FIELD OF THE INVENTION
The present invention relates to novel spiro compounds and a method of modulating chemokine receptor activity using these compounds. The present invention is also directed to novel spiro compounds which are useful in the prevention or treatment of diseases associated with the modulation of CCR5 chemokine receptor activity. The present invention is further directed to a method of blocking cellular entry of HIV in a subject and to compositions using these compounds.
BACKGROUND OF THE INVENTION
Chemokines are chemotactic cytokines that are released by a wide variety of cells to attract macrophages, T cells, eosinophils, basophils and neutrophils to sites of inflammation and they also play a role in the maturation of cells of the immune system. Chemokines play an important role in immune and inflammatory responses in various diseases and disorders, including asthma, rhinitis and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis. Chemokines are small 70 to 80 amino acid proteins with well-characterized three-dimensional structures, usually stabilized by two disulfide bridges. They are divided into four families on the basis of pattern of conserved cysteine residues. Chemokine receptors have been designated such as, CCR1, CCR2, CCR2A, CCR2B, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CCR10, CXCR1, CXCR2, CXCR3, and CXCR4 and therefore agents which modulate these receptors may be useful in the prevention and treatment of diseases as mentioned above.
One of them, the C—C chemokines family, includes potent chemoattractants of monocytes and lymphocytes such as RANTES (Regulated on Activation, Normal T Expressed and Secreted), eotaxin, MIP-1α and MIP-1β (Macrophage Inflammatory Proteins) and human monocyte chemotactic proteins 1-3 (MCP-1, MCP-2 and MCP-3). More specifically, C—C chemokine receptor 5 (CCR5), a β-chemokine receptor with a seven-transmembrane-protein structure, was found to serve as a coreceptor for non-syncytium-inducing or macrophage-tropic HIV-1 (R5 viruses). It was also established that CCR5 is the principal chemokine receptor required for the entry of HIV into the cell during primary infection. Therefore, interfering with the interaction between the viral receptor CCR5 and HIV can block HIV entry into the cell. It would therefore be useful to provide novel compounds which are modulators of chemokine receptor activity.
SUMMARY OF THE INVENTION
In one aspect, the present invention provides novel compounds represented by formula (I):
or pharmaceutically acceptable salts, hydrates or solvates thereof,
wherein Y, Z and X are each independently chosen from CH2, C═O or CR4R5;
W is H, optionally substituted C1-10 alkyl (e.g. C1-6 alkyl) optionally substituted C2-10 alkenyl (e.g. C2-6 alkenyl), optionally substituted C2-10 alkynyl (e.g. C2-6 alkynyl), optionally substituted C6-12 aryl, optionally substituted 3 to 10 membered heterocycle, optionally substituted C6-12 aralkyl or optionally substituted C3-10 heteroaralkyl;
R1 is H, OH, optionally substituted C1-10 alkyl (e.g. C1-6 alkyl), optionally substituted C2-10 alkenyl (e.g. C2-6 alkenyl), optionally substituted C2-10 alkynyl (e.g. C2-6 alkynyl), optionally substituted C6-12 aryl, NR8R9, optionally substituted O—C1-6 alkyl, optionally substituted O—C6-12 aryl, optionally substituted O—C6-12 aralkyl,
R2 is optionally substituted C1-10 alkyl, optionally substituted C2-10 alkenyl, optionally substituted C2-10 alkynyl, optionally substituted C6-12 aryl or optionally substituted 3 to 10 membered heterocycle;
R3 is H, optionally substituted C1-10 alkyl (e.g. C1-6 alkyl), optionally substituted C2-10 alkenyl (e.g. C2-6 alkenyl), optionally substituted C2-10 alkynyl (e.g. C2-6 alkynyl), or optionally substituted C6-12 aryl;
R4 and R5 are each independently H, optionally substituted C1-10 alkyl (e.g. C1-6 alkyl), optionally substituted C2-10 alkenyl (e.g. C2-6 alkenyl), optionally substituted C2-10 alkynyl (e.g. C2-6 alkynyl), or optionally substituted C6-12 aryl;
R6 and R″6 are each independently H, optionally substituted C1-10 alkyl (e.g. C1-4 alkyl), optionally substituted C2-10 alkenyl (e.g. C2-4 alkenyl), or optionally substituted C2-10 alkynyl (e.g. C2-4 alkynyl) and R7 is H, optionally substituted C1-10 alkyl, optionally substituted C2-10 alkenyl, optionally substituted C2-10 alkynyl, optionally substituted C6-12 aryl, optionally substituted 3 to 10 membered heterocycle, optionally substituted C6-12 aralkyl or optionally substituted 3 to 10 membered heteroaralkyl, or R″6 and R7 can be taken together to form an optionally substituted 3 to 10 membered heterocycle; and
R8 and R9 are each independently H, optionally substituted C1-10 alkyl (e.g. C1-6 alkyl), optionally substituted C2-10 alkenyl (e.g. C2-6 alkenyl), or optionally substituted C2-10 alkynyl (e.g. C2-6 alkynyl).
In another aspect, there is provided a method of modulating chemokine receptor activity in a subject comprising administering to the subject an effective amount of a compound of formula (I) or composition of the invention.
In still another aspect, there is provided a method for prevention or treatment of certain inflammatory diseases, immunoregulatory diseases, organ transplantation reactions and in the prevention and treatment of infectious diseases such as HIV infections in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or composition of the invention.
In still another aspect, there is provided a method for the prevention or treatment of diseases associated with the modulation of CCR5 chemokine receptor activity in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or composition of the invention.
In still another aspect, there is provided a method for blocking cellular entry of HIV in a subject comprising administering to the subject in need thereof an effective amount of a compound of formula (I) or composition of the invention to block HIV from cellular entry in said subject.
In still another aspect, there is provided a method for the prevention or treatment of diseases associated with the modulation of chemokine receptor activity in a subject in need of such treatment comprising administering to the subject a pharmaceutical combination comprising at least one compound of formula (I) and at least one further therapeutic agent.
In another aspect, there is provided a pharmaceutical formulation comprising the compound of the invention in combination with a pharmaceutically acceptable carrier or excipient.
In another aspect of the invention is the use of a compound according to formula (I), for the manufacture of a medicament for the prevention or treatment of diseases associated with the modulation of chemokine receptor activity.
DETAILED DESCRIPTION OF THE INVENTION
In one embodiment, compounds of the present invention comprise those wherein the following embodiments are present, either independently or in combination.
In one embodiment, the present invention provides novel compounds represented by formula I:
or pharmaceutically acceptable salts, hydrates or solvates thereof wherein Y, Z, X, W, R1, R2 and R3 are defined above.
In one embodiment, the present invention provides novel compounds represented by formula (Ia):
or pharmaceutically acceptable salts, hydrates or solvates thereof wherein Y, X, W, R1, R2 and R3 are defined above.
In one embodiment, the present invention provides novel compounds represented by formula (Ib):
or pharmaceutically acceptable salts, hydrates or solvates thereof wherein Z, X, W, R1, R2 and R3 are defined above.
In one embodiment, the present invention provides novel compounds represented by formula (Ic):
or pharmaceutically acceptable salts, hydrates or solvates thereof wherein Y, Z, W, R1, R2 and R3 are defined above.
In one embodiment, the present invention provides novel compounds represented by formula (Id):
or pharmaceutically acceptable salts, hydrates or solvates thereof wherein W, R1, R2 and R3 are defined above.
In one embodiment, the compounds of the present invention are in the (S)-enantiomer as represented by formula (Ie):
or pharmaceutically acceptable salts, hydrates or solvates thereof wherein Y, Z, X, W, R1, R2 and R3 are defined above.
In one embodiment, W is chosen from optionally substituted C6-12 aryl or optionally substituted 3 to 10 membered heterocycle.
In a further embodiment, W is optionally substituted C6-12 aryl.
In a further embodiment, W is optionally substituted 3 to 10 membered heterocycle.
In further embodiments:
W is phenyl;
W is phenyl substituted with a halogen;
W is phenyl substituted with Br;
W is phenyl substituted with F;
W is phenyl substituted with Cl;
W is phenyl substituted with at least one halogen;
W is phenyl substituted with a C1-3 alkoxy;
W is phenyl substituted with methoxy;
W is phenyl substituted with ethoxy;
W is phenyl substituted with SO2C1-3alkyl;
W is phenyl substituted with methanesulfonyl;
W is phenyl substituted with difluoromethoxy;
W is phenyl substituted with trifluoromethoxy;
W is phenyl substituted with trifluoromethyl;
W is phenyl substituted with CN;
W is phenyl substituted with pyrrazoyl;
W is phenyl optionally substituted in the para (p) position.
W is optionally substituted pyridine.
In a further embodiment, R1 is chosen from:
In a further embodiment, R1 is:
wherein R6 is as defined above and R7 is chosen from optionally substituted C1-10 alkyl, optionally substituted C6-12 aryl or optionally substituted 3 to 10 membered heterocycle.
In further embodiments, R1 is:
wherein:
R7 is methyl;
R7 is ethyl;
R7 is isopropyl;
R7 is cyclopropyl;
R7 is cyclobutyl;
R7 is cyclopentyl;
R7 is cyclohexyl;
R7 is cycloheptyl;
R7 is 4,4-difluorocyclohexyl;
R7 is CH2-cyclopropyl;
R7 is CH2-cyclobutyl;
R7 is CH2-cyclopentyl;
R7 is CH2-cyclohexyl.
R7 is phenyl;
R7 is phenyl substituted with methyl;
R7 is phenyl substituted with at least one methyl;
R7 is phenyl substituted with a halogen;
R7 is phenyl substituted with at least one halogen;
R7 is phenyl substituted with Cl;
R7 is phenyl substituted with Br;
R7 is phenyl substituted with F;
R7 is phenyl substituted with at least one Cl;
R7 is phenyl substituted with methoxy.
R7 is benzyl;
R7 is benzyl substituted with methyl;
R7 is benzyl substituted with at least one methyl;
R7 is benzyl substituted with a halogen;
R7 is benzyl substituted with at least one halogen;
R7 is benzyl substituted with Cl;
R7 is benzyl substituted with Br;
R7 is benzyl substituted with F;
R7 is benzyl substituted with at least one Cl;
R7 is benzyl substituted with methoxy.
R7 is optionally substituted pyridine.
In a further embodiment, R1 is:
wherein R6 and R6 are as defined above and R7 is optionally substituted C6-12 aryl, or R6 and R7 can be taken together to form an optionally substituted 3 to 10 membered heterocycle.
In a further embodiment, R1 is:
wherein:
R7 is phenyl;
R7 is phenyl substituted with methyl;
R7 is phenyl substituted with at least one methyl;
R7 is phenyl substituted with a halogen;
R7 is phenyl substituted with at least one halogen;
R7 is phenyl substituted with Cl;
R7 is phenyl substituted with Br;
R7 is phenyl substituted with F;
R7 is phenyl substituted with at least one Cl;
R7 is phenyl substituted with methoxy;
R7 is naphthyl.
R″6 and R7 can be taken together to form an optionally substituted piperidine.
R6 and R7 can be taken together to form an optionally substituted morpholine.
R6 and R7 can be taken together to form a morpholine.
R6 and R7 can be taken together to form an optionally substituted pyrrolidine.
R6 and R7 can be taken together to form a 3,3-difluoropyrrolidine.
In a further embodiment, R1 is:
wherein R6 is as defined above and R7 is optionally substituted C1-10 alkyl.
In further embodiments, R1 is:
wherein:
R7 is methyl;
R7 is ethyl;
R7 is tert-butyl;
R7 is cyclobutyl;
R7 is cyclopentyl;
R7 is cyclohexyl.
In a further embodiment, R1 is:
wherein R6 is as defined above and R7 is chosen from optionally substituted C1-10 alkyl, optionally substituted C6-12 aryl or optionally substituted 3 to 10 membered heterocycle.
In a further embodiment, R1 is:
wherein:
R7 is optionally substituted phenyl;
R7 is optionally substituted C1-10 alkyl;
R7 is isopropyl.
In a further embodiment, R1 is:
wherein R6 is as defined above and R7 is chosen from optionally substituted C1-10 alkyl or optionally substituted C6-12 aryl.
In a further embodiment, R1 is:
wherein:
R7 is optionally substituted cyclohexyl.
R7 is optionally substituted phenyl.
In a further embodiment, R2 is chosen from optionally substituted C6-12 aryl or optionally substituted 3 to 10 membered heterocycle.
In further embodiments:
R2 is optionally substituted C6-12 aryl.
R2 is phenyl;
R2 is phenyl substituted with halogen;
R2 is phenyl substituted with Cl;
R2 is phenyl substituted with at least one halogen;
R2 is phenyl substituted with methoxy;
R2 is phenyl substituted with at least one methoxy.
In a further embodiments:
R2 is optionally substituted 3 to 10 membered heterocycle.
R2 is optionally substituted thienyl.
R2 is optionally substituted pyridyl.
In a further embodiment, R3 is chosen from H or optionally substituted C1-4 alkyl.
In one embodiment, R3 is H.
In one embodiment, R3 is methyl.
The compounds of the present invention may have an asymmetric center. As two optical isomers can independently be obtained from each asymmetric center, compounds of the invention having one asymmetric center can be in the form of the enantiomers, i.e., the (+) enantiomer or (−) enantiomer, in pure or partially purified form, as well as mixtures of enantiomers.
In one embodiment, the compounds of the present invention are the (+) enantiomer having an enantiomeric excess of 99%.
In one embodiment, the compounds of the present invention are the (+) enantiomer having an enantiomeric excess of 95%.
In one embodiment, the compounds of the present invention are the (+) enantiomer having an enantiomeric excess of 90%.
In one embodiment, the compounds of the present invention are the (−) enantiomer having an enantiomeric excess of 99%.
In one embodiment, the compounds of the present invention are the (−) enantiomer having an enantiomeric excess of 95%.
In one embodiment, the compounds of the present invention are the (−) enantiomer having an enantiomeric excess of 90%.
Compounds of the present invention have also two asymmetric centers. As two optical isomers can independently be obtained from each asymmetric center, compounds of the invention having two asymmetric centers can be in the form of the diastereomers. It is intended that all the possible diastereomers in mixtures and as pure or partially purified compounds are included in this invention.
In one embodiment, the compounds of the present invention are in the form of the (R,R)-diastereomer;
In one embodiment, the compounds of the present invention are in the form of the (S,R)-diastereomer;
In one embodiment, the compounds of the present invention are in the form of the (R,S)-diastereomer;
In one embodiment, the compounds of the present invention are in the form of the (S,S)-diastereomer.
In one embodiment, the compounds of the present invention are a (R,R)-diastereomer having an optical purity in excess of 99%.
In one embodiment, the compounds of the present invention are a (R,R)-diastereomer having an optical purity in excess of 95%.
In one embodiment, the compounds of the present invention are a (R,R)-diastereomer having an optical purity in excess of 90%.
In one embodiment, the compounds of the present invention are a (S,R)-diastereomer having an optical purity in excess of 99%.
In one embodiment, the compounds of the present invention are a (S,R)-diastereomer having an optical purity in excess of 95%.
In one embodiment, the compounds of the present invention are a (S,R)-diastereomer having an optical purity in excess of 90%.
In one embodiment, the compounds of the present invention are a (R,S)-diastereomer having an optical purity in excess of 99%.
In one embodiment, the compounds of the present invention are a (R,S)-diastereomer having an optical purity in excess of 95%.
In one embodiment, the compounds of the present invention are a (R,S)-diastereomer having an optical purity in excess of 90%.
In one embodiment, the compounds of the present invention are a (S,S)-diastereomer having an optical purity in excess of 99%.
In one embodiment, the compounds of the present invention are a (S,S)-diastereomer having an optical purity in excess of 95%.
In one embodiment, the compounds of the present invention are a (S,S)-diastereomer having an optical purity in excess of 90%.
In one embodiment, there is provided a method of modulating chemokine receptor activity in a subject comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or composition of the invention.
In another embodiment, there is provided a method for the prevention or treatment of diseases associated with the modulation of chemokine receptor activity in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or composition of the invention.
In a further embodiment, there is provided a method for prevention or treatment of certain inflammatory diseases, immunoregulatory diseases, organ transplantation reactions and in the prevention and treatment of infectious diseases such as HIV infections in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or composition of the invention.
In another embodiment, there is provided a method for the prevention or treatment of diseases associated with the modulation of CCR5 chemokine receptor activity in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or composition of the invention.
In still another aspect, there is provided a method for blocking cellular entry of HIV in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound of formula (I) to block HIV from cellular entry in said subject.
In still another aspect, there is provided a method for prevention or treatment of HIV infections in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or composition of the invention.
In still another aspect, there is provided a method for delaying the onset of AIDS or treating AIDS in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or composition of the invention.
In a further embodiment, there is provided a method for the prevention or treatment of diseases associated with the modulation of chemokine receptor activity in a subject in need of such treatment comprising administering to the subject a pharmaceutical combination comprising at least one compound of formula (I) and at least one further therapeutic agent.
In a further embodiment, there is provided a method for the prevention or treatment of diseases associated with the modulation of CCR5 chemokine receptor activity in a subject in need of such treatment comprising administering to the subject a pharmaceutical combination comprising at least one compound of formula (I) and at least one further therapeutic agent.
In still another aspect, there is provided a method for blocking cellular entry of HIV in a subject or for the prevention or treatment of HIV infections in a subject in need of such treatment comprising administering to the subject a pharmaceutical combination comprising at least one compound of formula (I) and at least one further therapeutic agent.
In still another aspect, there is provided a method for delaying the onset of AIDS or treating AIDS in a subject in need of such treatment comprising administering to the subject a pharmaceutical combination comprising at least one compound of formula (I) and at least one further therapeutic agent.
In another embodiment, there is provided a combination useful for the prevention or treatment of diseases associated with the modulation of chemokine receptor activity which is a therapeutically effective amount of a compound of formula (I) and therapeutically effective amount of at least one further therapeutic agent.
In one embodiment, combinations of the present invention comprise those wherein the following embodiments are present, either independently or in combination.
In a further embodiment, the pharmaceutical combinations of this invention may contain at least one further therapeutic agent chosen from an agent used in inflammatory diseases, immunoregulatory diseases and in organ transplantation reactions.
In another embodiment, the pharmaceutical combination of this invention may contain at least one further therapeutic agent which is an antiviral agent.
In one embodiment, the pharmaceutical combination of this invention may contain at least one further antiviral agent which is chosen from nucleoside and nucleotide analog reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, attachment and fusion inhibitors, integrase inhibitors or maturation inhibitors.
In one embodiment, the pharmaceutical combinations of this invention may contain at least one other antiviral agent which is a nucleoside and nucleotide analog reverse transcriptase inhibitors chosen from 3TC (lamivudine, Epivir®), AZT (zidovudine, Retrovir®), Emtricitabine (Coviracil®, formerly FTC), d4T (2′,3′-dideoxy-2′,3′-didehydro-thymidine, stavudine and Zerit®), tenofovir (Viread®), 2′,3′-dideoxyinosine (ddl, didanosine, Videx®), 2′,3′-dideoxycytidine (ddC, zalcitabine, Hivid®), Combivir® (AZT/3TC or zidovudine/lamivudine combination), Trivizir® (AZT/3TC/abacavir or zidovudine/lamivudine/abacavir combination), abacavir (1592U89, Ziagen®), SPD-754, ACH-126,443 (Beta-L-Fd4C), Alovudine (MIV-310), DAPD (amdoxovir), Racivir, 9-[(2-hydroxymethyl)-1,3-dioxolan-4-yl]guanine or 2-amino-9-[(2-hydroxymethyl)-1,3-dioxolan-4-yl]adenine.
In another embodiment, the pharmaceutical combination of this invention may contain at least one other antiviral agent which is a non-nucleoside reverse transcriptase inhibitor chosen from Nevirapine (Viramune®, NVP, BI-RG-587), delavirdine (Rescriptor®, DLV), efavirenz (DMP 266, Sustiva®), (+)-Calanolide A, Capravirine (AG1549, formerly S-1153), DPCO83, MIV-150, TMC120, TMC125 or BHAP (delavirdine), calanolides or L-697,661 (2-Pyridinone 3benzoxazolMeNH derivative).
In another embodiment, the pharmaceutical combination of this invention may contain at least one other antiviral agent which ia a protease inhibitor chosen from nelfinavir (Viracept®, NFV), amprenavir (141W94, Agenerase®), indinavir (MK-639, IDV, Crixivan®), saquinavir (Invirase®, Fortovase®, SQV), ritonavir (Norvir®, RTV), lopinavir (ABT-378, Kaletra®), Atazanavir (BMS232632), mozenavir (DMβ-450), fosamprenavir (GW433908), R0033-4649, Tipranavir (PNU-140690), TMC114 or VX-385.
In another embodiment, the pharmaceutical combination of this invention may contain at least one other antiviral agent which is an attachment and fusion inhibitor chosen from T-20 (enfuvirtide, Fuzeon®), T-1249, Schering C (SCH-C), Schering D (SCH-D), FP21399, PRO-140, PRO 542, PRO 452, TNX-355, GW873140 (AK602), TAK-220, UK-427,857 or soluble CD4, CD4 fragments, CD4-hybrid molecules, BMS-806, BMS-488043,AMD3100, AMD070 or KRH-2731.
In another embodiment, the pharmaceutical combination of this invention may contain at least one other antiviral agent which is an integrase inhibitor chosen from S-1360, L-870,810, L-870,812 or C-2507.
In another embodiment, the pharmaceutical combination of this invention may contain at least one other antiviral agent which is a maturation inhibitor and is PA-457.
In another embodiment, the pharmaceutical combination of this invention may contain at least one other antiviral agent which is a zinc finger inhibitor and is azodicarbonamide (ADA).
In another embodiment, the pharmaceutical combination of this invention may contain at least one other antiviral agent which is an antisense drug and is HGTV43.
In another embodiment, the pharmaceutical combination of this invention may contain at least one other antiviral agent which is an immunomodulator, immune stimulator or cytokine chosen from interleukin-2 (IL-2, Aldesleukin, Proleukin), granulocyte macrophage colony stimulating factor (GM-CSF), erythropoietin, Multikine, Ampligen, thymomodulin, thymopentin, foscarnet, HE2000, Reticulose, Murabutide, Resveratrol, HRG214, HIV-1 Immunogen (Remune) or EP HIV-1090.
In another embodiment, the pharmaceutical combination of this invention may contain at least one other antiviral agent chosen from 2′,3′-dideoxyadenosine, 3′-deoxythymidine, 2′,3′-dideoxy-2′,3′-didehydrocytidine and ribavirin; acyclic nucleosides such as acyclovir, ganciclovir; interferons such as alpha-, beta-and gamma-interferon; glucuronation inhibitors such as probenecid; or TIBO drugs, HEPT, TSAO derivatives.
The combinations referred to above may conveniently be presented for use in the form of a pharmaceutical formulation and thus pharmaceutical formulations comprising a combination as defined above together with a pharmaceutically acceptable carrier thereof comprises a further aspect of the invention.
The individual components of such combinations may be administered either sequentially or simultaneously in separate or combined pharmaceutical formulations.
In a further embodiment, the said compound of formula (I) and said therapeutic agent are administered sequentially.
In a further embodiment, the said compound of formula (I) and said therapeutic agent are administered simultaneously.
The subject to which the compounds are administered can be, for example, a mammal or a human. Preferably, the subject is a human.
In one embodiment, the present invention further provides a pharmaceutical composition comprising at least one compound having the formula (I) or pharmaceutically acceptable salts or pharmaceutically acceptable hydrates or pharmaceutically acceptable solvates thereof and at least one pharmaceutically acceptable carrier or excipient.
In another embodiment, the invention provides the use of a compound having the formula (I) for the manufacture of a medicament for prevention and treatment of diseases associated with the modulation of CCR5 chemokine receptor activity in a host comprising administering a therapeutically effective amount of a compound of formula (I).
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
The term “alkyl” represents a linear, branched or cyclic hydrocarbon moiety having, for example, 1 to 10 carbon atoms, which may have one or more double bonds or triple bonds in the chain, and is optionally substituted. For example, suitable substituents include halogen, amino, amidino, amido, azido, cyano, guanido, hydroxyl, nitro, nitroso, urea, OS(O)2R21 (wherein R21 is selected from C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), OS(O)2OR22 (wherein R22 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), S(O)2OR23 (wherein R23 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), S(O)0-2R24 (wherein R24 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), OP(O)OR25OR26, P(O)OR25OR26 (wherein R25 and R26 are each independently selected from H or C1-6 alkyl), C(O)R27 (wherein R27 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), C(O)OR28 (wherein R28 is selected from H, C1-6 alkyl, C6-12 aryl, C6-12 aralkyl or 3 to 10 membered heterocycle), NR29C(O)R30, C(O)NR29R30 (wherein R29 is H or C1-6 alkyl and R30 is selected from H, C1-6 alkyl, C6-12 aryl, C6-12 aralkyl or 3 to 10 membered heterocycle, or R29 and R30 are taken together with the atoms to which they are attached to form a 3 to 10 membered heterocycle), SO2NR31R32, NR31SO2R32 (wherein R31 and R32 are each independently selected from the group consisting of H, C1-6 alkyl, C6-12 aryl, 3 to 10 membered heterocycle and C6-12 aralkyl), C (R33) NR34 or C (R33) NOR34 (wherein R33 and R34 are each independently selected from the group consisting of H, C1-6 alkyl, or C6-12aryl).
Preferred substituents for the alkyl groups include halogen (Br, Cl, I or F), cyano, nitro, oxo, amino, COOH, COO—C14 alkyl, CO—C14 alkyl, and phenyl.
Examples of alkyl groups include but are not limited to methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, isohexyl, neohexyl, allyl, vinyl, acetylenyl, ethylenyl, propenyl, isopropenyl butenyl, isobutenyl, hexenyl, butadienyl, pentenyl, pentadienyl, hexenyl, hexadienyl, hexatrienyl, heptenyl, heptadienyl, heptatrienyl, octenyl, octadienyl, octatrienyl, octatetraenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cycloheptyl, cyclohexenyl, cyclohex-dienyl and cyclohexyl.
The term alkyl is also meant to include alkyls in which one or more hydrogen atom is replaced by a halogen, i.e. an alkylhalide. Examples include but are not limited to trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, dichloromethyl, chloromethyl, trifluoroethyl, difluoroethyl, fluoroethyl, trichloroethyl, dichloroethyl, chloroethyl, chlorofluoromethyl, chlorodifluoromethyl, dichlorofluoroethyl.
The term “alkenyl” refers to alkyl groups may have one or more double bonds in the chain. The term “alkynyl” refers to alkyl groups may have one or more triple bonds in their chain. The alkenyl and alkynyl groups can be optionally substituted as described above for the alkyl groups.
The term “alkoxy” represents an alkyl which is covalently bonded to the adjacent atom through an oxygen atom. Examples include but are not limited to methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, isopentyloxy, neopentyloxy, tert-pentyloxy, hexyloxy, isohexyloxy and neohexyloxy.
The term “alkylamino” represents an alkyl which is covalently bonded to the adjacent atom through a nitrogen atom and may be monoalkylamino or dialkylamino, wherein the alkyl groups may be the same or different. Examples include but are not limited to methylamino, dimethylamino, ethylamino, diethylamino, methylethylamino, propylamino, isopropylamino, butylamino, isobutylamino, sec-butylamino, tert-butylamino, pentylamino, isopentylamino, neopentylamino, tert-pentylamino, hexylamino, isohexylamino and neohexylamino.
The term “alkyloxycarbonyl” represents an alkyloxy which is covalently bonded to the adjacent atom through carbonyl (C═O). Examples include but are not limited to methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, isopentyloxycarbonyl, neopentyloxycarbonyl, tert-pentyloxycarbonyl, hexyloxycarbonyl, isohexyloxycarbonyl and neohexyloxycarbonyl.
The term “amidino” represents —C(=NR10)NR11R12, wherein R10, R11 and R12 are each independently selected from H, C1-6 alkyl, C6-12 aryl or C6-12 aralkyl, or R11 and R12 are taken together with the nitrogen to which they are attached to form a 3 to 10 membered heterocycle.
The term “amido” represents —CONH2, —CONHR13 and —CONR13R14 wherein R13 and R14 are each independently selected from C1-6 alkyl, C6-12 aryl, 3 to 10 membered heterocycle or C6-12 aralkyl, or R13 and R14 are taken together with the nitrogen to which they are attached to form a 3 to 10 membered heterocycle.
The term “amino” represents a derivative of ammonia obtained by substituting one or more hydrogen atom and include —NH2, —NHR15 and —NR15R16, wherein R15 and R16 are each independently selected from C1-6 alkyl, C6-12 aryl or C6-12 aralkyl, or R15 and R16 are taken together with the nitrogen to which they are attached to form a 3 to 10 membered heterocycle.
The term “aryl” represents a carbocyclic moiety containing at least one benzenoid-type ring (i.e. the aryl group may be monocyclic or polycyclic), and which is optionally substituted with one or more substituents. For example, suitable substituents include halogen, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, amino, amidino, amido, azido, cyano, guanido, hydroxyl, nitro, nitroso, urea, OS(O)2R21 (wherein R21 is selected from C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), OS(O)2OR22 (wherein R22 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), S(O)2OR23 (wherein R23 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), S(O)0-2R24 (wherein R24 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), OP(O)OR25OR26, P(O)OR25OR26 (wherein R25 and R26 are each independently selected from H or C1-6 alkyl), C1-6alkyl, C6-12aralkyl, C1-6alkoxy, C6-12aralkyloxy, C6-12aryloxy, 3 to 10 membered heterocycle, C(O)R27 (wherein R27 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), C(O)OR28 (wherein R28 is selected from H, C1-6 alkyl, C6-12 aryl, C6-12 aralkyl or 3 to 10 membered heterocycle), NR29C(O)R30, C(O)NR29R30 (wherein R29 is H or C1-6 alkyl and R30 is selected from H, C1-6 alkyl, C6-12 aryl, C6-12 aralkyl or 3 to 10 membered heterocycle, or R29 and R30 are taken together with the atoms to which they are attached to form a 3 to 10 membered heterocycle), SO2NR31R32, NR31SO2R32 (wherein R31 and R32 are each independently selected from the group consisting of H, C1-6 alkyl, C6-12 aryl, 3 to 10 membered heterocycle and C6-12 aralkyl), C(R33)NR34 or C(R33)NOR34 (wherein R33 and R34 are each independently selected from the group consisting of H, C1-6 alkyl, or C6-12 aryl).
Preferred substituents for the aryl groups include halogen (Br, Cl, I or F), cyano, nitro, oxo, amino, C1-4 alkyl (e.g., CH3, C2H5, isopropyl), C1-4 alkoxy (e.g., OCH3, OC2H5), halogenated C1-4 alkyl (e.g., CF3, CHF2), halogenated C1-4 alkoxy (e.g., OCF3, OC2F5), COOH, COO—C1l4 alkyl, CO—C1-4 alkyl, C1-4 alkyl-S—(e.g., CH3S, C2H5S) , halogenated C1-4 alkyl-S—(e.g., CF3S, C2F5S), benzyloxy, and pyrazolyl.
Examples of aryl include but are not limited to phenyl, tolyl, dimethylphenyl, aminophenyl, anilinyl, naphthyl, anthryl, phenanthryl or biphenyl.
The term “aralkyl” represents an aryl group attached to the adjacent atom by a C1-6alkyl. Examples include but are not limited to benzyl, benzhydryl, trityl, phenethyl, 3-phenylpropyl, 2-phenylpropyl, 4-phenylbutyl and naphthylmethyl. The aryl and alkyl portions can be optionally substituted as described above.
The term “aralkyloxy” represents an aralkyl which is covalently bonded to the adjacent atom through an oxygen atom. Examples include but are not limited to benzyloxy, benzhydryloxy, trityloxy, phenethyloxy, 3-phenylpropyloxy, 2-phenylpropyloxy, 4-phenylbutyloxy and naphthylmethoxy. The aryl and alkyl portions can be optionally substituted as described above.
The term “aryloxy” represents an aryl which is covalently bonded to the adjacent atom through an oxygen atom. Examples include but are not limited to phenoxy and naphthyloxy. The aryl portion can be optionally substituted as described above.
The term “guanidino” represents —NR17C(═NR18)NR19R20 wherein R17, R18, R19 and R20 are each independently selected from H, C1-6 alkyl, C6-12 aryl or C6-12 aralkyl, or R19 and R20 are taken together with the nitrogen to which they are attached to form a 3 to 10 membered heterocycle.
The term “halogen” is specifically a fluoride atom, chloride atom, bromide atom or iodide atom.
The term “heterocycle” represents an optionally substituted saturated, unsaturated or aromatic cyclic moiety wherein said cyclic moiety is interrupted by at least one heteroatom selected from oxygen (O), sulfur (S) or nitrogen (N). Heterocycles may be monocyclic or polycyclic rings. For example, suitable substituents include halogen, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, amino, amidino, amido, azido, cyano, guanido, hydroxyl, nitro, nitroso, urea, OS(O)2R21 (wherein R21 is selected from C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), OS(O)2OR22 (wherein R22 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), S(O)2OR23 (wherein R23 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), S(O)0-2R24 (wherein R24 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), OP(O)OR25OR26, P(O)OR25OR26 (wherein R25 and R26 are each independently selected from H or C1-6 alkyl), C1-6alkyl, C6-12aralkyl, C1-6alkoxy, C6-12 aryl, C6-12aralkyloxy, C6-12aryloxy, C(Q)R27 (wherein R27 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), C(O)OR28 (wherein R28 is selected from H, C1-6 alkyl, C6-12 aryl, C6-12 aralkyl or 3 to 10 membered heterocycle), NR29C(O)R30, C(O)NR29R30 (wherein R29 is H or C1-6 alkyl and R30 is selected from H, C1-6 alkyl, C6-12 aryl, C6-12 aralkyl or 3 to 10 membered heterocycle, or R29 and R30 are taken together with the atoms to which they are attached to form a 3 to 10 membered heterocycle), SO2NR31R32, NR31SO2R32 (wherein R31 and R32 are each independently selected from the group consisting of H, C1-6 alkyl, C6-12 aryl, 3 to 10 membered heterocycle and C6-12 aralkyl), C(R33)NR34 or C(R33)NOR34 (wherein R33 and R34 are each independently selected from the group consisting of H, C1-6 alkyl, or C6-12 aryl)
Preferred substituents for the heterocycle groups include halogen (Br, Cl, I or F), cyano, nitro, oxo, amino, C1-4 alkyl (e.g., CH3, C2H5, isopropyl), C1-4 alkoxy (e.g., OCH3, OC2H5), halogenated C1-4 alkyl (e.g., CF3, CHF2), halogenated C1-4 alkoxy (e.g., OCF3, OC2F5), COOH, COO—C1-4 alkyl, CO—C1-4 alkyl, C1-4 alkyl-S—(e.g., CH3S, C2H5S), halogenated C1-4 alkyl-S—(e.g., CF3S, C2F5S), benzyloxy, and pyrazolyl.
Examples of heterocycles include but are not limited to azepinyl, aziridinyl, azetyl, azetidinyl, diazepinyl, dithiadiazinyl, dioxazepinyl, dioxolanyl, dithiazolyl, furanyl, isooxazolyl, isothiazolyl, imidazolyl, morpholinyl, morpholino, oxetanyl, oxadiazolyl, oxiranyl, oxazinyl, oxazolyl, piperazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, piperidyl, piperidino, pyridyl, pyranyl ,pyrazolyl, pyrrolyl, pyrrolidinyl, thiatriazolyl, tetrazolyl, thiadiazolyl, triazolyl, thiazolyl, thienyl, tetrazinyl, thiadiazinyl, triazinyl, thiazinyl, thiopyranyl furoisoxazolyl, imidazothiazolyl, thienoisothiazolyl, thienothiazolyl, imidazopyrazolyl, cyclopentapyrazolyl, pyrrolopyrrolyl, thienothienyl, thiadiazolopyrimidinyl, thiazolothiazinyl, thiazolopyrimidinyl, thiazolopyridinyl, oxazolopyrimidinyl, oxazolopyridyl, benzoxazolyl, benzisothiazolyl, benzothiazolyl, imidazopyrazinyl, purinyl, pyrazolopyrimidinyl, imidazopyridinyl, benzimidazolyl, indazolyl, benzoxathiolyl, benzodioxolyl, benzodithiolyl, indolizinyl, indolinyl, isoindolinyl, furopyrimidinyl, furopyridyl, benzofuranyl, isobenzofuranyl, thienopyrimidinyl, thienopyridyl, benzothienyl, cyclopentaoxazinyl, cyclopentafuranyl, benzoxazinyl, benzothiazinyl, quinazolinyl, naphthyridinyl, quinolinyl, isoquinolinyl, benzopyranyl, pyridopyridazinyl and pyridopyrimidinyl.
The term “heteroaralkyl” represents a heterocycle group attached to the adjacent atom by a C1-6 alkyl. The heterocycle and alkyl portions can be optionally substituted as described above.
The term “urea” represents —N(R35)CONR36R37 wherein R35 is H or C1-6 alkyl and wherein R36 and R37 are each independently selected from the group consisting of H, C1-6 alkyl, C6-12 aryl, 3 to 10 membered heterocycle and C6-12 aralkyl, or R36 and R37 are taken together with the nitrogen to which they are attached to form a 3 to 10 membered heterocycle.
The term “independently” means that a substituent can be the same or a different definition for each item.
The term “optionally substituted” represents one or more halogen, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, amino, amidino, amido, azido, cyano, guanido, hydroxyl, nitro, nitroso, urea, OS(O)2R21 (wherein R21 is selected from C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), OS(O)2OR22 (wherein R22 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), S(O)2OR23 (wherein R23 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), S(O)0-2R24 (wherein R24 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), OP(O)OR25OR26, P(O)OR25OR26 (wherein R25 and R26 are each independently selected from H or C1-6 alkyl), C1-6alkyl, C6-12aralkyl, C6-12 aryl, C1-6alkoxy, C6-12aralkyloxy, C6-12aryloxy, 3 to 10 membered heterocycle, C(O)R27 (wherein R27 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), C(O)OR28 (wherein R28 is selected from H, C1-6 alkyl, C6-12 aryl, C6-12 aralkyl or 3 to 10 membered heterocycle), NR29C(O)R30, C(O)NR29R30 (wherein R29 is H or C1-6 alkyl and R30 is selected from H, C1-6 alkyl, C6-12 aryl, C6-12 aralkyl or 3 to 10 membered heterocycle, or R29 and R30 are taken together with the atoms to which they are attached to form a 3 to 10 membered heterocycle), SO2NR31R32, NR31SO2R32 (wherein R3, and R32 are each independently selected from the group consisting of H, C1-6 alkyl, C6-12 aryl, 3 to 10 membered heterocycle and C6-12 aralkyl), C(R33)NR34 or C(R33)NOR34 (wherein R33 and R34 are each independently selected from the group consisting of H, C1-6 alkyl, or C6-12aryl).
There is also provided “enantiomers” and “diastereoisomers” of the present invention. It will be appreciated that the compounds in accordance with the present invention can contain one or more chiral centers. The compounds in accordance with the present invention may thus exist in the form of two different optical isomers, that is (+) or (−) enantiomers or in the form of different diastereomers. All such enantiomers, diastereomers and mixtures thereof, including racemic or other ratio mixtures of individual enantiomers and diastereomers, are included within the scope of the invention. The single diastereomer can be obtained by methods well known to those of ordinary skill in the art, such as HPLC, crystallization and chromatography. The single enantiomer can be obtained by methods well known to those of ordinary skill in the art, such as chiral HPLC, enzymatic resolution and chiral auxiliary derivatization.
The optical purity is numerically equivalent to the “enantiomeric excess”. The term “enantiomeric excess” is defined in percentage (%) value as follows: [mole fraction (major enantiomer)—mole fraction (minor enantiomer)] ×100. An example of enantiomeric excess of 99% represents a ratio of 99.5% of one enantiomer and 0.5% of the opposite enantiomer.
“Oxidation levels”: When there is a sulfur atom present, the sulfur atom can be at different oxidation levels, ie. S, SO, or SO2. All such oxidation levels are within the scope of the present invention. When there is a nitrogen atom present, the nitrogen atom can be at different oxidation levels, ie. N or NO. All such oxidation levels are within the scope of the present invention.
There is also provided “pharmaceutically acceptable hydrates” of the compounds of the present invention. “Hydrates” exist when the compound of the invention incorporates water. The hydrate may contain one or more molecule of water per molecule of compound of the invention. Illustrative non-limiting examples include monohydrate, dihydrate, trihydrate and tetrahydrate. The hydrate may contain one or more molecule of compound of the invention per molecule of water. An illustrative non-limiting example include semi-hydrate. In one embodiment, the water may be held in the crystal in various ways and thus, the water molecules may occupy lattice positions in the crystal, or they may form bonds with salts of the compounds as described herein. The hydrate must be “acceptable” in the sense of not being deleterious to the recipient thereof. The hydration may be assessed by methods known in the art such as Loss on Drying techniques (LOD) and Karl Fisher titration.
There is also provided “pharmaceutically acceptable salts” of the compounds of the present invention. By the term “pharmaceutically acceptable salts” of compounds are meant those derived from pharmaceutically acceptable inorganic and organic acids and bases. Examples of suitable acids include but are not limited to hydrochloric, hydrobromic, sulphuric, nitric, perchloric, fumaric, maleic, phosphoric, glycollic, lactic, salicylic, succinic, toleune-p-sulphonic, tartaric, acetic, trifluoroacetic, citric, methanesulphonic, formic, benzoic, malonic, naphthalene-2-sulphonic and benzenesulphonic acids. Other acids such as oxalic, while not in themselves pharmaceutically acceptable, may be useful as intermediates in obtaining the compounds of the invention and their pharmaceutically acceptable acid addition salts.
Salts derived from appropriate bases include alkali metal, alkaline earth metal or ammonium salts. The salt(s) must be “acceptable” in the sense of not being deleterious to the recipient thereof. Non-limiting examples of such salts known by those of ordinary skill in the art include without limitation calcium, potassium, sodium, choline, ethylenediamine, tromethamine, arginine, glycinelycine, lycine, magnesium and meglumine.
There is also provided a “pharmaceutically acceptable solvates” of the compounds of the present invention. The term “solvate” means that the compound of the invention incorporates one or more pharmaceutically acceptable solvent. The solvate may contain one or more molecule of solvent per molecule of compound of the invention or may contain one or more molecule of compound of the invention per molecule of solvent. In one embodiment, the solvent may be held in the crystal in various ways and thus, the solvent molecule may occupy lattice positions in the crystal, or they may form bonds with salts of the compounds as described herein. The solvate(s) must be “acceptable” in the sense of not being deleterious to the recipient thereof. The solvation may be assessed by methods known in the art such as Loss on Drying techniques (LOD).
Reference hereinafter to a compound according to the invention includes compounds of the general formula (I) and their pharmaceutically acceptable salts, hydrates and solvates.
“Polymorphs”: It will be appreciated by those skilled in the art that the compounds in accordance with the present invention can exist in several different crystalline forms due to a different arrangement of molecules in the crystal lattice. This may include solvate or hydrate (also known as pseudopolymorphs) and amorphous forms. All such crystalline forms and polymorphs are included within the scope of the invention. The polymorphs may be characterized by methods well known in the art. Examples of analytical procedures that may be used to determine whether polymorphism occurs include: melting point (including hot-stage microscopy), infrared (not in solution), X-ray powder diffraction, thermal analysis methods (e.g. differential scanning calorimetry (DSC), differential thermal analysis (DTA), thermogravimetric analysis (TGA)), Raman spectroscopy, comparative intrinsic dissolution rate, scanning electron microscopy (SEM).
In one aspect, the present invention provides novel compounds including:
Compound 1
- 2-(4-bromobenzyl)-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 2
- 8-(3-phenylpropyl)-2-(4-trifluoromethyl-benzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 3
- 2-(4-chlorobenzyl)-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 4
- 2-(4-fluorobenzyl)-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 5
- 8-(3-phenyl-propyl)-2-(4-trifluoromethoxy-benzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 6
- 2-(4-methylbenzyl)-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 7
- 4-[l-oxo-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]dec-2-ylmethyl]-benzonitrile hydrochloride
Compound 8
- 2-biphenyl-4-ylmethyl-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 9
- 2-naphthalen-2-ylmethyl-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 10
- 2-(4-bromobenzyl)-8-(3-phenyl-butyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 11
- 2-(4-bromobenzyl)-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 12
- 8-(3,3-diphenyl-propyl)-2-(4-trifluoromethoxy-benzyl)-2,8-diaza-spiro[4.5]decan-1-one
Compound 13
- 2-(4-bromobenzyl)-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-3-one hydrochloride
Compound 14
- 8-(3,3-diphenyl-propyl)-2-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 15
- 8-(3,3-diphenyl-propyl)-2-pyridin-4-ylmethyl-2,8-diaza-spiro[4.5]decan-1-one dihydrochloride
Compound 16
- 8-(3,3-diphenyl-propyl)-2-(4-methoxy-benzyl)-2,8-diaza-spiro[4.5]decan-1-one
Compound 17
- 8-(3,3-diphenyl-propyl)-2-(4-pyrazol-1-yl-benzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 18
- 2-benzothiazol-2-ylmethyl-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 19
- 8-(3,3-diphenyl-propyl)-2-(4-methanesulfonyl-benzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 20
- 8-(3,3-diphenyl-propyl)-2-(3-phenyl-allyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 21
- 8-(3,3-diphenyl-propyl)-2-phenethyl-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 22
- 2-(4-benzyloxy-benzyl)-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one
Compound 23
- 2-benzofuran-2-ylmethyl-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one
Compound 24
- 8-(3,3-diphenyl-propyl)-2-(4-isopropyl-benzyl)-2,8-diaza-spiro[4.5]decan-1-one
Compound 25
- 2-(5-chloro-benzo[b]thiophen-3-ylmethyl)-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one
Compound 26
- 8-(3,3-diphenyl-propyl)-2-(4-nitro-benzyl)-2,8-diaza-spiro[4.5]decan-1-one
Compound 27
- 2-(4-bromo-benzyl)-8-(3-pyridin-2-yl-propyl)-2,8-diaza-spiro[4.5]decan-1-one
Compound 28
- 2-[1-(4-bromophenyl)-ethyl]-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 29
- 8-(3,3-diphenyl-propyl)-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]decan-1-one dihydrochloride
Compound 30
- N-{4-[8-(3,3-diphenyl-propyl)-1-oxo-2,8-diaza-spiro[4.5]dec-2-ylmethyl]-phenyl}-acetamide hydrochloride
Compound 31
- 8-(3,3-diphenyl-propyl)-2-(6-trifluoromethyl-pyridin-3-ylmethyl)-2,8-diaza-spiro[4.5]decan-1-one dihydrochloride
Compound 32
- 4-[8-(3,3-diphenyl-propyl)-1-oxo-2,8-diaza-spiro[4.5]dec-2-ylmethyl]-benzoic acid hydrochloride
Compound 33
- 8-(3,3-diphenyl-propyl)-2-pyridin-2-ylmethyl-2,8-diaza-spiro[4.5]decan-1-one dihydrochloride
Compound 34
- 8-(3,3-diphenyl-propyl)-2-(4-trifluoromethylsulfanyl-benzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 35
- 8-(3,3-diphenyl-propyl)-2-(4-methyl-cyclohexylmethyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 36
- 4-[8-(3,3-diphenyl-propyl)-1-oxo-2,8-diaza-spiro[4.5]dec-2-ylmethyl]-benzoic acid methyl ester hydrochloride
Compound 37
- 8-(3,3-diphenyl-propyl)-2-(5-trifluoromethyl-furan-2-ylmethyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 38
- 8-(3,3-diphenyl-propyl)-2-(4-iodo-benzyl)-2,8-diaza-spiro[4.5]decan-1-one
Compound 39
- 2-(4-methanesulfonylbenzyl)-8-(3-phenyl-butyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 40
- 2-(4-bromobenzyl)-8-[3-hydroxy-3-(2-methoxyphenyl)-3-phenyl-propyl]-2,8-diaza-spiro[4.5]decan-1-one
Compound 41
- 2-(4-bromobenzyl)-8-[3-hydroxy-3-(3-methoxyphenyl)-3-phenyl-propyl]-2,8-diaza-spiro[4.5]decan-1-one
Compound 42
- 2-(4-bromobenzyl)-8-(3-hydroxy-3-phenyl-3-thiophen-2-yl-propyl)-2,8-diaza-spiro[4.5]decan-1-one
Compound 43
- 2-(4-bromobenzyl)-8-(3-hydroxy-3-phenyl-butyl)-2,8-diaza-spiro[4.5]decan-1-one
Compound 44
- 2-(4-bromobenzyl)-8-[3-(2-methoxyphenyl)-3-phenyl-propyl]-2,8-diaza-spiro[4.5]decan-1-one
Compound 45
- 2-(4-bromobenzyl)-8-[3-(3-chlorophenyl)-3-hydroxy-3-phenyl-propyl]-2,8-diaza-spiro[4.5]decan-1-one
Compound 46
- 2-(4-bromobenzyl)-8-[3-(4-chlorophenyl)-3-hydroxy-3-phenyl-propyl]-2,8-diaza-spiro[4.5]decan-1-one
Compound 47
- 2-(4-bromobenzyl)-8-[3-(3-chlorophenyl)-3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one
Compound 48
- 2-(4-bromobenzyl)-8-(3-phenyl-3-thiophen-2-yl-propyl)-2,8-diaza-spiro[4.5]decan-1-one
Compound 49
- 2-(4-bromobenzyl)-8-[3-(4-chlorophenyl)-3-phenyl-propyl]-2,8-diaza-spiro[4.5]decan-1-one
Compound 50
- 2-(4-Bromobenzyl)-8-(3-hydroxy-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one
Compound 51
- 8-(3-Benzyloxy-3-phenylpropyl)-2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 52
- 2-(4-Bromobenzyl)-8-(3-phenoxy-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one
Compound 53
- {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid tert-butyl ester
Compound 54
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride
Compound 55
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2,6-dimethyl-benzamide hydrochloride
Compound 56
- Cyclohexanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 57
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-phenyl-acetamide hydrochloride
Compound 58
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(2,4,6-trimethyl-phenyl)-acetamide hydrochloride
Compound 59
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-phenyl-propionamide hydrochloride
Compound 60
- {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-methyl-carbamic acid tert-butyl ester
Compound 61
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-N-methyl-benzamide hydrochloride
Compound 62
- Cyclohexanecarboxylic acid {3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-methyl-amide hydrochloride
Compound 63
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-N-methyl-2-phenyl-acetamide hydrochloride
Compound 64
- N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-N-methyl-2-(2,4,6-trimethyl-phenyl)-acetamide hydrochloride
Compound 65
- [3-(1 -oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-carbamic acid tert-butyl ester
Compound 66
- {3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid tert-butyl ester
Compound 67
- [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chloro-phenyl)-propyl]-carbamic acid tert-butyl ester
Compound 68
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochlroride
Compound 69
- Cyclopropanecarboxylic acid {3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 70
- N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 71
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-methyl-butyramide hydrochloride
Compound 72
- N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-chloro-benzamide hydrochloride
Compound 73
- N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-methoxy-benzamide hydrochloride
Compound 74
- Pyridine-2-carboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide dihydrochloride
Compound 75
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-chloro-benzamide hydrochloride
Compound 76
- N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-methoxy-benzamide hydrochloride
Compound 77
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-nicotinamide dihydrochloride
Compound 78
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl)-4-chloro-benzamide hydrochloride
Compound 79
- N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-4-methoxy-benzamide hydrochloride
Compound 80
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isonicotinamide dihydrochloride
Compound 81
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3,4-dichloro-benzamide hydrochloride
Compound 82
- N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3,4-dimethoxy-benzamide hydrochloride
Compound 83
- N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(2-chloro-phenyl)-acetamide hydrochloride
Compound 84
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(2-methoxy-phenyl)-acetamide hydrochloride
Compound 85
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(3-chloro-phenyl)-acetamide hydrochloride
Compound 86
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(3-methoxy-phenyl)-acetamide hydrochloride
Compound 87
- N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-pyridin-3-yl-acetamide dihydrochloride
Compound 88
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(4-methoxy-phenyl)-acetamide hydrochloride
Compound 89
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(3,4-dichloro-phenyl)-acetamide hydrochloride
Compound 90
- Tetrahydro-pyran-4-carboxylic acid{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 91
- Cyclopentanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 92
- Cyclobutanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 93
- Cycloheptanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 94
- N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclohexyl-acetamide hydrochloride
Compound 95
- N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 96
- Cyclopropanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 97
- N-{3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 98
- N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-methyl-butyramide hydrochloride
Compound 99
- 2-chloro-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride
Compound 100
- 2-methoxy-N-(3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride
Compound 101
- Pyridine-2-carboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide dihydrochloride
Compound 102
- 3-chloro-N-{3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride
Compound 103
- 3-methoxy-N-{3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride
Compound 104
- N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-nicotinamide dihydrochloride
Compound 105
- 4-chloro-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride
Compound 106
- 4-methoxy-N-{3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride
Compound 107
- N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isonicotinamide dihydrochloride
Compound 108
- (R)-cyclohexanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro [4.5]dec-8-yl]-1-phenyl-propyl}-amide
Compound 109
- 3,4-dichloro-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride
Compound 110
- 3,4-dimethoxy-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride
Compound 111
- 2-(2-chloro-phenyl)-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 112
- N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(2-methox-phenyl)-acetamide hydrochloride
Compound 113
- 2-(3-chlorophenyl)-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 114
- N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(3-methoxyphenyl)-acetamide hydrochloride
Compound 115
- N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-pyridin-3-yl-acetamide dihydrochloride
Compound 116
- N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-2-(4-methoxyphenyl)-acetamide hydrochloride
Compound 117
- 2-(3,4-dichlorophenyl)-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 118
- Tetrahydro-pyran-4-carboxylic acid{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 119
- Cyclopentanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 120
- Cyclobutanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 121
- Cycloheptanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 122
- 2-cyclohexyl-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 123
- (S)-cyclohexanecarboxylic acid 13-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide
Compound 124
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopentyl-acetamide hydrochloride
Compound 125
- Furan-2-carboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 126
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-ethyl-butyramide hydrochloride
Compound 127
- Thiophene-2-carboxylic acid {3-[2-(4-brom-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 128
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(3,4-dimethoxyphenyl)-acetamide hydrochloride
Compound 129
- 2-cyclopentyl-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 130
- Furan-2-carboxylic acid {3-[2-(4-methox-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 131
- 2-ethyl-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-butyramide hydrochloride
Compound 132
- Thiophene-2-carboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 133
- 2-(3,4-dimethoxy-phenyl)-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 134
- Cyclohexanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 135
- N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride
Compound 136
- N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-phenyl-acetamide hydrochloride
Compound 137
- N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 138
- Cyclopropanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}amide hydrochloride
Compound 139
- N-{3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 140
- N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-methyl-butyramide hydrochloride
Compound 141
- 2-chloro-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride
Compound 142
- N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-methoxy-benzamide hydrochloride
Compound 143
- Pyridine-2-carboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide dihydrochloride
Compound 144
- 3-chloro-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride
Compound 145
- N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-methoxy-benzamide hydrochloride
Compound 146
- N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-nicotinamide dihydrochloride
Compound 147
- 4-chloro-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride
Compound 148
- N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-4-methoxy-benzamide hydrochloride
Compound 149
- N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isonicotinamide dihydrochloride
Compound 150
- 3,4-dichloro-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride
Compound 151
- N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3,4-dimethoxy-benzamide hydrochloride
Compound 152
- 2-(2-chlorophenyl)-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 153
- N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(2-methoxyphenyl)-acetamide hydrochloride
Compound 154
- 2-(3-chlorophenyl)-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 155
- N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(3-methoxyphenyl)-acetamide hydrochloride
Compound 156
- N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride
Compound 157
- (S)-cyclohexanecarboxylic acid [3-(2-benzyl-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide
Compound 158
- N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(4-methoxyphenyl)-acetamide hydrochloride
Compound 159
- N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-phenyl-acetamide hydrochloride
Compound 160
- 2-(3,4-dichlorophenyl)-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 161
- Cyclopentanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 162
- Cyclobutanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 163
- Cycloheptanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 164
- 2-cyclohexyl-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 165
- 2-cyclopentyl-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 166
- Furan-2-carboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 167
- 2-ethyl-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-butyramide hydrochloride
Compound 168
- Thiophene-2-carboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 169
- 2-(3,4-dimethoxyphenyl)-N-{3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 170
- Cyclohexanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 171
- 4-methyl-cyclohexanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 172
- 2-methoxy-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide dihydrochloride
Compound 173
- 3-chloro-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide dihydrochloride
Compound 174
- 4-chloro-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide dihydrochloride
Compound 175
- 4-methoxy-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide dihydrochloride
Compound 176
- Cyclohexanecarboxylic acid [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chloro-phenyl)-propyl]-amide hydrochloride
Compound 177
- N-[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-benzamide hydrochloride
Compound 178
- N-[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-2-phenyl-acetamide hydrochloride
Compound 179
- {1-(3-chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester
Compound 180
- {1-(3,4-dichlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester
Compound 181
- N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride
Compound 182
- Cyclopropanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride
Compound 183
- N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-isobutyramide dihydrochloride
Compound 184
- 3-methyl-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-butyramide dihydrochloride
Compound 185
- 2-chloro-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide dihydrochloride
Compound 186
- Pyridine-2-carboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide trihydrochloride
Compound 187
- 3-methoxy-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide dihydrochloride
Compound 188
- N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-nicotinamide trihydrochloride
Compound 189
- N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-isonicotinamide trihydrochloride
Compound 190
- 3,4-dichloro-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide dihydrochloride
Compound 191
- 3,4-dimethoxy-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide dihydrochloride
Compound 192
- 2-(2-chlorophenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride
Compound 193
- 2-(2-methoxyphenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride
Compound 194
- N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide dihydrochloride
Compound 195
- 2-(3-chloro-phenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride
Compound 196
- 2-(3-methoxyphenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride
Compound 197
- 2-(4-methoxyphenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride
Compound 198
- N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-2-phenyl-acetamide dihydrochloride
Compound 199
- 2-(3,4-dichloro-phenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride
Compound 200
- Cyclopentanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride
Compound 201
- {1-(3-chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester
Compound 202
- Cyclobutanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5)dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride
Compound 203
- Cycloheptanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride
Compound 204
- 2-cyclohexyl-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride
Compound 205
- 2-cyclopentyl-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride
Compound 206
- Furan-2-carboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride
Compound 207
- 2-ethyl-N-[3-(1-oxo-2pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-butyramide dihydrochloride
Compound 208
- Thiophene-2-carboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride
Compound 209
- 2-(3,4-dimethoxyphenyl)-N-[3-(l-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride
Compound 210
- Cyclohexanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl)-amide dihydrochloride
Compound 211
- 4-methyl-cyclohexanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride
Compound 212
- [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester
Compound 213
- [3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester
Compound 214
- (S)-N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 215
- (S)-cyclopropanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 216
- (S)-N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 217
- (S)-N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl)-3-methyl-butyramide hydrochloride
Compound 218
- (S)-cyclopentanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 219
- (S)-cyclobutanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 220
- [3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester
Compound 221
- {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-carbamic acid tert-butyl ester
Compound 222
- {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-carbamic acid tert-butyl ester
Compound 223
- {1-(3,4-dichlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester
Compound 224
- 2-cyclopropyl-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 225
- 2-cyclopropyl-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 226
- [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester
Compound 227
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl-1-phenyl-propyl}-2-cyclopropyl-acetamide hydrochloride
Compound 228
- [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1(3,4-dimethoxyphenyl)-propyl]-carbamic acid tert-butyl ester
Compound 229
- {1-(3,4-dimethoxyphenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester
Compound 230
- Tetrahydro-pyran-4-carboxylic acid (3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 231
- [3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxy-phenyl)-propyl]-carbamic acid tertbutyl ester
Compound 232
- (S)-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid tert-butyl ester
Compound 233
- {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-carbamic acid tert-butyl ester
Compound 234
- {1-(3,4-dimethoxyphenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester
Compound 235
- {1-(4-chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester
Compound 236
- {1-(2-chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester
Compound 237
- {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid tert-butyl ester
Compound 238
- [3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester
Compound 239
- [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-chlorophenyl)-propyl]-carbamic acid tert-butyl ester
Compound 240
- [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-chlorophenyl)-propyl]-carbamic acid tert-butyl ester
Compound 241
- {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid tert-butyl ester
Compound 242
- {1-(4-chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester
Compound 243
- {1-(2-chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester
Compound 244
- {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid tert-butyl ester
Compound 245
- (S)-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide
Compound 246
- [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester
Compound 247
- [3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-carbamic acid tert-butyl ester
Compound 248
- [1-(2-chlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid tert-butyl ester
Compound 249
- [1-(3-chlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid tert-butyl ester
Compound 250
- [1-(3,4-dichlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid tert-butyl ester
Compound 251
- [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5)dec-8-yl)-1-thiophen-2-yl-propyl]-carbamic acid tert-butyl ester
Compound 252
- (S)-8-[3-(cyclopropanecarbonyl-amino)-3-phenyl-propyl]-2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane hydrochloride
Compound 253
- (S)-8-[3-(cyclopentanecarbonyl-amino)-3-phenyl-propyl]-2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane hydrochloride
Compound 254
- (S)-8-[3-(cyclohexanecarbonyl-amino)-3-phenyl-propyl]-2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane hydrochloride
Compound 255
- (S)-8-[3-(cyclopropanecarbonyl-amino)-3-phenyl-propyl]-2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5)decane hydrochloride
Compound 256
- (S)-8-(3-isobutyrylamino-3-phenyl-propyl)-2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane hydrochloride
Compound 257
- (S)-8-[3-(cyclopentanecarbonyl-amino)-3-phenyl-propyl]-2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane hydrochloride
Compound 258
- (S)-8-[3-(cyclohexanecarbonyl-amino)-3-phenyl-propyl]-2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5)decane hydrochloride
Compound 259
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-isobutyramide hydrochloride
Compound 260
- Cyclobutanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride
Compound 261
- Cyclopentanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride
Compound 262
- N-{3-[2-(4-bromo-enzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-propionamide hydrochloride
Compound 263
- N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl)-2-methoxy-acetamide hydrochloride
Compound 264
- Cyclohexanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride
Compound 265
- Cyclopropanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride
Compound 266
- N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-isobutyramide hydrochloride
Compound 267
- [3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester
Compound 268
- Cyclobutanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride
Compound 269
- Cyclopentanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride
Compound 270
- N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-propionamide hydrochloride
Compound 271
- 2-methoxy-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-acetamide hydrochloride
Compound 272
- Cyclohexanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride
Compound 273
- Cyclopropane carboxylic acid{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride
Compound 274
- N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-isobutyramide hydrochloride
Compound 275
- Cyclobutanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride
Compound 276
- Cyclopentanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride
Compound 277
- N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-propionamide hydrochloride
Compound 278
- N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-2-methoxy-acetamide hydrochloride
Compound 279
- Cyclohexanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride
Compound 280
- Cyclohexanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-amide dihydrochloride
Compound 281
- N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-isobutyramide dihydrochloride
Compound 282
- Cyclobutanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl)-amide dihydrochloride
Compound 283
- Cyclopentanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-amide dihydrochloride
Compound 284
- N-[3-(l-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-propionamide dihydrochloride
Compound 285
- Cyclohexanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-amide dihydrochloride
Compound 286
- Cyclopropanecarboxylic acid [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-amide hydrochloride
Compound 287
- N-[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-isobutyramide hydrochloride
Compound 288
- Cyclobutanecarboxylic acid [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-amide hydrochloride
Compound 289
- Cyclopentanecarboxylic acid [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-amide hydrochloride
Compound 290
- N-[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-propionamide hydrochloride
Compound 291
- N-[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-2-methoxy-acetamide hydrochloride
Compound 292
- 2-Cyclopropyl-N-{(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 293
- 2-Cyclopropyl-N-{(S)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 294
- Cyclopentanecarboxylic acid [(S)-3-(2-benzyl-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide hydrochloride
Compound 295
- Cyclopropanecarboxylic acid [(S)-3-(2-benzyl-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide hydrochloride
Compound 296
- Cyclohexanecarboxylic acid [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-amide hydrochloride
Compound 297
- Cyclopropanecarboxylic acid {l-(3-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 298
- N-{1-(3-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide hydrochloride
Compound 299
- Cyclobutanecarboxylic acid {l-(3-chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 300
- Cyclopentanecarboxylic acid {1-(3-chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 301
- N-{l-(3-Chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-propionamide hydrochloride
Compound 302
- N-{1-(3-Chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-2-methoxy-acetamide hydrochloride
Compound 303
- Cyclohexanecarboxylic acid {1-(3-chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 304
- Cyclopropanecarboxylic acid {l-(3-chlorophenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 305
- N-{l-(3-Chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide hydrochloride
Compound 306
- Cyclobutanecarboxylic acid {1-(3-chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 307
- Cyclopentanecarboxylic acid {1-(3-chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 308
- N-{l-(3-Chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-propionamide hydrochloride
Compound 309
- N-{l-(3-Chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-2-methoxy-acetamide hydrochloride
Compound 310
- Cyclopropanecarboxylic acid [1-(3-chlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride
Compound 311
- N-[1-(3-Chlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-isobutyramide dihydrochloride
Compound 312
- Cyclobutanecarboxylic acid [1-(3-chlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride
Compound 313
- Cyclopentanecarboxylic acid [1-(3-chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride
Compound 314
- N-[1-(3-Chlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-propionamide dihydrochloride
Compound 315
- N-[1-(3-Chlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-2-methoxy-acetamide dihydrochloride
Compound 316
- Cyclohexanecarboxylic acid [1-(3-chlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride
Compound 317
- Cyclopropanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-2-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride
Compound 318
- Cyclopentanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-2-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride
Compound 319
- Cyclopropanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride
Compound 320
- Cyclopentanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride
Compound 321
- Cyclopropanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-4-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride
Compound 322
- Cyclopentanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-4-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride
Compound 323
- Cyclopropanecarboxylic acid {(S)-3-[1-oxo-2-(1-oxy-pyridin-2-ylmethyl)-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 324
- Cyclopentanecarboxylic acid {(S)-3-[1-oxo-2-(1-oxy-pyridin-2-ylmethyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 325
- Cyclopropanecarboxylic acid {(S)-3-[1-oxo-2-(1-oxy-pyridin-3-ylmethyl)-2,8-diaza-spiro(4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 326
- Cyclopentanecarboxylic acid {(S)-3-[1-oxo-2-(1-oxy-pyridin-3-ylmethyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 327
- Cyclopropanecarboxylic acid {(S)-3-[1-oxo-2-(1-oxy-pyridin-4-ylmethyl)-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 328
- Cyclopentanecarboxylic acid { (S)-3-[1-oxo-2-(1-oxy-pyridin-4-ylmethyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 329
- Cyclopentanecarboxylic acid {3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-amide dihydrochloride
Compound 330
- N-{3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-propionamide dihydrochloride
Compound 331
- N-{3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-2-methoxy-acetamide dihydrochloride
Compound 332
- Cyclopropanecarboxylic acid {3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-pyridin-2-yl-propyl}-amide dihydrochloride
Compound 333
- N-{3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-isobutyramide dihydrochloride
Compound 334
- Cyclobutanecarboxylic acid {3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-amide dihydrochloride
Compound 335
- Cyclopentanecarboxylic acid {3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-amide dihydrochloride
Compound 336
- N-{3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-propionamide dihydrochloride
Compound 337
- 2-Methoxy-N-{3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-acetamide dihydrochloride
Compound 338
- Cyclopropanecarboxylic acid {3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-amide dihydrochloride
Compound 339
- N-{3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl)-isobutyramide dihydrochloride
Compound 340
- Cyclobutanecarboxylic acid {3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-amide dihydrochloride
Compound 341
- Cyclopropanecarboxylic acid {3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-amide dihydrochloride
Compound 342
- N-{3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-isobutyramide dihydrochloride
Compound 343
- Cyclobutanecarboxylic acid {3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-amide dihydrochloride
Compound 344
- Cyclopentanecarboxylic acid {3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-amide dihydrochloride
Compound 345
- N-{3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl)-propionamide dihydrochloride
Compound 346
- N-{(S)-3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-nicotinamide
Compound 347
- (R)-Tetrahydro-furan-2-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide
Compound 348
- (S)-Tetrahydro-furan-2-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide
Compound 349
- Tetrahydro-furan-3-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide
Compound 350
- (R)-N-{(S)-3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-phenyl-propionamide
Compound 351
- 3-Oxo-cyclopentanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide
Compound 352
- (S)-N-{(S)-3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-phenyl-propionamide
Compound 353
- (R)-N-[(S)-3-(1-Oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-2-phenyl-propionamide
Compound 354
- (S)-N-[(S)-3-(1-Oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-2-phenyl-propionamide
Compound 355
- (R)-Tetrahydro-furan-2-carboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide
Compound 356
- (S)-Tetrahydro-furan-2-carboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide
Compound 357
- Tetrahydro-furan-3-carboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide
Compound 358
- 3-Oxo-cyclopentanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide
Compound 359
- N-[(S)-3-(1-Oxo-2-pyridin-2-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-isobutyramide
Compound 360
- N-[(S)-3-(1-Oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-isobutyramide
Compound 361
- N-[(S)-3-(1-Oxo-2-pyridin-4-ylmethyl-2,8-diaza-spiro[4.5)dec-8-yl)-1-phenyl-propyl]-isobutyramide
Compound 362
- N-{(S)-3-[1-Oxo-2-(1-oxy-pyridin-4-ylmethyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide
Compound 363
- N-{(S)-3-[1-Oxo-2-(1-oxy-pyridin-2-ylmethyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide
Compound 364
- N-{(S)-3-[1-Oxo-2-(1-oxy-pyridin-3-ylmethyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide
Compound 365
- 1-Methyl-cyclopentanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide
Compound 366
- 1-Methyl-cyclohexanecarboxylic acid{(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide
Compound 367
- 2-Cyclopentyl-N-{(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-propionamide
Compound 368
- 2-Cyclopentyl-N-{(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-propionamide
Compound 369
- 1-Methyl-cyclopentanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethy-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide
Compound 370
- 1-Methyl-cyclohexanecarboxylic acid[(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide
Compound 371
- 2-Cyclopentyl-N-[(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5)dec-8-yl)-1-phenyl-propyl]-propionamide
Compound 372
- 2-Cyclopentyl-N-[(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-propionamide
Compound 373
- Cyclopropanecarboxylic acid (3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride
Compound 374
- N-[3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-isobutyramide hydrochloride
Compound 375
- Cyclobutanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride
Compound 376
- Tetrahydro-pyran-2-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide
Compound 377
- N-{3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-2,2-dimethyl-propionamide hydrochloride
Compound 378
- N-{3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-2,2-dimethyl-propionamide hydrochloride
Compound 379
- N-{l-(3-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-2,2-dimethyl-propionamide hydrochloride
Compound 380
- N-{1-(3-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-2,2-dimethyl-propionamide hydrochloride
Compound 381
- N-[1-(3-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-2,2-dimethyl-propionamide dihydrochloride
Compound 382
- N-{1-(2-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-propyl}-2,2-dimethyl-propionamide hydrochloride
Compound 383
- N-{1-(4-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-2,2-dimethyl-propionamide hydrochloride
Compound 384
- 1-Methyl-cyclopropanecarboxylic acid {3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride
Compound 385
- 1-Methyl-cyclopropanecarboxylic acid {3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride
Compound 386
- 1-Methyl-cyclopropanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-amide dihydrochloride
Compound 387
- 1-Methyl-cyclopropanecarboxylic acid {1-(3-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 388
- 1-Methyl-cyclopropanecarboxylic acid {1-(3-chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 389
- 1-Methyl-cyclopropanecarboxylic acid [1-(3-chloro-phenyl)-3-(l-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride
Compound 390
- 1-Methyl-cyclopropanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-propyl}-amide hydrochloride
Compound 391
- 1-Methyl-cyclopropanecarboxylic acid {1- (4-chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 392
- Tetrahydro-pyran-2-carboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide
Compound 393
- Cyclopentanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride
Compound 394
- N-[3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-propionamide hydrochloride
Compound 395
- N-[3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-2-methoxy-acetamide hydrochloride
Compound 396
- N-[3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-2-cyclopropyl-acetamide hydrochloride
Compound 397
- Cyclohexanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride
Compound 398
- Cyclopropanecarboxylic acid [3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride
Compound 399
- N-[3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-isobutyramide hydrochloride
Compound 400
- Cyclobutanecarboxylic acid [3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride
Compound 401
- Cyclopentanecarboxylic acid [3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride
Compound 402
- N-[3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-propionamide hydrochloride
Compound 403
- 2-Methoxy-N-[3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-acetamide hydrochloride
Compound 404
- 2-Cyclopropyl-N-[3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1(2-methoxy-phenyl)-propyl]-acetamide hydrochloride
Compound 405
- Cyclohexanecarboxylic acid [3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride
Compound 406
- Cyclopropanecarboxylic acid [3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride
Compound 407
- N-[3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-isobutyramide hydrochloride
Compound 408
- Cyclobutanecarboxylic acid [3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride
Compound 409
- Cyclopentanecarboxylic acid (3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride
Compound 410
- N-[3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-propionamide hydrochloride
Compound 411
- N-[3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-2-methoxy-acetamide hydrochloride
Compound 412
- 2-Cyclopropyl-N-[3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-acetamide hydrochloride
Compound 413
- Cyclopropanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-amide hydrochloride
Compound 414
- N-[3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-isobutyramide hydrochloride
Compound 415
- Cyclobutanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-amide hydrochloride
Compound 416
- Cyclopentanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-amide hydrochloride
Compound 417
- N-[3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl)-propionamide hydrochloride
Compound 418
- N-[3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-2-methoxy-acetamide hydrochloride
Compound 419
- Cyclopropanecarboxylic acid [3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-amide hydrochloride
Compound 420
- N-[3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-isobutyramide hydrochloride
Compound 421
- Cyclobutanecarboxylic acid [3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-amide hydrochloride
Compound 422
- Cyclopentanecarboxylic acid [3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-amide hydrochloride
Compound 423
- N-[3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-propionamide hydrochloride
Compound 424
- Cyclohexanecarboxylic acid [3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride
Compound 425
- Cyclopentanecarboxylic acid [1-(3-methoxy-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride
Compound 426
- N-[1-(3-Methoxy-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-propionamide dihydrochloride
Compound 427
- 2-Methoxy-N-[1-(3-methoxy-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-acetamide dihydrochloride
Compound 428
- 3-Hydroxy-cyclopentanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide
Compound 429
- 3-Hydroxy-cyclopentanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide
Compound 430
- Cyclopropanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 431
- N-{1-(2-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide hydrochloride
Compound 432
- Cyclobutanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 433
- Cyclopentanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 434
- N-{1-(2-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-propionamide hydrochloride
Compound 435
- N-{1-(2-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-2-methoxy-acetamide hydrochloride
Compound 436
- Cyclohexanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 437
- Cyclopropanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 438
- N-{1-(2-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide hydrochloride
Compound 439
- Cyclobutanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 440
- Cyclopentanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 441
- N-{1-(2-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-propionamide hydrochloride
Compound 442
- N-{1-(2-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-2-methoxy-acetamide hydrochloride
Compound 443
- Cyclohexanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 444
- Cyclopropanecarboxylic acid [1-(2-chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride
Compound 445
- N-[1-(2-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-isobutyramide dihydrochloride
Compound 446
- Cyclobutanecarboxylic acid [1-(2-chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride
Compound 447
- Cyclopentanecarboxylic acid [1-(2-chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride
Compound 448
- N-[1-(2-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-propionamide dihydrochloride
Compound 449
- N-[1-(2-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-2-methoxy-acetamide dihydrochloride
Compound 450
- Cyclohexanecarboxylic acid [1-(2-chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride
Compound 451
- Cyclopropanecarboxylic acid {1-(4-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 452
- N-{1-(4-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide hydrochloride
Compound 453
- Cyclobutanecarboxylic acid {1-(4-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 454
- Cyclopentanecarboxylic acid {1-(4-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 455
- N-{1-(4-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-propionamide hydrochloride
Compound 456
- N-{1-(4-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyll-2-methoxy-acetamide hydrochloride
Compound 457
- Cyclohexanecarboxylic acid {1-(4-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 458
- N-{1-(4-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-propionamide hydrochloride
Compound 459
- N-{1-(4-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-2-methoxy-acetamide hydrochloride
Compound 460
- Cyclohexanecarboxylic acid {1-(4-chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 461
- Cyclopropanecarboxylic acid [1-(4-chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride
Compound 462
- N-[1-(4-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-isobutyramide dihydrochloride
Compound 463
- Cyclobutanecarboxylic acid [1-(4-chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl)-amide dihydrochloride
Compound 464
- Cyclopentanecarboxylic acid [1-(4-chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride
Compound 465
- N-[1-(4-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-propionamide dihydrochloride
Compound 466
- N-[1-(4-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-2-methoxy-acetamide dihydrochloride
Compound 467
- Cyclohexanecarboxylic acid [1-(4-chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride
Compound 468
- Cyclopropanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-chloro-phenyl)-propyl]-amide hydrochloride
Compound 469
- Cyclopropanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-chloro-phenyl)-propyl]-amide hydrochloride
Compound 470
- Cyclopropanecarboxylic acid {l-(3,4-dichloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 471
- Cyclopropanecarboxylic acid {l-(3,4-dichloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 472
- Cyclopropanecarboxylic acid [1-(3,4-dichloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride
Compound 473
- Cyclopentanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-chloro-phenyl)-propyl]-amide hydrochloride
Compound 474
- Cyclopentanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-chloro-phenyl)-propyl]-amide hydrochloride
Compound 475
- Cyclopentanecarboxylic acid {(S)-3-[2-(4-fluoro-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 476
- Cyclopentanecarboxylic acid {(S)-3-[2-(4-chloro-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 477
- Cyclopentanecarboxylic acid {(S)-3-[2-(4-cyano-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 478
- Cyclopentanecarboxylic acid {(S)-3-[2-(4-difluoromethoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 479
- Cyclopentanecarboxylic acid {(S)-3-[l-oxo-2-(4-trifluoromethoxy-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 480
- Cyclopentanecarboxylic acid {(S)-3-[2-(4-methylsulfanyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 481
- Cyclopentanecarboxylic acid {(S)-3-[1-oxo-2-(4-pyrazol-1-yl-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 482
- Cyclopentanecarboxylic acid [(S)-3-(2-isobutyl-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide hydrochloride
Compound 483
- Cyclopentanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 484
- Cyclopentanecarboxylic acid { (S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 485
- Cyclopropanecarboxylic acid {(S)-3-[2-(4-fluoro-benzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 486
- Cyclopropanecarboxylic acid {(S)-3-[2-(4-chloro-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 487
- Cyclopropanecarboxylic acid {(S)-3-[2-(4-cyano-benzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 488
- Cyclopropanecarboxylic acid {(S)-3-[2- (4-difluoromethoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 489
- Cyclopropanecarboxylic acid {(S)-3-[1-oxo-2-(4-pyrazol-1-yl-benzyl)-2,.8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 490
- Cyclopropanecarboxylic acid [(S)-3-(2-cyclohexylmethyl-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide hydrochloride
Compound 491
- Cyclopropanecarboxylic acid [(S)-3-(2-isobutyl-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide hydrochloride
Compound 492
- Cyclopropanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 493
- Cyclopropanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 494
- N-[(S)-3-(2-Benzyl-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-isobutyramide hydrochloride
Compound 495
- N-{(S)-3-[2-(4-Fluoro-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 496
- Cyclopropanecarboxylic acid {(S)-3-[1-oxo-2-(4-trifluoromethoxy-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl}-amide hydrochloride
Compound 497
- Cyclopropanecarboxylic acid {(S)-3-[2-(4-methylsulfanyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 498
- N-{(S)-3-[2-(4-Chloro-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 499
- N-{(S)-3-[2-(4-Cyano-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 500
- N-{(S)-3-[2-(4-Difluoromethoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 501
- N-{(S)-3-[1-Oxo-2-(4-trifluoromethoxy-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 502
- N-{(S)-3-[2-(4-Methylsulfanyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 503
- N-{(S)-3-[2-(4-Methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 504
- 2-Methoxy-cyclopent-1-enecarboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide
Compound 505
- 2-Methoxy-cyclopent-1-enecarboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide
Compound 506
- Cyclopentanecarboxylic acid {1-(3,4-dichloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 507
- Cyclopentanecarboxylic acid {1-(3,4-dichloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 508
- Cyclopentanecarboxylic acid [1-(3,4-dichloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride
Compound 509
- N-{(S)-3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-propionamide hydrochloride
Compound 510
- N-{(S)-3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2,2-dimethyl-propionamide hydrochloride
Compound 511
- Thiophene-2-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 512
- Thiophene-3-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 513
- (R)-Tetrahydro-furan-2-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 514
- (S)-Tetrahydro-furan-2-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 515
- Tetrahydro-furan-3-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 516
- 3-Oxo-cyclopentanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 517
- 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 518
- Tetrahydro-pyran-4-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 519
- 4,6-Dimethyl-pyrimidine-5-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide trihydrochloride
Compound 520
- Adamantane-1-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 521
- N-{(S)-3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-propionamide hydrochloride
Compound 522
- N-{(S)-3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2,2-dimethyl-propionamide hydrochloride
Compound 523
- Thiophene-2-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 524
- Thiophene-3-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 525
- 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 526
- Tetrahydro-pyran-4-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 527
- N-{(S)-3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-nicotinamide dihydrochloride
Compound 528
- Pyrimidine-5-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide trihydrochloride
Compound 529
- 4,6-Dimethyl-pyrimidine-5-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide trihydrochloride
Compound 530
- Adamantane-1-carboxylic acid {(S)-3-[2- (4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 531
- N-{(S)-3-[2-(4-Ethoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 532
- Cyclopropanecarboxylic acid {(S)-3-[2-(4-ethoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 533
- 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 534
- 2-Cyclopropyl-N-{(S)-3-[2-(4-methanesulfonyl-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 535
- 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 536
- N-{3-[2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenylpropyl}-benzenesulfonamide hydrochloride
Compound 537
- Propane-2-sulfonic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 538
- Propane-2-sulfonic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 539
- Piperidine-1-carboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 540
- Piperidine-1-carboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 541
- Piperidine-1-carboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}amide hydrochloride
Compound 542
- 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-phenyl-urea hydrochloride
Compound 543
- 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(2-chloro-phenyl)-urea hydrochloride
Compound 544
- 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(2-methoxy-phenyl)-urea hydrochloride
Compound 545
- 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(3-chloro-phenyl)-urea hydrochloride
Compound 546
- 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(3-methoxy-phenyl)-urea hydrochloride
Compound 547
- 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(4-chloro-phenyl)-urea hydrochloride
Compound 548
- 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(4-methoxy-phenyl)-urea hydrochloride
Compound 549
- 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(2,6-dimethyl-phenyl)-urea hydrochloride
Compound 550
- 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-naphthalen-1-yl-urea hydrochloride
Compound 551
- 1-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-phenyl-urea hydrochloride
Compound 552
- 1-(2-chlorophenyl)-3-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea hydrochloride
Compound 553
- 1-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(2-methoxyphenyl)-urea hydrochloride
Compound 554
- 1-(3-chlorophenyl)-3-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea hydrochloride
Compound 555
- 1-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(3-methoxyphenyl)-urea hydrochloride
Compound 556
- -{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(4-methoxyphenyl)-urea hydrochloride
Compound 557
- 1-(2,6-dimethylphenyl)-3-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea hydrochloride
Compound 558
- 1-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-naphthalen-1-yl-urea hydrochloride
Compound 559
- 1-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-phenyl-urea hydrochloride
Compound 560
- 1-(2-chlorophenyl)-3-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea hydrochloride
Compound 561
- 1-{3-[2-(4-methanesulfonylbenzyl)--oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(2-methoxyphenyl)-urea hydrochloride
Compound 562
- 1-(3-chlorophenyl)-3-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea hydrochloride
Compound 563
- 1-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(3-methoxyphenyl)-urea hydrochloride
Compound 564
- 1-(4-chlorophenyl)-3-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea hydrochloride
Compound 565
- 1-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-3-(4-methoxyphenyl)-urea hydrochloride
Compound 566
- 1-(2,6-dimethylphenyl)-3-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea hydrochloride
Compound 567
- 1-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-naphthalen-1-yl-urea hydrochloride
Compound 568
- Morpholine-4-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 569
- Morpholine-4-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 570
- 3,3-Difluoro-pyrrolidine-1-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 571
- 3,3-Difluoro-pyrrolidine-1-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 572
- {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid methyl ester hydrochloride
Compound 573
- {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid ethyl ester hydrochloride
Compound 574
- {3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-carbamic acid cyclohexyl ester
Compound 575
- {(S)-3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid cyclohexyl ester
Compound 576
- {(S)-3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid cyclobutyl ester
Compound 577
- {(S)-3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid cyclopentyl ester
Compound 578
- [(S)-3-(1-Oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-carbamic acid cyclobutyl ester
Compound 579
- [(S)-3-(1-Oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-carbamic acid cyclopentyl ester
Compound 580
- [(S)-3-(1-Oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-carbamic acid 1-methyl-cyclopentyl ester
Compound 581
- [(S)-3-(1-Oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-carbamic acid cyclohexyl ester
Compound 582
- {3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid ethyl ester hydrochloride
Compound 583
- {3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid ethyl ester hydrochloride
Compound 584
- [3-(1-Oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-carbamic acid ethyl ester dihydrochloride
Compound 585
- {1-(2-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid ethyl ester hydrochloride
Compound 586
- {1-(2-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid ethyl ester hydrochloride
Compound 587
- [1-(2-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid ethyl ester dihydrochloride
Compound 588
- [3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chloro-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride
Compound 589
- {1-(3-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid ethyl ester hydrochloride
Compound 590
- {1-(3-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid ethyl ester hydrochloride
Compound 591
- [1-(3-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid ethyl ester dihydrochloride
Compound 592
- {1-(4-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid ethyl ester hydrochloride
Compound 593
- [1-(4-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid ethyl ester dihydrochloride
Compound 594
- {3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid methyl ester hydrochloride
Compound 595
- {3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid methyl ester hydrochloride
Compound 596
- {3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid methyl ester hydrochloride
Compound 597
- 3-(1-Oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-carbamic acid methyl ester dihydrochloride
Compound 598
- {1-(2-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid methyl ester hydrochloride
Compound 599
- {1-(2-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid methyl ester hydrochloride
Compound 600
- [1-(2-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid methyl ester dihydrochloride
Compound 601
- [3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chloro-phenyl)-propyl]-carbamic acid methyl ester hydrochloride
Compound 602
- {1-(3-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid methyl ester hydrochloride
Compound 603
- {3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-carbamic acid ethyl ester hydrochloride
Compound 604
- {3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-carbamic acid ethyl ester dihydrochloride
Compound 605
- 3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride
Compound 606
- [3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride
Compound 607
- [3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride
Compound 608
- [1-(4-Methoxy-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid ethyl ester dihydrochloride
Compound 609
- [3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3,4-dimethoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride
Compound 610
- {1-(3,4-Dimethoxy-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid ethyl ester hydrochloride
Compound 611
- {1-(3,4-Dimethoxy-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid ethyl ester hydrochloride
Compound 612
- [1-(3,4-Dimethoxy-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid ethyl ester dihydrochloride
Compound 613
- [3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride
Compound 614
- [3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride
Compound 615
- [3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride
Compound 616
- [1-(3-Methoxy-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid ethyl ester dihydrochloride
Compound 617
- [3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride
Compound 618
- [3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride
Compound 619
- [3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride
Compound 620
- [3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3,4-dimethoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride
Compound 621
- (1-(3,4-Dimethoxy-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid methyl ester hydrochloride
Compound 622
- {1-(3,4-Dimethoxy-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid methyl ester hydrochloride
Compound 623
- [1-(3,4-Dimethoxy-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid methyl ester dihydrochloride
Compound 624
- [3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride
Compound 625
- [3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride
Compound 626
- [3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride
Compound 627
- [1-(3-Methoxy-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid methyl ester dihydrochloride
Compound 628
- {1-(3-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl)-carbamic acid methyl ester hydrochloride
Compound 629
- 1-(3-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid methyl ester dihydrochloride
Compound 630
- {1-(4-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid methyl ester hydrochloride
Compound 631
- {1-(4-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid methyl ester hydrochloride
Compound 632
- [1-(4-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid methyl ester dihydrochloride
Compound 633
- [3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl}-carbamic acid methyl ester hydrochloride
Compound 634
- [3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride
Compound 635
- [3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride
Compound 636
- [3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride
Compound 637
- [3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride
Compound 638
- [3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride
Compound 639
- (4-Bromophenyl)-[8-(3,3-diphenylpropyl)-2,8-diaza-spiro[4.5]dec-2-yl]-methanone hydrochloride
Compound 640
- 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyric acid methyl ester
Compound 641
- 4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyric acid methyl ester
Compound 642
- 4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyric acid methyl ester
Compound 643
- 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2,N-diphenyl-butyramide hydrochloride
Compound 644
- N-benzyl-4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride
Compound 645
- 2-(4-bromobenzyl)-8-(4-oxo-3-phenyl-4-piperidin-1-yl-butyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 646
- 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-N-cyclohexyl-2-phenyl-butyramide hydrochloride
Compound 647
- 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-N-cyclohexyl-n-methyl-2-phenyl-butyramide hydrochloride
Compound 648
- 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-N-cyclopropyl-2-phenyl-butyramide hydrochloride
Compound 649
- 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-N-cyclobutyl-2-phenyl-butyramide hydrochloride
Compound 650
- N-cyclohexyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-n-methyl-2-phenyl-butyramide hydrochloride
Compound 651
- N-cyclopropyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride
Compound 652
- N-cyclobutyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride
Compound 653
- 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-N-cyclopentyl-2-phenyl-butyramide hydrochloride
Compound 654
- 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-N-isopropyl-2-phenyl-butyramide hydrochloride
Compound 655
- N-benzyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride
Compound 656
- 2-(4-methanesulfonylbenzyl)-8-(4-oxo-3-phenyl-4-piperidin-1-yl -butyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 657
- N-cyclohexyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride
Compound 658
- N-cyclopentyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride
Compound 659
- N-isopropyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride
Compound 660
- 4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2,N-diphenyl-butyramide hydrochloride
Compound 661
- N-benzyl-4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride
Compound 662
- 2-(4-methoxybenzyl)-8-(4-oxo-3-phenyl-4-piperidin-1-yl-butyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
Compound 663
- N-cyclohexyl-4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride
Compound 664
- N-cyclopropyl-4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride
Compound 665
- N-cyclobutyl-4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride
Compound 666
- N-cyclopentyl-4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride
Compound 667
- N-isopropyl-4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride
Compound 668
- Cyclopropanecarboxylic acid {(S)-1-(3-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 669
- Cyclopropanecarboxylic acid {(S)-1-(3-fluoro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 670
- Cyclopropanecarboxylic acid {(S)-3-[2- (4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride
Compound 671
- Cyclopropanecarboxylic acid {(S)-3-(2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-3-yl-propyl}-amide hydrochloride
Compound 672
- N-{(S)-1-(3-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide hydrochloride
Compound 673
- N-{(S)-1-(3-Fluoro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide hydrochloride
Compound 674
- N-{(S)-3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-isobutyramide hydrochloride
Compound 675
- N-{(S)-3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-3-yl-propyl}-isobutyramide hydrochloride
Compound 676
- N-{(S)-3-[2-(4-Chloro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 677
- N-{(S)-3-[2-(4-Fluoro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 678
- N-{(S)-3-[2-(4-Cyano-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 679
- N-{(S)-3-[2-(4-Ethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 680
- N-{(S)-3-[2-(4-Difluoromethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 681
- N-{(S)-3-[3-Oxo-2-(4-trifluoromethoxy-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 682
- N-{(S)-3-[3-Oxo-2-(4-trifluoromethyl-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 683
- N-{(S)-3-[3-Oxo-2-(4-pyrazol-1-yl-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride
Compound 684
- Cyclopropanecarboxylic acid {(S)-3-[2-(4-chloro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 685
- Cyclopropanecarboxylic acid {(S)-3-[2-(4-fluoro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 686
- Cyclopropanecarboxylic acid {(S)-3-[2-(4-cyano-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 687
- Cyclopropanecarboxylic acid {(S)-3-[2-(4-ethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 688
- Cyclopropanecarboxylic acid {(S)-3-[2-(4-difluoromethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 689
- Cyclopropanecarboxylic acid {(S)-3-[2-(4-trifluoromethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 690
- Cyclopropanecarboxylic acid {(S)-3-[2-(4-trifluoromethyl-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 691
- Cyclopropanecarboxylic acid {(S)-3-[3-oxo-2-(4-pyrazol-1-yl-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 692
- 2-Cyclopropyl-N-{(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 693
- N-{(S)-3-[2-(4-Chloro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide hydrochloride
Compound 694
- N-{(S)-3-[2-(4-Fluoro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide hydrochloride
Compound 695
- N-{(S)-3-[2-(4-Cyano-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide hydrochloride
Compound 696
- N-{(S)-3-[2-(4-Ethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide hydrochloride
Compound 697
- N-{(S)-3-[2-(4-Difluoromethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide hydrochloride
Compound 698
- N-{(S)-3-[2-(4-Trifluoromethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide hydrochloride
Compound 699
- N-{(S)-3-[2-(4-Trifluoromethyl-benzyl)-3-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide hydrochloride
Compound 700
- 2-Cyclopropyl-N-{(S)-3-[3-oxo-2-(4-pyrazol-1-yl-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride
Compound 701
- 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-chloro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 702
- 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-fluoro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 703
- 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-cyano-benzyl)-3-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 704
- 4,4-Difluoro-cyclohexanecarboxylic acid {((S)-3-[2-(4-ethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 705
- 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[3-oxo-2-(4-pyrazol-1-yl-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 706
- Cyclopropanecarboxylic acid {(S)-1-(3-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 707
- Cyclopropanecarboxylic acid {(S)-1-(3-fluoro-phenyl)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride
Compound 708
- Cyclopropanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride
Compound 709
- Cyclopropanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-3-yl-propyl}-amide hydrochloride
Compound 710
- N-{(S)-1-(3-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide hydrochloride
Compound 711
- N-{(S)-1-(3-Fluoro-phenyl)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide hydrochloride
Compound 712
- N-{(S)-3-[2-(4-Methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-isobutyramide hydrochloride
Compound 713
- N-{(S)-3-[2-(4-Methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-3-yl-propyl}-isobutyramide hydrochloride
Compound 714
- Propane-2-sulfonic acid {(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 715 3-{(S)-3-[2-(4-Methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-1,1-dimethyl-urea hydrochloride
Compound 716
- Morpholine-4-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 717
- 3,3-Difluoro-pyrrolidine-1-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride
Compound 718
- {(S)-3-[2-(4-Methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid methyl ester hydrochloride
Compound 719
- (S)-3-[2-(4-Methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid ethyl ester hydrochloride
and pharmaceutically acceptable salts, hydrates or solvates thereof. While the compounds are listed above as their hydrochloride salts, this aspect of the invention includes their non-salt forms, as well as pharmaceutically acceptable salts, hydrates and solvates thereof.
It will be appreciated that the amount of a compound of the invention required for use in treatment will vary not only with the particular compound selected but also with the route of administration, the nature of the condition for which treatment is required and the age and condition of the patient and will be ultimately at the discretion of the attendant physician or veterinarian. In general however a suitable dose will be in the range of from about 0.1 to about 750 mg/kg of body weight per day, preferably in the range of 0.5 to 60 mg/kg/day, most preferably in the range of 1 to 20 mg/kg/day.
The desired dose may conveniently be presented in a single dose or as divided dose administered at appropriate intervals, for example as two, three, four or more doses per day.
The compound is conveniently administered in unit dosage form; for example containing 10 to 1500 mg, conveniently 20 to 1000 mg, most conveniently 50 to 700 mg of active ingredient per unit dosage form.
Ideally the active ingredient should be administered to achieve peak plasma concentrations of the active compound of from about 1 to about 75 μM, preferably about 2 to 50 μM, most preferably about 3 to about 30 μM. This may be achieved, for example, by the intravenous injection of a 0.1 to 5% solution of the active ingredient, optionally in saline, or orally administered as a bolus containing about 1 to about 500 mg of the active ingredient. Desirable blood levels may be maintained by a continuous infusion to provide about 0.01 to about 5.0 mg/kg/hour or by intermittent infusions containing about 0.4 to about 15 mg/kg of the active ingredient.
While it is possible that, for use in therapy, a compound of the invention may be administered as the raw chemical it is preferable to present the active ingredient as a pharmaceutical formulation. The invention thus further provides a pharmaceutical formulation comprising a compound of formula (I) or a pharmaceutically acceptable derivative thereof together with one or more pharmaceutically acceptable carriers therefor and, optionally, other therapeutic and/or prophylactic ingredients. The carrier(s) must be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.
Pharmaceutical formulations include those suitable for oral, rectal, nasal, topical (including buccal and sub-lingual), transdermal, vaginal or parenteral (including intramuscular, sub-cutaneous and intravenous) administration or in a form suitable for administration by inhalation or insufflation. The formulations may, where appropriate, be conveniently presented in discrete dosage units and may be prepared by any of the methods well known in the art of pharmacy. All methods include the step of bringing into association the active compound with liquid carriers or finely divided solid carriers or both and then, if necessary, shaping the product into the desired formulation.
Pharmaceutical formulation suitable for oral administration may conveniently be presented as discrete units such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution, a suspension or as an emulsion. The active ingredient may also be presented as a bolus, electuary or paste. Tablets and capsules for oral administration may contain conventional excipients such as binding agents, fillers, lubricants, disintegrants, or wetting agents. The tablets may be coated according to methods well known in the art. Oral liquid preparations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups or elixirs, or may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations may contain conventional additives such as suspending agents, emulsifying agents, non-aqueous vehicles (which may include edible oils), or preservatives.
The compounds according to the invention may also be formulated for parenteral administration (e.g. by injection, for example bolus injection or continuous infusion) and may be presented in unit dose form in ampoules, pre-filled syringes, small volume infusion or in multi-dose containers with an added preservative. The compositions may take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. Alternatively, the active ingredient may be in powder form, obtained by aseptic isolation of sterile solid or by lyophilisation from solution, for constitution with a suitable vehicle, e.g. sterile, pyrogen-free water, before use.
For topical administration to the epidermis, the compounds according to the invention may be formulated as ointments, creams or lotions, or as a transdermal patch. Such transdermal patches may contain penetration enhancers such as linalool, carvacrol, thymol, citral, menthol and t-anethole. Ointments and creams may, for example, be formulated with an aqueous or oily base with the addition of suitable thickening and/or gelling agents. Lotions may be formulated with an aqueous or oily base and will in general also contain one or more emulsifying agents, stabilizing agents, dispersing agents, suspending agents, thickening agents, or colouring agents.
Formulations suitable for topical administration in the mouth include lozenges comprising active ingredient in a flavoured base, usually sucrose and acacia or tragacanth; pastilles comprising the active ingredient in an inert base such as gelatin and glycerin or sucrose and acacia; and mouthwashes comprising the active ingredient in a suitable liquid carrier.
Pharmaceutical formulations suitable for rectal administration wherein the carrier is a solid are most preferably presented as unit dose suppositories. Suitable carriers include cocoa butter and other materials commonly used in the art, and the suppositories may be conveniently formed by admixture of the active compound with the softened or melted carrier(s) followed by chilling and shaping in moulds.
Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or sprays containing in addition to the active ingredient such carriers as are known in the art to be appropriate.
For intra-nasal administration the compounds of the invention may be used as a liquid spray or dispersible powder or in the form of drops. Drops may be formulated with an aqueous or non-aqueous base also comprising one more dispersing agents, solubilising agents or suspending agents. Liquid sprays are conveniently delivered from pressurized packs.
For administration by inhalation the compounds according to the invention are conveniently delivered from an insufflator, nebulizer or a pressurized pack or other convenient means of delivering an aerosol spray. Pressurized packs may comprise a suitable propellant such as dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount.
Alternatively, for administration by inhalation or insufflation, the compounds according to the invention may take the form of a dry powder composition, for example a powder mix of the compound and a suitable powder base such as lactose or starch. The powder composition may be presented in unit dosage form in, for example, capsules or cartridges or e.g. gelatin or blister packs from which the powder may be administered with the aid of an inhalator or insufflator.
When desired the above described formulations adapted to give sustained release of the active ingredient may be employed.
When the compound (I) or a pharmaceutically acceptable salt, hydrate or solvate thereof is used in combination with a second therapeutic active agent, the dose of each compound may be either the same as or different from that when the compound is used alone. Conventional doses and regimens are readily appreciated by those skilled in the art, including doses described in the Physicians Desk Reference, 56th edition, 2002.
The present invention is directed to the use of the compounds as modulators of CCR5 chemokine receptor activity. In particular, the compounds of the invention have been found to have activity in binding to the CCR5 receptor in the biological assay, as described in Example 15, generally with an IC50 value of less than 25 μM. The terms “modulator” or “modulation” are meant to include antagonism, agonism, mixed and partial antagonism and agonism.
Certain compounds of the present invention have also been tested in an assay for HIV activity, as described in Example 15, and generally having an IC50 value of less than 1 μM.
The purity and mass of the following examples were characterized by mass spectra (LC/MS) and or NMR spectra.
The following general schemes and examples are provided to illustrate various embodiments of the present invention and shall not be considered as limiting in scope.
The following abbreviations may be used as follows:
- br broad
- DCC 1,3-dicyclohexylcarbodiimide
- DCE 1,2-dichloroethane
- DCM dichloromethane
- DIPEA N,N-diisopropylethylamine
- DMF N,N-dimethylformamide
- Hal halogen
- LAH lithium aluminium hydride
- TFA trifluoroacetic acid
- THF tetrahydrofuran
The semi-preparative HPLC purification procedures used are described below:
Column: Phenomenex Luna C18(2), 5 microns, 10×250 mm
Buffer A: 3 mM HCl in H2O (pH 2.4-2.6)
Buffer B: acetonitrile
Method A: 15-55% B in 30 min. (1.4%/min)
Method B: 10-60% B in 50 min. (1%/min)
Method C: 20-50% B in 21 min. (1.4%/min)
Method D: 10-60% B in 42 min. (1.2%/min)
Method E: 15-45% B in 21 min. (1.4%/min) or
Buffer A: H2O
Buffer B: acetonitrile
Method F: 15-55% B in 40 min. (1%/min)
Preparation 1
2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester
Sodium hydride 600 mg (14.7 mmol) (60% suspension in mineral oil) was added in a 500 mL round bottom flask under nitrogen followed by 20 mL of anhydrous DMF and 2.5 g (9.8 mmol) of 1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester previously dissolved in 20 mL of anhydrous DMF. After agitating one hour at room temperature, 2.5 g (9.8 mmol) of 4-bromobenzylbromide diluted in 20 mL of anhydrous DMF were added and the reaction mixture was agitated an additional hour at room temperature. Then 100 mL of water were added and the solution was extracted with diethyl ether (2×150 mL). The combined organic layers were dried (Na2SO4), filtered and evaporated under reduced pressure to yield 4.63 g 2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester as a yellow oil.
1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.51 (d, 2H), 7.12 (d, 2H), 4.31 (s, 2H), 3.8 (br d, 2H), 3.14 (t, 2H), 2.86 (br s, 2H), 1.89 (t, 2H), 1.54 (t×d, 2H), 1.37 (s, 9H), 1.32 (br d, 2H).
Preparation 2
2-(4-Bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
To 4.62 g of crude 2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester from preparation 1 was added 50 mL of 4N solution of dioxane/HCl. The reaction mixture was agitated 15 minutes at room temperature and 3.05 g (77.8%) of 2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride was collected, as a colorless solid by filtration followed by trituration with diethyl ether.
1H NMR (400 MHz, DMSO-d6): δ[ppm] 9.15 (br s, 1H), 8.83 (br s, 1H), 7.51 (d, 2H), 7.14 (d, 2H), 4.31 (s, 2H), 3.24 (br d, 2H), 3.15 (t, 2H), 2.92 (q, 2H), 1.95-1.84 (m, 4H), 1.56 (br d, 2H).
Preparation 3
2-(4-Methylsulfanylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester
This spiro compound was prepared as described in preparation 1, starting from 7 g (27.5 mmol) of 1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester, excepted it was purified by flash chromatography on silica gel (ethyl acetate/hexanes 0:100 to 20:80) yielding 8.05 g (74.9%) of 2-(4-methylsulfanylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester as a pale yellow solid.
1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.21 (d, 2H), 7.11 (d, 2H), 4.3 (s, 2H), 3.8 (br d, 2H), 3.13 (t, 2H), 2.88 (br s, 2H), 2.43 (s, 3H), 1.89 (t, 2H), 1.54 (t×d, 2H), 1.38 (s, 9H), 1.31 (br d, 2H).
Preparation 4
2-(4-Methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester
To a solution of 7.73 g (19.8 mmol) of 2-(4-ethylsulfanylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-arboxylic acid tert-butyl ester in 100 mL of THF, was added 18.2 g (29.7 mmol) of Oxone® in 100 mL of water. The reaction mixture was agitated overnight at room temperature. An aqueous solution of sodium hydroxide (1N, 100 mL) was added and the solution was extracted with DCM (2×200 mL). The combined organic layers were dried (Na2SO4), filtered and evaporated under reduced pressure to yield 6.62 g (79.1%) of 2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester as a white solid.
1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.81 (d, 2H), 7.37 (d, 2H), 4.41 (s, 2H), 3.76 (br d, 2H), 3.15 (t, 2H), 3.14 (s, 3H), 2.86 (br s, 2H), 1.89 (t, 2H), 1.52 (t×d, 2H), 1.33 (s, 9H), 1.29 (br d, 2H).
LC/MS: m/z 423.2 (MH+).
Preparation 5
2-(4-Methanesulfonylbenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride
As described in preparation 2, 6.62 g (15.6 mmol) of 2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester was deprotected under acidic conditions giving access to 5.25 g (93.7%) of 2-(4- methanesulfonylbenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride as a white solid.
1H NMR (400 MHz, DMSO-d6): δ[ppm] 9.04 (br s, 1H), 8.74 (br s, 1H), 7.83 (d, 2H), 7.39 (d, 2H), 4.42 (s, 2H), 3.21 (br d, 2H), 3.15 (t, 2H), 3.13 (s, 3H), 2.89 (q, 2H), 1.92 (t, 2H), 1.84 (t×d, 2H), 1.55 (br d, 2H).
Preparation 6
2-(4-Bromobenzyl)-3-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester
This spiro compound was prepared as described in preparation 1, starting from 300 mg (1.18 mmol) of 3-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester which was purified by flash chromatography on silica gel (ethyl acetate/hexanes 0:100 to 60:40) yielding 290 mg (58%) of 2-(4-bromobenzyl)-3-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester as a colorless oil.
1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.52 (d, 2H), 7.16 (d, 2H), 4.31 (s, 2H), 3.32 (m, 2H), 3.16 (br s, 2H), 3.02 (s, 2H), 2.25 (s, 2H), 1.4 (m, 4H), 1.35 (s, 9H).
Preparation 7
2-(4-Bromobenzyl)-2,8-diaza-spiro[4.5]decan-3-one hydrochloride
As described in preparation 2, 290 mg (0.68 mmol) of 2-(4-bromobenzyl)-3-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester was deprotected under acidic conditions giving to 212 mg (86.6%) of 2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-3-one hydrochloride as a white solid.
1H NMR (400 MHz, DMSO-d6): δ[ppm] 8.63 (br s, 2H), 7.52 (d, 2H), 7.17 (d, 2H), 4.32 (s, 2H), 3.07 (s, 2H), 3.00 (m, 4H), 2.33 (s, 2H), 1.65 (m, 4H).
EXAMPLE 1
2-(4-Bromobenzyl)-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-3-one hydrochloride (Compound 13)
A mixture of 28.7 mg (80 μmol) of 2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-3-one-hydrochloride, 24.4 mg (88 μmol) of 3,3-diphenylpropyl bromide and 33.1 mg (240 μmol) of potassium carbonate in 1.5 mL of anhydrous DMF was heated overnight at 60° C. After cooling to room temperature, 0.5 mL of water was added and the solution was extracted with DCM (2×2 mL). The crude material was purified by semi-preparative HPLC (method A) yielding 22.6 mg (51%) of Compound 13 as a white solid.
1H NMR (400 MHz, DMSO-d6): δ[ppm] 9.96 (br s, 1H), 7.52 (d, 2H), 7.34-7.25 (m, 8H), 7.19-7.13 (m, 4H), 4.31 (s, 2H), 3.96 (q, 1H), 3.36 (m, 4H), 3.05 (d, 1H), 2.96-2.83 (m, 4H), 2.47 (s, 2H), 2.3 (d, 1H), 1.75 (m, 4H).
LC/MS: m/z 519.0 (MH+).
Table 1 of compounds illustrates some of the compounds of the present invention that were synthesized using the procedure described in scheme 1.
TABLE 1
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CPD
#MOL STRUCTURECOMPOUND NAMEMOL WTPURITY
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12-(4-bromobenzyl)-8-(3-phenyl- propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride477.87195.1% (LC/MS)
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28-(2-phenylpropyl)-2-(4- trrifluoromethyl-benzyl)-2,8-diaza- spiro[4.5]decan-1-one hydrochloride466.97299+(LC/MS)
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32-(4-chlorobenzyl)-8-(3-phenyl- propyl)-2,8-diaza-spiro[4.5]decan- 1-one hydrochloride433.4294.8% (HPLC)
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42-(4-fluorobenzyl)-8-(3-phenyl- propyl)-2,8-diaza-spiro[4.5]decan- 1-one hydrochloride416.96590.5% (HPLC)
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58-(3-phenyl-prropyl)-2-(4- trifluoromethoxy-benzyl)-2,8- diaza-spiro[4.5]decan-1-one hydrochloride482.97192.2% (HPLC)
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62-(4-methylbenzyl)-8-(3-phenyl- propyl)-2,8-diaza-spiro[4.5]decan- 1-one hydrochloride413.00293.7% (HPLC)
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74-[1-oxo-8-(3-phenyl-propyl)-2,8- diaza-spiro[4.5]dec-2-ylmethyl]- benzonitrile hydrochloiride423.98594.1% (HPLC)
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82-biphenyl-4-ylmethyl-8-(3-phenyl- propyl)-2,8-diaza-spiro[4.5]decan- 1-one hydrochloride475.07399+(HPLC)
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92-naphthalen-2-ylmethyl-8-(3- phenyl-propyl)-2,8-diaza- spiro[4.5]decan-1-one hydrochloride449.03599+(HPLC)
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102-(4-bromobenzyl)-8-(3-phenyl- butyl)-2,8-diaza-spiro[4.5]decan-1- one hydrochloride491.89890+(HPLC)
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112-(4-bromobenzyl)-8-(3,3- diphenyl-propyl)-2,8-diaza- spiro[4.5]decan-1-one hydrochloride553.96999+(HPLC)
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128-(3,3-diphenyl-propyl)-2-(4- trifluoromethoxy-benzyl)-2,8- diaza-spiro[4.5]decan-1-one522.608100% (LC/MS)
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132-(4-bromobenzyl)-8-(3,3- diphenyl-propyl)-2,8-diaza- spiro[4.5]decan-3-one hydrochloride553.969>95% (LC/MS)
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148-(3,3-diphenyl-propyl)-2-(3- phenyl-propyl)-2,8-diaza- spiro[4.5]decan-1-one hydrochloride503.126100% (LC/MS)
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158-(3,3-diphenyl-propyl)-2-pyridin- 4-ylmethyl-2,8-diaza- spiro[4.5]decan-1-one dihydrochloride512.521100% (LC/MS)
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168-(3,3-dipheenyl-propyl)-2-(4- methoxy-benzyl)-2,8-diaza- spiro[4.5]decan-1-one468.63793% (LC/MS)
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178-(3,3-diphenyl-propyl)-2-(4- pyrazol-1-yl-benzyl)-2,8-diaza- spiro[4.5]decan-1-one hydrochloride541.13598% (LC/MS)
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182-benzothiazol-2-ylmethyl-8-(3,3- diphenyl-propyl)-2,8-diaza- spiro[4.5]decan-1-one hydrochloride532.14993% (LC/MS)
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198-(3,3-diphenyl-propyl)-2-(4- methanesulfonyl-benzyl)-2,8- diaza-spiro[4.5]decan-1-one hydrochloride553.16398+(LC/MS)
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208-(3,3-diphenyl-propyl)-2-(3- phenyl-allyl)-2,8-diaza- spiro[4.5]decan-1-one hydrochloride501.1198% (LC/MS)
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218-(3,3-diphenyl-propyl)-2- phenethyl-2,8-diaza- spiro[4.5]decan-1-one hydrochloride489.09998% (LC/MS)
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222-(4-benzyloxy-benzyl)-8-(3,3- diphenyl-propyl)-2,8-diaza- spiro[4.5]decan-1-one544.735100% (LC/MS)
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232-benzofuran-2-ylmethyl-8-(3,3- diphenyl-propyl)-2,8-diaza- spiro[4.5]decan-1-one478.63390% (LC/MS)
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248-(3,3-diphenyl-propyl)-2-(4- isopropyl-benzyl)-2,8-diaza- spiro[4.,5]decan-1-one480.692100% (LC/MS)
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252-(5-chloro-benzo[b]thiophen-3- ylmethyl)-8-(3,3-diphenyl-propyl)- 2,8-diaza-spiro[4.5]decan-1-one529.145100% (LC/MS)
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268-(3,3-diphenyl-propyl)-2-(4-nitro- benzyl)-2,8-diaza-spiro[4.5]decan- 1-one483.609100% (LC/MS)
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272-(4-bromo-benzyl)-8-(3-pyridin-2- yl-propyl)-2,8-diaza- spiro[4.5]decan-1-one442.39897% (HPLC)
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282-[1-(4-bromopheenyl)-ethyl]-8-(3,3- diphenyl-propyl)-2,8-diaza- spiro[4.5]decan-1-one hydrochloride567.99598+(LC/MS)
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298-(3,3-diphenyl-propyl)-2-pyridin- 3-ylmethyl-2,8-diaza- spiro[4.5]decan-1-one dihydrochloride512.52198+(LC/MS)
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30N-{4-[8-(3,3-diphenyl-propyl)-1- oxo-2,8-diaza-spiro[4.5]dec-2- ylmethyl]-phenyl}-acetamide hydrochloride532.12498+(LC/MS)
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318-(3,3-diphenyl-propyl)-2-(6- trifluoromethyl-pyridin-3-ylmethyl)- 2,8-diaza-spiro[4.5]decan-1-one dihydrochloride580.51990+(LC/MS)
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324-[8-(3,3-diphenyl-propyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-2- ylmethyl]-benzoic acid hydrochloride519.08198+(LC/MS)
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338-(3,3-diphenyl-propyl)-2-pyridin- 2-ylmethyl-2,8-diaza- spiro[4.5]decan-1-one dihydrochloride512.52198+(LC/MS)
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348-(3,3-diphenyl-propyl)-2-(4- trifluoromethylsulfanyl-benzyl)-2,8- diaza-spiro[4.5]decan-1-one hydrochloride575.13690+(LC/MS)
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358-(3,3-diphenyl-propyl)-2-(4- methyl-cyclohexylmethyl)-2,8- diaza-spiro[4.5]decan-1-one hydrochloride495.14798+(LC/MS)
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364-[8-(3,3-diphenyl-propyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-2- ylmethyl)-benzoic acid methyl ester hydrochloride533.10890.7% (LC/MS)
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378-(3,3-diphenyl-propyl)-2-(5- trifluoromethyl-furan-2-ylmethyl)- 2,8-diaza-spiro[4.5]decan-1-one hydrochloride533.03198+(LC/MS)
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388-(3,3-diphenyl-propyl)-2-(4-iodo- benzyl)-2,8-diaza-spiro[4.5]decan- 1-one564.504>95% (1H NMR)
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392-(4-methanesulfonylbenzyl)-8-(3- phenyl-butyl)-2,8-diaza- spiro[4.5]decan-1-one hydrochloride491.09298+(LC/MS)
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Preparation 8
2-(4-Bromobenzyl)-8-(3-oxo-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one
To a stirred solution of 2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride (2.30 g, 6.39 mmol) in DMF (43 mL) was added DIPEA (4.2 mL, 3.80 mmol) followed by 3-chloro-1-phenyl-propan-1-one (1.08 g, 6.39 mmol). The reaction mixture was stirred at room temperature for 18 hours and then a saturated solution of NaHCO3 was added and the mixture was extracted with ethyl acetate (3×30 mL). The combined organic extracts were washed with water (3×30 mL) and brine (30 mL), dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography on silica gel (0% to 5% methanol/DCM) to give 2.53 g (87%) of 2-(4-bromobenzyl)-8-(3-oxo-3-phenylpropyl)-2,8-diaza-spiro(4.5]decan-1-one.
1H NMR (400 MHz, CDCl3): δ[ppm] 7.98-7.95 (m, 2H), 7.59-7.54 (m, 1H), 7.49-7.42 (m, 4H), 7.10-7.07 (m, 2H), 4.39 (s, 2H), 3.21 (t, 2H), 3.14 (t, 2H), 2.93-2.90 (m, 2H), 2.84 (t, 2H), 2.19-2.14 (m, 2H), 2.05-1.98 (m, 2H), 1.90 (t, 2H), 1.44-1.41 (m, 2H).
EXAMPLE 2
2-(4-Bromobenzyl)-8-[3-hydroxy-3-(2-methoxyphenyl)- 3-phenylpropyl]-2,8-diaza-spiro[4.5]decan-1-one (Compound 40)
To a stirred solution of 2-(4-bromobenzyl)-8-(3-oxo-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one (157 mg, 0.35 mmol) in THF (3.5 mL) at 0° C. was added a 1.0 M solution of 2-methoxyphenylmagnesium bromide (1.4 mL, 1.4 mmol). The reaction mixture was warmed to room temperature and stirred for 18 hours. Water was added and the mixture was extracted with ethyl acetate (3×10 mL). The combined organic extracts were washed with brine (10 mL), dried over Na2SO4, filtered and concentrated. The crude product was purified by semi-preparative HPLC (method F) to give 133 mg (69%) of Compound 40 as a yellow oil.
1H NMR (400 MHz, CDCl3): δ[ppm] 7.90 (d, 1H), 7.52-7.39 (m, 4H), 7.24 (m, 3H), 7.15 (m, 1H), 7.08-7.01 (m, 3H), 6.79 (d, 1H), 4.42-4.33 (m, 2H), 3.48 (s, 3H), 3.11 (t, 2H), 3.05 (m, 1H), 2.78 (m, 1H), 2.64 (m, 1H), 2.50-2.45 (m, 2H), 2.34 (m, 1H), 2.23 (m, 1H), 2.00-1.88 (m, 3H), 1.85 (m, 2H), 1.45-1.40 (m, 2H).
EXAMPLE 3
2-(4-Bromobenzyl)-8-[3-(2-methoxyphenyl)-3-phenylpropyl]-2,8-diaza-spiro[4.5]decan-1-one (Compound 44)
To trifluoroacetic acid (1.4 mL) at room temperature was added portion wise sodium borohydride (67 mg, 1.775 mmol). This mixture was stirred at room temperature for 30 minutes and then a solution of 2-(4-bromobenzyl)-8-[3-hydroxy-3-(2-methoxyphenyl)-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one (40 mg, 0.071 mmol) in DCM (0.5 mL) was slowly added. The reaction mixture was stirred at room temperature for 20 hours and then poured into an ice cold solution of sodium hydroxide (5 mL). The mixture was extracted with ethyl acetate (3×5 mL) and the combined organic extracts were washed with brine (5 mL), dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography on silica gel (0% to 4% methanol/DCM) to give 24 mg (61%) of Compound 44 as a yellow oil.
1H NMR (400 MHz, CDCl3): δ[ppm] 7.43 (d, 2H), 7.38-7.32 (m, 1H), 7.26-7.2 (m, 5H), 7.12-6.94 (m, 5H), 6.35 (t, 1H), 4.36 (s, 2H), 3.7 (s, 3H), 3.2-2.9 (m, 5H), 2.1-1.9 (m, 2H), 1.85 (t, 2H).
Table 2 of compounds illustrates some of the compounds of the present invention that were synthesized using the procedure described in scheme 2.
TABLE 2
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CPDMOL
#MOL STRUCTURECOMPOUND NAMEWTPURITY
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402-(4-bromobenzyl)-8-[3-hydroxy-3- (2-methoxyphenyl)-3-phenyl- propyl]-2,8-diaza-spiro[4.5]decan- 1-one563.53293% BY HPLC
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412-(4-bromobenzyl)-8-[3-hydroxy-3- (3-methoxyphenyl)-3-phenyl- propyl]-2,8-diaza-spiro[4.5]decan- 1-one563,53299% BY HPLC
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422-(4-bromobenzyl)-8-(3-hydroxy-3- phenyl-3-thiophen-2-yl-propyl)-2,8- diaza-spiro[4.5]decan-1-one539.53597% BY HPLC
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432-(4-bromobenzyl)-8-(3-hydroxy-3- phenyl-butyl)-2,8-diaza- spiro[4.5]decan-1-one471.43699% BY HPLC
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442-(4-bromobenzyl)-8-[3-(2- methoxyphenyl)-3-phenyl-propyl]- 2,8-diaza-spiro[4.5]decan-1-one547.53499% BY HPLC
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452-(4-bromobenzyl)-8-[3-(3- chlorophenyl)-3-hydroxy-3-phenyl- propyl]-2,8-diaza-spiro[4.5]decan- 1-one567.95294% BY HPLC
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462-(4-bromobenzyl)-8-[3-(4- chlorophenyl)-3-hydroxy-3-phenyl- propyl]-2,8-diaza-spiro[4.5]decan- 1-one567.95297% BY HPLC
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472-(4-bromobenzyl)-8-[3-(3- chlorophenyl)-3-phenyl-propyl]-2,8- diaza-spiro[4.5]decan-1-one551.95396% BY HPLC
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4832-(4-bromobenzyl)-8-(3-phenyl-3- thiophen-2-yl-propyl)-2,8-diaza- spiro[4.5]decan-1-one523.53689% BY HPLC
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492-(4-bromobenzyl)-8-[3-(4- chlorophenyl)-3-phenyl-propyl]-2,8- diaza-spiro[4.5]decan-1-one551.95396% BY HPLC
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EXAMPLE 4
2-(4-Bromobenzyl)-8-(3-hydroxy-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one (Compound 50)
To a cold stirred solution of 2-(4-bromobenzyl)-8-(3-oxo-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one (350 mg, 0.769 mmol) in THF-methanol (7:3, 4.0 mL) was added NaBH4 (85 mg, 2.3 mmol). After stirring for one hour, the reaction mixture was then quenched with an aqueous solution of sodium hydroxide (1N). The reaction mixture was portioned in a separating funnel and the aqueous solution was then extracted with ethyl acetate (3×10 mL). The combined organic extracts were washed with brine and dried over sodium sulfate. Evaporation of the solvent gave
Compound 50 as an oil (300 mg, 85.4%).
1H NMR (400 MHz, CDCl3): δ[ppm] 7.44 (d×d, 2H), 7.40-7.3 (m, 4H), 7.26-7.23 (m, 1H), 7.09 (d×d, 2H), 4.94 (d×d, 1H), 4.39 (s, 2H), 3.14 (t, 2H), 3.1-2.9 (m, 2H), 2.7-2.5 (m, 2H), 2.3-1.8 (m, 9H), 1.6-1.4 (m, 2H).
EXAMPLE 5
8-(3-Benzyloxy-3-phenylpropyl)-2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride (Compound 51)
To an ice-cold stirred suspension of sodium hydride (23 mg, 60% in mineral oil, 0.6 mmol) in THF (0.5 mL) was added dropwise a solution of 2-(4-bromobenzyl)-8-(3-hydroxy-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one (91.4 mg, 0.2 mmol) in THF (0.6 mL). After stirring the reaction mixture at 0° C. for 45 minutes benzyl bromide (0.071 mL, 0.6 mmol) was added and the mixture was then stirred overnight. The mixture was quenched with water and extracted with ethyl acetate (3×5 mL). The combined organic extracts were washed with brine, dried (Na2SO4), concentrated, and purified by semi-preparative HPLC (method B) to yield Compound 51 as a white solid (13.0 mg, 22%).
1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.53-7.41 (m, 9H), 7.37 (t, 2H), 7.29 (m, 1H), 7.14 (t, 2H), 5.65 (d×d, 1H), 4.69 (m, 1H), 4.59 (d, 2H), 4.31 (d, 2H), 3.62 (m, 1H), 3.45 (m, 2H), 3.32 (m, 2H), 3.17 (t×d, 2H), 2.15 (m, 2H), 2.02-1.89 (m, 5H), 1.75 (m, 1H).
EXAMPLE 6
2-(4-Bromobenzyl)-8-(3-phenoxy-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one (Compound 52)
To a stirred solution of 2-(4-bromobenzyl)-8-(3-hydroxy-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one (65 mg, 0.142 mol) and phenol (13.3 mg, 0.142 mmol) in THF was added triphenylphosphine (37 mg, 0.142 mmol) followed by diethylazodicarboxylate (DEAD) (0.023 mL, 0.142 mmol). After stirring for 24 hours, the reaction mixture was then concentrated and purified on silica gel preparative TLC using 20% ethyl acetate-hexanes as eluent. Compound 52 was isolated as oil (12 mg, 15.8%).
1H NMR (CDCl3, 400 MHz): δ[ppm] 7.40-7.0 (m, 11H), 6.82-6.76 (m, 3H), 5.19 (d×d, 1H), 4.32 (s, 2H), 3.06 (t, 2H), 2.72 (m, 2H) , 2.5-1.7 (m, 10H) , 1.4-1.25 (m, 2H)
LC/MS: m/z 534.5 (MH+).
EXAMPLE 7
{3-[2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenylpropyl}-carbamic acid tert-butyl ester (Compound 53)
To a solution of 2.16 g (6 mmol) of 2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride in 100 mL of anhydrous DCE were added successively 1.5 g (6 mmol) of (3-oxo-1-phenylpropyl)-carbamic acid tert-butyl ester and 836 μL (6 mmol) of triethylamine. The reaction mixture was agitated at room temperature for 10 minutes before adding 2 g (9 mmol) of sodium triacetoxyborohydride. After an overnight agitation, 60 mL of satured solution of sodium bicarbonate was added. The solution was then extracted with DCM, dried over sodium sulfate, filtered and concentrated in vacuo. The crude mixture was purified by flash chromatography on silica gel eluting with methanol/DCM (0% to 5%) giving
Compound 53 as a white solid (2.97 g, 88.9%).
1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.51 (d, 2H), 7.45 (d, 1H), 7.27 (m, 4H), 7.19 (m, 1H), 7.12 (d, 2H), 4.52 (q, 1H), 4.32 (s, 2H), 3.11 (t, 2H), 2.69 (m, 2H), 2.17 (m, 2H), 1.91 (br t, 2H), 1.82 (t, 2H), 1.71 (m, 4H), 1.33 (s, 9H), 1.29 (m, 2H).
Preparation 9
8-(3-Amino-3-phenylpropyl)-2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one
To 2.97 g (5.33 mmol) of {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenylpropyl}-carbamic acid tert-butyl ester was added 48 mL of a 20% TFA solution in DCM. The reaction mixture was agitated one hour at room temperature before neutralizing with 120 mL of an aqueous solution of sodium hydroxide (1N). The solution was then extracted with DCM, dried over sodium sulfate, filtered and evaporated in vacuo yielding 8-(3-amino-3-phenylpropyl)-2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one as a pale yellow oil (2.43 g, 100%).
1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.51 (d, 2H), 7.32-7.24 (m, 4H), 7.17 (m, 1H), 7.12 (d, 2H), 4.31 (s, 2H), 3.81 (t, 1H), 3.1 (t, 2H), 2.72 (d×d, 2H), 2.25-2.16 (m, 2H), 1.98 (br s, 2H), 1.86 (br q, 2H), 1.81 (t, 2H), 1.73-1.59 (m, 4H), 1.29 (br d, 2H).
EXAMPLE 8
N-{3-[2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenylpropyl}-benzamide hydrochloride (Compound 54)
To 100 mg (100 μmol, loading of 1 mmol/g) of phenylcarboxyl activated ester on polymeric 4-hydroxy-2,3,5,6-tetrafluorobenzamido (TFP) resin (see preparation in J. M. Salvino et al. J. Comb. Chem. 2000, 2, 691-697), preswollen with 0.5 mL of anhydrous DMF, was added 27.3 mg (60 μmol) of 8-(3-amino-3-phenylpropyl)-2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one dissolved in 1 mL of DMF. The reaction was agitated overnight at room temperature. The mixture was filtered and washed with DCM (2×2 mL) . The filtrates were collected and evaporated in vacuo. The crude mixture was purified by semi-preparative HPLC (method A) and 14.1 mg (39.4%) of Compound 54 was isolated as a colorless solid.
1H NMR (400 MHz, DMSO-d6): δ[ppm] 9.64 (br s, 1H), 8.91 (d, 1H), 7.88 (d, 2H), 7.55-7.42 (m, 7H), 7.35 (t, 2H), 7.25 (t, 1H), 7.14 (d, 2H), 5.12 (m, 1H), 4.33 (s, 2H), 3.46 (m, 2H), 3.16 (m, 4H), 2.97 (m, 2H), 2.35 (m, 1H), 2.2 (m, 1H), 1.98 (m, 3H), 1.83 (t, 1H), 1.6 (br d, 2H).
LC/MS: m/z 562.0 (MH+).
Table 3 of compounds illustrates some of the compounds of the present invention that were synthesized using the procedure described in scheme 4.
TABLE 3
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CPD #MOL STRUCTURECOMPOUND NAMEMOL WTPURITY
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53{3-[2-(4-bromobvenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- carbamic acid tert-butyl ester556.541>95% (1H NMR)
|
54N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-benzamide hydrochloride596.99498+(LC/MS)
|
55N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5υdec-8-yl]-1-phenyl- propyl}-2,6-dimethyl-benzamide hydrochloride625.04798+(LC/MS)
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56Cyclohexanecarboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride603.04198+(LC/MS)
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57N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-phenyl-acetamide hydrochloride611.0298+(LC/MS)
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58N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(2,4,6-trimethyl-phenyl)- acetamide hydrochloride653.10198+(LC/MS)
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59N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-phenyl-propionamide hydrochloride625.04798+(LC/MS)
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60{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- methyl-carbamic acid tert-butyl ester570.568>95% (1H NMR)
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61N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-N-methyl-benzamide hydrochloride611.0298+(LC/MS)
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62Cyclohexanecarboxylic acid {3-[2-(4- bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- methyl-amide hydrochloride617.06898+(LC/MS)
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63N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-N-methyl-2-phenyl-acetamide hydrochloride625.04798+(LC/MS)
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64N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spirto[4.5]dec-8-yl]-1-phenyl- propyl}-N-methyl-2-(2,4,6-trimethyl- phenyl)-acetamide hydrochloride667.12898+(LC/MS)
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65[3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-carbamic acid tert-butyl ester478.63395% BY HPLC
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66{3-[2-(4-methanesulfonyl-benzyl)-1- -oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-carbamic acid tert-butyl ester555.73694% (LC- MS)
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67[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(3-chloro-phenyl)- propyl]-carbamic acid tert-butyl ester590.986>95% (1H NMR)
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68N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride534.92394.6% (LC/MS)
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69Cyclopropanecarboxylic acid {3-[2-(4- bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride560.96195.2% (LC/MS)
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70N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-issobutyramide hydrochloride562.97695% (LC/MS)
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71N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-methyl-butyramide hydrochloride577.00398+(LC/MS)
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72N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-chloro-benzmaide hydrochloride631.43998+(LC/MS)
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73N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-methoxy-benzamide hydrochloride627.01998+(LC/MS)
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74Pyridine-2-carboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5υdec-8-yl]-1-phenyl-propyl}- amide hydrochloride634.44393.7% (LC/MS)
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75N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-methoxy-benzamide hydrochloride631.43998+(LC/MS)
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76N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-chloro-benzamide hydrochloride627.01998+(LC/MS)
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77N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-nicotinamide dihydrochloride634.44398+(LC/MS)
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78N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-4-chloro-benzamidehydrochloride631.43998+(LC/MS)
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79N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-4-methoxy-benzamide hydrochloride627.01998+(LC/MS)
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80N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-isonicotinamide dihydrochloride634.44398+(LC/MS)
|
81N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3,4-dichloro-benzamide hydrochloride665.88498+(LC/MS)
|
82N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3,4-dimethoxy-benzamide hydrochloride657.04598+(LC/MS)
|
83N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(2-chloro-phenyl)-acetamide hydrochloride645.46594.8% (LC/MS)
|
84N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(2-methoxy-phenyl)- acetamide hydrochloride641.04698+(LC/MS)
|
85N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(3-chloro-phenyl)-acetamide hydrochloride645.46592.9% (LC/MS)
|
86N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(3-methoxy-phenyl)- acetamide hydrochloride641.04698+(LC/MS)
|
87N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-pyridin-3-yl-acetamide dihydrochloride648.46995+(LC/MS)
|
88N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(4-methoxy-phenyl)- acetamide hydrochloride641.04698+(LC/MS)
|
89N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(3,4-dichloro-phenyl)- acetamide hydrochloride679.91195+(LC/MS)
|
90Tetrahydro-pyran-4-carboxylic acid{3- [2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dcec-8-yl]-1-phenyl-propyl}- amide hydrochloride605.01395+(LC/MS)
|
91Cyclopentanecarboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride589.01498+(LC/MS)
|
92Cyclobutanecarboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride574.98798+(LC/MS)
|
93Cycloheptanecarboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride617.06898+(LC/MS)
|
94N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-cyclohexyl-acetamide hydrochloride617.06898+(LC/MS)
|
95N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride486.05298+(LC/MS)
|
96Cyclopropanecarboxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride512.0998+(LC/MS)
|
97N-{3-[2-(4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-isobutyramide hydrochlooride514.10698+(LC/MS)
|
98N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-methyl-butyramide hydrochloride528.13398+(LC/MS)
|
992-chloro-N-{3-[2-(4-methoxybenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-benzamide hydrochloride582.56895+(LC/MS)
|
1002-methoxy-N-{3-[2-(4-methoxybenzyl)- 1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-benzamide hydrochloride578.14998+(LC/MS)
|
101Pyridine-2-carboxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide dihydrochloride585.57298+(LC/MS)
|
1023-chloro-N-{3-[2-(4-methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-benzamide hydrochloride582.56898+(LC/MS)
|
1033-methoxy-N-{3-[2-(4-methoxy-benzyl)- 1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-benzamide hydrochloride578.14998+(LC/MS)
|
104N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-nicotinamide dihydrochloride585.57298+(LC/MS)
|
1054-chloro-N-{3-[2-(4-methoxybenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-benzamide hydrochloride582.56898+(LC/MS)
|
1064-methoxy-N-{3-[2-(4-methoxy-benzyl)- 1-0oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-benzamide hydrochloride578.14998+(LC/MS)
|
107N-{3-[2-(4-methoxybenzyl)-1-oxxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-isonicotinamide dihydrochloride585.57298+(LC/MS)
|
108(R)-cyclohexanecarboxylicc acid {3-[2- (4-bromobenzyl)-1-oxo-2,8-diaza-spiro [4.5]dec-8-yl]-1-phenyl-propyl}-asmide566.58100% (LC/MS)
|
1093,4-dichloro-N-{3-[1-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- benzamide hydrochloride617..01398+(LC/MS)
|
1103,4-dimethoxy-N-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- benzamide hydrochloride608.17598+(LC/MS)
|
1112-(2-chloro-phenyl)-N-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- acetamide hydrochloride596.59598+(LC/MS)
|
112N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(2-methox-phenyl)-acetamide hydrochloride592.17698+(LC/MS)
|
1132-(3-chlorophenyl)-N-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- dspiro[4.5]dec-8-yl]-1-phenyl-propyl}- acetamide hydrochloride5596.59598+(LC/MS)
|
114N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(3-methoxyphenyl)-acetamide hydrochloride592.17698+(LC/MS)
|
115N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-pyridin-3-yl-acetamide dihydrochloride599.59990+(LC/MS)
|
116N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(4-methoxyphenyl)-acetamide hydrochloride592.17698+(LC/MS)
|
1172-(3,4-dichlorophenyl)-N-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- acetamide hydrochloride631.0495+(LC/MS)
|
118Tetrahydro-pyran-4-carboxylic acid{3- [2-(4-methoxybeenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride556.14395+(LC/MS)
|
119Cyclopentanecarboxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride540.14498+(LC/MS)
|
120Cyclobutanecarboxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride526.11795+(LC/MS)
|
121Cycloheptanecarboxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-prropyl}- amide hydrochloride568.19798+(LC/MS)
|
1222-cyclohexyl-N-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- acetamide hydrochloride568.19798+(LC/MS)
|
123(S)-cyclohexanecarboxylic acid {3-[2- (4-bromobenzyl)-1-oxo-2,8-diaza- spirro[44.5]dec-8-yl]-1-phenyl-propyl}- amide566.5899% BY HPLC
|
124N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-cyclopentyl-acetamide hydrochloride603.04198+(LC/MS)
|
125Furan-2-carboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride586.95598+(LC/MS)
|
126N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spirro[4.5]dec-8-yl]-1-phenyl- propyl}-2-ethyl-butyramide hydrochloride591.0398+(LC/MS)
|
127Thiophene-2-carboxylic acid {3-[2-(4- brom-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride603.02298+(LC/MS)
|
128N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(3,4-dimethoxyphenyl)- acetamide hydrochloride671.07298+(LC/MS)
|
1292-cyclopentyl-N-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- acetamide hydrochloride554.17198+(LC/MS)
|
130Furan-2-carboxylic acid {3-[2-(4 methox-benzyl)-1-oxxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride538.08498+(LC/MS)
|
1312-ethyl-N-{3-[2-(4-methoxybenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-butyramide hydrochloride542.1698+(LC/MS)
|
132Thiophene-2-carbopxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride554.15198+(LC/MS)
|
1332-(3,4-dimethoxy-phenyl)-N-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- acetamide hydrochloride622.20298+(LC/MS)
|
134Cyclohexanecarboxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spirro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride554.17198+(LC/MS)
|
135N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-beenzamide hydrochloride548.12398+(LC/MS)
|
136N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-phenyl-acetamide hydrochloride562.1598+(LC/MS)
|
137N-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-acetamide hydrochloride534.11798+(LC/MS)
|
138Cyclopropanecarboxylic acid {3-[2-(4- methanesulfonylben zyl)-1-oxxo-2,8- diaza-spirro[4.5]dec-8-yl]-1-phenyl- propyl} amide hydrochloride560.15598+(LC/MS)
|
139N-{3-[2-(4-methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-isobutyramide hydrochloride562.17195% (LC/MS)
|
140N-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-3-methyl-butyramide hydrochloride576.19898+(LC/MS)
|
1412-chloro-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-benzamide hydrochloride630.63398+(LC/MS)
|
142N-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-2-methoxy-benzamide hydrochloride626.21498+(LC/MS)
|
143Pyridine-2-carboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide dihydrochloride633.63794.4% (LC/MS)
|
1443-chloro-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-benzamide hydrochloride630.63394.1% (LC/MS)
|
145N-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-3-methoxy-benzamide hydrochloride626.21498+(LC/MS)
|
146N-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-nictotinamide dihydrochloride633.63798+(LC/MS)
|
1474-chloro-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-benzamide hydrochloride630.63398+(LC/MS)
|
148N-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-4-methoxy-benzamide hydrochloride626.21498+(LC/MS)
|
149N-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-isonicotinamide dihydrochloride633.63798+(LC/MS)
|
1503,4-dichloro-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-benzamide hydrochloride665.07898+(LC/MS)
|
151N-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- pheenyl-propyl}-3,4-dimethoxy- benzamide hydrochloride656.2498+(LC/MS)
|
1522-(2-chlorophenyl)-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride644.6688.1% (LC/MS)
|
153N-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-2-(2-methoxyphenyl)- acetamide hydrochloride640.24198+(LC/MS)
|
1542-(3-chlorophenyl)-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride644.6693% (LC/MS)
|
155N-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-2-(3-methoxyphenyl)- acetamide hydrochloride640.24198+(LC/MS)
|
156N-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-benzamide hydrochloride596.18898+(LC/MS)
|
157(S)-cyclohexanecarboxylic acid [3-(2- benzyl-1-oxo-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-amide487.684>95% (HPLC)
|
158N-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-2-(4-methoxyphenyl)- acetamide hydrochloride640.24198+(LC/MS)
|
159N-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-2-phenyl-acetamide hydrochloride610.21598+(LC/MS)
|
1602-(3,4-dichlorophenyl)-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride679.10594+(LC/MS)
|
161Cyclopentanecarboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride588.20998+(LC/MS)
|
162Cyclobutanecarboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride574.18298+(LC/MS)
|
163Cycloheptanecarboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride616.26298+(LC/MS)
|
1642-cyclohexyl-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride616.26298+(LC/MS)
|
1652-cyclopentyl-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride602.23698+(LC/MS)
|
166Furan-2-carboxylic acid {3-[2-(4- meethanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride586.14998+(LC/MS)
|
1672-ethyl-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-butyramide hydrochloride590.22598+(LC/MS)
|
168Thiophene-2-carboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride602.21698+(LC/MS)
|
1692-(3,4-dimethoxyphenyl)-N-{3-[2-(4- methanesulfonyl-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride670.26798+(LC/MS)
|
170Cyclohexanecarboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride602.23698+(LC/MS)
|
1714-methyl-cyclohexanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride616.26298+(LC/MS)
|
1722-methoxy-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-ylk)- 1-phenyl-propyl]-benzamide dihydrochloride585.57298+(LC/MS)
|
1733-chloro-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-benzamide dihydrochloride589.99298+(LC/MS)
|
1744-chloro-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-benzamide dihydrochloride589.99298+(LC/MS)
|
1754-methoxy-N-[3-(1-oxo-2-pyridin-3- ylmeethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-benzamide dihydrochloride585.57298+(LC/MS)
|
176Cyclohexanecarboxylic acid [3-[2-(4- bromobernzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(3-chloro-phenyl)- propyl]-amide hydrochloride637.48694.3% (LC/MS)
|
177N-[3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3- chlorophenyl)-propyl]-benzamide hydrochloride631.43998+(LC/MS)
|
178N-[3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3- chlorophenyl)-propyl]-2-phenyl- acetamide hydrochloride645.46598+(LC/MS)
|
179{1-(3-chlorophenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}carbamic acid tert-butyl ester542.116>95% (1H NMR)
|
180{1-(3,4-dichlorophenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester576.561>95% (1H NMR)
|
181N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-acetamide dihydrochloride493.47690+(LC/MS)
|
182Cyclopropanecarboxylic acid [3-(1-oxo- 2-pyrridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- amide dihydrochloride519.51398+(LC/MS)
|
183N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-0 diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-issobutyramide dihydrochloride521.52998+(LC/MS)
|
1843-methyl-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-butyramide dihydrochloride535.55698+(LC/MS)
|
1852-chloro-NM-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-benzamide dihydrochloride589.99298+(LC/M S)
|
186Pyridin-2-carboxylic acid [3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- amide trihydrochloride592.99598+(LC/MS)
|
1873-methoxy-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-benzamide dihydrochloride585.57298+(LC/MS)
|
188N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-nicotinamide trihydrochloride592.99598+(LC/MS)
|
189N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-isonicotinamide trihydrochloride592.99598+(LC/MS)
|
1903,4-dichloro-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-benzamide dihydrochloride624.43798+(LC/MS)
|
1913,4-dimethoxy-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-benzamide dihydrochloride615.59898+(LC/MS)
|
1922-(2-chlorophenyl)-N-[3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- acetamide dihydrochloride604.01898+(LC/MS)
|
1932-(2-methoxyphenyl)-N-[3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- acetamide dihydrochloride599.59998+(LC/MS)
|
194N-[3-(1-oxo-2-pyridin-3-ylmethyl)-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-benzamide dihydrochloride555.54698+(LC/MS)
|
1952-(3-chloro-phenyl)-N-[3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- acetamide dihydrochloride604.01898+(LC/MS)
|
1962-(3-methoxyphenyl)-N-[3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- acetamide dihydrochloride599.59993.3% (LC/MS)
|
1972-(4-methoxyphenyl)-N-[3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- acetamide dihydrochloride599.59998+(LC/MS)
|
198N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[45]dec-8-yl)-1-phenyl- propyl]-2-phenyl-acetamide dihydrochloride569.57393.3% (LC/MS)
|
1992-(3,4-dichloro-phenyl)-N-[3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- acetamide dihydrochloride638.46391.5% (LC/MS)
|
200Cyclopentanecarboxylic acid [3-(1-oxo- 2-pyrridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- amide dihydrochloride547.56798+(LC/MS)
|
201{1-(3-chlorophenyl)-3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- carbamic acid tert-butyl ester590.181>95% (1H NMR)
|
202Cyclobutanecarboxylic acid [3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- amide dihydrochloride533.5495+(LC/MS)
|
203Cycloheptanecarboxylic acid [3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl}- amide dihydrochloride575.62194.5% (LC/MS)
|
2042-cyclohexyl-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-acetamide dihydrochloride575.62193.4% (LC/MS)
|
2052-cyclopentyl-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-acetamide dihydrochloride561.59494.6% (LC/MS)
|
206Furan-2-carboxylic acid [3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- amide dihydrochloride545.50898+(LC/MS)
|
2072-ethyl-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-butyramide dihydrochloride549.58393.9% (LC/MS)
|
208Thiophene-2-carboxylic acid [3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-phenyl- propyl]-amide dihydrochloride561.57598+(LC/MS)
|
2092-(3,4-dimethoxyphenyl)-N-[3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- acetamide dihydrochloride629.62598+(LC/MS)
|
210Cyclohexanecarboxylic acid [3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spiro[44.5]dec-8-yl)-1-phenyl-propyl]- amide dihydrochloride561.59498+(LC/MS)
|
2114-methyl-cyclohexanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide dihydrochloride575.62192.1% (LC/MS)
|
212[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(3- methoxyphenyl)-propyl]-carbamic acid tert-butyl ester586.567>99% (LC/MS)
|
213[3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3- methoxyphenyl)-propyl]-carbamic acid tert-butyl ester537.697>99% (LC/MS)
|
214(S)-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride534.92398+(LC/MS)
|
215(S)-cyclopropanecarboxylic acid {3-[2- (4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride560.96198+(LC/MS)
|
216(S)-N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-isobutyramide hydrochloride562.87698+(LC/MS)
|
217(S)-N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-methyl-butyramide hydrochloride577.00398+(LC/MS)
|
218(S)-cyclopentanecarboxylic acid {3-[2- (4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride589.01498+(LC/MS)
|
219(S)-cyclobutanecarboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride574.98798+(LC/MS)
|
220[3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(4- methoxyphenyl)-propyl]carbamic acid tert-butyl ester537.69795% BY HPLC
|
221{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-pyridin-2-yl- propyl}-carbamic acid tert-butyl ester557.52999% BY HPLC
|
222{3-[2-(4-methoxybenzyl)-1-oxxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl- propyl}-carbamic acid tert-butyl ester508.65999% BY HPLC
|
223{1-(3,4-dichlorophenyl)-3-[22-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[44.5]dec-8-yl]-propyl}- carbamic acid tert-butyl ester624.626>95% (1H NMR)
|
2242-cyclopropyl-N-{3-[2-(4- methoxybenzyl)-1-oxxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- acetamide hydrochloride526.11798+(LC/MS)
|
2252-cyclopropyl-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride574.18294.4% (LC/MS)
|
226[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(4- methoxyphenyl)-propyl]-carbamic acid tert-butyl ester586.56795% BY HPLC
|
227N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-cyclopropyl-acetamide hydrochloride574.98798+(LC/MS)
|
228[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spirro[4.5]dec-8-yl]-1-(3,4- dimethoxyphenyl)-propyl]-carbamic acid tert-butyl ester616.59399% BY HPLC
|
229{1-(3,4-dimethoxyphenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester567.72297% BY HPLC
|
230Tetrahydro-pyran-4-carboxylic acid {3- [2-(4-methanesulfonylbenzyl)-1-oxo- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride604.208>95% (HPLC)
|
231[3-[2-(4-methanesulfonylbenzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(3- methoxy-phenyl)-propyl]-carbamic acid tertbutyl ester585.762>99% (HPLC)
|
232(S)-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-carbamic acid tert-butyl ester555.736>99% (HPLC)
|
233{3-0[2-(4-methanesulfonylbenzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin- 2-yl-propyl}-carbamic acid tert-butyl ester556.72495% BY HPLC
|
234{1-(3,4-dimethoxyphenyl)-3-[2-(4- meethanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- carbamic acid tert-butyl ester615.78797% BY HPLC
|
235{1-(4-chlorophenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester542.116>90% (HNMR)
|
236{1-(2-chlorophenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester542.116>90% (HNMR)
|
237{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-carbamic acid tert-butyl ester513.699>90% (HNMR)
|
238[3-[2-(4-methanesulfonylbenzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(4- methoxyphenyl)-propyl]-carbamic acid tert-butyl ester585.76295% BY HPLC
|
239[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(4-chlorophenyl)- propyl]-carbamic acid tert-butyl ester590.986>90% (HNMR)
|
240[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-chlorophenyl)- propyl]-carbamic acid tert-butyl ester590,986>90% (HNMR)
|
241{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-carbamic acid tert-butyl ester562.569>90% (HNMR)
|
242{1-(4-chlorophenyl)-3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- carbamic acid tert-butyl ester590.181>90% (HNMR)
|
243{1-(2-chlorophenyl)-3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- carbamic acid tert-butyl ester590.181>90% (HNMR)
|
244{3-[2-(4-methanesulfonylbenzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-carbamic acid tert-butyl ester561.764>90% (HNMR)
|
245(S)-N-{3-[2-(4-0methanesulfonylbenzyl)- 1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-isobutyramide525.7198+(LC/MS)
|
246[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2- methoxyphenyl)-propyl]-carbamic acid tert-butyl ester586.56789% BY HPLC
|
247[3-[2-(4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-carbamic acid tert-butyl ester537.69786% BY HPLC
|
248[1-(2-chlorophenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-propyl]-carbamic acid tert-butyl ester513.078>90% (HNMR)
|
249[1-(3-chlorophenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-propyl]-carbamic acid tert-butyl ester513.078>90% (HNMR)
|
250[1-(3,4-dichlorophenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-preopyl]-carbamic acid tert-butyl ester547.523>90% (HNMR)
|
251[3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-thiophen-2- yl-propyl]-carbamic acid tert-butyl ester484.661>90% (HNMR)
|
252(S)-8-[3-(cyclopropanecarbonyl-amino)- 3-phenyl-propyl]-2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]decane hydrochloride560.15598+(LC/MS)
|
253(S)-8-[3-(cyclopentanecarbonyl-amino)- 3-phenyl-propyl]-2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]decane hydrochloride588.20998+(LOC/MS)
|
254(S)-8-[3-(cyclohexanecarbonyl-amino)- 3-phenyl-propyl]-2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]decane hydrochloride602.23698+(LC/MS)
|
255(S)-8-[3-(cyclopropanecarbonyl-amino)- 3-phenyl-propyl]-2-(4-methoxybenzyl)- 1-oixo-2,8-diaza-spiro[4.5]decane hydrochloride512.0998+(LC/MS)
|
256(S)-8-3-isobutyrylamino-3-phenyl- propyl)-2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]decane hydrochloride514.01698+(LC/MS)
|
257(S)-8-[3-(cyclopentanecarbonyl-amino)- 3-phenyl-propyl]-2-(4-methoxybenzyl)- 1-oxo-2,8-diaza-spiro[4.5]decane hydrochloride540.14498+(LC/MS)
|
258(S)-8-[3-(cyclohexanecarbonyl-amino)- 3-phenyl-propyl]-2-(4-methoxybeenzyl)- 1-oxxo-2,8-diaza-spiro[4.5]decane hydrochloride554.17198+(LC/MS)
|
259N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-isobutyramide hydrochloride569.00598+(LC/MS)
|
260Cyclobutanecarboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-amide hydrochloride581.01698+(LC/MS)
|
261Cyclopentanecarboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-amide hydrochloride595.04298+(LC/MS)
|
262N-{3-[2-(4-bromo-enzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-propionamide hydrochloride554.97898+(LC/MS)
|
263N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-sspiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-2-methoxy-acetamide hydrochloride570.97798+(LC/MS)
|
264Cyclohexanecarboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-amide hydrochloride609.06998+(LC/MS)
|
265Cyclopropanecarboxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-amide hydrochloride518.11898+(LC/MS)
|
266N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-issobutyramide hydrochloride520.13498+(LC/MS)
|
267[3-[2-(4-methasnesulfonylbenzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxyphenyl)-propyl]-carbamic acid tert-butyl ester585.76289% BY HPLC
|
268Cyclobutanecarboxylic acid {3-0[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-amide hydrochloride532.14598+(LC/MS)
|
269Cyclopentanecarboxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-amide hydrochloride546.17298°(LC/MS)
|
270N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- sdiaza-spiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-propionamide hydrochloride506.10798+(LC/MS)
|
2712-methoxy-N -{3-[2-(4-methoxybenzyl)- 1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-acetamide hydrochloride522.10698+(LC/MS)
|
272Cyclohexanecarboxylicc acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-amide hydrochloride560.19998+(LC/MS)
|
273Cyclopropane carboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-amide hydrochloride566.18398+(LC/MS)
|
274N-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-isobutyramide hydrochloride568.19998+(LC/MS)
|
275Cyclobutanecarboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-amide hydrochloride580.2195.2% (LC/MS)
|
276Cyclopentanecarboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-amide hydrochloride594.23798+(LC/MS)
|
277N-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5υdec-8-yl]-1- thiophen-2-yl-propyl}-propionamide hydrochloride554.17298+(LC/MS)
|
278N-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-2-methoxy- acetamide hydrochloride570.17198+(LC/MS)
|
279Cyclohexanecarboxylic acid {3-[22-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-amide hydrochloride608.62498+(LC/MS)
|
280Cyclohexanecarboxylic acid [3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-thiophen-2-yl- propyl]-amide dihydrochloride525.54298+(LC/MS)
|
281N-[3-(1-oxxo-22-pyridin-3-ylmethyl-22,8- diaza-spiro[4.5]dec-8-yl)-1-thiophen-2- yl-propyl]-isobutyramide dihydrochloride527.55798+(LC/MS)
|
282Cyclobutanecarboxylic acid [3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-thiophen-2-yl- propyl]-amide dihydrochloride539.56898+(LC/MS)
|
283Cyclopentanecarboxylic acid [3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spirro[4.5]dec-8-yl)-1-thiophen-2-yl- propyl]-amide dihydrochloride553.59598+(LC/MS)
|
284N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-thiophen-2- yl-propyl]propionamide dihydrochloride513.53180.8% (LC/MS)
|
285Cyclohexanecarboxylic acid [3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-thiophen-2-yl- propyl]-amide dihydrochloride567.62294.3% (LC/MS)
|
286Cyclopropanecarboxylic acid [3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)- propyl]-amide hydrochloride595.40698+(LC/MS)
|
287N-[3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3- chlorophenyl)-propyl]-isobutyramide hydrochloride597.42198+(LC/MS)
|
288Cyclobutanecarboxylic acid [3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)- propyl]-amide hydrochloride609.43298+(LC/MS)
|
289Cyclopentanecarboxylic acid [3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)- propyl]-amide hydrochloride623.45998+(LC/MS)
|
290N-[3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3- chlorophenyl)-propyl]-propionamide hydrochloride583.39598+(LC/MS)
|
291N-[3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3- chlorophenyl)-propyl]-2-methoxy- acetamide hydrochloride599.39498+(LC/MS)
|
Table 3a of compounds illustrates some additional compounds of the present invention that were synthesized using the procedure described in scheme 4.
TABLE 3a
|
|
CPD #MOL STRUCTURECOMPOUND NAMEMOL WTPURITY
|
|
|
2922-Cyclopropyl-N-{(S)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-acetamide hydrochloride574.18299% (LC/MS)
|
2932-Cyclopropyl-N-{(S)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride526.11799% (LC/MS)
|
294Cyclopentanecarboxylic acid [(S)- 3-(2-benzy-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide hydrochloride510.11898+ (LC/MS)
|
295Cyclopropanecarboxylic acid [(S)- 3-(2-benzyl-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide hydrochloride482.06491.6% (LC/MS)
|
296Cyclohexancarboxylic acid [3-(2- (4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(3- chlorophenyl)-propyl]-amide hydroxhloride637.48698% (LC/MS)
|
297Cyclopropanecarboxylic acid {1-(3- chloro-phenyl)-3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride546.53598% (LC/MS)
|
298N-{1-(3-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}- isobutyramide hydrochloride548.55198% (LC/MS)
|
299Cyclobutanecarboxylic acid {1-(3- chlorophenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}-amide hydrochloride560.56298% (LC/MS)
|
300Cyclopentanecarboxylic acid {1-(3- chlorophenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,87-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride574.58998% (LC/MS)
|
301N-{1-(3-Chlorophenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}- propionamide hydropchloride543.52495% (LC/MS)
|
302N-{1-(3-Chlorophenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diazaq- spiro[4.5]dec-8-yl]-propyl}-2- methoxy-acetamide hydrochloride550.52398% (LC/MS)
|
303Cyclohexanecarboxylic acid {1-(3- chlorophenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}-amide hydrochloride588.61698% (LC/MS)
|
304Cyclopropylcarboxylic acid {1-(3- chlorophenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride594.698% (LC/MS)
|
305N-{1-(3-Chlorophenyl)-3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- isobutyramide hydrochloride596.61698% (LC/MS)
|
306Cyclobutanecarboxylic acid {1-(3- chlorophenyl)-3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- amide hydrochloride608.62798% (LC/MS)
|
307Cyclopentanecarboxylic acid {1-(3- chlorophenyl)-3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]propyl}- amide hydrochloride622.65498% (LC/MS)
|
308N-{1-(3-Chlorophenyl)-3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- propionamide hydrochloride582.58998% (LC/MS)
|
309N-{1-(3-Chlorophenyl)-3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}-2- methoxy-acetamide hydrochloride598.58895% (LC/MS)
|
310Cyclopropanecarboxylic acid [1-(3- chlorophenyl)-3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-propyl]-amide dihydrochloride553.95893.2% (LC/MS)
|
311N-[1-(3-Chlorophenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- isobutyramide dihydrochloride555.97494.1% (LC/MS)
|
312Cyclobutanecarboxylic acid [1-(3- chlorophenyl)-3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-propyl]-amide dihydrochloride567.98598% (LC/MS)
|
313Cyclopentanecarboxylic acid [1-(3- chloro-phenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec- 8-yl)-propyl]-amide dihydrochloride582.01298% (LC/MS)
|
314N-[1-(3-Chlorophenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- propionamide dihydrochloride541.94893.8% (LC/MS)
|
315N-[1-(3-Chlorophenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]-2- methoxy-acetamide dihydrochloride557.94694.4% (LC/MS)
|
316Cyclohexanecarboxylic acid [1-(3- chlorophenyl)-3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-propyl]-amide dihydrochloride596.03994.7% (LC/MS)
|
317Cyclopropanecarboxylic acid [(S)- 3-(1-oxo-2-pyridin-2-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide dihydrochloricde519.51398% (LC/MS)
|
318Cyclopentanecarboxylic acid [(S)- 3-(1-oxo-2-pyridin-2-ylmethyl-2,8- diaza-spiro[45]dec-8-yl)-1-phenyl- propyl]-amide dihydrochloride547.56798% (LC/MS)
|
319Cyclopropanecarboxylic acid [(S)- 3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide dihydrochloride519.51398% (LC/MS)
|
320Cyclopentanecarboxylic acid [(S)- 3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide dihydrochloride547.56798% (LC/MS)
|
321Cyclopropanecarboxylic acid [(S)- 3-(1-oxo-2-pyridin-4-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide dihydrochloride519.51398% (LC/MS)
|
322Cyclopropanecarboxylic acid [(S)- 3-(1-oxo-2-pyridin-4-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide dihydrochloride547.56798% (LC/MS)
|
323Cyclopropanecarboxylic acid {(S)- 3-[1-oxo-2-(1-oxy-pyridin-2- ylmethyl)-2,8-diaza-spiro[4.5]dec- 8-yl]-1-phenyl-propyl}-amide hydrochloride499.05298% (LC/MS)
|
324Cyclopentanecarboxylic acid {(S)- 3-[1-oxo-2-(1-oxy-pyridin-2- ylmethyl)-2,8-diaza-spiro[4.5]dec- 8-yl]-1-phenyl-propyl}-amide hydrochloride527.10598% (LC/MS)
|
325Cyclopropanecarboxylic acid {(S)- 3-[1-oxo-2-(1-oxy-pyridin-3- ylmethyl)-2,8-diaza-spiro[4.5]dec- 8-yl]-1-phenyl-propyl}-amide hydrochloride499.05298% (LC/MS)
|
326Cyclopentanecarboxylic acid {(S)- 3-[1-oxo-2-(1-oxy-pyridin-3- ylmethyl)-2,8-diaza-spiro[4.5]dec- 8-yl]-1-phenyl-propyl}-amide hydrochloride527.10598% (LC/MS)
|
327Cyclopropanecarboxylic acid {(S)- 3-[1-oxo-2-(1-oxy-pyridin-4- ylmethyl)-2,8-diaza-spiro[4.5]dec- 8-yl]-1-phenyl-propyl}-amide hydrochloride499.05298% (LC/MS)
|
328Cyclopentanecarboxylic acid {(S)- 3-[1-oxo-2-(1-oxy-pyridin-4- ylmethyl)-2,8-diaza-spiro[4.5]dec- 8-yl]-1-phenyl-propyl}-amide hydrochloride527.10598% (LC/MS)
|
329Cyclopentanecarboxylic acid {3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-pyridin-2-yl- propyl}-amide dihydrochloride626.46398% (LC/MS)
|
330N-{3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- pyridin-2-yl-propyl}-propionamide dihydrochloride586.39898% (LC/MS)
|
331N-{3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- pyridin-2-yl-propyl}-2-methoxy- acetamide dihydrochloride602.39898% (LC/MS)
|
332Cyclopropanecarboxylic acid {3-[2- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-pyridin- 2-yl-propyl}-amide dihydrochloride549.53998% (LC/MS)
|
333N-{3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- pyridin-2-yl-propyl}-isobutyramide dihydrochloride551.55598% (LC/MS)
|
334Cyclobutanecarboxylic acid {3-[2- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-pyridin- 2-yl-propyl}-amide dihydrochloride563.56698% (LC/MS)
|
335Cyclopentanecarboxylic acid {3-[2- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-pyridin- 2-yl-propyl}-amide dihydrochloride563.56698% (LC/MS)
|
336N-{3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- pyridin-2-yl-propyl}-propionamide dihydrochloride537.52898% (LC/MS)
|
3372-Methoxy-N-{3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-pyridin-2-yl- propyl}-acetamide dihydrochloride553.52798% (LC/MS)
|
338Cyclopropanecarboxylic acid {3-[2- (4-methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- pyridin-2-yl-propyl}-amide dihydrochloride597.60498% (LC/MS)
|
339N-{3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-pyridin-2-yl- propyl}-isobutylamide dihydrochloride599.6298% (LC/MS)
|
340Cyclobutanecarboxylic acid {3-[2- (4-methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- pyridin-2-yl-propyl}-amide dihydrochloride611.63198% (LC/MS)
|
341Cyclopropanecarboxylic acid {3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-pyridin-2-yl- propyl}-amide dihydrochloride598.40998% (LC/MS)
|
342N-{3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- pyridin-2-yl-propyl}-isobutyramide dihydrochloride600.42598% (LC/MS)
|
343Cyclobutanecarboxylic acid {3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-pyridin-02-yl- propyl}-amide dihydrochloride612.43698% (LC/MS)
|
344Cyclopentanecarboxylic acid {3-[2- (4-methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl-]-1- pyridin-2-yl-propyl}-amide dihydrochloride625.65898% (LC/MS)
|
345N-{3-[2-(4-Methanesulfonyl- benzyl}-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-pyridin-2-yl- propyl}-propionamide dihydrochloride585.59395.2% (LC/MS)
|
346N-{(S)-3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-nicotinamide560.71591% (HPLC)
|
347(R)-Tetrahydro-furan-2-carboxylic acid {(S)-3-[2-(4-meethanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide553.7299% (HPLC)
|
348(S)-Tetrahydro-furan-2-carboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide553.7299% (HPLC)
|
349Tetrahydro-furan-3-carboxylic acid {(S)-3-[2-(4-methansulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide553.7299% (HPLC)
|
350(R)-N-{(S)-3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-phenyl-propionamide587.78184% (HPLC)
|
3513-Oxo-cyclopentanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide565.73184% (HPLC)
|
352(S)-N-{(S)-3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-phenyl-propionamide587.78186% (HPLC)
|
353(R)-N-[(S)-3-(1-Oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-2-phenyl- propionamide510.67897% (HPLC)
|
354(S)-N-[(S)-3-(1-Oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-2-phenyl- propionamide510.67899% (HPLC)
|
355(R)-Tetrahydro-furan-2-carboxylic acid [(S)-3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl-1-phe3nyl-propyl]-amide476.61797% (HPLC)
|
356(S)-Tetrahydro-furan-2-carboxylic acid [(S)-3-(1-oxo-22-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-amide476.61799% (HPLC)
|
357Tetrahydro-furan-3-carboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl- 2,8-diaza-spiro[4.5]dec-8-yl)-1- phenyl-propyl]-amide476.61798% (HPLC)
|
3583-Oxo-cyclopentaecarboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl- 2,8-diaza-spiro[4.5]dec-8-yl)-1- phenyl-propyl]-amide488.62896% (HPLC)
|
359N-[(S)-3-(2-Oxo-2-pyridin-2- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-isobutylamide448.60797% (HPLC)
|
360N-[(S)-3-(1-Oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-isobutylamide448.60799% (HPLC)
|
361N-[(S)-3-(1-Oxo-2-pyridin-4- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-isobutyramide448.60798% (HPLC)
|
362N-{(S)-3-[1-Oxo-2-(1-oxy-pyridin-4- ylmethyl)-2,8-diaza-spiro[4.5]dec- 8-yl]-1-phenyl-propyl}- isobutyramide464.60690% (HPLC)
|
363N-{(S)-3-[1-Oxo-2-(1-oxy-pyridin-2- ylmethyl)-2,8-diaza-spiro[4.5]dec- 8-yl]-1-phenyl-propyl}- isobutyramide464.60698% (HPLC)
|
364N-{(S)-3-[1-Oxo-2-(1-oxy-pyridin-3- ylmethyl)-2,8-diaza-spiro[4.5]dec- 8-yl]-1-phenyl-propyl}- isobutyramide464.60699% (HPLC)
|
3651-Methyl-cyclopentanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide565.775100% (LC/MS)
|
3661-Methyl-cyclohexanecarboxylic acid{(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide579.802>80% (LC/MS)
|
3672-Cyclopentyl-N-{(S)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-propionamide579.802100% (LC/MS)
|
3682-Cyclopentyl-N-{(S)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-propionamide579.802100% (LC/MS)
|
3691-Methyl-cyclopentanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-amide488.672100% (LC/MS)
|
3701-Methyl-cyclohexanecarboxylic acid[(S)-3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-amide502.699100% (LC/MS)
|
3712-Cyclopentyl-N-[(S)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl- propyl]-propionamide502.699100% (LC/MS)
|
3722-Cyclopentyl-N-[(S)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl- propyl]-propionamide502.699100% (LC/MS)
|
373Cyclopropanecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-amide hydrochloride590.98698% (LC/MS)
|
374N-[3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]- isobutyramide hydrochloride593.00298% (LC/MS)
|
375Cyclobutanecarboxylic acid [3[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-amide hydrochloride605.01398% (LC/MS)
|
376Tetrahydro-pyran-2-carboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide567.74799% (HPLC)
|
377N-{3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-2,2-dimethyl- propionamide hydrochloride534.16198% (LC/MS)
|
378N-{3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-2,2-dimethyl-propionamide hydrochloride582.22698% (LC/MS)
|
379N-{1-(3-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-2,2- dimethyl-propionamide hydrochloride562.57893.9% (LC/MS)
|
380N-{1-(3-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-2,2-dimethyl-propionamide hydrochloride610.64398% (LC/MS)
|
381N-[1-(3-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]-2,2- dimethyl-propionamide dihydrochloride570.00198% (LC/MS)
|
382N-{1-(2-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-2,2-dimethyl-propionamide hydrochloride610.64398% (LC/MS)
|
383N-{1-(4-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-2,2-dimethyl-propionamide hydrochloride610.64398% (LC/MS)
|
384`1-Methyl-cyclopropanecarboxylic acid {3-[2-(4-methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-amide hydrochloride532.14598% (LC/MS)
|
3851-Methyl-cyclopropanecarboxylic acid {3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-amide hydrochloride580.2198% (LC/MS)
|
3861-Methyl-cyclopropanecarboxylic acid [3-(1-oxo-2-pyridin-33-ylmethyl- 2,8-diaza-spiro[4.5]dec-8-yl)-1- thiophen-2-yl-propyl]-amide dihydrochloride539.56898% (LC/MS)
|
3871-Methyl-cyclopropanecarboxylic acid {1-(3-chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}-amide hydrochloride560.56292.4% (LC/MS)
|
3881-Methyl-cyclopropanecarboxylic acid {1-(3-chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride608.62798% (LC/MS)
|
3891-Methyl-cyclopropanecarboxylic acid [1-(3-chloro-phenyl)-3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride567.98592.5% (LC/MS)
|
3901-Methyl-cyclopropanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride608.62798% (LC/MS)
|
3911-Methyl-cyclopropanecarboxylic acid {1-(4-chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride608.62798% (LC/MS)
|
392Tetrahydro-pyran-2-carboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl- 2,8-diaza-spiro[4.5]dec-8-yl)-1- phenyl-propyl]-amide490.64494% (HPLC)
|
393Cyclopentaecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-amide hydrochloride619.0498% (LC/MS)
|
394N-[3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]- propionamide hydrochloride578.97598% (LC/MS)
|
395N-[3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)propyl]-2- methoxy-acetamide hydrochloride594.97498% (LC/MS)
|
396N-[3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-2- cyclopropyl-acetamide hydrochloride605.01398% (LC/MS)
|
397Cyclohexanecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-amide hydrochloride633.06798% (LC/MS)
|
398Cyclopropanecarboxylic acid [3-[2- (4-methoxy-benzyl)-1-oxo-2,8 diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-amide hydrochloride542.11698% (LC/MS)
|
399N-[3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-tl]-1-(2- methoxy-phenyl)-propyl]- issobutyramide hydrochloride544.13298% (LC/MS)
|
400Cyclobutanecarboxylic acid [3-[2- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-amide hydrochloride556.14398% (LC/MS)
|
401Cyclopentanecarboxylic acid [3-[2- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-amide hydrochloride570.1798% (LC/MS)
|
402N-[3-[2-(4-Methoxy-beenzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]- propionamide hydrochloride530.10598% (LC/MS)
|
4032-Methoxy-N-[3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-acetamide hydrochloride546.10498% (LC/MS)
|
4042-Cyclopropyl-N-[3[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-acetamide hydrochloride556.14398% (LC/MS)
|
405Cyclohexanecarboxylic acid [3-[2- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)propyl]-amide hydrochloride584.19698% (LC/MS)
|
406Cyclopropanecarboxylic acid [3-[2- (4-methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-amide hydrochloride590.18198% (LC/MS)
|
407N-[3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-isobnutyramide hydrochloride592.19798% (LC/MS)
|
408Cyclobutanecarboxylic acid [3-[2- (4-methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- meethoxy-phenyl)-propyl]-amide hydrochloride604.20898% (LC/MS)
|
409Cyclopentanecarboxylic acid [3-[2- (4-methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-amide hydrochloride618.23598% (LC/MS)
|
410N-[3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-propionamide hydrochloride578.1798% (LC/MS)
|
411N-[3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-2-methoxy- acetamide hydrochloride594.16998% (LC/MS)
|
4122-Cyclopropyl-N-[3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-acetamide hydrochloride604.20898% (LC/MS)
|
413Cyclopropanecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(4-methoxy- phenyl)-propyl]-amide hydrochloride590.98698% (LC/MS)
|
414N-[3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]- isobutyramide hydrochloride593.00298% (LC/MS)
|
415Cyclobutanecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(4-methoxy- phenyl)-propyl]-amide hydrochloride605.01398% (LC/MS)
|
416Cyclopentanecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(4-methoxy- phenyl)-propyl]-amide hydrochloride619.0498% (LC/MS)
|
417N-[3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]- propionamide hydrochloride578.97598% (LC/MS)
|
418N-[3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]-2- methoxy-acetamide hydrochloride594.97498% (LC/MS)
|
419Cyclopropanecarboxylic acid [3-[2- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]-amide hydrochloride542.11698% (LC/MS)
|
420N-[3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]- isobutyramide hydrochloride544.13298% (LC/MS)
|
421Cyclobutanecarboxylic acid [3-[3- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]-amide hydrochloride556.14398% (LC/MS)
|
422Cyclopentanecarboxylic acid [3-[2- (4-methoxy-benzyl)-1-oxxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]-amide hydrochloride570.1798% (LC/MS)
|
423N-[3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]- propionamide hydrochloride530.10598% (LC/MS)
|
424Cyclohexanecarboxylic acid [3-[2- (4-methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-amide hydrochloride632.26198% (LC/MS)
|
425Cyclopentanecarboxylic acid [1-(3- methoxy-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride577.59398% (LC/MS)
|
426N-[1-(3-Methoxy-phenyl)-3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- propionamide dihydrochloride537.52898% (LC/MS)
|
4272-Methoxy-NM-[1-(3-methoxy- phenyl)-3-(1-oxo-2-pyridin-3- ylmeethyl-2,8-diaza-spiro[4.5]dec-8- yl)-propyl]-acetamide dihydrochloride553.52798% (LC/MS)
|
4283-Hydroxy-cyclopentanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide567.74790% (HPLC)
|
4293-Hydroxy-cyclopentanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-amide490.64497% (HPLC)
|
430Cyclopropanecarboxylic acid {1-(2- chloro-phenyl)-3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride546.53598% (LC/MS)
|
431N-{1-(2-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}- isobutyramide hydrochloride548.55198% (LC/MS)
|
432Cyclobutanecarboxylic acid {1-(2- chloro-phenyl)-3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}-amide hydrochloride560.56298% (LC/MS)
|
433Cyclopentanecarboxylic acid {1-(2- chloro-phenyl)-3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}-amide hydrochloride574.58998% (LC/MS)
|
434N-{1-(2-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}- propionamide hydrochloride534.52498% (LC/MS)
|
435N-{1-(2-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}-2- methoxy-acetamide hydrochloride550.52398% (LC/MS)
|
436Cyclohexanecarboxylic acid {1-(2- chloro-phenyl)-3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride588.61698% (LC/MS)
|
437Cyclopropanecarboxylic acid {1-(2- chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride594.698% (LC/MS)
|
438N-{1-(2-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-isobutyramide hydrochloride596.61698% (LC/MS)
|
439Cyclobutanecarboxylic acid {1-(2- chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride608.62798% (LC/MS)
|
440Cyclopentanecarboxylic acid {1-(2- chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride622.65498% (LC/MS)
|
441N-{1-(2-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-propionamide hydrochloride582.58998% (LC/MS)
|
442N-{1-(2-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-2-methoxy-acetamide hydrochloride598.58898% (LC/MS)
|
443Cyclohexanecarboxylic acid {1-(2- chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride636.68198% (LC/MS)
|
444Cyclopropanecarboxylic acid [1-(2- chloro-phenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec- 8-yl)-propyl]-amide hydrochloride553.95898% (LC/MS)
|
445N-[1-(2-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- isobutyramide dihydrochloride555.97498% (LC/MS)
|
446Cyclobutanecarboxylic acid [1-(2- chloro-phenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec- 8-yl)-propyl]-amide dihydrochloride567.98598% (LC/MS)
|
447Cyclopentanecarboxylic acid [1-(2- chloro-phenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec- 8-yl)-propyl]-amide dihydrochloride582.01298% (LC/MS)
|
448N-[1-(2-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- propionamide dihydrochloride541.94898% (LC/MS)
|
449N-[1-(2-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]-2- methoxy-acetamide dihydrochloride557.94693.6% (LC/MS)
|
450Cyclohexanecarboxylic acid [1-(2- chloro-phenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec- 8-yl)-propyl]-amide dihydrochloride596.03998+ (LC/MS)
|
451Cyclopropanecarboxylic acid {1-(4- chloro-phenyl)-3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride546.53598% (LC/MS)
|
452N-{1-(4-Chloro-phenyl)-3-[2-(4- meethoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}- isobutyramide hydrochloride548.55198% (LC/MS)
|
453Cyclobutanecarboxylic acid {1-(4- chloro-phenyl)-3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride560.56298% (LC/MS)
|
454Cyclopentanecarboxylic acid {1-(4- chloro-phenyl)-3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride574.58998% (LC/MS)
|
455N-{1-(4-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}- propionamide hydrochloride534.52498% (LC/MS)
|
456N-{1-(4-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-2- methoxy-acetamide hydrochloride550.52398% (LC/MS)
|
457Cyclohexanecarboxylic acid {1-(4- chloro-phenyl)-3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride588.61698% (LC/MS)
|
458N-{1-(4-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-propionamide hydrochloride592.58998% (LC/MS)
|
459N-{1-(4-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-0spiro[4.5]dec-8-yl]- propyl}-2-methoxy-acetamide hydrochloride598.58898% (LC/MS)
|
460Cyclohexanecarboxylic acid {1-(4- chloro-phenyl)-3-[2-(4- meethanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride636.68198% (LC/MS)
|
461Cyclopropanecarboxylic acid [1-(4- chloro-phenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec- 8-yl)-propyl]-amide dihydrochloride553.95898% (LC/MS)
|
462N-[1-(4-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl- isobutyramide dihydrochloride555.97498% (LC/MS)
|
463Cyclobutanecarboxylic acid [1-(4- chloro-phenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec- 8-yl)-propyl]-amide dihydrochloride567.98598% (LC/MS)
|
464Cyclopentanecarboxylic acid [1-(4- chloro-phenyl)-3-(1-oxo-2-pyridin- 3-ylmeethyl-2,8-diaza-spiro[4.5]dec- 8-yl)-propyl]-amide dihydrochloride582.01295% (LC/MS)
|
465N-[1-(4-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- propionamide dihydrochloride541.94893.5% (LC/MS)
|
466N-[1-(4-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]-2- methoxy-acetamide dihydrochloride557.94698% (LC/MS)
|
467Cyclohexanecarboxylic acid [1-(4- chloro-phenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec- 8-yl)-propyl]-amide dihydrochloride596.03994.4% (LC/MS)
|
468Cyclopropanecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-chloro- phenyl)-propyl]-amide hydrochloride595.40698% (LC/MS)
|
469Cyclopropanecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(4-chloro- phenyl)-propyl]-amide hydrochloride595.40698% (LC/MS)
|
470Cyclopropanecarboxylic acid {1- (3,4-dichloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride580.9898% (LC/MS)
|
471Cyclopropanecarboxylic acid {1- (3,4-dichloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride629.04598% (LC/MS)
|
472Cyclopropanecarboxylic acid [1- (3,4-dichloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride588.40498% (LC/MS)
|
473Cyclopentanecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-chloro- phenyl)-propyl]-amide hydrochloride623.45998% (LC/MS)
|
474Cyclopentanecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(4-chloro- phenyl)-propyl]-amide hydrochloride623.45998% (LC/MS)
|
475Cyclopentanecarboxylic acid {(S)- 3-[2-(4-fluoro-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride528.10898% (LC/MS)
|
476Cyclopentanecarboxylic acid {(S)- 3[2-(4-chloro-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride544.56398% (LC/MS)
|
477Cyclopentanecarboxylic acid {(S)- 3-[2-(4-cyano-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride535.12898% (LC/MS)
|
478Cyclopentanecarboxylic acid {(S)- 3-[2-(4-difluoromethoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride576.12498% (LC/MS)
|
479Cyclopentanecarboxylic acid {(S)- 3-[1-oxo-2-(4-trifluoromethoxy- benzyl)-2,8-diaza-spiro[4.5]dec-8- yl]-1-phenyl-propyl}-amide hydrochloride594.11498% (LC/MS)
|
480Cyclopentanecarboxylic acid {(S)- 3-[2-(4-methylsulfanyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride556.21198% (LC/MS)
|
481Cyclopentanecarboxylic acid {(S)- 3-[1-oxo-2-(4-pyrazol-1-yl-benzyl)- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride576.18198% (LC/MS)
|
482Cyclopentanecarboxylic acid [(S)- 3-(2-isobutyl-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide hydrochloride476.10195% (LC/MS)
|
483Cyclopentanecarboxylic acid {(S)- 3-[2-(4-meethanesulfonyl-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride588.20998% (LC/MS)
|
484Cyclopropanecarboxylic acid {(S)- 3-[2-(4-methoxy-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride540.11498% (LC/MS)
|
485Cyclopropanecarboxylic acid {(S)- 3-[2-(4-fluoro-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride500.05598% (LC/MS)
|
486Cyclopropanecarboxylic acid {(S)- 3-[2-(4-chloro-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]1-phenyl- propyl}-amide hydrochloride516.5198% (LC/MS)
|
487Cyclopropanecarboxylic acid {(S)- 3-[2-(4-cyano-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride507.07498% (LC/MS)
|
488Cyclopropanecarboxylic acid {(S)- 3-[2-(4-difluoromethoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride548.0798% (LC/MS)
|
489Cyclopropanecarboxylic acid {(S)- 3-[1-oxo-2-(4-pyrazol-1-yl-benzyl)- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride548.12798% (LC/MS)
|
490Cyclopropanecarboxylic acid [(S)- 3-(2-cyclohexylmethyl-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide hydrochloride488.11299% (LC/MS)
|
491Cyclopropanecarboxylic acid [(S)- 3-(2-isobutyl-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide hydrochloride448.04798% (LC/MS)
|
492Cyclopropanecarboxylic acid {(S)- 3-[2-(4-methanesulfonyl-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride560.15598% (LC/MS)
|
493Cyclopropanecarboxylic acid {(S)- 3-[2-(4-methoxy-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride512.0998% (LC/MS)
|
494N-[(S)-3-(2-Benzyl-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-isobutyramide hydrochloride484.0895% (LC/MS)
|
495N-{(S)-3-[2-(4-Fluoro-benzyl)-1- oxo-2,8-diaza-spirro[4.5]dec-8-yl]-1- phenyl-propyl}-isobutyramide hydrochloride502.0790% (LC/MS)
|
496Cyclopropanecarboxylic acid {(S)- 3-[1-oxxo-2-(4-trifluoromethoxy- benzyl)-2,8-diaza-spiro[4.5]dec-8- yl]-1-phenyl-propyl}-amide hydrochloride566.0698% (LC/MS)
|
497Cyclopropanecarboxylic acid {(S)- 3-[2-(4-methylsulfanyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride528.15798% (LC/MS)
|
498N-{(S)-3-[2-(4-Chloro-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-isobutyramide hydrochloride518.52595% (LC/MS)
|
499N-{(S)-3-[2-(4-Cyano-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-isobutyramide hydrochloride509.0998% (LC/MS)
|
500N-{(S)(-3-[2-(4-Difluoromethoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-isobutyramide hydrochloride556.08690% (LC/MS)
|
501N-{(S)-3-[1-Oxo-2-(4- trifluoromethoxy-benzyl)-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-isobutyramide hydrochloride568.07691.3% (LC/MS)
|
502N-{(S)-3-[2-(4-Methylsulfanyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-isobutyramide hydrochloride530.17390% (LC/MS)
|
503N-{(S)-3-[2-(4-Methoxy-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-isobutyramide hydrochloride514.10695% (LC/MS)
|
5042-Methoxy-cyclopent-1- enecarboxylic acid {(S)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide579.75887% (HPLC)
|
5052-Methoxy-cyclopent-1- enecarboxylic acid [(S)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide502.65584% (HPLC)
|
506Cyclopentanecarboxylic acid {1- (3,4-dichloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride609.03498% (LC/MS)
|
507Cyclopentanecarboxylic acid {1- (3,4-dichloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride616.45798% (LC/MS)
|
508Cyclopentanecarboxylic acid [1- (3,4-dichloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride616.45798% (LC/MS)
|
509N-{(S)-3-[2-(4-Methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-propionamide hydrochloride500.09100% (LC/MS)
|
510N-{(S)-3-[2-(4-Methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-2,2-dimethyl- propionamide hydrochloride528.14100% (LC/MS)
|
511Thiophene-2-cxarboxcylic acid {(S)-3- [2-(4-methoxy-benzyl)-1-oxo-2,8- diaza-spirto[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride554.16100% (LC/MS)
|
512Thiophene-3-carboxylic acid {(S)-3- [2-(4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride554.16100% (LC/MS)
|
513(R)-Tetrahydro-furan-2-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)- 1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-amide hydrochloride542.12100% (LC/MS)
|
514(S)-Tetrahydro-furan-2-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)- 1-oxo-2,8-diaza-spirro[4.5]dec-8-yl]- 1-phenyl-propyl}-amide hydrochloride542.12100% (LC/MS)
|
515Tetrahydro-furan-3-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride542.12100% (LC/MS)
|
5163-Oxo-cyclopentanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride554.13100% (LC/MS)
|
5174,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)- 1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-amide hydrochloride590.16100% (LC/MS)
|
518Tetrahydro-pyran-4-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride557.14100% (LC/MS)
|
5194,6-Dimethyl-pyrimidine-5- carboxylic acid {(S)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide trihydrochloride651.08100% (LC/MS)
|
520Adamantane-1-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride606.2590% (LC/MS)
|
521N-{(S)-3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-propionamide hydrochloride548.1596% (LC/MS)
|
522N-{(S)-3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2,2-dimethyl-propionamide hydrochloride576.2100% (LC/MS)
|
523Thiophene-2-carboxylic acid {(S)-3- [2-(4-methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride602.22100% (LC/MS)
|
524Thiophene-3-carboxylic acid {(S)-3- [2-(4-methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride602.22100% (LC/MS)
|
5254,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride638.22100% (LC/MS)
|
526Tetrahydro-pyran-4-carboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride603.82100% (LC/MS)
|
527N-{(S)-3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-nicotinamide dihydrochloride633.64100% (LC/MS)
|
528Pyrimidine-5-carboxylic acid {(S)-3- [2-(4-methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[44.5]dec-8-yl]-1- phenyl-propyl}-amide trihydrochloride671.09100% (LC/MS)
|
5294,6-Dimethyl-pyrimidine-5- carboxylic acid {(S)-3-[2-(4- methanesulfonyl-beenzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide trihydrochloride699.1490% (LC/MS)
|
530Adamantene-1-carboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride654.32100% (LC/MS)
|
531N-{(S)-3-[2-(4-Ethoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-isobutyramide hydrochloride528.14100% (LC/MS)
|
532Cyclopropanecarboxylic acid {(S)- 3-[2-(4-ethoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride526.12100% (LC/MS)
|
5334,4-Difluoro-cyclohexanecarboxylic acod {(S)-3-[2-(4-methoxy-benzyl)- 3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-amide hydrochloride590.16100% (LC/MS)
|
5342-Cyclopropyl-N-{(S)-3-[2-(4- methanesulfonyl-bgenzyl)-3-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-acetamide hydrochloride574.19100% (LC/MS)
|
5354,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-3-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride638.22100% (LC/MS)
|
EXAMPLE 9
N-{3-[2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenylpropyl}-benzenesulfonamide hydrochloride (Compound 536)
To 83 mg (100 μmol, loading of 1.2 mmol/g) of benzenesulfonate activated ester on polymeric 4-hydroxy-2,3,5,6-tetrafluorobenzamido (TFP) resin (see preparation in J. M. Salvino et al. J. Comb. Chem. 2000, 2, 691-697), preswollen with 0.5 mL of anhydrous DMF, was added 27.3 mg (60 μmol) of 8-(3-amino-3-phenylpropyl)-2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one diluted in 1 mL of DMF. The reaction was agitated overnight at room temperature. The mixture was filtered and washed with DCM (2×2 mL) . The filtrates were collected and evaporated in vacuo. The crude was purified by semi-preparative HPLC (method A) yielding 10.6 mg (27.9%) of Compound 536 as a colorless solid.
1H NMR (400 MHz, DMSO-d6): δ[ppm] 9.64 (br s, 1H), 8.44 (d, 1H), 7.53 (m, 4H), 7.44 (t, 1H), 7.35 (m, 2H), 7.12 (m, 7H), 4.33 (m, 3H), 3.35 (m, 2H), 3.16 (t, 3H), 3.05 (m, 1H), 2.9 (m, 2H), 2.08 (m, 1H), 1.95 (m, 4H), 1.82 (m, 1H), 1.56 (br d, 2H).
LC/MS: m/z 598.1 (MH+).
Table 4 of compounds illustrates some of the compounds of the present invention that were synthesized using the procedure described in scheme 5.
TABLE 4
|
|
CPD
#MOL STRUCTURECOMPOUND NAMEMOL WTPURITY
|
|
|
537Propane-2-sulfonic acid {(S)-3-[2-(4- methoy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride550.16100% (LC/MS)
|
538Propane-2-sulfonic acid {(S)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride598.2390% (LC/MS)
|
EXAMPLE 10
1-{3-[2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenylpropyl}-3-phenyl-urea hydrochloride (Compound 542)
To 27.3 mg (60 μmol) of 8-(3-amino-3-phenylpropyl)-2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one, diluted in 1 mL of anhydrous THF, was added 9.66 mg (80 μmol) of phenylisocyanate dissolved in 0.5 mL of anhydrous THF. The reaction mixture was agitated overnight at room temperature and evaporated in vacuo. The crude was purified by semi-preparative HPLC (method C) yielding 18.9 mg (51.5%) of Compound 542 as a pale yellow solid.
1H NMR (400 MHz, DMSO-d6): δ[ppm] 9.45 (br s, 1H), 8.64 (d, 1H), 7.51 (d, 2H), 7.37 (m, 6H), 7.28 (m, 1H), 7.21-7.13 (m, 4H), 6.93 (d, 1H), 6.87 (t×t, 1H), 4.8 (m, 1H), 4.33 (s, 2H), 3.48 (br t, 2H), 3.18-2.94 (m, 5H), 2.15 (m, 2H), 1.96 (m, 4H), 1.83 (m, 1H), 1.6 (br d, 2H).
Table 5 of compounds illustrates some of the compounds of the present invention that were synthesized using the procedure described in scheme 6.
TABLE 5
|
|
CPD
#MOL STRUCTURECOMPOUND NAMEMOL WTPURITY
|
|
|
539Piperidine-1-carboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride604.0393.5% (LC/MS)
|
540Piperidine-1-carboxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride555.1794.5% (LC/MS)
|
541Piperidine-1-carboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride603.22493.3% (LC/MS)
|
5421-{3-[2-(4-bromophenyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-phenyl-urea hydrochloride612.00898+(LC/MS)
|
5431-0{3-[2-(4-bromobhenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(2-chloro-phenyl)-urea hydrochloride646.45394.6% (LC/MS)
|
5441-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(2-methoxy-phenyl)-urea hydrochloride642.03498+(LC/MS)
|
5451-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(3-chloro-phenyl)-urea hydrochloride646.45398+(LC/MS)
|
5461-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(3-methoxy-phenyl)-urea hydrochloride642.03498+(LC/MS)
|
5471-{3-([2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(4-chloro-phenyl)-urea hydrochloride646.45398+(LC/MS)
|
5481-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(4-methoxy-phenyl)-urea hydrochloride642.03498+(LC/MS)
|
5491-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(2,6-dimethyl-phenyl)-urea hydrochloride640.06298+(LC/MS)
|
5501-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-naphtalen-1-yl-urea hydrochloride662.06898+(LC/MS)
|
5511-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-phenyl-urea hydrochloride563.13898+(LC/MS)
|
5521-(2-chlorophenyl)-3-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- urea hydrochloride597.58395+(LC/MS)
|
5531-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(2-methoxyphenyl)-urea hydrochloride593.16498+(LC/MS)
|
5541-(3-chlorophenyl)-3-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- urea hydrochloride597.58398+(LC/MS)
|
5551-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(3-methoxyphenyl)-urea hydrochloride593.16498+(LC/MS)
|
556-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(4-methoxyphenyl)-urea hydrochloride593.16498+(LC/MS)
|
5571-(2,6-dimethylphenyl)-33-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- urea hydrochloride591.19298+(LC/MS)
|
5581-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-naphthalen-1-yl-urea hydrochloride613.19898+(LC/MS)
|
5591-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-3-phenyl-urea hydrochloride611.20398+(LC/MS)
|
5601-(2-chlorophenyl)-3-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-urea hydrochloride645.64898+(LC/MS)
|
5611-{3-[2-(4-methanesulfonylbenzyl)- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-3-(2-methoxyphenyl)- urea hydrochloride641.22998+(LC/MS)
|
5621-(3-chlorophenyl)-3-{3-[2-(4- methanesulfonylbernzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-urea hydrochloride645.64898+(LC/MS)
|
5631-{3-[2-(4-methanesulfonylbeenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-3-(3-methoxyphenyl)- urea hydrochloride641.22998+(LC/MS)
|
5641-(4-chlorophenyl)-3-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-urea hydrochloride645.64898+(LC/MS)
|
5651-‡3-[22-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-3-(4-methoxyphenyl)- urea hydrochloride641.22998+(LC/MS)
|
5661-(2,6-dimethylphenyl)-3-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-urea hydrochloride639.52798+(LC/MS)
|
5671-{3-[2-(4-methanesulfonylnemzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-3-naphthalen-1-yl- urea hydrochloride661.26398+(LC/MS)
|
Table 5a of compounds illustrates some additional compounds of the present invention that were synthesized using the procedure described in scheme 6.
TABLE 5a
|
|
CPDPUR-
#MOL STRUCTURECOMPOUND NAMEMOL WTITY
|
|
|
568Morpholine-4-carboxylic acid {(S)-3- [2-(4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride557.14100% (LC/ MS)
|
569Morpholine-4-carboxylic acid {(S)-3- [2-(4-methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride605.290% (LC/ MS)
|
5703,3-Difluoro-pyrolidine-1-carboxylicp acid {(S)-3-[2-(4-methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloiride577.12100% (LC/ MS)
|
5713,3-Difluoro-pyrrolidine-1-carboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride625.18100% (LC/ MS)
|
EXAMPLE 11
(3-[2-(4-Methanesulfonylbenzyl)-1-oxo-2,8-diaza-5 spiro[4.5]dec-8-yl]-1-phenylpropyl}-carbamic acid methyl ester hydrochloride (Compound 572)
To a stirred solution of 8-(3-amino-3-phenylpropyl)-2-(4-methanesulfonylbenzyl)-2,8-diaza-spiro[4.5]decan-1-one (27.3 mg, 0.06 mmol) in DMF-DCE (1:1, 1.0 mL) was sequentially added triethylamine (0.01 mL, 0.072 mmol) and dimethyldicarbonate (0.07 mL, 0.066 mmol). The reaction mixture was stirred overnight at room temperature, concentrated and purified by semi-preparative HPLC (method D) affording Compound 572 (17.2 mg, 52%) as a white powder.
1H NMR (400 MHz, DMSO-d6): δ[ppm] 9.62 (br s, 1H), 7.88 (d, 2H), 7.44 (d, 2H), 7.33 (m, 4H), 7.25 (m, 1H), 4.59 (m, 1H), 4.47 (s, 2H), 3.50 (s, 3H), 3.42 (m, 2H), 3.22 (t, 2H), 3.19 (s, 3H), 3.09-2.91 (m, 4H), 2.12-1.95 (m, 6H), 1.86 (t, 1H), 20 1.64 (br d, 2H)
LC/MS: m/z 513.6 (MH+).
Table 6 of compounds illustrates some of the compounds of the present invention that were synthesized using the procedure described in scheme 7.
TABLE 6
|
|
CPDMOL
#MOL STRUCTURECOMPOUND NAMEWTPURITY
|
|
|
572{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-carbamic methyl ester hydrochloride550.11698+(LC/MS)
|
573{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-carbamic acid ethyl ester hydrochloride564.14398+(LC/MS)
|
Table 6a of compounds illustrates some additional compounds of the present invention that were synthesized using the procedure described in scheme 7.
TABLE 6a
|
|
CPD
#MOL STRUCTURECOMPOUND NAMEMOL WTPURITY
|
|
|
574{3-[2-(4-Methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- pyridin-2-yl-propyl}-carbamic acid cyclohexyl ester582.7783% (LC/MS)
|
575{(S)-3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-carbamic acid cyclohexyl ester581.7899% (LC/MS)
|
576{(S)-3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-carbamic acid cyclobutyl ester553.7399% (LC/MS)
|
577{(S)-3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-carbamic acid cyclopentyl ester567.7599% (LC/MS)
|
578[(S)-3-(1-Oxo-2-pyridin-3-ylmeethyl- 2,8-diaza-spiro[4.5]dec-8-yl)-1- phenyl-propyl]-carbamic acid cyclobutyl ester476.6298% (LC/MS)
|
579[(S)-3-(1-Oxo-2-pyridin-3-ylmethyl- 2,8-diaza-spiro[4.5]dec-8-yl)-1- phenyl-propyl]-carbamic acid cyclopentyl ester490.6599% (LC/MS)
|
580[(S)-3-(1-Oxo-2-pyridin-3-ylmethyl- 2,8-diaza-spiro[4.5]dec-8-yl)-1- phenyl-propyl]-carbamic acid 1- methyl-cyclopentyl ester504.6897% (LC/MS)
|
581[(S)-3-(1-Oxo-2-pyridin-3-ylmethyl- 2,8-diaza-spiro[4.5]dec-8-yl)-1- phenyl-propyl]-carbamic acid cyclohexyl ester504.68100% (LC/MS)
|
582{3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-carbamic acid ethyl ester hydrochloride570.9898+(LC/MS)
|
583{3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-carbamic acid ethyl ester hydrochloride522.1198+(LC/MS)
|
584[3-(1-Oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1- thiophen-2-yl-propyl]-carbamic acid ethyl ester dihydrochloride529.5398+(LC/MS)
|
585{1-(2-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}- carbamic acid ethyl ester hydrochloride550.5298+(LC/MS)
|
586{1-(2-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-carbamic acid ethyl ester hydrochloride598.5998+(LC/MS)
|
587[1-(2-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid ethyl ester dihydrochloride557.9598+(LC/MS)
|
588[3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(2- chloro-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride599.498+(LC/MS)
|
589{1-(3-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}- carbamic acid ethyl ester hydrochloride550.5298+(LC/MS)
|
590{1-(3-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-carbamic acid ethyl ester hydrochloride598.5998+(LC/MS)
|
591[1-(3-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid ethyl ester dihydrochloride557.9598+(LC/MS)
|
592{1-(4-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}- varbamic acid ethyl ester hydrochloride550.5298+(LC/MS)
|
593[1-(4-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid ethyl ester dihydrochloride557.9598+(LC/MS)
|
594{3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-carbamic acid methyl ester hydrochloride556.9598+(LC/MS)
|
595{3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-carbamic acid methyl ester hydrochloride508.0898+(LC/MS)
|
596{3-[2-(4-Methanesulfonyl=benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-carbamic acid methyl ester hydrochloride556.1498+(LC/MS)
|
597[3-(1-Oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1- thiophen-2-yl-propyl]-carbamic acid methyl ester dihydrochloride515.598+(LC/MS)
|
598{1-(2-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}- carbamic acid methyl ester hydrochloride536.598+(LC/MS)
|
599{1-(2-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-carbamic acid methyl ester hydrochloride554.5698+(LC/MS)
|
600[1-(2-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid methyl ester dihydrochloride543.9298+(LC/MS)
|
601[3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3- chloro-phenyl)-propyl]-carbamic acid methyl ester hydrochloride585.3798+(LC/MS)
|
602{1-(3-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}- carbamic acid methyl ester hydrochloride536.598+(LC/MS)
|
603{3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-pyridin- 2-yl-propyl}-carbamic acid ethyl ester hydrochloride602.4198% (LC/MS)
|
604{3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- pyridin-2-yl-propyl}-carbamic acid ethyl ester dihydrochloride553.5398% (LC/MS)
|
605[3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride594.9998% (LC/MS)
|
606[3-[2-(4-Methoxy-benzyl)-1-oxxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride546.1198% (LC/MS)
|
607[3-[2-(4-Methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- (4-methoxy-phenyl)-propyl]- carbamic acid ethyl ester hydrochloride594.1798% (LC/MS)
|
608[1-(4-Methoxy-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid ethyl ester dihydrochloride553.5398% (LC/MS)
|
609[3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3,4- dimethoxy-phenyl)-propyl]- carbamic acid ethyl ester hydrochloride625.0198% (LC/MS)
|
610{1-(3,4-Dimethoxy-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[44.5]dec-8-yl]-propyl}- carbamic acid ethyl ester hydrochloride576.1498% (LC/MS)
|
611{1-(3,4-Dimethoxy-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-carbamic acid ethyl ester hydrochloride624.298% (LC/MS)
|
612[1-(3,4-Dimethoxy-phenyl)-3-(1- oxo-2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid ethyl ester dihydrochloride583.5698% (LC/MS)
|
613[3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3- methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride594.9998% (LC/MS)
|
614[3-[2-(4-Methoxy-beenzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(3- methoxy-phenyl)propyl]-carbamic acid ethyyl ester hydrochloride546.1198% (LC/MS)
|
615[3-[2-(4-Methanesulfonyl-bhenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- (3-methoxy-phenyl)-propyl]- carbamic acid ethyl ester hydrochloride594.1798% (LC/MS)
|
616[1-(3-Methoxy-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid ethyl ester dihydrochloride553.5398% (LC/MS)
|
617[3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride580.9698% (LC/MS)
|
618[3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride532.0898% (LC/MS)
|
619[3-[2-(4-Methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- (4-methoxy-phenyl)propyl]- carbamic acid methyl ester hydrochloride580.1598% (LC/MS)
|
620[3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3,4- dimeethoxy-phenyl)-propyl]- carbamic acid methyl ester hydrochloride610.9998% (LC/MS)
|
621{1-(3,4-Dimethoxy-phenyl)-3-[2-(4- meethoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}- carbamic acid meethyl ester hydrochloride562.1198% (LC/MS)
|
622{1-(3,4-Dimethoxy-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-carbamic acid methyl ester hydrochloride610.1798% (LC/MS)
|
623[1-(3,4-Dimethoxy-phenyl)-3-(1- oxo-2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid methyl ester dihydrochloride569.5398% (LC/MS)
|
624[3-[2-(4-Bromo-benzyl)-1-oxxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3- methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride580.9698% (LC/MS)
|
625[3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(3- methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride532.0898% (LC/MS)
|
626[3-[2-(4-Methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- (3-methoxy-phenyl)-propyl]- carbamic acid methyl ester hydrochloride580.1598% (LC/MS)
|
627[1-(3-Methoxy-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid methyl ester dihydrochloride539.5198% (LC/MS)
|
628{1-(3-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-carbamic acid methyl ester hydrochloride584.5698+(LC/MS)
|
629[1-(3-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid methyl ester dihydrochloride543.9298+(LC/MS)
|
630{1-(4-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}- carbamic acid methyl ester hydrochloride536.598+(LC/MS)
|
631{1-(4-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-carbamic acid methyl ester hydrochloride584.5698+(LC/MS)
|
632[1-(4-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid methyl ester dihydrochloride543.9298+(LC/MS)
|
633[3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride580.9698+(LC/MS)
|
634[3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride594.9998+(LC/MS)
|
635[3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride532.0898+(LC/MS)
|
636[3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride546.1198+(LC/MS)
|
637[3-[2-(4-Methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- (2-methoxy-phenyl)-propyl]- carbamic acid methyl ester hydrochloride580.1598+(LC/MS)
|
638[3-[2-(4-Methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- (2-methoxy-phenyl)-propyl]- carbamic acid ethyl ester hydrochloride594.1798+(LC/MS)
|
Preparation 10
8-(3,3-Diphenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one
To a mixture of 1.49 g (7.8 mmol) of 2,8-diaza-spiro[4.5]decan-1-one hydrochloride, 2.39 g (8.6 mmol) of 3,3-diphenylpropyl bromide and 3.23 g (23.4 mmol) of potassium carbonate was added 40 mL of anhydrous DMF. The reaction mixture was stirred for 8 hours at 60° C. Then 10 mL of water was added and the solution was extracted with DCM (2×100 mL). The combined organic layers were dried over sodium sulfate, filtered and evaporated in vacuo. The yellow crude oil was purified by flash chromatography on silica gel (DCM/methanol 100:0 to 90:10) and 8-(3,3-diphenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one was isolated as a pale yellow solid (1.22 g, 44.9%).
1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.49 (br s, 1H) , 7.3-7.22 (m, 8H), 7.13 (m, 2H), 3.97 (t, 1H), 3.09 (t, 2H), 2.67 (m, H), 2.13 (m, 4H), 1.86 (m, 4H), 1.63 (t×d, 2H), 1.25 (br, 2H)
Preparation 11
8-(3,3-Diphenylpropyl)-2,8-diaza-spiro[4.5]decane
400 mg (1.14 mmol) of 8-(3,3-diphenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one were dissolved in 15 mL of anhydrous THF followed by 3.44 mL of a 1M solution of LAH in THF. The reaction mixture was refluxed for 5 hours and cooled. 5 mL of water and 10 mL of aqueous solution of sodium hydroxide (1N) were successively added and the solution was stirred for an additional one hour before filtering on celite. The filtrate was extracted with DCM (2×10 mL). The organic layers were dried over sodium sulfate, filtered and evaporated in vacuo to yield 8-(3,3-diphenylpropyl)-2,8-diaza-spiro[4.5]decane as a yellow oil (365.1 mg, 95.7%).
1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.29-7.22 (m, 8H), 7.12 (m, 2H), 3.95 (t, 1H), 3.34 (br s, 1H), 2.72 (t, 2H), 2.46 (s, 2H), 2.24-2.07 (m, 8H), 1.38 (m, 6H).
EXAMPLE 12
(4-Bromophenyl)-[8-(3,3-diphenylpropyl)-2,8-diaza-spiro[4.5]dec-2-yl]-methanone hydrochloride (Compound 639)
To 100 mg (100 μmol, loading of 1 mmol/g) of 4-bromophenylcarboxyl activated ester on polymeric 4-hydroxy-2,3,5,6-tetrafluorobenzamido (TFP) resin (see preparation in J. M. Salvino et al. J. Comb. Chem. 2000, 2, 691-697), preswollen with 0.5 mL of anhydrous DMF, was added 20 mg (60 μmol) of 8-(3,3-diphenylpropyl)-2,8-diaza-spiro[4.5]decane diluted in 1 mL of DMF. The reaction was agitated overnight at room temperature. The mixture was filtered and washed with DCM (2×2 mL). The filtrates were collected and evaporated in vacuo. The crude was purified by semi-preparative HPLC (method B) yielding Compound 639 as a colorless solid (9.8 mg, 29.5%).
1H NMR (400 MHz, DMSO-d6): δ[ppm] 9.9 (br s, 1H), 7.61 (d, 2H), 7.47 (d×d, 1H), 7.43 (d, 1H), 7.3 (m, 8H), 7.18 (t, 2H), 3.96 (t, 1H), 3.52-3.28 (m, 8H), 2.94 (m, 3H), 2.79 (m, 1H), 1.89-1.63 (m, 6H).
LC/MS: m/z 519.0 (MH+).
EXAMPLE 13
4-[2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyric acid methyl ester (Compound 640)
To a mixture of 500 mg (1.39 mmol) of 2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride in 10 mL of anhydrous DMF was added 484 μL (2.78 mmol) of DIPEA followed by a solution of 4-bromo-2-phenyl-butyric acid methyl ester (357 mg, 1.39 mmol) in 4 mL of anhydrous DMF. Then 576 mg (4.17 mmol) of potassium carbonate were added and the reaction mixture was stirred overnight at 60° C. After cooling, the mixture was poured in water and extracted with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. The crude was purified by flash chromatography on silica gel, eluting with ethyl acetate and DCM/methanol (9:1), and yielding 555 mg of Compound 640 as a colorless oil (80%).
1H NMR (400 MHz, CD2Cl2): δ[ppm] 7.47 (d, 2H), 7.34-7.24 (m, 5H), 7.11 (d, 2H), 4.38 (s, 2H), 3.73 (m, 1H), 3.66 (s, 3H), 3.13 (t, 2H), 2.85 (m, 1H), 2.72 (m, 1H), 2.35-2.24 (m, 3H), 2.07-1.81 (m, 7H), 1.37 (br d, 2H).
Preparation 12
4-[2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyric acid
To a mixture of 521 mg (1.043 mmol) of 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-2-phenyl-butyric acid methyl ester in 10 mL of methanol was added 101 mg (1.56 mmol) of potassium hydroxide in 5 mL of water. The reaction mixture was refluxed for 5 hours, cooled to room temperature, diluted with water (10 mL) and treated with concentrated acetic acid. The mixture was stirred for 30 minutes and left at room temperature to allow crystallisation. 4-[2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyric acid was collected as a white solid (390 mg, 77%) by filtration.
1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.51 (d, 2H), 7.32-7.2 (m, 5H), 7.12 (d, 2H), 4.32 (s, 2H), 3.58 (t, 1H), 3.43 (br s, 1H), 3.12 (t, 2H), 2.77 (m, 2H), 2.3-1.99 (m, 5H), 1.83 (t, 2H), 1.73 (m, 3H), 1.33 (d, 2H).
EXAMPLE 14
4-[2- (4-Bromobenzyl)-1-oxo-2,8-diaza-spiro [4.5] dec-8-yl]-N-cyclohexyl-2-phenyl-butyramide hydrochloride (Compound 646)
To a mixture of 24.2 mg (50 μmol) of 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyric acid in 0.5 mL of DCE was added 6. 4 mg (65 vol) of cyclohexylamine in 0. 5 mL of DCE and 13. 4 mg (65 μmol) of DCC in 0.5 mL of DCE. The reaction mixture was stirred at room temperature for 16 hours and concentrated. The crude mixture was purified by semi-preparative HPLC (method E) yielding 11.9 g (39%) of Compound 646 as a pale yellowish solid.
1H NMR (400 MHz, CD3OD): δ[ppm] 7.49 (d, 2H) , 7.38-7.25 (m, 5H), 7.16 (d, 2H), 4.41 (d, 2H), 3.65-3.27 (m, 8H), 3.11-2.95 (m, 3H), 2.41 (m, 1H), 2.24-2.05 (m, 4H), 1.96-1.85 (m, 2H), 1.77-1.59 (m, 5H), 1.39-1.04 (m, 5H).
Table 7 of compounds illustrates some of the compounds of the present invention that were synthesized using the procedure described in scheme 9.
TABLE 7
|
|
CPD
#MOL STRUCTURECOMPOUND NAMEMOL WTPURITY
|
|
|
64054-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2-phenyl- butyric acid methyl ester499.446100% (LC/MS)
|
6414-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-butyric acid methyl ester498.641100% (LC/MS)
|
6424-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2-phenyl- butyric acid methyl ester450.576>90% (HNMR)
|
6434-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2,N- diphenyl-butyramide hydrochloride596.99498+(LC/MS)
|
644N-benzyl-4-[2-(4-bromobenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2- phenyl-butyramide hydrochloride611.0298+(LC/MS)
|
6452-(4-bromobenzyl)-8-(4-oxo-3- phenyl-4-piperidin-1-yl-butyl)-2,8- diaza-spiro[4.5]decan-1-one hydrochloride589.10498+(LC/MS)
|
6464-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-N- cyclohexyl-2-phenyl-butyramide hydrochloride603.04198+(LC/MS)
|
6474-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-N- cyclohexyl-n-methyl-2-phenyl- butyramide hydrochloride617.06898+(LC/MS)
|
6484-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-N- cyclopropyl-2-phenyl-butyramide hydrochloride560.96198+(LC/MS)
|
6494-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-N- cyclobutyl-2-phenyl-butyramide hydrochloride574.98798+(LC/MS)
|
650N-cyclohexyl-4-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-n-methyl- 2-phenyl-butyramide hydrochloride616.26298+(LC/MS)
|
651N-cyclopropyl-4-[2-(4- methanesulfonylbnzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride560.15598+(LC/MS)
|
652N-cyclobutyl-44-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride574.18298+(LC/MS)
|
6534-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-N- cyclopentyl-2-phenyl-butyramide hydrochloride589.01498+(LC/MS)
|
6544-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-N- isopropyl-2-phenyl-butyramide hydrochloride562.97698+(LC/MS)
|
655N-benzyl-4-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride610.21598+(LC/MS)
|
6562-(4-methanesulfonylbenzyl)-8-(4- oxo-3-phenyl-4-piperidin-1-yl- butyl)-2,8-diaza-spiro[4.5]decan-1- one hydrochloride588.20998+(LC/MS)
|
657N-cyclohexyl-4-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride602.23698+(LC/MS)
|
658N-cyclopentyl-4-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride588.20998+(LC/MS)
|
659N-isopropyl-4-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride562.17198+(LC/MS)
|
6604-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2,N- diphenyl-butyramide hydrochloride548.12390.6% (LC/MS)
|
661N-benzyl-4-[2-(4-methoxybenzyl)- 1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 2-phenyl-butyramide hydrochloride562.1598+(LC/MS)
|
6622-(4-methoxybenzyl)-8-(4-oxo-3- phenyl-4-piperidin-1-yl-butyl)-2,8- diaza-spiro[4.5]decan-1-one hydrochloride540.14498+(LC/MS)
|
663N-cyclohexyl-4-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride554.17198+(LC/MS)
|
664N-cyclopropyl-4-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride512.0998+(LC/MS)
|
665N-cyclobutyl-4-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride526.11798+(LC/MS)
|
666N-cyclopentyl-4-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride540.14498+(LC/MS)
|
667N-isopropyl-4-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride514.10698+(LC/MS)
|
Table 8 of compounds illustrates some of the compounds of the present invention that can be synthesized using the procedure described in schemes 1-9.
TABLE 8
|
|
CPD
#MOL STRUCTURECOMPOUND NAMEMOL WT
|
|
|
668Cyclopropanecarboxylic acid {(S)- 1-(3-chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-ylp]propyl}-amide hydrochloride546.54
|
669Cyclopropanecarboxylic acid {(S)- 1-(3-fluoro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride530.09
|
670Cyclopropanecarboxylic acid {(S)- 3-[2-(4-methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-amide hydrochloride518.12
|
671Cyclopropanecarboxylic acid {(S)- 3-[2-(4-methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-3-yl-propyl}-amide hydrochloride518.12
|
672N-{(S)-1-(3-Chloro-phenyl)-3-[2- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]prropyl}- isobutyramide hydrochloride548.56
|
673N-{(S)-1-(3-Fluoro-phenyl)-3-[2- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- isobutyramide hydrochloride532.1
|
674N-{(S)-3-[2-(4-Methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-thiophen-2-yl-propyl}- isobutyramide hydrochloride520.14
|
675N-{(S)-3-[2-(4-Methoxy-bnzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-thiophen-3-yl-propyl}- isobutyramide hydrochloride520.14
|
676N-{(S)-3-[2-(4-Chloro-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-isobutyramide hydrochloride518.53
|
677N-{(S)(-3-[2-(4-Fluoro-benzyl)-3- oxo-2,8-diaza-spiro[44.5]dec-8-yl]- 1-phenyl-propyl}-isobutyramide hydrochloride502.08
|
678N-{(S)-3-[2-(4-Cyano-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-isobutyramide hydrochloride509.1
|
679N-{(S)-3-[2-(4-Ethoxy-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-isobutyramide hydrochloride528.1214
|
680N-{(S)-3-[2-(4-Difluoromethoxy- benzyl)-3-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-isobutyramide hydrochloride550.09
|
681N-{(S)-3-[3-Oco-2-(4- trifluoromethoxy-benzyl)-2,8- diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-isobutyramide hydrochloride568.08
|
682N-{(S)-3-[3-Oxo-2-(4- trifluoromethyl-benzyl)-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-isobutyramide hydrochloride552.08
|
683N-{(S)-3-[3-Oxo-2-(4-pyrazol-1-yl- benzyl)-2,8-diaza-spiro[4.5]dec-8- yl]-1-phenyl-propyl}- issobutyramide hydrochloride550.15
|
684Cyclopropanecarboxylic acid {(S)- 3-[2-(4-chloro-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride516.52
|
685Cyclopropanecarboxylic acid {(S)- 3-[2-(4-fluoro-benzyl)-2-oxo-2,8- dxiaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride500.06
|
686Cyclopropanecarboxylic acid {(S)- 3-[2-(4-cyano-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride507.08
|
687Cyclopropanecarboxylic acid {(S)- 3-[2-(4-ethoxy-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride526.12
|
688Cyclopropanecarboxylic acid {(S)- 3-[2-(4-difluoromethoxy-benzyl)- 3-oxo-2,8-diaza-spiro[4.5]dec-8- yl]-1-phenyl-propyl}-amide dihydrochloride548.08
|
689Cyclopropanecarboxylic acid {(S)- 3-[2-(4-trifluoromethoxy-benzyl)- 3-oxo-2,8-diaza-spiro[4.5]dec-8- yl]-1-phenyl-propyl}-amide hydrochloride566.07
|
690Cyclopropanecarboxylic acid {(S)- 3-[2-(4-trifluoromethyl-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-amide hydrochloride550.07
|
691Cyclopropanecarboxylic acid {(S)- 3-[3-oxo-2-(4-pyrazol-1-yl- benzyl)-2,8-diaza-spiro[4.5]dec-8- yl]-1-phenyl-propyl}-amide hydrochloride548.13
|
6922-Cyclopropyl-N-{(S)-3-[2-(4- methoxy-benzyl)-3-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride526.12
|
693N-{(S)-3-[2-(4-Chloro-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-2-cyclopropyl- acetamide hydrochloride530.54
|
694N-{(S)-3-[2-(4-Fluoro-beenzyl)-3- oxo-2,8-diaza-spiro[44.5]dec-8-yl]- 1-phenyl-propyl}-2-cyclopropyl- acetamide hydrochloride514.09
|
695N-{(S)-3-[2-(4-Cyano-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-2-cyclopropyl- acetamide hydrochloride521.11
|
696N-{(S)-3-[2-(4-Ethoxy-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-2-cyclopropyl- acetamide hydrochloride540.15
|
697N-{(S)-3-[2-(4-Difluoromethoxy- benzyl)-3-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-cyclopropyl-acetamide hydrochloride562.1
|
698N-{(S)-3-[2-(4-Trifluoromethoxy- benzyl)-3-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-cyclopropyl-acetamide hydrochloride580.09
|
699N-{(S)-3-[2-(4-trifluoromethyl- benzyl)-3-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-cyclopropyl-acetamide hydrochloride564.1
|
7002-Cyclopropyl-N-{(S)-3-[3-oxo-2- (4-pyrazol-1-yl-benzyl)-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride562.16
|
7014,4-Difluoro- cyclohexanecarboxylic acid {(S)- 3-0[2-(4-chloro-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride594.58
|
7024,4-Difluoro- cyclohexanecarboxylic acid {(S)- 3-[2-(4-cyano-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride578.12
|
7034,4-Difluoro- cyclohexanecarboxylic acid {(S)- 3-[2-(4-cyano-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride585.14
|
7044,4-Difluoro- cyclohexanecarboxylic acid {(S)- 3-[2-(4-ethoxy-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride604.19
|
7054,4-Difluoro- cyclohexanecarboxylic acid {(S)- 3-[3-oxo-2-(4-pyrazol-1-yl- benzyl)-2,8-diaza-spiro[4.5]dec-8- yl]-1-phenyl-propyl}-amide hydrochloride626.19
|
706Cyclopropanecarbocylic acid {(S)- 1-(3-chloro-phenyl)-3-[2-(4- methoxy-benzyl)-3-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride546.54
|
707Cyclopropanecarboxylic acid {(S)- 1-(3-fluoro-phenyl)-3-[2-(4- methoxy-benzyl)-3-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride530.09
|
708Cyclopropanecarboxylic acid {(S)- 3-[2-(4-methoxy-benzyl)-3-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-amide hydrochloride518.12
|
709Cyclopropanecarboxylic acid {(S)- 3-[2-(4-methoxy-benzyl)-3-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-3-yl-propyl}-amide hydrochloride518.12
|
710N-{(S)-1-(3-Chloro-phenyl)-3-[2- (4-methoxy-beenzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- isobutyramide hydrochloride548.56
|
711N-{(S)-1-(3-Fluoro-phenyl)-3-[2- (4-methoxy-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- isobutyramide hydrochloride532.1
|
712N-{(S)-3-[2-(4-Methoxy-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-thiophen-2-yl-propyl}- isobutyramide hydrochloride520.14
|
713N-{(S)-3-[2-(4-Methoxy-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-thiophen-3-yl-propyl}- isobutyramide hydrochloride520.14
|
714Propane-2-sulfonic acid {(S)-3-[2- (4-methoxy-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride550.16
|
7153-{(S)-3-[2-(4-Methoxy-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-1,1-dimethyl- urea hydrochloride515.1
|
716Morpholine-4-carboxylic acid {(S)- 3-[2-(4-methoxy-benzyl)-3-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride557.14
|
7173,3-Difluoro-yrrolidine-1- carboxylic acid {(S)-3-[2-(4- methoxy-benzyl)-3-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride577.12
|
718{(S)-3-[2-(4-Methoxy-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-carbamic acid methyl ester hydrochloride502.06
|
719{(S)-3-[2-(4-Methoxy-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-carbamic acid ethyl ester hydrochloride516.08
|
EXAMPLE 15
The following assay methods are suitable for evaluating the compounds of the invention.
Chemokine Binding assay: Membranes (1 μg/well) from human embryonic kidney (HEK-293) cells expressing human CCR5 were incubated with 0.1 nM 125I-labeled MIP-1α (Amersham) in the presence of varying concentrations of a test compound (10000-0.01 nM) in buffer (50 mM Hepes, pH 7.3/5 mM MgCl2/1 mM CaCl2/0.5% BSA) for 90 min at room temperature. Reaction mixtures (100 μL) were filtered through Multiscreen GFB filters (Millipore) and washed six times with cold wash buffer (50 mM Hepes, pH 7.3/0.5 M NaCl, 0.1% BSA). Bound 125I-MIP-1α was quantitated by liquid scintillation counting. The nonspecific binding of 125I-labeled MIP-1α to the membrane was determined based on the radioactivity from the wells added with 100 nM non-radiolabeled MIP-1α. IC50 and KD values were calculated by using GRAPHPAD PRISM software (Intuitive Software for Science, San Diego)
HIV-1 Replication in PBMC Cultures. Isolated PBMC were stimulated in vitro with 5 μg/ml phytohemagglutinin and 50 units/ml IL-2 for 3 days. The cells were resuspended at 4×106/ml in complete medium (RPMI, 10% FBS/50 units/ml IL-2), seeded into 96-well plates (2×105/well), incubated with inhibitor for 1 h at 37° C., and infected in triplicate with 25-100 tissue culture 50% infective dose (TCID50) per well of the R5 HIV-1JR-FL strain for 3-4 h. The cells were washed twice in PBS to remove residual virus and cultured in the presence of inhibitor for 4-6 days. HIV-1 replication was determined by the presence of viral RT activity in harvested supernatant fluid. The IC50 values for the virus were determined by using GRAPHPAD PRISM software.
The preceding examples can be repeated with similar success by substituting the generically or specifically described reactants and/or operating conditions of this invention for those used in the preceding examples.
From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention and, without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.
Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The preceding preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.
In the foregoing and in the examples, all temperatures are set forth uncorrected in degrees Celsius and, all parts and percentages are by weight, unless otherwise indicated.
The entire disclosures of all applications, patents and publications, cited herein and of corresponding U.S. Provisional Application Ser. No. 60/487,973, filed Jul. 18, 2003 is incorporated by reference herein.
The preceding examples can be repeated with similar success by substituting the generically or specifically described reactants and/or operating conditions of this invention for those used in the preceding examples.
From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention and, without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.