methyl-

isooxazol-4-yl)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H20-33)
(3S)-1-propyl-2,5-dioxo-3-(4-((5-methyl-2-phenyl-

1,2,3-triazol-4-yl)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H20-34)
(3S)-1-propyl-2,5-dioxo-3-(4-(2-(3-

methoxyphenyl)acetylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H20-35)
(3S)-1-propyl-2,5-dioxo-3-(4-(4-

methoxyphenylcarbonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

[1245]

403

TABLE 20A-6

Example

No
Compound Name

22(H20-36)
(3S)-1-propyl-2,5-dioxo-3-(4-((furan-2-

yl)carbonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H20-37)
(3S)-1-propyl-2,5-dioxo-3-(4-(2-benzyloxyacetyl-

amino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-38)
(3S)-1-propyl-2,5-dioxo-3-(4-(cyclobutylcarbonyl-

amino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-39)
(3S)-1-propyl-2,5-dioxo-3-(4-(2-(4-methoxy-

phenyl)acetylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H20-40)
(3S)-1-propyl-2,5-dioxo-3-(4-(acetylamino)butyl)-

9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H20-41)
(3S)-1-propyl-2,5-dioxo-3-(4-(4-methylpentanoyl-

amino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-42)
(3S)-1-propyl-2,5-dioxo-3-(4-(2-methoxyacetyl-

amino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[1246]

404

TABLE 20A-7

Example

No
Compound Name

22(H20-43)
(3S)-1-propyl-2,5-dioxo-3-(4-(3-

methylthiopropanoylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H20-44)
(3S)-1-propyl-2,5-dioxo-3-(4-(2-

cyclopentylacetylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H20-45)
(3S)-1-propyl-2,5-dioxo-3-(4-(pentanoylamino)butyl)-

9-(2-phenylethyl)-1,4,9-tri-

azaspiro[5.5]undecane

22(H20-46)
(3S)-1-propyl-2,5-dioxo-3-(4-(3-methylpropanoyl-

amino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-47)
(3S)-1-propyl-2,5-dioxo-3-(4-(2-phenylthioacetyl-

amino)butyl)-9-(2-phenylethyl)-1,4,9-tri-

azaspiro[5.5]undecane

22(H20-48)
(3S)-1-propyl-2,5-dioxo-3-(4-((4-methyl-1,2,3-

thiadiazol-5-yl)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H20-49)
(3S)-1-propyl-2,5-dioxo-3-(4-((3-

cyanophenyl)carbonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

[1247]

405

TABLE 20A-8

Example

No
Compound Name

22(H20-50)
(3S)-1-propyl-2,5-dioxo-3-(4-(butanoylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-51)
(3S)-1-propyl-2,5-dioxo-3-(4-(propanoylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-52)
(3S)-1-propyl-2,5-dioxo-3-(4-

(cyclopropylcarbonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H20-53)
(3S)-1-propyl-2,5-dioxo-3-(4-(2H-

benzo[3,4-d]1,3-dioxolan-5-ylcarbonyl-

amino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-54)
(3S)-1-propyl-2,5-dioxo-3-(4-((1-phenyl-5-

propylpyrazol-4-yl)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H20-55)
(3S)-1-propyl-2,5-dioxo-3-(4-((5-(1,1-dimethyl-

ethyl)-2-methylfuran-3-yl)carbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H20-56)
(3S)-1-propyl-2,5-dioxo-3-(4-((1-(1,1-dimethyl-

ethyl)-3-methylpyrazol-5-yl)carbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

[1248]

406

TABLE 20A-9

Example

No
Compound Name

22(H20-57)
(3S)-1-propyl-2,5-dioxo-3-(4-(methylsulfonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H20-58)
(3S)-1-propyl-2,5-dioxo-3-(4-(pentylsulfonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H20-59)
(3S)-1-propyl-2,5-dioxo-3-(4-(1-

methylethylsulfonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H20-60)
(3S)-1-propyl-2,5-dioxo-3-(4-(4-chlorophenyl-

sulfonyl)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-61)
(3S)-1-propyl-2,5-dioxo-3-(4-(2-

iodophenylsulfonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-62)
(3S)-1-propyl-2,5-dioxo-3-(4-(4-

nitrophenylsulfonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-63)
(3S)-1-propyl-2,5-dioxo-3-(4-(4-

(methylsulfonyl)phenylsulfonylamino)butyl)-9-(2-phenyl-

ethyl)-1,4,9-triazaspiro[5.5]undecane

[1249]

407

TABLE 20A-10

Example

No
Compound Name

22(H20-64)
(3S)-1-propyl-2,5-dioxo-3-(4-(4-

trifluoromethylphenylsulfonylamino)butyl)-9-(2-phenyl-

ethyl)-1,4,9-triazaspiro[5.5]undecane

22(H20-65)
(3S)-1-propyl-2,5-dioxo-3-(4-(4-

phenylphenylsulfonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H20-66)
(3S)-1-propyl-2,5-dioxo-3-(4-(2-

phenylphenylsulfonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H20-67)
(3S)-1-propyl-2,5-dioxo-3-(4-(3,4-

difluorophenylsulfonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H20-68)
(3S)-1-propyl-2,5-dioxo-3-(4-(2,6-

difluorophenylsulfonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H20-69)
(3S)-1-propyl-2,5-dioxo-3-(4-(2,5-

difluorophenylsulfonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H20-70)
(3S)-1-propyl-2,5-dioxo-3-(4-(2,5-

dimethoxyphenylsulfonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

[1250]

408

TABLE 20A-11

Example

No
Compound Name

22(H20-71)
(3S)-1-propyl-2,5-dioxo-3-(4-(2-chloro-4-

trifluoromethylphenylsulfonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H20-72)
(3S)-1-propyl-2,5-dioxo-3-(4-(2-naphthylsulfonyl-

amino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-73)
(3S)-1-propyl-2,5-dioxo-3-(4-((1E)-2-

phenylvinylsulfonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H20-74)
(3S)-1-propyl-2,5-dioxo-3-(4-(furan-2-ylsulfonyl-

amino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H20-75)
(3S)-1-propyl-2,5-dioxo-3-(4-(thiophen-2-

ylsulfonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[1251]

409

TABLE 21A-1

Example

No
Compound Name

22(H21-1)
(3S)-1-propyl-2,5-dioxo-3-(4-(4-bromo-2,5-dichloro-

thiophen-3-ylsulfonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H21-2)
(3S)-1-propyl-2,5-dioxo-3-(4-(5-phenylsulfonyl-

thiophen-2-ylsulfonylamino)butyl)-9-(2-phenyl-

ethyl)-1,4,9-triazaspiro[5.5]undecane

22(H21-3)
(3S)-1-propyl-2,5-dioxo-3-(4-(7-chlorobenzofurazan-

4-ylsulfonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-4)
(3S)-1-propyl-2,5-dioxo-3-(4-(4-methyl-2-acetylamino-

thiazol-5-ylsulfonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H21-5)
(3S)-1-propyl-2,5-dioxo-3-(4-(2-methoxy-dibenzofuran-

3-ylsulfonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-6)
(3S)-1-propyl-2,5-dioxo-3-(4-(3,4-

dichlorophenylsulfonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H21-7)
(3S)-1-propyl-2,5-dioxo-3-(4-(4-

methoxyphenylsulfonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

[1252]

410

TABLE 21A-2

Example

No
Compound Name

22(H21-8)
(3S)-1-propyl-2,5-dioxo-3-(4-(benzylsulfonyl-

amino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-9)
(3S)-1-propyl-2,5-dioxo-3-(4-

((ethylamino)carbonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H21-10)
(3S)-1-propyl-2,5-dioxo-3-(4-

((propylamino)carbonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H21-11)
(3S)-1-propyl-2,5-dioxo-3-(4-((1-

methylethylamino)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H21-12)
(3S)-1-propyl-2,5-dioxo-3-(4-

((butylamino)carbonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H21-13)
(3S)-1-propyl-2,5-dioxo-3-(4-((4-

chlorophenylamino)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H21-14)
(3S)-1-propyl-2,5-dioxo-3-(4-

((phenylamino)carbonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

[1253]

411

TABLE 21A-3

Example

No
Compound Name

22(H21-15)
(3S)-1-propyl-2,5-dioxo-3-(4-((4-

methylphenylamino)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H21-16)
(3S)-1-propyl-2,5-dioxo-3-(4-

((hexylamino)carbonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H21-17)
(3S)-1-propyl-2,5-dioxo-3-(4-((4-

fluorophenylamino)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H21-18)
(3S)-1-propyl-2,5-dioxo-3-(4-

((benzylamino)carbonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H21-19)
(3S)-1-propyl-2,5-dioxo-3-(4-

((cyclohexylamino)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H21-20)
(3S)-1-propyl-2,5-dioxo-3-(4-((3-

methylphenylamino)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H21-21)
(3S)-1-propyl-2,5-dioxo-3-(4-

((octylamino)carbonylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

[1254]

412

TABLE 21A-4

Example

No
Compound Name

22(H21-22)
(3S)-1-propyl-2,5-dioxo-3-(4-((4-

bromophenylamino)carbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-23)
(3S)-1-propyl-2,5-dioxo-3-(4-((2-(thiophen-

2-yl)ethylamino)carbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-24)
(3S)-1-propyl-2,5-dioxo-3-(4-((4-(1-

methylethyl)phenylamino)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H21-25)
(3S)-1-propyl-2,5-dioxo-3-(4-((3-

chlorophenylamino)carbonylamino)butyl)-9-

(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H21-26)
(3S)-1-propyl-2,5-dioxo-3-(4-((2,4,5-

trimethylphenylamino)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H21-27)
(3S)-1-propyl-2,5-dioxo-3-(4-((2,4,6-

trimethylphenylamino)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H21-28)
(3S)-1-propyl-2,5-dioxo-3-(4-((4-

phenyloxyphenylamino)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

[1255]

413

TABLE 21A-5

Example

No
Compound Name

22(H21-29)
(3S)-1-propyl-2,5-dioxo-3-(4-((4-

butyloxyphenylamino)carbonylamino)butyl)-9-

(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H21-30)
(3S)-1-propyl-2,5-dioxo-3-(4-((4-

phenylphenylamino)carbonylamino)butyl)-9-

(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H21-31)
(3S)-1-propyl-2,5-dioxo-3-(4-((2-

phenylphenylamino)carbonylamino)butyl)-9-

(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H21-32)
(3S)-1-propyl-2,5-dioxo-3-(4-((4-

trifluoromethylphenylamino)carbonylamino)butyl)-

9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H21-33)
(3S)-1-propyl-2,5-dioxo-3-(4-((3,4-

dichlorophenylamino)carbonylamino)butyl)-

9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H21-34)
(3S)-1-propyl-2,5-dioxo-3-(4-((4-

butyloxycarbonylphenylamino)carbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-35)
(3S)-1-propyl-2,5-dioxo-3-(4-((2,6-bis(1-

methylethyl)phenylamino)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

[1256]

414

TABLE 21A-6

Example

No
Compound Name

22(H21-36)
(3S)-1-propyl-2,5-dioxo-3-(4-((2,5-

dimethylphenylamino)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H21-37)
(3S)-1-propyl-2,5-dioxo-3-(4-((2-ethyl-6-(1-

methylethyl)phenylamino)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H21-38)
(3S)-1-propyl-2,5-dioxo-3-(4-((2,4,6-

trichlorophenylamino)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H21-39)
(3S)-1-propyl-2,5-dioxo-3-(4-((3,4-

dimethylphenylamino)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H21-40)
(3S)-1-propyl-2,5-dioxo-3-(4-((2-

methylthiophenylamino)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H21-41)
(3S)-1-propyl-2,5-dioxo-3-(4-((4-

methylthiophenylamino)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H21-42)
(3S)-1-propyl-2,5-dioxo-3-(4-((4-

butylphenylamino)carbonylamino)butyl)-9-(2-

phenylethyl)-1,4,9-triazaspiro[5.5]undecane

[1257]

415

TABLE 21A-7

Example

No
Compound Name

22(H21-43)
(3S)-1-propyl-2,5-dioxo-3-(4-((2-chloro-5-

trifluoromethylphenylamino)carbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-44)
(3S)-1-propyl-2,5-dioxo-3-(4-((2,6-dibromo-4-

ethylphenylamino)carbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H21-45)
(3S)-1-propyl-2,5-dioxo-3-(4-((1-ethoxycarbonyl-2-

methylpropylamino)carbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

22(H21-46)
(3S)-1-propyl-2,5-dioxo-3-(4-

((phenylcarbonylamino)carbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-47)
(3S)-1-propyl-2,5-dioxo-3-(4-((2,4,6-

tribromophenylamino)carbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-48)
(3S)-1-propyl-2,5-dioxo-3-(4-((2,5-

difluorophenylamino)carbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-49)
(3S)-1-propyl-2,5-dioxo-3-(4-((3,5-

bis(methoxycarbonyl)phenylamino)carbon-

ylamino)butyl)-9-(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

[1258]

416

TABLE 21A-8

Example

No
Compound Name

22(H21-50)
(3S)-1-propyl-2,5-dioxo-3-(4-((6,7-

methylenedioxycoumarin-4-

ylmethylamino)carbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-51)
(3S)-1-propyl-2,5-dioxo-3-(4-((2,6-

dimethylphenylamino)carbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-52)
(3S)-1-propyl-2,5-dioxo-3-(4-((2-

methylpropyloxy)carbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-53)
(3S)-1-propyl-2,5-dioxo-3-(4-((2-

ethylhexyloxy)carbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-54)
(3S)-1-propyl-2,5-dioxo-3-(4-

(ethoxycarbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-55)
(3S)-1-propyl-2,5-dioxo-3-(4-

(allyloxycarbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-56)
(3S)-1-propyl-2,5-dioxo-3-(4-

(propyloxycarbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[1259]

417

TABLE 21A-9

Example

No
Compound Name

22(H21-57)
(3S)-1-propyl-2,5-dioxo-3-(4-

(butyloxycarbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-58)
(3S)-1-propyl-2,5-dioxo-3-(4-

(hexyloxycarbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-59)
(3S)-1-propyl-2,5-dioxo-3-(4-((2,2,2-

trichloroethyloxy)carbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-60)
(3S)-1-propyl-2,5-dioxo-3-(4-((fluoren-9-

ylmethyloxy)carbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-61)
(3S)-1-propyl-2,5-dioxo-3-(4-((1S,5S,2R)-

5-methyl-2-(1-

methylethyl)cyclohexyloxycarbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-62)
(3S)-1-propyl-2,5-dioxo-3-(4-((2-

methoxyethoxy)carbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-63)
(3S)-1-propyl-2,5-dioxo-3-(4-

(pentyloxycarbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[1260]

418

TABLE 21A-10

Example

No
Compound Name

22(H21-64)
(3S)-1-propyl-2,5-dioxo-3-(4-((1-

methylethyloxy)carbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-65)
(3S)-1-propyl-2,5-dioxo-3-(4-((3-

butenyloxy)carbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-66)
(3S)-1-propyl-2,5-dioxo-3-(4-

((2S,1R,5R)-methyl-2-(1-

methylethyl)cyclohexyloxycarbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-67)
(3S)-1-propyl-2,5-dioxo-3-(4-

(cyclopentyloxycarbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-68)
(3S)-1-propyl-2,5-dioxo-3-(4-((1,1-

dimethylethyloxy)carbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-69)
(3S)-1-propyl-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-70)
(3S)-1-propyl-2,5-dioxo-3-(4-((N,N-

diphenylamino)carbonylamino)butyl)-

9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[1261]

419

TABLE 21A-11

Example

No
Compound Name

22(H21-71)
(3S)-1-propyl-2,5-dioxo-3-(4-((N-phenyl-N-

methylamino)carbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-72)
(3S)-1-propyl-2,5-dioxo-3-(4-((N,N-

dimethylamino)carbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-73)
(3S)-1-propyl-2,5-dioxo-3-(4-((N,N-

diethylamino)carbonylamino)butyl)-9-

(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-74)
(3S)-1-propyl-2,5-dioxo-3-(4-((N,N-bis(1-

methylethyl)amino)carbonylamino)butyl)-9-

(2-phenylethyl)-

1,4,9-triazaspiro[5.5]undecane

22(H21-75)
(3S)-1-propyl-2,5-dioxo-3-(4-(morpholin-4-

ylcarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-76)
(3S)-1-propyl-2,5-dioxo-3-(4-(carbazol-9-

ylcarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

22(H21-77)
(3S)-1-propyl-2,5-dioxo-3-(4-(pyrrolidin-1-

ylcarbonylamino)butyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[1262]

420

TABLE 20B-1

1982

Example No
R3
R4

22(H20-1)
H

1983

22(H20-2)
H

1984

22(H20-3)
H

1985

22(H20-4)
H

1986

22(H20-5)
H

1987

[1263]

421

TABLE 20B-2

1988

Example No
R3
R4

22(H20-6)
H

1989

22(H20-7)
H

1990

22(H20-8)
H

1991

22(H20-9)
H

1992

22(H20-10)
H

1993

22(H20-11)
H

1994

[1264]

422

TABLE 20B-3

1995

Example

No
R3
R4

22(H20-12)
H

1996

22(H20-13)
H

1997

22(H20-14)
H

1998

22(H20-15)
H

1999

22(H20-16)
H

2000

22(H20-17)
H

2001

[1265]

423

TABLE 20B-4

2002

Example No
R3
R4

22(H20-18)
H

2003

22(H20-19)
H

2004

22(H20-20)
H

2005

22(H20-21)
H

2006

22(H20-22)
H

2007

22(H20-23)
H

2008

[1266]

424

TABLE 20B-5

2009

Example No
R3
R4

22(H20-24)
H

2010

22(H20-25)
H

2011

22(H20-26)
H

2012

22(H20-27)
H

2013

22(H20-28)
H

2014

22(H20-29)
H

2015

22(H20-30)
H

2016

[1267]

425

TABLE 20B-6

2017

Example No
R3
R4

22(H20-31)
H

2018

22(H20-32)
H

2019

22(H20-33)
H

2020

22(H20-34)
H

2021

22(H20-35)
H

2022

22(H20-36)
H

2023

[1268]

426

TABLE 20B-7

2024

Example No
R3
R4

22(H20-37)
H

2025

22(H20-38)
H

2026

22(H20-39)
H

2027

22(H20-40)
H

2028

22(H20-41)
H

2029

22(H20-42)
H

2030

22(H20-43)
H

2031

22(H20-44)
H

2032

[1269]

427

TABLE 20B-8

2033

Example No
R3
R4

22(H20-45)
H

2034

22(H20-46)
H

2035

22(H20-47)
H

2036

22(H20-48)
H

2037

22(H20-49)
H

2038

22(H20-50)
H

2039

22(H20-51)
H

2040

22(H20-52)
H

2041

[1270]

428

TABLE 20B-9

2042

Example No
R3
R4

22(H20-53)
H

2043

22(H20-54)
H

2044

22(H20-55)
H

2045

22(H20-56)
H

2046

22(H20-57)
H

2047

22(H20-58)
H

2048

22(H20-59)
H

2049

[1271]

429

TABLE 20B-10

2050

Example No
R3
R4

22(H20-60)
H

2051

22(H20-61)
H

2052

22(H20-62)
H

2053

22(H20-63)
H

2054

22(H20-64)
H

2055

22(H20-65)
H

2056

[1272]

430

TABLE 20B-11

2057

Example No
R3
R4

22(H20-66)
H

2058

22(H20-67)
H

2059

22(H20-68)
H

2060

22(H20-69)
H

2061

22(H20-70)
H

2062

22(H20-71)
H

2063

[1273]

431

TABLE 20B-12

2064

Example No
R3
R4

22(H20-72)
H

2065

22(H20-73)
H

2066

22(H20-74)
H

2067

22(H20-75)
H

2068

[1274]

432

TABLE 21B-1

2069

Example No
R3
R4

22(H21-1)
H

2070

22(H21-2)
H

2071

22(H21-3)
H

2072

22(H21-4)
H

2073

22(H21-5)
H

2074

22(H21-6)
H

2075

22(H21-7)
H

2076

[1275]

433

TABLE 21B-2

2077

Example No
R3
R4

22(H21-8)
H

2078

22(H21-9)
H

2079

22(H21-10)
H

2080

22(H21-11)
H

2081

22(H21-12)
H

2082

22(H21-13)
H

2083

22(H21-14)
H

2084

22(H21-15)
H

2085

[1276]

434

TABLE 21B-3

2086

Example No
R3
R4

22(H21-16)
H

2087

22(H21-17)
H

2088

22(H21-18)
H

2089

22(H21-19)
H

2090

22(H21-20)
H

2091

22(H21-21)
H

2092

22(H21-22)
H

2093

22(H21-23)
H

2094

[1277]

435

TABLE 21B-4

2095

Example No
R3
R4

22(H21-24)
H

2096

22(H21-25)
H

2097

22(H21-26)
H

2098

22(H21-27)
H

2099

22(H21-28)
H

2100

22(H21-29)
H

2101

22(H21-30)
H

2102

[1278]

436

TABLE 21B-5

2103

Example No
R3
R4

22(H21-31)
H

2104

22(H21-32)
H

2105

22(H21-33)
H

2106

22(H21-34)
H

2107

22(H21-35)
H

2108

22(H21-36)
H

2109

[1279]

437

TABLE 21B-6

2110

Example No
R3
R4

22(H21-37)
H

2111

22(H21-38)
H

2112

22(H21-39)
H

2113

22(H21-40)
H

2114

22(H21-41)
H

2115

22(H21-42)
H

2116

[1280]

438

TABLE 21B-7

2117

Example No
R3
R4

22(H21-43)
H

2118

22(H21-44)
H

2119

22(H21-45)
H

2120

22(H21-46)
H

2121

22(H21-47)
H

2122

22(H21-48)
H

2123

[1281]

439

TABLE 21B-8

2124

Example No
R3
R4

22(H21-49)
H

2125

22(H21-50)
H

2126

22(H21-51)
H

2127

22(H21-52)
H

2128

22(H21-53)
H

2129

22(H21-54)
H

2130

[1282]

440

TABLE 21B-9

2131

Example No
R3
R4

22(H21-55)
H

2132

22(H21-56)
H

2133

22(H21-57)
H

2134

22(H21-58)
H

2135

22(H21-59)
H

2136

22(H21-60)
H

2137

22(H21-61)
H

2138

[1283]

441

TABLE 21B-10

2139

Example No
R3
R4

22(H21-62)
H

2140

22(H21-63)
H

2141

22(H21-64)
H

2142

22(H21-65)
H

2143

22(H21-66)
H

2144

22(H21-67)
H

2145

22(H21-68)
H

2146

[1284]

442

TABLE 21B-11

2147

Example No
R3
R4

22(H21-69)
H

2148

22(H21-70)
H

2149

22(H21-71)
H

2150

22(H21-72)
H

2151

22(H21-73)
H

2152

22(H21-74)
H

2153

[1285]

443

TABLE 21B-12

2154

Example

No
R3
R4

22(H21-75)
H

2155

22(H21-76)
H

2156

22(H21-77)
H

2157

[1286]

444

TABLE 20C-1

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

22(H20-1)
F
3.43
581 (M + H)+.
ESI (Pos., 20 V)

22(H20-2)
F
3.43
581 (M + H)+.
ESI (Pos., 20 V)

22(H20-3)
F
3.09
548 (M + H)+.
ESI (Pos., 20 V)

22(H20-4)
F
3.32
620 (M + H)+.
ESI (Pos., 20 V)

22(H20-5)
F
3.24
523 (M + H)+.
ESI (Pos., 20 V)

22(H20-6)
F
3.23
523 (M + H)+.
ESI (Pos., 20 V)

22(H20-7)
F
3.20
523 (M + H)+.
ESI (Pos., 20 V)

22(H20-8)
F
3.17
497 (M + H)+.
ESI (Pos., 20 V)

22(H20-9)
F
3.26
519 (M + H)+.
ESI (Pos., 20 V)

22(H20-10)
F
3.20
535 (M + H)+.
ESI (Pos., 20 V)

22(H20-11)
F
3.16
485 (M + H)+.
ESI (Pos., 20 V)

22(H20-12)
F
2.95
506 (M + H)+.
ESI (Pos., 20 V)

22(H20-13)
F
3.11
506 (M + H)+.
ESI (Pos., 20 V)

22(H20-14)
F
3.20
519 (M + H)+.
ESI (Pos., 20 V)

22(H20-15)
F
3.25
535 (M + H)+.
ESI (Pos., 20 V)

22(H20-16)
F
3.05
569 (M + H)+.
ESI (Pos., 20 V)

22(H20-17)
F
3.25
614 (M + H)+.
ESI (Pos., 20 V)

22(H20-18)
F
3.31
598 (M + H)+.
ESI (Pos., 20 V)

22(H20-19)
F
3.23
535 (M + H)+.
ESI (Pos., 20 V)

22(H20-20)
F
3.17
525 (M + H)+.
ESI (Pos., 20 V)

22(H20-21)
F
3.24
499 (M + H)+.
ESI (Pos., 20 V)

22(H20-22)
F
3.25
519 (M + H)+.
ESI (Pos., 20 V)

22(H20-23)
F
3.06
471 (M + H)+.
ESI (Pos., 20 V)

22(H20-24)
F
3.33
525 (M + H)+.
ESI (Pos., 20 V)

22(H20-25)
F
3.28
531 (M + H)+.
ESI (Pos., 20 V)

22(H20-26)
F
3.20
519 (M + H)+.
ESI (Pos., 20 V)

[1287]

445

TABLE 20C-2

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

22(H20-27)
F
3.20
499 (M + H)+.
ESI (Pos., 20 V)

22(H20-28)
F
3.23
511 (M + H)+.
ESI (Pos., 20 V)

22(H20-29)
F
3.18
505 (M + H)+.
ESI (Pos., 20 V)

22(H20-30)
F
3.16
511 (M + H)+.
ESI (Pos., 20 V)

22(H20-31)
F
3.36
551 (M + H)+.
ESI (Pos., 20 V)

22(H20-32)
F
3.27
586 (M + H)+.
ESI (Pos., 20 V)

22(H20-33)
F
3.42
586 (M + H)+.
ESI (Pos., 20 V)

22(H20-34)
F
3.20
549 (M + H)+.
ESI (Pos., 20 V)

22(H20-35)
F
3.20
535 (M + H)+.
ESI (Pos., 20 V)

22(H20-36)
F
3.09
495 (M + H)+.
ESI (Pos., 20 V)

22(H20-37)
F
3.27
549 (M + H)+.
ESI (Pos., 20 V)

22(H20-38)
F
3.11
483 (M + H)+.
ESI (Pos., 20 V)

22(H20-39)
F
3.20
549 (M + H)+.
ESI (Pos., 20 V)

22(H20-40)
F
2.96
443 (M + H)+.
ESI (Pos., 20 V)

22(H20-41)
F
3.22
499 (M + H)+.
ESI (Pos., 20 V)

22(H20-42)
F
3.00
473 (M + H)+.
ESI (Pos., 20 V)

22(H20-43)
F
3.07
503 (M + H)+.
ESI (Pos., 20 V)

22(H20-44)
F
3.23
511 (M + H)+.
ESI (Pos., 20 V)

22(H20-45)
F
3.16
485 (M + H)+.
ESI (Pos., 20 V)

22(H20-46)
F
3.12
485 (M + H)+.
ESI (Pos., 20 V)

22(H20-47)
F
3.27
551 (M + H)+.
ESI (Pos., 20 V)

22(H20-48)
F
3.11
527 (M + H)+.
ESI (Pos., 20 V)

22(H20-49)
F
3.20
530 (M + H)+.
ESI (Pos., 20 V)

22(H20-50)
F
3.07
471 (M + H)+.
ESI (Pos., 20 V)

22(H20-51)
F
3.01
457 (M + H)+.
ESI (Pos., 20 V)

22(H20-52)
F
3.07
469 (M + H)+.
ESI (Pos., 20 V)

[1288]

446

TABLE 20C-3

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

22(H20-53)
F
3.18
549 (M + H)+.
ESI (Pos., 20 V)

22(H20-54)
F
3.34
613 (M + H)+.
ESI (Pos., 20 V)

22(H20-55)
F
3.49
565 (M + H)+.
ESI (Pos., 20 V)

22(H20-56)
F
3.22
565 (M + H)+.
ESI (Pos., 20 V)

22(H20-57)
F
3.03
479 (M + H)+.
ESI (Pos., 20 V)

22(H20-58)
F
3.34
535 (M + H)+.
ESI (Pos., 20 V)

22(H20-59)
F
3.14
507 (M + H)+.
ESI (Pos., 20 V)

22(H20-60)
F
3.40
575 (M + H)+.
ESI (Pos., 20 V)

22(H20-61)
F
3.38
667 (M + H)+.
ESI (Pos., 20 V)

22(H20-62)
F
3.35
586 (M + H)+.
ESI (Pos., 20 V)

22(H20-63)
F
3.22
619 (M + H)+.
ESI (Pos., 20 V)

22(H20-64)
F
3.45
609 (M + H)+.
ESI (Pos., 20 V)

22(H20-65)
F
3.51
617 (M + H)+.
ESI (Pos., 20 V)

22(H20-66)
F
3.49
617 (M + H)+.
ESI (Pos., 20 V)

22(H20-67)
F
3.38
557 (M + H)+.
ESI (Pos., 20 V)

22(H20-68)
F
3.29
577 (M + H)+.
ESI (Pos., 20 V)

22(H20-69)
F
3.33
577 (M + H)+.
ESI (Pos., 20 V)

22(H20-70)
F
3.29
601 (M + H)+.
ESI (Pos., 20 V)

22(H20-71)
F
3.51
643 (M + H)+.
ESI (Pos., 20 V)

22(H20-72)
F
3.42
591 (M + H)+.
ESI (Pos., 20 V)

22(H20-73)
F
3.39
567 (M + H)+.
ESI (Pos., 20 V)

22(H20-74)
F
3.22
531 (M + H)+.
ESI (Pos., 20 V)

22(H20-75)
F
3.23
547 (M + H)+.
ESI (Pos., 20 V)

[1289]

447

TABLE 21C-1

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

22(H21-1)
F
3.51
694 (M + H)+.
ESI (Pos., 20 V)

22(H21-2)
F
3.45
687 (M + H)+.
ESI (Pos., 20 V)

22(H21-3)
F
3.40
617 (M + H)+.
ESI (Pos., 20 V)

22(H21-4)
F
3.17
619 (M + H)+.
ESI (Pos., 20 V)

22(H21-5)
F
3.52
661 (M + H)+.
ESI (Pos., 20 V)

22(H21-6)
F
3.47
609 (M + H)+.
ESI (Pos., 20 V)

22(H21-7)
F
3.28
571 (M + H)+.
ESI (Pos., 20 V)

22(H21-8)
F
3.29
555 (M + H)+.
ESI (Pos., 20 V)

22(H21-9)
F
3.03
472 (M + H)+.
ESI (Pos., 20 V)

22(H21-10)
F
3.09
486 (M + H)+.
ESI (Pos., 20 V)

22(H21-11)
F
3.07
486 (M + H)+.
ESI (Pos., 20 V)

22(H21-12)
F
3.16
500 (M + H)+.
ESI (Pos., 20 V)

22(H21-13)
F
3.33
554 (M + H)+.
ESI (Pos., 20 V)

22(H21-14)
F
3.22
520 (M + H)+.
ESI (Pos., 20 V)

22(H21-15)
F
3.27
534 (M + H)+.
ESI (Pos., 20 V)

22(H21-16)
F
3.34
528 (M + H)+.
ESI (Pos., 20 V)

22(H21-17)
F
3.25
538 (M + H)+.
ESI (Pos., 20 V)

22(H21-18)
F
3.22
534 (M + H)+.
ESI (Pos., 20 V)

22(H21-19)
F
3.25
526 (M + H)+.
ESI (Pos., 20 V)

22(H21-20)
F
3.29
534 (M + H)+.
ESI (Pos., 20 V)

22(H21-21)
F
3.52
556 (M + H)+.
ESI (Pos., 20 V)

22(H21-22)
F
3.37
600 (M + H)+.
ESI (Pos., 20 V)

22(H21-23)
F
3.24
554 (M + H)+.
ESI (Pos., 20 V)

22(H21-24)
F
3.44
562 (M + H)+.
ESI (Pos., 20 V)

22(H21-25)
F
3.34
554 (M + H)+.
ESI (Pos., 20 V)

22(H21-26)
F
3.36
562 (M + H)+.
ESI (Pos., 20 V)

[1290]

448

TABLE 21C-2

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

22(H21-27)
F
3.31
562(M + H)+.
ESI (Pos., 20 V)

22(H21-28)
F
3.47
612(M + H)+.
ESI (Pos., 20 V)

22(H21-29)
F
3.47
592(M + H)+.
ESI (Pos., 20 V)

22(H21-30)
F
3.47
596(M + H)+.
ESI (Pos., 20 V)

22(H21-31)
F
3.40
596(M + H)+.
ESI (Pos., 20 V)

22(H21-32)
F
3.42
588(M + H)+.
ESI (Pos., 20 V)

22(H21-33)
F
3.44
588(M + H)+.
ESI (Pos., 20 V)

22(H21-34)
F
3.49
620(M + H)+.
ESI (Pos., 20 V)

22(H21-35)
F
3.47
604(M + H)+.
ESI (Pos., 20 V)

22(H21-36)
F
3.31
548(M + H)+.
ESI (Pos., 20 V)

22(H21-37)
F
3.42
590(M + H)+.
ESI (Pos., 20 V)

22(H21-38)
F
3.36
623(M + H)+.
ESI (Pos., 20 V)

22(H21-39)
F
3.33
548(M + H)+.
ESI (Pos., 20 V)

22(H21-40)
F
3.29
566(M + H)+.
ESI (Pos., 20 V)

22(H21-41)
F
3.31
566(M + H)+.
ESI (Pos., 20 V)

22(H21-42)
F
3.53
576(M + H)+.
ESI (Pos., 20 V)

22(H21-43)
F
3.49
622(M + H)+.
ESI (Pos., 20 V)

22(H21-44)
F
3.42
706(M + H)+.
ESI (Pos., 20 V)

22(H21-45)
F
3.25
572(M + H)+.
ESI (Pos., 20 V)

22(H21-46)
F
3.23
548(M + H)+.
ESI (Pos., 20 V)

22(H21-47)
F
3.40
757(M + H)+.
ESI (Pos., 20 V)

22(H21-48)
F
3.33
556(M + H)+.
ESI (Pos., 20 V)

22(H21-49)
F
3.33
636(M + H)+.
ESI (Pos., 20 V)

22(H21-50)
F
3.18
646(M + H)+.
ESI (Pos., 20 V)

22(H21-51)
F
3.23
548(M + H)+.
ESI (Pos., 20 V)

22(H21-52)
F
3.30
501(M + H)+.
ESI (Pos., 20 V)

[1291]

449

TABLE 21C-3

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

22(H21-53)
F
3.64
557 (M + H)+.
ESI (Pos., 20 V)

22(H21-54)
F
3.13
473 (M + H)+.
ESI (Pos., 20 V)

22(H21-55)
F
3.20
485 (M + H)+.
ESI (Pos., 20 V)

22(H21-56)
F
3.21
487 (M + H)+.
ESI (Pos., 20 V)

22(H21-57)
F
3.31
501 (M + H)+.
ESI (Pos., 20 V)

22(H21-58)
F
3.49
529 (M + H)+.
ESI (Pos., 20 V)

22(H21-59)
F
3.38
575 (M + H)+.
ESI (Pos., 20 V)

22(H21-60)
F
3.57
623 (M + H)+.
ESI (Pos., 20 V)

22(H21-61)
F
3.69
583 (M + H)+.
ESI (Pos., 20 V)

22(H21-62)
F
3.09
503 (M + H)+.
ESI (Pos., 20 V)

22(H21-63)
F
3.40
515 (M + H)+.
ESI (Pos., 20 V)

22(H21-64)
F
3.22
487 (M + H)+.
ESI (Pos., 20 V)

22(H21-65)
F
3.25
499 (M + H)+.
ESI (Pos., 20 V)

22(H21-66)
F
3.69
583 (M + H)+.
ESI (Pos., 20 V)

22(H21-67)
F
3.31
513 (M + H)+.
ESI (Pos., 20 V)

22(H21-68)
F
3.28
501 (M + H)+.
ESI (Pos., 20 V)

22(H21-69)
F
3.34
535 (M + H)+.
ESI (Pos., 20 V)

22(H21-70)
F
3.40
596 (M + H)+.
ESI (Pos., 20 V)

22(H21-71)
F
3.23
534 (M + H)+.
ESI (Pos., 20 V)

22(H21-72)
F
3.01
472 (M + H)+.
ESI (Pos., 20 V)

22(H21-73)
F
3.12
500 (M + H)+.
ESI (Pos., 20 V)

22(H21-74)
F
3.27
528 (M + H)+.
ESI (Pos., 20 V)

22(H21-75)
F
3.01
514 (M + H)+.
ESI (Pos., 20 V)

22(H21-76)
F
3.49
574 (M + H)+.
ESI (Pos., 20 V)

22(H21-77)
F
3.07
498 (M + H)+.
ESI (Pos., 20 V)

EXAMPLE 23

[1292] 1-cyclopropylmethyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenoxyphenyl)-1,3,9-triazaspiro[5.5]undecane.acetate

2158

[1293] To a suspension of Resin (3) prepared in Reference Example 2 (0.5 g) in tetrahydrofuran/methanol (1:1; 5 ml) were added N-allyloxycarbonyl-4-piperidone (0.396 g), cyclopropylmethylamine (0.189 ml) and N-(t-butyloxycarbonyl)leucine (0.542 g), and it was stirred for 18 hours at 65° C. The reaction solution was cooled to room temperature and the resin was collected by filtration. The obtained resin was washed with dimethylformamide (5 ml×2), dichloromethane (5 ml×2), methanol (5 ml×2) and dichloromethane (5 ml×2). To a suspension of the obtained resin in dichloromethane (5 ml) were added acetic acid (0.149 ml), tributyltin hydride (0.351 ml) and tetrakis(triphenylphosphine)palladium (0) complex (50 mg), and it was stirred for 6 hours at room temperature. The resin was collected by filtration from the reaction solution, and was washed with dichloromethane (5 ml×4) and dimethylformamide (5 ml×3). The obtained resin was suspended in 1% acetic acid-dimethylformamide solution (5 ml), and 4-phenyloxybenzaldehyde (0.252 g), and sodium triacetoxyborohydride (0.277 g) were added thereto. It was stirred for 15 hours at room temperature. The resin was collected by filtration from reaction mixture, and was washed with methanol (5 ml×1), dimethylformamide (5 ml×3), methanol (5 ml×4) and dichloromethane (5 ml×4). The obtained resin was suspended in 50% trifluoroacetic acid-dichloromethane solution (5 ml), and it was stirred for 5 minutes at room temperature. The reaction solution was filtrated, and the obtained resin was suspended in 50% trifluoroacetic acid-dichloromethane solution (5 ml), and it was stirred for 30 minutes at room temperature. The obtained resin by filtration from the reaction solution was washed with dichloromethane (5 ml×3) and 1.25M acetic acid-toluene solution (5 ml×3). The obtained resin was suspended in 1.25M acetic acid-toluene solution (5 ml), and it was stirred for 23 hours at 90° C. The reaction solution was filtrated. The obtained resin was washed with chloroform-methanol (1:1; 2 ml×2). The filtrate and the washings were concentrated to give the compound of the present invention (274 mg) having the following physical data.

[1294] TLC: Rf 0.40 (chloroform:methanol=20:1);

[1295] NMR (CD3OD): δ 7.49 (m, 2H), 7.40 (m, 2H), 7.18 (m, 2H), 7.04 (m, 3H), 4.33 (s, 2H), 4.04 (dd, J=8.1, 4.8 Hz, 1H), 3.78 (m, 2H), 3.52 (m, 2H), 3.35 (m, 2H), 2.45-2.10 (m, 4H), 1.98 (s, 3H, CH3COOH), 1.97-1.58 (m, 4H), 0.94 (d, J=6.0 Hz, 6H), 0.51 (m, 2H), 0.36 (m, 2H).

EXAMPLE 23(1)

[1296] 1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenoxyphenyl)-1,3,9-triazaspiro[5.5]undecane.acetate

2159

[1297] By the same procedure as described in Example 23 using Resin (3) prepared in Reference Example 2 (0.5 g), N-allyloxycarbonyl-4-piperidone (0.396 g), thiophen-2-ylmethylamine (0.205 ml) and N-(t-butyloxycarbonyl)leucine (0.542 g), 4-phenoxybenzaldehyde (0.252 g), the compound of the present invention (274 mg) having the following physical data was obtained.

[1298] TLC: Rf 0.39 (chloroform:methanol=20:1);

[1299] NMR (CD3OD): δ 7.48 (m, 2H), 7.39 (m, 2H), 7.28 (m, 1H), 7.18 (m, 2H), 7.04 (m, 4H), 6.91 (m, 1H), 4.86 (s, 2H), 4.32 (s, 2H), 4.12 (dd, J=8.1, 4.5 Hz, 1H), 3.77 (m, 2H), 3.49 (m, 2H), 2.60-2.30 (m, 2H), 2.19 (m, 2H), 1.98 (s, 3H), 1.97-1.58 (m, 3H), 0.94 (d, J=6.0 Hz, 6H).

EXAMPLE 23(H22-1)˜23(H31-31)

[1300] By the same procedure as described in Example 23 or 23(1), using Resin (3) prepared in Reference Example 2, the corresponding 4-piperidone derivatives, the corresponding amine derivatives, the corresponding amino acid derivatives, and the corresponding aldehyde derivatives, the compounds of the present invention, whose names were shown in the following Table 22A-1˜31A-4, and whose structures were shown in the following Table 22B-1˜31B-5, were obtained. Also, physical data of the above compound were shown in the followings Table 22C-1˜31C-2.

450TABLE 22A-1ExampleNoCompound Name23(H22-1)(3S)-1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane23(H22-2)(3R)-1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane23(H22-3)(3S)-1-propyl-2,5-dioxo-3-methyl-9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane23(H22-4)(3S)-1-propyl-2,5-dioxo-3-benzyl-9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane23(H22-5)(3S)-1-propyl-2,5-dioxo-3-(1-(benzyloxymethyl)imidazol-5-ylmethyl)-9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane23(H22-6)(3S)-1-propyl-2,5-dioxo-3-(benzyloxymethyl)-9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane23(H22-7)(3S)-1-propyl-2,5-dioxo-3-(4-methoxyphenylmethyl)-9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane23(H22-8)(3S)-1-propyl-2,5-dioxo-3-((1R)-1-(benzyloxy)ethyl)-9-(6-phenylhexyl)-1,4,9-triazaspiro[5.5]undecane

[1301]

451

TABLE 22A-2

Example

No
Compound Name

23(H22-9)
(3S)-1-propyl-2,5-dioxo-3-(pyridin-3-

ylmethyl)-9-(6-phenylnexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-10)
(3S)-1-propyl-2,5-dioxo-3-butyl-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-11)
(3S)-1-propyl-2,5-dioxo-3-

(cyclohexyloxycarbonylmethyl)-

9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-12)
(3S)-1-propyl-2,5-dioxo-3-

(cyclohexylmethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-13)
(3R)-1-propyl-2,5-dioxo-3-

(cyclohexyloxycarbonylmethyl)-

9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-14)
(3R)-1-propyl-2,5-dioxo-3-(2-

(cyclohexyloxycarbonyl)ethyl)-

9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-15)
(3R)-1-propyl-2,5-dioxo-3-(4-

(benzyloxy)phenylmethyl)-

9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-16)
(3S)-1-propyl-2,5-dioxo-3-

hydroxymethyl-9-(6-phenylhexyl)-

1,4,9-triazaspiro[5.5]undecane

[1302]

452

TABLE 22A-3

Example

No
Compound Name

23(H22-17)
(3S)-1-propyl-2,5-dioxo-3-(4-

(benzyloxy)phenylmethyl)-

9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-18)
(3R)-1-propyl-2,5-dioxo-3-butyl-9-

(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-19)
(3R)-1-propyl-2,5-dioxo-3-

(cyclohexylmethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-20)
(3R)-1-propyl-2,5-dioxo-3-((1S)-1-

(benzyloxy)ethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-21)
(3R)-1-propyl-2,5-dioxo-3-

(benzyloxymethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-22)
(3R)-1-propyl-2,5-dioxo-3-((4-

methoxyphenylmethylthio)methyl)-9-

(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-23)
(3R)-1-propyl-2,5-dioxo-3-

(benzylthiomethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-24)
(3S)-1-propyl-2,5-dioxo-9-

(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

[1303]

453

TABLE 22A-4

Example

No
Compound Name

23(H22-25)
(3S)-1-propyl-2,5-dioxo-3-

(imidazol-4-ylmethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-26)
(3S)-1-propyl-2,5-dioxo-3-

hydroxymethyl-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-27)
(3R)-1-propyl-2,5-dioxo-3-

((3-nitropyridin-2-

yl)disulfanylmethyl)-9-

(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-28)
(3S)-1-propyl-2,5-dioxo-3-(1-benzylimidazol-

4-ylmethyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-29)
(3R)-1-propyl-2,5-dioxo-3-(4-

hydroxyphenylmethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-30)
(3S)-1-propyl-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)phenylmethyl)-

9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-31)
(3R)-1-propyl-2,5-dioxo-3-(3-

(aminocarbonylamino)propyl)-

9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-32)
(3R)-1-propyl-2,5-dioxo-3-(1-

naphthylmethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

[1304]

454

TABLE 22A-5

Example

No
Compound Name

23(H22-33)
(3S)-1-propyl-2,5-dioxo-3-

(3,4-dichlorophenylmethyl)-

9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-34)
(3R)-1-propyl-2,5-dioxo-3-((1,1-

dimethylethylthio)methyl)-

9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-35)
(3S)-1-propyl-2,5-dioxo-3-

(2-methylpropyl)-4-methyl-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-36)
(3S)-1-propyl-2,5-dioxo-3-propyl-9-

(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-37)
(3S)-1-propyl-2,5-dioxo-3-

(4-benzyloxyphenylmethyl)-4-

methyl-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-38)
(3S)-1-propyl-2,5-dioxo-3-

((1R)-1-hydroxyethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-39)
(3S)-1-propyl-2,5-dioxo-3-

(aminocarbonylmethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-40)
(3S)-1-propyl-2,5-dioxo-3-

((1R)-1-hydroxyethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-41)
(3R)-1-propyl-2,5-dioxo-3-

methyl-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

[1305]

455

TABLE 22A-6

Example

No
Compound Name

23(H22-42)
(3R)-1-propyl-2,5-dioxo-3-

(pyridin-3-ylmethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-43)
(3S)-1-propyl-2,5-dioxo-3-

(carboxymethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-44)
(3S)-1-propyl-2,5-dioxo-3-

(4-hydroxyphenylmethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-45)
(3S)-1-propyl-2,5-dioxo-3-

(2-methylthioethyl)-9-(6-

phenylnexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-46)
(3R)-1-propyl-2,5-dioxo-3-

((methylcarbonylamino)-

methylthiomethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-47)
(3R)-1-propyl-2,5-dioxo-3-

((1S)-1-hydroxyethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-48)
(3S)-1-propyl-2,5-dioxo-3-

(2-chlorophenylmethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-49)
(3S)-1-propyl-2,5-dioxo-3-

(1-naphthylmethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-50)
(3S)-1-propyl-2,5-dioxo-3-

(4-fluorophenylmethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

[1306]

456

TABLE 22A-7

Example

No
Compound Name

23(H22-51)
(3S)-1-propyl-2,5-dioxo-3-

(cyanomethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-52)
(3R)-1-propyl-2,5-dioxo-3-

(indol-3-ylmethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-53)
(3S)-1-propyl-2,5-dioxo-3-(4-(2-

chlorophenylmethyloxycarbonylamino)-

butyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-54)
(3R)-1-propyl-2,5-dioxo-3-

(benzyloxycarbonylmethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-55)
(3S)-1-propyl-2,5-dioxo-3-

(3-(1-imino-1-(2,4,6-

trimethylphenylsulfonylamino)-

methylamino)propyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-56)
(3S)-1-propyl-2,5-dioxo-3-

(benzyloxycarbonylmethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-57)
(3S)-1-propyl-2,5-dioxo-3-

(4-(benzyloxycarbonylamino)butyl)-

9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-58)
(3R)-1-propyl-2,5-dioxo-3-

(4-methoxyphenylmethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

[1307]

457

TABLE 22A-8

Example

No
Compound Name

23(H22-59)
(3R)-1-propyl-2,5-dioxo-3-(4-

(benzyloxycarbonylamino)butyl)-9-

(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-60)
(3S)-1-propyl-2,5-dioxo-3-(3-

(benzyloxycarbonylamino)propyl)-9-

(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-61)
(3R)-1-propyl-2,5-dioxo-3-(1-

(benzyloxymethyl)imidazol-4-

ylmethyl)-9-(6-phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-62)
(3R)-1-propyl-2,5-dioxo-3-

(4-ethoxyphenylmethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-63)
(3S)-1-propyl-2,5-dioxo-3-

(4-phenylphenylmethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

23(H22-64)
(3S)-1-propyl-2,5-dioxo-3-

(1,1-diphenylmethyl)-9-(6-

phenylhexyl)-1,4,9-

triazaspiro[5.5]undecane

[1308]

458

TABLE 23A-1

Example

No
Compound Name

23(H23-1)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-

9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H23-2)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

methoxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H23-3)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

diethylaminophenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H23-4)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(3,5-dimethyl-1-

phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H23-5)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

benzyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H23-6)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H23-7)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

allyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H23-8)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(dibenzofuran-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H23-9)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-

phenylimidazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1309]

459

TABLE 23A-2

Example

No
Compound Name

23(H23-10)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(1,4-benzodioxan-6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H23-11)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-

methoxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H23-12)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-

diethylaminophenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H23-13)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(3,5-dimethyl-1-phenylpyrazol-4-

ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H23-14)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-

benzyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H23-15)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-

phenyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H23-16)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-

allyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H23-17)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(dibenzofuran-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H23-18)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(2-phenylimidazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1310]

460

TABLE 24A-1

Example

No
Compound Name

23(H24-1)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(1,4-benzodioxan-6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-2)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(3,5-dimethyl-1-phenylpyrazol-

4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-3)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-methylfuran-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-4)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-bromothiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-5)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(3-methylthiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-6)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-ethylfuran-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-7)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(pyridin-4-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H24-8)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(1-methylindol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-9)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(4-methylimidazol-5-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1311]

461

TABLE 24A-2

Example

No
Compound Name

23(H24-10)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(2,4-dioxo-1,3-dihydropyrimidin-5-

ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-11)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(2-

chlorophenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-12)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(3-

chlorophenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-13)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(indol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-14)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-

(hydroxymethyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-15)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(carboxy)thiophen-2-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H24-16)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(carboxy)furan-2-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H24-17)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-ethylthiophen-2-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H24-18)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-(1-

methylbenzimidazol-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1312]

462

TABLE 24A-3

Example

No
Compound Name

23(H24-19)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(2-

trifluoromethoxyphenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-20)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-

(methoxycarbonyl)indol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-21)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-

(2,6-dichloro-4-trifluoromethylphenyl)

furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-22)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(4-bromothiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-23)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(2-chloro-5-trifluoromethylphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-24)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(3-trifluoromethylphenyl)furan-2-

ylmethyl)-1,4,9-triazaspiro[5.5]undecane

23(H24-25)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(1-acetylindol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1313]

463

TABLE 24A-4

Example

No
Compound Name

23(H24-26)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(3,5-bis(trifluoromethyl)phenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-27)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-chloro-3-methyl-1-

phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-28)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(4-methoxyphenyl)thiophen-2-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H24-29)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(2-trifluoromethylphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-30)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-

9-(2,5-dimethyl-1-(4-

carboxyphenyl)pyrrol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H24-31)
1-ethyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(4-chlorophenyl)furan-2-ylmethyl)-

1,4,9-triazaspiro[5.6]undecane

[1314]

464

TABLE 25A-1

Example

No
Compound Name

23(H25-1)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(1,4-benzodioxan-6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-2)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H25-3)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-methylfuran-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-4)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-bromothiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-5)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(3-methylthiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-6)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-ethylfuran-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-7)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(1-methylindol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-8)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(4-methylimidazol-5-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1315]

465

TABLE 25A-2

Example

No
Compound Name

23(H25-9)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(2,4-dioxo-1,3-dihydropyrimidin-5-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H25-10)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(2-chlorophenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-11)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(indol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-12)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-

(hydroxymethyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-13)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(carboxy)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-14)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-ethylthiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-15)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(1-

methylbenzimidazol-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-16)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(2-

trifluoromethoxyphenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1316]

466

TABLE 25A-3

Example

No
Compound Name

23(H25-17)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-

(methoxycarbonyl)indol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-18)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-

(2,6-dichloro-4-trifluoromethylphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-19)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(4-bromothiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-20)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(2-chloro-5-trifluoromethylphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-21)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(3-

trifluoromethylphenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-22)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(1-acetylindol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-23)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(3,5-bis(trifluoromethyl)phenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1317]

467

TABLE 25A-4

Example

No
Compound Name

23(H25-24)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-chloro-3-methyl-

1-phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-25)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(4-methoxyphenyl)thiophen-2-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H25-26)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(2-trifluoromethylphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-27)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(2,5-dimethyl-1-(4-carboxyphenyl)pyrrol-3-

ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H25-28)
1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(4-chlorophenyl)furan-2-ylmethyl)-

1,4,9-triazaspiro[5.6]undecane

[1318]

468

TABLE 26A-1

Example

No
Compound Name

23(H26-1)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(1,4-benzodioxan-6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-2)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H26-3)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-methylfuran-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-4)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-bromothiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-5)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(3-methylthiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-6)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-ethylfuran-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-7)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(pyridin-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-8)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(1-methylindol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-9)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(4-methylimidazol-5-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1319]

469

TABLE 26A-2

Example

No
Compound Name

23(H26-10)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(2,4-dioxo-1,3-dihydropyrimidin-5-

ylmethyl)-1,4,9-triazaspiro[5.5]undecane

23(H26-11)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(2-chlorophenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-12)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(3-

chlorophenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-13)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(indol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-14)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-

(hydroxymethyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-15)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-

(carboxy)thiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-16)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(carboxy)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-17)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-ethylthiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-18)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(1-

methylbenzimidazol-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1320]

470

TABLE 26A-3

Example

No
Compound Name

23(H26-19)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(2-

trifluoromethoxyphenyl)furan-2-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H26-20)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-

(methoxycarbonyl)indol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-21)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(2,6-

dichloro-4-trifluoromethylphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-22)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(4-bromothiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-23)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(2-chloro-5-trifluoromethylphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-24)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(3-

trifluoromethylphenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-25)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(1-acetylindol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1321]

471

TABLE 26A-4

Example

No
Compound Name

23(H26-26)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(3,5-bis(trifluoromethyl)phenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-27)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-chloro-3-methyl-1-

phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-28)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(4-methoxyphenyl)thiophen-2-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H26-29)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(2-

trifluoromethylphenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-30)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(2,5-dimethyl-1-(4-carboxyphenyl)

pyrrol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H26-31)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-

(5-(4-chlorophenyl)furan-2-ylmethyl)-

1,4,9-triazaspiro[5.6]undecane

[1322]

472

TABLE 27A-1

Example

No
Compound Name

23(H27-1)
1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-

benzyl-1,4,9-triazaspiro[5.5]undecane

23(H27-2)
1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

methoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-3)
1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-

(1,4-benzodioxan-6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-4)
1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

phenoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-5)
1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-((4-

benzyloxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-6)
1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-

(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H27-7)
1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-

(2-phenylimidazol-5-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-8)
1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-

((4-hydroxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-9)
1-((2-methoxyphenyl)methyl)-2,5-dioxo-3-

(2-methylpropyl)-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

[1323]

473

TABLE 27A-2

Example

No
Compound Name

23(H27-10)
1-((2-methoxyphenyl)methyl)-2,5-dioxo-3-

(2-methylpropyl)-9-

((4-methoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-11)
1-((2-methoxyphenyl)methyl)-2,5-dioxo-3-

(2-methylpropyl)-9-

(1,4-benzodioxan-6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-12)
1-((2-methoxyphenyl)methyl)-2,5-dioxo-3-

(2-methylpropyl)-9-

((4-phenoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-13)
1-((2-methoxyphenyl)methyl)-2,5-dioxo-3-

(2-methylpropyl)-9-

((4-benzyloxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-14)
1-((2-methoxyphenyl)methyl)-2,5-dioxo-3-

(2-methylpropyl)-9-

(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-15)
1-((2-methoxyphenyl)methyl)-2,5-dioxo-3-

(2-methylpropyl)-9-

(2-phenylimidazol-5-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-16)
1-((2-methoxyphenyl)methyl)-2,5-dioxo-3-

(2-methylpropyl)-9-

((4-hydroxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

[1324]

474

TABLE 27A-3

Example

No
Compound Name

23(H27-17)
1-((3-methoxyphenyl)methyl)-2,5-dioxo-3-

(2-methylpropyl)-9-

benzyl-1,4,9-triazaspiro[5.5]undecane

23(H27-18)
1-((3-methoxyphenyl)methyl)-2,5-dioxo-3-

(2-methylpropyl)-9-

((4-methoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-19)
1-((3-methoxyphenyl)methyl)-2,5-dioxo-3-

(2-methylpropyl)-9-

((4-phenoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-20)
1-((3-methoxyphenyl)methyl)-2,5-dioxo-3-

(2-methylpropyl)-9-

((4-benzyloxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-21)
1-((3-methoxyphenyl)methyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(3,5-dimethyl-1-

phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-22)
1-((3-methoxyphenyl)methyl)-2,5-dioxo-3-

(2-methylpropyl)-9-(2-phenylimidazol-5-

ylmethyl)-1,4,9-triazaspiro[5.5]undecane

23(H27-23)
1-((3-methoxyphenyl)methyl)-2,5-dioxo-3-

(2-methylpropyl)-9-((4-hydroxyphenyl)methyl)-

1,4,9-triazaspiro[5.5]undecane

[1325]

475

TABLE 27A-4

Example

No
Compound Name

23(H27-24)
1-((4-methoxyphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

23(H27-25)
1-((4-methoxyphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-(1,4-benzodioxan-

6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-26)
1-((4-methoxyphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

((4-phenoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-27)
1-((4-methoxyphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

((4-benzyloxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-28)
1-((4-methoxyphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-(3,5-dimethyl-1-

phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-29)
1-((4-methoxyphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-(2-phenylimidazol-

5-ylmethyl)-1,4,9-triazaspiro[5.5]undecane

23(H27-30)
1-((4-methoxyphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

((4-hydroxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

[1326]

476

TABLE 27A-5

Example

No
Compound Name

23(H27-31)
1-(pyridin-2-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

23(H27-32)
1-(pyridin-2-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-((4-

methoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-33)
1-(pyridin-2-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

(2H,3H-benzo[3,4-e]1,4-dioxan-

6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-34)
1-(pyridin-2-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-((4-

phenoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-35)
1-(pyridin-2-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-((4-

benzyloxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-36)
1-(pyridin-2-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-(3,5-

dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-37)
1-(pyridin-2-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-(2-

phenylimidazol-5-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1327]

477

TABLE 27A-6

Example

No
Compound Name

23(H27-38)
1-(pyridin-2-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-((4-

hydroxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-39)
1-(pyridin-3-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

23(H27-40)
1-(pyridin-3-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-((4-

methoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-41)
1-(pyridin-3-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-(1,4-

benzodioxan-6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-42)
1-(pyridin-3-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-((4-

phenoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-43)
1-(pyridin-3-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-((4-

benzyloxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-44)
1-(pyridin-3-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-(3,5-

dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1328]

478

TABLE 27A-7

Example

No
Compound Name

23(H27-45)
1-(pyridin-3-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-(2-

phenylimidazol-5-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-46)
1-(pyridin-3-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-((4-

hydroxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-47)
1-(pyridin-4-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

23(H27-48)
1-(pyridin-4-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-((4-

methoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-49)
1-(pyridin-4-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-(1,4-

benzodioxan-6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-50)
1-(pyridin-4-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-((4-

phenoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-51)
1-(pyridin-4-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-((4-

benzyloxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

[1329]

479

TABLE 27A-8

Example

No
Compound Name

23(H27-52)
1-(pyridin-4-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-(3,5-

dimethyl-1-phenylpyrazol-4-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H27-53)
1-(pyridin-4-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-(2-

phenylimidazol-5-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-54)
1-(pyridin-4-ylmethyl)-2,5-dioxo-

3-(2-methylpropyl)-9-((4-

hydroxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-55)
1-((2-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

23(H27-56)
1-((2-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

((4-methoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-57)
1-((2-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

(1,4-benzodioxan-6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-58)
1-((2-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

((4-phenoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

[1330]

480

TABLE 27A-9

Example

No
Compound Name

23(H27-59)
1-((2-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

((4-benzyloxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-60)
1-((2-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-61)
1-((2-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

(2-phenylimidazol-5-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-62)
1-((2-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

((4-hydroxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-63)
1-((3-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

benzyl-1,4,9-triazaspiro[5.5]undecane

23(H27-64)
1-((3-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

((4-methoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-65)
1-((3-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

(1,4-benzodioxan-6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1331]

481

TABLE 27A-10

Example

No
Compound Name

23(H27-66)
1-((3-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

((4-phenoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-67)
1-((3-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

((4-benzyloxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-68)
1-((3-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-(3,5-dimethyl-1-

phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-69)
1-((3-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

(2-phenylimidazol-5-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-70)
1-((3-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

((4-hydroxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-71)
1-((4-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-benzyl-1,4,9-

triazaspiro[5.5]undecane

23(H27-72)
1-((4-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-((4-

methoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

[1332]

482

TABLE 27A-11

Example

No
Compound Name

23(H27-73)
1-((4-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

(1,4-benzodioxan-6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-74)
1-((4-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

((4-phenoxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-75)
1-((4-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

((4-benzyloxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-76)
1-((4-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-(3,5-dimethyl-

1-phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-77)
1-((4-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

(2-phenylimidazol-5-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H27-78)
1-((4-methylphenyl)methyl)-2,5-dioxo-

3-(2-methylpropyl)-9-

((4-hydroxyphenyl)methyl)-1,4,9-

triazaspiro[5.5]undecane

[1333]

483

TABLE 28A-1

Example

No
Compound Name

23(H28-1)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(1,4-benzodioxan-6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-2)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H28-3)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-methylfuran-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-4)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-bromothiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-5)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(3-methylthiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-6)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-ethylfuran-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-7)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(pyridin-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-8)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(1-methylindol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-9)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(4-methylimidazol-5-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1334]

484

TABLE 28A-2

Example

No
Compound Name

23(H28-10)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(2,4-dioxo-1,3-dihydropyrimidin-5-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H28-11)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-(2-

chlorophenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-12)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-(3-

chlorophenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-13)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-

(hydroxymethyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-14)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-

(carboxy)thiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-15)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(carboxy)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-16)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-ethylthiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-17)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-(1-

methylbenzimidazol-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1335]

485

TABLE 28A-3

Example

No
Compound Name

23(H28-18)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(2-trifluoromethoxyphenyl)furan-2-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H28-19)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-(6-

(methoxycarbonyl)indol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-20)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-

9-(5-(2,6-dichloro-4-

trifluoromethylphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-21)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(4-bromothiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-22)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(2-chloro-5-trifluoromethylphenyl)

furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-23)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(3-trifluoromethylphenyl)furan-2-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H28-24)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(1-acetylindol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1336]

486

TABLE 28A-4

Example

No
Compound Name

23(H28-25)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-

9-(5-(3,5-bis(trifluoromethyl)phenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-26)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-

9-(5-chloro-3-methyl-

1-phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-27)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(4-methoxyphenyl)thiophen-2-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H28-28)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(2-trifluoromethylphenyl)furan-2-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H28-29)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(2,5-dimethyl-1-(4-carboxyphenyl)pyrrol-

3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H28-30)
1-propyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(4-chlorophenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.6]undecane

[1337]

487

TABLE 29A-1

Example

No
Compound Name

23(H29-1)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(1,4-benzodioxan-6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-2)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H29-3)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-methylfuran-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-4)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-bromothiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-5)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(3-methylthiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-6)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-ethylfuran-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-7)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(pyridin-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-8)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(1-methylindol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-9)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(4-methylimidazol-5-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1338]

488

TABLE 29A-2

Example

No
Compound Name

23(H29-10)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(2,4-dioxo-1,3-dihydropyrimidin-5-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H29-11)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-(2-

chlorophenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-12)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-(3-

chlorophenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-13)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(indol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-14)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-

(hydroxymethyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-15)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(carboxy)thiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-16)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(carboxy)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-17)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-ethylthiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-18)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(1-methylbenzimidazol-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1339]

489

TABLE 29A-3

Example

No
Compound Name

23(H29-19)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-(2-

trifluoromethoxyphenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-20)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(6-

(methoxycarbonyl)indol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-21)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(2,6-dichloro-4-trifluoromethylphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-22)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(4-bromothiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-23)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(2-chloro-5-trifluoromethylphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-24)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(3-trifluoromethylphenyl)furan-2-

ylmethyl)-1,4,9-triazaspiro[5.5]undecane

23(H29-25)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(1-acetylindol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1340]

490

TABLE 29A-4

Example

No
Compound Name

23(H29-26)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(3,5-bis(trifluoromethylmethyl)phenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-27)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-chloro-3-methyl-1-

phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-28)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(4-methoxyphenyl)thiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-29)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-(2-

trifluoromethylmethylphenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-30)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-

(2,5-dimethyl-1-(4-carboxyphenyl)pyrrol-

3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H29-31)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-(4-

chlorophenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.6]undecane

[1341]

491

TABLE 30A-1

Example

No
Compound Name

23(H30-1)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(1,4-

benzodioxan-6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-2)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(3,5-

dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-3)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(5-

methylfuran-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-4)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(5-

bromothiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-5)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(3-

methylthiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-6)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(5-

ethylfuran-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-7)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(pyridin-

4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane

23(H30-8)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(1-

methylindol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1342]

492

TABLE 30A-2

Example

No
Compound Name

23(H30-9)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(4-

methylimidazol-5-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-10)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(2,4-

dioxo-1,3-dihydropyrimidin-5-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-11)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(5-(2-

chlorophenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-12)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(5-(3-

chlorophenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-13)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(indol-3-

ylmethyl)-1,4,9-triazaspiro[5.5]undecane

23(H30-14)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(5-

(hydroxymethyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-15)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(5-

(carboxy)thiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1343]

493

TABLE 30A-3

Example

No
Compound Name

23(H30-16)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(5-

(carboxy)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-17)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(5-

ethylthiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-18)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(1-

methylbenzimidazol-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-19)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(5-(2-

trifluoromethoxyphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-20)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(6-

(methoxycarbonyl)indol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-21)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(5-(2,6-

dichloro-4-trifluoromethylphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-22)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(4-

bromothiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1344]

494

TABLE 30A-4

Example

No
Compound Name

23(H30-23)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(5-(2-

chloro-5-trifluoromethylphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-24)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(5-(3-

trifluoromethylphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-25)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(1-

acetylindol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-26)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(5-(3,5-

bis(trifluoromethyl)phenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-27)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(5-chloro-

3-methyl-1 -phenylpyrazol-

4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-28)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(5-(4-

methoxyphenyl)thiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-29)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(5-(2-

trifluoromethylphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1345]

495

TABLE 30A-5

Example

No
Compound Name

23(H30-30)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(2,5-

dimethyl-1-(4-carboxyphenyl)pyrrol-

3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H30-31)
1-(2-methoxyethyl)-2,5-dioxo-

3-cyclohexylmethyl-9-(5-(4-

chlorophenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.6]undecane

[1346]

496

TABLE 31A-1

Example

No
Compound Name

23(H31-1)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(1,4-benzodioxan-6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-2)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H31-3)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-methylfuran-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-4)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-bromothiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-5)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(3-methylthiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-6)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-ethylfuran-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-7)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(pyridin-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-8)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(1-methylindol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-9)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(4-methylimidazol-5-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1347]

497

TABLE 31A-2

Example

No
Compound Name

23(H31-10)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(2,4-dioxo-1,3-dihydropyrimidin-5-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H31-11)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(2-chlorophenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-12)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(3-chlorophenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-13)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(indol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-14)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-

(hydroxymethyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-15)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-

(carboxy)thiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-16)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-

(carboxy)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-17)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-ethylthiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-18)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-(1-

methylbenzimidazol-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1348]

498

TABLE 31A-3

Example

No
Compound Name

23(H31-19)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(2-trifluoromethoxyphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-20)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-(6-

(methoxycarbonyl)indol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-21)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(2,6-dichloro-4-trifluoromethylphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-22)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(4-bromothiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-23)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(2-chloro-5-trifluoromethylphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-24)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(3-trifluoromethylphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-25)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(1-acetylindol-3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[1349]

499

TABLE 31A-4

Example

No
Compound Name

23(H31-26)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(3,5-bis(trifluoromethyl)phenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-27)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-chloro-3-methyl-

1-phenylpyrazol-4-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-28)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(4-methoxyphenyl)thiophen-2-ylmethyl)-

1,4,9-triazaspiro[5.5]undecane

23(H31-29)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(2-trifluoromethylphenyl)furan-

2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-30)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(2,5-dimethyl-1-(4-carboxyphenyl)pyrrol-

3-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

23(H31-31)
1-benzyl-2,5-dioxo-3-cyclohexylmethyl-9-

(5-(4-chlorophenyl)furan-2-ylmethyl)-1,4,9-

triazaspiro[5.6]undecane

[1350]

500

TABLE 22B-1

2160

Example

No
R3
R4
R5

23(H22-1)
H

2161

H

23(H22-2)
H

2162

H

23(H22-3)
H

2163

H

23(H22-4)
H

2164

H

23(H22-5)
H

2165

H

23(H22-6)
H

2166

H

23(H22-7)
H

2167

H

23(H22-8)
H

2168

[1351]

501

TABLE 22B-2

2169

Example No
R3
R4
R5

23(H22-9)
H

2170

H

23(H22-10)
H

2171

H

23(H22-11)
H

2172

H

23(H22-12)
H

2173

H

23(H22-13)
H

2174

H

23(H22-14)
H

2175

H

23(H22-15)
H

2176

H

23(H22-16)
H

2177

[1352]

502

TABLE 22B-3

2178

Example

No
R3
R4
R5

23(H22-17)
H

2179

H

23(H22-18)
H

2180

H

23(H22-19)
H

2181

H

23(H22-20)
H

2182

H

23(H22-21)
H

2183

H

23(H22-22)
H

2184

H

23(H22-23)
H

2185

H

23(H22-24)
H
H
H

[1353]

503

TABLE 22B-4

2186

Example

No
R3
R4
R5

23(H22-25)
H

2187

H

23(H22-26)
H

2188

H

23(H22-27)
H

2189

H

23(H22-28)
H

2190

H

23(H22-29)
H

2191

H

23(H22-30)
H

2192

H

23(H22-31)
H

2193

[1354]

504

TABLE 22B-5

2194

Example No
R3
R4
R5

23(H22-32)
H

2195

H

23(H22-33)
H

2196

H

23(H22-34)
H

2197

H

23(H22-35)
H

2198

X5—CH3

23(H22-36)
H

2199

H

23(H22-37)
H

2200

X5—CH3

23(H22-38)
H

2201

H

23(H22-39)
H

2202

[1355]

505

TABLE 22B-6

2203

Example No
R3
R4
R5

23(H22-40)
H

2204

H

23(H22-41)
H

2205

H

23(H22-42)
H

2206

H

23(H22-43)
H

2207

H

23(H22-44)
H

2208

H

23(H22-45)
H

2209

H

23(H22-46)
H

2210

H

23(H22-47)
H

2211

H

23(H22-48)
H

2212

[1356]

506

TABLE 22B-7

2213

Example No
R3
R4
R5

23(H22-49)
H

2214

H

23(H22-50)
H

2215

H

23(H22-51)
H

2216

H

23(H22-52)
H

2217

H

23(H22-53)
H

2218

H

23(H22-54)
H

2219

H

23(H22-55)
H

2220

[1357]

507

TABLE 22B-8

2221

Example No
R3
R4
R5

23(H22-56)
H

2222

H

23(H22-57)
H

2223

H

23(H22-58)
H

2224

H

23(H22-59)
H

2225

H

23(H22-60)
H

2226

H

23(H22-61)
H

2227

[1358]

508

TABLE 22B-9

2228

Example No
R3
R4
R5

23(H22-62)
H

2229

H

23(H22-63)
H

2230

H

23(H22-64)
H

2231

[1359]

509

TABLE 23B-1

2232

Example No
R1
R3
R4

23(H23-1)

2233

2234

23(H23-2)

2235

2236

23(H23-3)

2237

2238

23(H23-4)

2239

2240

23(H23-5)

2241

2242

23(H23-6)

2243

2244

23(H23-7)

2245

2246

23(H23-8)

2247

2248

[1360]

510

TABLE 23B-2

2249

Example No
R1
R3
R4

23(H23-9)

2250

2251

23(H23-10)

2252

2253

23(H23-11)

2254

2255

23(H23-12)

2256

2257

23(H23-13)

2258

2259

23(H23-14)

2260

2261

23(H23-15)

2262

2263

[1361]

511

TABLE 23B-3

2264

Example No
R1
R3
R4

23(H23-16)

2265

2266

23(H23-17)

2267

2268

23(H23-18)

2269

2270

[1362]

512

TABLE 24B-1

2271

Example No
R1

23(H24-1)

2272

23(H24-2)

2273

23(H24-3)

2274

23(H24-4)

2275

23(H24-5)

2276

23(H24-6)

2277

23(H24-7)

2278

23(H24-8)

2279

[1363]

513

TABLE 24B-2

2280

Example No
R1

23(H24-9)

2281

23(H24-10)

2282

23(H24-11)

2283

23(H24-12)

2284

23(H24-13)

2285

23(H24-14)

2286

23(H24-15)

2287

23(H24-16)

2288

[1364]

514

TABLE 24B-3

2289

Example No
R1

23(H24-17)

2290

23(H24-18)

2291

23(H24-19)

2292

23(H24-20)

2293

23(H24-21)

2294

23(H24-22)

2295

[1365]

515

TABLE 24B-4

2296

Example No
R1

23(H24-23)

2297

23(H24-24)

2298

23(H24-25)

2299

23(H24-26)

2300

23(H24-27)

2301

23(H24-28)

2302

[1366]

516

TABLE 24B-5

2303

Example No
R1

23(H24-29)

2304

23(H24-30)

2305

23(H24-31)

2306

[1367]

517

TABLE 25B-1

2307

Example No
R1

23(H25-1)

2308

23(H25-2)

2309

23(H25-3)

2310

23(H25-4)

2311

23(H25-5)

2312

23(H25-6)

2313

23(H25-7)

2314

23(H25-8)

2315

[1368]

518

TABLE 25B-2

2316

Example No
R1

23(H25-9)

2317

23(H25-10)

2318

23(H25-11)

2319

23(H25-12)

2320

23(H25-13)

2321

23(H25-14)

2322

23(H25-15)

2323

[1369]

519

TABLE 25B-3

2324

Example No
R1

23(H25-16)

2325

23(H25-17)

2326

23(H25-18)

2327

23(H25-19)

2328

23(H25-20)

2329

23(H25-21)

2330

[1370]

520

TABLE 25B-4

2331

Example No
R1

23(H25-22)

2332

23(H25-23)

2333

23(H25-24)

2334

23(H25-25)

2335

23(H25-26)

2336

23(H25-27)

2337

[1371]

521

TABLE 25B-5

2338

Example No
R1

23(H25-28)

2339

[1372]

522

TABLE 26B-1

2340

Example No
R1

23(H26-1)

2341

23(H26-2)

2342

23(H26-3)

2343

23(H26-4)

2344

23(H26-5)

2345

23(H26-6)

2346

23(H26-7)

2347

23(H26-8)

2348

[1373]

523

TABLE 26B-2

2349

Example No
R1

23(H26-9)

2350

23(H26-10)

2351

23(H26-11)

2352

23(H26-12)

2353

23(H26-13)

2354

23(H26-14)

2355

23(H26-15)

2356

[1374]

524

TABLE 26B-3

2357

Example No
R1

23(H26-16)

2358

23(H26-17)

2359

23(H26-18)

2360

23(H26-19)

2361

23(H26-20)

2362

23(H26-21)

2363

23(H26-22)

2364

[1375]

525

TABLE 26B-4

2365

Example No
R1

23(H26-23)

2366

23(H26-24)

2367

23(H26-25)

2368

23(H26-26)

2369

23(H26-27)

2370

[1376]

526

TABLE 26B-5

2371

Example No
R1

23(H26-28)

2372

23(H26-29)

2373

23(H26-30)

2374

23(H26-31)

2375

[1377]

527

TABLE 27B-1

2376

Example No
R1
R2

23(H27-1)

2377

2378

23(H27-2)

2379

2380

23(H27-3)

2381

2382

23(H27-4)

2383

2384

23(H27-5)

2385

2386

23(H27-6)

2387

2388

23(H27-7)

2389

2390

23(H27-8)

2391

2392

[1378]

528

TABLE 27B-2

2393

Example No
R1
R2

23(H27-9)

2394

2395

23(H27-10)

2396

2397

23(H27-11)

2398

2399

23(H27-12)

2400

2401

23(H27-13)

2402

2403

23(H27-14)

2404

2405

[1379]

529

TABLE 27B-3

2406

Example No
R1
R2

23(H27-15)

2407

2408

23(H27-16)

2409

2410

23(H27-17)

2411

2412

23(H27-18)

2413

2414

23(H27-19)

2415

2416

23(H27-20)

2417

2418

23(H27-21)

2419

2420

[1380]

530

TABLE 27B-4

2421

Example No
R1
R2

23(H27-22)

2422

2423

23(H27-23)

2424

2425

23(H27-24)

2426

2427

23(H27-25)

2428

2429

23(H27-26)

2430

2431

23(H27-27)

2432

2433

23(H27-28)

2434

2435

23(H27-29)

2436

2437

[1381]

531

TABLE 27B-5

2438

Example No
R1
R2

23(H27-30)

2439

2440

23(H27-31)

2441

2442

23(H27-32)

2443

2444

23(H27-33)

2445

2446

23(H27-34)

2447

2448

23(H27-35)

2449

2450

23(H27-36)

2451

2452

23(H27-37)

2453

2454

[1382]

532

TABLE 27B-6

2455

Example No
R1
R2

23(H27-38)

2456

2457

23(H27-39)

2458

2459

23(H27-40)

2460

2461

23(H27-41)

2462

2463

23(H27-42)

2464

2465

23(H27-43)

2466

2467

23(H27-44)

2468

2469

23(H27-45)

2470

2471

[1383]

533

TABLE 27B-7

2472

Example No
R1
R2

23(H27-46)

2473

2474

23(H27-47)

2475

2476

23(H27-48)

2477

2478

23(H27-49)

2479

2480

23(H27-50)

2481

2482

23(H27-51)

2483

2484

23(H27-52)

2485

2486

23(H27-53)

2487

2488

[1384]

534

TABLE 27B-8

2489

Example No
R1
R2

23(H27-54)

2490

2491

23(H27-55)

2492

2493

23(H27-56)

2494

2495

23(H27-57)

2496

2497

23(H27-58)

2498

2499

23(H27-59)

2500

2501

23(H27-60)

2502

2503

[1385]

535

TABLE 27B-9

2504

Example No
R1
R2

23(H27-61)

2505

2506

23(H27-62)

2507

2508

23(H27-63)

2509

2510

23(H27-64)

2511

2512

23(H27-65)

2513

2514

23(H27-66)

2515

2516

23(H27-67)

2517

2518

[1386]

536

TABLE 27B-10

2519

Example No
R1
R2

23(H27-68)

2520

2521

23(H27-69)

2522

2523

23(H27-70)

2524

2525

23(H27-71)

2526

2527

23(H27-72)

2528

2529

23(H27-73)

2530

2531

23(H27-74)

2532

2533

23(H27-75)

2534

2535

[1387]

537

TABLE 27B-11

2536

Example No
R1
R2

23(H27-76)

2537

2538

23(H27-77)

2539

2540

23(H27-78)

2541

2542

[1388]

538

TABLE 28B-1

2543

Example No
R1

23(H28-2)

2544

23(H28-2)

2545

23(H28-3)

2546

23(H28-4)

2547

23(H28-5)

2548

23(H28-6)

2549

23(H28-7)

2550

23(H28-8)

2551

[1389]

539

TABLE 28B-2

2552

Example No.
R1

23(H28-9)

2553

23(H28-10)

2554

23(H28-11)

2555

23(H28-12)

2556

23(H28-13)

2557

23(H28-14)

2558

23(H28-15)

2559

23(H28-16)

2560

[1390]

540

TABLE 28B-3

2561

Example No
R1

23(H28-17)

2562

23(H28-18)

2563

23(H28-19)

2564

23(H28-20)

2565

23(H28-21)

2566

23(H28-22)

2567

[1391]

541

TABLE 28B-4

2568

Example No
R1

23(H28-23)

2569

23(H28-24)

2570

23(H28-25)

2571

23(H28-26)

2572

23(H28-27)

2573

23(H28-28)

2574

[1392]

542

TABLE 28B-5

2575

Example No
R1

23(H28-29)

2576

23(H28-30)

2577

[1393]

543

TABLE 29B-1

2578

Example No
R1

23(H29-1)

2579

23(H29-2)

2580

23(H29-3)

2581

23(H29-4)

2582

23(H29-5)

2583

23(H29-6)

2584

23(H29-7)

2585

[1394]

544

TABLE 29B-2

2586

Example No
R1

23(H29-8)

2587

23(H29-9)

2588

23(H29-10)

2589

23(H29-11)

2590

23(H29-12)

2591

23(H29-13)

2592

23(H29-14)

2593

[1395]

545

TABLE 29B-3

2594

Example No
R1

23(H29-15)

2595

23(H29-16)

2596

23(H29-17)

2597

23(H29-18)

2598

23(H29-19)

2599

23(H29-20)

2600

23(H29-21)

2601

[1396]

546

TABLE 29B-4

2602

Example No
R1

23(H29-22)

2603

23(H29-23)

2604

23(H29-24)

2605

23(H29-25)

2606

23(H29-26)

2607

[1397]

547

TABLE 29B-5

2608

Example No
R1

23(H29-27)

2609

23(H29-28)

2610

23(H29-29)

2611

23(H29-30)

2612

23(H29-31)

2613

[1398]

548

TABLE 30B-1

2614

Example No
R1

23(H30-1)

2615

23(H30-2)

2616

23(H30-3)

2617

23(H30-4)

2618

23(H30-5)

2619

23(H30-6)

2620

23(H30-7)

2621

[1399]

549

TABLE 30B-2

2622

Example No
R1

23(H30-8)

2623

23(H30-9)

2624

23(H30-10)

2625

23(H30-11)

2626

23(H30-12)

2627

23(H30-13)

2628

23(H30-14)

2629

[1400]

550

TABLE 30B-3

2630

Example No
R1

23(H30-15)

2631

23(H30-16)

2632

23(H30-17)

2633

23(H30-18)

2634

23(H30-19)

2635

23(H30-20)

2636

[1401]

551

TABLE 30B-4

2637

Example No
R1

23(H30-21)

2638

23(H30-22)

2639

23(H30-23)

2640

23(H30-24)

2641

23(H30-25)

2642

[1402]

552

TABLE 30B-5

2643

Example No
R1

23(H30-26)

2644

23(H30-27)

2645

23(H30-28)

2646

23(H30-29)

2647

23(H30-30)

2648

23(H30-31)

2649

[1403]

553

TABLE 31B-1

2650

Example No
R1

23(H31-1)

2651

23(H31-2)

2652

23(H31-3)

2653

23(H31-4)

2654

23(H31-5)

2655

23(H31-6)

2656

23(H31-7)

2657

[1404]

554

TABLE 31B-2

2658

Example No
R1

23(H31-8)

2659

23(H31-9)

2660

23(H31-10)

2661

23(H31-11)

2662

23(H31-12)

2663

23(H31-13)

2664

23(H31-14)

2665

[1405]

555

TABLE 31B-3

2666

Example No
R1

23(H31-15)

2667

23(H31-16)

2668

23(H31-17)

2669

23(H31-18)

2670

23(H31-19)

2671

23(H31-20)

2672

23(H31-21)

2673

[1406]

556

TABLE 31B-4

2674

Example No
R1

23(H31-22)

2675

23(H31-23)

2676

23(H31-24)

2677

23(H31-25)

2678

23(H31-26)

2679

[1407]

557

TABLE 31B-5

2680

Example No
R1

23(H31-27)

2681

23(H31-28)

2682

23(H31-29)

2683

23(H31-30)

2684

23(H31-31)

2685

[1408]

558

TABLE 22C-1

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

23(H22-1)
E
3.67
442 (M + H)+,
APCI (Pos., 40 V)

369.

23(H22-2)
E
3.67
442 (M + H)+,
APCI (Pos., 40 V)

440, 369.

23(H22-3)
E
3.22
400 (M + H)+,
APCI (Pos., 40 V)

398, 370, 327.

23(H22-4)
E
3.76
476 (M + H)+,
APCI (Pos., 40 V)

400.

23(H22-5)
E
3.36
586 (M + H)+.
APCI (Pos., 40 V)

23(H22-6)
E
3.78
506 (M + H)+,
APCI (Pos., 40 V)

398.

23(H22-7)
E
3.73
506 (M + H)+.
APCI (Pos., 40 V)

23(H22-8)
E
3.97
520 (M + H)+,
APCI (Pos., 40 V)

412, 356.

23(H22-9)
E
2.99
477 (M + H)+,
APCI (Pos., 40 V)

400.

23(H22-10)
E
3.70
442 (M + H)+,
APCI (Pos., 40 V)

412, 369.

23(H22-11)
E
4.03
526 (M + H)+,
APCI (Pos., 40 V)

453, 372.

23(H22-12)
E
4.06
482 (M + H)+,
APCI (Pos., 40 V)

409.

23(H22-13)
E
4.04
526 (M + H)+,
APCI (Pos., 40 V)

453, 372.

23(H22-14)
E
4.10
540 (M + H)+,
APCI (Pos., 40 V)

416.

23(H22-15)
E
4.29
582 (M + H)+,
APCI (Pos., 40 V)

492.

23(H22-16)
E
3.15
416 (M + H)+,
APCI (Pos., 40 V)

398.

23(H22-17)
E
4.29
582 (M + H)+,
APCI (Pos., 40 V)

492.

23(H22-18)
E
3.71
442 (M + H)+,
APCI (Pos., 40 V)

440, 412, 369.

23(H22-19)
E
4.05
482 (M + H)+,
APCI (Pos., 40 V)

452, 409.

23(H22-20)
E
3.97
520 (M + H)+,
APCI (Pos., 40 V)

478, 412.

23(H22-21)
E
3.89
506 (M + H)+,
APCI (Pos., 40 V)

398.

23(H22-22)
E
4.02
552 (M + H)+,
APCI (Pos., 40 V)

398.

23(H22-23)
E
4.03
522 (M + H)+,
APCI (Pos., 40 V)

432, 398.

23(H22-24)
E
3.20
386 (M + H)+.
APCI (Pos., 40 V)

23(H22-25)
E
2.93
466 (M + H)+.
APCI (Pos., 40 V)

23(H22-26)
E
3.79
416 (M + H)+.
APCI (Pos., 40 V)

[1409]

559

TABLE 22C-2

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

23(H22-27)
E
4.16
586 (M + H)+,
APCI (Pos., 40 V)

432, 398, 295.

23(H22-28)
E
3.34
556 (M + H)+.
APCI (Pos., 40 V)

23(H22-29)
E
3.33
492 (M + H)+.
APCI (Pos., 40 V)

23(H22-30)
E
4.12
625 (M + H)+,
APCI (Pos., 40 V)

491.

23(H22-31)
E
3.10
486 (M + H)+,
APCI (Pos., 40 V)

484.

23(H22-32)
E
4.06
526 (M + H)+.
APCI (Pos., 40 V)

23(H22-33)
E
4.22
544 (M + H)+.
APCI (Pos., 40 V)

23(H22-34)
E
3.90
488 (M + H)+,
APCI (Pos., 40 V)

398.

23(H22-35)
E
3.82
456 (M + H)+.
APCI (Pos., 40 V)

23(H22-36)
E
3.11
428 (M + H)+,
APCI (Pos., 40 V)

355.

23(H22-37)
E
4.39
596 (M + H)+.
APCI (Pos., 40 V)

23(H22-38)
E
3.18
430 (M + H)+,
APCI (Pos., 40 V)

386

23(H22-39)
E
3.12
443 (M + H)+.
APCI (Pos., 40 V)

23(H22-40)
E
3.18
430 (M + H)+,
APCI (Pos., 40 V)

386, 356.

23(H22-41)
E
3.22
400 (M + H)+,
APCI (Pos., 40 V)

398, 370, 327.

23(H22-42)
E
2.98
477 (M + H)+.
APCI (Pos., 40 V)

23(H22-43)
E
3.17
444 (M + H)+,
APCI (Pos., 40 V)

398.

23(H22-44)
E
3.32
492 (M + H)+.
APCI (Pos., 40 V)

23(H22-45)
E
4.53
460 (M + H)+.
APCI (Pos., 40 V)

23(H22-46)
E
2.26
503 (M + H)+,
APCI (Pos., 40 V)

432, 398, 263.

23(H22-47)
E
3.20
430 (M + H)+,
APCI (Pos., 40 V)

386.

23(H22-48)
E
3.87
510 (M + H)+,
APCI (Pos., 40 V)

472.

23(H22-49)
E
4.11
526 (M + H)+.
APCI (Pos., 40 V)

23(H22-50)
E
3.89
494 (M + H)+.
APCI (Pos., 40 V)

23(H22-51)
E
3.27
425 (M + H)+.
APCI (Pos., 40 V)

23(H22-52)
E
3.74
515 (M + H)+.
APCI (Pos., 40 V)

[1410]

560

TABLE 22C-3

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

23(H22-53)
E
4.19
625 (M + H)+.
APCI (Pos., 40 V)

23(H22-54)
E
3.93
534 (M + H)+,
APCI (Pos., 40 V)

458.

23(H22-55)
E
4.08
667 (M + H)+.
APCI (Pos., 40 V)

23(H22-56)
E
3.94
534 (M + H)+,
APCI (Pos., 40 V)

458.

23(H22-57)
E
4.02
591 (M + H)+,
APCI (Pos., 40 V)

457.

23(H22-58)
E
3.79
506 (M + H)+.
APCI (Pos., 40 V)

23(H22-59)
E
4.01
591 (M + H)+.
APCI (Pos., 40 V)

23(H22-60)
E
3.91
577 (M + H)+.
APCI (Pos., 40 V)

23(H22-61)
E
3.47
586 (M + H)+.
APCI (Pos., 40 V)

23(H22-62)
E
3.94
520 (M + H)+.
APCI (Pos., 40 V)

23(H22-63)
E
4.33
552 (M + H)+.
APCI (Pos., 40 V)

23(H22-64)
E
4.21
552 (M + H)+.
APCI (Pos., 40 V)

[1411]

561

TABLE 23C

HPLC
Retention

Example
condi-
time

No
tion
(min)
Mass data
Mass condition

23(H23-1)
E
3.00
444 (M + H)+.
APCI (Pos., 40 V)

23(H23-2)
E
3.07
416 (M + H)+.
APCI (Pos., 40 V)

23(H23-3)
E
2.52
457 (M + H)+,
APCI (Pos., 40 V)

296, 162.

23(H23-4)
E
3.17
480 (M + H)+,
APCI (Pos., 40 V)

296, 217, 185.

23(H23-5)
E
3.80
492 (M + H)+.
APCI (Pos., 40 V)

23(H23-6)
E
3.79
478 (M + H)+.
APCI (Pos., 40 V)

23(H23-7)
E
3.43
442 (M + H)+,
APCI (Pos., 40 V)

402, 336, 296.

23(H23-8)
E
3.86
498 (M + Na)+,
APCI (Pos., 40 V)

476 (M + H)+.

23(H23-9)
E
2.90
452 (M + H)+,
APCI (Pos., 40 V)

296.

23(H23-10)
E
3.57
484 (M + H)+,
APCI (Pos., 40 V)

332.

23(H23-11)
E
3.62
456 (M + H)+.
APCI (Pos., 40 V)

23(H23-12)
E
3.22
497 (M + H)+,
APCI (Pos., 40 V)

336, 162.

23(H23-13)
E
3.69
520 (M + H)+,
APCI (Pos., 40 V)

185.

23(H23-14)
E
4.16
532 (M + H)+.
APCI (Pos., 40 V)

23(H23-15)
E
4.16
518 (M + H)+.
APCI (Pos., 40 V)

23(H23-16)
E
3.89
482 (M + H)+,
APCI (Pos., 40 V)

442, 376, 336.

23(H23-17)
E
4.21
516 (M + H)+.
APCI (Pos., 40 V)

23(H23-18)
E
3.48
492 (M + H)+,
APCI (Pos., 40 V)

336, 189, 157.

[1412]

562

TABLE 24C-1

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

23(H24-1)
F
3.07
416 (M + H)+.
ESI (Pos., 20 V)

23(H24-2)
F
3.11
452 (M + H)+.
ESI (Pos., 20 V)

23(H24-3)
F
3.04
362 (M + H)+.
ESI (Pos., 20 V)

23(H24-4)
F
3.16
442 (M + H)+.
ESI (Pos., 20 V)

23(H24-5)
F
3.07
378 (M + H)+.
ESI (Pos., 20 V)

23(H24-6)
F
3.12
376 (M + H)+.
ESI (Pos., 20 V)

23(H24-7)
F
2.74
359 (M + H)+.
ESI (Pos., 20 V)

23(H24-8)
F
3.18
411 (M + H)+.
ESI (Pos., 20 V)

23(H24-9)
F
2.76
362 (M + H)+.
ESI (Pos., 20 V)

23(H24-10)
F
2.76
392 (M + H)+.
ESI (Pos., 20 V)

23(H24-11)
F
3.35
458 (M + H)+.
ESI (Pos., 20 V)

23(H24-12)
F
3.38
458 (M + H)+.
ESI (Pos., 20 V)

23(H24-13)
F
3.12
397 (M + H)+.
ESI (Pos., 20 V)

23(H24-14)
F
2.87
378 (M + H)+.
ESI (Pos., 20 V)

23(H24-15)
F
2.92
408 (M + H)+.
ESI (Pos., 20 V)

23(H24-16)
F
2.89
392 (M + H)+.
ESI (Pos., 20 V)

23(H24-17)
F
3.18
392 (M + H)+.
ESI (Pos., 20 V)

23(H24-18)
F
3.01
412 (M + H)+.
ESI (Pos., 20 V)

23(H24-19)
F
3.44
508 (M + H)+.
ESI (Pos., 20 V)

23(H24-20)
F
3.11
455 (M + H)+.
ESI (Pos., 20 V)

23(H24-21)
F
3.53
560 (M + H)+.
ESI (Pos., 20 V)

23(H24-22)
F
3.12
442 (M + H)+.
ESI (Pos., 20 V)

23(H24-23)
F
3.49
526 (M + H)+.
ESI (Pos., 20 V)

23(H24-24)
F
3.42
492 (M + H)+.
ESI (Pos., 20 V)

23(H24-25)
F
3.16
439 (M + H)+.
ESI (Pos., 20 V)

23(H24-26)
F
3.57
560 (M + H)+.
ESI (Pos., 20 V)

[1413]

563

TABLE 24C-2

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

23(H24-27)
F
3.18
472 (M + H)+.
ESI (Pos., 20 V)

23(H24-28)
F
3.33
470 (M + H)+.
ESI (Pos., 20 V)

23(H24-29)
F
3.38
492 (M + H)+.
ESI (Pos., 20 V)

23(H24-30)
F
3.16
495 (M + H)+.
ESI (Pos., 20 V)

23(H24-31)
F
3.38
458 (M + H)+.
ESI (Pos., 20 V)

[1414]

564

TABLE 25C-1

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

230H25-1)
F
3.16
430 (M + H)+.
ESI (Pos., 20 V)

23(H25-2)
F
3.18
466 (M + H)+.
ESI (Pos., 20 V)

23(H25-3)
F
3.11
376 (M + H)+.
ESI (Pos., 20 V)

23(H25-4)
F
3.23
456 (M + H)+.
ESI (Pos., 20 V)

23(H25-5)
F
3.16
392 (M + H)+.
ESI (Pos., 20 V)

23(H25-6)
F
3.20
390 (M + H)+.
ESI (Pos., 20 V)

23(H25-7)
F
3.28
425 (M + H)+.
ESI (Pos., 20 V)

23(H25-8)
F
2.85
376 (M + H)+.
ESI (Pos., 20 V)

23(H25-9)
F
2.89
406 (M + H)+.
ESI (Pos., 20 V)

23(H25-10)
F
3.44
472 (M + H)+.
ESI (Pos., 20 V)

23(H25-11)
F
3.18
411 (M + H)+.
ESI (Pos., 20 V)

23(H25-12)
F
3.45
392 (M + H)+.
ESI (Pos., 20 V)

23(H25-13)
F
2.96
406 (M + H)+.
ESI (Pos., 20 V)

23(H25-14)
F
3.27
406 (M + H)+.
ESI (Pos., 20 V)

23(H25-15)
F
3.09
426 (M + H)+.
ESI (Pos., 20 V)

23(H25-16)
F
3.53
522 (M + H)+.
ESI (Pos., 20 V)

23(H25-17)
F
3.18
469 (M + H)+.
ESI (Pos., 20 V)

23(H25-18)
F
3.60
574 (M + H)+.
ESI (Pos., 20 V)

23(H25-19)
F
3.22
456 (M + H)+.
ESI (Pos., 20 V)

23(H25-20)
F
3.55
540 (M + H)+.
ESI (Pos., 20 V)

23(H25-21)
F
3.49
506 (M + H)+.
ESI (Pos., 20 V)

23(H25-22)
F
3.25
453 (M + H)+.
ESI (Pos., 20 V)

23(H25-23)
F
3.64
574 (M + H)+.
ESI (Pos., 20 V)

23(H25-24)
F
3.25
486 (M + H)+.
ESI (Pos., 20 V)

23(H25-25)
F
3.42
484 (M + H)+.
ESI (Pos., 20 V)

23(H25-26)
F
3.47
506 (M + H)+.
ESI (Pos., 20 V)

[1415]

565

TABLE 25C-2

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

23(H25-27)
F
3.24
509 (M + H)+.
ESI (Pos., 20 V)

23(H25-28)
F
3.47
472 (M + H)+.
ESI (Pos., 20 V)

[1416]

566

TABLE 26C-1

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

23(H26-1)
F
3.25
444 (M + H)+.
ESI (Pos., 20 V)

23(H26-2)
F
3.26
480 (M + H)+.
ESI (Pos., 20 V)

23(H26-3)
F
3.22
390 (M + H)+.
ESI (Pos., 20 V)

23(H26-4)
F
3.33
470 (M + H)+.
ESI (Pos., 20 V)

23(H26-5)
F
3.23
406 (M + H)+.
ESI (Pos., 20 V)

23(H26-6)
F
3.29
404 (M + H)+.
ESI (Pos., 20 V)

23(H26-7)
F
2.93
387 (M + H)+.
ESI (Pos., 20 V)

23(H26-8)
F
3.34
439 (M + H)+.
ESI (Pos., 20 V)

23(H26-9)
F
2.93
390 (M + H)+.
ESI (Pos., 20 V)

23(H26-10)
F
2.97
420 (M + H)+.
ESI (Pos., 20 V)

23(H26-11)
F
3.50
486 (M + H)+.
ESI (Pos., 20 V)

23(H26-12)
F
3.52
486 (M + H)+.
ESI (Pos., 20 V)

23(H26-13)
F
3.28
425 (M + H)+.
ESI (Pos., 20 V)

23(H26-14)
F
3.04
406 (M + H)+.
ESI (Pos., 20 V)

23(H26-15)
F
3.11
436 (M + H)+.
ESI (Pos., 20 V)

23(H26-16)
F
3.04
420 (M + H)+.
ESI (Pos., 20 V)

23(H26-17)
F
3.35
420 (M + H)+.
ESI (Pos., 20 V)

23(H26-18)
F
3.20
440 (M + H)+.
ESI (Pos., 20 V)

23(H26-19)
F
3.58
536 (M + H)+.
ESI (Pos., 20 V)

23(H26-20)
F
3.25
483 (M + H)+.
ESI (Pos., 20 V)

23(H26-21)
F
3.68
588 (M + H)+.
ESI (Pos., 20 V)

23(H26-22)
F
3.30
472 (M + H)+.
ESI (Pos., 20 V)

23(H26-23)
F
3.62
554 (M + H)+.
ESI (Pos., 20 V)

23(H26-24)
F
3.57
520 (M + H)+.
ESI (Pos., 20 V)

23(H26-25)
F
3.33
467 (M + H)+.
ESI (Pos., 20 V)

23(H26-26)
F
3.71
588 (M + H)+.
ESI (Pos., 20 V)

[1417]

567

TABLE 26C-2

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

23(H26-27)
F
3.33
500 (M + H)+.
ESI (Pos., 20 V)

23(H26-28)
F
3.49
498 (M + H)+.
ESI (Pos., 20 V)

23(H26-29)
F
3.52
520 (M + H)+.
ESI (Pos., 20 V)

23(H26-30)
F
3.32
523 (M + H)+.
ESI (Pos., 20 V)

23(H26-31)
F
3.55
486 (M + H)+.
ESI (Pos., 20 V)

[1418]

568

TABLE 27C-1

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

23(H27-1)
F
3.31
420 (M + H)+.
ESI (Pos., 20 V)

23(H27-2)
F
3.33
450 (M + H)+.
ESI (Pos., 20 V)

23(H27-3)
F
3.31
478 (M + H)+.
ESI (Pos., 20 V)

23(H27-4)
F
3.55
512 (M + H)+.
ESI (Pos., 20 V)

23(H27-5)
F
3.58
526 (M + H)+.
ESI (Pos., 20 V)

23(H27-6)
F
3.33
514 (M + H)+.
ESI (Pos., 20 V)

23(H27-7)
F
3.16
486 (M + H)+.
ESI (Pos., 20 V)

23(H27-8)
F
3.18
436 (M + H)+.
ESI (Pos., 20 V)

23(H27-9)
F
3.31
450 (M + H)+.
ESI (Pos., 20 V)

23(H27-10)
F
3.33
480 (M + H)+.
ESI (Pos., 20 V)

23(H27-11)
F
3.33
508 (M + H)+.
ESI (Pos., 20 V)

23(H27-12)
F
3.58
542 (M + H)+.
ESI (Pos., 20 V)

23(H27-13)
F
3.60
556 (M + H)+.
ESI (Pos., 20 V)

23(H27-14)
F
3.34
544 (M + H)+.
ESI (Pos., 20 V)

23(H27-15)
F
3.18
516 (M + H)+.
ESI (Pos., 20 V)

23(H27-16)
F
3.22
466 (M + H)+.
ESI (Pos., 20 V)

23(H27-17)
F
3.29
450 (M + H)+.
ESI (Pos., 20 V)

23(H27-18)
F
3.33
480 (M + H)+.
ESI (Pos., 20 V)

23(H27-19)
F
3.56
542 (M + H)+.
ESI (Pos., 20 V)

23(H27-20)
F
3.58
556 (M + H)+.
ESI (Pos., 20 V)

23(H27-21)
F
3.33
544 (M + H)+.
ESI (Pos., 20 V)

23(H27-22)
F
3.18
516 (M + H)+.
ESI (Pos., 20 V)

23(H27-23)
F
3.20
466 (M + H)+.
ESI (Pos., 20 V)

23(H27-24)
F
3.29
450 (M + H)+.
ESI (Pos., 20 V)

23(H27-25)
F
3.31
508 (M + H)+.
ESI (Pos., 20 V)

23(H27-26)
F
3.55
542 (M + H)+.
ESI (Pos., 20 V)

[1419]

569

TABLE 27C-2

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

23(H27-27)
F
3.56
556 (M + H)+.
ESI (Pos., 20 V)

23(H27-28)
F
3.33
544 (M + H)+.
ESI (Pos., 20 V)

23(H27-29)
F
3.17
516 (M + H)+.
ESI (Pos., 20 V)

23(H27-30)
F
3.20
466 (M + H)+.
ESI (Pos., 20 V)

23(H27-31)
F
2.92
421 (M + H)+.
ESI (Pos., 20 V)

23(H27-32)
F
2.97
451 (M + H)+.
ESI (Pos., 20 V)

23(H27-33)
F
2.96
479 (M + H)+.
ESI (Pos., 20 V)

23(H27-34)
F
3.22
513 (M + H)+.
ESI (Pos., 20 V)

23(H27-35)
F
3.25
527 (M + H)+.
ESI (Pos., 20 V)

23(H27-36)
F
3.00
515 (M + H)+.
ESI (Pos., 20 V)

23(H27-37)
F
2.87
487 (M + H)+.
ESI (Pos., 20 V)

23(H27-38)
F
2.83
437 (M + H)+.
ESI (Pos., 20 V)

23(H27-39)
F
2.90
421 (M + H)+.
ESI (Pos., 20 V)

23(H27-40)
F
2.94
451 (M + H)+.
ESI (Pos., 20 V)

23(H27-41)
F
2.92
479 (M + H)+.
ESI (Pos., 20 V)

23(H27-42)
F
3.16
513 (M + H)+.
ESI (Pos., 20 V)

23(H27-43)
F
3.20
527 (M + H)+.
ESI (Pos., 20 V)

23(H27-44)
F
2.98
515 (M + H)+.
ESI (Pos., 20 V)

23(H27-45)
F
2.85
487 (M + H)+.
ESI (Pos., 20 V)

23(H27-46)
F
2.81
437 (M + H)+.
ESI (Pos., 20 V)

23(H27-47)
F
2.89
421 (M + H)+.
ESI (Pos., 20 V)

23(H27-48)
F
2.94
451 (M + H)+.
ESI (Pos., 20 V)

23(H27-49)
F
2.92
479 (M + H)+.
ESI (Pos., 20 V)

23(H27-50)
F
3.16
513 (M + H)+.
ESI (Pos., 20 V)

23(H27-51)
F
3.18
527 (M + H)+.
ESI (Pos., 20 V)

23(H27-52)
F
2.98
515 (M + H)+.
ESI (Pos., 20 V)

[1420]

570

TABLE 27C-3

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

23(H27-53)
F
2.83
487 (M + H)+.
ESI (Pos., 20 V)

23(H27-54)
F
2.81
437 (M + H)+.
ESI (Pos., 20 V)

23(H27-55)
F
3.33
434 (M + H)+.
ESI (Pos., 20 V)

23(H27-56)
F
3.36
464 (M + H)+.
ESI (Pos., 20 V)

23(H27-57)
F
3.34
492 (M + H)+.
ESI (Pos., 20 V)

23(H27-58)
F
3.60
526 (M + H)+.
ESI (Pos., 20 V)

23(H27-59)
F
3.62
540 (M + H)+.
ESI (Pos., 20 V)

23(H27-60)
F
3.36
528 (M + H)+.
ESI (Pos., 20 V)

23(H27-61)
F
3.20
500 (M + H)+.
ESI (Pos., 20 V)

23(H27-62)
F
3.23
450 (M + H)+.
ESI (Pos., 20 V)

23(H27-63)
F
3.36
434 (M + H)+.
ESI (Pos., 20 V)

23(H27-64)
F
3.38
464 (M + H)+.
ESI (Pos., 20 V)

23(H27-65)
F
3.36
492 (M + H)+.
ESI (Pos., 20 V)

23(H27-66)
F
3.62
526 (M + H)+.
ESI (Pos., 20 V)

23(H27-67)
F
3.62
540 (M + H)+.
ESI (Pos., 20 V)

23(H27-68)
F
3.38
528 (M + H)+.
ESI (Pos., 20 V)

23(H27-69)
F
3.23
500 (M + H)+.
ESI (Pos., 20 V)

23(H27-70)
F
3.25
450 (M + H)+.
ESI (Pos., 20 V)

23(H27-71)
F
3.36
434 (M + H)+.
ESI (Pos., 20 V)

23(H27-72)
F
3.38
464 (M + H)+.
ESI (Pos., 20 V)

23(H27-73)
F
3.36
492 (M + H)+.
ESI (Pos., 20 V)

23(H27-74)
F
3.62
526 (M + H)+.
ESI (Pos., 20 V)

23(H27-75)
F
3.62
540 (M + H)+.
ESI (Pos., 20 V)

23(H27-76)
F
3.36
528 (M + H)+.
ESI (Pos., 20 V)

23(H27-77)
F
3.22
500 (M + H)+.
ESI (Pos., 20 V)

23(H27-78)
F
3.23
450 (M + H)+.
ESI (Pos., 20 V)

[1421]

571

TABLE 28C-1

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

23(H28-1)
F
3.36
470 (M + H)+.
ESI (Pos., 20 V)

23(H28-2)
F
3.37
506 (M + H)+.
ESI (Pos., 20 V)

23(H28-3)
F
3.31
416 (M + H)+.
ESI (Pos., 20 V)

23(H28-4)
F
3.42
498 (M + H)+.
ESI (Pos., 20 V)

23(H28-5)
F
3.35
432 (M + H)+.
ESI (Pos., 20 V)

23(H28-6)
F
3.41
430 (M + H)+.
ESI (Pos., 20 V)

23(H28-7)
F
3.04
413 (M + H)+.
ESI (Pos., 20 V)

23(H28-8)
F
3.45
465 (M + H)+.
ESI (Pos., 20 V)

23(H28-9)
F
3.03
416 (M + H)+.
ESI (Pos., 20 V)

23(H28-10)
F
3.77
446 (M + H)+.
ESI (Pos., 20 V)

23(H28-11)
F
3.61
512 (M + H)+.
ESI (Pos., 20 V)

23(H28-12)
F
3.61
512 (M + H)+.
ESI (Pos., 20 V)

23(H28-13)
F
3.15
432 (M + H)+.
ESI (Pos., 20 V)

23(H28-14)
F
3.22
462 (M + H)+.
ESI (Pos., 20 V)

23(H28-15)
F
3.16
446 (M + H)+.
ESI (Pos., 20 V)

23(H28-16)
F
3.46
446 (M + H)+.
ESI (Pos., 20 V)

23(H28-17)
F
3.29
466 (M + H)+.
ESI (Pos., 20 V)

23(H28-18)
F
3.68
562 (M + H)+.
ESI (Pos., 20 V)

23(H28-19)
F
3.36
509 (M + H)+.
ESI (Pos., 20 V)

23(H28-20)
F
3.76
614 (M + H)+.
ESI (Pos., 20 V)

23(H28-21)
F
3.42
498 (M + H)+.
ESI (Pos., 20 V)

23(H28-22)
F
3.71
580 (M + H)+.
ESI (Pos., 20 V)

23(H28-23)
F
3.66
546 (M + H)+.
ESI (Pos., 20 V)

23(H28-24)
F
3.44
493 (M + H)+.
ESI (Pos., 20 V)

23(H28-25)
F
3.79
614 (M + H)+.
ESI (Pos., 20 V)

23(H28-26)
F
3.42
526 (M + H)+.
ESI (Pos., 20 V)

[1422]

572

TABLE 28C-2

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

23(H28-27)
F
3.58
524 (M + H)+.
ESI (Pos., 20 V)

23(H28-28)
F
3.62
546 (M + H)+.
ESI (Pos., 20 V)

23(H28-29)
F
3.42
549 (M + H)+.
ESI (Pos., 20 V)

23(H28-30)
F
3.62
512 (M + H)+.
ESI (Pos., 20 V)

[1423]

573

TABLE 29C-1

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

23(H29-1)
F
3.44
484 (M + H)+.
ESI (Pos., 20 V)

23(H29-2)
F
3.44
520 (M + H)+.
ESI (Pos., 20 V)

23(H29-3)
F
3.42
430 (M + H)+.
ESI (Pos., 20 V)

23(H29-4)
F
3.53
512 (M + H)+.
ESI (Pos., 20 V)

23(H29-5)
F
3.44
446 (M + H)+.
ESI (Pos., 20 V)

23(H29-6)
F
3.49
444 (M + H)+.
ESI (Pos., 20 V)

23(H29-7)
F
3.09
427 (M + H)+.
ESI (Pos., 20 V)

23(H29-8)
F
3.53
479 (M + H)+.
ESI (Pos., 20 V)

23(H29-9)
F
3.11
430 (M + H)+.
ESI (Pos., 20 V)

23(H29-10)
F
3.14
460 (M + H)+.
ESI (Pos., 20 V)

23(H29-11)
F
3.67
526 (M + H)+.
ESI (Pos., 20 V)

23(H29-12)
F
3.69
526 (M + H)+.
ESI (Pos., 20 V)

23(H29-13)
F
3.47
465 (M + H)+.
ESI (Pos., 20 V)

23(H29-14)
F
3.23
446 (M + H)+.
ESI (Pos., 20 V)

23(H29-15)
F
3.29
476 (M + H)+.
ESI (Pos., 20 V)

23(H29-16)
F
3.24
460 (M + H)+.
ESI (Pos., 20 V)

23(H29-17)
F
3.55
460 (M + H)+.
ESI (Pos., 20 V)

23(H29-18)
F
3.35
480 (M + H)+.
ESI (Pos., 20 V)

23(H29-19)
F
3.73
576 (M + H)+.
ESI (Pos., 20 V)

23(H29-20)
F
3.44
523 (M + H)+.
ESI (Pos., 20 V)

23(H29-21)
F
3.83
628 (M + H)+.
ESI (Pos., 20 V)

23(H29-22)
F
3.49
510 (M + H)+.
ESI (Pos., 20 V)

23(H29-23)
F
3.77
594 (M + H)+.
ESI (Pos., 20 V)

23(H29-24)
F
3.72
560 (M + H)+.
ESI (Pos., 20 V)

23(H29-25)
F
3.52
507 (M + H)+.
ESI (Pos., 20 V)

23(H29-26)
F
3.85
628 (M + H)+.
ESI (Pos., 20 V)

[1424]

574

TABLE 29C-2

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

23(H29-27)
F
3.51
540 (M + H)+.
ESI (Pos., 20 V)

23(H29-28)
F
3.66
538 (M + H)+.
ESI (Pos., 20 V)

23(H29-29)
F
3.69
560 (M + H)+.
ESI (Pos., 20 V)

23(H29-30)
F
3.47
563 (M + H)+.
ESI (Pos., 20 V)

23(H29-31)
F
3.68
526 (M + H)+.
ESI (Pos., 20 V)

[1425]

575

TABLE 30C-1

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

23(H30-1)
F
3.27
486 (M + H)+.
ESI (Pos., 20 V)

23(H30-2)
F
3.31
522 (M + H)+.
ESI (Pos., 20 V)

23(H30-3)
F
3.24
432 (M + H)+.
ESI (Pos., 20 V)

23(H30-4)
F
3.34
512 (M + H)+.
ESI (Pos., 20 V)

23(H30-5)
F
3.29
448 (M + H)+.
ESI (Pos., 20 V)

23(H30-6)
F
3.33
446 (M + H)+.
ESI (Pos., 20 V)

23(H30-7)
F
2.98
429 (M + H)+.
ESI (Pos., 20 V)

23(H30-8)
F
3.38
481 (M + H)+.
ESI (Pos., 20 V)

23(H30-9)
F
2.98
432 (M + H)+.
ESI (Pos., 20 V)

23(H30-10)
F
3.01
462 (M + H)+.
ESI (Pos., 20 V)

23(H30-11)
F
3.51
528 (M + H)+.
ESI (Pos., 20 V)

23(H30-12)
F
3.55
528 (M + H)+.
ESI (Pos., 20 V)

23(H30-13)
F
3.33
467 (M + H)+.
ESI (Pos., 20 V)

23(H30-14)
F
3.09
448 (M + H)+.
ESI (Pos., 20 V)

23(H30-15)
F
3.16
478 (M + H)+.
ESI (Pos., 20 V)

23(H30-16)
F
3.09
462 (M + H)+.
ESI (Pos., 20 V)

23(H30-17)
F
3.36
462 (M + H)+.
ESI (Pos., 20 V)

23(H30-18)
F
3.22
482 (M + H)+.
ESI (Pos., 20 V)

23(H30-19)
F
3.60
578 (M + H)+.
ESI (Pos., 20 V)

23(H30-20)
F
3.31
525 (M + H)+.
ESI (Pos., 20 V)

23(H30-21)
F
3.69
630 (M + H)+.
ESI (Pos., 20 V)

23(H30-22)
F
3.33
512 (M + H)+.
ESI (Pos., 20 V)

23(H30-23)
F
3.64
596 (M + H)+.
ESI (Pos., 20 V)

23(H30-24)
F
3.59
562 (M + H)+.
ESI (Pos., 20 V)

23(H30-25)
F
3.34
509 (M + H)+.
ESI (Pos., 20 V)

23(H30-26)
F
3.71
630 (M + H)+.
ESI (Pos., 20 V)

[1426]

576

TABLE 30C-2

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

23(H30-27)
F
3.34
542 (M + H)+.
ESI (Pos., 20 V)

23(H30-28)
F
3.51
540 (M + H)+.
ESI (Pos., 20 V)

23(H30-29)
F
3.53
562 (M + H)+.
ESI (Pos., 20 V)

23(H30-30)
F
3.34
565 (M + H)+.
ESI (Pos., 20 V)

23(H30-31)
F
3.55
528 (M + H)+.
ESI (Pos., 20 V)

[1427]

577

TABLE 31C-1

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

23(H31-1)
F
3.47
518 (M + H)+.
ESI (Pos., 20 V)

23(H31-2)
F
3.47
554 (M + H)+.
ESI (Pos., 20 V)

23(H31-3)
F
3.45
464 (M + H)+.
ESI (Pos., 20 V)

23(H31-4)
F
3.55
544 (M + H)+.
ESI (Pos., 20 V)

23(H31-5)
F
3.47
480 (M + H)+.
ESI (Pos., 20 V)

23(H31-6)
F
3.53
478 (M + H)+.
ESI (Pos., 20 V)

23(H31-7)
F
3.14
461 (M + H)+.
ESI (Pos., 20 V)

23(H31-8)
F
3.56
513 (M + H)+.
ESI (Pos., 20 V)

23(H31-9)
F
3.14
464 (M + H)+.
ESI (Pos., 20 V)

23(H31-10)
F
3.20
494 (M + H)+.
ESI (Pos., 20 V)

23(H31-11)
F
3.69
560 (M + H)+.
ESI (Pos., 20 V)

23(H31-12)
F
3.71
560 (M + H)+.
ESI (Pos., 20 V)

23(H31-13)
F
3.51
499 (M + H)+.
ESI (Pos., 20 V)

23(H31-14)
F
3.27
480 (M + H)+.
ESI (Pos., 20 V)

23(H31-15)
F
3.33
510 (M + H)+.
ESI (Pos., 20 V)

23(H31-16)
F
3.29
494 (M + H)+.
ESI (Pos., 20 V)

23(H31-17)
F
3.58
494 (M + H)+.
ESI (Pos., 20 V)

23(H31-18)
F
3.40
514 (M + H)+.
ESI (Pos., 20 V)

23(H31-19)
F
3.75
610 (M + H)+.
ESI (Pos., 20 V)

23(H31-20)
F
3.49
557 (M + H)+.
ESI (Pos., 20 V)

23(H31-21)
F
3.86
662 (M + H)+.
ESI (Pos., 20 V)

23(H31-22)
F
3.53
544 (M + H)+.
ESI (Pos., 20 V)

23(H31-23)
F
3.80
628 (M + H)+.
ESI (Pos., 20 V)

23(H31-24)
F
3.75
594 (M + H)+.
ESI (Pos., 20 V)

23(H31-25)
F
3.57
541 (M + H)+.
ESI (Pos., 20 V)

23(H31-26)
F
3.86
662 (M + H)+.
ESI (Pos., 20 V)

[1428]

578

TABLE 31C-2

Retention

Example
HPLC
time

No
condition
(min)
Mass data
Mass condition

23(H31-27)
F
3.53
574 (M + H)+.
ESI (Pos., 20 V)

23(H31-28)
F
3.67
572 (M + H)+.
ESI (Pos., 20 V)

23(H31-29)
F
3.71
594 (M + H)+.
ESI (Pos., 20 V)

23(H31-30)
F
3.51
597 (M + H)+.
ESI (Pos., 20 V)

23(H31-31)
F
3.73
560 (M + H)+.
ESI (Pos., 20 V)

EXAMPLE 24(1)˜24(119)

[1429] By the same procedure as described in Reference Example 3→Reference Example 4 using Resin (3) prepared in Reference Example 2 and N-allyloxycarbonyl-4-piperidone, using the corresponding compounds respectively instead of n-propylamine and N-(t-butyloxycarbonyl) leucine, and furthermore by the same procedure as described in Reference Example 5→Reference Example 6→Example 1 using the corresponding compound instead of 3,5-dimethyl-1-phenyl-4-formylpyrazole, the following compounds of the present invention were obtained.

EXAMPLE 24(1)

[1430] (3S)-1-butyl-2,5-dioxo-3-(4-methoxyphenylmethyl)-9-cyclohexyl methyl-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2686

[1431] TLC: Rf 0.44 (chloroform:methanol=10:1);

[1432] NMR (CD3OD): δ 7.06 (d, J=9.0 Hz, 2H), 6.84 (d, J=9.0 Hz, 2H), 4.31 (dd, J=4.5, 3.6 Hz, 1H), 3.82-3.67 (m, 4H), 3.49-3.30 (m, 3H), 3.25 (dd, J=13.8, 3.6 Hz, 1H), 3.23-3.10 (m, 2H), 2.95-2.87 (m, 2H), 2.87 (dd, J=13.8, 4.5 Hz, 1H), 2.31 (m, 1H), 2.05 (m, 1H), 1.91-1.64 (m, 7H), 1.56-1.14 (m, 7H), 1.09-0.91 (m, 5H), 0.26 (m, 1H).

EXAMPLE 24(2)

[1433] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-(4-chlorophenyl)thiophen-5-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2687

[1434] TLC: Rf 0.60 (chloroform:methanol=10:1);

[1435] NMR (CD3OD): δ 7.65 (d, J=8.7 Hz, 2H), 7.42 (d, J=8.7 Hz, 2H), 7.42 (d, J=3.6 Hz, 1H), 7.34 (d, J=3.6 Hz, 1H), 4.61 (brs, 2H), 4.01 (dd, J=7.8, 4.5 Hz, 1H), 3.95-3.72 (m, 2H), 3.65-3.50 (m, 2H), 3.44-3.34 (m, 2H), 2.50-2.12 (m, 4H), 1.89-1.45 (m, 5H), 1.45-1.28 (m, 2H), 1.13-0.89 (m, 9H).

EXAMPLE 24(3)

[1436] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-(4-methoxyphenyl)thiophen-5-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2688

[1437] TLC: Rf 0.60 (chloroform:methanol=10:1);

[1438] NMR (CD3OD): δ 7.57 (d, J=9.0 Hz, 2H), 7.33-7.26 (m, 2H), 6.97 (d, J=9.0 Hz, 2H), 4.58 (brs, 2H), 4.01 (dd, J=7.5, 4.5 Hz, 1H), 3.93-3.71 (m, 5H), 3.64-3.50 (m, 2H), 3.44-3.34 (m, 2H), 2.49-2.12 (m, 4H), 1.90-1.45 (m, 5H), 1.45-1.28 (m, 2H), 1.03-0.88 (m, 9H).

EXAMPLE 24(4)

[1439] 1-((2E)-2-butenyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2689

[1440] TLC: Rf 0.32 (chloroform:methanol=20:1);

[1441] NMR (CD3OD): δ 7.52 (d, J=8.7 Hz, 2H), 7.44-7.35 (m, 2H), 7.22-7.14 (m, 1H), 7.06 (d, J=8.7 Hz, 2H), 7.10-7.00 (m, 2H), 5.75-5.60 (m, 1H), 5.52-5.38 (m, 1H), 4.33 (s, 2H), 4.15-3.93 (m, 2H), 4.03 (dd, J=7.8, 4.5 Hz, 1H), 3.88-3.66 (m, 2H), 3.55-3.42 (m, 2H), 2.52-2.35 (m, 2H), 2.28-2.08 (m, 2H), 1.90-1.57 (m, 3H), 1.65 (dd, J=6.3, 1.5 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H), 0.94 (d, J=6.6 Hz, 3H).

EXAMPLE 24(5)

[1442] 1-(furan-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2690

[1443] TLC: Rf 0.33 (chloroform:methanol=20:1);

[1444] NMR (CD3OD): δ 7.52 (d, J=8.7 Hz, 2H), 7.43-7.36 (m, 3H), 7.18 (t, J=7.2 Hz, 1H), 7.09-6.99 (m, 4H), 6.33 (m, 1H), 6.28 (d, J=3.0 Hz, 1H), 4.69 (s, 2H), 4.33 (s, 2H), 4.08 (dd, J=7.8, 4.5 Hz, 1H), 3.87-3.72 (m, 2H), 3.57-3.42 (m, 2H), 2.65-2.38 (m, 2H), 2.30-2.12 (m, 2H), 1.90-1.56 (m, 3H), 0.93 (d, J=6.6 Hz, 3H), 0.91 (d, J=6.6 Hz, 3H).

EXAMPLE 24(6)

[1445] 1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2691

[1446] TLC: Rf 0.39 (chloroform:methanol=20:1);

[1447] NMR (CD3OD): δ 7.53 (d, J=8.7 Hz, 2H), 7.43-7.34 (m, 2H), 7.27 (dd, J=5.1, 1.2 Hz, 1H), 7.18 (t, J=7.2 Hz, 1H), 7.09-7.00 (m, 5H), 6.91 (dd, J=5.1, 3.3 Hz, 1H), 4.92 (brs, 2H), 4.32 (s, 2H), 4.11 (dd, J=7.8, 4.5 Hz, 1H), 3.84-3.66 (m, 2H), 3.53-3.41 (m, 2H), 2.68-2.46 (m, 2H), 2.23-2.06 (m, 2H), 1.95-1.59 (m, 3H), 0.95 (d, J=6.6 Hz, 6H).

EXAMPLE 24(7)

[1448] 1-cyclopropylmethyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2692

[1449] TLC: Rf 0.40 (chloroform:methanol=20:1);

[1450] NMR (CD3OD): δ 7.53 (d, J=8.7 Hz, 2H), 7.43-7.35 (m, 2H), 7.18 (t, J=7.2 Hz, 1H), 7.08-7.00 (m, 4H), 4.33 (s, 2H), 4.04 (dd, J=7.8, 4.5 Hz, 1H), 3.87-3.68 (m, 2H), 3.56-3.43 (m, 2H), 3.46-3.35 (m 2H), 2.56-2.35 (m, 2H), 2.23-2.12 (m, 2H), 1.95-1.58 (m, 3H), 1.10-0.95 (m, 1H), 0.95 (d, J=6.6 Hz, 6H), 0.56-0.45 (m, 2H), 0.42-0.34 (m, 2H).

EXAMPLE 24(8)

[1451] 1-(2-fluorophenylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2693

[1452] TLC: Rf 0.43 (chloroform:methanol=20:1);

[1453] NMR (CD3OD): δ 7.48 (d, J=9.0 Hz, 2H), 7.42-7.34 (m, 2H), 7.32-7.21 (m, 1H), 7.17 (t, J=7.5 Hz, 1H), 7.14-7.06 (m, 3H), 7.06-6.98 (m, 4H), 4.80 (brs, 2H), 4.30 (s, 2H), 4.18 (dd, J=8.1, 4.8 Hz, 1H), 3.86-3.68 (m, 2H), 3.50-3.35 (m, 2H), 2.50-2.30 (m, 1H), 2.30-2.14 (m, 3H), 1.94-1.62 (m, 3H), 0.97 (d, J=6.3 Hz, 6H).

EXAMPLE 24(9)

[1454] 1-(3-methyl-2-butenyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2694

[1455] TLC: Rf 0.29 (chloroform:methanol=20:1);

[1456] NMR (CD3OD): δ 7.52 (d, J=8.4 Hz, 2H), 7.43-7.35 (m, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.09-7.00 (m, 4H), 4.97 (br, 1H), 4.32 (s, 2H), 4.20-4.00 (m, 2H), 4.02 (dd, J=7.8, 4.5 Hz, 1H), 3.90-3.68 (m, 2H), 3.55-3.45 (m, 2H), 2.52-2.32 (m, 2H), 2.30-2.08 (m, 2H), 1.90-1.56 (m, 3H), 1.74 (s, 3H), 1.69 (s, 3H), 0.94 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 24(10)

[1457] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(quinolin-3-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2695

[1458] TLC: Rf 0.25 (chloroform:methanol=20:1);

[1459] NMR (CD3OD): δ 9.52 (d, J=1.5 Hz, 1H), 9.35 (d, J=1.5 Hz, 1H), 8.35 (d, J=8.7 Hz, 1H), 8.27 (d, J=8.7 Hz, 1H), 8.24-8.16 (m, 1H), 8.04-7.96 (m, 1H), 4.76 (s, 2H), 4.03 (dd, J 7.5, 4.5 Hz, 1H), 4.00-3.85 (m, 2H), 3.68-3.55 (m, 2H), 3.55-3.43 (m, 2H), 2.76-2.56 (m, 2H), 2.27-2.05 (m, 2H), 1.82-1.10 (m, 15H), 1.05-0.83 (m, 2H), 0.92 (t, J=7.2 Hz, 3H).

EXAMPLE 24(11)

[1460] 1-butyl-2,5-dioxo-3-(benzyloxycarbonylmethyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2696

[1461] TLC: Rf 0.74 (chloroform:methanol=9:1);

[1462] NMR (CD3OD): δ 7.52 (d, J=7.0 Hz, 2H), 7.40 (t, J=7.5 Hz, 2H), 7.33 (m, 5H), 7.18 (t, J=7.5 Hz, 1H), 7.05 (m, 4H), 5.12 (s, 2H), 4.33 (s, 2H), 4.31 (m, 1H), 3.88 (m, 1H), 3.66 (m, 1H), 3.50-3.35 (m, 4H), 3.08 (dd, J=17.7, 4.8 Hz, 1H), 2.86 (dd, J=17.7, 3.0 Hz, 1H), 2.34 (m, 2H), 2.25 (m, 2H), 1.50 (m, 2H), 1.36 (m, 2H), 0.94 (t, J=7.5 Hz, 3H).

EXAMPLE 24(12)

[1463] 1-(3-methyl-2-butenyl)-2,5-dioxo-3-cyclohexylmethyl-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2697

[1464] TLC: Rf 0.63 (chloroform:methanol=10:1);

[1465] NMR (CD3OD): δ 7.04 (d, J=2.1 Hz, 1H), 6.96 (dd, J=8.1, 2.1 Hz, 1H), 6.92 (d, J=8.1 Hz, 1H), 4.96 (m, 1H), 4.26 (s, 4H), 4.22 (s, 2H), 4.10-4.00 (m, 3H), 3.84-3.68 (m, 2H), 3.52-3.40 (m, 2H), 2.43-2.08 (m, 4H), 1.84-1.42 (m, 13H), 1.38-1.12 (m, 4H), 1.04-0.85 (m, 2H).

EXAMPLE 24(13)

[1466] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-((2E)-3-phenyl-2-propenyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2698

[1467] TLC: Rf 0.28 (chloroform:methanol=20:1);

[1468] NMR (CD3OD): δ 7.53-7.48 (m, 2H), 7.30-7.40 (m, 3H), 6.95 (d, J=16.2 Hz, 1H), 6.36 (dd, J=16.2, 8.1 Hz, 1H), 4.07 (dd, J=7.5, 4.5 Hz, 1H), 3.96 (d, J=8.1 Hz, 2H), 3.86-3.75 (m, 2H), 3.60-3.52 (m, 2H), 3.42-3.34 (m, 2H), 2.42-2.18 (m, 4H), 1.82-1.14 (m, 15H), 0.96 (t, J=7.2 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 24(14)

[1469] (3S)-1-butyl-2,5-dioxo-3-(1,1-dimethylethyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2699

[1470] TLC: Rf 0.50 (chloroform:methanol=10:1);

[1471] NMR (CD3OD): δ 7.54 (d, J=8.5 Hz, 2H), 7.39 (m, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.08-7.02 (m, 4H), 4.34 (s, 2H), 3.88 (m, 2H), 3.62 (s, 1H), 3.46 (m, 4H), 2.45 (m, 2H), 2.13 (m, 2H), 1.66-1.47 (m, 2H), 1.36 (m, 2H), 1.02 (s, 9H), 0.95 (t, J=7.0 Hz, 3H).

EXAMPLE 24(15)

[1472] (3S)-1-butyl-2,5-dioxo-3-(1,1-dimethylethyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2700

[1473] TLC: Rf 0.47 (chloroform:methanol=10:1);

[1474] NMR (CD3OD): δ 7.07 (m, 1H), 6.99 (d, J=8.0 Hz, 1H), 6.91 (d, J=8.0 Hz, 1H), 4.26 (m, 4H), 4.24 (s, 2H), 3.83 (m, 2H), 3.62 (s, 1H), 3.45 (m, 4H), 2.42 (m, 2H), 2.11 (m, 2H), 1.64-1.5 (m, 2H), 1.38 (m, 2H), 1.01 (s, 9H), 0.95 (t, J=7.0 Hz, 3H).

EXAMPLE 24(16)

[1475] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-methylthiazol-2-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2701

[1476] TLC: Rf 0.67 (chloroform:methanol=10:1);

[1477] NMR (CD3OD): δ 7.34 (s, 1H), 4.73 (s, 2H), 4.01 (dd, J=8.0, 4.5 Hz, 1H), 3.93 (m, 2H), 3.65 (m, 2H), 3.41 (m, 2H), 2.53-2.41 (m, 2H), 2.48 (s, 3H), 2.23 (m, 2H), 1.85-1.52 (m, 5H), 1.38 (m, 2H), 0.96 (t, J=7.0 Hz, 3H), 0.94 (d, J=6.5 Hz, 3H), 0.93 (d, J=6.5 Hz, 3H).

EXAMPLE 24(17)

[1478] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-methylthiazol-2-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2702

[1479] TLC: Rf 0.66 (chloroform:methanol=10:1);

[1480] NMR (CD3OD): δ 7.34 (s, 1H), 4.72 (s, 2H), 4.04 (dd, J=7.5, 4.5 Hz, 1H), 3.98-3.86 (m, 2H), 3.67-3.63 (m, 2H), 3.44-3.38 (m, 2H), 2.56-2.42 (m, 2H), 2.48 (s, 3H), 2.30-2.14 (m, 2H), 1.84-1.18 (m, 15H), 0.96 (t, J=7.2 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 24(18)

[1481] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-methylthiazol-2-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2703

[1482] TLC: Rf 0.63 (chloroform:methanol=10:1);

[1483] NMR (CD3OD): δ 7.63 (s, 1H), 4.69 (s, 2H), 4.03 (dd, J=7.3, 4.5 Hz, 1H), 3.96-3.82 (m, 2H), 3.72-3,58 (m, 2H), 3.42-3.37 (m, 2H), 2.52 (s, 3H), 2.56-2.36 (m, 2H), 2.28-2.12 (m, 2H), 1.80-1.12 (m, 15H), 0.96 (t, J=7.5 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 24(19)

[1484] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-methylthiazol-2-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2704

[1485] TLC: Rf 0.70 (chloroform:methanol=10:1);

[1486] NMR (CD3OD): δ 7.63 (s, 1H), 4.69 (brs, 2H), 4.01 (dd, J=7.8, 4.5 Hz, 1H), 3.99-3.83 (m, 2H), 3.70-3.58 (m, 2H), 3.44-3.34 (m, 2H), 2.53 (s, 3H), 2.50-2.33 (m, 2H), 2.32-2.12 (m, 2H), 1.88-1.46 (m, 5H), 1.45-1.31 (m, 2H), 1.01-0.90 (m, 9H).

EXAMPLE 24(20)

[1487] (3R)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2705

[1488] TLC: Rf 0.59 (chloroform:methanol=10:1);

[1489] NMR (CD3OD): δ 7.04 (d, J=2.0 Hz, 1H), 6.97 (dd, J=8.5, 2.0 Hz, 1H), 6.93 (d, J=8.5 Hz, 1H), 4.26 (s, 4H), 4.24 (s, 2H), 4.04 (dd, J=7.5, 5.0 Hz, 1H), 3.76 (m, 2H), 3.46 (m, 4H), 2.39-2.11 (m, 4H), 1.78-1.17 (m, 15H), 0.95 (t, J=7.0 Hz, 3H), 0.95 (m, 2H).

[1490] HPLC condition

[1491] Column: YMC CHIRAL-CD BR, 0.46×25 cm, YMC, DB12S05-2546WTI;

[1492] Flow rate: 0.5 mL/min;

[1493] Eluent

[1494] Component A: 0.1 M potassium dihydrogenphosphate aqueous solution

[1495] Component B: acetonitrile

[1496] A:B=84:16;

[1497] UV: 235 nm;

[1498] Retention time: 18 min.

EXAMPLE 24(21)

[1499] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2706

[1500] TLC: Rf 0.59 (chloroform:methanol=10:1);

[1501] NMR (CD3OD): δ 7.04 (d, J=2.0 Hz, 1H), 6.97 (dd, J=8.5, 2.0 Hz, 1H), 6.93 (d, J=8.5 Hz, 1H), 4.26 (s, 4H), 4.24 (s, 2H), 4.04 (dd, J=7.5, 5.0 Hz, 1H), 3.76 (m, 2H), 3.46 (m, 4H), 2.39-2.11 (m, 4H), 1.78-1.17 (m, 15H), 0.95 (t, J=7.0 Hz, 3H), 0.95 (m, 2H).

[1502] HPLC condition

[1503] Column: YMC CHIRAL-CD BR, 0.46×25 cm, YMC, DB12S05-2546WTI;

[1504] Flow rate: 0.5 mL/min;

[1505] Eluent

[1506] Component A: 0.1 M potassium dihydrogenphosphate aqueous solution

[1507] Component B: acetonitrile

[1508] A: B=84:16;

[1509] UV: 235 nm;

[1510] Retention time: 20 min.

EXAMPLE 24(22)

[1511] (3R)-1-butyl-2,5-dioxo-3-((1R)-1-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2707

[1512] TLC: Rf 0.59 (chloroform:methanol=10:1);

[1513] NMR (CD3OD): δ 7.53 (d, J=8.5 Hz, 2H), 7.39 (m, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.08-7.01 (m, 4H), 4.33 (s, 2H), 3.96 (d, J=2.5 Hz, 1H), 3.92 (m, 1H), 3.75 (m, 1H), 3.53-3.44 (m, 4H), 2.49-2.32 (m, 2H), 2.16 (m, 2H), 2.06-1.98 (m, 1H), 1.61-1.21 (m, 6H), 1.00-0.89 (m, 9H).

EXAMPLE 24(23)

[1514] (3S)-1-butyl-2,5-dioxo-3-((1S)-1-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2708

[1515] TLC: Rf 0.59 (chloroform:methanol=10:1);

[1516] NMR (CD3OD): δ 7.53 (d, J=8.5 Hz, 2H), 7.39 (m, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.08-7.01 (m, 4H), 4.33 (s, 2H), 3.96 (d, J=2.5 Hz, 1H), 3.92 (m, 1H), 3.75 (m, 1H), 3.53-3.44 (m, 4H), 2.49-2.32 (m, 2H), 2.16 (m, 2H), 2.06-1.98 (m, 1H), 1.61-1.21 (m, 6H), 1.00-0.89 (m, 9H).

EXAMPLE 24(24)

[1517] 1-(2-butynyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2709

[1518] TLC: Rf 0.70 (chloroform:methanol=10:1);

[1519] NMR (CD3OD): δ 7.51 (d, J=8.7 Hz, 2H), 7.39 (dd, J=8.7, 7.2 Hz, 2H), 7.18 (t, J=7.2 Hz, 1H), 7.09-7.00 (m, 4H), 4.33 (brs, 2H), 4.28-4.10 (m, 2H), 4.05 (dd, J=7.8, 4.5 Hz, 1H), 3.86-3.70 (m, 2H), 3.56-3.43 (m, 2H), 2.59-2.40 (m, 2H), 2.34-2.15 (m, 2H), 1.89-1.57 (m, 6H), 0.94 (d, J=6.6 Hz, 3H), 0.93 (d, J=6.6 Hz, 3H).

EXAMPLE 24(25)

[1520] 1-(2-butynyl)-2,5-dioxo-3-cyclohexylmethyl-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2710

[1521] TLC: Rf 0.52 (chloroform:methanol=10:1);

[1522] NMR (CD3OD): δ 7.04 (d, J=2.1 Hz, 1H), 6.97 (dd, J=8.4, 2.1 Hz, 1H), 6.93 (d, J=8.4 Hz, 1H), 4.26 (s, 4H), 4.23 (s, 2H), 4.18 (brs, 2H), 4.07 (dd, J=6.9, 4.8 Hz, 1H), 3.84-3.68 (m, 2H), 3.55-3.42 (m, 2H), 2.57-2.40 (m, 2H), 2.32-2.12 (m, 2H), 1.85-1.42 (m, 11H), 1.38-1.13 (m, 3H), 1.04-0.85 (m, 2H).

EXAMPLE 24(26)

[1523] 1-pentyl-2,5-dioxo-3-cyclohexylmethyl-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2711

[1524] TLC: Rf 0.61 (chloroform:methanol=10:1);

[1525] NMR (CD3OD): δ 7.04 (d, J=2.1 Hz, 1H), 6.97 (dd, J=8.4, 2.1 Hz, 1H), 6.92 (d, J=8.4 Hz, 1H), 4.26 (s, 4H), 4.22 (brs, 2H), 4.03 (dd, J=7.2, 4.5 Hz, 1H), 3.84-3.67 (m, 2H), 3.52-3.33 (m, 4H), 2.43-2.07 (m, 4H), 1.83-1.42 (m, 9H), 1.41-1.13 (m, 8H), 1.04-0.85 (m, 5H).

EXAMPLE 24(27)

[1526] 1-(3-methoxyphenylmethyl)-2,5-dioxo-3-(benzyloxymethyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2712

[1527] TLC: Rf 0.45 (chloroform:methanol=10:1);

[1528] NMR (CD3OD): δ 7.60-7.43 (m, 5H), 7.38-7.24 (m, 5H), 7.14 (t, J=8.4 Hz, 1H), 6.83-6.72 (m, 3H), 4.96-4.70 (m, 2H), 4.60 (d, J=11.4 Hz, 1H), 4.50 (d, J=11.4 Hz, 1H), 4.29 (t, J=2.4 Hz, 1H), 4.24 (s, 2H), 4.02 (dd, J=9.6, 2.4 Hz, 1H), 3.93-3.79 (m, 1H), 3.72 (s, 3H), 3.70 (dd, J=9.6, 2.4 Hz, 1H), 3.70-3.60 (m, 1H), 3.55-3.44 (m, 1H), 3.35-3.23 (m, 1H), 2.58-2.05 (m, 10H).

EXAMPLE 24(28)

[1529] (3R)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2713

[1530] TLC: Rf 0.29 (chloroform:methanol=10:1);

[1531] NMR (CD3OD): δ 7.54 (d, J=8.7 Hz, 2H), 7.42-7.36 (m, 2H), 7.18 (m, 1H), 7.05 (d, J=8.7 Hz, 2H), 7.05-7.02 (m, 2H), 4.32 (s, 2H), 4.01 (dd, J=7.8, 4.8 Hz, 1H), 3.85-3.72 (m, 2H), 3.50-3.39 (m, 4H), 2.52-2.38 (m, 2H), 2.24-2.11 (m, 2H), 1.84-1.20 (m, 7H), 0.95 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.93 (d, J=6.3 Hz, 3H).

[1532] HPLC condition

[1533] Column: CHIRALCEL OD-R, 0.46×25 cm, DAICEL, ODROCE-HD028;

[1534] Flow rate: 0.4 mL/min;

[1535] Eluent

[1536] Component A: 0.2M potassium dihydrogenphosphate aqueous solution

[1537] Component B: acetonitrile

[1538] A:B=64:36;

[1539] UV: 235 nm;

[1540] Retention time: 30 min.

EXAMPLE 24(29)

[1541] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2714

[1542] TLC: Rf 0.29 (chloroform:methanol=10:1);

[1543] NMR (CD3OD): δ 7.54 (d, J=8.7 Hz, 2H), 7.42-7.36 (m, 2H), 7.18 (m, 1H), 7.05 (d, J=8.7 Hz, 2H), 7.05-7.02 (m, 2H), 4.33 (s, 2H), 3.98 (dd, J=8.1, 4.5 Hz, 1H), 3.86-3.72 (m, 2H), 3.53-3.37 (m, 4H), 2.47-2.36 (m, 2H), 2.24-2.12 (m, 2H), 1.80-1.30 (m, 7H), 0.95 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.93 (d, J=6.3 Hz, 3H).

[1544] HPLC condition

[1545] Column: CHIRALCEL OD-R, 0.46×25 cm, DAICEL, ODROCE-HD028;

[1546] Flow rate: 0.4 mL/min;

[1547] Eluent

[1548] Component A: 0.2M potassium dihydrogenphosphate aqueous solution

[1549] Component B: acetonitrile

[1550] A:B=64:36;

[1551] UV: 235 nm;

[1552] Retention time: 28 min.

EXAMPLE 24(30)

[1553] 1-butyl-2,5-dioxo-3-cyclopentylmethyl-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2715

[1554] TLC: Rf 0.53 (chloroform:methanol=10:1);

[1555] NMR (CD3OD): δ 7.05 (d, J=2.0 Hz, 1H), 6.98 (dd, J=8.5, 2.0 Hz, 1H), 6.93 (d, J=8.5 Hz, 1H), 4.26 (s, 4H), 4.23 (s, 2H), 3.99 (t, J=6.0 Hz, 1H), 3.77 (m, 2H), 3.46 (m, 2H), 3.37 (m, 2H), 2.36 (m, 2H), 2.15 (m, 2H), 1.96 (m, 1H), 1.81 (m, 4H), 1.59 (m, 6H), 1.36 (m, 2H), 1.15 (m, 2H), 0.95 (t, J=7.0 Hz, 3H).

EXAMPLE 24(31)

[1556] 1-propyl-2,5-dioxo-3-(cyclohexylmethyloxymethyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2716

[1557] TLC: Rf 0.63 (chloroform:methanol=10:1);

[1558] NMR (CD3OD): δ 7.59-7.46(m, 5H), 4.33 (s, 2H), 4.08 (m, 1H), 4.00 (m, 1H), 3.83 (m, 1H), 3.77 (m, 1H), 3.59 (m, 2H), 3.52 (m, 1H), 3.25 (d, J=6.5 Hz, 2H), 2.53 (m, 2H), 2.42 (m, 1H), 2.40 (s, 3H), 2.39 (s, 3H), 2.21 (m, 2H), 1.69 (m, 6H), 1.52 (m, 2H), 1.21 (m, 4H), 0.95 (t, J=7.0 Hz, 3H), 0.88 (m, 2H).

EXAMPLE 24(32)

[1559] (3S)-1-butyl-2,5-dioxo-3-(1-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2717

[1560] TLC: Rf 0.47 (chloroform:methanol=10:1);

[1561] NMR (CD3OD): δ 7.06-6.90 (m, 3H), 4.26 (s, 4H), 4.23 (s, 2H), 3.95 (d, J=3.3 Hz, 1H), 3.87 (m, 1H), 3.70 (m, 1H), 3.58-3.42 (m, 4H), 2.56-2.30 (m, 2H), 2.20-1.98 (m, 2H), 1.54-1.00 (m, 7H), 0.99 (d, J=7.2 Hz, 3H), 0.95 (t, J=7.5 Hz, 3H), 0.91 (t, J=7.5 Hz, 3H).

EXAMPLE 24(33)

[1562] (3R)-1-butyl-2,5-dioxo-3-(1-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2718

[1563] TLC: Rf 0.47 (chloroform:methanol=10:1);

[1564] NMR (CD3OD): δ 7.06-6.91 (m, 3H), 4.26 (s, 4H), 4.23 (s, 2H), 3.95 (d, J=3.3 Hz, 1H), 3.87 (m, 1H), 3.70 (m, 1H), 3.56-3.40 (m, 4H), 2.50-2.32 (m, 2H), 2.18-1.96 (m, 2H), 1.62-1.17 (m, 7H), 0.99 (d, J=7.2 Hz, 3H), 0.95 (t, J=7.2 Hz, 3H), 0.91 (t, J=7.5 Hz, 3H).

EXAMPLE 24(34)

[1565] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-phenylmethylthiophen-2-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2719

[1566] TLC: Rf 0.56 (chloroform:methanol=10:1);

[1567] NMR (CD3OD): δ 7.32-7.21 (m, 5H), 7.17 (d, J=3.6 Hz, 1H), 6.89 (d, J=3.6 Hz, 1H), 4.51 (s, 2H), 4.17 (s, 2H), 4.00 (dd, J=7.8 Hz, 4.5 Hz, 1H), 3.84-3.72 (m, 2H), 3.56-3.44 (m, 2H), 3.38-3.32 (m, 2H), 2.42-2.14 (m, 4H), 1.84-1.30 (m, 7H), 0.95 (t, J=6.9 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H), 0.92 (d, J=6.3 Hz, 3H).

EXAMPLE 24(35)

[1568] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-phenylmethylthiophen-5-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2720

[1569] TLC: Rf 0.59 (chloroform:methanol=10:1);

[1570] NMR (CD3OD): δ 7.32-7.21 (m, 5H), 7.18 (d, J=3.6 Hz, 1H), 6.89 (d, J=3.6 Hz, 1H), 4.51 (s, 2H), 4.17 (s, 2H), 4.03 (dd, J=7.8, 4.8 Hz, 1H), 3.84-3.72 (m, 2H), 3.58-3.44 (m, 2H), 3.40-3.36 (m, 2H), 2.44-2.08 (m, 4H), 1.81-1.07 (m, 15H), 0.95 (t, J=7.2 Hz, 3H), 0.95 (m, 2H).

EXAMPLE 24(36)

[1571] (3R)-1-butyl-2,5-dioxo-3-(2,2-dimethylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2721

[1572] TLC: Rf 0.41 (chloroform:methanol=20:1);

[1573] NMR (CD3OD): δ 7.05 (s, 1H), 6.98 (d, J=8.4 Hz, 1H), 6.92 (d, J=8.4 Hz, 1H), 4.26 (s, 4H), 4.23 (s, 2H), 4.00 (dd, J=7.0, 3.0 Hz, 1H), 3.83-3.64 (m, 2H), 3.50 (m, 2H), 3.38 (m, 2H), 2.35 (m, 2H), 2.25 (m, 2H), 1.99 (m, 1H), 1.55 (m, 1H), 1.50 (m, 2H), 1.35 (m, 2H), 0.99 (s, 9H), 0.95 (t, J=7.0 Hz, 3H).

EXAMPLE 24(37)

[1574] (3S)-1-butyl-2,5-dioxo-3-(2,2-dimethylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2722

[1575] TLC: Rf 0.41 (chloroform:methanol=20:1);

[1576] NMR (CD3OD): δ 7.05 (s, 1H), 6.98 (d, J=8.4 Hz, 1H), 6.92 (d, J=8.4 Hz, 1H), 4.26 (s, 4H), 4.23 (s, 2H), 4.00 (dd, J=7.0, 3.0 Hz, 1H), 3.83-3.63 (m, 2H), 3.50 (m, 2H), 3.38 (m, 2H), 2.35 (m, 2H), 2.25 (m, 2H), 1.99 (dd, J=14.0, 3.0 Hz, 1H), 1.55 (dd, J=14.0, 7.0 Hz, 1H), 1.50 (m, 2H), 1.35 (m, 2H), 0.99 (s, 9H), 0.95 (t, J=7.0 Hz, 3H).

EXAMPLE 24(38)

[1577] (3R)-1-(2-butynyl)-2,5-dioxo-3-(2,2-dimethylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2723

[1578] TLC: Rf 0.60 (chloroform:methanol=10:1);

[1579] NMR (CD3OD): δ 7.51 (d, J=8.7 Hz, 2H), 7.39 (dd, J=8.7, 7.5 Hz, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.10-7.00 (m, 4H), 4.33 (brs, 2H), 4.33-4.09 (m, 2H), 4.03 (dd, J=6.9, 3.3 Hz, 1H), 3.85-3.68 (m, 2H), 3.58-3.43 (m, 2H), 2.59-2.41 (m, 2H), 2.40-2.20 (m, 2H), 2.03 (dd, J=14.4, 3.3 Hz, 1H), 1.75 (brs, 3H), 1.56 (dd, J=14.4, 6.9 Hz, 1H), 0.99 (s, 9H).

EXAMPLE 24(39)

[1580] (3S)-1-(2-butynyl)-2,5-dioxo-3-(2,2-dimethylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2724

[1581] TLC: Rf 0.60 (chloroform:methanol=10:1);

[1582] NMR (CD3OD): δ 7.51 (d, J=8.7 Hz, 2H), 7.39 (dd, J=8.7, 7.5 Hz, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.10-7.00 (m, 4H), 4.33 (brs, 2H), 4.33-4.09 (m, 2H), 4.03 (dd, J=6.9, 3.3 Hz, 1H), 3.85-3.68 (m, 2H), 3.58-3.43 (m, 2H), 2.59-2.41 (m, 2H), 2.40-2.20 (m, 2H), 2.03 (dd, J=14.4, 3.3 Hz, 1H), 1.75 (brs, 3H), 1.56 (dd, J=14.4, 6.9 Hz, 1H), 0.99 (s, 9H).

EXAMPLE 24(40)

[1583] 1-butyl-2,5-dioxo-3-cycloheptylmethyl-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2725

[1584] TLC: Rf 0.70 (chloroform:methanol=10:1);

[1585] NMR (CD3OD): δ 7.04 (d, J=2.1 Hz, 1H), 6.97 (dd, J=8.4, 2.1 Hz, 1H), 6.93 (d, J=8.4 Hz, 1H), 4.26 (s, 4H), 4.24 (s, 2H), 3.99 (dd, J=8.1, 4.2 Hz, 1H), 3.84-3.70 (m, 2H), 3.45 (m, 2H), 3.36 (m, 2H), 2.37-2.11 (m, 4H), 1.80-1.49 (m, 15H), 1.36(m, 2H), 1.22 (m, 2H), 0.95 (t, J=7.5 Hz, 3H).

EXAMPLE 24(41)

[1586] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2,4,6-trimethoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2726

[1587] TLC: Rf 0.55 (chloroform:methanol=10:1);

[1588] NMR (CD3OD): δ 6.31 (s, 2H), 4.26 (s, 2H), 4.03 (dd, J=7.8, 4.5 Hz, 1H), 3.89 (s, 6H), 3.84 (s, 3H), 3.84-3.73 (m, 2H), 3.54-3.33 (m, 4H), 2.44-2.25 (m, 2H), 2.24-2.03 (m, 2H), 1.84-1.12 (m, 15H), 1.06-0.85 (m, 5H).

EXAMPLE 24(42)

[1589] 1-butyl-2,5-dioxo-3-(3-cyclohexylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2727

[1590] TLC: Rf 0.71 (chloroform:methanol=10:1);

[1591] NMR (CD3OD): δ 7.05-6.91 (m, 3H), 4.26 (s, 4H), 4.22 (s, 2H), 4.04 (t, J=5.4 Hz, 1H), 3.84 (m, 1H), 3.67 (m, 1H), 3.54-3.40 (m, 3H), 3.35 (m, 1H), 2.44-2.08 (m, 4H), 1.90-1.16 (m, 19H), 0.95 (t, J=7.5 Hz, 3H), 0.95 (m, 2H).

EXAMPLE 24(43)

[1592] 1-butyl-2,5-dioxo-3-(3-cyclohexylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2728

[1593] TLC: Rf 0.76 (chloroform:methanol=10:1);

[1594] NMR (CD3OD): δ 7.53-7.49 (m, 2H), 7.42-7.36 (m, 2H), 7.18 (m, 1H), 7.10-7.02 (m, 4H), 4.32 (s, 2H), 4.04 (t, J=4.8 Hz, 1H), 3.87 (m, 1H), 3.71 (m, 1H), 3.56-3.40 (m, 3H), 3.35 (m, 1H), 2.48-2.12 (m, 4H), 1.86-1.10 (m, 19H), 0.95 (t, J=7.5 Hz, 3H), 0.95 (m, 2H).

EXAMPLE 24(44)

[1595] 1-butyl-2,5-dioxo-3-(3-cyclohexylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2729

[1596] TLC: Rf 0.64 (chloroform:methanol=10:1);

[1597] NMR (CD3OD): δ 7.59-7.45 (m, 5H), 4.31 (s, 2H), 4.06 (t, J=5.0 Hz, 1H), 3.92 (m, 1H), 3.77 (m, 1H), 3.63-3.37 (m, 4H), 2.44 (m, 2H), 2.39 (s, 3H), 2.38 (s, 3H), 2.21 (m, 2H), 1.85-1.68 (m, 7H), 1.54 (m, 2H), 1.39 (m, 4H), 1.23 (m, 6H), 0.96 (t, J=7.5 Hz, 3H), 0.89 (m, 2H).

EXAMPLE 24(45)

[1598] 1-butyl-2,5-dioxo-3-(2-hydroxy-2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2730

[1599] TLC: Rf 0.52 (chloroform:methanol=10:1);

[1600] NMR (CD3OD): δ 7.50 (d, J=8.7 Hz, 2H), 7.39 (dd, J=8.7, 7.5 Hz, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.09-7.00 (m, 4H), 4.32 (brs, 2H), 4.29 (dd, J=9.9, 3.0 Hz, 1H), 4.04-3.88 (m, 2H), 3.59-3.40 (m, 4H), 2.46-2.21 (m, 4H), 2.18 (dd, J=14.4, 3.0 Hz, 1H), 1.75 (dd, J=14.4, 9.9 Hz, 1H), 1.61-1.43 (m, 2H), 1.42-1.29 (m, 2H), 1.28 (s, 6H), 0.95 (t, J=7.5 Hz, 3H).

EXAMPLE 24(46)

[1601] 1-(2-butynyl)-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2731

[1602] TLC: Rf 0.41 (chloroform:methanol=10:1);

[1603] NMR (CD3OD): δ 7.61-7.45 (m, 5H), 4.32 (s, 2H), 4.31-4.18 (m, 2H), 4.06 (dd, J=7.8, 4.5 Hz, 1H), 3.93-3.77 (m, 2H), 3.68-3.57 (m, 2H), 2.72-2.57 (m, 2H), 2.40 (s, 3H), 2.38 (s, 3H), 2.36-2.16,(m, 2H), 1.92-1.59 (m, 6H), 0.95 (d, J=6.6 Hz, 3H), 0.94 (d, J=6.6 Hz, 3H).

EXAMPLE 24(47)

[1604] 1-(2-butynyl)-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-phenyl pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2732

[1605] TLC: Rf 0.37 (chloroform:methanol=10:1);

[1606] NMR (CD3OD): 7.60-7.43 (m, 5H), 4.32 (s, 2H), 4.23 (d, J=2.1 Hz, 2H), 4.09 (dd, J=7.2, 4.8 Hz, 1H), 3.92-3.78 (m, 2H), 3.68-3.56 (m, 2H), 2.66-2.51 (m, 2H), 2.38 (s, 3H), 2.36 (s, 3H), 2.36-2.16 (m, 2H), 1.83-1.60 (m, 10H), 1.59-1.43 (m, 1H), 1.38-1.12 (m, 3H), 1.06-0.87 (m, 2H).

EXAMPLE 24(48)

[1607] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2733

[1608] TLC: Rf 0.35 (chloroform:methanol=20:1);

[1609] NMR (CD3OD): δ 7.63-7.48 (m, 5H), 4.33 (s, 2H), 4.05 (dd, J=7.8, 4.5 Hz, 1H), 3.95-3.74 (m, 2H), 3.67-3.56 (m, 2H), 3.48 (m, 2H), 2.72-2.58 (m, 2H), 2.45 (s, 3H), 2.41 (s, 3H), 2.30-2.07 (m, 2H), 1.84-1.10 (m, 15H), 1.02-0.92 (m, 2H), 0.96 (t, J=7.2 Hz, 3H).

EXAMPLE 24(49)

[1610] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-phenyloxypyridin-3-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2734

[1611] TLC: Rf 0.23 (chloroform:methanol=10:1);

[1612] NMR (CD3OD): δ 8.19 (m, 1H), 8.07 (m, 1H), 7.47-7.42 (m, 2H), 7.29-7.19 (m, 4H), 4.55 (s, 2H), 4.03 (dd, J=7.8, 4.5 Hz, 1H), 3.94 (m, 2H), 3.64 (m, 2H), 3.38 (m, 2H), 2.54-2.16 (m, 4H), 1.90-1.28 (m, 7H), 0.96 (t, J=6.9 Hz, 3H), 0.96 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 24(50)

[1613] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-phenyloxypyridin-3-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2735

[1614] TLC: Rf 0.62 (chloroform:methanol=10:1);

[1615] NMR (CD3OD): δ 8.19 (m, 1H), 8.09 (m, 1H), 7.47-7.42 (m, 2H), 7.29-7.19 (m, 4H), 4.55 (s, 2H), 4.05 (dd, J=7.8, 4.8 Hz, 1H), 3.96 (m, 2H), 3.64 (m, 2H), 3.42 (m, 2H), 2.48 (m, 2H), 2.36-2.16 (m, 2H), 1.82-1.14 (m, 15H), 0.96 (t, J=7.5 Hz, 3H), 0.95-0.84 (m, 2H).

EXAMPLE 24(51)

[1616] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-methylbenzomorpholin-7-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2736

[1617] TLC: Rf 0.69 (chloroform:methanol=10:1);

[1618] NMR (CDCl3): δ 6.93 (d, J=8.7 Hz, 1H), 6.86 (s, 1H), 6.75 (d, J=8.7 Hz, 1H), 4.28-4.25 (m, 2H), 4.17 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.80-3.65 (m, 2H), 3.50-3.40 (m, 2H), 3.40-3.30 (m, 2H), 2.91 (s, 3H), 2.38-2.06 (m, 4H), 1.78-1.63 (m, 8H), 1.63-1.42 (m, 3H), 1.40-1.18 (m, 6H), 1.05-0.90 (m, 2H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 24(52)

[1619] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-methylbenzomorpholin-7-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2737

[1620] TLC: Rf 0.56 (chloroform:methanol=10:1);

[1621] NMR (CDCl3): δ 7.00 (d, J=7.2 Hz, 1H), 6.94 (s, 1H), 6.85 (d, J=7.2 Hz, 1H), 4.31-4.29 (m, 2H), 4.19 (s, 2H), 4.00 (dd, J=7.8, 4.5 Hz, 1H), 3.79-3.66 (m, 2H), 3.47-3.34 (m, 6H), 2.97 (s, 3H), 2.45-2.34 (m, 2H), 2.22-2.10 (m, 2H), 1.84-1.75 (m, 1H), 1.71-1.46 (m, 4H), 1.42-1.32 (m, 2H), 0.97-0.92 (m, 9H).

EXAMPLE 24(53)

[1622] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(N-methyl-N-phenylamino)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2738

[1623] TLC: Rf 0.40 (chloroform:methanol=20:1);

[1624] NMR (CD3OD): δ 7.40-7.28 (m, 4H), 7.19-7.10 (m, 3H), 6.94-6.86 (m, 2H), 4.23 (s, 2H), 4.00 (dd, J=7.8, 4.5 Hz, 1H), 3.86-3.63 (m, 2H), 3.55-3.30 (m, 4H), 3.31 (s, 3H), 2.46-2.27 (m, 2H), 2.26-2.06 (m, 2H), 1.90-1.42 (m, 5H), 1.44-1.26 (m, 2H), 0.98-0.91 (m, 9H).

EXAMPLE 24(54)

[1625] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(N-methyl-N-phenylamino) phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2739

[1626] TLC: Rf 0.52 (chloroform:methanol=20:1);

[1627] NMR (CD3OD): δ 7.40-7.28 (m, 4H), 7.20-7.12 (m, 3H), 6.93-6.86 (m, 2H), 4.24 (s, 2H), 4.03 (dd, J=7.5, 4.8 Hz, 1H), 3.85-3.66 (m, 2H), 3.55-3.40 (m, 2H), 3.40-3.30 (m, 2H), 3.32 (s, 3H), 2.44-2.07 (m, 4H), 1.84-1.40 (m, 10H), 1.40-1.10 (m, 5H), 1.06-0.85 (m, 2H), 0.95 (t, J=7.5 Hz, 3H).

EXAMPLE 24(55)

[1628] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-(3,5-dimethylpyrazol-1-yl)-5-methoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2740

[1629] TLC: Rf 0.58 (chloroform:methanol=10:1);

[1630] NMR (CD3OD): δ 7.53 (d, J=3.0 Hz, 1H), 7.44 (d, J=8.7 Hz, 1H), 7.22 (dd, J=8.7, 3.0 Hz, 1H), 6.29 (s, 1H), 4.09 (s, 2H), 4.02 (dd, J=7.5, 4.5 Hz, 1H), 3.94 (s, 3H), 3.74 (m, 2H), 3.42 (m, 4H), 2.44 (m, 2H), 2.37 (s, 3H), 2.22 (s, 3H), 2.22 (m, 2H), 1.86-1.30 (m, 7H), 0.96 (t, J=7.8 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 24(56)

[1631] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-(3,5-dimethylpyrazol-1-yl)-5-methoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2741

[1632] TLC: Rf 0.61 (chloroform:methanol=10:1);

[1633] NMR (CD3OD): δ 7.43 (d, J=8.7 Hz, 1H), 7.40 (d, J=2.7 Hz, 1H), 7.22 (dd, J=8.7, 2.7 Hz, 1H), 6.22 (s, 1H), 4.09 (s, 2H), 4.06 (dd, J=7.5, 4.2 Hz, 1H), 3.93 (s, 3H), 3.80 (m, 2H), 3.42 (m, 4H), 2.38 (m, 2H), 2.34 (s, 3H), 2.22 (s, 3H), 2.20 (m, 2H), 1.80-1.16 (m, 15H), 0.96 (t, J=7.2 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 24(57)

[1634] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-diethyl-1-(4-chlorophenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2742

[1635] TLC: Rf 0.47 (chloroform:methanol=20:1);

[1636] NMR (CD3OD): δ 7.53 (d, J=9.0 Hz, 2H), 7.49 (d, J=9.0 Hz, 2H), 4.31 (s, 2H), 4.02 (dd, J=7.8, 4.5 Hz, 1H), 3.94-3.73 (m, 2H), 3.65-3.54 (m, 2H), 3.49-3.38 (m, 2H), 2.88 (q, J=7.5 Hz, 2H), 2.77 (q, J=7.5 Hz, 2H), 2.58-2.38 (m, 2H), 2.30-2.12 (m, 2H), 1.90-1.56 (m, 5H), 1.55-1.30 (m, 2H), 1.31 (t, J=7.5 Hz, 3H), 0.99-0.94 (m, 12H).

EXAMPLE 24(58)

[1637] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-diethyl-1-(4-chlorophenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2743

[1638] TLC: Rf 0.51 (chloroform:methanol=20:1);

[1639] NMR (CD3OD): δ 7.58 (d, J=9.0 Hz, 2H), 7.48 (d, J=9.0 Hz, 2H), 4.31 (s, 2H), 4.05 (dd, J=7.5, 4.5 Hz, 1H), 3.94-3.73 (m, 2H), 3.65-3.54 (m, 2H), 3.50-3.38 (m, 2H), 2.88 (q, J=7.5 Hz, 2H), 2.77 (q, J=7.5 Hz, 2H), 2.60-2.40 (m, 2H), 2.28-2.09 (m, 2H), 1.85-1.10 (m, 15H), 1.31 (t, J=7.5 Hz, 3H), 1.04-0.85 (m, 2H), 0.96 (t, J=7.5 Hz, 3H), 0.94 (t, J=7.5 Hz, 3H).

EXAMPLE 24(59)

[1640] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-phenyloxypyridin-3-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2744

[1641] TLC: Rf 0.65 (chloroform:methanol=10:1);

[1642] NMR (CD3OD): δ 8.32 (s, 1H), 8.06 (m, 1H), 7.44 (t, J=7.5 Hz, 2H), 7.26 (t, J=7.5 Hz, 1H), 7.14 (d, J=7.5 Hz, 2H), 7.06 (d, J=8.7 Hz, 1H), 4.39 (s, 2H), 4.01 (dd, J=7.5, 4.5 Hz, 1H), 3.90-3.70 (m, 2H), 3.53-3.41 (m, 4H), 2.45 (m, 2H), 2.25-2.12 (m, 2H), 1.78 (m, 1H), 1.72-1.50 (m, 4H), 1.36 (m, 2H), 0.97-0.93 (m, 9H).

EXAMPLE 24(60)

[1643] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(6-phenyloxypyridin-3-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2745

[1644] TLC: Rf 0.67 (chloroform:methanol=10:1);

[1645] NMR (CD3OD): δ 8.31 (s, 1H), 8.07 (d, J=8.3 Hz, 1H), 7.44 (t, J=7.5 Hz, 2H), 7.26 (t, J=7.5 Hz, 1H), 7.14 (d, J=7.5 Hz, 2H), 7.06 (d, J=8.3 Hz, 1H), 4.39 (s, 2H), 4.04 (dd, J=7.8, 4.6 Hz, 1H), 3.90-3.76 (m, 2H), 3.52-3.38 (m, 4H), 2.58-2.36 (m, 2H), 2.25-2.11 (m, 2H), 1.80-1.42 (m, 10H), 1.42-1.17 (m, 5H), 1.05-0.85 (m, 2H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 24(61)

[1646] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(1,3-benzodioxolan-5-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2746

[1647] TLC: Rf 0.38 (chloroform:methanol=10:1);

[1648] NMR (CD3OD): δ 7.05-7.00 (m, 2H), 6.92 (m, 1H), 6.03 (s, 2H), 4.26 (s, 2H), 4.02 (dd, J=7.5, 4.5 Hz, 1H), 3.84-3.68 (m, 2H), 3.52-3.36 (m, 4H), 2.42-2.10 (m, 4H), 1.88-1.32 (m, 7H), 0.96 (t, J=6.9 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 24(62)

[1649] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(1,3-benzodioxolan-5-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2747

[1650] TLC: Rf 0.42 (chloroform:methanol=10:1);

[1651] NMR (CD3OD): δ 7.06-7.01 (m, 2H), 6.92 (m, 1H), 6.03 (s, 2H), 4.27 (s, 2H), 4.04 (dd, J=7.5, 4.5 Hz, 1H), 3.82-3.70 (m, 2H), 3.56-3.36 (m, 4H), 2.48-2.10 (m, 4H), 1.82-1.16 (m, 15H), 0.96 (t, J=7.5 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 24(63)

[1652] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-hydroxy-4-methoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2748

[1653] TLC: Rf 0.88 (chloroform:methanol=10:1);

[1654] NMR (CD3OD): δ 7.26 (d, J=8.5 Hz, 1H), 6.51 (dd, J=8.5, 2.5 Hz, 1H), 6.48 (d, J=2.5 Hz, 1H), 4.26 (s, 2H), 4.03 (m, 1H), 3.77 (m, 5H), 3.47 (m, 2H), 3.37 (m, 2H), 2.34 (m, 2H), 2.15 (m, 2H), 1.69 (m, 6H), 1.52 (m, 4H), 1.31 (m, 5H), 0.95 (m, 5H).

EXAMPLE 24(64)

[1655] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-methylthiophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2749

[1656] TLC: Rf 0.83 (chloroform:methanol=10:1);

[1657] NMR (CD3OD): δ 7.44 (d, J=8.7 Hz, 2H), 7.36 (d, J=8.7 Hz, 2H), 4.32 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.80 (m, 2H), 3.49 (m, 2H), 3.34 (m, 2H), 2.50 (s, 3H), 2.36-2.11 (m, 4H), 1.69 (m, 10H), 1.39-1.23 (m, 5H), 0.95 (m, 5H).

EXAMPLE 24(65)

[1658] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(N,N-diphenylamino)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2750

[1659] TLC: Rf 0.48 (chloroform:methanol=20:1);

[1660] NMR (CD3OD): δ 7.40-7.25 (m, 6H), 7.13-7.01 (m, 8H), 4.27 (s, 2H), 4.01 (dd, J=7.8, 4.5 Hz, 1H), 3.87-3.68 (m, 2H), 3.56-3.44 (m, 2H), 3.44-3.32 (m, 2H), 2.48-2.32 (m, 2H), 2.29-2.10 (m, 2H), 1.90-1.44 (m, 5H), 1.44-1.30 (m, 2H), 0.96 (t, J=6.9 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 24(66)

[1661] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(N,N-diphenylamino) phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2751

[1662] TLC: Rf 0.53 (chloroform:methanol=20:1);

[1663] NMR (CD3OD): 67.41-7.26 (m, 6H), 7.14-7.00 (m, 8H), 4.27 (s, 2H), 4.04 (dd, J=7.5, 4.5 Hz, 1H), 3.88-3.68 (m, 2H), 3.57-3.45 (m, 2H), 3.44-3.36 (m, 2H), 2.48-2.32 (m, 2H), 2.28-2.07 (m, 2H), 1.84-1.44 (m, 10H), 1.44-1.14 (m, 5H), 1.00-0.90 (m, 2H), 0.96 (t, J=6.9 Hz, 3H).

EXAMPLE 24(67)

[1664] (3S)-1-(2-butynyl)-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-phenyl pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2752

[1665] TLC: Rf 0.32 (chloroform:methanol=20:1);

[1666] NMR (CD3OD): δ 7.59-7.46 (m, 5H), 4.32 (s, 2H), 4.24 (s, 2H), 4.09 (dd, J=7.5, 4.5 Hz, 1H), 3.86 (m, 2H), 3.65 (m, 2H), 2.60 (m, 2H),2.39 (s, 3H), 2.38 (s, 3H), 2.26 (m, 2H), 1.88-1.66 (m, 10H), 1.53 (m, 1H), 1.25 (m, 3H), 0.96 (m, 2H).

EXAMPLE 24(68)

[1667] (3S)-1-(2-butynyl)-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2753

[1668] TLC: Rf 0.43 (chloroform:methanol=20:1);

[1669] NMR (CD3OD): δ 7.60-7.46 (m, 5H), 4.32 (s, 2H), 4.26 (m, 2H), 4.06 (dd, J=7.5, 4.5 Hz, 1H), 3.85 (m, 2H), 3.62 (m, 2H), 2.60 (m, 2H), 2.39 (s, 3H), 2.38 (s, 3H), 2.27 (m, 2H), 1.89-1.61 (m, 6H), 0.95 (d, J=6.5 Hz, 3H), 0.94 (d, J=6.5 Hz, 3H).

EXAMPLE 24(69)

[1670] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2754

[1671] TLC: Rf 0.57 (chloroform:methanol=20:1);

[1672] NMR (CD3OD): δ 7.59-7.45 (m, 5H), 4.32 (s, 2H), 4.06 (dd, J 7.8, 4.5 Hz, 1H), 3.85 (m, 2H), 3.60 (m, 2H), 3.43 (m, 2H), 2.53-2.44 (m, 2H), 2.45 (s, 3H), 2.41 (s, 3H), 2.32-2.16 (m, 2H), 1.80-1.17 (m, 15H), 1.02-0.93 (m, 2H), 0.96 (d, J=7.0 Hz, 3H).

EXAMPLE 24(70)

[1673] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-methylphenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2755

[1674] TLC: Rf 0.46 (chloroform:methanol=10:1);

[1675] NMR (CD3OD): δ 7.36 (d, J=8.4 Hz, 2H), 7.31 (d, J=8.4 Hz, 2H), 4.30 (s, 2H), 4.02 (dd, J=7.8, 4.8 Hz, 1H), 3.84 (m, 2H), 3.60 (m, 2H), 3.38 (m, 2H), 2.42 (s, 3H), 2.37 (s, 3H), 2.35 (s, 3H), 2.52-2.18 (m, 4H), 1.90-1.32 (m, 7H), 0.96 (t, J=7.8 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 24(71)

[1676] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-methylphenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2756

[1677] TLC: Rf 0.51 (chloroform:methanol=10:1);

[1678] NMR (CD3OD): δ 7.38 (d, J=8.4 Hz, 2H), 7.33 (d, J=8.4 Hz, 2H), 4.31 (s, 2H), 4.06 (dd, J=7.5, 4.5 Hz, 1H), 3.82 (m, 2H), 3.60 (m, 2H), 3.42 (m, 2H), 2.43 (s, 3H), 2.38 (s, 3H), 2.36 (s, 3H), 2.56-2.14 (m, 3H), 1.84-1.16 (m, 15H), 0.97 (t, J=7.2 Hz, 3H), 0.97 (m, 2H).

EXAMPLE 24(72)

[1679] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-chlorophenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2757

[1680] TLC: Rf 0.30 (chloroform:methanol=20:1);

[1681] NMR (CD3OD): δ 7.57 (d, J=9.0 Hz, 2H), 7.49 (d, J=9.0 Hz, 2H), 4.31 (s, 2H), 4.02 (dd, J=7.8, 4.5 Hz, 1H), 3.91-3.80 (m, 2H), 3.60 (m, 2H), 3.46 (m, 2H), 2.52 (m, 2H), 2.40 (s, 3H), 2.39 (s, 3H), 2.27-2.15 (m, 2H), 1.86-1.81 (m, 1H), 1.76-1.51 (m, 4H), 1.44-1.32 (m, 2H), 0.96 (t, J=7.0 Hz, 3H), 0.95 (d, J=6.0 Hz, 3H), 0.94 (d, J=6.0 Hz, 3H).

EXAMPLE 24(73)

[1682] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-chlorophenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2758

[1683] TLC: Rf 0.27 (chloroform:methanol=20:1);

[1684] NMR (CD3OD): δ 7.57 (d, J=8.5 Hz, 2H), 7.48 (d, J=8.5 Hz, 2H), 4.31 (s, 2H), 4.04 (dd, J=7.8, 4.5 Hz, 1H), 3.91-3.77 (m, 2H), 3.60 (m, 2H), 3.45 (m, 2H), 2.50 (m, 2H), 2.39 (s, 6H), 2.27-2.14 (m, 2H), 1.80-1.51 (m, 9H), 1.44-1.17 (m, 6H), 1.03-0.89 (m, 5H).

EXAMPLE 24(74)

[1685] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-trifluoromethylphenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2759

[1686] TLC: Rf 0.23 (chloroform:methanol=20:1);

[1687] NMR (CD3OD): δ 7.87 (d, J=8.7 Hz, 2H), 7.72 (d, J=8.7 Hz, 2H), 4.32 (s, 2H), 4.02 (dd, J=7.8, 4.5 Hz, 1H), 3.93-3.78 (m, 2H), 3.60 (m, 2H), 3.43 (m, 2H), 2.50 (m, 2H), 2.45 (s, 3H), 2.40 (s, 3H), 2.29-2.16 (m, 2H), 1.86-1.77 (m, 1H), 1.74-1.54 (m, 4H), 1.44-1.34 (m, 2H), 0.96 (t, J=7.0 Hz, 3H), 0.95 (d, J=6.0 Hz, 3H), 0.94 (d, J=6.0 Hz, 3H).

EXAMPLE 24(75)

[1688] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-trifluoromethylphenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2760

[1689] TLC: Rf 0.37 (chloroform:methanol=20:1);

[1690] NMR (CD3OD): δ 7.87 (d, J=8.4 Hz, 2H), 7.72 (d, J=8.4 Hz, 2H), 4.32 (s, 2H), 4.05 (dd, J=7.8, 4.5 Hz, 1H), 3.92-3.78 (m, 2H), 3.60 (m, 2H), 3.45 (m, 2H), 2.50 (m, 2H), 2.45 (s, 3H), 2.40 (s, 3H), 2.28-2.15 (m, 2H), 1.80-1.51 (m, 9H), 1.44-1.21 (m, 6H), 1.03-0.93 (m, 5H).

EXAMPLE 24(76)

[1691] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-diethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2761

[1692] TLC: Rf 0.70 (chloroform:methanol=10:1);

[1693] NMR (CD3OD): δ 7.61-7.53 (m, 3H), 7.53-7.46 (m, 2H), 4.32 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.95-3.79 (m, 2H), 3.65-3.58 (m, 2H), 3.50-3.38 (m, 2H), 2.85-2.75 (m, 4H), 2.47 (br, 2H), 2.28-2.16 (m, 2H), 1.83-1.46 (m, 3H), 1.41-1.29 (m, 4H), 0.98-0.91 (m, 15H).

EXAMPLE 24(77)

[1694] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-diethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2762

[1695] TLC: Rf 0.67 (chloroform:methanol=10:1);

[1696] NMR (CD3OD): δ 7.61-7.53 (m, 3H), 7.53-7.46 (m, 2H), 4.32 (s, 2H), 4.05 (dd, J=7.5, 4.5 Hz, 1H), 3.95-3.79 (m, 2H), 3.70-3.55 (m, 2H), 3.47-3.31 (m, 2H), 2.91-2.75 (m, 4H), 2.60-2.45 (m, 2H), 2.30-2.14 (m, 2H), 1.80-1.43 (m, 9H), 1.43-1.15 (m, 8H), 0.98-0.91 (m, 9H).

EXAMPLE 24(78)

[1697] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-phenylthiazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2763

[1698] TLC: Rf 0.62 (chloroform:methanol=10:1);

[1699] NMR (CD3OD): δ 8.03-8.00 (m, 2H), 7.87 (s, 1H), 7.52-7.49 (m, 3H), 4.54 (s, 2H), 4.04 (dd, J=7.6, 4.8 Hz, 1H), 4.04-3.87 (m, 2H), 3.70-3.58 (m, 2H), 3.51-3.39 (m, 2H), 2.58-2.38 (m, 2H), 2.26-2.13 (m, 2H), 1.78-1.43 (m, 9H), 1.40-1.15 (m, 6H), 1.10-0.90 (m, 5H).

EXAMPLE 24(79)

[1700] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-phenylthiazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2764

[1701] TLC: Rf 0.38 (chloroform:methanol=10:1);

[1702] NMR (CD3OD): δ 8.02-8.01 (m, 2H), 7.85 (s, 1H), 7.51-7.50 (m, 3H), 4.55 (s, 2H), 4.03-3.86 (m, 3H), 3.68-3.59 (m, 2H), 3.45-3.36 (m, 2H), 2.50-2.34 (m, 2H), 2.29-2.16 (m, 2H), 1.88-1.45 (m, 5H), 1.36 (q, J=7.2 Hz, 2H), 0.97-0.93 (m, 9H).

EXAMPLE 24(80)

[1703] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-(1,4-benzodioxan-2-yl)thiazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2765

[1704] TLC: Rf 0.36 (chloroform:methanol=10:1);

[1705] NMR (CD3OD): δ 7.88 (s, 1H), 7.00 (m, 1H), 6.94-6.87 (m, 3H), 5.66 (dd, J=6.0, 2.7 Hz, 1H), 4.62 (dd, J=11.7, 2.7 Hz, 1H), 4.51 (s, 2H), 4.42 (dd, J=11.7, 6.0 Hz, 1H), 4.02 (dd, J=7.5, 4.5 Hz, 1H), 3.88 (m, 2H), 3.58 (m, 2H), 3.40 (m, 2H), 2.48-2.16 (m, 4H), 1.90-1.28 (m, 7H), 0.97 (t, J=7.5 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 24(81)

[1706] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-trifluoromethyl-2-(morpholin-1-yl)thiazol-5-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2766

[1707] TLC: Rf 0.78 (chloroform:methanol=10:1);

[1708] NMR (CD3OD): δ 4.63 (s, 2H), 4.03 (dd, J=7.8, 4,8 Hz, 1H), 3.86-3.78 (m, 6H), 3.58 (m, 6H), 3.40 (m, 2H), 2.44 (m, 2H), 2.22 (m, 2H), 1.88-1.32 (m, 8H), 0.97 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H), 0.94 (d, J=6.6 Hz, 3H).

EXAMPLE 24(82)

[1709] 1-butyl-2,5-dioxo-3-(tetrahydropyran-4-ylmethyl)-9-(3,5-dimethyl-1-phenyl pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2767

[1710] TLC: Rf 0.31 (chloroform:methanol=10:1);

[1711] NMR (CD3OD): δ 7.60-7.46 (m, 5H), 4.33 (s, 2H), 4.09 (dd, J=7.5, 4.5 Hz, 1H), 3.98-3.78 (m, 4H), 3.68-3.56 (m, 2H), 3.50-3.36 (m, 4H), 2.58-2.16 (m, 4H), 2.40 (s, 3H), 2.39 (s, 3H), 1.84-1.20 (m, 11H), 0.97 (t, J=7.2 Hz, 3H).

EXAMPLE 24(83)

[1712] 1-butyl-2,5-dioxo-3-(tetrahydropyran-4-ylmethyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2768

[1713] TLC: Rf 0.34 (chloroform:methanol=10:1);

[1714] NMR (CD3OD): δ 7.06-6.92 (m, 3H), 4.27 (s, 4H), 4,24 (s, 2H), 4.07 (dd, J=7.5, 4.5 Hz, 1H), 3.96-3.86 (m, 2H), 3.84-3.68 (m, 2H), 3.52-3.36 (m, 6H), 2.44-2.10 (m, 4H), 1.82-1.22 (m, 11H), 0.96 (t, J=7.2 Hz, 3H).

EXAMPLE 24(84)

[1715] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-carboxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2769

[1716] TLC: Rf 0.58 (chloroform:methanol:acetic acid=20:2:1);

[1717] NMR (CD3OD): δ 8.14 (d, J=8.4 Hz, 2H), 7.68 (d, J=8.4 Hz, 2H), 4.45 (s, 2H), 4.04 (dd, J=7.5, 4.5 Hz, 1H), 3.94-3.76 (m, 2H), 3.56-3.43 (m, 2H), 3.43-3.34 (m, 2H), 2.50-2.31 (m, 2H), 2.28-2.08 (m, 2H), 1.84-1.12 (m, 15H), 1.06-0.90 (m, 2H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 24(85)

[1718] 1-butyl-2,5-dioxo-3-(2-cyclohexylethyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2770

[1719] TLC: Rf 0.47 (chloroform:methanol=10:1);

[1720] NMR (CD3OD): δ 7.56-7.45 (m, 5H), 4.32 (s, 2H), 4.02 (t, J=4.8 Hz, 1H), 3.98-3.85 (m, 1H), 3.85-3.70 (m, 1H), 3.65-3.56 (m, 2H), 3.56-3.42 (m, 1H), 3.42-3.30 (m, 1H), 2.55-2.37 (m, 2H), 2.38 (s, 3H), 2.37 (s, 3H), 2.30-2.13 (m, 2H), 1.92-1.78 (m, 2H), 1.78-1.60 (m, 5H), 1.60-1.48 (m, 2H), 1.48-1.32 (m, 2H), 1.32-1.08 (m, 6H), 0.96 (t, J=7.2 Hz, 3H), 0.96-0.85 (m, 2H).

EXAMPLE 24(86)

[1721] 1-butyl-2,5-dioxo-3-(2-cyclohexylethyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2771

[1722] TLC: Rf 0.50 (chloroform:methanol=10:1);

[1723] NMR (CD3OD): δ 7.05 (d, J=2.1 Hz, 1H), 6.98 (dd, J 8.1, 2.1 Hz, 1H), 6.92 (d, J=8.1 Hz, 1H), 4.26 (s, 4H), 4.23 (s, 2H), 4.03 (t, J=4.8 Hz, 1H), 3.90-3.79 (m, 1H), 3.76-3.62 (m, 1H), 3.50-3.38 (m, 3H), 3.38-3.30 (m, 1H), 2.43-2.06 (m, 4H), 1.92-1.78 (m, 2H), 1.78-1.60 (m, 5H), 1.60-1.45 (m, 2H), 1.42-1.30 (m, 2H), 1.30-1.08 (m, 6H), 0.95 (t, J=7.2 Hz, 3H), 0.97-0.88 (m, 2H).

EXAMPLE 24(87)

[1724] (3R)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2772

[1725] TLC: Rf 0.43 (chloroform:methanol=10:1);

[1726] NMR (CD3OD): δ 7.61-7.48 (m, 5H), 4.33 (s, 2H), 4.06 (dd, J=7.5, 4.5 Hz, 1H), 3.95-3.78 (m, 2H), 3.68-3.58 (m, 2H), 3.50-3.40 (m, 2H), 2.62-2.45 (m, 2H), 2.42 (s, 3H), 2.40 (s, 3H), 2.30-2.12 (m, 2H), 1.82-1.12 (m, 15H), 0.97 (t, J=7.2 Hz, 3H), 0.97 (m, 2H).

EXAMPLE 24(88)

[1727] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-methyl-2-phenylthiazol-5-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2773

[1728] TLC: Rf 0.75 (chloroform:methanol=10:1);

[1729] NMR (CD3OD): δ 7.98-7.95 (m, 2H), 7.55-7.50 (m, 3H), 4.69 (s, 2H), 4.01 (dd, J=7.5, 4.5 Hz, 1H), 3.98-3.78 (m, 2H), 3.65-3.56 (m, 2H), 3.50-3.40 (m, 2H), 2.58 (s, 3H), 2.60-2.48 (m, 2H), 2.27-2.14 (m, 2H), 1.88-1.48 (m, 5H), 1.48-1.30 (m, 2H), 0.97-0.93 (m, 9H).

EXAMPLE 24(89)

[1730] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-(thiophen-1-yl)thiazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2774

[1731] TLC: Rf 0.60 (chloroform:methanol=10:1);

[1732] NMR (CD3OD): δ 7.81 (s, 1H), 7.67 (d, J=3.9 Hz, 1H), 7.60 (d, J=5.4 Hz, 1H), 7.14 (dd, J=5.4, 3.9 Hz, 1H), 4.49 (s, 2H), 4.00 (dd, J=7.8, 4.5 Hz, 1H), 3.98-3.82 (m, 2H), 3.62-3.55 (m, 2H), 3.42 (t, J=7.5 Hz, 2H), 2.58-2.40 (m, 2H), 2.28-2.10 (m, 2H), 1.86-1.42 (m, 5H), 1.46-1.30 (m, 2H), 0.97-0.93 (m, 9H).

EXAMPLE 24(90)

[1733] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-(pyridin-4-yl)thiazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2775

[1734] TLC: Rf 0.51 (chloroform:methanol=10:1);

[1735] NMR (CD3OD): δ 8.98 (d, J=6.9 Hz, 2H), 8.71 (d, J=6.9 Hz, 2H), 8.37 (s, 1H), 4.66 (s, 2H), 4.01 (dd, J=7.8, 4.8 Hz, 1H), 4.00-3.87 (m, 2H), 3.70-3.59 (m, 2H), 3.50 (t, J=7.8 Hz, 2H), 2.72-2.58 (m, 2H), 2.25-2.08 (m, 2H), 1.88-1.46 (m, 5H), 1.46-1.35 (m, 2H), 0.97-0.92 (m, 9H).

EXAMPLE 24(91)

[1736] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,4-dimethoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2776

[1737] TLC: Rf 0.28 (chloroform:methanol=10:1);

[1738] NMR (CD3OD): a 7.23 (s, 1H), 7.09 (d, J=8.4 Hz, 1H), 7.03 (d, J=8.4 Hz, 1H), 4.29 (s, 2H), 4.04 (dd, J=7.5, 4.8 Hz, 1H), 3.90 (s, 3H), 3.86 (s, 3H), 3.88-3.64 (m, 2H), 3.56-3.38 (m, 4H), 2.58-2.37 (m, 2H), 2.24-2.08 (m, 2H), 1.82-1.10 (m, 15H), 0.96 (t, J=7.2 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 24(92)

[1739] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2777

[1740] TLC: Rf 0.31 (chloroform:methanol=10:1);

[1741] NMR (CD3OD): δ 6.74 (d, J=1.8 Hz, 2H), 6.60 (t, J=1.8 Hz, 1H), 4.28 (s, 2H), 4.04 (dd, J=7.8, 4.8 Hz, 1H), 3.86-3.70 (m, 2H), 3.83 (s, 6H), 3.58-3.36 (m, 4H), 2.52-2.36 (m, 2H), 2.24-2.08 (m, 2H), 1.82-1.10 (m, 15H), 0.96 (t, J=7.2 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 24(93)

[1742] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(pyridin-2-yl)furan-2-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2778

[1743] TLC: Rf 0.39 (chloroform:methanol=10:1);

[1744] NMR (CD3OD): δ 8.76 (dd, J=5.4, 1.5 Hz, 1H), 8.51 (ddd, J=8.1, 7.5, 1.5 Hz, 1H), 8.39 (d, J=7.5 Hz, 1H), 7.85 (dd, J=8.1, 5.4 Hz, 1H), 7.61 (d, J=3.6 Hz, 1H), 7.08 (d, J=3.6 Hz, 1H), 4.63 (s, 2H), 4.00 (dd, J=7.8, 4.5 Hz, 1H), 3.98-3.81 (m, 2H), 3.65-3.55 (m, 2H), 3.49 (t, J=8.1 Hz, 2H), 2.72-2.55 (m, 2H), 2.28-2.10 (m, 2H), 1.90-1.27 (m, 7H), 1.00-0.89 (m, 9H).

EXAMPLE 24(94)

[1745] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(pyridin-3-yl)furan-2-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2779

[1746] TLC: Rf 0.45 (chloroform:methanol=10:1);

[1747] NMR (CD3OD): δ 9.34 (d, J=1.8 Hz, 1H), 8.94 (dd, J=8.1, 1.8 Hz, 1H), 8.75 (d, J=5.4 Hz, 1H), 8.10 (dd, J=8.1, 5.4 Hz, 1H), 7.34 (d, J=3.6 Hz, 1H), 6.98 (d, J=3.6 Hz, 1H), 4.57 (s, 2H), 4.00 (dd, J=7.8, 4.5 Hz, 1H), 3.98-3.77 (m, 2H), 3.63-3.43 (m, 4H), 2.73-2.55 (m, 2H), 2.28-2.09 (m, 2H), 1.89-1.27 (m, 7H), 1.00-0.89 (m, 9H).

EXAMPLE 24(95)

[1748] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(3,5-dimethylpyrazol-1-yl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2780

[1749] TLC: Rf 0.52 (chloroform:methanol=10:1);

[1750] NMR (CD3OD): δ 7.94 (d, J=8.1 Hz, 2H), 7.71 (d, J=8.1 Hz, 2H), 6.51 (s, 1H), 4.49 (s, 2H), 4.01 (dd, J=7.8, 4.5 Hz, 1H), 3.85-3.76 (m, 2H), 3.58-3.48 (m, 4H), 2.72-2.58 (m, 2H), 2.45 (s, 3H), 2.39 (s, 3H), 2.23-2.06 (m, 2H), 1.88-1.45 (m, 5H), 1.45-1.34 (m, 2H), 0.97-0.92 (m, 9H).

EXAMPLE 24(96)

[1751] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(5-chloropyridin-3-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2781

[1752] TLC: Rf 0.57 (chloroform:methanol=10:1);

[1753] NMR (CD3OD): δ 8.54 (bs, 1H), 8.45 (bs, 1H), 7.87 (bs, 1H), 7.71 (d, J=8.4 Hz, 2H), 7.26 (d, J=8.4 Hz, 2H), 4.39 (s, 2H), 4.01 (dd, J=7.8, 4.8 Hz, 1H), 3.90-3.73 (m, 2H), 3.56-3.40 (m, 4H), 2.64-2.46 (m, 2H), 2.24-2.09 (m, 2H), 1.86-1.42 (m, 5H), 1.42-1.30 (m, 2H), 0.97-0.92 (m, 9H).

EXAMPLE 24(97)

[1754] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(pyrimidin-2-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2782

[1755] TLC: Rf 0.61 (chloroform:methanol=10:1);

[1756] NMR (CD3OD): δ 8.62 (d, J=4.8 Hz, 2H), 7.68 (d, J=8.4 Hz, 2H), 7.32 (d, J=8.4 Hz, 2H), 7.26 (t, J=4.8 Hz, 1H), 4.40 (s, 2H), 4.02 (dd, J=7.5, 4.5 Hz, 1H), 3.93-3.72 (m, 2H), 3.60-3.35 (m, 4H), 2.58-2.40 (m, 2H), 2.28-2.07 (m, 2H), 1.90-1.45 (m, 5H), 1.45-1.36 (m, 2H), 0.98-0.90 (m, 9H).

EXAMPLE 24(98)

[1757] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(pyridin-3-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2783

[1758] TLC: Rf 0.61 (chloroform:methanol=10:1);

[1759] NMR (CD3OD): δ 8.76 (d, J=2.7 Hz, 1H), 8.63 (d, J=5.7 Hz, 1H), 8.28 (dd, J=8.7, 2.7 Hz, 1H), 8.07 (dd, J=8.7, 5.7 Hz, 1H), 7.78 (d, J=8.4 Hz, 2H), 7.35 (d, J=8.4 Hz, 2H), 4.41 (s, 2H), 4.02 (dd, J=7.8, 4.5 Hz, 1H), 3.93-3.72 (m, 2H), 3.58-3.40 (m, 4H), 2.68-2.48 (m, 2H), 2.26-2.06 (m, 2H), 1.90-1.46 (m, 5H), 1.46-1.30 (m, 2H), 0.98-0.91 (m, 9H).

EXAMPLE 24(99)

[1760] 1-(2-butynyl)-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-methylphenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2784

[1761] TLC: Rf 0.28 (chloroform:methanol=19:1);

[1762] NMR (CD3OD): δ 7.39-7.29 (m, 4H), 4.31 (s, 2H), 4.27-4.20 (m, 2H), 4.06 (dd, J=7.5, 4.8 Hz, 1H), 3.84 (m, 2H), 3.62 (m, 2H), 2.59 (m, 2H), 2.42 (s, 3H), 2.37 (s, 3H), 2.34 (s, 3H), 2.28 (m, 2H), 1.92-1.60 (m, 6H), 0.96 (d, J=6.3 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H).

EXAMPLE 24(100)

[1763] (3R)-1-(2-butynyl)-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2785

[1764] TLC: Rf 0.29 (chloroform:methanol=19:1);

[1765] NMR (CD3OD): δ 7.59-7.43 (m, 5H), 4.31 (s, 2H), 4.25 (q, J=2.1 Hz, 2H), 4.09 (dd, J=7.2, 4.8 Hz, 1H), 3.85 (dt, J=3.0, 12.3 Hz, 2H), 3.68-3.56 (m, 2H), 2.61 (m, 2H), 2.38 (s, 3H), 2.37 (s, 3H), 2.26 (m, 2H), 1.83-1.43 (m, 8H), 1.75 (t, J=2.1 Hz, 3H), 1.38-1.12 (m, 3H), 0.96 (m, 2H).

EXAMPLE 24(101)

[1766] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-hydroxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2786

[1767] TLC: Rf 0.46 (chloroform:methanol=10:1);

[1768] NMR (CD3OD): δ 7.47 (d, J=9.0 Hz, 2H), 6.97 (d, J=9.0 Hz, 2H), 6.88 (d, J=9.0 Hz, 2H), 6.80 (d, J=9.0 Hz, 2H), 4.30 (s, 2H), 4.00 (dd, J=7.5, 4.8 Hz, 1H), 3.86-3.70 (m, 2H), 3.52-3.34 (m, 4H), 2.48-2.30 (m, 2H), 2.28-2.10 (m, 2H), 1.88-1.44 (m, 5H), 1.44-1.28 (m, 2H), 0.97-0.92 (m, 9H).

EXAMPLE 24(102)

[1769] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(pyridin-2-yl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2787

[1770] TLC: Rf 0.50 (chloroform:methanol=10:1);

[1771] NMR (CD3OD): δ 8.89 (d, J=7.8 Hz, 1H), 8.70 (t, J=7.8 Hz, 1H), 8.43 (d, J=8.4 Hz, 1H), 8.10-8.06 (m, 3H), 7.98 (d, J=8.7 Hz, 2H), 4.51 (s, 2H), 4.01 (dd, J=7.8, 4.8 Hz, 1H), 3.96-3.78 (m, 2H), 3.56-3.45 (m, 4H), 2.72-2.58 (m, 2H), 2.24-2.08 (m, 2H), 1.84-1.44 (m, 5H), 1.44-1.34 (m, 2H), 0.97-0.92 (m, 9H).

EXAMPLE 24(103)

[1772] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(pyridin-3-yl) phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2788

[1773] TLC: Rf 0.47 (chloroform:methanol=10:1);

[1774] NMR (CD3OD): δ 9.24 (s, 1H), 8.98 (d, J=8.4 Hz, 1H), 8.88 (d, J=8.4 Hz, 1H), 8.21 (dd, J=8.4, 5.7 Hz, 1H), 7.96 (d, J=8.4 Hz, 2H), 7.87 (d, J=8.4 Hz, 2H), 4.47 (s, 2H), 4.01 (dd, J=7.5, 4.8 Hz, 1H), 3.96-3.75 (m, 2H), 3.58-3.44 (m, 4H), 2.64-2.50 (m, 2H), 2.25-2.08 (m, 2H), 1.88-1.48 (m, 5H), 1.48-1.32 (m, 2H), 0.97-0.92 (m, 9H).

EXAMPLE 24(104)

[1775] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-carboxyphenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2789

[1776] TLC: Rf 0.27 (chloroform:methanol=10:1);

[1777] NMR (CD3OD): δ 8.19 (d, J=8.4 Hz, 2H), 7.61 (d, J=8.4 Hz, 2H), 4.32 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.96-3.74 (m, 2H), 3.66-3.55 (m, 2H), 3.48-3.36 (m, 2H), 2.58-2.40 (m, 2H), 2.45 (s, 3H), 2.40 (s, 3H), 2.32-2.14 (m, 2H), 1.90-1.46 (m, 5H), 1.46-1.30 (m, 2H), 0.99-0.95 (m, 9H).

EXAMPLE 24(105)

[1778] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(pyrazin-2-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2790

[1779] TLC: Rf 0.48 (chloroform:methanol=20:1);

[1780] NMR (CD3OD): 88.47 (d, J=1.5 Hz, 1H), 8.32 (d, J=2.7 Hz, 1H), 8.13 (dd, J=2.7, 1.5 Hz, 1H), 7.65 (d, J=8.4 Hz, 2H), 7.32 (d, J=8.4 Hz, 2H), 4.40 (s, 2H), 4.02 (dd, J=7.5, 4.5 Hz, 1H), 3.94-3.73 (m, 2H), 3.58-3.46 (m, 2H), 3.44-3.34 (m, 2H), 2.52-2.34 (m, 2H), 2.30-2.10 (m, 2H), 1.90-1.43 (m, 5H), 1.43-1.26 (m, 2H), 0.99-0.90 (m, 9H).

EXAMPLE 24(106)

[1781] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-carboxyphenyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2791

[1782] TLC: Rf 0.20 (chloroform:methanol=10:1);

[1783] NMR (CD3OD): δ 8.11 (d, J=8.4 Hz, 2H), 7.83 (d, J=8.4 Hz, 2H), 7.77 (d, J=8.4 Hz, 2H), 7.69 (d, J=8.4 Hz, 2H), 4.43 (s, 2H), 4.01 (dd, J=7.8, 4.5 Hz, 1H), 3.96-3.74 (m, 2H), 3.58-3.36 (m, 4H), 2.55-2.38 (m, 2H), 2.28-2.10 (m, 2H), 1.88-1.44 (m, 5H), 1.44-1.30 (m, 2H), 0.97-0.92 (m, 9H).

EXAMPLE 24(107)

[1784] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(pyridin-4-yl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2792

[1785] TLC: Rf 0.50 (chloroform:methanol=10:1);

[1786] NMR (CD3OD): δ 8.91 (d, J=6.9 Hz, 2H), 8.45 (d, J=6.9 Hz, 2H), 8.11 (d, J=7.8 Hz, 2H), 7.91 (d, J=7.8 Hz, 2H), 4.49 (s, 2H), 4.01 (dd, J=7.8, 4.8 Hz, 1H), 3.96-3.78 (m, 2H), 3.58-3.40 (m, 4H), 2.64-2.48 (m, 2H), 2.26-2.08 (m, 2H), 1.90-1.28 (m, 7H), 0.96-0.93 (m, 9H).

EXAMPLE 24(108)

[1787] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(pyridin-2-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2793

[1788] TLC: Rf 0.46 (chloroform:methanol=10:1);

[1789] NMR (CD3OD): δ 8.44-8.15 (m, 2H), 7.82 (d, J=7.2 Hz, 2H), 7.60-7.40 (m, 1H), 7.42 (d, J=7.2 Hz, 2H), 7.27-7.24 (m, 1H), 4.43 (s, 2H), 4.02 (dd, J=7.5, 4.5 Hz, 1H), 3.92-3.70 (m, 2H), 3.58-3.40 (m, 4H), 2.64-2.42 (m, 2H), 2.28-2.06 (m, 2H), 1.92-1.28 (m, 7H), 0.97-0.94 (m, 9H).

EXAMPLE 24(109)

[1790] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(naphthalen-2-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2794

[1791] TLC: Rf 0.71 (chloroform:methanol=10:1);

[1792] NMR (CD3OD): δ 8.08-7.93 (m, 4H), 7.64-7.57 (m, 3H), 4.54 (s, 2H), 4.04 (dd, J=7.5, 4.8 Hz, 1H), 3.96-3.80 (m, 2H), 3.60-3.44 (m, 2H), 3.42-3.36 (m, 2H), 2.42-2.08 (m, 4H), 1.82-1.16 (m, 15H), 0.95 (t, J=7.5 Hz, 3H), 0.95 (m, 2H).

EXAMPLE 24(110)

[1793] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(6-methoxynaphthalen-2-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2795

[1794] TLC: Rf 0.75 (chloroform:methanol=10:1);

[1795] NMR (CD3OD): δ 7.98 (s, 1H), 7.91 (d, J=8.7 Hz, 1H), 7.85 (d, J=8.7 Hz, 1H), 7.58 (d, J=8.7 Hz, 1H), 7.31 (d, J=2.4 Hz, 1H), 7.22 (dd, J=8.7, 2.4 Hz, 1H), 4.48 (s, 2H), 4.04 (dd, J=7.8, 4.8 Hz, 1H), 3.94-3.78 (m, 2H), 3.93 (s, 3H), 3.58-3.44 (m, 2H), 3.42-3.36 (m, 2H), 2.48-2.30 (m, 2H), 2.24-2.08 (m, 2H), 1.82-1.10 (m, 15H), 0.95 (t, J=7.2 Hz, 3H), 0.95 (m, 2H).

EXAMPLE 24(111)

[1796] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-carboxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2796

[1797] TLC: Rf 0.27 (chloroform:methanol=10:1);

[1798] NMR (CD3OD): δ 8.03 (d, J=8.7 Hz, 2H), 7.63 (d, J=8.4 Hz, 2H), 7.17 (d, J=8.4 Hz, 2H), 7.07 (d, J=8.7 Hz, 2H), 4.37 (s, 2H), 4.01 (dd, J=7.5, 4.5 Hz, 1H), 3.90-3.70 (m, 2H), 3.56-3.36 (m, 4H), 2.56-2.38 (m, 2H), 2.25-2.10 (m, 2H), 1.84-1.44 (m, 5H), 1.44-1.39 (m, 2H), 0.98-0.93 (m, 9H).

EXAMPLE 24(112)

[1799] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(pyridin-4-yl)furan-2-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2797

[1800] TLC: Rf 0.39 (chloroform:methanol=10:1);

[1801] NMR (CD3OD): δ 8.80 (d, J=6.9 Hz, 2H), 8.39 (d, J=6.9 Hz, 2H), 7.69 (d, J=3.6 Hz, 1H), 7.08 (d, J=3.6 Hz, 1H), 4.62 (s, 2H), 4.00 (dd, J=7.8, 4.5, Hz, 1H), 3.99-3.79 (m, 2H), 3.65-3.43 (m, 4H), 2.72-2.54 (m, 2H), 2.30-2.10 (m, 2H), 1.88-1.26 (m, 7H), 1.00-0.84 (m, 9H).

EXAMPLE 24(113)

[1802] 1-butyl-2,5-dioxo-3-cyclopentylmethyl-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2798

[1803] TLC: Rf 0.66 (chloroform:methanol=10:1);

[1804] NMR (CD3OD): δ 7.52 (d, J=8.5 Hz, 2H), 7.40 (t, J=7.5 Hz, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.05 (m, 4H), 4.34 (s, 2H), 4.00 (t, J=6.0 Hz, 1H), 3.82 (m, 2H), 3.49 (m, 2H), 3.39 (m, 2H), 2.37 (m, 2H), 2.17 (m, 2H), 1.96 (m, 1H), 1.81 (m, 4H), 1.58 (m, 6H), 1.38 (m, 2H), 1.17 (m, 2H), 0.95 (t, J=7.0 Hz, 3H).

EXAMPLE 24(114)

[1805] (3R)-1-butyl-2,5-dioxo-3-(2,2-dimethylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2799

[1806] TLC: Rf 0.52 (chloroform:methanol=20:1);

[1807] NMR (CD3OD): δ 7.52 (d, J=9.0 Hz, 2H), 7.40 (t, J=7.5 Hz, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.04 (m, 4H), 4.33 (s, 2H), 4.01 (dd, J=7.2, 3.3 Hz, 1H), 3.82 (m, 1H), 3.71 (m, 1H), 3.50 (m, 2H), 3.43 (m, 2H), 2.38 (m, 2H), 2.24 (m, 2H), 2.00 (dd, J=14.0, 3.3 Hz, 1H), 1.55 (dd, J=14.0, 7.2 Hz, 1H), 1.50 (m, 2H), 1.36 (m, 2H), 0.99 (s, 9H), 0.95 (t, J=7.0 Hz, 3H).

EXAMPLE 24(115)

[1808] (3S)-1-butyl-2,5-dioxo-3-(2,2-dimethylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2800

[1809] TLC: Rf 0.52 (chloroform:methanol=20:1);

[1810] NMR (CD3OD): δ 7.52 (d, J=9.0 Hz, 2H), 7.40 (t, J=7.5 Hz, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.04 (m, 4H), 4.33 (s, 2H), 4.01 (dd, J=7.2, 3.3 Hz, 1H), 3.82 (m, 1H), 3.71 (m, 1H),3.50 (m, 2H), 3.43 (m, 2H), 2.38 (m, 2H), 2.24 (m, 2H), 2.00 (dd, J=14.0, 3.3 Hz, 1H), 1.55 (dd, J=14.0, 7.2 Hz, 1H), 1.50 (m, 2H), 1.36 (m, 2H), 0.99 (s, 9H), 0.95 (t, J=7.0 Hz, 3H).

EXAMPLE 24(116)

[1811] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-nitrophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2801

[1812] TLC: Rf 0.68 (chloroform:methanol=10:1);

[1813] NMR (CD3OD): δ 8.33 (d, J=8.7 Hz, 2H), 7.78 (d, J=8.7 Hz, 2H), 4.49 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.93-3.76 (m, 2H), 3.55-3.43 (m, 2H), 3.40-3.31 (m, 2H), 2.45-2.28 (m, 2H), 2.27-2.08 (m, 2H), 1.83-1.14 (m, 15H), 1.04-0.86 (m, 5H).

EXAMPLE 24(117)

[1814] (3R)-1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-phenylmethyl-9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2802

[1815] TLC: Rf 0.55 (chloroform:methanol=10:1);

[1816] NMR (CDCl3): δ 7.38-7.14 (m, 10H), 6.00-5.75 (m, 1H), 4.40-4.15 (m, 2H), 3.92-3.58 (m, 3H), 3.58-2.25 (m, 13H), 2.18-1.45 (m, 10H).

EXAMPLE 24(118)

[1817] (3S)-1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-phenylmethyl-9-(4-phenylbutyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2803

[1818] TLC: Rf 0.55 (chloroform:methanol=10:1);

[1819] NMR (CDCl3): δ 7.40-7.15 (m, 10H), 6.05-5.80 (m, 1H), 4.40-4.10 (m, 2H), 3.90-3.55 (m, 3H), 3.55-2.20 (m, 13H), 2.18-1.45 (m, 10H).

EXAMPLE 24(119)

[1820] (3S)-1-propyl-2,5-dioxo-3-(3-(benzyloxycarbonyl amino) propyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2804

[1821] TLC: Rf 0.32 (chloroform:methanol=10:1);

[1822] NMR (CD3OD): δ 7.40-7.20 (m, 10H), 5.06 (s, 2H), 4.09 (dd, J=5.2, 4.6 Hz, 1H), 4.00-3.70 (m, 2H), 3.70-3.55 (m, 2H), 3.50-3.30 (m, 4H), 3.20-3.00 (m, 4H), 2.65-2.35 (m, 2H), 2.30-2.10 (m, 2H), 2.00-1.75 (m, 2H), 1.70-1.40 (m, 4H), 0.96 (t, J=7.4 Hz, 3H).

EXAMPLE 25

[1823] 1-butyl-2,5-dioxo-3-(carboxymethyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2805

[1824] To a solution of the compound prepared in Example 24(11) (173 mg) in methanol (5 mL) was added 2N aqueous solution of sodium hydroxide (2 ml). The reaction mixture was stirred for 3 hours at room temperature. The reaction mixture was acidified to pH 4 by adding 2N hydrochloric acid, and was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated. The obtained residue was dissolved in 1,4-dioxane, and 4N hydrogen chloride-1,4-dioxane solution was added thereto. The reaction mixture was concentrated. The obtained residue was washed with diethyl ether and dried to give the compound of the present invention (127 mg) having the following physical data.

[1825] TLC: Rf 0.51 (chloroform:methanol:acetic acid=20:4:1);

[1826] NMR (CD3OD): 7.55-7.53 (m, 2H), 7.42-7.36 (m, 2H), 7.20-7.15 (m, 1H), 7.07-7.02 (m, 4H), 4.33 (s, 2H), 4.27 (t, J=4.5 Hz, 1H), 3.96-3.90 (m, 1H), 3.72-3.66 (m, 1H), 3.54-3.38 (m, 4H), 2.97 (dd, J=18.0,4.8Hz, 1H), 2.79 (dd, J=18.0, 4.8 Hz, 1H), 2.50-2.36 (m, 3H), 2.27-2.16 (m, 1H), 1.62-1.48 (m, 2H), 1.41-1.30 (m, 2H), 0.94 (t, J=7.2 Hz, 3H).

EXAMPLE 26(1)-26(3)

[1827] By the same procedure as described in Reference Example 3→Reference Example 4 using Resin (3) prepared in Reference Example 2 and N-allyloxycarbonyl-4-piperidone, using the corresponding compounds respectively instead of n-propylamine and N-(t-butyloxycarbonyl) leucine, and furthermore by the same procedure as described in Reference Example 5→Reference Example 6→Example 1 using the corresponding compound instead of 3,5-dimethyl-1-phenyl-4-formylpyrazole, and furthermore by the same procedure as described in Example 25 because of acetylation of a part of hydroxy group, the following compounds of the present invention were obtained.

EXAMPLE 26(1)

[1828] 1-(3-hydroxybutyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2806

[1829] TLC: Rf 0.49 (chloroform:methanol=10:1);

[1830] NMR (CD3OD): δ 7.54 (d, J=8.5 Hz, 2H), 7.39 (t, J=7.5 Hz, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.04 (m, 4H), 4.33 (s, 2H), 4.02 (m, 1H), 3.80 (m, 3H), 3.51 (m, 4H), 2.46 (m, 2H), 2.19 (m, 2H), 1.85-1.57 (m, 5H), 1.17 (d, J=6.0 Hz, 3H), 0.94 (d, J=9.0 Hz, 6H).

EXAMPLE 26(2)

[1831] 1-(3-hydroxypropyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2807

[1832] TLC: Rf 0.46 (chloroform:methanol=10:1);

[1833] NMR (CD3OD): δ 7.51 (d, J=8.5 Hz, 2H), 7.40 (t, J=7.5 Hz, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.04 (m, 4H), 4.34 (s, 2H), 4.02 (dd, J=7.5, 4.0 Hz, 1H), 3.80 (m, 2H), 3.60 (t, J=6.0 Hz, 2H), 3.48 (m, 4H), 2.40 (m, 2H), 2.20 (m, 2H), 1.82-1.58 (m, 5H), 0.94 (d, J=6.0 Hz, 3H), 0.93 (d, J=6.0 Hz, 3H).

EXAMPLE 26(3)

[1834] 1-(2-hydroxybutyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2808

[1835] TLC: Rf 0.49 (chloroform:methanol=10:1);

[1836] NMR (CD3OD): δ 7.50 (d, J=8.7 Hz, 2H), 7.39 (dd, J=8.7, 7.5 Hz, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.10-7.00 (m, 4H), 4.32 (s, 2H), 4.03 (dd, J=8.1, 4.8 Hz, 1H), 3.96-3.41 (m, 6H), 3.27-3.14 (m, 1H), 2.68-2.53 (m, 1H), 2.37-2.26 (m, 3H), 1.94-1.24 (m, 5H), 1.08-0.82 (m, 9H).

EXAMPLE 27

[1837] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-aminophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2809

[1838] Under an atmosphere of argon, to a solution of the compound prepared in Example 24(116) (50 mg) in methanol was added 5% palladium on carbon (10 mg). Under an atmosphere of hydrogen, the reaction mixture was stirred for 20 minutes at room temperature. The reaction mixture was filtrated through Celite (brand name). The filtrate was concentrated. The residue was purified by column chromatography on silica gel (chloroform:methanol=50:1→30:1→20:1). The obtained compound was dissolved in methanol, and 4N-hydrogen chloride/ethyl acetate solution was added thereto. It was concentrated. The obtained residue was washed with diethyl ether and dried to give the compound of the present invention (34 mg) having the following physical data.

[1839] TLC: Rf 0.21 (chloroform:methanol=10:1);

[1840] NMR (CD3OD): δ 7.80 (d, J=8.4 Hz, 2H), 7.47 (d, J=8.4 Hz, 2H), 4.41 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.86-3.74 (m, 2H), 3.52-3.45 (m, 4H), 2.65-2.52 (m, 2H), 2.24-2.08 (m, 2H), 1.80-1.16 (m, 15H), 0.94 (t, J=7.5 Hz, 3H), 0.94 (m, 2H).

EXAMPLE 28

[1841] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-((4-methylphenyl)sulfonylamino)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2810

[1842] To a solution of the compound prepared in Example 28 (33 mg) in pyridine (2 ml) was added p-toluenesulfonyl chloride (21 mg). The reaction mixture was stirred for 27 hours at room temperature. The reaction mixture was concentrated, and saturated aqueous solution of sodium hydrogen carbonate was added thereto. It was extracted with ethyl acetate. The extract was washed with saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by column chromatography on silica gel (chloroform:methanol=10:1). The obtained compound was dissolved in methanol, and 4N hydrogen chloride/ethyl acetate solution was added thereto, and it was concentrated. The residue was washed with diethyl ether and dried to give the compound of the present invention (27 mg) having the following physical data.

[1843] TLC: Rf 0.63 (chloroform:methanol=10:1);

[1844] NMR (CD3OD): δ 7.70 (d, J=8.4 Hz, 2H), 7.41 (d, J=8.4 Hz, 2H), 7.30 (d, J=8.4 Hz, 2H), 7.22 (d, J=8.4 Hz, 2H), 4.25 (s, 2H), 4.03 (dd, J=7.2, 4.5 Hz, 1H), 3.78 (m, 2H), 3.42 (m, 4H), 2.42-2.06 (m, 4H), 2.37 (s, 3H), 1.82-1.10 (m, 15H), 0.95 (t, J=7.2 Hz, 3H), 0.95 (m, 2H).

EXAMPLE 28(1)

[1845] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(phenylcarbonylamino)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2811

[1846] By the same procedure as described in Example 28 using benzoyl chloride instead of p-toluenesulfonyl chloride, the compound of the present invention having the following physical data was obtained.

[1847] TLC: Rf 0.43 (chloroform:methanol=10:1);

[1848] NMR (CD3OD): δ 7.93 (d, J=8.4 Hz, 2H), 7.88 (d, J=8.4 Hz, 2H), 7.61-7.50 (m, 5H), 4.34 (s, 2H), 4.05 (dd, J=7.8, 4.5 Hz, 1H), 3.80 (m, 2H), 3.42 (m, 4H), 2.24 (m, 4H), 1.82-1.16 (m, 15H), 0.96 (t, J=7.2 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 29

[1849] (3S)-1-butyl-2,5-dioxo-3-benzyloxymethyl-9-benzyloxycarbonyl-1,4,9-triazaspiro[5.5]undecane

2812

[1850] By the same procedure as described in Reference Example 3→Reference Example 6→Example 1 using Resin (3) prepared in Reference Example 2 and N-benzyloxycarbonyl-4-piperidone, O-benzyl-N-(t-butyloxycarbonyl)-L-serine, the compound of the present invention having the following physical data was obtained.

[1851] TLC: Rf 0.66 (chloroform:methanol=20:1);

[1852] NMR (CDCl3): 87.40-7.25 (m, 10H), 6.09 (brs, 1H), 5.15 (s, 2H), 4.54 (s, 2H), 4.20-3.98 (br, 2H), 4.18(dd, J=8.4, 3.6 Hz, 1H), 3.93 (dd, J=9.3, 3.6 Hz, 1H), 3.80-3.56 (br, 1H), 3.66 (dd, J=9.3, 8.4, Hz, 1H), 3.45-3.12 (m, 3H), 2.02-1.75 (m, 4H), 1.57-1.39 (m, 2H), 1.38-1.20.(m, 2H), 0.91 (t, J=7.2 Hz, 3H).

EXAMPLE 30

[1853] (3S)-1-butyl-2,5-dioxo-3-hydroxymethyl-9-benzyloxycarbonyl-1,4,9-triazaspiro[5.5]undecane

2813

[1854] To a solution of the compound prepared in Example 29 (245 mg) in dichloromethane (5 ml) was added a 1 M solution of tribromoborane in dichloromethane (1.4 ml) at −40° C., and it was stirred for 3 hours at −20° C. To the reaction mixture were added water and saturated aqueous solution of sodium hydrogen carbonate, and it was extracted with ethyl acetate. The extract was washed with water and saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by column chromatography on silica gel (chloroform:methanol=30:1) to give the compound of the present invention (173 mg) having the following physical data.

[1855] TLC: Rf 0.29 (chloroform:methanol=20:1);

[1856] NMR (CDCl3): δ 7.42-7.27 (m, 5H), 6.26-6.15 (br, 1H), 5.16 (s, 2H), 4.26-4.00 (m, 2H), 3.98-3.82 (m, 2H), 3.84-3.60 (br, 1H), 3.43-3.13 (m, 4H), 2.80-2.68 (br, 1H), 2.05-1.75 (m, 4H), 1.58-1.40 (m, 2H), 1.40-1.20 (m, 2H), 0.92 (t, J=7.5 Hz, 3H).

EXAMPLE 31

[1857] (3S)-1-butyl-2,5-dioxo-3-hydroxymethyl-1,4,9-triazaspiro[5.5]undecane

2814

[1858] By the same procedure as described in Example 9 using the compound prepared in Example 30, the compound of the present invention having the following physical data was obtained.

[1859] TLC: Rf 0.21 (chloroform: methanol: acetic acid=20:4:1);

[1860] NMR (d6-DMSO): 67.83 (brs, 1H), 5.10-4.90 (br, 1H), 3.88-3.78 (m, 1H), 3.76-3.65 (m, 1H), 3.58-3.48 (m, 1H), 3.28-3.18 (m, 1H), 3.18-3.04 (m, 3H), 2.88-2.75 (m, 2H), 1.94-1.83 (m, 1H), 1.83-1.64 (m, 3H), 1.56-1.42 (m, 1H), 1.42-1.20 (m, 3H), 0.88 (t, J=7.2 Hz, 3H).

EXAMPLE 32(1)

[1861] (3S)-1-butyl-2,5-dioxo-3-hydroxymethyl-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2815

[1862] By the same procedure as described in Example 10 using 4-phenyloxybenzaldehyde and the compound prepared in Example 31, the compound of the present invention having the following physical data was obtained.

[1863] TLC: Rf 0.49 (chloroform:methanol=10:1);

[1864] NMR (CD3OD): δ 7.52 (d, J=8.7 Hz, 2H), 7.43-7.35 (m, 2H), 7.22-7.14 (m, 1H), 7.06 (d, J=8.7 Hz, 2H), 7.06-7.00 (m, 2H), 4.33 (s, 2H), 4.03-3.90 (m, 3H), 3.79-3.66 (m, 1H), 3.65 (dd, J=10.5, 2.4 Hz, 1H), 3.61-3.42 (m, 3H), 3.30-3.18 (m, 1H), 2.50-2.24 (m, 3H), 2.24-2.12 (m, 1H), 1.76-1.58 (m, 1H), 1.54-1.26 (m, 3H), 0.95 (t, J=7.5 Hz, 3H).

EXAMPLE 32(2)

[1865] (3S)-1-butyl-2,5-dioxo-3-hydroxymethyl-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2816

[1866] By the same procedure as described in Example 10 using 1-phenyl-3,5-dimethyl-4-formylpyrazole and the compound prepared in Example 31, the compound of the present invention having the following physical data was obtained.

[1867] TLC: Rf 0.47 (chloroform:methanol=10:1);

[1868] NMR (CD3OD): δ 7.61-7.46 (m, 5H), 4.32 (s, 2H), 4.08-3.92 (m, 3H), 3.83-3.70 (m, 1H), 3.66 (dd, J=10.5, 2.4 Hz, 1H), 3.66-3.52 (m, 3H), 3.40-3.25 (m, 1H), 2.64-2.50 (m, 1H), 2.50-2.40 (m, 2H), 2.41 (s, 3H), 2.39 (s, 3H), 2.28-2.15 (m, 1H), 1.80-1.58 (m, 1H), 1.58-1.30 (m, 3H), 0.96 (t, J=7.5 Hz, 3H).

REFERENCE EXAMPLE 11

Preparation of Compound (7)

[1869]

2817

[1870] By the same procedure as described in Reference Example 3→Reference Example 4 using Resin (3) prepared in Reference Example 2 and N-allyloxycarbonyl-4-piperidone, n-butylamine and N-(t-butyloxycarbonyl)leucine, and furthermore by the same procedure as described in Reference Example 5 using 4-hydroxybenzaldehyde instead of 3,5-dimethyl-1-phenyl-4-formylpyrazole, compound (7) was obtained.

REFERENCE EXAMPLE 12

Preparation of Compound (8)

[1871]

2818

[1872] To a suspension of the compound prepared in Reference Example 11 (60 mg) in dichloromethane (2 ml) were added triphenylphosphine (80 mg), 1 M cyclopentanol-dichloromethane solution (0.302 ml) and diethylazodicarboxylate (0.137 ml). The reaction mixture was stirred for 18 hours at room temperature. The reaction solution was filtrated. The obtained resin was washed with dichloromethane (2 ml×4), methanol (2 ml×3), and dichloromethane (3 ml×4) to give compound (8).

EXAMPLE 33

[1873] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-cyclopentyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2819

[1874] By the same procedure as described in Reference Example 6→Example 1 using the compound prepared in Reference Example 12, the compound of the present invention having the following physical data was obtained.

[1875] TLC: Rf 0.49 (chloroform:methanol=10:1);

[1876] NMR (CD3OD): δ 7.41 (d, J=8.7 Hz, 2H), 6.98 (d, J=8.7 Hz, 2H), 4.83 (m, 1H), 4.25 (brs, 2H), 4.00 (dd, J=7.8, 4.5 Hz, 1H), 3.86-3.65 (m, 2H), 3.53-3.27 (m, 4H), 2.40-2.06 (m, 4H), 2.02-1.43 (m, 13H), 1.43-1.24 (m, 2H), 1.01-0.90 (m, 9H).

EXAMPLE 33(1)˜33(6)

[1877] By the same procedure as described in Reference Example 11 using the corresponding compounds instead of n-butylamine and N-(t-butyloxycarbonyl)leucine, and by the same procedure as described in Reference Example 12→Example 33 using the corresponding compounds instead of cyclopentanol, the following compounds of the present invention were obtained.

EXAMPLE 33(1)

[1878] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(2-diethylaminoethyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2820

[1879] TLC: Rf 0.54 (chloroform:methanol: 28% NH4OH=80:10:1);

[1880] NMR (CD3OD): δ 7.57 (d, J=8.7 Hz, 2H), 7.12 (d, J=8.7 Hz, 2H), 4.40 (t, J=4.8 Hz, 2H), 4.30 (s, 2H), 4.03 (dd, J=7.5, 5.1 Hz, 1H), 3.84-3.67 (m, 2H), 3.63 (t, J=4.8 Hz, 2H), 3.50-3.40 (m, 4H), 3.40-3.31 (m, 4H), 2.58-2.41 (m, 2H), 2.23-2.04 (m, 2H), 1.82-1.42 (m, 10H), 1.41-1.12 (m, 11H), 1.04-0.87 (m, 5H).

EXAMPLE 33(2)

[1881] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(2-dimethylaminoethyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2821

[1882] TLC: Rf 0.46 (chloroform:methanol: 28% NH4OH=80:10:1);

[1883] NMR (CD3OD): δ 7.57 (d, J=8.7 Hz, 2H), 7.13 (d, J=8.7 Hz, 2H), 4.39 (t, J=4.8 Hz, 2H), 4.30 (s, 2H), 4.02 (dd, J=7.5, 4.5 Hz, 1H), 3.84-3.67 (m, 2H), 3.61 (t, J=4.8 Hz, 2H), 3.50-3.38 (m, 4H), 2.98 (s, 6H), 2.59-2.42 (m, 2H), 2.24-2.03 (m, 2H), 1.83-1.12 (m, 15H), 1.04-0.86 (m, 5H).

EXAMPLE 33(3)

[1884] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-propyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2822

[1885] TLC: Rf 0.59 (chloroform:methanol=10:1);

[1886] NMR (CD3OD): δ 7.43 (d, J=8.7 Hz, 2H), 7.01 (d, J=8.7 Hz, 2H), 4.27 (brs, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.96 (t, J=6.6 Hz, 2H), 3.85-3.67 (m, 2H), 3.53-3.33 (m, 4H), 2.45-2.27 (m, 2H), 2.26-2.07 (m, 2H), 1.86-1.14 (m, 17H), 1.03 (t, J=7.2 Hz, 3H), 1.00-0.89 (m, 5H).

EXAMPLE 33(4)

[1887] 1-(thiophen-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-9-(4-cyclopropylmethyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2823

[1888] TLC: Rf 0.61 (chloroform:methanol=10:1);

[1889] NMR (CD3OD): δ 7.42 (d, J=8.7 Hz, 2H), 7.27 (dd, J=5.4, 0.9 Hz, 1H), 7.06-6.97 (m, 3H), 6.91 (dd, J=5.4, 3.6 Hz, 1H), 4.95-4.85 (m, 2H), 4.27 (brs, 2H), 4.14 (dd, J=7.5, 4.5 Hz, 1H), 3.84 (d, J=6.6 Hz, 2H), 3.84-3.66 (m, 2H), 3.51-3.39 (m, 2H), 2.59-2.36 (m, 2H), 2.24-2.07 (m, 2H), 1.84-1.44 (m, 8H), 1.35-1.12 (m, 4H),1.04-0.85 (m, 2H), 0.66-0.57 (m, 2H), 0.38-0.31 (m, 2H).

EXAMPLE 33(5)

[1890] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-cyclopropylmethyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2824

[1891] TLC: Rf 0.61 (chloroform:methanol=10:1);

[1892] NMR (CD3OD): δ 7.42 (d, J=8.4 Hz, 2H), 7.01 (d, J=8.4 Hz, 2H), 4.26 (brs, 2H), 4.03 (dd, J=7.8, 4.8 Hz, 1H), 3.84 (d, J=6.9 Hz, 2H), 3.83-3.66 (m, 2H), 3.51-3.33 (m, 4H), 2.44-2.26 (m, 2H), 2.25-2.06 (m, 2H), 1.82-1.12 (m, 16H), 1.04-0.86 (m, 5H), 0.66-0.57 (m, 2H), 0.38-0.31 (m, 2H).

EXAMPLE 33(6)

[1893] 1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-cyclopropylmethyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2825

[1894] TLC: Rf 0.55 (chloroform:methanol=10:1);

[1895] NMR (CD3OD): δ 7.42 (d, J=8.7 Hz, 2H), 7.01 (d, J=8.7 Hz, 2H), 4.26 (brs, 2H), 4.00 (dd, J=7.8, 4.5 Hz, 1H), 3.84 (d, J=6.9 Hz, 2H), 3.84-3.66 (m, 2H), 3.50-3.33 (m, 4H), 2.43-2.26 (m, 2H), 2.26-2.08 (m, 2H), 1.89-1.43 (m, 5H), 1.43-1.17 (m, 3H), 1.00-0.88 (m, 9H), 0.66-0.58 (m, 2H), 0.38-0.31 (m, 2H).

EXAMPLE 34

[1896] 1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(dimethylamino)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2826

[1897] By the same procedure as described in Example 10 using 4-dimethylaminobenzaldehyde and the compound prepared in Example 9(1), the compound of the present invention having the following physical data was obtained.

[1898] TLC: Rf 0.26 (chloroform:methanol=10:1);

[1899] NMR (CD3OD): δ 7.78 (d, J=8.7 Hz, 2H), 7.59 (d, J=8.7 Hz, 2H), 4.39 (s, 2H), 4.03 (dd, J=7.5, 4.8, Hz, 1H), 3.90-3.70 (m, 2H), 3.52-3.40 (m, 4H), 3.26 (s, 6H), 2.64-2.47 (m, 2H), 2.24-2.04 (m, 2H), 1.82-1.12 (m, 15H), 1.04-0.88 (m, 5H).

EXAMPLE 34(1)

[1900] 1-butyl-2,5-dioxo-3-cyclohexyl methyl-9-(4-(diethylamino) phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2827

[1901] By the same procedure as described in Example 34 using 4-diethylaminobenzaldehyde instead of 4-dimethylaminobenzaldehyde, the compound of the present invention having the following physical data was obtained.

[1902] TLC: Rf 0.28 (chloroform:methanol: acetic acid=10:1);

[1903] NMR (CD3OD): δ 7.94-7.78 (m, 2H), 7.72-7.52 (m, 2H), 4.43 (s, 2H), 4.03 (dd, J=7.5, 4.8, Hz, 1H), 3.92-3.73 (m, 2H), 3.73-3.60 (m, 4H), 3.54-3.40 (m, 4H), 2.63-2.45 (m, 2H), 2.25-2.05 (m, 2H), 1.82-1.10 (m, 21H), 1.04-0.86 (m, 5H).

EXAMPLE 35

[1904] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-benzyloxycarbonyl-1,4,9-triazaspiro[5.5]undecane

2828

[1905] By the same procedure as described in Reference Example 3→Reference Example 6→Example 1 using Resin (3) prepared in Reference Example 2, N-benzyloxycarbonyl-4-piperidone, n-butylamine and N-(t-butyloxycarbonyl)-L-leucine, the compound of the present invention having the following physical data was obtained.

[1906] TLC: Rf 0.67 (chloroform:methanol=20:1);

[1907] NMR (CD3OD): δ 7.35 (m, 5H), 6.50 (brs, 1H), 5.15 (s, 2H), 4.08 (m, 2H), 3.96 (m, 1H), 3.62 (brs, 1H), 3.44(brs, 1H), 3.26 (m, 2H), 1.95-1.76 (m, 4H), 1.61-1.45 (m, 5H), 1.31 (m, 2H), 0.96 (d, J=6.3 Hz, 3H), 0.93 (d, J=6.3 Hz, 3H), 0.91 (t, J=7.2 Hz, 3H).

EXAMPLE 36

[1908] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2829

[1909] By the same procedure as described in Example 9 using the compound prepared in Example 35, the compound of the present invention having the following physical data was obtained.

[1910] TLC: Rf 0.18 (chloroform:methanol=4:1);

[1911] NMR (CD3OD): δ 4.02 (dd, J=7.8, 4.6 Hz, 1H), 3.80 (dd, J=12.5, 4.0 Hz, 1H), 3.72 (dd, J=12.5, 4.0 Hz, 1H), 3.39 (m, 4H), 2.34-2.09 (m, 4H), 1.88-1.50 (m, 5H), 1.37 (m, 2H), 0.96 (t, J=7.5 Hz, 3H), 0.95 (d, J=6.5 Hz, 3H), 0.94 (d, J=6.5 Hz, 3H).

EXAMPLE 37(1)˜37(88)

[1912] By the same procedure as described in Example 10 using the compound prepared in Example 36 and the corresponding aldehyde derivatives, the following compounds of the present invention were obtained.

EXAMPLE 37(1)

[1913] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(3-methyl-4-chlorophenyl)-1-(4-methylphenylmethyl) pyrazol-3-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2830

[1914] TLC: Rf 0.46 (chloroform:methanol=20:1);

[1915] NMR (CD3OD): δ 7.42 (d, J=8.1 Hz, 1H), 7.28 (d, J=1.5 Hz, 1H), 7.19 (dd, J=8.1, 1.5 Hz, 1H), 7.11 (d, J=8.1 Hz, 2H), 6.92 (d, J=8.1 Hz, 2H), 6.65 (s, 1H), 5.35 (s, 2H), 4.40 (s, 2H), 4.02 (dd, J=7.5, 4.5 Hz, 1H), 3.97-3.76 (m, 2H), 3.64-3.52 (m, 2H), 3.46-3.35 (m, 2H), 2.56-2.38 (m, 2H), 2.35 (s, 3H), 2.28 (s, 3H), 2.30-2.10 (m, 2H), 1.91-1.46 (m, 5H), 1.46-1.30 (m, 2H), 0.96 (t, J=6.9 Hz, 3H), 0.95 (d, J=6.3 Hz, 6H).

EXAMPLE 37(2)

[1916] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-dimethylaminophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2831

[1917] TLC: Rf 0.47 (chloroform:methanol=10:1);

[1918] NMR (CD3OD): δ 7.78 (d, J=8.7 Hz, 2H), 7.58 (d, J=8.7 Hz, 2H), 4.40 (s, 2H), 4.01 (dd, J=7.8, 4.5 Hz, 1H), 3.82 (m, 2H), 3.42 (m, 4H), 3.26 (s, 6H), 2.56 (m, 2H), 2.18 (m, 2H), 1.88-1.30 (m, 7H), 0.95 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 37(3)

[1919] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-diethylaminophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2832

[1920] TLC: Rf 0.34 (chloroform:methanol=10:1);

[1921] NMR (CD3OD): δ 7.96-7.82 (m, 2H), 7.74-7.55 (m, 2H), 4.40 (s, 2H), 4.00 (dd, J=7.5, 4.5 Hz, 1H), 3.93-3.60 (m, 6H), 3.55-3.40 (m, 4H), 2.65-2.48 (m, 2H), 2.25-2.06 (m, 2H), 1.89-1.26 (m, 7H), 1.15 (t, J=7.2 Hz, 6H), 1.00-0.87 (m, 9H).

EXAMPLE 37(4)

[1922] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-cyclohexyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2833

[1923] TLC: Rf 0.61 (chloroform:methanol=10:1);

[1924] NMR (CD3OD): δ 7.45-7.42 (m, 2H), 7.02-6.99 (m, 2H), 4.40-4.31 (m, 1H), 4.27 (s, 2H), 4.00 (dd, J=8.0, 4.5 Hz, 1H), 3.83-3.70 (m, 2H), 3.47 (brd, 2H), 3.42-3.35 (m, 2H), 2.43-2.32 (m, 2H), 2.24-2.11 (m, 2H), 2.00-1.93 (m, 2H), 1.86-1.32 (m, 15H), 0.97-0.92 (m, 9H).

EXAMPLE 37(5)

[1925] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-methylphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2834

[1926] TLC: Rf 0.70 (chloroform:methanol=10:1);

[1927] NMR (CD3OD): δ 7.52-7.47 (m, 2H), 7.22-7.19 (m, 2H), 7.04-7.00 (m, 2H), 6.94-6.90 (m, 2H), 4.32 (s, 2H), 4.01 (dd, J=8.0, 4.5 Hz, 1H), 3.86-3.73 (m, 2H), 3.48 (brd, 2H), 3.42-3.34 (m, 2H), 2.45-2.33 (m, 5H), 2.25-2.12 (m, 2H), 1.85-1.48 (m, 5H), 1.41-1.31 (m, 2H), 0.97-0.92 (m, 9H).

EXAMPLE 37(6)

[1928] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-methoxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2835

[1929] TLC: Rf 0.65 (chloroform:methanol=10:1);

[1930] NMR (CD3OD): δ 7.49-7.46 (m, 2H), 7.00-6.94 (m, 6H), 4.31 (s, 2H), 4.01 (dd, J=8.0, 4.5 Hz, 1H), 3.84-3.71 (m, 5H), 3.48 (brd, 2H), 3.40-3.31 (m, 2H), 2.42-2.30 (m, 2H), 2.25-2.12 (m, 2H), 1.83-1.48 (m, 5H), 1.41-1.30 (m, 2H), 0.97-0.92 (m, 9H).

EXAMPLE 37(7)

[1931] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-butyl phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2836

[1932] TLC: Rf 0.35 (chloroform:methanol=10:1);

[1933] NMR (CD3OD): δ 7.46 (d, J=8.1 Hz, 2H), 7.32 (d, J=8.1 Hz, 2H), 4.31 (s, 2H), 4.01 (dd, J=7.8, 4.5 Hz, 1H), 3.84-3.68 (m, 2H), 3.54-3.36 (m, 4H), 2.67 (t, J=7.8 Hz, 2H), 2.48-2.30 (m, 2H), 2.26-2.08 (m, 2H), 1.90-1.28 (m, 11H), 0.96 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H), 0.94 (t, J=7.2 Hz, 3H).

EXAMPLE 37(8)

[1934] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(2-methylpropyl) phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2837

[1935] TLC: Rf 0.38 (chloroform:methanol=10:1);

[1936] NMR (CD3OD): δ 7.47 (d, J=6.9 Hz, 2H),7.30 (d, J=6.9 Hz, 2H), 4.33 (s, 2H), 4.01 (dd, J=7.5, 4.5 Hz, 1H), 3.90-3.70 (m, 2H), 3.56-3.34 (m, 4H), 2.53 (d, J=7.2 Hz, 2H), 2.53-2.30 (m, 2H), 2.24-2.08 (m, 2H), 1.96-1.26 (m, 8H), 0.95 (t, J=7.8 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H), 0.94 (d, J=6.6 Hz, 3H), 0.91 (d, J=6.6 Hz, 6H).

EXAMPLE 37(9)

[1937] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-fluorophenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2838

[1938] TLC: Rf 0.36 (chloroform:methanol=10:1);

[1939] NMR (CD3OD): δ 7.53 (d, J=8.4 Hz, 2H), 7.17 (d, J=8.4 Hz, 2H), 7.16-7.04 (m, 4H), 4.33 (s, 2H), 4.02 (dd, J=7.8, 4.8 Hz, 1H), 3.88-3.68 (m, 2H), 3.58-3.36 (m, 4H), 2.46-2.10 (m, 4H), 1.90-1.24(m, 7H), 0.96 (t, J=6.9 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H), 0.94 (d, J=6.6 Hz, 3H).

EXAMPLE 37(10)

[1940] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-hydroxy-4-methoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2839

[1941] TLC: Rf 0.20 (chloroform:methanol=10:1);

[1942] NMR (CD3OD): δ 7.03-6.94 (m, 3H), 4.23 (s, 2H), 4.01 (dd, J=7.8, 4.5 Hz, 1H), 3.89 (s, 3H), 3.84-3.68 (m, 2H), 3.56-3.36 (m, 4H), 2.42-2.08 (m, 4H), 1.88-1.24(m, 7H), 0.96 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 37(11)

[1943] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-fluorophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2840

[1944] TLC: Rf 0.48 (hexane:ethyl acetate=1:1);

[1945] NMR (CD3OD): δ 7.64-7.54 (m, 2H), 7.37-7.27 (m, 2H), 4.45 (s, 2H), 4.01 (dd, J=7.5, 4.5 Hz, 1H), 3.94-3.81 (m, 2H), 3.54 (m, 2H), 3.36 (m, 2H), 2.38 (m, 2H), 2.19 (m, 2H), 1.82-1.49 (m, 5H), 1.35 (m, 2H), 0.95 (t, J=7.5 Hz, 3H), 0.94 (d, J=6.5 Hz, 3H), 0.93 (d, J=6.5 Hz, 3H).

EXAMPLE 37(12)

[1946] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-fluorophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2841

[1947] TLC: Rf 0.52 (hexane:ethyl acetate=1:1);

[1948] NMR (CD3OD): δ 7.52 (dt, J=8.3, 6.0 Hz, 1H), 7.41-7.37 (m, 2H), 7.26 (t, J=8.3 Hz, 1H), 4.39 (s, 2H), 4.01 (dd, J=7.5, 4.5 Hz, 1H), 3.89-3.76 (m, 2H), 3.50-3.38 (m, 4H), 2.48-2.38 (m, 2H), 2.25-2.12 (m, 2H), 1.84-1.75 (m, 1H), 1.72-1.46 (m, 4H), 1.42-1.28 (m, 2H), 0.99-0.92 (m, 9H).

EXAMPLE 37(13)

[1949] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-fluorophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2842

[1950] TLC: Rf 0.33 (hexane:ethyl acetate=1:1);

[1951] NMR (CD3OD): δ 7.60 (dd, J=8.7, 5.4 Hz, 2H), 7.24 (t, J=8.7 Hz, 2H), 4.36 (s, 2H), 3.99 (dd, J=7.5, 4.5 Hz, 1H), 3.78 (m, 2H), 3.49-3.35 (m, 4H), 2.44-2.13 (m, 4H), 1.84-1.46 (m, 5H), 1.37 (m, 2H), 0.99-0.95 (m, 9H).

EXAMPLE 37(14)

[1952] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-chlorophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2843

[1953] TLC: Rf 0.62 (hexane:ethyl acetate=1:1);

[1954] NMR (CD3OD): δ 7.72 (d, J=7.0 Hz, 1H), 7.60 (dd, J=8.0, 1.5 Hz, 1H), 7.56-7.45 (m, 2H), 4.55 (s, 2H), 4.00 (dd, J=7.5, 4.5 Hz, 1H), 3.94 (m, 2H), 3.55 (m, 2H), 3.42-3.32 (m, 2H), 2.43-2.37 (m, 2H), 2.26-2.13 (m, 2H), 1.85-1.46 (m, 5H), 1.35 (m, 2H), 0.97-0.92 (m, 9H).

EXAMPLE 37(15)

[1955] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-chlorophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2844

[1956] TLC: Rf 0.50 (chloroform:methanol=10:1);

[1957] NMR (CD3OD): δ 7.55 (d, J=8.7 Hz, 2H), 7.51 (d, J=8.7 Hz, 2H), 4.34 (s, 2H), 4.00 (dd, J=7.8, 4.5, Hz, 1H), 3.88-3.68 (m, 2H), 3.51-3.34 (m, 4H), 2.49-2.52 (m, 2H), 2.26-2.08 (m, 2H), 1.90-1.44 (m, 5H), 1.44-1.29 (m, 2H), 1.00-0.89 (m, 9H).

EXAMPLE 37(16)

[1958] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-chlorophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2845

[1959] TLC: Rf 0.55 (chloroform:methanol=20:1);

[1960] NMR (CD3OD): 87.68-7.64 (m, 1H), 7.56-7.45 (m, 3H), 4.37 (s, 2H), 4.00 (dd, J=7.8, 4.5 Hz, 1H), 3.91-3.72 (m, 2H), 3.54-3.32 (m, 4H), 2.53-2.34 (m, 2H), 2.27-2.08 (m, 2H), 1.90-1.44 (m, 5H), 1.44-1.27 (m, 2H), 0.99-0.89 (m, 9H).

EXAMPLE 37(17)

[1961] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-methyl-4-methoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2846

[1962] TLC: Rf 0.34 (chloroform:methanol=20:1);

[1963] NMR (CD3OD): δ 7.38-7.30 (m, 2H), 6.99 (d, J=8.1 Hz, 1H), 4.25 (s, 2H), 4.00 (dd, J=7.8, 4.5 Hz, 1H), 3.85 (s, 3H), 3.85-3.65 (m, 2H), 3.52-3.33 (m, 4H), 2.50-2.30 (m, 2H), 2.22 (s, 3H), 2.20-2.07 (m, 2H), 1.90-1.43 (m, 5H), 1.43-1.28 (m, 2H), 0.99-0.88 (m, 9H).

EXAMPLE 37(18)

[1964] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(7-methoxy-1,3-benzodioxolan-5-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2847

[1965] TLC: Rf 0.36 (chloroform:methanol=20:1);

[1966] NMR (CD3OD): δ 6.85 (d, J=1.8 Hz, 1H), 6.74 (d, J=1.8 Hz, 1H), 5.99 (s, 2H), 4.25 (s, 2H), 4.01 (dd, J=7.8, 4.5 Hz, 1H), 3.92 (s, 3H), 3.87-3.66 (m, 2H), 3.52-3.32 (m, 4H), 2.52-2.34 (m, 2H), 2.26-2.08 (m, 2H), 1.90-1.43 (m, 5H), 1.43-1.29 (m, 2H), 0.99-0.90 (m, 9H).

EXAMPLE 37(19)

[1967] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenylthiophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2848

[1968] TLC: Rf 0.52 (chloroform:methanol=20:1);

[1969] NMR (CD3OD): δ 7.50-7.36 (m, 7H), 7.30 (d, J=8.7 Hz, 2H), 4.31 (s, 2H), 4.00 (dd, J=7.8, 4.5 Hz, 1H), 3.88-3.68 (m, 2H), 3.53-3.32 (m, 4H), 2.50-2.30 (m, 2H), 2.26-2.06 (m, 2H), 1.90-1.42 (m, 5H), 1.42-1.27 (m, 2H), 0.98-0.89 (m, 9H).

EXAMPLE 37(20)

[1970] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-methylphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2849

[1971] TLC: Rf 0.41 (chloroform:methanol=19:1);

[1972] NMR (CD3OD): δ 7.57 (d, J=7.8 Hz, 1H), 7.42-7.28 (m, 3H), 4.41 (s, 2H), 4.01 (dd, J=7.8, 4.8 Hz, 1H), 3.89 (m, 2H), 3.53 (m, 2H), 3.42 (m, 2H), 2.48 (s, 3H), 2.48 (m, 2H), 2.16 (m, 2H), 1.90-1.42 (m, 5H), 1.36 (sextet, J=7.2 Hz, 2H), 0.94 (d, J=6.6 Hz, 3H), 0.94 (t, J=7.2 Hz, 3H), 0.93 (d, J=6.6 Hz, 3H).

EXAMPLE 37(21)

[1973] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-methylphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2850

[1974] TLC: Rf 0.31 (chloroform:methanol=19:1);

[1975] NMR (CD3OD): δ 7.41-7.29 (m, 4H), 4.31 (s, 2H), 4.00 (dd, J=7.8, 4.8 Hz, 1H), 3.79 (m, 2H), 3.52-3.34 (m, 4H), 2.40 (m, 2H), 2.40 (s, 3H), 2.17 (m, 2H), 1.90-1.44 (m, 5H), 1.36 (sextet, J=7.5 Hz, 2H), 0.94 (t, J=7.5 Hz, 3H), 0.94 (d, J=6.6 Hz, 3H), 0.93 (d, J=6.6 Hz, 3H).

EXAMPLE 37(22)

[1976] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-methylphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2851

[1977] TLC: Rf 0.31 (chloroform:methanol=19:1);

[1978] NMR (CD3OD): δ 7.43 (d, J=7.8 Hz, 2H), 7.31 (d, J=7.8 Hz, 2H), 4.31 (s, 2H), 4.00 (dd, J=7.8, 4.8 Hz, 1H), 3.78 (m, 2H), 3.52-3.35 (m, 4H), 2.40 (m, 2H), 2.37 (s, 3H), 2.17 (m, 2H), 1.88-1.44 (m, 5H), 1.36 (sextet, J=7.5 Hz, 2H), 0.94 (t, J=7.5 Hz, 3H), 0.94 (d, J=6.6 Hz, 3H), 0.93 (d, J=6.6 Hz, 3H).

EXAMPLE 37(23)

[1979] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(1-methylethyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2852

[1980] TLC: Rf 0.49 (chloroform:methanol=10:1);

[1981] NMR (CD3OD): δ 7.48 (d, J=8.4 Hz, 2H), 7.38 (d, J=8.4 Hz, 2H), 4.32 (s, 2H), 4.01 (dd, J=7.8, 4.5 Hz, 1H), 3.88-3.70 (m, 2H), 3.54-3.36 (m, 4H), 3.04-2.88 (m, 1H), 2.48-2.30 (m, 2H), 2.28-2.08 (m, 2H), 1.90-1.28(m, 7H), 1.26 (d, J=6.9 Hz, 6H), 0.95 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.9 Hz, 3H), 0.94 (d, J=6.9 Hz, 3H).

EXAMPLE 37(24)

[1982] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-fluoro-4-methoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2853

[1983] TLC: Rf 0.44 (chloroform:methanol=10:1);

[1984] NMR (CD3OD): δ 7.40-7.32 (m, 2H), 7.21 (m, 1H), 4.31 (s, 2H), 4.01 (dd, J=7.5, 4.5 Hz, 1H), 3.92 (s, 3H), 3.86-3.64 (m, 2H), 3.58-3.36 (m, 4H), 2.56-2.32 (m, 2H), 2.28-2.08 (m, 2H), 1.90-1.26(m, 7H), 0.96 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H), 0.94 (d, J=6.6 Hz, 3H).

EXAMPLE 37(25)

[1985] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(2-hydroxyethyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2854

[1986] TLC: Rf 0.22 (chloroform:methanol=10:1);

[1987] NMR (CD3OD): δ 7.48 (d, J=8.7 Hz, 2H), 7.07 (d, J=8.7 Hz, 2H), 4.29 (s, 2H), 4.09 (t, J=5.1 Hz, 2H), 4.01 (dd, J=7.5, 4.5 Hz, 1H), 3.88 (t, J=5.1 Hz, 2H), 3.86-3.64 (m, 2H), 3.54-3.36 (m, 4H), 2.50-2.30 (m, 2H), 2.26-2.08 (m, 2H), 1.90-1.24(m, 7H), 0.96 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H), 0.94 (d, J=6.6 Hz, 3H).

EXAMPLE 37(26)

[1988] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-hydroxy-3-methylphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2855

[1989] TLC: Rf 0.66 (chloroform:methanol=10:1);

[1990] NMR (CD3OD): δ 7.24 (d, J=7.7 Hz, 2H), 6.89 (t, J=7.7 Hz, 1H), 4.36 (s, 2H), 4.02 (dd, J=7.5, 4.5 Hz, 1H), 3.95-3.76 (m, 2H), 3.58-3.36 (m, 4H), 2.44-2.08 (m, 4H), 2.89 (s, 3H), 1.90-1.24(m, 7H), 0.96 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H), 0.94 (d, J=6.6 Hz, 3H).

EXAMPLE 37(27)

[1991] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-trifluoromethyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2856

[1992] TLC: Rf 0.49 (chloroform:methanol=10:1);

[1993] NMR (CD3OD): δ 7.71 (d, J=7.8 Hz, 2H), 7.42 (d, J=7.8 Hz, 2H), 4.41 (s, 2H), 4.01 (dd, J=7.8, 4.8 Hz, 1H), 3.90-3.72 (m, 2H), 3.56-3.36 (m, 4H), 2.56-2.36 (m, 2H), 2.26-2.08 (m, 2H), 1.90-1.28(m, 7H), 0.95 (t, J=7.5 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 37(28)

[1994] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-methyl-5-chloro-1-phenyl pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2857

[1995] TLC: Rf 0.39 (chloroform:methanol=10:1);

[1996] NMR (CD3OD): δ 7.59-7.50 (m, 5H), 4.35 (s, 2H), 4.03 (dd, J=7.8, 4.5 Hz, 1H), 3.98-3.80 (m, 2H), 3.72-3.58 (m, 2H), 3.46-3.38 (m, 2H), 2.58-2.38 (m, 2H), 2.45 (s, 3H), 2.36-2.18 (m, 2H), 1.92-1.24 (m, 7H), 0.97 (t, J=7.5 Hz, 3H), 0.96 (d, J=6.6 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H).

EXAMPLE 37(29)

[1997] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-phenylpyridin-3-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2858

[1998] TLC: Rf 0.28 (chloroform:methanol=10:1);

[1999] NMR (CD3OD): δ 9.17 (s, 1H), 8.80 (m, 1H), 8.39 (m, 1H), 8.03-7.97 (m, 2H), 7.73-7.65 (m, 3H), 4.65 (s, 2H), 4.03 (dd, J=7.2, 4.2 Hz, 1H), 4.02-3.82 (m, 2H), 3.64-3.42 (m, 2H), 3.78-3.56 (m, 2H), 2.30-2.08 (m, 2H), 1.88-1.24 (m, 7H), 0.96 (d, J=6.3 Hz, 3H), 0.95 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H).

EXAMPLE 37(30)

[2000] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-methylsulfonylaminophenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2859

[2001] TLC: Rf 0.18 (chloroform:methanol=10:1);

[2002] NMR (CD3OD): δ 7.54 (d, J=8.7 Hz, 2H), 7.30 (d, J=9.0 Hz, 2H), 7.08 (d, J=8.7 Hz, 2H), 7.04 (d, J=9.0 Hz, 2H), 4.34 (s, 2H), 4.02 (dd, J 7.8, 4.5 Hz, 1H), 3.88-3.68 (m, 2H), 3.56-3.35 (m, 4H), 2.96 (s, 3H), 2.50-2.08 (m, 4H), 1.88-1.26 (m, 7H), 0.96 (t, J=6.9 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H), 0.94 (d, J=6.6 Hz, 3H).

EXAMPLE 37(31)

[2003] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-methylsulfonylaminophenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2860

[2004] TLC: Rf 0.15 (chloroform:methanol=10:1);

[2005] NMR (CD3OD): δ 7.49 (d, J=8.7 Hz, 2H), 7.43 (d, J=8.7 Hz, 2H), 4.33 (s, 2H), 4.03 (dd, J=7.8, 4.8 Hz, 1H), 3.96-3.76 (m, 2H), 3.66-3.58 (m, 2H), 3.56-3.42 (m, 2H), 3.05 (s, 3H), 2.68-2.46 (m, 2H), 2.44 (s, 3H), 2.41 (s, 3H), 2.32-2.10 (m, 2H), 1.90-1.28 (m, 7H), 0.97 (t, J=6.6 Hz, 3H), 0.96 (d, J=6.3 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H).

EXAMPLE 37(32)

[2006] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(5-methylpyridin-2-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2861

[2007] TLC: Rf 0.29 (chloroform:methanol=10:1);

[2008] NMR (CD3OD): b 8.12 (s, 1H), 7.93 (d, J=8.4 Hz, 1H), 7.68 (d, J=8.7 Hz, 2H), 7.30 (d, J=8.7 Hz, 2H), 7.06 (d, J=8.4 Hz, 1H), 4.40 (s, 2H), 4.03 (dd, J=7.8, 4.8 Hz, 1H), 3.94-3.76 (m, 2H), 3.58-3.40 (m, 4H), 2.56-2.36 (m, 2H), 2.38 (s, 3H), 2.30-2.08 (m, 2H), 1.88-1.24 (m, 7H), 0.96 (t, J=7.8 Hz, 3H), 0.96 (d, J=6.6 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H).

EXAMPLE 37(33)

[2009] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(6-methylpyridin-1-oxide-3-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2862

[2010] TLC: Rf 0.24 (chloroform:methanol=10:1);

[2011] NMR (CD3OD): δ 8.47 (s, 1H), 7.71 (d, J=8.7 Hz, 2H), 7.62-7.48 (m, 2H), 7.29 (d, J=8.7 Hz, 2H), 4.40 (s, 2H), 4.02 (dd, J=7.8, 4.5 Hz, 1H), 3.92-3.72 (m, 2H), 3.58-3.38 (m, 4H), 2.64-2.40 (m, 2H), 2.60 (s, 3H), 2.28-2.10 (m, 2H), 1.90-1.28 (m, 7H), 0.96 (t, J=7.8 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H), 0.94 (d, J=6.6 Hz, 3H).

EXAMPLE 37(34)

[2012] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(1-(2-methylpropyloxycarbonyl)indol-5-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2863

[2013] TLC: Rf 0.23 (chloroform:methanol=10:1);

[2014] NMR (CD3OD): δ 8.16 (d, J=8.4 Hz, 1H), 7.82 (d, J=1.5 Hz, 1H), 7.78 (d, J=3.6 Hz, 1H), 7.50 (dd, J=8.4, 1.5 Hz, 1H), 6.75 (d, J=3.6 Hz, 1H), 4.46 (s, 2H), 4.27 (d, J=6.6 Hz, 2H), 4.01 (dd, J=7.8, 4.5 Hz, 1H), 3.82-3.74 (m, 2H), 3.58-3.36 (m, 4H), 2.48-2.30 (m, 2H), 2.26-2.08 (m, 3H), 1.88-1.24 (m, 7H), 1.09 (s, 3H), 1.06 (s, 3H), 0.95 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 37(35)

[2015] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-phenyl-5-methyloxazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2864

[2016] TLC: Rf 0.32 (chloroform:methanol=10:1);

[2017] NMR (CD3OD): δ 8.05-8.02 (m, 2H), 7.52-7.50 (m, 3H), 4.35 (s, 2H), 4.02 (dd, J=7.8, 4.5 Hz, 1H), 3.98-3.80 (m, 2H), 3.70-3.58 (m, 2H), 3.44-3.38 (m, 2H), 2.53 (s, 3H), 2.53-2.36 (m, 2H), 2.34-2.14 (m, 2H), 1.90-1.26 (m, 7H), 0.96 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 37(36)

[2018] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(tetrahydropyran-4-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2865

[2019] TLC: Rf 0.33 (chloroform:methanol=10:1);

[2020] NMR (CD3OD): δ 7.47 (d, J=8.4 Hz, 2H), 7.07 (d, J=8.4 Hz, 2H), 4.64 (m, 1H), 4.29 (s, 2H), 4.01 (dd, J=7.5, 4.5 Hz, 1H), 3.98-3.91 (m, 2H), 3.84-3.68 (m, 2H), 3.64-3.56 (m, 2H), 3.50-3.37 (m, 4H), 2.50-2.30 (m, 2H), 2.24-1.98 (m, 4H), 1.88-1.26 (m, 9H), 0.95 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 37(37)

[2021] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(6-methylpyridin-3-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2866

[2022] TLC: Rf 0.22 (chloroform:methanol=10:1);

[2023] NMR (CD3OD): δ 8.55 (d, J=2.7 Hz, 1H), 8.10 (dd, J=9.0, 2.7 Hz, 1H), 7.84 (d, J=9.0 Hz, 1H), 7.72 (d, J=8.7 Hz, 2H), 7.29 (d, J=8.7 Hz, 2H), 4.40 (s, 2H), 4.02 (dd, J=7.8, 4.5 Hz, 1H), 3.94-3.70 (m, 2H), 3.58-3.38 (m, 4H), 2.74 (s, 3H), 2.60-2.42 (m, 2H), 2.28-2.08 (m, 2H), 1.90-1.26 (m, 7H), 0.96 (t, J=7.5 Hz, 3H), 0.96 (d, J=6.6 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H).

EXAMPLE 37(38)

[2024] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-fluorophenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2867

[2025] TLC: Rf 0.58 (chloroform:methanol=10:1);

[2026] NMR (CD3OD): δ 7.55-7.46 (m, 2H), 7.36-7.25 (m, 2H), 4.30 (s, 2H), 4.02 (dd, J=7.8, 4.5 Hz, 1H), 3.95-3.73 (m, 2H), 3.66-3.55 (m, 2H), 3.52-3.40 (m, 2H), 2.63-2.45 (m, 2H), 2.39 (s, 3H), 2.37 (s, 3H), 2.30-2.10 (m, 2H), 1.90-1.43 (m, 5H), 1.43-1.30 (m, 2H), 0.99-0.91 (m, 9H).

EXAMPLE 37(39)

[2027] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(pyridin-2-yl) pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2868

[2028] TLC: Rf 0.52 (chloroform:methanol=10:1);

[2029] NMR (CD3OD): δ 8.55 (d, J=4.8 Hz, 1H), 8.12 (dd, J=8.4, 7.2 Hz, 1H), 7.87 (d, J=8.4 Hz, 1H), 7.50 (dd, J=7.2, 4.8 Hz, 1H), 4.32 (s, 2H), 4.02 (dd, J=7.8, 4.5 Hz, 1H), 3.96-3.73 (m, 2H), 3.67-3.55 (m, 2H), 3.54-3.40 (m, 2H), 2.69 (s, 3H), 2.70-2.48 (m, 2H), 2.44 (s, 3H), 2.28-2.08 (m, 2H), 1.92-1.43 (m, 5H), 1.43-1.26 (m, 2H), 0.99-0.90 (m, 9H).

EXAMPLE 37(40)

[2030] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-hydroxyphenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2869

[2031] TLC: Rf 0.48 (chloroform:methanol=10:1);

[2032] NMR (CD3OD): δ 7.30 (d, J=9.0 Hz, 2H), 6.95 (d, J=9.0 Hz, 2H),4.33 (s, 2H), 4.02 (dd, J=7.5, 4.5 Hz, 1H), 3.92-3.77 (m, 2H), 3.61 (m, 2H), 3.47 (m, 2H), 2.58 (m, 2H), 2.45 (s, 3H), 2.36 (s, 3H), 2.20 (m, 2H), 1.88-1.76 (m, 1H), 1.73-1.32 (m, 6H), 0.96 (t, J=7.5 Hz, 3H), 0.95 (d, J=6.5 Hz, 3H), 0.94 (d, J=6.5 Hz, 3H).

EXAMPLE 37(41)

[2033] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(2-carboxyethyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2870

[2034] TLC: Rf 0.38 (chloroform:methanol=10:1);

[2035] NMR (CD3OD): δ 7.47 (d, J=8.0 Hz, 2H), 7.37 (d, J=8.0 Hz, 2H),4.31 (s, 2H), 4.00 (dd, J=7.5, 4.5 Hz, 1H), 3.86-3.73 (m, 2H), 3.49-3.35 (m, 4H), 2.96 (t, J=7.5 Hz, 2H), 2.62 (t, J=7.5 Hz, 2H), 2.44-2.33 (m, 2H), 2.23-2.11 (m, 2H), 1.84-1.32 (m, 7H), 0.94 (t, J=7.5 Hz, 3H), 0.94 (d, J=6.5 Hz, 3H), 0.93 (d, J=6.5 Hz, 3H).

EXAMPLE 37(42)

[2036] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-(dimethylaminosulfonyl)phenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2871

[2037] TLC: Rf 0.54 (chloroform:methanol=9:1);

[2038] NMR (CD3OD): δ 7.96 (d, J=8.7 Hz, 2H), 7.77 (d, J=8.7 Hz, 2H), 4.32 (s, 2H), 4.02 (dd, J=7.8, 4.8 Hz, 1H), 3.95-3.75 (m, 2H), 3.66-3.56 (m, 2H), 3.47 (m, 2H), 2.74 (s, 6H), 2.56 (m, 2H), 2.48 (s, 3H), 2.41 (s, 3H), 2.30-2.12 (m, 2H), 1.90-1.46 (m, 5H), 1.38 (sextet, J=7.2 Hz, 2H), 0.98-0.93 (m, 9H).

EXAMPLE 37(43)

[2039] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(5-methylpyridin-1-oxide-2-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2872

[2040] TLC: Rf 0.41 (chloroform:methanol=9:1);

[2041] NMR (CD3OD): δ 7.77 (brs, 1H), 7.65-7.59 (m, 2H), 7.56 (dd, J=9.3, 2.4 Hz, 1H), 7.03-6.97 (m, 2H), 6.73 (d, J=9.3 Hz, 1H), 4.33 (s, 2H), 4.00 (dd, J=7.8, 4.8 Hz, 1H), 3.86-3.68 (m, 2H), 3.51-3.36 (m, 4H), 2.46 (m, 2H), 2.25-2.07 (m, 2H), 2.18 (s, 3H), 1.90-1.44 (m, 5H), 1.36 (sextet, J=7.2 Hz, 2H), 0.97-0.91 (m, 9H).

EXAMPLE 37(44)

[2042] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(2-carboxy-1-ethenyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2873

[2043] TLC: Rf 0.20 (chloroform:methanol=10:1);

[2044] NMR (CD3OD): δ 7.75 (d, J=8.4 Hz, 2H), 7.70 (d, J=16.2 Hz, 1H), 7.61 (d, J=8.4 Hz, 2H), 6.58 (d, J=16.2 Hz, 2H), 4.39 (s, 2H), 4.02 (dd, J=7.8, 4.5 Hz, 1H), 3.92-3.74 (m, 2H), 3.58-3.36 (m, 4H), 2.50-2.32 (m, 2H), 2.30-2.10 (m, 2H), 1.90-1.24 (m, 7H), 0.96 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 37(45)

[2045] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-(2-carboxy-1-ethenyl)phenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2874

[2046] TLC: Rf 0.34 (chloroform:methanol=10:1);

[2047] NMR (CD3OD): δ 7.69-7.57 (m, 5H), 7.14 (d, J=8.4 Hz, 2H), 7.05 (d, J=8.7 Hz, 2H), 6.42 (d, J=15.9 Hz, 1H), 4.36 (s, 2H), 4.01 (dd, J=7.8, 4.5 Hz, 1H), 3.92-3.70 (m, 2H), 3.56-3.35 (m, 4H), 2.48-2.30 (m, 2H), 2.30-2.12 (m, 2H), 1.88-1.25 (m, 7H), 0.98-0.88 (m, 9H).

EXAMPLE 37(46)

[2048] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-aminocarbonylphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2875

[2049] TLC: Rf 0.38 (chloroform:methanol=10:1);

[2050] NMR (CD3OD): δ 7.90 (d, J=8.7 Hz, 2H), 7.60 (d, J=8.7 Hz, 2H), 7.15 (d, J=8.7 Hz, 2H), 7.07 (d, J=8.7 Hz, 2H), 4.36 (s, 2H), 4.01 (dd, J=7.8, 4.5, Hz, 1H), 3.90-3.70 (m, 2H), 3.58-3.35 (m, 4H), 2.54-2.36 (m, 2H), 2.30-2.10 (m, 2H), 1.90-1.26 (m, 7H), 1.00-0.86 (m, 9H).

EXAMPLE 37(47)

[2051] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-aminosulfonylphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2876

[2052] TLC: Rf 0.41 (chloroform:methanol=10:1);

[2053] NMR (CD3OD): δ 7.90 (d, J=8.7 Hz, 2H), 7.57 (d, J=8.7 Hz, 2H), 7.17 (d, J=8.7 Hz, 2H), 7.13 (d, J=8.7 Hz, 2H), 4.28 (brs, 2H), 4.01 (dd, J=7.8, 4.5, Hz, 1H), 3.83-3.60 (m, 2H), 3.49-3.34 (m, 4H), 2.44-2.26 (m, 2H), 2.26-2.09 (m, 2H), 1.89-1.26 (m, 7H), 1.00-0.88 (m, 9H).

EXAMPLE 37(48)

[2054] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-benzylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2877

[2055] TLC: Rf 0.40 (chloroform:methanol=10:1);

[2056] NMR (CD3OD): δ 7.41-7.33 (m, 3H), 7.21-7.19 (m, 2H), 5.45 (s, 2H), 4.30 (s, 2H), 4.01 (dd, J=7.5, 4.5 Hz, 1H), 3.89-3.73 (m, 2H), 3.60-3.46 (m, 4H), 2.61 (m, 2H), 2.48 (s, 3H), 2.46 (s, 3H), 2.23-2.11 (m, 2H), 1.87-1.31 (m, 7H), 0.95 (t, J=7.0 Hz, 3H), 0.94 (d, J=6.5 Hz, 3H), 0.93 (d, J=6.5 Hz, 3H).

EXAMPLE 37(49)

[2057] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(2,4-difluorophenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2878

[2058] TLC: Rf 0.40 (chloroform:methanol=10:1);

[2059] NMR (CD3OD): 87.61-7.53 (m, 1H), 7.33-7.26 (m, 1H), 7.23-7.16 (m, 1H),4.31 (s, 2H), 4.02 (dd, J=7.5, 4.5 Hz, 1H), 3.92-3.76 (m, 2H), 3.63-3.56 (m, 2H), 3.49-3.45 (m, 2H), 2.57 (m, 2H), 2.40 (s, 3H), 2.29 (s, 3H), 2.19 (m, 2H), 1.86-1.34 (m, 7H), 0.96 (t, J=7.0 Hz, 3H), 0.95 (d, J=6.5 Hz, 3H), 0.94 (d, J=6.5 Hz, 3H).

EXAMPLE 37(50)

[2060] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(pyrrolidin-1-ylmethyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2879

[2061] TLC: Rf 0.10 (chloroform:methanol=10:1);

[2062] NMR (CD3OD): δ 7.75 (d, J=8.4 Hz, 2H), 7.65 (d, J=8.4 Hz, 2H), 4.43 (s, 2H), 4.40 (s, 2H), 4.00 (dd, J 7.5, 4.5 Hz, 1H), 3.92-3.70 (m, 2H), 3.56-3.40 (m, 6H), 3.25-3.12 (m, 2H), 2.68-2.48 (m, 2H), 2.28-1.95 (m, 6H), 1.88-1.42 (m, 5H), 1.42-1.30 (m, 2H), 0.98-0.90 (m, 9H).

EXAMPLE 37(51)

[2063] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-(morpholin-4-ylsulfonyl)phenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2880

[2064] TLC: Rf 0.43 (chloroform:methanol=20:1);

[2065] NMR (CD3OD): δ 7.95 (d, J=8.7 Hz, 2H), 7.80 (d, J=8.7 Hz, 2H), 4.32 (s, 2H), 4.02 (dd, J=7.8, 4.8 Hz, 1H), 3.95-3.72 (m, 2H), 3.76-3.67 (m, 4H), 3.66-3.57 (m, 2H), 3.56-3.42 (m, 2H), 3.08-2.95 (m, 4H), 2.70-2.50 (m, 2H), 2.50 (s, 3H), 2.42 (s, 3H), 2.31-2.10 (m, 2H), 1.90-1.44 (m, 5H), 1.44-1.30 (m, 2H), 1.00-0.91 (m, 9H).

EXAMPLE 37(52)

[2066] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-(methylaminosulfonyl)phenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2881

[2067] TLC: Rf 0.21 (chloroform:methanol=10:1);

[2068] NMR (CD3OD): δ 8.01 (d, J=8.4 Hz, 2H), 7.73 (d, J=8.4 Hz, 2H), 4.34 (s, 2H), 4.04 (dd, J=7.8, 4.8 Hz, 1H), 3.98-3.78 (m, 2H), 3.66-3.58 (m, 2H), 3.44-3.30 (m, 2H), 2.59 (s, 3H), 2.54-2.38 (m, 2H), 2.47 (s, 3H), 2.40 (s, 3H), 2.36-2.16 (m, 2H), 1.90-1.26 (m, 7H), 0.97 (t, J=7.5 Hz, 3H), 0.96 (d, J=6.6 Hz, 6H).

EXAMPLE 37(53)

[2069] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-cyanophenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2882

[2070] TLC: Rf 0.30 (chloroform:methanol=10:1);

[2071] NMR (CD3OD): δ 7.75 (d, J=8.4 Hz, 2H), 7.66 (d, J=8.7 Hz, 2H), 7.21 (d, J=8.4 Hz, 2H), 7.14 (d, J=8.7 Hz, 2H), 4.39 (s, 2H), 4.02 (dd, J=7.8, 4.5 Hz, 1H), 3.94-3.72 (m, 2H), 3.58-3.36 (m, 4H), 2.58-2.38 (m, 2H), 2.28-2.08 (m, 2H), 1.88-1.24 (m, 7H), 0.96 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 37(54)

[2072] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(dimethylaminomethyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2883

[2073] TLC: Rf 0.16 (chloroform:methanol=10:1);

[2074] NMR (CD3OD): δ 7.76 (d, J=8.1 Hz, 2H), 7.63 (d, J=8.1 Hz, 2H), 4.41 (s, 2H), 4.37 (s, 2H), 4.00 (dd, J=7.8, 4.8 Hz, 1H), 3.90-3.72 (m, 2H), 3.50-3.42 (m, 4H), 2.87 (s, 6H), 2.65-2.50 (m, 2H), 2.22-2.04 (m, 2H), 1.88-1.32 (m, 7H), 0.97-0.92 (m, 9H).

EXAMPLE 37(55)

[2075] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-(2-dimethylaminoethylaminosulfonyl)phenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.3 hydrochloride

2884

[2076] TLC: Rf 0.13 (chloroform:methanol=10:1);

[2077] NMR (CD3OD): δ 8.07 (d, J=8.7 Hz, 2H), 7.78 (d, J=8.7 Hz, 2H), 4.31 (s, 2H), 4.01 (dd, J=8.1, 5.1 Hz, 1H), 3.95-3.74 (m, 2H), 3.68-3.45 (m, 4H), 3.40-3.20 (m, 4H), 2.95 (s, 6H), 2.70-2.50 (m, 2H), 2.49 (s, 3H), 2.41 (s, 3H), 2.28-2.12 (m, 2H), 1.88-1.34 (m, 7H), 0.98-0.92 (m, 9H).

EXAMPLE 37(56)

[2078] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-(4-hydroxyphenyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2885

[2079] TLC: Rf 0.53 (chloroform:methanol=10:1);

[2080] NMR (CD3OD): δ 7.81 (s, 1H), 7.69 (d, J=7.5 Hz, 1H), 7.53 (d, J=9.0 Hz, 2H), 7.55-7.48 (m, 1H), 7.45 (d, J=7.5 Hz, 1H), 6.87 (d, J=9.0 Hz, 2H), 4.40 (s, 2H), 4.00 (dd, J=7.5, 4.5 Hz, 1H), 3.94-3.73 (m, 2H), 3.56-3.44 (m, 2H), 3.44-3.30 (m, 2H), 2.53-2.33 (m, 2H), 2.26-2.08 (m, 2H), 1.90-1.40 (m, 5H), 1.43-1.25 (m, 2H), 0.94 (d, J=6.3 Hz, 3H), 0.94 (t, J=7.2 Hz, 3H), 0.93 (d, J=6.3 Hz, 3H).

EXAMPLE 37(57)

[2081] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(3-methoxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2886

[2082] TLC: Rf 0.54 (chloroform:methanol=10:1);

[2083] NMR (CD3OD): δ 7.53 (d, J=8.5 Hz, 2H), 7.28 (t, J=8.3 Hz, 1H), 7.07 (d, J=8.5 Hz, 2H), 6.75 (ddd, J=8.3, 2.3, 1.0 Hz, 1H), 6.60-6.57 (m, 2H), 4.33 (s, 2H), 4.01 (dd, J=7.5, 4.5 Hz, 1H), 3.86-3.73 (m, 2H), 3.77 (s, 3H), 3.51-3.34 (m, 4H), 2.41 (m, 2H), 2.42-2.12 (m, 2H), 1.84-1.33 (m, 7H), 0.95 (t, J=7.2 Hz, 3H), 0.94 (d, J=6.5 Hz, 3H), 0.93 (d, J=6.5 Hz, 3H).

EXAMPLE 37(58)

[2084] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(quinoxalin-2-yl) pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2887

[2085] TLC: Rf 0.52 (chloroform:methanol=10:1);

[2086] NMR (CD3OD): δ 9.51 (s, 1H), 8.12 (d, J=8.0 Hz, 1H),8.04 (d, J=8.0 Hz, 1H), 7.90-7.80 (m, 2H), 4.37 (s, 2H), 4.02 (dd, J=7.5, 4.5 Hz, 1H), 3.96-3.81 (m, 2H), 3.63 (m, 2H), 3.44 (m, 2H), 2.92 (s, 3H), 2.47 (s, 3H), 2.47 (m, 2H), 2.29-2.17 (m, 2H), 1.86-1.33 (m, 7H), 0.95 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.5 Hz, 3H), 0.94 (d, J=6.5 Hz, 3H).

EXAMPLE 37(59)

[2087] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenylcarbonylphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2888

[2088] TLC: Rf 0.76 (chloroform:methanol=10:1);

[2089] NMR (CD3OD): δ 7.88 (d, J=8.4 Hz, 2H), 7.81-7.67 (m, 5H), 7.57-7.52 (m, 2H), 4.49 (s, 2H), 4.01 (dd, J=8.1, 4.8 Hz, 1H), 4.00-3.78 (m, 2H), 3.59-3.48 (m, 2H), 3.44-3.35 (m, 2H), 2.50-2.32 (m, 2H), 2.32-2.14 (m, 2H), 1.88-1.24 (m, 7H), 1.02-0.88 (m, 9H).

EXAMPLE 37(60)

[2090] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-(N-(2-hydroxyethyl)-N-methylaminosulfonyl)phenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2889

[2091] TLC: Rf 0.34 (chloroform:methanol=10:1);

[2092] NMR (CD3OD): δ 8.00 (d, J=8.7 Hz, 2H), 7.76 (d, J=8.7 Hz, 2H), 4.34 (s, 2H), 4.04 (dd, J=7.8, 4.5 Hz, 1H), 3.98-3.76 (m, 2H), 3.70 (t, J=5.7 Hz, 2H), 3.68-3.58 (m, 2H), 3.50-3.38 (m, 2H), 3.20 (t, J=5.7 Hz, 2H), 2.88 (s, 3H), 2.58-2.38 (m, 2H), 2.48 (s, 3H), 2.41 (s, 3H), 2.36-2.16 (m, 2H), 1.90-1.24 (m, 7H), 0.97 (t, J=6.9 Hz, 3H), 0.96 (d, J=6.3 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H).

EXAMPLE 37(61)

[2093] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(2-phenylethyl) pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2890

[2094] TLC: Rf 0.24 (chloroform:methanol=10:1);

[2095] NMR (CD3OD): δ 7.31-7.23 (m, 3H), 7.10 (d, J=6.6 Hz, 2H), 4.44 (t, J=6.3 Hz, 2H), 4.21 (s, 2H), 4.03 (dd, J=7.8, 4.8 Hz, 1H), 3.82-3.60 (m, 2H), 3.58-3.32 (m, 4H), 3.13 (t, J=6.3 Hz, 2H), 2.72-2.52 (m, 2H), 2.50 (s, 3H), 2.24-2.04 (m, 2H), 1.99 (s, 3H), 1.90-1.36 (m, 7H), 0.97 (t, J=7.2 Hz, 3H), 0.96 (d, J=6.6 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H).

EXAMPLE 37(62)

[2096] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(1,3,5-trimethylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2891

[2097] TLC: Rf 0.43 (chloroform:methanol=10:1);

[2098] NMR (CD3OD): δ 4.28 (s, 2H), 4.00 (dd, J=7.8, 4.8 Hz, 1H), 3.87 (s, 3H), 3.87-3.69 (m, 2H), 3.60-3.43 (m, 4H), 2.69-2.50 (m, 2H), 2.46 (s, 3H), 2.44 (s, 3H), 2.26-2.08 (m, 2H), 1.90-1.28 (m, 7H), 0.98-0.85 (m, 9H).

EXAMPLE 37(63)

[2099] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(morpholin-4-ylmethyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2892

[2100] TLC: Rf 0.56 (chloroform:methanol=10:1);

[2101] NMR (CD3OD): δ 7.74 (d, J=8.4 Hz, 2H), 7.66 (d, J=8.4 Hz, 2H), 4.40 (s, 4H), 4.00 (dd, J=7.5, 4.5 Hz, 1H), 4.10-3.70 (m, 6H), 3.54-3.42 (m, 4H), 3.40-3.16 (m, 4H), 2.65-2.46 (m, 2H), 2.24-2.03 (m, 2H), 1.88-1.28 (m, 7H), 1.02-0.88 (m, 9H).

EXAMPLE 37(64)

[2102] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-methylpiperazin-1-ylmethyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.3 Hydrochloride

2893

[2103] TLC: Rf 0.64 (chloroform:methanol=5:1);

[2104] NMR (CD3OD): δ 7.45 (m, 4H), 4.55 (s, 2H), 4.42 (s, 2H), 4.01 (dd, J=7.5, 4.5 Hz, 1H), 3.88-3.56 (m, 10H), 3.53-3.43 (m, 4H), 3.01 (s, 3H), 2.59-2.47 (m, 2H), 2.22-2.09 (m, 2H), 1.85-1.33 (m, 7H), 0.94 (t, J=7.2 Hz, 3H), 0.94 (d, J=6.5 Hz, 3H), 0.93 (d, J=6.5 Hz, 3H).

EXAMPLE 37(65)

[2105] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenylsulfonylphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2894

[2106] TLC: Rf 0.70 (ethyl acetate:methanol=9:1);

[2107] NMR (CD3OD): δ 8.08 (d, J=8.4 Hz, 2H), 8.02-7.96 (m, 2H), 7.80 (d, J=8.4 Hz, 2H), 7.70-7.55 (m, 3H), 4.43 (s, 2H), 3.99 (dd, J=7.8, 4.8 Hz, 1H), 3.91-3.72 (m, 2H), 3.48-3.34 (m, 4H), 2.48-2.32 (m, 2H), 2.23-2.06 (m, 2H), 1.88-1.43 (m, 5H), 1.34 (sextet, J=7.2 Hz, 2H), 0.96-0.90 (m, 9H).

EXAMPLE 37(66)

[2108] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-cyclohexylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2895

[2109] TLC: Rf 0.28 (ethyl acetate: methanol=9:1);

[2110] NMR (CD3OD): δ 4.35-4.20 (m, 3H), 4.01 (dd, J=7.8, 4.8 Hz, 1H), 3.90-3.68 (m, 2H), 3.58-3.41 (m, 4H), 2.60-2.46 (m, 2H), 2.45 (s, 3H), 2.40 (s, 3H), 2.26-2.08 (m, 2H), 1.98-1.26 (m, 17H), 0.98-0.91 (m, 9H).

EXAMPLE 37(67)

[2111] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(3-carboxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2896

[2112] TLC: Rf 0.11 (ethyl acetate: methanol 9:1);

[2113] NMR (CD3OD): δ 7.83 (ddd, J=7.8, 1.5, 0.9 Hz, 1H), 7.61 (dd, J=2.4, 1.5 Hz, 1H), 7.58 (d, J=8.7 Hz, 2H), 7.51 (t, J=7.8 Hz, 1H), 7.29 (ddd, J=7.8, 2.4, 0.9 Hz, 1H), 7.11 (d, J=8.7 Hz, 2H), 4.35 (s, 2H), 4.01 (dd, J=7.8, 4.8 Hz, 1H), 3.90-3.72 (m, 2H), 3.57-3.36 (m, 4H), 2.50-2.34 (m, 2H), 2.28-2.09 (m, 2H), 1.89-1.44 (m, 5H), 1.36 (sextet, J=7.2 Hz, 2H), 0.98-0.91 (m, 9H).

EXAMPLE 37(68)

[2114] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(piperidin-1-ylmethyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2897

[2115] TLC: Rf 0.52 (chloroform:methanol=9:1);

[2116] NMR (CD3OD): δ 7.75 (d, J=8.4 Hz, 2H), 7.65 (d, J=8.4 Hz, 2H), 4.41 (s, 2H), 4.34 (s, 2H), 4.00 (dd, J=7.8, 4.5 Hz, 1H), 3.91-3.71 (m, 2H), 3.54-3.41 (m, 6H), 3.05-2.91 (m, 2H), 2.67-2.49 (m, 2H), 2.25-2.05 (m, 2H), 2.00-1.28 (m, 13H), 0.98-0.91 (m, 9H).

EXAMPLE 37(69)

[2117] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-(pyrrolidin-1-ylsulfonyl)phenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2898

[2118] TLC: Rf 0.36 (ethyl acetate: methanol=9:1);

[2119] NMR (CD3OD): δ 8.01 (d, J=8.7 Hz, 2H), 7.76 (d, J=8.7 Hz, 2H), 4.32 (s, 2H), 4.02 (dd, J=7.8, 4.8 Hz, 1H), 3.95-3.74 (m, 2H), 3.66-3.55 (m, 2H), 3.50-3.40 (m, 2H), 3.34-3.24 (m, 4H), 2.62-2.47 (m, 2H), 2.48 (s, 3H), 2.40 (s, 3H), 2.30-2.11 (m, 2H), 1.90-1.45 (m, 9H), 1.38 (sextet, J=7.2 Hz, 2H), 1.00-0.90 (m, 9H).

EXAMPLE 37(70)

[2120] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2,3-dihydrobenzofuran-5-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2899

[2121] TLC: Rf 0.56 (ethyl acetate: methanol=9:1);

[2122] NMR (CD3OD): δ 7.40 (brs, 1H), 7.26 (dd, J=8.1, 1.8 Hz, 1H), 6.80 (d, J=8.1 Hz, 1H), 4.59 (t, J=8.7 Hz, 2H), 4.26 (s, 2H), 4.00 (dd, J=7.8, 4.8 Hz, 1H), 3.84-3.66 (m, 2H), 3.52-3.36 (m, 4H), 3.24 (t, J=8.7 Hz, 2H), 2.49-2.35 (m, 2H), 2.25-2.08 (m, 2H), 1.89-1.43 (m, 5H), 1.36 (sextet, J=7.2 Hz, 2H), 0.98-0.91 (m, 9H).

EXAMPLE 37(71)

[2123] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-(2-hydroxyethylaminosulfonyl)phenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2900

[2124] TLC: Rf 0.35 (chloroform:methanol=10:1);

[2125] NMR (CD3OD): δ 8.03 (d, J=8.7 Hz, 2H), 7.72 (d, J=8.7 Hz, 2H), 4.32 (s, 2H), 4.02 (dd, J=7.5, 4.5 Hz, 1H), 3.95-3.73 (m, 2H), 3.67-3.57 (m, 2H), 3.56 (t, J=5.7 Hz, 2H), 3.51-3.40 (m, 2H), 3.01 (t, J=5.7 Hz, 2H), 2.63-2.42 (m, 2H), 2.47 (s, 3H), 2.41 (s, 3H), 2.32-2.12 (m, 2H), 1.92-1.44 (m, 5H), 1.44-1.30 (m, 2H), 1.00-0.91 (m, 9H).

EXAMPLE 37(72)

[2126] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(carboxymethyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2901

[2127] TLC: Rf 0.30 (chloroform:methanol=10:1);

[2128] NMR (CD3OD): δ 7.47 (d, J=8.7 Hz, 2H), 7.04 (d, J=8.7 Hz, 2H), 4.71 (s, 2H), 4.29 (s, 2H), 4.00 (dd, J=7.8, 4.5 Hz, 1H), 3.88-3.67 (m, 2H), 3.53-3.33 (m, 4H), 2.46-2.28 (m, 2H), 2.26-2.08 (m, 2H), 1.90-1.27 (m, 7H), 0.99-0.90 (m, 9H).

EXAMPLE 37(73)

[2129] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(1-phenyl-1-hydroxymethyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2902

[2130] TLC: Rf 0.23 (chloroform:methanol=10:1);

[2131] NMR (CD3OD): δ 7.62-7.18 (m, 9H), 5.82 (s, 1H), 4.33 (s, 2H), 4.00 (dd, J=7.8, 4.8 Hz, 1H), 3.88-3.68 (m, 2H), 3.56-3.36 (m, 4H), 2.48-2.28 (m, 2H), 2.24-2.06 (m, 2H), 1.88-1.24 (m, 7H), 0.95 (t, J=6.6 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H), 0.93 (d, J=6.3 Hz, 3H).

EXAMPLE 37(74)

[2132] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-hydroxypiperidin-1-ylmethyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2903

[2133] TLC: Rf 0.16 (chloroform:methanol=10:1);

[2134] NMR (CD3OD): δ 7.73 (d, J=7.8 Hz, 2H), 7.69-7.61 (m, 2H), 4.42 (s, 2H), 4.40-4.34 (m, 2H), 4.11-4.05 (m, 1H), 4.00 (dd, J=7.5, 4.5 Hz, 1H), 3.93-3.72 (m, 2H), 3.55-3.38 (m, 4H), 3.16-3.00 (m, 1H), 2.60-2.38 (m, 2H), 2.26-2.06(m, 3H), 2.00-1.88 (m, 2H), 1.88-1.43 (m, 9H), 1.43-1.14 (m, 2H), 0.98-0.90 (m, 9H).

EXAMPLE 37(75)

[2135] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(3-carboxyphenylmethyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2904

[2136] TLC: Rf 0.58 (chloroform:methanol=5:1);

[2137] NMR (CD3OD): δ 8.10 (s, 1H), 7.98 (d, J=8.1 Hz, 1H), 7.68 (d, J=8.7 Hz, 1H), 7.50 (t, J=8.1 Hz, 1H), 7.47 (d, J=8.7 Hz, 2H), 7.13 (d, J=8.7 Hz, 2H), 5.22 (s, 2H), 4.29 (s, 2H), 4.01 (dd, J=7.5, 4.5 Hz, 1H), 3.86-3.68 (m, 2H), 3.54-3.32 (m, 4H), 2.42-2.08 (m, 4H), 1.90-1.28 (m, 7H), 0.95 (t, J=6.9 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 37(76)

[2138] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(bis(methylsulfonyl)amino)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2905

[2139] TLC: Rf 0.64 (chloroform:methanol=5:1);

[2140] NMR (CD3OD): δ 7.72 (d, J=8.4 Hz, 2H), 7.61 (d, J=8.4 Hz, 2H), 4.44 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.96-3.78 (m, 2H), 3.58-3.36 (m, 4H), 3.47 (s, 6H), 2.50-2.12 (m, 4H), 1.92-1.28 (m, 7H), 0.96 (t, J=6.9 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 37(77)

[2141] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(1,4-benzodioxan-6-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2906

[2142] TLC: Rf 0.34 (chloroform:methanol=10:1);

[2143] NMR (CD3OD): δ 7.49 (d, J=8.7 Hz, 2H), 7.02 (d, J=8.7 Hz, 2H), 6.85 (m, 1H), 6.55-6.51 (m, 2H), 4.33 (s, 2H), 4.24 (s, 4H), 4.02 (dd, J=7.5, 4.8 Hz, 1H), 3.88-3.70 (m, 2H), 3.56-3.32 (m, 4H), 2.42-2.10 (m, 4H), 1.92-1.24 (m, 7H), 0.96 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H), 0.94 (d, J=6.6 Hz, 3H).

EXAMPLE 37(78)

[2144] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-(3-hydroxyphenyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2907

[2145] TLC: Rf 0.19 (chloroform:methanol=10:1);

[2146] NMR (CD3OD): δ 7.83 (s, 1H), 7.74 (m, 1H), 7.59-7.51 (m, 2H), 7.28 (m, 1H), 7.16-7.09 (m, 2H), 6.81 (m, 1H), 4.44 (s, 2H), 4.01 (dd, J=7.8, 4.5 Hz, 1H), 3.94-3.76 (m, 2H), 3.58-3.32 (m, 4H), 2.50-2.32 (m, 2H), 2.28-2.08 (m, 2H), 1.88-1.26 (m, 7H), 0.95 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 37(79)

[2147] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(methylsulfonylamino)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2908

[2148] TLC: Rf 0.40 (chloroform:methanol=10:1);

[2149] NMR (CD3OD): δ 7.52 (d, J=8.4 Hz, 2H), 7.34 (d, J=8.4 Hz, 2H), 4.32 (s, 2H), 4.01 (dd, J=7.8, 4.8 Hz, 1H), 3.88-3.72 (m, 2H), 3.52-3.14 (m, 4H), 3.01 (s, 3H), 2.46-2.30 (m, 2H), 2.28-2.10 (m, 2H), 1.88-1.10 (m, 7H), 0.98-0.90 (m, 9H).

EXAMPLE 37(80)

[2150] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-(4-methoxyphenyloxy)pyridin-3-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2909

[2151] TLC: Rf 0.48 (chloroform:methanol=10:1);

[2152] NMR (CD3OD): δ 8.30 (m, 1H), 8.05 (m, 1H), 7.10-6.86 (m, 5H), 4.39 (s, 2H), 4.01 (dd, J=7.8, 4.8 Hz, 1H), 3.90-3.74 (m, 2H), 3.81 (s, 3H), 3.54-3.32 (m, 4H), 2.54-2.32 (m, 2H), 2.28-2.05 (m, 2H), 1.88-1.26 (m, 7H), 0.98-0.90 (m, 9H).

EXAMPLE 37(81)

[2153] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-methylaminocarbonylphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2910

[2154] TLC: Rf 0.54 (chloroform:methanol=10:1);

[2155] NMR (CD3OD): δ 8.39 (brd, J=4.5 Hz, 1H), 7.84 (d, J=9.0 Hz, 2H), 7.59 (d, J=9.0 Hz, 2H), 7.15 (d, J=9.0 Hz, 2H), 7.07 (d, J=9.0 Hz, 2H), 4.35 (s, 2H), 4.01 (m, 1H), 3.86-3.73 (m, 2H), 3.53-3.41 (m, 4H), 2.91 (d, J=4.5 Hz, 3H), 2.55-2.30 (m, 2H), 2.30-2.10 (m, 2H), 1.90-1.30 (m, 7H), 0.95 (t, J=6.9 Hz, 3H), 0.94 (d, J=6.6 Hz, 3H), 0.93 (d, J=6.6 Hz, 3H).

EXAMPLE 37(82)

[2156] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-chlorophenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2911

[2157] TLC: Rf 0.59 (chloroform:methanol=10:1);

[2158] NMR (CD3OD): δ 7.53 (d, J=8.4 Hz, 2H), 7.38 (d, J=9.0 Hz, 2H), 7.08 (d, J=8.4 Hz, 2H), 7.02 (d, J=9.0 Hz, 2H), 4.31 (s, 2H), 4.01 (m, 1H), 3.90-3.70 (m, 2H), 3.60-3.30 (m, 4H), 2.50-2.10 (m, 4H), 1.90-1.30 (m, 7H), 0.95 (t, J=7.2 Hz, 3H), 0.94 (d, J=6.6 Hz, 3H), 0.93 (d, J=6.6 Hz, 3H).

EXAMPLE 37(83)

[2159] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-(4-carboxyphenyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2912

[2160] TLC: Rf 0.60 (chloroform:methanol=5:1);

[2161] NMR (CD3OD): δ 8.13 (d, J=9.0 Hz, 2H), 7.93 (s, 1H), 7.84 (m, 1H), 7.81 (d, J=9.0 Hz, 2H), 7.66-7.56 (m, 2H), 4.46 (s, 2H), 4.02 (dd, J=7.5, 4.8 Hz, 1H), 3.96-3.74 (m, 2H), 3.58-3.36 (m, 4H), 2.48-2.08 (m, 4H), 1.88-1.24 (m, 7H), 0.95 (t, J=6.9 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 37(84)

[2162] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(phenylaminocarbonyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2913

[2163] TLC: Rf 0.27 (chloroform:methanol=10:1);

[2164] NMR (CD3OD): δ 8.07 (d, J=8.4 Hz, 2H), 7.74 (d, J=8.4 Hz, 2H), 7.72-7.67 (m, 2H), 7.38 (t, J=7.5 Hz, 2H), 7.17 (t, J=7.5 Hz, 1H), 4.47 (s, 2H), 4.02 (dd, J=7.8, 4.5 Hz, 1H), 3.96-3.76 (m, 2H), 3.58-3.36 (m, 4H), 2.54-2.36 (m, 2H), 2.28-2.12 (m, 2H), 1.90-1.24 (m, 7H), 0.96 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 37(85)

[2165] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-methylthiophenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2914

[2166] TLC: Rf 0.49 (chloroform:methanol=10:1);

[2167] NMR (CD3OD): δ 7.53 (d, J=8.7 Hz, 2H), 7.33 (d, J=8.7 Hz, 2H), 7.07 (d, J=8.7 Hz, 2H), 7.00 (d, J=8.7 Hz, 2H), 4.34 (s, 2H), 4.02 (dd, J=7.8, 4.5 Hz, 1H), 3.88-3.68 (m, 2H), 3.56-3.36 (m, 4H), 2.48 (s, 3H), 2.48-2.32 (m, 2H), 2.28-2.08 (m, 2H), 1.90-1.28 (m, 7H), 0.96 (t, J=7.2 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H).

EXAMPLE 37(86)

[2168] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-(2-dimethylaminoethylaminocarbonyl)phenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2915

[2169] TLC: Rf 0.11 (chloroform:methanol=10:1);

[2170] NMR (CD3OD): δ 7.93 (d, J=9.0 Hz, 2H), 7.64 (d, J=8.7 Hz, 2H), 7.15 (d, J=8.7 Hz, 2H), 7.10 (d, J=9.0 Hz, 2H), 4.36 (s, 2H), 4.01 (dd, J=7.8, 4.8 Hz, 1H), 3.88-3.70 (m, 4H), 3.54-3.36 (m, 6H), 2.98 (s, 6H), 2.62-2.44 (m, 2H), 2.24-2.08 (m, 2H), 1.88-1.30 (m, 7H), 0.98-0.90 (m, 9H).

EXAMPLE 37(87)

[2171] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-aminocarbonylphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2916

[2172] TLC: Rf 0.17 (chloroform:methanol=10:1);

[2173] NMR (CD3OD): δ 7.98 (d, J=8.7 Hz, 2H), 7.70 (d, J=8.7 Hz, 2H), 4.43 (s, 2H), 4.00 (dd, J=7.5, 4.5 Hz, 1H), 3.92-3.74 (m, 2H), 3.52-3.36 (m, 4H), 2.58-2.40 (m, 2H), 2.26-2.08 (m, 2H), 1.88-1.28 (m, 7H), 0.98-0.88 (m, 9H).

EXAMPLE 37(88)

[2174] (3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-dimethylaminocarbonylphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2917

[2175] TLC: Rf 0.31 (chloroform:methanol=10:1);

[2176] NMR (CD3OD): δ 7.68 (d, J=8.1 Hz, 2H), 7.54 (d, J=8.1 Hz, 2H), 4.41 (s, 2H), 4.01 (dd, J=7.8, 4.8 Hz, 1H), 3.92-3.82 (m, 2H), 3.54-3.36 (m, 4H), 3.11 (s, 3H), 2.99 (s, 3H), 2.56-2.38 (m, 2H), 2.26-2.08 (m, 2H), 1.86-1.28 (m, 7H), 1.00-0.86 (m, 9H).

EXAMPLE 38

[2177] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-benzyloxycarbonyl-1,4,9-triazaspiro[5.5]undecane

2918

[2178] By the same procedure as described in Example 35 using N-(t-butyloxycarbonyl)-L-cyclohexylalanine instead of N-(t-butyloxycarbonyl-L-leucine, the compound of the present invention having the following physical data was obtained.

[2179] TLC: Rf 0.35 (hexane:ethyl acetate=1:1);

[2180] NMR (CDCl3): δ 7.39-7.31 (m, 5H), 6.48 (brs, 1H), 5.16 (s, 2H), 4.15 (brs, 2H), 4.00 (ddd, J=9.6, 4.8, 1.5 Hz, 1H), 3.76-3.16 (m, 4H), 2.02-1.12 (m, 19H), 1.08-0.88 (m, 2H), 0.92 (t, J=7.2 Hz, 3H).

EXAMPLE 39

[2181] (3S)-1-butyl-2,5-dioxo-3-cyclohexyl methyl-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2919

[2182] By the same procedure as described in Example 9 using the compound prepared in Example 38, the compound of the present invention having the following physical data was obtained.

[2183] TLC: Rf 0.08 (chloroform:methanol: acetic acid=90:10:1);

[2184] NMR (CD3OD): δ 4.05 (dd, J=7.8, 4.8 Hz, 1H), 3.84-3.68 (m, 2H), 3.46-3.34 (m, 4H), 2.40-2.04 (m, 4H), 1.83-1.46 (m, 10H), 1.39 (sextet, J=7.5 Hz, 2H), 1.33-1.15 (m, 3H), 1.05-0.86 (m, 2H), 0.97 (t, J=7.2 Hz, 3H).

EXAMPLE 40(1)˜40(90)

[2185] By the same procedure as described in Example 10 using the compound prepared in Example 39 and the corresponding aldehyde derivatives, the following compounds of the present invention were obtained.

EXAMPLE 40(1)

[2186] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-methylphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2920

[2187] TLC: Rf 0.71 (ethyl acetate);

[2188] NMR (CD3OD): δ 7.50 (d, J=8.7 Hz, 2H), 7.19 (d, J=8.7 Hz, 2H), 7.02 (d, J=8.7 Hz, 2H), 6.92 (d, J=8.7 Hz, 2H), 4.32 (s, 2H), 4.04 (dd, J=7.5, 4.5 Hz, 1H), 3.87-3.69 (m, 2H), 3.55-3.42 (m, 2H), 3.42-3.34 (m, 2H), 2.49-2.30 (m, 2H), 2.33 (s, 3H), 2.30-2.08 (m, 2H), 1.82-1.10 (m, 15H), 1.05-0.85 (m, 2H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 40(2)

[2189] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-methoxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2921

[2190] TLC: Rf 0.67 (ethyl acetate);

[2191] NMR (CD3OD): δ 7.49 (d, J=8.4 Hz, 2H), 7.02-6.92 (m, 6H), 4.31 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.86-3.69 (m, 2H), 3.79 (s, 3H), 3.54-3.30 (m, 4H), 2.50-2.30 (m, 2H), 2.28-2.06 (m, 2H), 1.83-1.10 (m, 15H), 1.05-0.83 (m, 2H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 40(3)

[2192] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-fluorophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2922

[2193] TLC: Rf 0.38 (hexane:ethyl acetate=1:1);

[2194] NMR (CD3OD): δ 7.70-7.53 (m, 2H), 7.38-7.23 (m, 2H), 4.44 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.95-3.77 (m, 2H), 3.60-3.45 (m, 2H), 3.45-3.30 (m, 2H), 2.53-2.34 (m, 2H), 2.28-2.08 (m, 2H), 1.83-1.10 (m, 15H), 1.05-0.82 (m, 2H), 0.94 (t, J=7.2 Hz, 3H).

EXAMPLE 40(4)

[2195] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3-fluorophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2923

[2196] TLC: Rf 0.40 (hexane:ethyl acetate=1:1);

[2197] NMR (CD3OD): δ 7.57-7.48 (m, 1H), 7.44-7.37 (m, 2H), 7.30-7.21 (m, 1H), 4.38 (s, 2H), 4.03 (dd, J=7.8, 4.8 Hz, 1H), 3.90-3.72 (m, 2H), 3.55-3.33 (m, 4H), 2.56-2.37 (m, 2H), 2.25-2.04 (m, 2H), 1.82-1.08 (m, 15H), 1.06-0.83 (m, 2H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 40(5)

[2198] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-fluorophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2924

[2199] TLC: Rf 0.27 (hexane:ethyl acetate=1:1);

[2200] NMR (CD3OD): δ 7.62 (dd, J=8.7, 5.1 Hz, 2H), 7.23 (dd, J=8.7, 8.7 Hz, 2H), 4.36 (s, 2H), 4.03 (dd, J=7.8, 4.8 Hz, 1H), 3.88-3.71 (m, 2H), 3.53-3.33 (m, 4H), 2.53-2.35 (m, 2H), 2.27-2.04 (m, 2H), 1.82-1.10 (m, 15H), 1.05-0.82 (m, 2H), 0.94 (t, J=7.2 Hz, 3H).

EXAMPLE 40(6)

[2201] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3-chlorophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2925

[2202] TLC: Rf 0.60 (hexane:ethyl acetate=1:1);

[2203] NMR (CD3OD): δ 7.65 (m, 1H), 7.55-7.49 (m, 3H), 4.37 (s, 2H), 4.04 (dd, J=7.0, 4.5 Hz, 1H), 3.83 (m, 2H), 3.54-3.47 (m, 2H), 3.41-3.35 (m, 2H), 2.38 (m, 2H), 2.18 (m, 2H), 1.78-1.47 (m, 9H), 1.42-1.17 (m, 6H), 0.95 (t, J=7.5 Hz, 3H), 0.97-0.92 (m, 2H).

EXAMPLE 40(7)

[2204] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-cyclohexyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2926

[2205] TLC: Rf 0.36 (chloroform:methanol=10:1);

[2206] NMR (CD3OD): δ 7.41 (d, J=8.7 Hz, 2H), 7.00 (d, J=8.7 Hz, 2H), 4.36 (m, 1H), 4.24 (s, 2H), 4.03 (dd, J=7.8, 4.5 Hz, 1H), 3.82-3.65 (m, 2H), 3.50-3.30 (m, 4H), 2.42-2.25 (m, 2H), 2.25-2.06 (m, 2H), 2.02-1.92 (m, 2H), 1.84-1.14 (m, 23H), 1.04-0.89 (m, 5H).

EXAMPLE 40(8)

[2207] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-methoxy-3-hydroxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2927

[2208] TLC: Rf 0.34 (chloroform:methanol=10:1);

[2209] NMR (CD3OD): δ 7.01 (d, J=7.8 Hz, 1H), 6.99-6.93 (m, 2H), 4.22 (s, 2H), 4.03 (dd, J=7.5, 4.8 Hz, 1H), 3.87 (s, 3H), 3.83-3.67 (m, 2H), 3.52-3.42 (m, 2H), 3.42-3.33 (m, 2H), 2.44-2.27 (m, 2H), 2.26-2.07 (m, 2H), 1.83-1.12 (m, 15H), 1.04-0.89 (m, 5H).

EXAMPLE 40(9)

[2210] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-chlorophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2928

[2211] TLC: Rf 0.77 (chloroform:methanol=10:1);

[2212] NMR (CD3OD): δ 7.69 (dd, J=7.5, 2.1 Hz, 1H), 7.60 (dd, J=7.5, 2.1 Hz, 1H), 7.51 (dt, J=2.1, 7.5 Hz, 1H), 7.47 (dt, J=2.1, 7.5 Hz, 1H), 4.52 (s, 2H), 4.04 (dd, J=7.8, 4.8 Hz, 1H), 4.00-3.82 (m, 2H), 3.60-3.48 (m, 2H), 3.43-3.34 (m, 2H), 2.48-2.29 (m, 2H), 2.28-2.07 (m, 2H), 1.83-1.44 (m, 10H), 1.43-1.12 (m, 5H), 1.04-0.88 (m, 5H).

EXAMPLE 40(10)

[2213] (3S)-1-butyl-2,5-dioxo-3-cyclohexyl methyl-9-(2-methylphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2929

[2214] TLC: Rf 0.77 (chloroform:methanol=10:1);

[2215] NMR (CD3OD): δ 7.56 (d, J=7.2 Hz, 1H), 7.41-7.30 (m, 3H), 4.41 (s, 2H), 4.04 (dd, J=7.5, 4.5 Hz, 1H), 3.98-3.79 (m, 2H), 3.57-3.48 (m, 2H), 3.44-3.39 (m, 2H), 2.56-2.38 (m, 2H), 2.48 (s, 3H), 2.26-2.06 (m, 2H), 1.82-1.15 (m, 15H), 1.02-0.84 (m, 5H).

EXAMPLE 40(11)

[2216] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3-methylphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2930

[2217] TLC: Rf 0.58 (chloroform:methanol=10:1);

[2218] NMR (CD3OD): δ 7.40-7.28 (m, 4H), 4.31 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.84-3.70 (m, 2H), 3.52-3.46 (m, 4H), 2.51-2.30 (m, 2H), 2.39 (s, 3H), 2.24-2.04 (m, 2H), 1.80-1.12 (m, 15H), 1.02-0.84 (m, 5H).

EXAMPLE 40(12)

[2219] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-methylphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2931

[2220] TLC: Rf 0.61 (chloroform:methanol=10:1);

[2221] NMR (CD3OD): δ 7.44 (d, J=8.4 Hz, 2H), 7.31 (d, J=8.4 Hz, 2H), 4.31 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.88-3.70 (m, 2H), 3.52-3.36 (m, 4H), 2.48-2.30 (m, 2H), 2.38 (s, 3H), 2.30-2.08 (m, 2H), 1.81-1.10 (m, 15H), 1.04-0.82 (m, 5H).

EXAMPLE 40(13)

[2222] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-phenylthiophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2932

[2223] TLC: Rf 0.74 (chloroform:methanol=10:1);

[2224] NMR (CD3OD): δ 7.50-7.37 (m, 7H), 7.29 (d, J=8.4 Hz, 2H), 4.31 (s, 2H), 4.03 (dd, J=7.5, 4.8 Hz, 1H), 3.84-3.70 (m, 2H), 3.50-3.32 (m, 4H), 2.56-2.38 (m, 2H), 2.24-2.05 (m, 2H), 1.81-1.06 (m, 15H), 1.02-0.84 (m, 5H).

EXAMPLE 40(14)

[2225] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3-(2-methylpropyl) phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2933

[2226] TLC: Rf 0.41 (chloroform:methanol=19:1);

[2227] NMR (CD3OD): δ 7.47 (d, J=7.5 Hz, 2H), 7.29 (d, J=7.5 Hz, 2H), 4.32 (s, 2H), 4.03 (dd, J=7.8, 4.8 Hz, 1H), 3.80 (m, 2H), 3.56-3.36 (m, 4H), 2.52 (d, J=7.2 Hz, 2H), 2.45 (m, 2H), 2.16 (m, 2H), 1.96-1.14 (m, 16H), 0.97-0.89 (m, 11H).

EXAMPLE 40(15)

[2228] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3-butylphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2934

[2229] TLC: Rf 0.37 (chloroform:methanol=19:1);

[2230] NMR (CD3OD): δ 7.46 (d, J=8.4 Hz, 2H), 7.32 (d, J=8.4 Hz, 2H), 4.31 (s, 2H), 4.03 (dd, J=7.2, 4.8 Hz, 1H), 3.79 (m, 2H), 3.56-3.36 (m, 4H), 2.66 (t, J=7.5 Hz, 2H), 2.41 (m, 2H), 2.16 (m, 2H), 1.82-1.20 (m, 19H), 1.00-0.89 (m, 2H), 0.94 (t, J=7.2 Hz, 3H), 0.93 (t, J=7.2 Hz, 3H).

EXAMPLE 40(16)

[2231] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-isopropylphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2935

[2232] TLC: Rf 0.63 (chloroform:methanol=10:1);

[2233] NMR (CD3OD): δ 7.46 (d, J=8.4 Hz, 2H), 7.37 (d, J=8.4 Hz, 2H), 4.32 (s, 2H), 4.03 (dd, J=7.8, 4.8 Hz, 1H), 3.88-3.74 (m, 2H), 3.52-3.43 (m, 2H), 3.43-3.32 (m, 2H), 3.02-2.90 (m, 1H), 2.45-2.25 (m, 2H), 2.25-2.08 (m, 2H), 1.80-1.12 (m, 21H), 1.04-0.88 (m, 5H).

EXAMPLE 40(17)

[2234] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-methoxy-3-fluorophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2936

[2235] TLC: Rf 0.58 (chloroform:methanol=10:1);

[2236] NMR (CD3OD): 87.40-7.31 (m, 2H), 7.22-7.17 (m, 1H), 4.30 (s, 2H), 4.03 (dd, J=7.8, 4.8 Hz, 1H), 3.90 (s, 3H), 3.86-3.70 (m, 2H), 3.50-3.38 (m, 4H), 2.52-2.32 (m, 2H), 2.26-2.05 (m, 2H), 1.80-1.15 (m, 15H), 1.01-0.88 (m, 5H).

EXAMPLE 40(18)

[2237] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(2-hydroxyethoxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2937

[2238] TLC: Rf 0.40 (chloroform:methanol=10:1);

[2239] NMR (CD3OD): δ 7.47 (d, J=8.7 Hz, 2H), 7.06 (d, J=8.7 Hz, 2H), 4.29 (s, 2H), 4.08-4.00 (m, 3H), 3.89-3.84 (m, 2H), 3.84-3.68 (m, 2H), 3.52-3.36 (m, 4H), 2.48-2.30 (m, 2H), 2.25-2.08 (m, 2H), 1.80-1.10 (m, 15H), 1.04-0.86 (m, 5H).

EXAMPLE 40(19)

[2240] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-hydroxy-3-methyl phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2938

[2241] TLC: Rf 0.85 (chloroform:methanol=10:1);

[2242] NMR (CD3OD): δ 7.30-7.21 (m, 2H), 6.88 (t, J=7.5 Hz, 1H), 4.36 (s, 2H), 4.03 (dd, J=7.8, 4.2 Hz, 1H), 3.94-3.78 (m, 2H), 3.56-3.46 (m, 2H), 3.42-3.32 (m, 2H), 2.50-2.30 (m, 2H), 2.28 (s, 3H), 2.28-2.06 (m, 2H), 1.82-1.01 (m, 15H), 1.00-0.87 (m, 5H).

EXAMPLE 40(20)

[2243] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-chlorophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2939

[2244] TLC: Rf 0.60 (chloroform:methanol=20:1);

[2245] NMR (CD3OD): δ 7.57 (d, J=8.7 Hz, 2H), 7.51 (d, J=8.7 Hz, 2H), 4.36 (s, 2H), 4.03 (dd, J=7.5, 4.8 Hz, 1H), 3.89-3.71 (m, 2H), 3.53-3.33 (m, 4H), 2.52-2.32 (m, 2H), 2.26-2.07 (m, 2H), 1.83-1.06 (m, 15H), 1.04-0.84 (m, 2H), 0.95 (t, J=6.9 Hz, 3H).

EXAMPLE 40(21)

[2246] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(7-methoxy-1,3-benzodioxolan-5-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2940

[2247] TLC: Rf 0.43 (chloroform:methanol=20:1);

[2248] NMR (CD3OD): δ 6.85 (s, 1H), 6.74 (s, 1H), 5.99 (s, 2H), 4.25 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.92 (s, 3H), 3.87-3.67 (m, 2H), 3.54-3.34 (m, 4H), 2.53-2.30 (m, 2H), 2.25-2.05 (m, 2H), 1.83-1.10 (m, 15H), 1.06-0.83 (m, 2H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 40(22)

[2249] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3-methyl-4-methoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2941

[2250] TLC: Rf 0.38 (chloroform:methanol=20:1);

[2251] NMR (CD3OD): δ 7.37-7.28 (m, 2H), 6.99 (d, J=8.1 Hz, 1H), 4.25 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.85 (s, 3H), 3.84-3.66 (m, 2H), 3.52-3.32 (m, 4H), 2.48-2.28 (m, 2H), 2.22 (s, 3H), 2.22-2.05 (m, 2H), 1.83-1.10 (m, 15H), 1.06-0.83 (m, 2H), 0.94 (t, J=6.9 Hz, 3H).

EXAMPLE 40(23)

[2252] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-fluorophenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2942

[2253] TLC: Rf 0.53 (chloroform:methanol=20:1);

[2254] NMR (CD3OD): δ 7.53 (d, J=8.7 Hz, 2H), 7.18-7.00 (m, 6H), 4.33 (s, 2H), 4.04 (dd, J=7.5, 4.5 Hz, 1H), 3.87-3.69 (m, 2H), 3.55-3.32 (m, 4H), 2.52-2.32 (m, 2H), 2.28-2.08 (m, 2H), 1.83-1.12 (m, 15H), 1.06-0.83 (m, 2H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 40(24)

[2255] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-trifluoromethoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2943

[2256] TLC: Rf 0.60 (chloroform:methanol=10:1);

[2257] NMR (CD3OD): δ 7.72-7.69 (m, 2H), 7.41 (d, J=7.8 Hz, 2H), 4.40 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.90-3.75 (m, 2H), 3.52-3.38 (m, 4H), 2.54-2.32 (m, 2H), 2.28-2.10 (m, 2H), 1.80-1.10 (m, 15H), 1.02-0.88 (m, 5H).

EXAMPLE 40(25)

[2258] (3S)-1-butyl-2,5-dioxo-3-cyclohexyl methyl-9-(3-methyl-5-chloro-1-phenyl pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2944

[2259] TLC: Rf 0.50 (chloroform:methanol=10:1);

[2260] NMR (CD3OD): δ 7.56-7.50 (m, 5H), 4.33 (s, 2H), 4.05 (dd, J=7.8, 4.5 Hz, 1H), 3.98-3.80 (m, 2H), 3.70-3.59 (m, 2H), 3.50-3.40 (m, 2H), 2.60-2.38 (m, 2H), 2.45 (s, 3H), 2.32-2.14 (m, 2H), 1.82-1.14 (m, 15H), 1.02-0.86 (m, 5H).

EXAMPLE 40(26)

[2261] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2,3-dimethyl-5-oxo-1-phenylpyrazolin-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2945

[2262] TLC: Rf 0.27 (chloroform:methanol=10:1);

[2263] NMR (CD3OD): 87.62-7.48 (m, 3H), 7.44-7.38 (m, 2H), 4.13 (s, 2H), 4.04 (dd, J=7.5, 4.5 Hz, 1H), 3.88-3.72 (m, 2H), 3.64-3.52 (m, 2H), 3.50-3.38 (m, 2H), 3.35 (s, 3H), 2.60-2.40 (m, 2H), 2.48 (s, 3H), 2.28-2.10 (m, 2H), 1.82-1.10 (m, 15H), 1.02-0.84 (m, 5H).

EXAMPLE 40(27)

[2264] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(1-(2-methylpropyloxycarbonyl)indol-5-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2946

[2265] TLC: Rf 0.55 (chloroform:methanol=10:1);

[2266] NMR (CD3OD): δ 8.26 (d, J=8.4 Hz, 1H), 7.82 (s, 1H), 7.76 (d, J=3.6 Hz, 1H), 7.50 (dd, J=8.4, 1.8 Hz, 1H), 6.74 (d, J=3.6 Hz, 1H), 4.44 (s, 2H), 4.25 (d, J=6.6 Hz, 2H), 4.03 (dd, J=7.8, 4.8 Hz, 1H), 3.86-3.72 (m, 2H), 3.52-3.40 (m, 4H), 2.52-2.36 (m, 2H), 2.25-2.06 (m, 3H), 1.80-1.10 (m, 15H), 1.07 (d, J=9.0 Hz, 6H), 1.00-0.84 (m, 5H).

EXAMPLE 40(28)

[2267] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-methyl-2-phenyloxazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2947

[2268] TLC: Rf 0.48 (chloroform:methanol=10:1);

[2269] NMR (CD3OD): δ 8.04-8.00 (m, 2H), 7.51-7.49 (m, 3H), 4.34 (s, 2H), 4.04 (dd, J=7.8, 4.8 Hz, 1H), 3.98-3.82 (m, 2H), 3.70-3.60 (m, 2H), 3.44-3.38 (m, 2H), 2.52 (s, 3H), 2.50-2.36 (m, 2H), 2.28-2.12 (m, 2H), 1.80-1.12 (m, 15H), 1.00-0.86 (m, 5H).

EXAMPLE 40(29)

[2270] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-methylsulfonylaminophenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2948

[2271] TLC: Rf 0.32 (chloroform:methanol=10:1);

[2272] NMR (CD3OD): δ 7.47 (d, J=9.0 Hz, 2H), 7.41 (d, J=9.0 Hz, 2H), 4.32 (s, 2H), 4.04 (dd, J=7.8, 4.8 Hz, 1H), 3.92-3.76 (m, 2H), 3.65-3.58 (m, 2H), 3.52-3.45 (m, 2H), 3.04 (s, 3H), 2.64-2.50 (m, 2H), 2.43 (s, 3H), 2.40 (s, 3H), 2.28-2.12 (m, 2H), 1.82-1.10 (m, 15H), 1.00-0.88 (m, 5H).

EXAMPLE 40(30)

[2273] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-methylsulfonylaminophenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2949

[2274] TLC: Rf 0.42 (chloroform:methanol=10:1);

[2275] NMR (CD3OD): δ 7.53 (d, J=9.0 Hz, 2H), 7.29 (d, J=9.0 Hz, 2H), 7.08-7.00 (m, 4H), 4.33 (s, 2H), 4.03 (dd, J=7.5, 4.8 Hz, 1H), 3.85-3.72 (m, 2H), 3.54-3.36 (m, 4H), 2.95 (s, 3H), 2.48-2.34 (m, 2H), 2.25-2.08 (m, 2H), 1.80-1.14 (m, 15H), 0.98-0.88 (m, 5H).

EXAMPLE 40(31)

[2276] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(6-methylpyridin-3-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2950

[2277] TLC: Rf 0.42 (chloroform:methanol=10:1);

[2278] NMR (CD3OD): δ 8.58 (d, J=2.7 Hz, 1H), 8.17 (m, 1H), 7.90 (d, J=8.4 Hz, 1H), 7.75 (d, J=9.0 Hz, 2H), 7.30 (d, J=9.0 Hz, 2H), 4.39 (s, 2H), 4.03 (dd, J=7.5, 4.8 Hz, 1H), 3.88-3.72 (m, 2H), 3.56-3.44 (m, 4H), 2.76 (s, 3H), 2.68-2.50 (m, 2H), 2.24-2.06 (m, 2H), 1.82-1.14 (m, 15H), 1.02-0.88 (m, 5H).

EXAMPLE 40(32)

[2279] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(6-methylpyridin-1-oxide-3-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2951

[2280] TLC: Rf 0.38 (chloroform:methanol=10:1);

[2281] NMR (CD3OD): δ 8.40 (m, 1H), 7.69 (d, J=8.4 Hz, 2H), 7.69 (m, 1H), 7.54 (m, 1H), 7.27 (d, J=8.4 Hz, 2H), 4.39 (s, 2H), 4.04 (dd, J=7.5, 4.8 Hz, 1H), 3.88-3.72 (m, 2H), 3.58-3.39 (m, 4H), 2.59 (s, 3H), 2.58-2.40 (m, 2H), 2.28-2.06 (m, 2H), 1.82-1.10 (m, 15H), 1.02-0.84 (m, 5H).

EXAMPLE 40(33)

[2282] (3S)-1-butyl-2,5-dioxo-3-cyclohexyl methyl-9-(4-(tetrahydropyran-4-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2952

[2283] TLC: Rf 0.48 (chloroform:methanol=10:1);

[2284] NMR (CD3OD): δ 7.49 (d, J=8.4 Hz, 2H), 7.05 (d, J=8.4 Hz, 2H), 4.63 (m, 1H), 4.27 (s, 2H), 4.02 (dd, J=7.8, 4.8 Hz, 1H), 3.97-3.90 (m, 2H), 3.84-3.66 (m, 2H), 3.62-3.52 (m, 2H), 3.50-3.38 (m, 3H), 2.54-2.38 (m, 2H), 2.22-1.98 (m, 4H), 1.80-1.10 (m, 18H), 1.00-0.86 (m, 5H).

EXAMPLE 40(34)

[2285] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(6-phenylpyridin-3-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2953

[2286] TLC: Rf 0.50 (chloroform:methanol=10:1);

[2287] NMR (CD3OD): δ 9.14 (m, 1H), 8.75 (m, 1H), 8.36 (m, 1H), 8.02-7.99 (m, 2H), 7.68-7.62 (m, 3H), 4.63 (s, 2H), 4.05 (dd, J=7.5, 4.5 Hz, 1H), 4.02-3.94 (m, 2H), 3.64-3.42 (m, 4H), 2.72-2.56 (m, 2H), 2.25-2.06 (m, 2H), 1.80-1.10 (m, 15H), 1.00-0.86 (m, 5H).

EXAMPLE 40(35)

[2288] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-fluorophenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2954

[2289] TLC: Rf 0.60 (chloroform:methanol=10:1);

[2290] NMR (CD3OD): δ 7.58-7.50 (m, 2H), 7.37-7.28 (m, 2H), 4.32 (s, 2H), 4.05 (dd, J=7.5, 4.5 Hz, 1H), 3.94-3.73 (m, 2H), 3.67-3.55 (m, 2H), 3.53-3.42 (m, 2H), 2.70-2.48 (m, 2H), 2.43 (s, 3H), 2.39 (s, 3H), 2.30-2.08 (m, 2H), 1.84-1.10 (m, 15H), 1.08-0.93 (m, 2H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 40(36)

[2291] (3S)-1-butyl-2,5-dioxo-3-cyclohexyl methyl-9-(3,5-dimethyl-1-(pyridin-2-yl) pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2955

[2292] TLC: Rf 0.60 (chloroform:methanol=10:1);

[2293] NMR (CD3OD): δ 8.53 (dd, J=4.8, 1.5 Hz, 1H), 8.11-8.00 (m, 1H), 7.84 (d, J=8.4 Hz, 1H), 7.49-7.41 (m, 1H), 4.32 (s, 2H), 4.05 (dd, J=7.5, 4.5 Hz, 1H), 3.95-3.74 (m, 2H), 3.66-3.54 (m, 2H), 3.50-3.37 (m, 2H), 2.68 (s, 3H), 2.64-2.40 (m, 2H), 2.43 (s, 3H), 2.30-2.08 (m, 2H), 1.93-1.10 (m, 15H), 1.08-0.92 (m, 2H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 40(37)

[2294] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-hydroxyphenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2956

[2295] TLC: Rf 0.48 (chloroform:methanol=10:1);

[2296] NMR (CD3OD): δ 7.34 (d, J=9.0 Hz, 2H), 6.96 (d, J=9.0 Hz, 2H),4.35 (s, 2H), 4.05 (dd, J=7.5, 4.5 Hz, 1H), 3.93-3.78 (m, 2H), 3.64-3.61 (m, 2H), 3.50 (t, J=8.0 Hz, 2H), 2.68-2.56 (m, 2H), 2.49 (s, 3H), 2.39 (s, 3H), 2.25-2.12 (m, 2H), 1.81-1.19 (m, 15H), 0.95 (t, J=7.5 Hz, 3H), 0.99-0.91 (m, 2H).

EXAMPLE 40(38)

[2297] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(2-carboxyethyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2957

[2298] TLC: Rf 0.43 (chloroform:methanol=10:1);

[2299] NMR (CD8OD): δ 7.46 (d, J=8.3 Hz, 2H), 7.38 (d, J=8.3 Hz, 2H),4.32 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.85-3.74 (m, 2H), 3.50-3.46 (m, 2H), 3.40-3.35 (m, 2H), 2.96 (t, J=7.2 Hz, 2H), 2.62 (t, J=7.2 Hz, 2H), 2.42-2.30 (m, 2H), 2.34-2.10 (m, 2H), 1.78-1.18 (m, 15H), 0.94 (t, J=7.2 Hz, 3H), 0.94 (m, 2H).

EXAMPLE 40(39)

[2300] (3S)-1-butyl-2,5-dioxo-3-cyclohexyl methyl-9-(4-(4-hydroxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2958

[2301] TLC: Rf 0.54 (chloroform:methanol=10:1);

[2302] NMR (CD3OD): δ 7.47 (d, J=8.4 Hz, 2H), 6.97 (d, J=8.4 Hz, 2H), 6.88 (d, J=9.0 Hz, 2H), 6.80 (d, J=9.0 Hz, 2H), 4.30 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.83-3.72 (m, 2H), 3.49-3.34 (m, 4H), 2.38 (m, 2H), 2.23-2.10 (m, 2H), 1.78-1.16 (m, 15H), 1.02-0.92 (m, 2H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 40(40)

[2303] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-carboxyphenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2959

[2304] TLC: Rf 0.25 (chloroform:methanol=10:1);

[2305] NMR (CD3OD): δ 8.19 (d, J=8.4 Hz, 2H), 7.61 (d, J=8.4 Hz, 2H), 4.33 (s, 2H), 4.06 (dd, J=7.5, 4.5 Hz, 1H), 3.93-3.80 (m, 2H), 3.61 (m, 2H), 3.43-3.38 (m, 2H), 2.44 (s, 3H), 2.40 (m, 2H), 2.39 (s, 3H), 2.21 (m, 2H), 1.75-1.18 (m, 15H), 0.96 (m, 2H), 0.96 (t, J=7.2 Hz, 3H).

EXAMPLE 40(41)

[2306] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-(dimethylaminosulfonyl)phenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2960

[2307] TLC: Rf 0.54 (chloroform:methanol=9:1);

[2308] NMR (CD3OD): δ 7.96 (d, J=8.7 Hz, 2H), 7.78 (d, J=8.7 Hz, 2H), 4.31 (s, 2H), 4.05 (dd, J=7.8, 4.5 Hz, 1H), 3.94-3.74 (m, 2H), 3.66-3.56 (m, 2H), 3.48 (m, 2H), 2.74 (s, 6H), 2.59 (m, 2H), 2.49 (s, 3H), 2.41 (s, 3H), 2.29-2.10 (m, 2H), 1.84-1.16 (m, 13H), 1.06-0.86 (m, 5H).

EXAMPLE 40(42)

[2309] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(5-methylpyridin-1-oxide-2-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2961

[2310] TLC: Rf 0.49 (chloroform:methanol=9:1);

[2311] NMR (CD3OD): δ 7.77 (brs, 1H), 7.61 (d, J=7.5 Hz, 2H), 7.56 (dd, J 9.3, 2.4 Hz, 1H), 7.00 (d, J=7.5 Hz, 2H), 6.73 (d, J=9.3 Hz, 1H), 4.34 (s, 2H), 4.03 (dd, J=7.8, 4.8 Hz, 1H), 3.86-3.69 (m, 2H), 3.52-3.35 (m, 4H), 2.44 (m, 2H), 2.25-2.06 (m, 2H), 2.18 (s, 3H), 1.84-1.14 (m, 15H), 1.04-0.96 (m, 5H).

EXAMPLE 40(43)

[2312] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(2-carboxy-1-ethynyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2962

[2313] TLC: Rf 0.17 (chloroform:methanol=10:1);

[2314] NMR (CD3OD): δ 7.75 (d, J=8.4 Hz, 2H), 7.70 (d, J=15.9 Hz, 1H), 7.61 (d, J=8.4 Hz, 2H), 6.57 (d, J=15.9 Hz, 1H), 4.39 (s, 2H),4.04 (dd, J=7.2, 4.8 Hz, 1H), 3.90-3.72 (m, 2H), 3.58-3.36 (m, 4H), 2.50-2.32 (m, 2H), 2.28-2.08 (m, 2H), 1.92-1.10 (m, 15H), 0.96 (t, J=7.2 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 40(44)

[2315] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-((1E)-2-carboxy-1-ethynyl) phenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2963

[2316] TLC: Rf 0.44 (chloroform:methanol=10:1);

[2317] NMR (CD3OD): δ 7.69-7.63 (m, 3H), 7.57 (d, J=8.7 Hz, 2H), 7.14 (d, J=8.7 Hz, 2H), 7.05 (d, J=8.4 Hz, 2H), 6.42 (d, J=15.9 Hz, 1H), 4.36 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.90-3.74 (m, 2H), 3.55-3.36 (m, 4H), 2.50-2.30 (m, 2H), 2.30-2.08 (m, 2H), 1.82-1.10 (m, 15H), 1.02-0.88 (m, 5H).

EXAMPLE 40(45)

[2318] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-aminocarbonylphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2964

[2319] TLC: Rf 0.41 (chloroform:methanol=10:1);

[2320] NMR (CD3OD): δ 7.90 (d, J=9.0 Hz, 2H), 7.60 (d, J=9.0 Hz, 2H), 7.15 (d, J=9.0 Hz, 2H), 7.07 (d, J=9.0 Hz, 2H), 4.36 (s, 2H), 4.04 (dd, J=7.5, 4.5, Hz, 1H), 3.90-3.72 (m, 2H), 3.56-3.35 (m, 4H), 2.53-2.35 (m, 2H), 2.28-2.08 (m, 2H), 1.84-1.13 (m, 15H), 1.06-0.86 (m, 5H).

EXAMPLE 40(46)

[2321] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-aminosulfonylphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2965

[2322] TLC: Rf 0.33 (chloroform:methanol=10:1); NMR (d6-DMSO): δ 11.03 (brs, 1H), 8.42 (brs, 1H), 7.82 (d, J=8.7 Hz, 2H), 7.71 (d, J=8.7 Hz, 2H), 7.33 (brs, 2H), 7.16 (d, J=8.7 Hz, 4H), 4.38-4.23 (m, 2H), 3.91 (m, 1H), 3.61-3.23 (m, 6H), 2.58-2.30 (m, 2H), 2.18-1.91 (m, 2H), 1.76-1.00 (m, 15H), 0.98-0.71 (m, 5H).

EXAMPLE 40(47)

[2323] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-benzylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2966

[2324] TLC: Rf 0.40 (chloroform:methanol=10:1);

[2325] NMR (CD3OD): δ 7.41-7.33 (m, 3H), 7.22-7.20 (m, 2H), 5.46 (s, 2H), 4.31 (s, 2H), 4.04 (dd, J=7.5, 4.5 Hz, 1H), 3.88-3.74 (m, 2H), 3.58-3.48 (m, 4H), 2.61 (m, 2H), 2.47 (s, 6H), 2.24-2.09 (m, 2H), 1.80-1.16 (m, 15H), 0.95 (t, J=7.2 Hz, 3H), 0.95 (m, 2H).

EXAMPLE 40(48)

[2326] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(2,4-difluorophenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2967

[2327] TLC: Rf 0.48 (chloroform:methanol=10:1);

[2328] NMR (CD3OD): δ 7.58-7.51 (m, 1H), 7.33-7.25 (m, 1H), 7.22-7.16 (m, 1H),4.31 (s, 2H), 4.05 (dd, J=7.5, 4.5 Hz, 1H), 3.91-3.78 (m, 2H), 3.59 (m, 2H), 3.44 (m, 2H), 2.49 (m, 2H), 2.38 (s, 3H), 2.28 (s, 3H), 2.27-2.15 (m, 2H), 1.81-1.16 (m, 15H), 0.96 (t, J=7.0 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 40(49)

[2329] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(pyrrolidin-1-ylmethyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2968

[2330] TLC: Rf 0.14 (chloroform:methanol=10:1);

[2331] NMR (CD3OD): δ 7.74 (d, J=8.4 Hz, 2H), 7.65 (d, J=8.4 Hz, 2H), 4.43 (s, 2H), 4.40 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.90-3.70 (m, 2H), 3.56-3.38 (m, 6H), 3.28-3.10 (m, 2H), 2.66-2.48 (m, 2H), 2.26-1.92 (m, 6H), 1.83-1.10 (m, 15H), 1.06-0.83 (m, 2H), 0.94 (t, J=7.2 Hz, 3H).

EXAMPLE 40(50)

[2332] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-(morpholin-4-ylsulfonyl)phenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2969

[2333] TLC: Rf 0.46 (chloroform:methanol=20:1);

[2334] NMR (CD3OD): δ 7.95 (d, J=8.7 Hz, 2H), 7.80 (d, J=8.7 Hz, 2H), 4.32 (s, 2H), 4.05 (dd, J=7.8, 4.5 Hz, 1H), 3.94-3.74 (m, 2H), 3.76-3.67 (m, 4H), 3.66-3.56 (m, 2H), 3.56-3.42 (m, 2H), 3.10-2.92 (m, 4H), 2.68-2.50 (m, 2H), 2.50 (s, 3H), 2.42 (s, 3H), 2.30-2.08 (m, 2H), 1.84-1.08 (m, 15H), 1.08-0.83 (m, 2H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 40(51)

[2335] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-cyanophenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2970

[2336] TLC: Rf 0.33 (chloroform:methanol=10:1);

[2337] NMR (CD3OD): δ 7.75 (d, J=9.3 Hz, 2H), 7.64 (d, J=9.0 Hz, 2H), 7.22 (d, J=9.0 Hz, 2H), 7.14 (d, J=9.3 Hz, 2H), 4.40 (s, 2H), 4.05 (dd, J=7.5, 4.8 Hz, 1H), 3.92-3.74 (m, 2H), 3.58-3.36 (m, 4H), 2.52-2.36 (m, 2H), 2.32-2.08 (m, 2H), 1.84-1.12 (m, 15H), 0.96 (t, J=7.2 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 40(52)

[2338] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-(N-(2-hydroxyethyl)-N-methylaminosulfonyl)phenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2971

[2339] TLC: Rf 0.68 (chloroform:methanol=5:1);

[2340] NMR (CD3OD): δ 8.00 (d, J=8.7 Hz, 2H), 7.78 (d, J=8.7 Hz, 2H), 4.33 (s, 2H), 4.06 (dd, J=7.5, 4.5 Hz, 1H), 3.86-3.76 (m, 2H), 3.70 (t, J=5.7 Hz, 2H), 3.68-3.60 (m, 2H), 3.58-3.42 (m, 2H), 3.20 (t, J=5.7 Hz, 2H), 2.88 (s, 3H), 2.72-2.58 (m, 2H), 2.50 (s, 3H), 2.44 (s, 3H), 2.28-2.06 (m, 2H), 1.82-1.10 (m, 15H), 0.96 (t, J=7.2 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 40(53)

[2341] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(2-phenylethyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2972

[2342] TLC: Rf 0.24 (chloroform:methanol=10:1);

[2343] NMR (CD3OD): δ 7.28-7.23 (m, 3H), 7.10-7.07 (m, 2H), 4.40 (t, J=6.6 Hz, 2H), 4.19 (s, 2H), 4.06 (dd, J=7.2, 4.8 Hz, 1H), 3.80-3.60 (m, 2H), 3.58-3.36 (m, 4H), 3.12 (t, J=6.6 Hz, 2H), 2.64-2.45 (m, 2H), 2.45 (s, 3H), 2.26-2.04 (m, 2H), 1.95 (s, 3H), 1.84-1.14 (m, 15H), 0.97 (t, J=7.5 Hz, 3H), 0.97 (m, 2H).

EXAMPLE 40(54)

[2344] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(dimethylaminomethyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2973

[2345] TLC: Rf 0.16 (chloroform:methanol=10:1);

[2346] NMR (CD3OD): δ 7.76 (d, J=8.1 Hz, 2H), 7.63 (d, J=8.1 Hz, 2H), 4.41 (s, 2H), 4.37 (s, 2H), 4.03 (dd, J=7.8, 5.1 Hz, 1H), 3.90-3.75 (m, 2H), 3.52-3.38 (m, 4H), 2.87 (s, 6H), 2.64-2.48 (m, 2H), 2.22-2.04 (m, 2H), 1.80-1.15 (m, 15H), 1.00-0.86 (m, 5H).

EXAMPLE 40(55)

[2347] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3-(4-hydroxyphenyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2974

[2348] TLC: Rf 0.58 (chloroform:methanol=10:1);

[2349] NMR (CD3OD): δ 7.81 (s, 1H), 7.69 (d, J=7.5 Hz, 1H), 7.54 (d, J=9.0 Hz, 2H), 7.55-7.48 (m, 1H), 7.45 (d, J=7.5 Hz, 1H), 6.87 (d, J=9.0 Hz, 2H), 4.40 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.92-3.73 (m, 2H), 3.58-3.43 (m, 2H), 3.43-3.32 (m, 2H), 2.55-2.35 (m, 2H), 2.28-2.06 (m, 2H), 1.82-1.10 (m, 15H), 1.08-0.83 (m, 2H), 0.94 (t, J=7.2 Hz, 3H).

EXAMPLE 40(56)

[2350] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(quinoxalin-2-yl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2975

[2351] TLC: Rf 0.67 (chloroform:methanol=10:1);

[2352] NMR (CD3OD): δ 9.51 (s, 1H), 8.13 (d, J=8.0 Hz, 1H),8.05 (d, J=8.0 Hz, 1H), 7.91-7.80 (m, 2H), 4.38 (s, 2H), 4.05 (dd, J=7.5, 4.5 Hz, 1H), 3.96-3.82 (m, 2H), 3.63 (m, 2H), 3.42 (m, 2H), 2.92 (s, 3H), 2.47 (s, 3H), 2.47 (m, 2H), 2.29-2.16 (m, 2H), 1.80-1.18 (m, 15H), 0.95 (t, J=7.2 Hz, 3H), 0.95 (m, 2H).

EXAMPLE 40(57)

[2353] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(phenylcarbonyl) phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2976

[2354] TLC: Rf 0.68 (chloroform:methanol=10:1);

[2355] NMR (CD3OD): δ 7.87 (d, J=8.4 Hz, 2H), 7.82-7.74 (m, 4H), 7.67 (t, J=8.4 Hz, 1H), 7.57-7.51 (m, 2H), 4.48 (s, 2H), 4.04 (dd, J=7.8, 4.8 Hz, 1H), 3.84-3.78 (m, 2H), 3.58-3.38 (m, 4H), 2.58-2.40 (m, 2H), 2.30-2.10 (m, 2H), 1.82-1.14 (m, 15H), 1.02-0.86 (m, 5H).

EXAMPLE 40(58)

[2356] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-methylaminosulfonylphenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2977

[2357] TLC: Rf 0.30 (chloroform:methanol=10:1);

[2358] NMR (CD3OD): δ 8.01 (d, J=8.7 Hz, 2H), 7.74 (d, J=8.7 Hz, 2H), 4.33 (s, 2H), 4.06 (dd, J=7.8, 4.5 Hz, 1H), 3.86-3.78 (m, 2H), 3.68-3.58 (m, 2H), 3.52-3.36 (m, 2H), 2.59 (s, 3H), 2.59-2.38 (m, 2H), 2.48 (s, 3H), 2.41 (s, 3H), 2.34-2.10 (m, 2H), 1.84-1.16 (m, 15H), 0.97 (t, J=7.2 Hz, 3H), 0.97 (m, 2H).

EXAMPLE 40(59)

[2359] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(1,3,5-trimethylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2978

[2360] TLC: Rf 0.43 (chloroform:methanol=10:1);

[2361] NMR (CD3OD): δ 4.28 (s, 2H), 4.03 (dd, J=7.8, 4.5 Hz, 1H), 3.87 (s, 3H), 3.87-3.69 (m, 2H), 3.61-3.43 (m, 4H), 2.69-2.50 (m, 2H), 2.46 (s, 3H), 2.44 (s, 3H), 2.25-2.06 (m, 2H), 1.83-1.12 (m, 15H), 1.05-0.86 (m, 5H).

EXAMPLE 40(60)

[2362] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(morpholin-4-ylmethyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2979

[2363] TLC: Rf 0.56 (chloroform:methanol=10:1);

[2364] NMR (CD3OD): δ 7.74 (d, J=8.4 Hz, 2H), 7.66 (d, J=8.4 Hz, 2H), 4.40 (s, 4H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 4.00-3.70 (m, 6H), 3.54-3.40 (m, 4H), 3.35-3.18 (m, 4H), 2.63-2.47 (m, 2H), 2.24-2.02 (m, 2H), 1.83-1.12 (m, 15H), 1.06-0.85 (m, 5H).

EXAMPLE 40(61)

[2365] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(3-methoxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2980

[2366] TLC: Rf 0.57 (chloroform:methanol=10:1);

[2367] NMR (CD3OD): δ 7.53 (d, J=8.7 Hz, 2H), 7.28 (t, J=8.4 Hz, 1H), 7.07 (d, J=8.7 Hz, 2H), 6.75 (ddd, J=8.4, 2.4, 1.0 Hz, 1H), 6.61-6.57 (m, 2H), 4.34 (s, 2H), 4.04 (dd, J=7.5, 4.5 Hz, 1H), 3.85-3.55 (m, 2H), 3.77 (s, 3H), 3.53-3.47 (m, 2H), 3.40 (m, 2H), 2.50-2.35 (m, 2H), 2.25-2.11 (m, 2H), 1.80-1.23 (m, 15H), 0.95 (t, J=7.2 Hz, 3H), 0.95 (m, 2H).

EXAMPLE 40(62)

[2368] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-methylpiperazin-1-ylmethyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.3 Hydrochloride

2981

[2369] TLC: Rf 0.69 (chloroform:methanol=5:1);

[2370] NMR (CD3OD): δ 7.74 (s, 4H), 4.54 (s, 2H), 4.41 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.87-3.42 (m, 14H), 3.00 (s, 3H), 2.61-2.46 (m, 2H), 2.21-2.07 (m, 2H), 1.79-1.15 (m, 15H), 1.02-0.92 (m, 2H), 0.94 (t, J=7.2 Hz, 3H).

EXAMPLE 40(63)

[2371] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(pyridin-1-oxide-3-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2982

[2372] TLC: Rf 0.42 (chloroform:methanol=9:1);

[2373] NMR (CD3OD): δ 8.45 (t, J=1.8 Hz, 1H), 8.37 (brd, J=6.3 Hz, 1H), 7.71 (dd, J=8.4, 6.3 Hz, 1H), 7.72 (d, J=8.7 Hz, 2H), 7.59 (brdd, J=8.4, 1.8 Hz, 1H), 7.31 (d, J=8.7 Hz, 2H), 4.40 (s, 2H), 4.04 (dd, J=7.8 Hz, 1H), 3.90-3.74 (m, 2H), 3.57-3.40 (m, 4H), 2.58-2.40 (m, 2H), 2.28-2.08 (m, 2H), 1.82-1.14 (m, 15H), 1.04-0.90 (m, 5H).

EXAMPLE 40(64)

[2374] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-phenylsulfonylphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2983

[2375] TLC: Rf 0.77 (ethyl acetate: methanol=9:1);

[2376] NMR (CD3OD): δ 8.08 (d, J=8.4 Hz, 2H), 8.02-7.96 (m, 2H), 7.80 (d, J=8.4 Hz, 2H), 7.70-7.55 (m, 3H), 4.43 (s, 2H), 4.02 (dd, J=7.8, 4.8 Hz, 1H), 3.89-3.73 (m, 2H), 3.49-3.34 (m, 4H), 2.48-2.33 (m, 2H), 2.23-2.04 (m, 2H), 1.82-1.14 (m, 15H), 1.03-0.85 (m, 5H).

EXAMPLE 40(65)

[2377] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-cyclohexylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2984

[2378] TLC: Rf 0.32 (ethyl acetate: methanol=9:1);

[2379] NMR (CD3OD): δ 4.42-4.28 (m, 1H), 4.28 (s, 2H), 4.04 (dd, J=7.5, 4.5 Hz, 1H), 3.90-3.72 (m, 2H), 3.60-3.43 (m, 4H), 2.68-2.50 (m, 2H), 2.50 (s, 3H), 2.46 (s, 3H), 2.25-2.06 (m, 2H), 2.04-1.15 (m, 25H), 1.05-0.89 (m, 5H).

EXAMPLE 40(66)

[2380] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(3-carboxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2985

[2381] TLC: Rf 0.16 (ethyl acetate: methanol=9:1);

[2382] NMR (CD3OD): δ 7.83 (ddd, J=7.8, 1.5, 1.2 Hz, 1H), 7.60 (dd, J=2.4, 1.5 Hz, 1H), 7.57 (d, J=8.7 Hz, 2H), 7.51 (t, J=7.8 Hz, 1H), 7.29 (ddd, J=7.8, 2.4, 1.2 Hz, 1H), 7.12 (d, J=8.7 Hz, 2H), 4.35 (s, 2H), 4.04 (dd, J 7.5, 4.5 Hz, 1H), 3.90-3.74 (m, 2H), 3.58-3.35 (m, 4H), 2.49-2.34 (m, 2H), 2.28-2.09 (m, 2H), 1.93-1.10 (m, 15H), 1.07-0.85 (m, 5H).

EXAMPLE 40(67)

[2383] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(piperidin-1-ylmethyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2986

[2384] TLC: Rf 0.56 (chloroform:methanol=9:1);

[2385] NMR (CD3OD): δ 7.75 (d, J=8.4 Hz, 2H), 7.64 (d, J=8.4 Hz, 2H), 4.40 (s, 2H), 4.34 (s, 2H), 4.03 (dd, J=7.8, 4.8 Hz, 1H), 3.90-3.72 (m, 2H), 3.53-3.38 (m, 6H), 3.05-2.91 (m, 2H), 2.66-2.49 (m, 2H), 2.24-2.04 (m, 2H), 2.00-1.13 (m, 21H), 1.04-0.86 (m, 5H).

EXAMPLE 40(68)

[2386] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-(pyrrolidin-1-ylsulfonyl)phenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2987

[2387] TLC: Rf 0.40 (ethyl acetate: methanol=9:1);

[2388] NMR (CD3OD): δ 8.01 (d, J=8.7 Hz, 2H), 7.76 (d, J=8.7 Hz, 2H), 4.32 (s, 2H), 4.05 (dd, J=7.5, 4.5 Hz, 1H), 3.94-3.75 (m, 2H), 3.66-3.56 (m, 2H), 3.49-3.41 (m, 2H), 3.32-3.25 (m, 4H), 2.60-2.46 (m, 2H), 2.48 (s, 3H), 2.40 (s, 3H), 2.30-2.11 (m, 2H), 1.83-1.14 (m, 19H), 1.05-0.87 (m, 5H).

EXAMPLE 40(69)

[2389] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2,3-dihydrobenzofuran-5-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2988

[2390] TLC: Rf 0.61 (ethyl acetate: methanol=9:1);

[2391] NMR (CD3OD): δ 7.39 (d, J=1.8 Hz, 1H), 7.26 (dd, J=8.4, 1.8 Hz, 1H), 6.81 (d, J=8.4 Hz, 1H), 4.59 (t, J=8.7 Hz, 2H), 4.26 (s, 2H), 4.04 (dd, J=7.8, 4.8 Hz, 1H), 3.84-3.67 (m, 2H), 3.54-3.34 (m, 4H), 3.25 (t, J=8.7 Hz, 2H), 2.48-2.31 (m, 2H), 2.26-2.07 (m, 2H), 1.83-1.14 (m, 15H), 1.04-0.87 (m, 5H).

EXAMPLE 40(70)

[2392] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-carboxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2989

[2393] TLC: Rf 0.55 (ethyl acetate: methanol=9:1);

[2394] NMR (CD3OD): δ 8.04 (d, J=8.7 Hz, 2H), 7.61 (d, J=8.7 Hz, 2H), 7.18 (d, J=8.7 Hz, 2H), 7.07 (d, J=8.7 Hz, 2H), 4.38 (s, 2H), 4.05 (dd, J=7.8, 4.8 Hz, 1H), 3.91-3.74 (m, 2H), 3.57-3.35 (m, 4H), 2.50-2.33 (m, 2H), 2.29-2.09 (m, 2H), 1.84-1.14 (m, 15H), 1.05-0.86 (m, 5H).

EXAMPLE 40(71)

[2395] (3S)-1-butyl-2,5-dioxo-3-cyclohexyl methyl-9-(3,5-dimethyl-1-(4-(2-hydroxyethylaminosulfonyl)phenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2990

[2396] TLC: Rf 0.38 (chloroform:methanol=10:1);

[2397] NMR (CD3OD): δ 8.03 (d, J=8.7 Hz, 2H), 7.72 (d, J=8.7 Hz, 2H), 4.31 (s, 2H), 4.05 (dd, J=7.5, 4.5 Hz, 1H), 3.94-3.74 (m, 2H), 3.66-3.56 (m, 2H), 3.56 (t, J=5.7 Hz, 2H), 3.51-3.41 (m, 2H), 3.01 (t, J=5.7 Hz, 2H), 2.63-2.43 (m, 2H), 2.47 (s, 3H), 2.40 (s, 3H), 2.32-2.10 (m, 2H), 1.93-1.10 (m, 15H), 1.06-0.93 (m, 2H), 0.96 (t, J=7.2 Hz, 3H).

EXAMPLE 40(72)

[2398] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-(2-dimethylaminoethylaminosulfonyl)phenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.3 Hydrochloride

2991

[2399] TLC: Rf 0.13 (chloroform:methanol=10:1);

[2400] NMR (CD3OD): δ 8.07 (d, J=8.7 Hz, 2H), 7.79 (d, J=8.7 Hz, 2H), 4.31 (s, 2H), 4.04 (dd, J=7.5, 4.2 Hz, 1H), 3.82-3.76 (m, 2H), 3.68-3.48 (m, 4H), 3.34-3.24 (m, 4H), 2.95 (s, 6H), 2.76-2.52 (m, 2H), 2.50 (s, 3H), 2.43 (s, 3H), 2.25-2.08 (m, 2H), 1.82-1.14 (m, 15H), 1.02-0.88 (m, 5H).

EXAMPLE 40(73)

[2401] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(1-hydroxy-1-phenylmethyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2992

[2402] TLC: Rf 0.30 (chloroform:methanol=10:1);

[2403] NMR (CD3OD): δ 7.62-7.18 (m, 9H), 5.82 (s, 1H), 4.34 (s, 2H), 4.03 (dd, J 7.5, 4.5 Hz, 1H), 3.88-3.72 (m, 2H), 3.58-3.30 (m, 4H), 2.42-2.04 (m, 4H), 1.82-1.24 (m, 15H), 0.94 (t, J=7.2 Hz, 3H), 0.94 (m, 2H).

EXAMPLE 40(74)

[2404] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(carboxymethyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2993

[2405] TLC: Rf 0.30 (chloroform:methanol=10:1);

[2406] NMR (CD3OD): δ 7.47 (d, J=8.7 Hz, 2H), 7.04 (d, J=8.7 Hz, 2H), 4.70 (s, 2H), 4.29 (s, 2H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.86-3.69 (m, 2H), 3.54-3.33 (m, 4H), 2.44-2.28 (m, 2H), 2.26-2.06 (m, 2H), 1.83-1.12 (m, 15H), 1.04-0.85 (m, 5H).

EXAMPLE 40(75)

[2407] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-hydroxypiperidin-1-ylmethyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2994

[2408] TLC: Rf 0.17 (chloroform:methanol=10:1);

[2409] NMR (CD3OD): δ 7.76 (d, J=7.8 Hz, 2H), 7.70-7.61 (m, 2H), 4.40 (s, 2H), 4.38-4.32 (m, 2H), 4.10-4.05 (m, 1H), 4.03 (dd, J=7.5, 4.5 Hz, 1H), 3.90-3.68 (m, 2H), 3.56-3.40 (m, 4H), 3.18-3.00 (m, 1H), 2.70-2.48 (m, 2H), 2.23-1.82 (m, 5H), 1.82-1.10 (m, 19H), 1.06-0.83 (m, 2H), 0.94 (t, J=7.2 Hz, 3H).

EXAMPLE 40(76)

[2410] (3S)-1-butyl-2,5-dioxo-3-cyclohexyl methyl-9-(4-(3-carboxyphenylmethyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2995

[2411] TLC: Rf 0.57 (chloroform:methanol=5:1);

[2412] NMR (CD3OD): δ 8.10 (s, 1H), 7.98 (d, J=7.8 Hz, 1H), 7.68 (d, J=7.8 Hz, 1H), 7.50 (t, J=7.8 Hz, 1H), 7.46 (d, J=8.7 Hz, 2H), 7.13 (d, J=8.7 Hz, 2H), 5.22 (s, 2H), 4.28 (s, 2H), 4.04 (dd, J=7.8, 4.8 Hz, 1H), 3.84-3.68 (m, 2H), 3.52-3.32 (m, 4H), 2.42-2.08 (m, 4H), 1.82-1.16 (m, 15H), 0.95 (t, J=7.8 Hz, 3H), 0.95 (m, 2H).

EXAMPLE 40(77)

[2413] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(1,4-benzodioxan-6-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2996

[2414] TLC: Rf 0.41 (chloroform:methanol=10:1);

[2415] NMR (CD3OD): δ 7.48 (d, J=9.0 Hz, 2H), 7.02 (d, J=9.0 Hz, 2H), 6.86 (m, 1H), 6.55-6.51 (m, 2H), 4.31 (s, 2H), 4.24 (s, 4H), 4.05 (dd, J=7.5, 4.5 Hz, 1H), 3.86-3.70 (m, 2H), 3.58-3.36 (m, 4H), 2.42-2.08 (m, 4H), 1.82-1.12 (m, 15H), 0.96 (t, J=7.2 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 40(78)

[2416] (3S)-1-butyl-2,5-dioxo-3-cyclohexyl methyl-9-(3-(3-hydroxyphenyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2997

[2417] TLC: Rf 0.24 (chloroform:methanol=10:1);

[2418] NMR (CD3OD): δ 7.81 (s, 1H), 7.74 (m, 1H), 7.60-7.50 (m, 2H), 7.28 (m, 1H), 7.15-7.08 (m, 2H), 6.82 (m, 1H), 4.43 (s, 2H), 4.04 (dd, J 7.5, 4.5 Hz, 1H), 3.86-3.78 (m, 2H), 3.58-3.34 (m, 4H), 2.48-2.08 (m, 4H), 1.84-1.12 (m, 15H), 0.95 (t, J=7.2 Hz, 3H), 0.95 (m, 2H).

EXAMPLE 40(79)

[2419] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(methylsulfonylamino)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

2998

[2420] TLC: Rf 0.40 (chloroform:methanol=10:1);

[2421] NMR (CD3OD): δ 7.53 (d, J=8.4 Hz, 2H), 7.34 (d, J=8.4 Hz, 2H), 4.32 (s, 2H), 4.03 (dd, J=7.8, 4.8 Hz, 1H), 3.86-3.72 (m, 2H), 3.52-3.34 (m, 4H), 3.01 (s, 3H), 2.50-2.32 (m, 2H), 2.24-2.06 (m, 2H), 1.82-1.10 (m, 15H), 1.02-0.86 (m, 5H).

EXAMPLE 40(80)

[2422] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(6-(4-methoxyphenyl) pyridin-3-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

2999

[2423] TLC: Rf 0.67 (chloroform:methanol=10:1);

[2424] NMR (CD3OD): δ 8.26 (m, 1H), 8.02 (m, 1H), 7.08-6.84 (m, 5H), 4.38 (s, 2H), 4.04 (dd, J=7.8, 4.8 Hz, 1H), 3.90-3.72 (m, 2H), 3.81 (s, 3H), 3.56-3.44 (m, 2H), 3.42-3.32 (m, 2H), 2.50-2.30 (m, 2H), 2.30-2.08 (m, 2H), 1.82-1.14 (m, 15H), 1.02-0.88 (m, 5H).

EXAMPLE 40(81)

[2425] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-methylaminocarbonylphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3000

[2426] TLC: Rf 0.46 (chloroform:methanol=10:1);

[2427] NMR (CD3OD): δ 8.39 (br d, J=4.5 Hz, 1H), 7.84 (d, J=9.0 Hz, 2H), 7.58 (d, J=8.4 Hz, 2H), 7.15 (d, J=8.4 Hz, 2H), 7.07 (d, J=9.0 Hz, 2H), 4.35 (s, 2H), 4.04 (m, 1H), 3.85-3.74 (m, 2H), 3.53-3.38 (m, 4H), 2.91 (d, J=4.5 Hz, 3H), 2.55-2.30 (m, 2H), 2.30-2.10 (m, 2H), 1.80-1.10 (m, 15H), 1.10-0.90 (m, 2H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 40(82)

[2428] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-chlorophenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3001

[2429] TLC: Rf 0.76 (chloroform:methanol=10:1);

[2430] NMR (CD3OD): δ 7.52 (d, J=9.0 Hz, 2H), 7.38 (d, J=9.0 Hz, 2H), 7.09 (d, J=9.0 Hz, 2H), 7.02 (d, J=9.0 Hz, 2H), 4.32 (s, 2H), 4.04 (m, 1H), 3.90-3.70 (m, 2H), 3.60-3.30 (m, 4H), 2.50-2.10 (m, 4H), 1.90-1.10 (m, 15H), 1.10-0.90 (m, 2H), 0.95 (t, J=7.5 Hz, 3H).

EXAMPLE 40(83)

[2431] (3S)-1-butyl-2,5-dioxo-3-cyclohexyl methyl-9-(4-bis(methylsulfonyl)aminophenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3002

[2432] TLC: Rf 0.60 (chloroform:methanol=5:1);

[2433] NMR (CD3OD): δ 7.69 (d, J=8.4 Hz, 2H), 7.60 (d, J=8.4 Hz, 2H), 4.41 (s, 2H), 4.05 (dd, J=7.8, 4.8 Hz, 1H), 3.92-3.70 (m, 2H), 3.56-3.36 (m, 4H), 3.47 (s, 6H), 2.46-2.08 (m, 4H), 1.84-1.16 (m, 15H), 0.96 (t, J=7.5 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 40(84)

[2434] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3-(4-carboxyphenyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3003

[2435] TLC: Rf 0.60 (chloroform:methanol=5:1);

[2436] NMR (CD3OD): δ 8.13 (d, J=9.0 Hz, 2H), 7.95 (s, 1H), 7.84 (m, 1H), 7.82 (d, J=9.0 Hz, 2H), 7.66-7.61 (m, 2H), 4.46 (s, 2H), 4.04 (dd, J=7.5, 4.5 Hz, 1H), 3.96-3.78 (m, 2H), 3.62-3.36 (m, 4H), 2.54-2.32 (m, 2H), 2.28-2.08 (m, 2H), 1.82-1.08 (m, 15H), 0.95 (t, J=7.2 Hz, 3H), 0.95 (m, 2H).

EXAMPLE 40(85)

[2437] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(phenylaminocarbonyl) phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3004

[2438] TLC: Rf 0.25 (chloroform:methanol=10:1);

[2439] NMR (CD3OD): δ 8.07 (d, J=8.1 Hz, 2H), 7.73-7.67 (m, 2H), 7.71 (d, J=8.1 Hz, 2H), 7.38 (t, J=7.5 Hz, 2H), 7.17 (t, J=7.5 Hz, 1H), 4.45 (s, 2H), 4.05 (dd, J=7.8, 4.8 Hz, 1H), 3.92-3.72 (m, 2H), 3.58-3.36 (m, 4H), 2.50-2.08 (m, 4H), 1.84-1.08 (m, 15H), 0.96 (t, J=7.8 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 40(86)

[2440] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-methylthiophenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3005

[2441] TLC: Rf 0.48 (chloroform:methanol=10:1);

[2442] NMR (CD3OD): δ 7.54 (d, J=8.7 Hz, 2H), 7.33 (d, J=8.7 Hz, 2H), 7.06 (d, J=8.7 Hz, 2H), 7.00 (d, J=8.7 Hz, 2H), 4.34 (s, 2H), 4.05 (dd, J=7.5, 4.5 Hz, 1H), 3.86-3.70 (m, 2H), 3.56-3.36 (m, 4H), 2.48 (s, 3H), 2.48-2.32 (m, 2H), 2.28-2.08 (m, 2H), 1.82-1.14 (m, 15H), 0.96 (t, J=7.2 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 40(87)

[2443] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-(2-dimethylaminoethylaminocarbonyl)phenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3006

[2444] TLC: Rf 0.11 (chloroform:methanol=10:1);

[2445] NMR (CD3OD): δ 7.94 (d, J=9.0 Hz, 2H), 7.64 (d, J=8.7 Hz, 2H), 7.15 (d, J=8.7 Hz, 2H), 7.10 (d, J=9.0 Hz, 2H), 4.36 (s, 2H), 4.04 (dd, J=7.8, 4.8 Hz, 1H), 3.88-3.72 (m, 4H), 3.52-3.36 (m, 6H), 2.98 (s, 6H), 2.62-2.44 (m, 2H), 2.24-2.08 (m, 2H), 1.80-1.10 (m, 15H), 1.00-0.88 (m, 5H).

EXAMPLE 40(88)

[2446] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-aminocarbonylphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3007

[2447] TLC: Rf 0.19 (chloroform:methanol=10:1);

[2448] NMR (CD3OD): δ 7.98 (d, J=8.4 Hz, 2H), 7.68 (d, J=8.4 Hz, 2H), 4.43 (s, 2H), 4.03 (dd, J=7.5, 4.8 Hz, 1H), 3.92-3.76 (m, 2H), 3.54-3.28 (m, 4H), 2.52-2.36 (m, 2H), 2.24-2.08 (m, 2H), 1.82-1.10 (m, 15H), 1.02-0.88 (m, 5H).

EXAMPLE 40(89)

[2449] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(dimethylaminocarbonyl)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3008

[2450] TLC: Rf 0.33 (chloroform:methanol=10:1);

[2451] NMR (CD3OD): δ 7.67 (d, J=8.1 Hz, 2H), 7.54 (d, J=8.1 Hz, 2H), 4.41 (s, 2H), 4.04 (dd, J=7.5, 4.2 Hz, 1H), 3.92-3.76 (m, 2H), 3.54-3.32 (m, 4H), 3.11 (s, 3H), 2.99 (s, 3H), 2.52-2.32 (m, 2H), 2.26-2.08 (m, 2H), 1.82-1.10 (m, 15H), 1.02-0.86 (m, 5H).

EXAMPLE 40(90)

[2452] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

3009

[2453] TLC: Rf 0.73 (chloroform:methanol=10:1);

[2454] NMR (CDCl3): δ 7.37-7.25 (m, 4H), 7.10 (m, 1H), 7.04-6.98 (m, 2H), 6.96 (d, J=8.7 Hz, 2H), 5.81 (brs, 1H), 3.99 (m, 1H), 3.52 (s, 2H), 3.52-3.32 (m, 2H), 2.92-2.74 (m, 3H), 2.57 (dt, J=12.0, 3.0 Hz, 1H), 2.18-1.88 (m, 5H), 1.76-1.13 (m, 14H), 1.07-0.88 (m, 2H), 0.93 (t, J=7.5 Hz, 3H).

EXAMPLE 41

[2455] By the same procedure as described in Reference Example 3-Reference Example 4 using Resin (3) prepared in Reference Example 2, N-allyloxycarbonyl-4-piperidone, n-butylamine and (2R*, 3R*)-N-(t-butyloxycarbonyl)-2-amino-3-hydroxy-4-methylpentanoic acid, and furthermore by the same procedure as described in Reference Example 5→Reference Example 6→Example 1 using 1,4-benzodioxan-6-carboxyaldehyde, the following compounds (1) and (2) of the present invention were obtained respectively.

EXAMPLE 40(1)

[2456] 1-butyl-2,5-dioxo-3-(1-hydroxy-2-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3010

[2457] (Symbol * means the mixture of syn form and anti form (syn: anti=2:3.)

[2458] TLC: Rf 0.47 (chloroform:methanol=10:1);

[2459] NMR (CD3OD): δ 7.04 (d, J=2.1 Hz, 1H), 6.97 (dd, J=8.4, 2.1 Hz, 1H), 6.93 (d, J=8.4 Hz, 1H), 4.26 (s, 4H), 4.23 (s, 2H), 4.13 (d, J=2.1 Hz, 0.6H), 4.08 (d, J=1.2 Hz, 0.4H), 4.05-3.90 (m, 1H), 3.76-3.63 (m, 1H), 3.62-3.35 (m, 3.4H), 3.19 (dd, J=9.6, 2.1 Hz, 0.6H), 3.20-3.10 (m, 1H), 2.55-2.33 (m, 2H), 2.30-1.95 (m, 3H), 1.80-1.60 (m, 1H), 1.55-1.25 (m, 3H), 1.05-0.89 (m, 9H).

EXAMPLE 41(2)

[2460] (Z)-1-butyl-2,5-dioxo-3-(2-methylpropylidene)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3011

[2461] TLC: Rf 0.52 (chloroform:methanol=20:1);

[2462] NMR (CD3OD): b 7.04 (d, J=2.1 Hz, 1H), 6.97 (dd, J=8.4, 2.1 Hz, 1H), 6.93 (d, J=8.4 Hz, 1H), 5.84 (d, J=10.5 Hz, 1H), 4.26 (s, 4H), 4.23 (s, 2H), 3.72-3.55 (m, 2H), 3.53-3.35 (m, 4H), 2.80-2.60 (m, 1H), 2.43-2.26 (m, 2H), 2.25-2.15 (m, 2H), 1.62-1.48 (m, 2H), 1.45-1.30 (m, 2H), 1.04 (d, J=6.6 Hz, 6H), 0.95 (t, J=7.5 Hz, 3H).

EXAMPLE 41(3)˜41(5)

[2463] By the same procedure as described in Example 41 using the corresponding compounds instead of (2R*, 3R*)-N-(t-butyloxycarbonyl)-2-amino-3-hydroxy-4-methylpentanoic acid, and the corresponding compounds instead of 1,4-benzodioxan-6-carboxyaldehyde, the following compounds of the present invention were obtained.

EXAMPLE 41(3)

[2464] (3S)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxyethyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3012

[2465] TLC: Rf 0.39 (chloroform:methanol=10:1);

[2466] NMR (CD3OD): δ 7.54 (d, J=8.7 Hz, 2H), 7.43-7.35 (m, 2H), 7.21-7.14 (m, 1H), 7.08-7.00 (m, 4H), 4.32 (s, 2H), 4.19 (dq, J=1.5, 6.9 Hz, 1H), 4.10-3.97 (m, 1H), 3.78 (d, J=1.5 Hz, 1H), 3.72-3.51 (m, 2H), 3.51-3.40 (m, 2H), 3.28-3.14 (m, 1H), 2.57-2.42 (m, 2H), 2.40-2.25 (m, 1H), 2.21-2.10 (m, 1H), 1.81-1.60 (m, 1H), 1.50-1.30 (m, 3H), 1.22 (d, J=6.9 Hz, 3H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 41(4)

[2467] (Z)-1-butyl-2,5-dioxo-3-ethylidene-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3013

[2468] TLC: Rf 0.29 (chloroform:methanol=20:1);

[2469] NMR (CD3OD): δ 7.53 (d, J=9.0 Hz, 2H), 7.43-7.35 (m, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.09-7.00 (m, 4H), 6.08 (q, J=7.5 Hz, 1H), 4.33 (s, 2H), 3.76-3.61 (m, 2H), 3.57-3.40 (m, 4H), 2.45-2.30 (m, 2H), 2.28-2.15 (m, 2H), 1.77 (d, J=7.5 Hz, 3H), 1.62-1.46 (m, 2H), 1.44-1.28 (m, 2H), 0.96 (t, J=7.5 Hz, 3H).

EXAMPLE 41(5)

[2470] (Z)-1-butyl-2,5-dioxo-3-(2-methylpropylidene)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3014

[2471] TLC: Rf 0.42 (chloroform:methanol=20:1);

[2472] NMR (CD3OD): δ 7.51 (d, J=8.7 Hz, 2H), 7.43-7.35 (m, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.06 (d, J=8.7 Hz, 2H), 7.08-7.01 (m, 2H), 5.85 (d, J=10.5 Hz, 1H), 4.34 (s, 2H), 3.78-3.64 (m, 2H), 3.57-3.40 (m, 4H), 2.78-2.62 (m, 1H), 2.43-2.18 (m, 4H), 1.62-1.48 (m, 2H), 1.46-1.30 (m, 2H), 1.04 (d, J=6.6 Hz, 6H), 0.96 (t, J=7.5 Hz, 3H).

EXAMPLE 42

[2473] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-benzyloxycarbonyl-1,4,9-triazaspiro[5.5]undecane

3015

[2474] By the same procedure as described in Example 35 using (2R*,3R*)-N-(t-butyloxycarbonyl)-2-amino-3-hydroxy-4-methyl pentanoic acid instead of N-(t-butyloxycarbonyl)-L-leucine, the compound of the present invention having the following physical data was obtained.

[2475] TLC: Rf 0.43 (chloroform:methanol=10:1);

[2476] NMR (CD3OD): δ 7.39-7.30 (m, 5H), 5.13 (br, 2H), 4.12 (d, J=2.5 Hz, 1H), 4.10-4.00 (m, 2H), 3.76-3.50 (m, 2H), 3.39-3.25 (m, 2H), 3.10-2.94 (m, 1H), 2.18 (m, 1H), 2.08-1.83 (m, 4H), 1.70-1.56 (m, 1H), 1.45-1.15 (m, 3H), 1.01-0.89 (m, 9H).

EXAMPLE 43

[2477] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3016

[2478] By the same procedure as described in Example 9 using the compound prepared in Example 42, the compound of the present invention having the following physical data was obtained.

[2479] TLC: Rf 0.08 (chloroform:methanol=10:1);

[2480] NMR (CD3OD): δ 4.15 (d, J=2.0 Hz, 1H), 3.96 (dt, J=13.0, 4.0 Hz, 1H), 3.71 (dt, J=13.0, 4.0 Hz, 1H), 3.57-3.47 (m, 1H), 3.40-3.34 (m, 2H), 3.23-3.12 (m, 2H), 2.47-2.30 (m, 2H), 2.25-1.98 (m, 3H), 1.79-1.66 (m, 1H), 1.52-1.28 (m, 3H), 1.07-0.94 (m, 9H).

EXAMPLE 44(1)˜44(13)

[2481] By the same procedure as described in Example 10 using the compound prepared in Example 43 and the corresponding aldehyde derivatives, the following compounds were obtained.

EXAMPLE 44(1)

[2482] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3017

[2483] TLC: Rf 0.51 (chloroform:methanol=10:1);

[2484] NMR (CD3OD): δ 7.52 (d, J=8.7 Hz, 2H), 7.44-7.35 (m, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.10-7.00 (m, 4H), 4.33 (s, 2H), 4.14 (d, J=2.1 Hz, 1H), 4.06-3.93 (m, 1H), 3.80-3.67 (m, 1H), 3.56-3.40 (m, 3H), 3.19 (dd, J=9.3, 2.1 Hz, 1H), 3.20-3.10 (m, 1H), 2.53-2.35 (m, 2H), 2.35-2.20 (m, 1H), 2.19-2.08 (m, 1H), 2.07-1.91 (m, 1H), 1.80-1.70 (m, 1H), 1.50-1.25 (m, 3H), 0.99 (d, J=6.6 Hz, 3H), 0.97 (d, J=6.6 Hz, 3H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 44(2)

[2485] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

3018

[2486] TLC: Rf 0.38 (chloroform:methanol=10:1);

[2487] NMR (CD3OD): δ 7.60-7.45 (m, 5H), 4.30 (s, 2H), 4.15 (d, J=2.4 Hz, 1H), 4.05 (m, 1H), 3.79 (m, 1H), 3.62-3.48 (m, 3H), 3.29-3.16 (m, 2H), 2.60-2.45 (m, 2H), 2.44-2.30 (m, 7H), 2.17 (m, 1H), 2.01 (m, 1H), 1.70 (m, 1H), 1.51-1.31 (m, 3H), 1.03-0.91 (m, 9H).

EXAMPLE 44(3)

[2488] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(6-phenyloxypyridin-3-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

3019

[2489] TLC: Rf 0.51 (chloroform:methanol=10:1);

[2490] NMR (CD3OD): δ 8.39 (d, J=2.1 Hz, 1H), 8.16 (dd, J=8.4, 2.1 Hz, 1H), 7.46 (t, J=7.8 Hz, 2H), 7.29 (t, J=7.8 Hz, 1H), 7.17 (d, J=7.8 Hz, 2H), 7.08 (d, J=8.4 Hz, 1H), 4.40 (s, 2H), 4.13 (d, J=2.1 Hz, 1H), 4.07-3.94 (m, 1H), 3.83-3.69 (m, 1H), 3.60-3.42 (m, 3H), 3.29-3.22 (m, 1H), 3.19 (dd, J=9.6, 2.1 Hz, 1H), 2.62-2.32 (m, 3H), 2.18-2.07 (m, 1H), 2.06-1.94 (m, 1H), 1.78-1.60 (m, 1H), 1.50-1.31 (m, 3H), 1.07-0.87 (m, 9H).

EXAMPLE 44(4)

[2491] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-(4-methylphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3020

[2492] TLC: Rf 0.46 (chloroform:methanol=10:1);

[2493] NMR (CD3OD): δ 7.47 (d, J=8.7 Hz, 2H), 7.20 (d, J=8.7 Hz, 2H), 7.02 (d, J=8.7 Hz, 2H), 6.92 (d, J=8.7 Hz, 2H), 4.29 (s, 2H), 4.14 (d, J=2.1 Hz, 1H), 3.97 (m, 1H), 3.72 (m, 1H), 3.56-3.39 (m, 2H), 3.25-3.09 (m, 3H), 2.53-2.08 (m, 7H), 2.01 (m, 1H), 1.70 (m, 1H), 1.48-1.28 (m, 3H), 1.05-0.88 (m, 9H).

EXAMPLE 44(5)

[2494] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-cyclohexyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3021

[2495] TLC: Rf 0.43 (chloroform:methanol=10:1);

[2496] NMR (CD3OD): δ 7.40 (d, J=8.7 Hz, 2H), 7.00 (d, J=8.7 Hz, 2H), 4.37 (m, 1H), 4.24 (brs, 2H), 4.13 (d, J=2.1 Hz, 1H), 3.94 (m, 1H), 3.68 (m, 1H), 3.52-3.34 (m, 2H), 3.29-3.07 (m, 3H), 2.52-1.92 (m, 7H), 1.85-1.27 (m, 12H), 1.04-0.89 (m, 9H).

EXAMPLE 44(6)

[2497] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-(tetrahydropyran-4-yl oxy) phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3022

[2498] TLC: Rf 0.20 (ethyl acetate: methanol=10:1);

[2499] NMR (CD3OD): a 7.45 (d, J=8.7 Hz, 2H), 7.06 (d, J=8.7 Hz, 2H), 4.67-4.59 (m, 1H), 4.28 (s, 2H), 4.13 (d, J=2.5 Hz, 1H), 4.00-3.90 (m, 3H), 3.75-3.67 (m, 1H), 3.63-3.53 (m, 2H), 3.50-3.41 (m, 3H), 3.18 (dd, J=9.0, 2.0 Hz, 1H), 3.18 (m, 1H), 2.49-1.96 (m, 7H), 1.77-1.65 (m, 3H), 1.44-1.30 (m, 3H), 0.98 (d, J=6.5 Hz, 3H), 0.96 (d, J=6.5 Hz, 3H), 0.94 (t, J=7.2 Hz, 3H).

EXAMPLE 44(7)

[2500] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-(pyridin-3-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

3023

[2501] TLC: Rf 0.22 (ethyl acetate:methanol=10:1);

[2502] NMR (CD3OD): δ 8.76 (d, J=2.5 Hz, 1H), 8.63 (d, J=6.0 Hz, 1H), 8.29 (dd, J=9.0, 2.5 Hz, 1H), 8.08 (dd, J=9.0, 6.0 Hz, 1H), 7.77 (d, J=9.0 Hz, 2H), 7.35 (d, J=9.0 Hz, 2H), 4.41 (s, 2H), 4.14 (d, J=2.0 Hz, 1H), 4.00 (m, 1H), 3.76 (m, 1H), 3.61-3.47 (m, 3H), 3.20 (dd, J=9.5, 2.0 Hz, 1H), 3.20 (m, 1H), 2.62 (m, 1H), 2.46 (m, 2H), 2.10 (m, 1H), 2.05-1.95 (m, 1H), 1.69 (m, 1H), 1.41-1.35 (m, 3H), 0.99 (d, J=6.5 Hz, 3H), 0.97 (d, J=6.5 Hz, 3H), 0.95 (t, J=7.5 Hz, 3H).

EXAMPLE 44(8)

[2503] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-isopropylphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3024

[2504] TLC: Rf 0.55 (chloroform:methanol=10:1);

[2505] NMR (CD3OD) δ 7.47 (d, J=8.1 Hz, 2H), 7.37 (d, J=8.1 Hz, 2H), 4.31 (s, 2H), 4.13 (d, J=2.1 Hz, 1H), 4.05-3.91 (m, 1H), 3.80-3.65 (m, 1H), 3.57-3.38 (m, 3H), 3.26-3.13 (m, 1H), 3.19 (dd, J=9.3, 2.1 Hz, 1H), 3.03-2.86 (m, 1H), 2.53-2.38 (m, 2H), 2.38-2.23 (m, 1H), 2.16-2.05 (m, 1H), 2.06-1.92 (m, 1H), 1.77-1.56 (m, 1H), 1.49-1.26 (m, 3H), 1.25 (d, J=6.9 Hz, 6H), 0.98 (d, J=6.6 Hz, 3H), 0.97 (d, J=6.6 Hz, 3H), 0.94 (t, J=7.2 Hz, 3H).

EXAMPLE 44(9)

[2506] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(3,5-dimethyl-1-(4-methylphenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

3025

[2507] TLC: Rf 0.49 (chloroform:methanol=10:1);

[2508] NMR (CD3OD): δ 7.40 (s, 4H), 4.33 (s, 2H), 4.15 (d, J=2.1 Hz, 1H), 4.11-3.97 (m, 1H), 3.86-3.72 (m, 1H), 3.64-3.50 (m, 3H), 3.39-3.30 (m, 1H), 3.21 (dd, J=9.3, 2.1 Hz, 1H), 2.72-2.55 (m, 1H), 2.53-2.40 (m, 2H), 2.46 (s, 3H), 2.44 (s, 3H), 2.40 (s, 3H), 2.18-2.07 (m, 1H), 2.07-1.96 (m, 1H), 1.78-1.60 (m, 1H), 1.50-1.30 (m, 3H), 1.00 (d, J=6.6 Hz, 3H), 0.98 (d, J=6.6 Hz, 3H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 44(10)

[2509] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(3-methyl-5-chloro-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

3026

[2510] TLC: Rf 0.56 (chloroform:methanol=10:1);

[2511] NMR (CD3OD): δ 7.58-7.47 (m, 5H), 4.33 (s, 2H), 4.15 (d, J=2.1 Hz, 1H), 4.15-4.02 (m, 1H), 3.89-3.75 (m, 1H), 3.65-3.48 (m, 3H), 3.30-3.20 (m, 1H), 3.20 (dd, J=9.6, 2.1 Hz, 1H), 2.64-2.46 (m, 2H), 2.44 (s, 3H), 2.44-2.32 (m, 1H), 2.21-2.10 (m, 1H), 2.08-1.93 (m, 1H), 1.80-1.60 (m, 1H), 1.52-1.30 (m, 3H), 0.99 (d, J=6.6 Hz, 3H), 0.98 (d, J=6.6 Hz, 3H), 0.96 (t, J=7.2 Hz, 3H).

EXAMPLE 44(11)

[2512] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-(4-carboxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3027

[2513] TLC: Rf 0.29 (chloroform:methanol=10:1);

[2514] NMR (CD3OD): δ 8.04 (d, J=9.0 Hz, 2H), 7.60 (d, J=8.7 Hz, 2H), 7.18 (d, J=8.7 Hz, 2H), 7.07 (d, J=9.0 Hz, 2H), 4.37 (s, 2H), 4.14 (d, J=2.1 Hz, 1H), 4.10-3.94 (m, 1H), 3.83-3.69 (m, 1H), 3.59-3.40 (m, 3H), 3.25-3.12 (m, 1H), 3.19 (dd, J=9.3, 2.1 Hz, 1H), 2.55-2.37 (m, 2H), 2.37-2.22 (m, 1H), 2.19-2.08 (m, 1H), 2.08-1.94 (m, 1H), 1.79-1.60 (m, 1H), 1.52-1.26 (m, 3H), 0.99 (d, J=6.6 Hz, 3H), 0.97 (d, J=6.6 Hz, 3H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 44(12)

[2515] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(3,5-dimethyl-1-(pyridin-2-yl) pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

3028

[2516] TLC: Rf 0.28 (chloroform:methanol=10:1);

[2517] NMR (CD3OD): δ 8.53 (d, J=5.1 Hz, 1H), 8.05 (t, J=7.8 Hz, 1H), 7.81 (d, J=7.8 Hz, 1H), 7.44 (dd, J=7.8, 5.1 Hz, 1H), 4.33 (s, 2H), 4.16 (d, J=2.1 Hz, 1H), 4.06 (m, 1H), 3.78 (m, 1H), 3.62-3.44 (m, 3H), 3.26 (m, 1H), 3.21 (dd, J=9.6, 2.1 Hz, 1H), 2.68 (s, 3H), 2.60-2.30 (m, 3H), 2.42 (s, 3H), 2.16 (m, 1H), 2.02 (m, 1H), 1.72 (m, 1H), 1.50-1.26 (m, 3H), 1.00 (d, J=6.6 Hz, 3H), 0.99 (d, J=6.6 Hz, 3H), 0.96 (t, J=7.2 Hz, 3H).

EXAMPLE 44(13)

[2518] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(3,5-dimethyl-1-(4-carboxyphenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

3029

[2519] TLC: Rf 0.25 (chloroform:methanol: acetic acid=20:2:1);

[2520] NMR (CD3OD): δ 8.19 (d, J=8.7 Hz, 2H), 7.62 (d, J=8.7 Hz, 2H), 4.32 (s, 2H), 4.16 (d, J=2.1 Hz, 1H), 4.12-3.98 (m, 1H), 3.87-3.74 (m, 1H), 3.63-3.45 (m, 3H), 3.30-3.10 (m, 1H), 3.20 (dd, J=9.3, 2.1 Hz, 1H), 2.59-2.48 (m, 2H), 2.44 (s, 3H), 2.40-2.23 (m, 1H), 2.39 (s, 3H), 2.23-2.10 (m, 1H), 2.10-1.96 (m, 1H), 1.80-1.62 (m, 1H), 1.52-1.24 (m, 3H), 1.00 (d, J=6.6 Hz, 3H), 0.98 (d, J=6.6 Hz, 3H), 0.96 (t, J=7.2 Hz, 3H).

EXAMPLE 45

[2521] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-benzyloxycarbonyl-1,4,9-triazaspiro[5.5]undecane

3030

[2522] By the same procedure as described in Example 35 using (2R*,3R*)-N-(t-butyloxycarbonyl)-2-amino-3-hydroxy-3-cyclohexylpropanoic acid instead of N-(t-butyloxycarbonyl)-L-leucine, the compound of the present invention having the following physical data was obtained.

[2523] TLC: Rf 0.53 (chloroform:methanol=10:1);

[2524] NMR (CD3OD): δ 7.39-7.27 (m, 5H), 5.13 (m, 2H), 4.13 (d, J=2.5 Hz, 1H), 4.06-4.02 (m, 2H), 3.78-3.48 (m, 2H), 3.36-3.29 (m, 2H), 3.02 (br, 1H), 2.17 (m, 1H), 2.03-1.58 (m, 10H), 1.47-1.13 (m, 6H), 1.02-0.89 (m, 5H).

EXAMPLE 46

[2525] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-1,4,9-triazaspiro[5.5]undecane

3031

[2526] By the same procedure as described in Example 9 using the compound prepared in Example 45, the compound of the present invention having the following physical data was obtained.

[2527] TLC: Rf 0.33 (chloroform:methanol: acetic acid=20:6:1);

[2528] NMR (CD3OD): δ 4.13 (d, J=2.5 Hz, 1H), 3.48-3.22 (m, 5H), 2.97-2.89 (m, 2H), 2.12-1.65 (m, 10H), 1.56-1.16 (m, 7H), 1.03-0.85 (m, 5H).

EXAMPLE 47(1)˜47(8)

[2529] By the same procedure as described in Example 10 using the compound prepared in Example 46 and the corresponding aldehyde compounds, the following compounds of the present invention were obtained.

EXAMPLE 47(1)

[2530] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3032

[2531] TLC: Rf 0.44 (chloroform:methanol=10:1);

[2532] NMR (CD3OD): δ 7.55-7.51 (m, 2H), 7.42-7.36 (m, 2H), 7.18 (tt, J=7.5, 1.0 Hz, 1H), 7.08-7.01 (m, 4H), 4.32 (s, 2H), 4.15 (d, J=2.0 Hz, 1H), 3.98 (dt, J=3.5, 12.5 Hz, 1H), 3.73 (dt, J=3.5, 12.5 Hz, 1H), 3.57-3.39 (m, 3H), 3.26 (d, J=2.0 Hz, 1H), 3.20 (m, 1H), 2.52-2.39 (m, 2H), 2.30 (m, 1H), 2.12 (d, J=15.5 Hz, 1H), 2.04-1.92 (m, 2H), 1.80-1.62 (m, 5H), 1.48-1.11 (m, 6H), 1.01-0.82 (m, 5H).

EXAMPLE 47(2)

[2533] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexyl methyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

3033

[2534] TLC: Rf 0.41 (chloroform:methanol=10:1);

[2535] NMR (CD3OD): δ 7.60-7.50 (m, 5H), 4.33 (s, 2H), 4.17 (d, J=2.5 Hz, 1H), 4.04 (m, 1H), 3.85-3.75 (m, 1H), 3.61-3.51 (m, 3H), 3.35-3.27 (m, 2H), 2.62 (m, 1H), 2.49-2.44 (m, 5H), 2.41 (s, 3H), 2.15 (m, 1H), 2.05-1.92 (m, 2H), 1.77-1.65 (m, 5H), 1.44-1.15 (m, 6H), 1.01-0.85 (m, 5H).

EXAMPLE 47(3)

[2536] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-isopropyl phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3034

[2537] TLC: Rf 0.69 (chloroform:methanol=10:1);

[2538] NMR (CD3OD): δ 7.48 (d, J=8.4 Hz, 2H), 7.36 (d, J=8.4 Hz, 2H), 4.31 (s, 2H), 4.14 (d, J=2.1 Hz, 1H), 3.98 (m, 1H), 3.72 (m, 1H), 3.55-3.40 (m, 3H), 3.29-3.16 (m, 2H), 2.95 (m, 1H), 2.52-2.24 (m, 3H), 2.15-1.86 (m, 3H), 1.80-1.60 (m, 5H), 1.48-1.10 (m, 6H), 1.25 (d, J=6.9 Hz, 6H), 1.02-0.82 (m, 5H).

EXAMPLE 47(4)

[2539] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(6-methylpyridin-3-yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

3035

[2540] TLC: Rf 0.51 (ethyl acetate: methanol=10:1);

[2541] NMR (CD3OD): δ 8.59 (d, J=2.7 Hz, 1H), 8.19 (dd, J=9.0, 2.7 Hz, 1H), 7.91 (d, J=9.0 Hz, 1H), 7.75 (d, J=8.4 Hz, 2H), 7.30 (d, J=8.4 Hz, 2H), 4.39 (s, 2H), 4.15 (d, J=2.0 Hz, 1H), 3.99 (m, 1H), 3.73 (m, 1H), 3.61-3.46 (m, 3H), 3.37-3.26 (m, 2H), 2.77 (s, 3H), 2.62 (m, 1H), 2.45 (m, 1H), 2.13-1.92 (m, 3H), 1.73 (m, 4H), 1.40-1.14 (m, 8H), 1.01-0.86 (m, 2H), 0.95 (t, J=7.0 Hz, 3H).

EXAMPLE 47(5)

[2542] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(3,5-dimethyl-1-(4-fluorophenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

3036

[2543] TLC: Rf 0.49 (ethyl acetate:methanol=10:1);

[2544] NMR (CD3OD): δ 7.57 (m, 2H), 7.37-7.31 (m, 2H), 4.32 (s, 2H), 4.16 (d, J=2.0 Hz, 1H), 4.08-4.00 (m, 1H), 3.79 (m, 1H), 3.63-3.52 (m, 3H), 3.37-3.27 (m, 2H), 2.65 (m, 1H), 2.48 (m, 1H), 2.45 (s, 3H), 2.39 (s, 3H), 2.16-1.92 (m, 3H), 1.73 (m, 4H), 1.42-1.15 (m, 8H), 1.01-0.88 (m, 2H), 0.95 (t, J=7.0 Hz, 3H).

EXAMPLE 47(6)

[2545] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-methoxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3037

[2546] TLC: Rf 0.25 (chloroform:methanol=10:1);

[2547] NMR (CD3OD): δ 7.47 (d, J=9.0 Hz, 2H), 7.00 (d, J=9.0 Hz, 2H), 6.99-6.92 (m, 4H), 4.30 (s, 2H), 4.16 (d, J=2.1 Hz, 1H), 3.98 (m, 1H), 3.80 (s, 3H), 3.72 (m, 1H), 3.58-3.38 (m, 3H), 3.30-3.08 (m, 2H), 2.54-1.88 (m, 6H), 1.82-1.60 (m, 5H), 1.50-1.10 (m, 6H), 0.96 (t, J=7.5 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 47(7)

[2548] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-fluorophenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3038

[2549] TLC: Rf 0.28 (chloroform:methanol=10:1);

[2550] NMR (CD3OD): δ 7.51 (d, J=8.7 Hz, 2H), 7.13 (d, J=8.7 Hz, 2H), 7.10-7.04 (m, 4H), 4.33 (s, 2H), 4.16 (d, J=2.1 Hz, 1H), 4.00 (m, 1H), 3.72 (m, 1H), 3.58-3.40 (m, 3H), 3.30-3.08 (m, 2H), 2.56-1.88 (m, 6H), 1.82-1.60 (m, 5H), 1.54-1.10 (m, 6H), 0.96 (t, J=7.2 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 47(8)

[2551] (3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-methylsulfonylaminophenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3039

[2552] TLC: Rf 0.52 (ethyl acetate: methanol=10:1);

[2553] NMR (CD3OD): δ 7.53 (d, J=8.1 Hz, 2H), 7.30 (d, J=9.0 Hz, 2H), 7.08 (d, J=8.1 Hz, 2H), 7.04 (d, J=9.0 Hz, 2H), 4.34 (s, 2H), 4.16 (d, J=2.1 Hz, 1H), 4.00 (m, 1H), 3.76 (m, 1H), 3.58-3.42 (m, 3H), 3.30-3.08 (m, 2H), 2.96 (s, 3H), 2.54-1.88 (m, 6H), 1.82-1.62 (m, 5H), 1.50-1.14 (m, 6H), 0.96 (t, J=7.2 Hz, 3H), 0.96 (m, 2H).

EXAMPLE 48

[2554] (3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-allyloxycarbonyl-1,4,9-triazaspiro[5.5]undecane

3040

[2555] By the same procedure as described in Reference Example 3→Reference Example 6→Example 1 using Resin (3) prepared in Reference Example 2, N-allyloxycarbonyl-4-piperidone, 2-butynylamine, and (2R*,3R*)-N-(t-butyloxycarbonyl)-2-amino-3-hydroxy-3-cyclohexylpropanoic acid, the compound of the present invention having the following physical data was obtained.

[2556] TLC: Rf 0.32 (chloroform:methanol=15:1);

[2557] NMR (CD3OD): δ 6.04-5.91 (m, 1H), 5.35-5.27 (m, 1H), 5.23-5.19 (m, 1H), 4.60-4.58 (m, 2H), 4.27 (dq, J=17.5, 2.5 Hz, 1H), 4.19 (d, J=2.5 Hz, 1H), 4.07-4.01 (m, 2H), 3.89 (dq, J=17.5, 2.5 Hz, 1H), 3.75-3.50 (m, 2H), 3.38 (dd, J=9.0, 2.5 Hz, 1H), 2.32-2.17 (m, 2H), 2.07-1.70 (m, 11H), 1.33-1.14 (m, 3H), 1.00-0.85 (m, 2H).

EXAMPLE 49

[2558] (3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-1,4,9-triazaspiro[5.5]undecane

3041

[2559] By the same procedure as described in Reference Example 4 using the compound prepared in Example 48, the compound of the present invention having the following physical data was obtained.

[2560] TLC: Rf 0.33 (chloroform:methanol: acetic acid=20:6:1);

[2561] NMR (CD3OD): δ 4.28 (dq, J=17.5, 2.5 Hz, 1H), 4.18 (d, J=2.5 Hz, 1H), 4.03 (dq, J=17.5, 2.5 Hz, 1H), 3.48-3.29 (m, 3H), 2.99-2.90 (m, 2H), 2.26-1.73 (m, 14H), 1.32-1.18 (m, 3H), 1.01-0.91 (m, 2H).

EXAMPLE 50(1)˜50(6)

[2562] By the same procedure as described in Example 10 using the compound prepared in Example 49 and the corresponding aldehyde compounds, the following compounds of the present invention were obtained.

EXAMPLE 50(1)

[2563] (3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

3042

[2564] TLC: Rf 0.37 (chloroform:methanol=10:1);

[2565] NMR (CD3OD): δ 7.60-7.50 (m, 5H), 4.42-4.33 (m, 3H), 4.21 (d, J=2.5 Hz, 1H), 4.08-3.99 (m, 2H), 3.85-3.75 (m, 1H), 3.65-3.57 (m, 2H), 3.32 (m, 1H), 2.79 (m, 1H), 2.48-2.43 (m, 5H), 2.40 (s, 3H), 2.22 (m, 1H), 2.05-1.93 (m, 2H), 1.80-1.64 (m, 7H), 1.39-1.11 (m, 3H), 1.03-0.84 (m, 2H).

EXAMPLE 50(2)

[2566] (3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(3,5-dimethyl-1-(4-methylphenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

3043

[2567] TLC: Rf 0.35 (chloroform:methanol=10:1);

[2568] NMR (CD3OD): 67.40 (s, 4H),4.45-4.30 (m, 3H), 4.20 (m, 1H), 4.16-3.98 (m, 2H), 3.78 (m, 1H), 3.68-3.56 (m, 2H), 3.30 (m, 1H), 2.82 (m, 1H), 2.56-2.42 (m, 8H), 2.39 (s, 3H), 2.28-1.88 (m, 3H), 1.80-1.60 (m, 7H), 1.40-1.10 (m, 3H), 1.12-0.82 (m, 2H).

EXAMPLE 50(3)

[2569] (3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-isopropylphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3044

[2570] TLC: Rf 0.33 (chloroform:methanol=10:1);

[2571] NMR (CD3OD): δ 7.47 (d, J=8.1 Hz, 2H), 7.36 (d, J=8.1 Hz, 2H), 4.38-4.28 (m, 3H), 4.17 (m, 1H), 4.04-3.88 (m, 2H), 3.74 (m, 1H), 3.50-3.40 (m, 2H), 3.28 (m, 1H), 2.92 (m, 1H), 2.64 (m, 1H), 2.50-1.86 (m, 5H),1.80-1.62 (m, 7H), 1.36-1.04 (m, 3H), 1.25 (d, J=7.2 Hz, 6H), 1.00-0.82 (m, 2H).

EXAMPLE 50(4)

[2572] (3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3045

[2573] TLC: Rf 0.39 (chloroform:methanol=10:1);

[2574] NMR (CD3OD): δ 7.53 (d, J=9.0 Hz, 2H), 7.42-7.37 (m, 2H), 7.17 (t, J=7.5 Hz, 1H), 7.06-7.02 (m, 4H), 4.40-4.30 (m, 3H), 4.18 (m, 1H), 4.04-3.90 (m, 2H), 3.72 (m, 1H), 3.30-3.20 (m, 2H), 3.28 (m, 1H), 2.68 (m, 1H), 2.52-1.86 (m, 5H), 1.80-1.60 (m, 7H), 1.38-1.10 (m, 3H), 1.02-0.82 (m, 2H).

EXAMPLE 50(5)

[2575] (3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-methylphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3046

[2576] TLC: Rf 0.45 (chloroform:methanol=10:1);

[2577] NMR (CD3OD): δ 7.50 (d, J=8.4 Hz, 2H), 7.20 (d, J=8.7 Hz, 2H), 7.01 (d, J=8.7 Hz, 2H), 6.92 (d, J=8.4 Hz, 2H), 4.40-4.28 (m, 3H), 4.18 (m, 1H), 4.04-3.88 (m, 2H), 3.74 (m, 1H), 3.52-3.40 (m, 2H), 3.26 (m, 1H), 2.64 (m, 1H), 2.54-1.86 (m, 5H), 2.33 (s, 3H), 1.80-1.62 (m, 7H), 1.38-1.10 (m, 3H), 1.02-0.82 (m, 2H).

EXAMPLE 50(6)

[2578] (3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3047

[2579] TLC: Rf 0.33 (chloroform:methanol=10:1);

[2580] NMR (CD3OD): δ 7.04 (s, 1H), 6.99-6.91 (m, 2H), 4.35 (m, 1H), 4.27 (s, 4H), 4.24 (s, 2H), 4.18 (m, 1H), 4.04-3.84 (m, 2H), 3.70 (m, 1H), 3.56-3.38 (m, 2H), 3.28 (m, 1H), 2.68-1.88 (m, 6H), 1.80-1.60 (m, 7H), 1.40-1.10 (m, 3H), 1.02-0.80 (m, 2H).

EXAMPLE 51

[2581] (3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-1,4,9-triazaspiro[5.5]undecane.acetate

3048

[2582] By the same procedure as described in Example 48 Example 49 using (2R*,3R*)-N-(t-butyloxycarbonyl)-2-amino-3-hydroxy-4-methylpentanoic acid instead of (2R*,3R*)-N-(t-butyloxycarbonyl)-2-amino-3-hydroxy-3-cyclohexylpropanoic acid, the compound of the present invention having the following physical data was obtained.

[2583] TLC: Rf 0.22 (chloroform:methanol: acetic acid=20:6:1);

[2584] NMR (CD3OD): δ 4.36 (dq, J=17.0, 2.5 Hz, 1H), 4.19 (d, J=2.0 Hz, 1H), 3.95-3.79 (m, 2H), 3.62 (dt, J=3.5, 13.0 Hz, 1H), 3.34-3.26 (m, 2H), 3.22 (dd, J=9.5, 2.0 Hz, 1H), 2.54-2.43 (m, 1H), 2.37 (m, 1H), 2.20-1.98 (m, 3H), 1.91 (s, 3H), 1.75 (t, J=2.5 Hz, 3H), 1.01-0.97 (m, 6H).

EXAMPLE 52(1)˜52(5)

[2585] By the same procedure as described in Example 10 using the compound prepared in Example 51 and the corresponding aldehyde compounds, the following compounds of the present invention were obtained.

EXAMPLE 52(1)

[2586] (3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(3,5-dimethyl-1-(4-methylphenyl)pyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3049

[2587] TLC: Rf 0.28 (chloroform:methanol=10:1);

[2588] NMR (CD3OD): δ 7.38 (d, J=3.9 Hz, 2H), 7.35 (d, J=3.9 Hz, 2H), 4.33 (s, 2H), 4.20 (d, J=2.1 Hz, 1H), 4.10-3.90 (m, 2H), 3.78 (m, 1H), 3.68-3.52 (m, 2H), 3.22 (dd, J=9.3, 2.1 Hz, 1H), 2.74 (m, 1H), 2.54-2.20 (m, 3H), 2.44 (s, 3H), 2.40 (s, 3H), 2.36 (s, 3H), 1.98 (m, 1H), 1.75 (t, J=2.1 Hz, 3H), 1.01 (d, J=6.6 Hz, 3H), 0.99 (d, J=6.6 Hz, 3H).

EXAMPLE 52(2)

[2589] (3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-(4-methylphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3050

[2590] TLC: Rf 0.26 (chloroform:methanol=10:1);

[2591] NMR (CD3OD): δ 7.49 (d, J=9.0 Hz, 2H), 7.21 (d, J=8.4 Hz, 2H), 7.04 (d, J=9.0 Hz, 2H), 6.93 (d, J=8.4 Hz, 2H), 4.40 (m, 1H), 4.34 (s, 2H), 4.19 (d, J=2.1 Hz, 1H), 4.08-3.82 (m, 2H), 3.76 (m, 1H), 3.58-3.40 (m, 2H), 3.20 (dd, J=9.6, 2.1 Hz, 1H), 2.72-2.42 (m, 2H), 2.35 (s, 3H), 2.35-2.18 (m, 2H), 2.00 (m, 1H), 1.74 (t, J=2.1 Hz, 3H), 1.00 (d, J=6.6 Hz, 3H), 0.98 (d, J=6.6 Hz, 3H).

EXAMPLE 52(3)

[2592] (3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3051

[2593] TLC: Rf 0.34 (chloroform:methanol=10:1);

[2594] NMR (CD3OD): δ 7.06-6.92 (m, 3H), 4.38 (m, 1H), 4.28 (s, 4H), 4.25 (s, 2H), 4.19 (d, J=2.1 Hz, 1H), 4.02-3.84 (m, 2H), 3.70 (m, 1H), 3.52-3.36 (m, 2H), 3.20 (dd, J=9.6, 2.1 Hz, 1H), 2.60 (m, 1H), 2.48 (m, 1H), 2.32-2.16 (m, 2H), 2.00 (m, 1H), 1.74 (t, J=2.1 Hz, 3H), 1.00 (d, J=6.6 Hz, 3H), 0.98 (d, J=6.6 Hz, 3H).

EXAMPLE 52(4)

[2595] (3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-isopropylphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3052

[2596] TLC: Rf 0.29 (chloroform:methanol=10:1);

[2597] NMR (CD3OD): δ 7.47 (d, J=8.1 Hz, 2H), 7.38 (d, J=8.1 Hz, 2H), 4.40 (m, 1H), 4.33 (s, 2H), 4.19 (d, J=2.1 Hz, 1H), 4.08-3.84 (m, 2H), 3.76 (m, 1H), 3.52-3.40 (m, 2H), 3.20 (dd, J=9.6, 2.1 Hz, 1H), 2.96 (m, 1H), 2.62 (m, 1H), 2.48 (m, 1H), 2.36-2.12 (m, 2H), 2.00 (m, 1H), 1.74 (t, J=2.1 Hz, 3H), 1.24 (d, J=7.2 Hz, 6H), 1.00 (d, J=6.6 Hz, 3H), 0.98 (d, J=6.6 Hz, 3H).

EXAMPLE 52(5)

[2598] (3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3053

[2599] TLC: Rf 0.24 (chloroform:methanol=10:1);

[2600] NMR (CD3OD): δ 7.52 (d, J=9.0 Hz, 2H), 7.41 (t, J=7.2 Hz, 2H), 7.19 (t, J=7.2 Hz, 1H), 7.09-7.03 (m, 4H), 4.40 (m, 1H), 4.35 (s, 2H), 4.19 (d, J=2.1 Hz, 1H), 4.08-3.84 (m, 2H), 3.78 (m, 1H), 3.58-3.42 (m, 2H), 3.21 (dd, J=9.6, 2.1 Hz, 1H), 2.72-2.42 (m, 2H), 2.38-2.18 (m, 2H), 2.00 (m, 1H), 1.74 (t, J=2.1 Hz, 3H), 1.00 (d, J=6.6 Hz, 3H), 0.98 (d, J=6.6 Hz, 3H).

EXAMPLE 53

[2601] (3R*)-1-butyl-2,5-dioxo-3-((1 S*)-1-hydroxy-1-cyclohexylmethyl)-9-benzyl-1,4,9-triazaspiro[5.5]undecane

3054

[2602] By the same procedure as described in Reference Example 3→Reference Example 6→Example 1 using Resin (3) prepared in Reference Example 2, N-benzyl-4-piperidone, n-butylamine, (2R*,3S*)—N-(t-butyloxycarbonyl)-2-amino-3-hydroxy-3-cyclohexylpropanoic acid, the compound of the present invention having the following physical data was obtained.

[2603] TLC: Rf 0.33 (chloroform:methanol=10:1);

[2604] NMR (CD3OD): δ 7.40-7.20 (m, 5H), 4.04 (d, J=1.5 Hz, 1H), 3.65-3.45 (m, 2H), 3.57 (s, 2H), 3.30 (m, 1H), 3.05 (m 1H), 2.86-2.77 (m, 3H), 2.30-2.00 (m, 4H), 1.90-1.60 (m, 6H), 1.60-1.10 (m, 9H), 1.10-0.90 (m, 2H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 54

[2605] (3R*)-1-butyl-2,5-dioxo-3-((1 S*)-1-hydroxy-1-cyclohexylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3055

[2606] By the same procedure as described in Example 9 using the compound prepared in Example 53, the compound of the present invention having the following physical data was obtained.

[2607] TLC: Rf 0.59 (chloroform:methanol: acetic acid=10:2:1);

[2608] NMR (CD3OD): 64.08 (d, J=1.5 Hz, 1H), 4.03 (m, 1H), 3.70-3.12 (m, 7H), 2.50-2.02 (m, 5H), 1.85-1.66 (m, 5H), 1.55-1.10 (m, 7H), 1.10-0.85 (m, 2H), 0.97 (t, J=6.9 Hz, 3H).

EXAMPLE 55(1)˜55(3)

[2609] By the same procedure as described in Example 10 using the compound prepared in Example 54 and the corresponding aldehyde compounds, the following compounds of the present invention were obtained.

EXAMPLE 55(1)

[2610] (3R*)-1-butyl-2,5-dioxo-3-((1 S*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3056

[2611] TLC: Rf 0.46 (chloroform:methanol=10:1);

[2612] NMR (CD3OD): δ 7.50 (d, J=8.7 Hz, 2H), 7.39 (dd, J=8.7, 7.5 Hz, 2H), 7.17 (t, J=7.5 Hz, 1H), 7.09-7.00 (m, 4H), 4.30 (brs, 2H), 4.08 (d, J=1.2 Hz, 1H), 4.04 (m, 1H), 3.74-3.36 (m, 5H), 3.16 (m, 1H), 2.55-2.33 (m, 2H), 2.32-2.09 (m, 2H), 2.04 (m, 1H), 1.84-1.61 (m, 5H), 1.53-1.12 (m, 7H), 1.04-0.86 (m, 5H).

EXAMPLE 55(2)

[2613] (3R*)-1-butyl-2,5-dioxo-3-((1 S*)-1-hydroxy-1-cyclohexylmethyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3057

[2614] TLC: Rf 0.41 (chloroform:methanol=10:1);

[2615] NMR (CD3OD): δ 7.04 (d, J=2.1 Hz, 1H), 6.97 (dd, J=8.1, 2.1 Hz, 1H), 6.92 (d, J=8.1 Hz, 1H), 4.26 (s, 4H), 4.21 (s, 2H), 4.07 (d, J=1.2 Hz, 1H), 4.01 (m, 1H), 3.70-3.34 (m, 5H), 3.16 (m, 1H), 2.53-2.32 (m, 2H), 2.31-2.08 (m, 2H), 2.03 (m, 1H), 1.84-1.60 (m, 5H), 1.52-1.12 (m, 7H), 1.04-0.85 (m, 5H).

EXAMPLE 55(3)

[2616] (3R*)-1-butyl-2,5-dioxo-3-((1 S*)-1-hydroxy-1-cyclohexylmethyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

3058

[2617] TLC: Rf 0.31 (chloroform:methanol=10:1);

[2618] NMR (CD3OD): δ 7.61-7.44 (m, 5H), 4.31 (s, 2H), 4.19-4.06 (m, 2H), 3.73 (m, 1H), 3.66-3.52 (m, 4H), 3.26 (m, 1H), 2.62-2.48 (m, 2H), 2.45-2.30 (m, 7H), 2.19 (m, 1H), 2.04 (m, 1H), 1.84-1.63 (m, 5H), 1.54-1.12 (m, 7H), 1.05-0.86 (m, 5H).

EXAMPLE 56

[2619] (3S)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylpropyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3059

[2620] By the same procedure as described in Example 42 Example 43 using (2S,3S)—N-(t-butyloxycarbonyl)-2-amino-3-hydroxy-4-methylpentanoic acid instead of (2R*,3R*)-N-(t-butyloxycarbonyl)-2-amino-3-hydroxy-4-methylpentanoic acid, the compound of the present invention having the following physical data was obtained.

[2621] TLC: Rf 0.08 (chloroform:methanol=10:1);

[2622] NMR (CD3OD): δ 4.15 (d, J=2.0 Hz, 1H), 3.96 (dt, J=13.0, 4.0 Hz, 1H), 3.71 (dt, J=13.0, 4.0 Hz, 1H), 3.57-3.47 (m, 1H), 3.40-3.34 (m, 2H), 3.23-3.12 (m, 2H), 2.47-2.30 (m, 2H), 2.25-1.98 (m, 3H), 1.79-1.66 (m, 1H), 1.52-1.28 (m, 3H), 1.07-0.94 (m, 9H);

[2623] Optical rotation: [α]D−13.8 (c 1.00, methanol).

EXAMPLE 57(1)-57(4)

[2624] By the same procedure as described in Example 10 using the compound prepared in Example 56 and the corresponding aldehyde compounds, the following compounds of the present invention were obtained.

EXAMPLE 57(1)

[2625] (3S)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

3060

[2626] TLC: Rf 0.43 (chloroform:methanol=10:1);

[2627] NMR (CD3OD): δ 7.61-7.43 (m, 5H), 4.32 (s, 2H), 4.16 (d, J=2.1 Hz, 1H), 4.12-3.99 (m, 1H), 3.90-3.72 (m, 1H), 3.64-3.44 (m, 3H), 3.30-3.12 (m, 1H), 3.20 (dd, J=9.3, 2.1 Hz, 1H), 2.60-2.30 (m, 9H), 2.24-2.10 (m, 1H), 2.10-1.95 (m, 1H), 1.78-1.60 (m, 1H), 1.54-1.30 (m, 3H), 1.00 (d, J=6.6 Hz, 3H), 0.98 (d, J=6.6 Hz, 3H), 0.96 (t, J=6.9 Hz, 3H).

EXAMPLE 57(2)

[2628] (3S)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3061

[2629] TLC: Rf 0.51 (chloroform:methanol=10:1);

[2630] NMR (CD3OD): δ 7.52 (d, J=8.7 Hz, 2H), 7.43-7.36 (m, 2H), 7.21-7.14 (m, 1H), 7.10-7.00 (m, 4H), 4.33 (s, 2H), 4.14 (d, J=2.1 Hz, 1H), 4.06-3.92 (m, 1H), 3.81-3.66 (m, 1H), 3.58-3.40 (m, 3H), 3.30-3.10 (m, 1H), 3.19 (dd, J=9.6, 2.1 Hz, 1H), 2.53-2.37 (m, 2H), 2.37-2.18 (m, 1H), 2.18-2.08 (m, 1H), 2.06-1.95 (m, 1H), 1.78-1.60 (m, 1H), 1.50-1.26 (m, 3H), 0.99 (d, J=6.6 Hz, 3H), 0.97 (d, J=6.6 Hz, 3H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 57(3)

[2631] (3S)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3062

[2632] TLC: Rf 0.43 (chloroform:methanol=10:1);

[2633] NMR (CD3OD): δ 7.06 (d, J=2.1 Hz, 1H), 6.98 (dd, J=8.1, 2.1 Hz, 1H), 6.92 (d, J=8.1 Hz, 1H), 4.26 (s, 4H), 4.23 (s, 2H), 4.13 (d, J=2.4 Hz, 1H), 4.02-3.87 (m, 1H), 3.77-3.62 (m, 1H), 3.57-3.35 (m, 3H), 3.28-3.08 (m, 1H), 3.19 (dd, J=9.6, 2.4 Hz, 1H), 2.51-2.35 (m, 2H), 2.35-2.18 (m, 1H), 2.17-2.05 (m, 1H), 2.05-1.90 (m, 1H), 1.80-1.58 (m, 1H), 1.50-1.26 (m, 3H), 0.98 (d, J=6.6 Hz, 3H), 0.97 (d, J=6.6 Hz, 3H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 57(4)

[2634] (3S)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylpropyl)-9-(4-(4-methylsulfonylaminophenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3063

[2635] TLC: Rf 0.35 (chloroform:methanol=10:1);

[2636] NMR (CD3OD): δ 7.53 (d, J=8.7 Hz, 2H), 7.29 (d, J=9.0 Hz, 2H), 7.10-7.00 (m, 4H), 4.33 (s, 2H), 4.14 (d, J=2.1 Hz, 1H), 4.06-3.92 (m, 1H), 3.81-3.66 (m, 1H), 3.58-3.40 (m, 3H), 3.25-3.10 (m, 1H), 3.19 (dd, J=9.6, 2.1 Hz, 1H), 2.95 (s, 3H),2.54-2.37 (m, 2H), 2.37-2.22 (m, 1H), 2.18-2.08 (m, 1H), 2.08-1.92 (m, 1H), 1.78-1.60 (m, 1H), 1.50-1.28 (m, 3H), 0.99 (d, J=6.6 Hz, 3H), 0.97 (d, J=6.6 Hz, 3H), 0.95 (t, J=7.5 Hz, 3H).

EXAMPLE 58

[2637] (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3064

[2638] By the same procedure as described in Example 42 Example 43 using (2R,3R)-N-(t-butyloxycarbonyl)-2-amino-3-hydroxy-4-methylpentanoic acid instead of (2R*,3R*)-N-(t-butyloxycarbonyl)-2-amino-3-hydroxy-4-methylpentanoic acid, the compound of the present invention having the following physical data was obtained.

[2639] TLC: Rf 0.08 (chloroform:methanol=10:1);

[2640] NMR (CD3OD): δ 4.15 (d, J=2.0 Hz, 1H), 3.96 (dt, J=13.0, 4.0 Hz, 1H), 3.71 (dt, J=13.0, 4.0 Hz, 1H), 3.57-3.47 (m, 1H), 3.40-3.34 (m, 2H), 3.23-3.12 (m, 2H), 2.47-2.30 (m, 2H), 2.25-1.98 (m, 3H), 1.79-1.66 (m, 1H), 1.52-1.28 (m, 3H), 1.07-0.94 (m, 9H);

[2641] Optical rotation: [α]D+13.9 (c 1.00, methanol).

EXAMPLE 59(1)˜59(4)

[2642] By the same procedure as described in Example 10 using the compound prepared in Example 58 and the corresponding aldehyde compounds, the following compounds of the present invention were obtained.

EXAMPLE 59(1)

[2643] (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

3065

[2644] TLC: Rf 0.43 (chloroform:methanol=10:1);

[2645] NMR (CD3OD): δ 7.61-7.43 (m, 5H), 4.32 (s, 2H), 4.16 (d, J=2.1 Hz, 1H), 4.12-3.99 (m, 1H), 3.90-3.72 (m, 1H), 3.64-3.44 (m, 3H), 3.30-3.12 (m, 1H), 3.20 (dd, J=9.3, 2.1 Hz, 1H), 2.60-2.30 (m, 9H), 2.24-2.10 (m, 1H), 2.10-1.95 (m, 1H), 1.78-1.60 (m, 1H), 1.54-1.30 (m, 3H), 1.00 (d, J=6.6 Hz, 3H), 0.98 (d, J=6.6 Hz, 3H), 0.96 (t, J=6.9 Hz, 3H).

EXAMPLE 59(2)

[2646] (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3066

[2647] TLC: Rf 0.51 (chloroform:methanol=10:1);

[2648] NMR (CD3OD): δ 7.52 (d, J=8.7 Hz, 2H), 7.43-7.36 (m, 2H), 7.21-7.14 (m, 1H), 7.10-7.00 (m, 4H), 4.33 (s, 2H), 4.14 (d, J=2.1 Hz, 1H), 4.06-3.92 (m, 1H), 3.81-3.66 (m, 1H), 3.58-3.40 (m, 3H), 3.30-3.10 (m, 1H), 3.19 (dd, J=9.6, 2.1 Hz, 1H), 2.53-2.37 (m, 2H), 2.37-2.18 (m, 1H), 2.18-2.08 (m, 1H), 2.06-1.95 (m, 1H), 1.78-1.60 (m, 1H), 1.50-1.26 (m, 3H), 0.99 (d, J=6.6 Hz, 3H), 0.97 (d, J=6.6 Hz, 3H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 59(3)

[2649] (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3067

[2650] TLC: Rf 0.43 (chloroform:methanol=10:1);

[2651] NMR (CD3OD): δ 7.06 (d, J=2.1 Hz, 1H), 6.98 (dd, J=8.1, 2.1 Hz, 1H), 6.92 (d, J=8.1 Hz, 1H), 4.26 (s, 4H), 4.23 (s, 2H), 4.13 (d, J=2.4 Hz, 1H), 4.02-3.87 (m, 1H), 3.77-3.62 (m, 1H), 3.57-3.35 (m, 3H), 3.28-3.08 (m, 1H), 3.19 (dd, J=9.6, 2.4 Hz, 1H), 2.51-2.35 (m, 2H), 2.35-2.18 (m, 1H), 2.17-2.05 (m, 1H), 2.05-1.90 (m, 1H), 1.80-1.58 (m, 1H), 1.50-1.26 (m, 3H), 0.98 (d, J=6.6 Hz, 3H), 0.97 (d, J=6.6 Hz, 3H), 0.95 (t, J=7.2 Hz, 3H).

EXAMPLE 594(4)

[2652] (3R)-1-butyl-2,5-dioxo-3-((1R)-11-hydroxy-2-methylpropyl)-9-(4-(4-methylsulfonylaminophenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3068

[2653] TLC: Rf 0.35 (chloroform:methanol=10:1);

[2654] NMR (CD3OD): δ 7.53 (d, J=8.7 Hz, 2H), 7.29 (d, J=9.0 Hz, 2H), 7.10-7.00 (m, 4H), 4.33 (s, 2H), 4.14 (d, J=2.1 Hz, 1H), 4.06-3.92 (m, 1H), 3.81-3.66 (m, 1H), 3.58-3.40 (m, 3H), 3.25-3.10 (m, 1H), 3.19 (dd, J=9.6, 2.1 Hz, 1H), 2.95 (s, 3H), 2.54-2.37 (m, 2H), 2.37-2.22 (m, 1H), 2.18-2.08 (m, 1H), 2.08-1.92 (m, 1H), 1.78-1.60 (m, 1H), 1.50-1.28 (m, 3H), 0.99 (d, J=6.6 Hz, 3H), 0.97 (d, J=6.6 Hz, 3H), 0.95 (t, J=7.5 Hz, 3H).

EXAMPLE 60

[2655] (3R)-1l-butyl-2,5-dioxo-3-((l S)-1l-hydroxy-2-methylpropyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3069

[2656] By the same procedure as described in Example 53 Example 54 using (2R,3S)—N-(t-butyloxycarbonyl)-2-amino-3-hydroxy-4-methyl pentanoic acid instead of (2 R*,3S*)-N-(t-butyloxycarbonyl)-2-amino-3-hydroxy-3-cyclohexylpropanoic acid, the compound of the present invention having the following physical data was obtained.

[2657] TLC: Rf 0.51 (chloroform:methanol: acetic acid=10:2:1);

[2658] NMR (CD3OD): δ 4.08 (d, J=1.5 Hz, 1H), 4.02 (dt, J=12.6, 3.9 Hz, 1H), 3.70-3.00 (m, 6H), 2.50-2.10 (m, 4H), 1.80-1.60 (m, 2H), 1.55-1.35 (m, 3H), 1.02 (d, J=6.6 Hz, 3H), 0.99 (t, J=6.6 Hz, 3H), 0.93 (d, J=6.6 Hz, 3H);

[2659] Optical rotation: [α]D+21.2 (c 1.00, methanol).

EXAMPLE 61(1)˜61(3)

[2660] By the same procedure as described in Example 10 using the compound prepared in Example 60 and the corresponding aldehyde compounds, the following compounds of the present invention were obtained.

EXAMPLE 61(1)

[2661] (3R)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

3070

[2662] TLC: Rf 0.44 (chloroform:methanol=10:1);

[2663] NMR (CD3OD): δ 7.64-7.46 (m, 5H), 4.32 (s, 2H), 4.19-4.06 (m, 1H), 4.10 (d, J=1.5 Hz, 1H), 3.80-3.53 (m, 4H), 3.51 (dd, J=10.2, 1.5 Hz, 1H), 3.40-3.20 (m, 1H), 2.70-2.30 (m, 9H), 2.23-2.10 (m, 1H), 1.83-1.60 (m, 2H), 1.53-1.30 (m, 3H), 1.02 (d, J=6.6 Hz, 3H), 0.96 (t, J=7.2 Hz, 3H), 0.93 (d, J=6.6 Hz, 3H).

EXAMPLE 61(2)

[2664] (3R)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3071

[2665] TLC: Rf 0.44 (chloroform:methanol=10:1);

[2666] NMR (CD3OD): δ 7.06 (d, J=2.1 Hz, 1H), 6.98 (dd, J=8.1, 2.1 Hz, 1H), 6.92 (d, J=8.1 Hz, 1H), 4.26 (s, 4H), 4.23 (s, 2H), 4.08 (d, J=1.5 Hz, 1H), 4.08-3.96 (m, 1H), 3.72-3.35 (m, 4H), 3.49 (dd, J=10.2, 1.5 Hz, 1H), 3.28-3.08 (m, 1H), 2.55-2.35 (m, 2H), 2.35-2.18 (m, 1H), 2.18-2.08 (m, 1H), 1.82-1.62 (m, 2H), 1.52-1.25 (m, 3H), 1.01 (d, J=6.6 Hz, 3H), 0.95 (t, J=7.2 Hz, 3H), 0.92 (d, J=6.6 Hz, 3H).

EXAMPLE 61(3)

[2667] (3R)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylpropyl)-9-(4-(4-methylsulfonylaminophenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3072

[2668] TLC: Rf 0.42 (chloroform:methanol=10:1);

[2669] NMR (CD3OD): δ 7.53 (d, J=8.7 Hz, 2H), 7.29 (d, J=9.0 Hz, 2H), 7.07 (d, J=8.7 Hz, 2H), 7.03 (d, J=9.0 Hz, 2H), 4.33 (s, 2H), 4.13-4.00 (m, 1H), 4.09 (d, J=1.5 Hz, 1H), 3.75-3.62 (m, 1H), 3.62-3.39 (m, 3H), 3.49 (dd, J=10.5, 1.5 Hz, 1H), 3.26-3.12 (m, 1H), 2.95 (s, 3H), 2.56-2.37 (m, 2H), 2.37-2.20 (m, 1H), 2.20-2.10 (m, 1H), 1.82-1.63 (m, 2H), 1.50-1.30 (m, 3H), 1.01 (d, J=6.6 Hz, 3H), 0.95 (t, J=7.2 Hz, 3H), 0.92 (d, J=6.6 Hz, 3H).

EXAMPLE 62

[2670] (3S)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3073

[2671] By the same procedure as described in Example 53 Example 54 using (2S,3R)-N-(t-butyloxycarbonyl)-2-amino-3-hydroxy-4-methylpentanoic acid instead of (2R*,3S*)-N-(t-butyloxycarbonyl)-2-amino-3-hydroxy-3-cyclohexylpropanoic acid, the compound of the present invention having the following physical data was obtained.

[2672] TLC: Rf 0.51 (chloroform:methanol: acetic acid=10:2:1);

[2673] NMR (CD3OD): a 4.08 (d, J=1.5 Hz, 1H), 4.02 (dt, J=12.6, 3.9 Hz, 1H), 3.70-3.00 (m, 6H), 2.50-2.10 (m, 4H), 1.80-1.60 (m, 2H), 1.55-1.35 (m, 3H), 1.02 (d, J=6.6 Hz, 3H), 0.99 (t, J=6.6 Hz, 3H), 0.93 (d, J=6.6 Hz, 3H);

[2674] Optical rotation: [α]D−23.4 (c 1.00, methanol).

EXAMPLE 63(1)˜63(3)

[2675] By the same procedure as described in Example 10 using the compound prepared in Example 62 and the corresponding aldehyde compounds, the following compounds of the present invention were obtained.

EXAMPLE 63(1)

[2676] (3S)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.2 Hydrochloride

3074

[2677] TLC: Rf 0.44 (chloroform:methanol=10:1);

[2678] NMR (CD3OD): δ 7.64-7.46 (m, 5H), 4.32 (s, 2H), 4.19-4.06 (m, 1H), 4.10 (d, J=1.5 Hz, 1H), 3.80-3.53 (m, 4H), 3.51 (dd, J=10.2, 1.5 Hz, 1H), 3.40-3.20 (m, 1H), 2.70-2.30 (m, 9H), 2.23-2.10 (m, 1H), 1.83-1.60 (m, 2H), 1.53-1.30 (m, 3H), 1.02 (d, J=6.6 Hz, 3H), 0.96 (t, J=7.2 Hz, 3H), 0.93 (d, J=6.6 Hz, 3H).

EXAMPLE 63(2)

[2679] (3S)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3075

[2680] TLC: Rf 0.44 (chloroform:methanol=10:1);

[2681] NMR (CD3OD): δ 7.06 (d, J=2.1 Hz, 1H), 6.98 (dd, J=8.1, 2.1 Hz, 1H), 6.92 (d, J=8.1 Hz, 1H), 4.26 (s, 4H), 4.23 (s, 2H), 4.08 (d, J=1.5 Hz, 1H), 4.08-3.96 (m, 1H), 3.72-3.35 (m, 4H), 3.49 (dd, J=10.2, 1.5 Hz, 1H), 3.28-3.08 (m, 1H), 2.55-2.35 (m, 2H), 2.35-2.18 (m, 1H), 2.18-2.08 (m, 1H), 1.82-1.62 (m, 2H), 1.52-1.25 (m, 3H), 1.01 (d, J=6.6 Hz, 3H), 0.95 (t, J=7.2 Hz, 3H), 0.92 (d, J=6.6 Hz, 3H).

EXAMPLE 63(3)

[2682] (3S)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-9-(4-(4-methylsulfonylaminophenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3076

[2683] TLC: Rf 0.42 (chloroform:methanol=10:1);

[2684] NMR (CD3OD): δ 7.53 (d, J=8.7 Hz, 2H), 7.29 (d, J=9.0 Hz, 2H), 7.07 (d, J=8.7 Hz, 2H), 7.03 (d, J=9.0 Hz, 2H), 4.33 (s, 2H), 4.13-4.00 (m, 1H), 4.09 (d, J=1.5 Hz, 1H), 3.75-3.62 (m, 1H), 3.62-3.39 (m, 3H), 3.49 (dd, J=10.5, 1.5 Hz, 1H), 3.26-3.12 (m, 1H), 2.95 (s, 3H), 2.56-2.37 (m, 2H), 2.37-2.20 (m, 1H), 2.20-2.10 (m, 1H), 1.82-1.63 (m, 2H), 1.50-1.30 (m, 3H), 1.01 (d, J=6.6 Hz, 3H), 0.95 (t, J=7.2 Hz, 3H), 0.92 (d, J=6.6 Hz, 3H).

EXAMPLE 64

[2685] (3S)-2,5-dioxo-3-(3-benzyloxycarbonylaminopropyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane.hydrochloride

3077

[2686] By the same procedure as described in Reference Example 9→Reference Example 10→Example 1 using Resin (3) prepared in Reference Example 2, N-(2-phenylethyl)-4-piperidone, 2,4,6-trimethoxybenzylamine and Nα-(t-butyloxycarbonyl)-Nδ-(benzyloxycarbonyl)-L-ornithine, the compound of the present invention having the following physical data was obtained.

[2687] TLC: Rf 0.33 (chloroform:methanol=10:1);

[2688] NMR (DMSO-d6): δ 10.80-10.00 (m, 1H), 8.65-8.45 (m, 1H), 8.33 (s, 1H), 7.50-7.20 (m, 10H), 5.01 (s, 2H), 4.01 (m, 1H), 3.70-3.45 (m, 3H), 3.45-3.20 (m, 3H), 3.15-2.90 (m, 4H), 2.50-2.30 (m, 2H), 2.10-1.90 (m, 1H), 1.87-1.60 (m, 3H), 1.60-1.35 (m, 2H).

EXAMPLE 65

[2689] (3S)-1-methyl-2,5-dioxo-3-(3-benzyloxycarbonylaminopropyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane.acetate

3078

[2690] By the same procedure as described in Example 19 using Resin (3) prepared in Reference Example 2, N-(2-phenylethyl)-4-piperidone, methylamine and Nα-(t-butyloxycarbonyl)-Nδ-(benzyloxycarbonyl)-L-ornithine, the compound of the present invention having the following physical data was obtained.

[2691] TLC: Rf 0.36 (chloroform:methanol=10:1);

[2692] MS (ESI, Pos., 40 V): 493(M+H)+;

[2693] HPLC condition: F;

[2694] HPLC retention time: 3.36 min.

EXAMPLE 66

[2695] (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-phenyloxyphenylmethyl)-9-oxide-1,4,9-triazaspiro[5.5]undecane

3079

[2696] To a solution of the compound prepared in Example 40(90) (104 mg) in acetone (4 ml) were added water (1 ml), sodium hydrogen carbonate (210 mg) and OXONE (615 mg) (brand name). The reaction mixture was stirred for 1 hour at room temperature. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous solution of sodium hydrogen carbonate, and saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by preparative thin layer chromatography (chloroform:methanol=30:1, 20:1) to give the compound of the present invention (73 mg) having the following physical data.

[2697] TLC: Rf 0.50 (chloroform:methanol=9:1);

[2698] NMR (CDCl3): δ 7.49 (dt, J=8.7, 2.1 Hz, 2H), 7.36 (ddt, J=8.7, 7.2, 2.1 Hz, 2H), 7.14 (tt, J=7.2, 1.2 Hz, 1H), 7.04 (dq, J=8.7, 1.2 Hz, 2H), 7.01 (dt, J=8.7, 2.1 Hz, 2H), 5.82 (brs, 1H), 4.32 (s, 2H), 4.07-3.85 (m, 3H), 3.55-3.46 (m, 2H), 3.19-2.97 (m, 4H), 2.02-1.49 (m, 11H), 1.48-1.12 (m, 6H), 1.08-0.90 (m, 2H), 0.90 (t, J=7.2 Hz, 3H).

EXAMPLE 67(H32-1)˜67(H34-15)

[2699] By the same procedure as described in Example 23 using Resin (3) prepared in Reference Example 2, the corresponding 4-piperidone derivatives, the corresponding amine derivatives, the corresponding amino acid derivatives, and the corresponding aldehyde derivatives, the compounds of the present invention, whose names were shown in the following Table 32A-1˜34A-2, and whose structures were shown in the following Table 32B-1˜34B-3, were obtained. Also, physical data of the above compounds were shown in the following Table 32C-1˜34C-1.

579TABLE 32A-1Example NoCompound Name67(H32-1)1-butyl-2,5-dioxo-3-benzyl-9-(4-methoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane67(H32-2)1-butyl-2,5-dioxo-3-benzyl-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane67(H32-3)1-butyl-2,5-dioxo-3-benzyl-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane67(H32-4)1-butyl-2,5-dioxo-3-benzyl-9-(4-benzyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane67(H32-5)1-butyl-2,5-dioxo-3-benzyl-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane67(H32-6)1-butyl-2,5-dioxo-3-benzyl-9-(2-phenylimidazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane67(H32-7)1-(2-methoxyethyl)-2,5-dioxo-3-benzyl-9-(4-methoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane67(H32-8)1-(2-methoxyethyl)-2,5-dioxo-3-benzyl-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane67(H32-9)1-(2-methoxyethyl)-2,5-dioxo-3-benzyl-9-(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

[2700]

580

TABLE 32A-2

Example No
Compound Name

67(H32-10)
1-(2-methoxyethyl)-2,5-dioxo-3-benzyl-9-(4-

benzyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H32-11)
1-(2-methoxyethyl)-2,5-dioxo-3-benzyl-9-(3,5-dimethyl-1-

phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H32-12)
1-(2-methoxyethyl)-2,5-dioxo-3-benzyl-9-(2-

phenylimidazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H32-13)
1-benzyl-2,5-dioxo-3-benzyl-9-(4-methoxyphenylmethyl)-

1,4,9-triazaspiro[5.5]undecane

67(H32-14)
1-benzyl-2,5-dioxo-3-benzyl-9-(1,4-benzodioxan-6-

ylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H32-15)
1-benzyl-2,5-dioxo-3-benzyl-9-(4-phenyloxyphenylmethyl)-

1,4,9-triazaspiro[5.5]undecane

67(H32-16)
1-benzyl-2,5-dioxo-3-benzyl-9-(4-benzyloxyphenylmethyl)-

1,4,9-triazaspiro[5.5]undecane

67(H32-17)
1-benzyl-2,5-dioxo-3-benzyl-9-(3,5-dimethyl-1-

phenylpyrazol-4-ylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H32-18)
1-benzyl-2,5-dioxo-3-benzyl-9-(2-phenylimidazol-4-

ylmethyl)-1,4,9-triazaspiro[5.5]undecane

[2701]

581

TABLE 32A-3

Example No
Compound Name

67(H32-19)
(3S)-1-butyl-2,5-dioxo-3-(4-methoxybenzyl)-9-

cyclohexylmethyl-1,4,9-triazaspiro[5.5]undecane

67(H32-20)
(3S)-1-butyl-2,5-dioxo-3-(4-methoxybenzyl)-9-(2-

methylpropyl)-1,4,9-triazaspiro[5.5]undecane

67(H32-21)
(3R)-1-butyl-2,5-dioxo-3-(4-methoxybenzyl)-9-

cyclohexylmethyl-1,4,9-triazaspiro[5.5]undecane

67(H32-22)
(3R)-1-butyl-2,5-dioxo-3-(4-methoxybenzyl)-9-(2-

methylpropyl)-1,4,9-triazaspiro[5.5]undecane

67(H32-23)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(4-

chlorophenyl)thiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

67(H32-24)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(4-

methoxyphenyl)thiophen-2-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[2702]

582

TABLE 33A-1

Example No
Compound Name

67(H33-1)
1-(2-chlorophenylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-

(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H33-2)
1-(2-fluorophenylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-

(4-phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H33-3)
1-(2-trifluoromethylphenylmethyl)-2,5-dioxo-3-(2-

methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

67(H33-4)
1-cyclopropylmethyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H33-5)
1-(2,2-dimethylpropyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H33-6)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H33-7)
1-(furan-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H33-8)
1-((2E)-2-butenyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

[2703]

583

TABLE 33A-2

Example No
Compound Name

67(H33-9)
1-(2-methoxyethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(5-

ethylthiophen-2-ylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H33-10)
1-(2-phenyloxyethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H33-11)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-

9-(2-chloro-4-hydroxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

67(H33-12)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-chloro-4-

hydroxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H33-13)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-9-

(4-hydroxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H33-14)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-

hydroxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H33-15)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(2-

chloro-4-hydroxyphenylmethyl)-1,4,9-triazaspiro[5.5]

undecane

67(H33-16)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-chloro-4-

hydroxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

[2704]

584

TABLE 33A-3

Example No
Compound Name

67(H33-17)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

hydroxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H33-18)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

hydroxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

[2705]

585

TABLE 34A-1

Example No
Compound Name

67(H34-1)
(3S)-1-butyl-2,5-dioxo-3-((1S)-1-methylpropyl)-9-(4-

phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H34-2)
(3S)-1-butyl-2,5-dioxo-3-((1S)-1-methylpropyl)-9-(1,4-

benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H34-3)
(3S)-1-(2-methoxyethyl)-2,5-dioxo-3-((1S)-1-

methylpropyl)-9-(4-phenyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]

67(H34-4)
(3S)-1-(2-methoxyethyl)-2,5-dioxo-3-((1S)-1-

methylpropyl-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-

triazaspiro[5.5]undecane

67(H34-5)
(3S)-1-butyl-2,5-dioxo-3-(cyclohexylmethyloxymethyl)-9-

(4-phenyloxypheflylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H34-6)
(3S)-1-butyl-2,5-dioxo-3-(cyclohexylmethyloxymethyl)-9-

(1,4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]

undecane

67(H34-7)
(3S)-1-(2-methoxyethyl)-2,5-dioxo-3-

(cyclohexylmethyloxymethyl)-9-(4-

phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

[2706]

586

TABLE 34A-2

Example No
Compound Name

67(H34-8)
(3S)-1-(2-methoxyethyl)-2,5-dioxo-3-

(cyclohexylmethyloxymethyl)-9-(1,4-benzodioxan-6-

ylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H34-9)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-chloro-1,3-

benzodioxolan-5-ylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H34-10)
1-(2-methoxyethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

chloro-1,3-benzodioxolan-5-ylmethyl)-1,4,9-triazaspiro[5.5]

undecane

67(H34-11)
1-(3-methyl-2-butenyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

phenyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H34-12)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-((2E)-3-phenyl-2-

propenyl)-1,4,9-triazaspiro[5.5]undecane

67(H34-13)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-((2E)-3-phenyl-2-

propenyl)-1,4,9-triazaspiro[5.5]undecane

67(H34-14)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(quinolin-3-

ylmethyl)-1,4,9-triazaspiro[5.5]undecane

67(H34-15)
1-(3-methyl-2-butenyl)-2,5-dioxo-3-cyclohexylmethyl-9-(1,

4-benzodioxan-6-ylmethyl)-1,4,9-triazaspiro[5.5]undecane

[2707]

587

TABLE 32B-1

3080

Example No
R1
R2
R3
R4
R5

67(H32-1)

3081

3082

3083

H

67(H32-2)

3084

3085

3086

H

67(H32-3)

3087

3088

3089

H

67(H32-4)

3090

3091

3092

H

67(H32-5)

3093

3094

3095

H

67(H32-6)

3096

3097

3098

[2708]

588

TABLE 32B-2

3099

Example No
R1
R2
R3
R4
R5

67(H32-7)

3100

3101

3102

H

67(H32-8)

3103

3104

3105

H

67(H32-9)

3106

3107

3108

H

67(H32-10)

3109

3110

3111

H

67(H32-11)

3112

3113

3114

H

67(H32-12)

3115

3116

3117

[2709]

589

TABLE 32B-3

3118

Example No
R1
R2
R3
R4
R5

67(H32-13)

3119

3120

3121

H

67(H32-14)

3122

3123

3124

H

67(H32-15)

3125

3126

3127

H

67(H32-16)

3128

3129

3130

H

67(H32-17)

3131

3132

3133

H

67(H32-18)

3134

3135

3136

H

67(H32-19)

3137

3138

3139

[2710]

590

TABLE 32B-4

3140

Example No
R1
R2
R3
R4
R5

67(H32-20)

3141

3142

3143

H

67(H32-21)

3144

3145

3146

H

67(H32-22)

3147

3148

3149

H

67(H32-23)

3150

3151

3152

H

67(H32-24)

3153

3154

3155

[2711]

591

TABLE 33B-1

3156

Example No
R1
R2
R3
R4
R5

67(H33-1)

3157

3158

3159

H

67(H33-2)

3160

3161

3162

H

67(H33-3)

3163

3164

3165

H

67(H33-4)

3166

3167

3168

H

67(H33-5)

3169

3170

3171

H

67(H33-6)

3172

3173

3174

[2712]

592

TABLE 33B-2

3175

Example No
R1
R2
R3
R4
R5

67(H33-7)

3176

3177

3178

H

67(H33-8)

3179

3180

3181

H

67(H33-9)

3182

3183

3184

H

67(H33-10)

3185

3186

3187

H

67(H33-11)

3188

3189

3190

H

67(H33-12)

3191

3192

3193

H

67(H33-13)

3194

3195

3196

[2713]

593

TABLE 33B-3

3197

Exam-

ple No
R1
R2
R3
R4
R5

67(H33- 14)

3198

3199

3200

H

67(H33- 15)

3201

3202

3203

H

67(H33- 16)

3204

3205

3206

H

67(H33- 17)

3207

3208

3209

H

67(H33- 18)

3210

3211

3212

[2714]

594

TABLE 34B-1

3213

Example No
R1
R2
R3
R4
R5

67(H34-1)

3214

3215

3216

H

67(H34-2)

3217

3218

3219

H

67(H34-3)

3220

3221

3222

H

67(H34-4)

3223

3224

3225

H

67(H34-5)

3226

3227

3228

[2715]

595

TABLE 34B-2

3229

Example No
R1
R2
R3
R4
R5

67(H34-6)

3230

3231

3232

H

67(H34-7)

3233

3234

3235

H

67(H34-8)

3236

3237

3238

H

67(H34-9)

3239

3240

3241

H

67(H34-10)

3242

3243

3244

H

67(H34-11)

3245

3246

3247

[2716]

596

TABLE 34B-3

3248

Example No
R1
R2
R3
R4
R5

67(H34-12)

3249

3250

3251

H

67(H34-13)

3252

3253

3254

H

67(H34-14)

3255

3256

3257

H

67(H34-15)

3258

3259

3260

[2717]

597

TABLE 32C-1

Re-

HPLC
tention

con-
time

Example No
dition
(min)
Mass data
Mass condition

67(H32-1)
F
3.42
450 (M + H)+, 121.
ESI (Pos., 40 V)

67(H32-2)
F
3.40
478 (M + H)+, 149.
ESI (Pos., 40 V)

67(H32-3)
F
3.72
512 (M + H)+, 183.
ESI (Pos., 40 V)

67(H32-4)
F
3.71
526 (M + H)+, 197.
ESI (Pos., 40 V)

67(H32-5)
F
3.42
514 (M + H)+,
ESI (Pos., 40 V)

303, 185.

67(H32-6)
F
3.31
486 (M + H)+.
ESI (Pos., 40 V)

67(H32-7)
F
3.27
452 (M + H)+, 121.
ESI (Pos., 40 V)

67(H32-8)
F
3.27
480 (M + H)+, 149.
ESI (Pos., 40 V)

67(H32-9)
F
3.55
514 (M + H)+,
ESI (Pos., 40 V)

339, 183.

67(H32-10)
F
3.58
528 (M + H)+,
ESI (Pos., 40 V)

339, 197.

67(H32-11)
F
3.29
516 (M + H)+, 185.
ESI (Pos., 40 V)

67(H32-12)
F
3.12
488 (M + H)+.
ESI (Pos., 40 V)

67(H32-13)
F
3.47
484 (M + H)+,
ESI (Pos., 40 V)

303, 121.

67(H32-14)
F
3.47
512 (M + H)+,
ESI (Pos., 40 V)

303, 148.

67(H32-15)
F
3.73
546 (M + H)+, 183.
ESI (Pos., 40 V)

67(H32-16)
F
3.75
560 (M + H)+, 197.
ESI (Pos., 40 V)

67(H32-17)
F
3.49
548 (M + H)+,
ESI (Pos., 40 V)

303, 185.

67(H32-18)
F
3.33
520 (M + H)+, 404.
ESI (Pos., 40 V)

67(H32-19)
F
3.52
456 (M + H)+.
ESI (Pos., 40 V)

67(H32-20)
F
3.29
416 (M + H)+.
ESI (Pos., 40 V)

67(H32-21)
F
3.49
456 (M + H)+.
ESI (Pos., 40 V)

67(H32-22)
F
3.31
416 (M + H)+.
ESI (Pos., 40 V)

67(H32-23)
F
3.78
502 (M + H)+, 206.
ESI (Pos., 40 V)

67(H32-24)
F
3.69
498 (M + H)+,
ESI (Pos., 40 V)

279, 203.

[2718]

598

TABLE 33C-1

Retention

HPLC
time

Example No
condition
(min)
Mass data
Mass condition

67(H33-1)
F
3.78
546 (M + H)+,
ESI (Pos., 40 V)

183.

67(H33-2)
F
3.75
530 (M + H)+,
ESI (Pos., 40 V)

183.

67(H33-3)
F
3.84
580 (M + H)+.
ESI (Pos., 40 V)

67(H33-4)
F
3.66
476 (M + H)+,
ESI (Pos., 40 V)

339, 183.

67(H33-5)
F
3.80
492 (M + H)+,
ESI (Pos., 40 V)

183.

67(H33-6)
F
3.73
518 (M + H)+,
ESI (Pos., 40 V)

183.

67(H33-7)
F
3.67
502 (M + H)+,
ESI (Pos., 40 V)

182.

67(H33-8)
F
3.67
476 (M + H)+,
ESI (Pos., 40 V)

183.

67(H33-9)
F
3.36
422 (M + H)+,
ESI (Pos., 40 V)

298, 125.

67(H33-10)
F
3.80
542 (M + H)+,
ESI (Pos., 40 V)

183.

67(H33-11)
F
3.44
515 (M + H)+.
ESI (Pos., 20 V)

67(H33-12)
F
3.44
476 (M + H)+.
ESI (Pos., 20 V)

67(H33-13)
F
3.38
482 (M + H)+.
ESI (Pos., 20 V)

67(H33-14)
F
3.36
442 (M + H)+.
ESI (Pos., 20 V)

67(H33-15)
F
3.26
476 (M + H)+.
ESI (Pos., 20 V)

67(H33-16)
F
3.22
436 (M + H)+.
ESI (Pos., 20 V)

67(H33-17)
F
3.20
442 (M + H)+.
ESI (Pos., 20 V)

67(H33-18)
F
3.15
402 (M + H)+.
ESI (Pos., 20 V)

[2719]

599

TABLE 34C-1

Retention

HPLC
time

Example No
condition
(min)
Mass data
Mass condition

67(H34-1)
F
3.71
478 (M + H)+,
ESI (Pos., 40 V)

279, 183.

67(H34-2)
F
3.42
444 (M + H)+,
ESI (Pos., 40 V)

149.

67(H34-3)
F
3.55
480 (M + H)+,
ESI (Pos., 40 V)

183.

67(H34-4)
F
3.23
446 (M + H)+,
ESI (Pos., 40 V)

149.

67(H34-5)
F
3.9
548 (M + H)+.
ESI (Pos., 40 V)

67(H34-6)
F
3.65
514 (M + H)+,
ESI (Pos., 40 V)

279, 149.

67(H34-7)
F
3.76
550 (M + H)+,
ESI (Pos., 40 V)

183.

67(H34-8)
F
3.49
516 (M + H)+,
ESI (Pos., 40 V)

149.

67(H34-9)
F
3.47
464 (M + H)+.
ESI (Pos., 40 V)

67(H34-10)
F
3.31
466 (M + H)+.
ESI (Pos., 40 V)

67(H34-11)
F
3.73
490 (M + H)+,
ESI (Pos., 40 V)

279, 183.

67(H34-12)
F
3.55
412 (M + H)+,
ESI (Pos., 40 V)

117.

67(H34-13)
F
3.72
452 (M + H)+,
ESI (Pos., 40 V)

379, 279, 117.

67(H34-14)
F
3.44
477 (M + H)+,
ESI (Pos., 40 V)

404, 345.

67(H34-15)
F
3.64
496 (M + H)+,
ESI (Pos., 40 V)

279, 149.

EXAMPLE 68(H35-1)˜H35-61)

[2720] By the same procedure as described in Reference Example 11 using Resin (3) prepared in Reference Example 2, the corresponding 4-piperidone derivatives, the corresponding amine derivatives, and the corresponding amino acid derivatives, and by the same procedure as described in Reference Example 12→Example 33 using the corresponding alcohol derivatives, and by cleavage from resin, the compounds of the present invention, whose names were shown in the following Table 35A-1˜35A-8, and whose structures were shown in the following Table 35B-1˜35B-13, were obtained. Also, physical data of the above compounds were shown in the following Table 35C-1˜35C-3.

600TABLE 35A-1Example NoCompound Name68(H35-1)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-chloro-4-(2-(N,N-diethylamino)ethyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane68(H35-2)1-(thiophen-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-9-(4-(2-(N,N-diethylamino)ethyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane68(H35-3)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(2-(N,N-diethylamino)ethyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane68(H35-4)1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(2-chloro-4-(2-(N,N-diethylamino)ethyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane68(H35-5)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-chloro-4-(2-(N,N-diethylamino)ethyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane68(H35-6)1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-(2-(N,N-diethylamino)ethyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane68(H35-7)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(2-(N,N-diethylamino)ethyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane

[2721]

601

TABLE 35A-2

Example No
Compound Name

68(H35-8)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-9-

(2-chloro-4-methoxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

68(H35-9)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-chloro-4-

methoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-10)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-9-

(4-methoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-11)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-

methoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-12)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(2-

chloro-4-methoxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

68(H35-13)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-chloro-4-

methoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-14)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

methoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-15)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-9-

(2-chloro-4-ethoxyphenylmethyl)-1,4,9-triazaspiro[5.5]

undecane

[2722]

602

TABLE 35A-3

Example No
Compound Name

68(H35-16)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-chloro-4-

ethoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-17)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-

9-(4-ethoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-18)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-

ethoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-19)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(2-

chloro-4-ethoxyphenylmethyl)-1,4,9-triazaspiro[5.5]

undecane

68(H35-20)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-chloro-4-

ethoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-21)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

ethoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-22)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

ethoxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-23)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-

9-(2-chloro-4-propyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[2723]

603

TABLE 35A-4

Example No
Compound Name

68(H35-24)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-chloro-4-

propyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-25)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-9-

(4-propyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-26)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-

propyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-27)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(2-

chloro-4-propyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

68(H35-28)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-chloro-4-

propyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-29)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

propyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-30)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-9-

(2-chloro-4-isopropyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

68(H35-31)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-chloro-4-

isopropyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

[2724]

604

TABLE 35A-5

Example

No
Compound Name

68(H35-32)
1-(thiophen-2-ylmethyl)-2,5-

dioxo-3-cyclohexylmethyl-9-(4-

isopropyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-33)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-

isopropyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-34)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(2-

chloro-4-isopropyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

68(H35-35)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-chloro-4-

isopropyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-36)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

isopropyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-37)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

isopropyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-38)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-9-

(2-chloro-4-(cyclopropylmethyloxy)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[2725]

605

TABLE 35A-6

Example No
Compound Name

68(H35-39)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-chloro-4-

(cyclopropylmethyloxy)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

68(H35-40)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-9-

(4-(cyclopropylmethyloxy)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

68(H35-41)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-

(cyclopropylmethyloxy)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

68(H35-42)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(2-

chloro-4-(cyclopropylmethyloxy)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

68(H35-43)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-chloro-4-

(cyclopropylmethyloxy)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

68(H35-44)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

(cyclopropylmethyloxy)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

68(H35-45)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

(cyclopropylmethyloxy)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[2726]

606

TABLE 35A-7

Example No
Compound Name

68(H35-46)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-9-(2-

chloro-4-cyclobutyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

68(H35-47)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-chloro-4-

cyclobutyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-48)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-9-(4-

cyclobutyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-49)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-9-(2-

chloro-4-cyclopentyloxylmethyl)-1,4,9-

triazaspiro[5.5]undecane

68(H35-50)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-chloro-4-

cyclopentyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-51)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-9-(4-

cyclopentyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-52)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-

cyclopentyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-53)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(2-

chloro-4-cyclopentyloxyphenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

[2727]

607

TABLE 35A-8

Example No
Compound Name

68(H35-54)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-chloro-4-

cyclopentyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-55)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-

cyclopentyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-56)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

cyclopentyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-57)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-9-(2-

chloro-4-(tetrahydropyran-4-yloxy)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

68(H35-58)
1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-chloro-4-

(tetrahydropyran-4-yloxy)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

68(H35-59)
1-(thiophen-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(2-

chloro-4-(tetrahydropyran-4-yloxy)phenylmethyl)-1,4,9-

triazaspiro[5.5]undecane

68(H35-60)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-

cyclobutyloxyphenylmethyl)-1,4,9-triazaspiro[5.5]undecane

68(H35-61)
1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(tetrahydropyran-4-

yloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane

[2728]

608

TABLE 35B-1

3261

Example

No
R1
R2
R3
R4
R5

68(H35-1)

3262

3263

3264

H

68(H35-2)

3265

3266

3267

H

68(H35-3)

3268

3269

3270

H

68(H35-4)

3271

3272

3273

[2729]

609

TABLE 35B-2

3274

Example

No
R1
R2
R3
R4
R5

68(H35-5)

3275

3276

3277

H

68(H35-6)

3278

3279

3280

H

68(H35-7)

3281

3282

3283

H

68(H35-8)

3284

3285

3286

H

68(H35-9)

3287

3288

3289

[2730]

610

TABLE 35B-3

3290

Example No
R1
R2
R3
R4
R5

68(H35-10)

3291

3292

3293

H

68(H35-11)

3294

3295

3296

H

68(H35-12)

3297

3298

3299

H

68(H35-13)

3300

3301

3302

H

68(H35-14)

3303

3304

3305

H

68(H35-15)

3306

3307

3308

[2731]

611

TABLE 35B-4

3309

Example No
R1
R2
R3
R4
R5

68(H35-16)

3310

3311

3312

H

68(H35-17)

3313

3314

3315

H

68(H35-18)

3316

3317

3318

H

68(H35-19)

3319

3320

3321

H

68(H35-20)

3322

3323

3324

[2732]

612

TABLE 35B-5

3325

Example No
R1
R2
R3
R4
R5

68(H35-21)

3326

3327

3328

H

68(H35-22)

3329

3330

3331

H

68(H35-23)

3332

3333

3334

H

68(H35-24)

3335

3336

3337

H

68(H35-25)

3338

3339

3340

[2733]

613

TABLE 35B-6

3341

Example No
R1
R2
R3
R4
R5

68(H35-26)

3342

3343

3344

H

68(H35-27)

3345

3346

3347

H

68(H35-28)

3348

3349

3350

H

68(H35-29)

3351

3352

3353

H

68(H35-30)

3354

3355

3356

[2734]

614

TABLE 35B-7

3357

Example

No
R1
R2
R3
R4
R5

68 (H35-31)

3358

3359

3360

H

68 (H35-32)

3361

3362

3363

H

68 (H35-33)

3364

3365

3366

H

68 (H35-34)

3367

3368

3369

H

68 (H35-35)

3370

3371

3372

[2735]

615

TABLE 35B-8

3373

Example No
R1
R2
R3
R4
R5

68(H35-36)

3374

3375

3376

H

68(H35-37)

3377

3378

3379

H

68(H35-38)

3380

3381

3382

H

68(H35-39)

3383

3384

3385

H

68(H35-40)

3386

3387

3388

[2736]

616

TABLE 35B-9

3389

Example No
R1
R2
R3
R4
R5

68(H35-41)

3390

3391

3392

H

68(H35-42)

3393

3394

3395

H

68(H35-43)

3396

3397

3398

H

68(H35-44)

3399

3400

3401

H

68(H35-45)

3402

3403

3404

[2737]

617

TABLE 35B-10

3405

Example No
R1
R2
R3
R4
R5

68(H35-46)

3406

3407

3408

H

68(H35-47)

3409

3410

3411

H

68(H35-48)

3412

3413

3414

H

68(H35-49)

3415

3416

3417

H

68(H35-50)

3418

3419

3420

[2738]

618

TABLE 35B-11

3421

Example

No
R1
R2
R3
R4
R5

68(H35- 51)

3422

3423

3424

H

68(H35- 52)

3425

3426

3427

H

68(H35- 53)

3428

3429

3430

H

68(H35- 54)

3431

3432

3433

H

68(H35- 55)

3434

3435

3436

[2739]

619

TABLE 35B-12

3437

Example

No.
R1
R2
R3
R4
R5

68 (H35-56)

3438

3439

3440

H

68 (H35-57)

3441

3442

3443

H

68 (H35-58)

3444

3445

3446

H

68 (H35-59)

3447

3448

3449

H

68 (H35-60)

3450

3451

3452

[2740]

620

TABLE 35B-13

3453

Example No
R1
R2
R3
R4
R5

68(H35-61)

3454

3455

3456

[2741]

621

TABLE 35C-1

Retention

HPLC
time

Example No
condition
(min)
Mass data
Mass condition

68(H35-1)
F
3.31
575 (M + H)+.
ESI (Pos., 20 V)

68(H35-2)
F
3.24
581 (M + H)+.
ESI (Pos., 20 V)

68(H35-3)
F
3.22
541 (M + H)+.
ESI (Pos., 20 V)

68(H35-4)
F
3.11
575 (M + H)+.
ESI (Pos., 20 V)

68(H35-5)
F
3.11
534 (M + H)+.
ESI (Pos., 20 V)

68(H35-6)
F
3.09
540 (M + H)+.
ESI (Pos., 20 V)

68(H35-7)
F
3.05
501 (M + H)+.
ESI (Pos., 20 V)

68(H35-8)
F
3.57
530 (M + H)+.
ESI (Pos., 20 V)

68(H35-9)
F
3.57
548 (M + H)+.
ESI (Pos., 20 V)

68(H35-10)
F
3.51
496 (M + H)+.
ESI (Pos., 20 V)

68(H35-11)
F
3.49
456 (M + H)+.
ESI (Pos., 20 V)

68(H35-12)
F
3.40
490 (M + H)+.
ESI (Pos., 20 V)

68(H35-13)
F
3.36
450 (M + H)+.
ESI (Pos., 20 V)

68(H35-14)
F
3.29
415 (M + H)+.
ESI (Pos., 20 V)

68(H35-15)
F
3.66
544 (M + H)+.
ESI (Pos., 20 V)

68(H35-16)
F
3.64
504 (M + H)+.
ESI (Pos., 20 V)

68(H35-17)
F
3.58
510 (M + H)+.
ESI (Pos., 20 V)

68(H35-18)
F
3.59
469 (M + H)+.
ESI (Pos., 20 V)

68(H35-19)
F
3.47
504 (M + H)+.
ESI (Pos., 20 V)

68(H35-20)
F
3.45
463 (M + H)+.
ESI (Pos., 20 V)

68(H35-21)
F
3.40
470 (M + H)+.
ESI (Pos., 20 V)

68(H35-22)
F
3.38
430 (M + H)+.
ESI (Pos., 20 V)

68(H35-23)
F
3.76
558 (M + H)+.
ESI (Pos., 20 V)

68(H35-24)
F
3.74
518 (M + H)+.
ESI (Pos., 20 V)

68(H35-25)
F
3.68
524 (M + H)+.
ESI (Pos., 20 V)

68(H35-26)
F
3.66
484 (M + H)+.
ESI (Pos., 20 V)

68(H35-27)
F
3.58
518 (M + H)+.
ESI (Pos., 20 V)

68(H35-28)
F
3.57
478 (M + H)+.
ESI (Pos., 20 V)

[2742]

622

TABLE 35C-2

Retention

HPLC
time

Example No
condition
(min)
Mass data
Mass condition

68(H35-29)
F
3.51
484 (M + H)+.
ESI (Pos., 20 V)

68(H35-30)
F
3.71
558 (M + H)+.
ESI (Pos., 20 V)

68(H35-31)
F
3.70
518 (M + H)+.
ESI (Pos., 20 V)

68(H35-32)
F
3.66
524 (M + H)+.
ESI (Pos., 20 V)

68(H35-33)
F
3.64
484 (M + H)+.
ESI (Pos., 20 V)

68(H35-34)
F
3.55
518 (M + H)+.
ESI (Pos., 20 V)

68(H35-35)
F
3.52
478 (M + H)+.
ESI (Pos., 20 V)

68(H35-36)
F
3.48
484 (M + H)+.
ESI (Pos., 20 V)

68(H35-37)
F
3.45
444 (M + H)+.
ESI (Pos., 20 V)

68(H35-38)
F
3.71
570 (M + H)+.
ESI (Pos., 20 V)

68(H35-39)
F
3.72
530 (M + H)+.
ESI (Pos., 20 V)

68(H35-40)
F
3.66
536 (M + H)+.
ESI (Pos., 20 V)

68(H35-41)
F
3.64
496 (M + H)+.
ESI (Pos., 20 V)

68(H35-42)
F
3.55
530 (M + H)+.
ESI (Pos., 20 V)

68(H35-43)
F
3.53
490 (M + H)+.
ESI (Pos., 20 V)

68(H35-44)
F
3.48
496 (M + H)+.
ESI (Pos., 20 V)

68(H35-45)
F
3.47
456 (M + H)+.
ESI (Pos., 20 V)

68(H35-46)
F
3.78
570 (M + H)+.
ESI (Pos., 20 V)

68(H35-47)
F
3.77
530 (M + H)+.
ESI (Pos., 20 V)

68(H35-48)
F
3.54
557 (M + H)+.
ESI (Pos., 20 V)

68(H35-49)
F
3.81
584 (M + H)+.
ESI (Pos., 20 V)

68(H35-50)
F
3.83
545 (M + H)+.
ESI (Pos., 20 V)

68(H35-51)
F
3.74
550 (M + H)+.
ESI (Pos., 20 V)

68(H35-52)
F
3.74
510 (M + H)+.
ESI (Pos., 20 V)

68(H35-53)
F
3.64
544 (M + H)+.
ESI (Pos., 20 V)

68(H35-54)
F
3.65
504 (M + H)+.
ESI (Pos., 20 V)

68(H35-55)
F
3.57
510 (M + H)+.
ESI (Pos., 20 V)

68(H35-56)
F
3.57
470 (M + H)+.
ESI (Pos., 20 V)

[2743]

623

TABLE 35C-3

Retention

HPLC
time

Example No
condition
(min)
Mass data
Mass condition

68(H35-57)
F
3.53
600 (M + H)+.
ESI (Pos., 20 V)

68(H35-58)
F
3.59
560 (M + H)+.
ESI (Pos., 20 V)

68(H35-59)
F
3.42
560 (M + H)+.
ESI (Pos., 20 V)

68(H35-60)
F
3.66
456 (M + H)+,
ESI (Pos., 40 V)

279, 161.

68(H35-61)
F
3.45
586 (M + H)+,
ESI (Pos., 40 V)

369, 191.

EXAMPLE 69(H36-1)˜69(H36-24)

[2744] By the same procedure as described in Example 22 using the corresponding amine derivatives and acid chloride derivatives instead of the compound prepared in Example 14, the compounds of the present invention, whose names were shown in the following Table 36A-1˜36A-4, and whose structures were shown in the following Table 36B-1˜36B-5, were obtained. Also, physical data of the above compounds were shown in the following Table 36C-1.

624TABLE 36A-1ExampleNoCompound Name69(H36-1)(3S)-1-propyl-2,5-dioxo-3-((2-phenylphenyl)carbonylaminomethyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane69(H36-2)(3S)-1-propyl-2,5-dioxo-3-((3-phenylphenyl)carbonylaminomethyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane69(H36-3)(3S)-1-propyl-2,5-dioxo-3-((4-phenylphenyl)carbonylaminomethyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane69(H36-4)(3S)-1-propyl-2,5-dioxo-3-((2-phenylphenyl)acetylaminomethyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane69(H36-5)(3S)-1-propyl-2,5-dioxo-3-((3-phenylphenyl)acetylaminomethyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane69(H36-6)(3S)-1-propyl-2,5-dioxo-3-((4-phenylphenyl)acetylaminomethyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane69(H36-7)(3S)-1-propyl-2,5-dioxo-3-(2-(2-phenylphenyl)carbonylaminoethyl)-9-(2-phenylethyl)-1,4,9-triazaspiro[5.5]undecane

[2745]

625

TABLE 36A-2

Example No
Compound Name

69(H36-8)
(3S)-1-propyl-2,5-dioxo-3-(2-(3-

phenylphenyl)carbonylaminoethyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

69(H36-9)
(3S)-1-propyl-2,5-dioxo-3-(2-(4-

phenylphenyl)carbonylaminoethyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

69(H36-10)
(3S)-1-propyl-2,5-dioxo-3-(2-(2-

phenylphenyl)acetylaminoethyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

69(H36-11)
(3S)-1-propyl-2,5-dioxo-3-(2-(3-

phenylphenyl)acetylaminoethyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

69(H36-12)
(3S)-1-propyl-2,5-dioxo-3-(2-(4-

phenylphenyl)acetylaminoethyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

69(H36-13)
(3S)-1-propyl-2,5-dioxo-3-(3-(2-

phenylphenyl)carbonylaminopropyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

69(H36-14)
(3S)-1-propyl-2,5-dioxo-3-(3-(3-

phenylphenyl)carbonylaminopropyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[2746]

626

TABLE 36A-3

Example No
Compound Name

69(H36-15)
(3S)-1-propyl-2,5-dioxo-3-(3-(4-

phenylphenyl)carbonylaminopropyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

69(H36-16)
(3S)-1-propyl-2,5-dioxo-3-(3-(2-

phenylphenyl)acetylaminopropyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

69(H36-17)
(3S)-1-propyl-2,5-dioxo-3-(3-(3-

phenylphenyl)acetylaminopropyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

69(H36-18)
(3S)-1-propyl-2,5-dioxo-3-(3-(4-

phenylphenyl)acetylaminopropyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

69(H36-19)
(3S)-1-propyl-2,5-dioxo-3-(4-(2-

phenylphenyl)carbonylaminobutyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

69(H36-20)
(3S)-1-propyl-2,5-dioxo-3-(4-(3-

phenylphenyl)carbonylaminobutyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

69(H36-21)
(3S)-1-propyl-2,5-dioxo-3-(4-(4-

phenylphenyl)carbonylaminobutyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[2747]

627

TABLE 36A-4

Example No
Compound Name

69(H36-22)
(3S)-1-propyl-2,5-dioxo-3-(4-(2-

phenylphenyl)acetylaminobutyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

69(H36-23)
(3S)-1-propyl-2,5-dioxo-3-(4-(3-

phenylphenyl)acetylaminobutyl)-9-(2-phenlylethyl)-1,4,9-

triazaspiro[5.5]undecane

69(H36-24)
(3S)-1-propyl-2,5-dioxo-3-(4-(4-

phenylphenyl)acetylaminobutyl)-9-(2-phenylethyl)-1,4,9-

triazaspiro[5.5]undecane

[2748]

628

TABLE 36B-1

3457

Example

No
R3
R4
R5

69 (H36-1)
H

3458

H

69 (H36-2)
H

3459

H

69 (H36-3)
H

3460

H

69 (H36-4)
H

3461

H

69 (H36-5)
H

3462

H

69 (H36-6)
H

3463

[2749]

629

TABLE 36B-2

3464

Example

No
R3
R4
R5

69 (H36-7)
H

3465

H

69 (H36-8)
H

3466

H

69 (H36-9)
H

3467

H

69 (H36-10)
H

3468

H

69 (H36-11)
H

3469

H

69 (H36-12)
H

3470

H

69 (H36-13)
H

3471

[2750]

630

TABLE 36B-3

3472

Example No
R3
R4
R5

69(H36-14)
H

3473

H

69(H36-15)
H

3474

H

69(H36-16)
H

3475

H

69(H36-17)
H

3476

[2751]

631

TABLE 36B-4

3477

Example No
R3
R4
R5

69(H36-18)
H

3478

H

69(H36-19)
H

3479

H

69(H36-20)
H

3480

H

69(H36-21)
H

3481

H

69(H36-22)
H

3482

[2752]

632

TABLE 36B-5

3483

Example No
R3
R4
R5

69(H36-23)
H

3484

H

69(H36-24)
H

3485

[2753]

633

TABLE 36C-1

Retention

HPLC
time

Example No
condition
(min)
Mass data
Mass condition

69(H36-1)
F
3.38
539 (M + H)+.
ESI (Pos., 20 V)

69(H36-2)
F
3.47
539 (M + H)+.
ESI (Pos., 20 V)

69(H36-3)
F
3.47
539 (M + H)+.
ESI (Pos., 20 V)

69(H36-4)
F
3.45
553 (M + H)+.
ESI (Pos., 20 V)

69(H36-5)
F
3.44
553 (M + H)+.
ESI (Pos., 20 V)

69(H36-6)
F
3.44
553 (M + H)+.
ESI (Pos., 20 V)

69(H36-7)
F
3.40
553 (M + H)+.
ESI (Pos., 20 V)

69(H36-8)
F
3.49
553 (M + H)+.
ESI (Pos., 20 V)

69(H36-9)
F
3.49
553 (M + H)+.
ESI (Pos., 20 V)

69(H36-10)
F
3.47
567 (M + H)+.
ESI (Pos., 20 V)

69(H36-11)
F
3.49
567 (M + H)+.
ESI (Pos., 20 V)

69(H36-12)
F
3.49
567 (M + H)+.
ESI (Pos., 20 V)

69(H36-13)
F
3.36
567 (M + H)+.
ESI (Pos., 20 V)

69(H36-14)
F
3.47
567 (M + H)+.
ESI (Pos., 20 V)

69(H36-15)
F
3.47
567 (M + H)+.
ESI (Pos., 20 V)

69(H36-16)
F
3.45
581 (M + H)+.
ESI (Pos., 20 V)

69(H36-17)
F
3.47
581 (M + H)+.
ESI (Pos., 20 V)

69(H36-18)
F
3.47
581 (M + H)+.
ESI (Pos., 20 V)

69(H36-19)
F
3.40
581 (M + H)+.
ESI (Pos., 20 V)

69(H36-20)
F
3.49
581 (M + H)+.
ESI (Pos., 20 V)

69(H36-21)
F
3.43
581 (M + H)+.
ESI (Pos., 20 V)

69(H36-22)
F
3.47
595 (M + H)+.
ESI (Pos., 20 V)

69(H36-23)
F
3.49
595 (M + H)+.
ESI (Pos., 20 V)

69(H36-24)
F
3.49
595 (M + H)+.
ESI (Pos., 20 V)

FORMULATION EXAMPLE

FORMULATION EXAMPLE 1

[2754] The following components were admixed in a conventional technique, punched out to give 100 tablets each containing 50 mg of active ingredient.

6349-((3,5-dimethyl-1-phenyl)-4-pyrazolyl)methyl)-2,5-dioxo-3-(2-methyl-1-5.0 gpropyl)-1-propyl-1,4,9-triazaspiro[5.5]undecane.2 hydrochloridecalcium carboxymethylcellulose (disintegrant)0.2 gmagnesium stearate (lubricant)0.1 gmicrocrystalline cellulose4.7 g

FORMULATION EXAMPLE 2

[2755] The following components were admixed in a conventional technique. The solution was sterilized in a conventional technique, filled in ampoules 5 ml each and freeze-dried in a conventional technique to give 100 ampoules each containing 20 mg of active ingredient.

6359-((3,5-dimethyl-1-phenyl)-4-pyrazolyl)methyl)-2,5-dioxo-3-(2-methyl-1-2.0gpropyl)-1-propyl-1,4,9-triazaspiro[5.5]undecane.2 hydrochloridemannitol20gdistilled water500ml

[2756]

Number	Date	Country
11-344967	Dec 1999	JP
2000-18673	Jan 2000	JP
2000-27968	Feb 2000	JP
2000-147882	May 2000	JP

Triazaspiro[5.5]undecane derivatives and drugs containing the same as the active ingredient

Information

Publication Number

Date Filed

Date Published

Inventors

CPC

US Classifications

International Classifications

Abstract

Description

Claims

Priority Claims (4)

PCT Information