Fused thiophone derivatives and drugs containing the same as the active ingredient

Abstract

The present invention relates to a fused thiophene derivative of the formula (I) (wherein all the symbols are defined as described in the specification) and an inhibitor of producing interleukin-6 and/or interleukin-12 comprising the said derivative as an active ingredient.

Description

TECHNICAL FIELD

[0001] The present invention relates to fused thiophene derivatives and inhibitors of producing Interleukin-6 (abbreviated as IL-6 hereafter) and/or Interleukin-12 (abbreviated as IL-12 hereafter) containing fused thiophene derivatives as an active ingredient.

[0002] More particularly, the present invention relates to inhibitors of producing IL-6 and/or IL-12 comprising, as an active ingredient, fused thiophene derivatives of the formula (I) 2

[0003] (wherein all the symbols are as defined hereafter.) and non-toxic salts thereof, novel fused thiophene derivatives of the said formula (IA) or non-toxic salts thereof and methods for preparation thereof.

[0004] Moreover, the present invention relates to a method for preparation of a compound of the formula (XI) which is an intermediate for the compounds of the formula (I).

BACKGROUND

[0005] Cytokine is a multifunctional factor which plays an important role in the host defence system of living body and it relates to various life phenomena. However, there are many diseases which may be caused by overproduction thereof or by overresponse thereto.

[0006] IL-6 is a cytokine produced from various cells, e.g. T cells, B cells, macrophages, kidney mesangial cells, fibroblasts etc., and its various physiological effects are known e.g. induction of B cell differentiation to antibody-producing cells, activation of T cells, increase of platelets, and production of acute phase protein from liver cells etc. But, an abnormal production of IL-6 has been observed in various inflammations, autoimmune diseases and neoplastic diseases and it is suggested that IL-6 plays a certain role in the causes of such pathophysiological situations. In the experiment using an animal model in which IL-6 was forcibly expressed, various types of diseases could be observed and such results strongly suggest the existence of relationship between the abnormal production of IL-6 and the cause of certain diseases (Biochem. J., 265, 621 (1990), Immunol. Today, 11, 443 (1990), J. Autoimmun., 5 Suppl A, 123 (1992), Clin. Immunol. Immunopathol., 62, S60 (1992)).

[0007] IL-12 is a cytokine produced from macrophages and dendritic cells etc. and its effects are known; e.g. activation of natural killer (abbreviated as NK hereafter) cells, induction of Interferon-γ (abbreviated as IFN-γ hereafter) production from NK cells and T cells, and regulation of Th1 and Th2 balance etc. Helper T cells are classified into Th1 which stimulates cellular-mediated immunity and Th2 which assists humoral immunity. IL-12 functions to induce Th1 from helper T cell precursors. It is thought that succeedingly, IL-12 induces production of IFN-γ from Th1 cells (which are further differentiated) and accelerates killer activity, so that IL-12 plays a role as a main cytokine causing inflammatory immune reaction which leads to organ disorders (Blood, 84, 4008 (1994)).

[0008] Therefore, inhibition of IL-6 and/or IL-12 production(s) is expected to improve various kinds of diseases such as inflammatory diseases as a representative The present invention is targeted for these cytokines and provides novel medicines through inhibiting the production thereof.

[0009] Clinical application of the compounds of the present invention involves those diseases which may be caused and be changed to worse by abnormal production of IL-6 and/or IL-12 or by overresponse to them. Inhibitors of producing IL-6 may be used for the prevention and/or treatment of various inflammatory diseases, sepsis, multiple myeloma, plasma cell leukemia, osteoporosis, cachexia, psoriasis, nephritis, renal cell carcinoma, Kaposi's sarcoma, rheumatoid arthritis, gammopathy, Castleman's disease, atrial myxoma, diabetes mellitus, autoimmune diseases (J. Immunol., 145, 4185 (1990), J. Exp. Med., 172: 1505 (1990), J. Clin. Invest., 87,739 (1991), J. Clin. Invest., 89 1681 (1992), EMBO J., 1, 1189 (1994), Hematol. Oncol. Clin. North Am., 11 159 (1997)). Inhibitors of producing IL-12 may be used for the prevention and/or treatment of various inflammatory diseases, diabetes mellitus, hepatitis, multiple sclerosis, colitis, graft versus host immune diseases, rheumatoid arthritis, infectious diseases, autoimmune diseases (J. Exp. Med., 181, 817 (1995), J. Exp. Med., 181, 381 (1995), J. Exp. Med., 182 128, (1995), Ann, NY Acad. Sci., 795, 371 (1996), Int. Immunol., 8, 569 (1996), Proc. Natl. Acad. Sci. USA, 92, 4823 (1996)).

[0010] Further, a compound of the formula (Xl) is an important intermediate of pharmaceutical agents and an efficient method for preparation thereof has been desired.

[0011] For example,

[0012] (1) In the specifications of U.S. Pat. No. 3,629,438 and U.S. Pat. No. 3,686,216, it is disclosed that a benzothiophene-1,1-dioxide derivative of the formula (X) 3

[0013] (wherein Xx is halogen, nitro, alkyl, alkoxy, haloalkyl, carboxy or sulfonylhalide,

[0014] Yx is hydrogen, lower alkyl, lower alkoxy, halogen or hydroxy,

[0015] Zx is alkyl, alkoxy, halogen, carboxy, haloalkyl or nitro,

[0016] aX is 0 or an integer of 2,

[0017] bX is an integer of 2,

[0018] cX is 0 or an integer of 1˜5 or

[0019] dX is 0 or an integer of 1˜4.)

[0020] has an anti-fungal and anti-vital activities.

[0021] (2) In the specification of FR1585930, a compound of the formula (Y) 4

[0022] (wherein R1Y is hydrogen, halogen or C1˜3 alkyl; R2Y and R3Y are hydrogen or C1˜3 alkyl) is described as an intermediate of diuretic agent, but there is no description about its biological activity.

[0023] (3) In the specification of SU591474, it is described that a compound of the formula (Z) 5

[0024] (wherein RZ, R1Z, R2Z and R3Z are hydrogen or methyl.) has an anti-spasm activity.

[0025] (4) In the specification of EP50326, it is described that a compound of the formula (U) 6

[0026] (wherein R1U and R2U are each hydrogen or C1˜6 alkyl, C3˜6 cycloalkyl or phenyl which may be substituted with 1-2 of halogen, hydroxy, C1˜6 alkyl or alkoxy, R3U is hydrogen or ZU, ZU is C1˜6 alkyl or CR4UR5UR6U, R4U and R5U are hydrogen or C1˜6 alkyl, R6U is COOH, CH2—OH, C1˜6 alkoxycarbonyl or hydroxyaminocarbonyl, XU is hydrogen, halogen or C1˜6 alkyl, nU is 1 or 2, mU is 0˜2) has a diuretic activity (In the explanation of groups, essential parts are extracted).

[0027] (5) In the specification of WO9527710, it is described that a compound of the formula (V) 7

[0028] (wherein R1V is t-butyl, R1V is hydrogen, lower alkyl or acyl, a broken line is arbitrary bond, R2V and R3V are hydrogen, alkyl which may be substituted or alkenyl which may be substituted, R4V does not represent anything when arbitrary bond exists and represents the same meaning as R1V when arbitrary bond does not exist and nV is 0˜2.) has an activity as antioxidant of low-density lipoprotein (LDL) (In the explanation of groups, essential parts are extracted).

[0029] (6) In the specification of Japanese Patent Application Kokai Hei 10-298180, it is described that a compound of the formula (W) 8

[0030] (wherein ZW is oxygen atom or sulfur atom; R1W, R2W, R3W and R4W are the same or different, are hydrogen etc.); EW and FW are the same or different, are nitrogen atom or CH which may be substituted with XW or YW; XW is straight or branched C1-6 alkyloxy, C3-8 cycloalkyloxy or straight or branched C1-3 alkyloxy substituted with C3˜8 cycloalkyl; Y is 9

[0031] (wherein GW is —CONH—, O(O)O—, —NHCO— or —OC(O)—; R5W is (a) straight or branched C1-6 alkyl, (b) C3-8 cycloalkyl, (c) C7-12 spiroalkyl, (d) C7-12 bicycloalkyl, (e) aryl, (f) aralkyl, (g) heteroarylalkyl, (h) non-aromatic heterocyclic ring which may be substituted with phenyl or (i) C3-8 cycloalkyl-C1˜3 alkyl. Each of them may be substituted with one or more of substituent selected from a group consisting of i) straight or branched C1-6 alkyl, ii) straight or branched C1-8 alkyloxy, iii) C1-3 haloalkyl, iv) halogen, v) C3-8 cycloalkyl, vi) carboxy, vii) alkyloxycarbonyl, viii) acyl, ix) formyl and x) nitro; nW is an integer of 1-3, pW is an integer of 1-3, (CH2)w and (CH2)pW may be substituted with a straight or branched C1-6 alkyl or C1-3 haloalkyl) has an antagonistic activity against dopamine receptor.

[0032] (7) In the specification of Japanese Patent Application Kokai Hei 10-513470, it is described that a compound of the formula (T) 10

[0033] [wherein R1T and R3T are independently hydrogen, —CH3, —C(O)—(C1˜6 alkyl), or —C(O)—ArT (ArT is phenyl which may optionally be substituted); R2T is selected from a group consisting of pyrrolidino, hexamethyleneimino and piperidino], a pharmaceutically acceptable salt thereof or a solvent additive has an activity of inhibiting the effect of IL-6.

[0034] (8) In the specification of Japanese Patent Application Kokai Hei 11-49765, it is described that a compound of the formula (S) 11

[0035] [wherein each R1S and R2S is hydrogen or hydrocarbon group which may contain substituent(s) or R1S and R2S taken together with the neighboring carbon atom represents 3- to 8-membered homo or heterocyclic ring which may contain substituent(s), R3S is hydrogen or lower alkyl which may contain subtstituent(s) or aromatic group which may contain substituent(s), R4S is (1) aromatic group which may contain substituent(s), (2) aliphatic hydrocarbon which contains aromatic group (this group is unsubstituted or substituted.) and which may contain additional substituent(s) or (3) acyl, XS and YS are each oxygen atom or sulfur atom which may be oxidized, is single bond or double bond, ring AS is benzene ring which contains a group of the formula —XSR4S (wherein each symbols represent the same meaning as defined hereinbefore) and which may contain additional substituent(s), with the proviso that when is single bond and both XS and YS are oxygen atom, then R45 is not acyl.] or a salt thereof have an excellent inhibitory effect of neurodegeneration.

[0036] (9) Further, the following compounds are known.

[0037] Compound (1): 3-(Thiophen-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene (Maybridge, Catalog No. KM 08156),

[0038] Compound (2): 6-Nitro-3-(thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene (Maybridge, catalog No. KM 08165),

[0039] Compound (3): 3-(Thiophen-2-yl)thio-2,3-dihydro-11-dioxidebenzo[b]thiophene (Maybridge, Catalog No. KM 08138),

[0040] Compound (4): 3-Phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene (Maybridge, Catalog No. KM 08140),

[0041] Compound (5): 4,5-Dimethyl-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 102036-04-4),

[0042] Compound (6): 4,6-Dimethyl-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 102036-05-5),

[0043] Compound (7): 4,7-Dimethyl-11-dioxidebenzo[b]thiophene (CAS Registry No. 102036-06-6),

[0044] Compound (8): 5,6-Dimethyl-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 102036-07-7),

[0045] Compound (9): 5,7-Dimethyl-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 102036-08-8),

[0046] Compound (10) 6,7-Dimethyl-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 102036-09-9),

[0047] Compound (11) 4-Carboxymethyl-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 102539-83-3),

[0048] Compound (12): 6-(2,2-Bis(ethoxycarbonyl)ethenyl)amino-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 118675-43-7),

[0049] Compound (13): 4-Methylaminocarbonyloxy-1,1 -dioxidebenzo[b]thiophene (CAS Registry No. 13687-26-8),

[0050] Compound (14): 5-(2-(N-(5-Methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-N-methylamino)ethyl)-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 188110-86-3),

[0051] Compound (15): 5-(2-Hydroxyethyl)-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 188111-49-1),

[0052] Compound (16): 5-Bromo-7-methyl-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 19076-24-5),

[0053] Compound (17): 7-Bromo-5-methyl-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 19076-25-6),

[0054] Compound (18): 5-Bromo-6-methyl-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 19076-26-7),

[0055] Compound (19): 5-Bromo-4-methyl-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 19076-27-8),

[0056] Compound (20): 6-Bromo-5-methyl-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 19076-28-9),

[0057] Compound (21): 4-Bromo-5-methyl-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 19076-29-0),

[0058] Compound (22): 6-Amino-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 20503-40-6),

[0059] Compound (23): 6-Acetyamino-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 20503-41-7),

[0060] Compound (24): 6-(4-Diethylaminophenyl)-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 33431-95-7),

[0061] Compound (25): 1,1-Dioxidethieno[2,3-b]pyridine (CAS Registry No. 37049-39-1),

[0062] Compound (26): 1,1-Dioxidethieno[3,2-b]pyridine (CAS Registry No. 37049-40-4),

[0063] Compound (27): 1,1-Dioxidethieno([2,3-c]pyridine (CAS Registry No. 37049-41-5),

[0064] Compound (28): 5-Amino-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 51956-01-5),

[0065] Compound (29): 5-(3-Methyl-5-oxo-4,5-dihydropyrazol-1-yl)-1,1-dioxidebenzo[b]thiophene (GAS Registry No. 51956-06-0),

[0066] Compound (30): 4-(2-(1,1-Dioxidebenzo[b]thiophen-3-yl)ethyl)-1,1-dioxidebenzo[b]thiophene (CAS Registry No. 57011-92-4),

[0067] Compound (31): 7-Methyl-1,1-dioxidethieno[2,3-c]pyridine (CAS Registry No. 76905-90-3),

[0068] Compound (32): 1,1-Dioxidebenzo[b]thiophene (CAS Registry No. 825-44-5),

[0069] Compound (33): 4-(4-Methoxyphenyl)-1,1 -dioxidethieno[3,2-c]pyridine (CAS Registry No. 97104-25-1).

[0070] (10) In addition, as to a method for preparation of a compound of the formula (XI), for example, the method of the following Reaction Scheme 2 is known.

[0071] These are described in detail in Nihonkagakuzasshi 1966, 87(2), 186-189, J. Org. Chem., 1953, Vol. 18, 1511 and J. Org. Chem. 1973, Vol. 38, 146. 12

[0072] In Reaction Scheme 2, Me is methyl, Ac is acetyl and NBS is N-bromosuccinimide.

[0073] The above method of Reaction Scheme 2 requires 5 or 6 steps in total and Ag2O, which is an expensive reagent, in oxidation reaction from the compound of the formula (XI-A-6) to the compound of the formula (XI).

[0074] Further, in the specification of Japanese Patent Application Kokai Hei 6-49058, the following Reaction Scheme 3 is disclosed as a method for preparation of the compound of the formula (XI). 13

[0075] In Reaction Scheme 3, Et is ethyl.

[0076] The above method of Reaction Scheme 3 requires 5 steps in total and the total yield is around 2˜3%.

[0077] In Tetrahedron Letters, 1996, Vol. 37, No. 19, 3243 and Tetrahedron Letters 1990, Vol.31, No.28, 4011, a reaction wherein ketone is converted into nitrile, followed by dehydrogenation to give aromatic ring is disclosed (Reaction Scheme 4). 14

[0078] In Reaction Scheme 4, TMS is trimethylsilyl, DDQ is 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.

[0079] This reaction is a method for preparation of aromatic nitrile of the formula (XI-C-2) which comprises that cyclic ketone of the formula (XI-C-1) is converted into cyanohydrin, followed by dehydration to give nitrile of the formula (XI-C-2), and then followed by dehydrogenation by an oxidizer.

DISCLOSURE OF THE INVENTION

[0080] The present inventors have investigated to find new compounds possessing an inhibitory activity of producing IL-6 and/or IL-12, so that the present inventors have found that the purpose has been achieved by fused thiophene derivatives of the formula (I).

[0081] Fused heterocyclic compounds of the formula (I) of the present invention has not been known as inhibitors of producing IL-6 and/or IL-12 at all. Further, a fused thiophene derivative of the formula (IA) is a novel compound which is not known at all.

[0082] In addition, the present inventors have investigated to find an efficient method for preparation at a low cost, so that the present inventor have found a method of the following Reaction Scheme 5. 15

[0083] The old methods require 5-6 steps, whereas the method of the present invention diminishes to 3 steps in total, so it become possible to produce efficiently. In addition, it is also confirmed that in mass-production of it, the cost for the production is reduced, so that the present inventors have completed the present invention.

[0084] The present invention relates to

[0085] (1) an inhibitor of producing Interleukin-6 and/or Interleukin-12 comprising, as an active ingredient, a fused thiophene derivative of the formula (I) 16

[0086] [wherein is a single or double bond, Y is (i) 17

[0087] or

[0088] (ii) hydrogen

[0089] (with a proviso that when is a double bond, Y is hydrogen, and when is a single bond, Y is 18

[0090] m and n are each independently 0 or an integer of 1-2,

[0091] p is 0 or an integer of 1-4,

[0092] q is 0 or an integer of 1-5,

[0093] Z is single bond, C1-8 alkylene, C2-8 alkenylene or C2-8 alkynylene, 19

[0094] is

[0095] (i) benzene ring or

[0096] (ii) 6-membered monocyclic hetero aryl containing 1-2 nitrogen atom(s), 20

[0097] is

[0098] (i) C3-15 mono-, bi- or tricyclic carbo ring or

[0099] (ii) 4-18 membered mono-, bi- or tricyclic hetero ring containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom, each R1 of (R1)p is independently,

[0100] (i) C1-8 alkyl,

[0101] (ii) C2-8 alkenyl,

[0102] (iii) C2-8 alkynyl,

[0103] (iv) nitro,

[0104] (v) cyano,

[0105] (vi) halogen,

[0106] (vii) Cyc1,

[0107] (viii) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with halogen or Cyc1or

[0108] (ix) —A1—A2—A3,

[0109] A1 is

[0110] (i) single bond,

[0111] (ii) C1-8 alkylene,

[0112] (iii) C2-8 alkenylene or

[0113] (iv) C2-8 alkynylene,

[0114] A2 is

[0115] (i) —O—,

[0116] (ii) —NR3—

[0117] (iii) —C(O)—,

[0118] (iv) —CH(OH)—,

[0119] (v) —C(O)NR4—,

[0120] (vi) —NR11C(O)—,

[0121] (vii) —C(O)O—,

[0122] (viii) —OC(O)—,

[0123] (ix) —SO2NR6—,

[0124] (x) —NR7SO2—,

[0125] (xi) —C(O)NR9O—,

[0126] (xii) —OC(O)NR10—,

[0127] (xiii) —NR11C(O)NR12—,

[0128] (xiv) —NR13C(O)O— or

[0129] (xv) —OC(O)O—

[0130] (wherein R3, R4, R5, R6 R7, R9, R10, R11, R12 and R13 are each independently, hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted with Cyc1, —OR14 (wherein R14 is hydrogen or C1-8 alkyl.) or cyano, with the proviso that the linkage of the right side of each group represented by A2 binds to A3.

[0131] A3 is

[0132] (i) hydrogen,

[0133] (ii) C1-8 alkyl,

[0134] (iii) C2-8 alkenyl,

[0135] (iv) C2-8 alkynyl,

[0136] (v) Cyc1 or

[0137] (vi) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with 1-3 groups selected from the following (a)-(i):

[0138] (a) halogen,

[0139] (b) cyano,

[0140] (c) —P(O)(R15)2,

[0141] (d) —Si(R16)3,

[0142] (e) Cyc1,

[0143] (f) —C(O)R17,

[0144] (g) —OR18,

[0145] (h) —NR19R20,

[0146] (i) —SR21;

[0147] plural R15s are each independently, hydroxy or C1-8 alkoxy,

[0148] plural R16s are each independently C1-8 alkyl,

[0149] R17 is

[0150] (i) hydrogen,

[0151] (ii) C1-8 alkyl,

[0152] (iii) hydroxy,

[0153] (iv) C1-8 alkoxy,

[0154] (v) Cyc1 or

[0155] (vi) —NR22R23 (wherein R22 is hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted with phenyl, R23 is hydrogen, C1-8 alkyl, Cyc1 or C1-8 alkyl substituted with Cyc1 or NR24R25 (R24 and R25 are each independently hydrogen, C1-8 alkyl, phenyl, C1-8 alkyl substituted with phenyl.).),

[0156] R18 is

[0157] (i) hydrogen,

[0158] (ii) C1 -8 alkyl,

[0159] (iii) C2-8 alkenyl,

[0160] (iv) Cyc1 or

[0161] (v) C1-8 alkyl substituted with Cyc′, Si(R26)3 (wherein plural R27 are each independently C1-8 alkyl.) or —OR27 (wherein R27 is hydrogen, C1-8 alkyl or C2-5 acyl.),

[0162] R19 is

[0163] (i) hydrogen,

[0164] (ii) C1-8 alkyl,

[0165] (iii) phenyl or

[0166] (iv) C1-8 alkyl substituted with phenyl,

[0167] R20 is

[0168] (i) hydrogen,

[0169] (ii) C1-8 alkyl or

[0170] (iii) —C(O)R28 (wherein R28 is C1-8 alkyl, C1-8 alkoxy, Cyc1 or NR29R30 (wherein R29 and R30 are each independently, hydrogen or C1-8 alkyl.).),

[0171] (iv) Cyc1 or

[0172] (v) C1-8 alkyl substituted with Cyc1 or cyano,

[0173] R21 is

[0174] (i) hydrogen,

[0175] (ii) C1-8 alkyl or

[0176] (iii) Cyc1,

[0177] Cyc1 is

[0178] (i) C3-15 mono-, bi- or tricyclic carbo ring or

[0179] (ii) 4-18 membered mono-, bi- or tricyclic hetero ring containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom, the said carbocyclic ring or heterocyclic ring may be substituted with one or more of (i) C1-8 alkyl, (ii) C2-8 alkenyl, (iii) C2-8 alkynyl, (iv) oxo, (v) cyano, (vi) nitro, (vii) trihalomethyl, (viii) trihalomethoxy, (ix) halogen, (x) diphenylmethyl, (xi) triphenylmethyl, (xii) Cyc2, (xiii) —OR3, (xiv) —SR32, (xv) —NR33R34, (xvi) —SO2NR35 R36 (xvii) —C(O)R37 or (xviii) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with Cyc2, hydroxy, halogen or —C(O)—Cyc2,

[0180] R31 and R32 are each independently, hydrogen, C1-8 alkyl or Cyc2,

[0181] R33 is hydrogen or C1-8 alkyl,

[0182] R34 is hydrogen, C1-8 alkyl or —C(O)-Cyc2,

[0183] R37 is hydrogen or C1-8 alkyl, R36 is hydrogen, C1-8 alkyl or Cyc2,

[0184] R37 is hydrogen, C1-8 alkyl, —OR38, —NR39R40, Cyc2, or C1-8 alkyl substituted with Cyc2 or —C(O)-Cyc2,

[0185] R38, R39 and R40 are each independently, hydrogen, C1-8 alkyl, or C1-8 alkyl substituted with Cyc2,

[0186] Cyc2 is

[0187] (i) C3-15 mono-, bi- or tricyclic carbo ring or

[0188] (ii) 4-18 membered mono-, bi- or tricyclic hetero ring containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom,

[0189] the said carbocyclic ring or heterocyclic ring may be substituted with one or more of (i) C1-8 alkyl, (ii) C2-8 alkenyl, (iii) C2-8 alkynyl, (iv) oxo, (v) cyano, (vi) nitro, (vii) trihalomethyl, (viii) trihalomethoxy, (ix) halogen, (x) —OR41, (xi) —SR42, (xii) —NR43R44, (xiii) —SO2NR45R46, (xiv) —C(O)R47, (xv) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with hydroxy or halogen or (xvi) phenyl,

[0190] R41, R42, R43, R44, R45 and R46 are each independently, hydrogen or C1-8 alkyl,

[0191] R47 is hydrogen, C1-8 alkyl or C1-8 alkoxy

[0192] each R2 of (R2)q is independently,

[0193] (i) C1-8 alkyl,

[0194] (ii) C2-8 alkenyl,

[0195] (iii) C2-8 alkynyl,

[0196] (iv) —OR48

[0197] (v) —NR49R50,

[0198] (vi) —C(O)R51,

[0199] (vii) nitro,

[0200] (viii) cyano,

[0201] (ix) halogen or

[0202] (x) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with —OR48, —NR49R50, —C(O)R51, halogen or Cyc3,

[0203] R48 is

[0204] (i) hydrogen,

[0205] (ii) C1-8 alkyl,

[0206] (iii) C2-8 alkenyl,

[0207] (iv) C2-8 alkynyl,

[0208] (v) Cyc3 or

[0209] (vi) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with halogen, —OR52, —NR53R54, —C(O)R55 or Cyc3,

[0210] R49 and R50 are each independently, hydrogen, C1-8 alkyl or —COR59,

[0211] R51 is hydrogen, C1-8 alkyl, hydroxy, C1-8 alkoxy or —NR50R61,

[0212] R52 is hydrogen, C1-8 alkyl, Cyc3, or C1-8 alkyl substituted with Cyc3,

[0213] —R53 and R54 are each independently, hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl or —C(O)R56 (wherein R56 is C1-8 alkyl, C1-8 alkoxy, Cyc3, or C1-8 alkyl substituted with Cyc3),

[0214] R55 is hydroxy, C1-8 alkoxy, or —NR57R58 (wherein R57 and R58 are each independently, hydrogen, C1-8 alkyl, or C1-8 alkyl substituted with Cyc3),

[0215] R59 is C1-8 alkyl or C1-8 alkoxy,

[0216] R60 and R61 are each independently, hydrogen or C1-8 alkyl,

[0217] Cyc3 is

[0218] (i) C3-15 mono-, bi- or tricyclic carbo ring or

[0219] (ii) 4-18 membered mono-, bi- or tricyclic hetero ring containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom,

[0220] the said carbocyclic ring or heterocyclic ring may be substituted with one or more of (i) C1-8 alkyl, (ii) C1-8 alkoxy, (iii) nitro, (iv) halogen, (v) cyano, (vi) hydroxy, (vii) benzyloxy, (viii) —NR62R63, (ix) —COOR64, (x) trihalomethyl, (xi) trihalomethoxy, (xii) phenyl, (xiii) phenoxy, (xiv) phenylthio, (xv) C1-8 alkyl or C1-8 alkoxy substituted with phenyl, phenoxy, phenylthio, hydroxy, —NR62R63 or —COOR64,

[0221] R62 and R63 are each independently, hydrogen or C1-8 alkyl,

[0222] R64 is hydrogen or C1-8 alkyl,

[0223] with the proviso that when A2 is (vi) —NR5C(O)—, (x) —NR7SO2—, (xiv) —NR13C(O)O— or (xv) —OC(O)O—, then A3 is not hydrogen.],

[0224] an N-oxide derivative thereof or a non-toxic salt thereof,

[0225] (2) a fused thiophene derivative of the formula (IA) 21

[0226] [wherein is a single or double bond,

[0227] Y is (i) 22

[0228] or

[0229] (ii) hydrogen

[0230] (with a proviso that when is a double bond, Y is hydrogen, and when is a single bond, Y is 23

[0231] m and n are each independently 0 or an integer of 1-2,

[0232] p is 0 or an integer of 1-4,

[0233] q is 0 or an integer of 1-5,

[0234] Z is single bond, C1-8 alkylene, C2-8 alkenylene or C2-8 alkynylene, 24

[0235] is

[0236] (i) benzene ring or

[0237] (ii) 6-membered monocyclic hetero aryl containing 1-2 nitrogen atom(s), 25

[0238] is

[0239] (i) C3-15 mono-, bi- or tricyclic carbo ring or

[0240] (ii) 4-18 membered mono-, bi- or tricyclic hetero ring containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom,

[0241] each R1 of (R1)p is independently,

[0242] (i) C1-8 alkyl,

[0243] (ii) C2-8 alkenyl,

[0244] (iii) C2-8 alkynyl,

[0245] (iv) nitro,

[0246] (v) cyano,

[0247] (vi) halogen,

[0248] (vii) Cyc1,

[0249] (viii) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with halogen or Cyc1 or

[0250] (ix) —A1—A2—A3,

[0251] A1 is

[0252] (i) single bond,

[0253] (ii) C1-8 alkylene,

[0254] (iii) C2-8 alkenylene or

[0255] (iv) C2-8 alkynylene,

[0256] A 2 is

[0257] (i) —O—,

[0258] (ii) —NR3—

[0259] (iii) —C(O)—,

[0260] (iv) —CH(OH)—,

[0261] (v) —C(O)NR4—,

[0262] (vi) —NR5C(O)—,

[0263] (vii) —C(O)O—,

[0264] (viii) —OC(O)—,

[0265] (ix) —SO2NR6,

[0266] (x) —NR7SO2—,

[0267] (xi) —C(O)NR9O—,

[0268] (xii) —OC(O)NR10—,

[0269] (xiii) —NR11C(O)NR12—,

[0270] (xiv) —NR13C(O)O— or

[0271] (xv) —OC(O)O—

[0272] (wherein R3, R4, R5, R6, R7, R9, R10, R11, R12 and R13 are each independently, hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted with Cyc1, —OR14 (wherein R14 is hydrogen or C1-8 alkyl.) or cyano, with the proviso that the linkage of the right side of each group represented by A2 binds to A3.

[0273] A3 is

[0274] (i) hydrogen,

[0275] (ii) C1-8 alkyl,

[0276] (iii) C2-8 alkenyl,

[0277] (iv) C2-8 alkynyl,

[0278] (v) Cyc1 or

[0279] (vi) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with 1-3 groups selected from the following (a)-(i):

[0280] (a) halogen,

[0281] (b) cyano,

[0282] (c) —P(O)(R15)2,

[0283] (d) —Si(R16)3,

[0284] (e) Cyc1,

[0285] (f) —C(O)R17,

[0286] (g) —OR18,

[0287] (h) —NR19R20,

[0288] (i) —SR21;

[0289] plural R15s are each independently, hydroxy or C1-8 alkoxy,

[0290] plural R16s are each independently C1-8 alkyl,

[0291] R17 is

[0292] (i) hydrogen,

[0293] (ii) C1-8 alkyl,

[0294] (iii) hydroxy,

[0295] (iv) C1-8 alkoxy,

[0296] (v) Cyc1 or

[0297] (vi) —NR22R23 (wherein R22 is hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted with phenyl, R23 is hydrogen, C1-8 alkyl, Cyc1 or C1-8 alkyl substituted with Cyc1 or NR24R25 (R24 and R25 are each independently hydrogen, C1-8 alkyl, phenyl, C1-8 alkyl substituted with phenyl.).),

[0298] R18 is

[0299] (i) hydrogen,

[0300] (ii) C1-8 alkyl,

[0301] (iii) C2-8 alkenyl,

[0302] (iv) Cyc1 or

[0303] (v) C1-8 alkyl substituted with Cyc1, Si(R26)3 (wherein plural R26s are each independently C1-8 alkyl.) or —OR27 (wherein R27 is hydrogen, C1-8 alkyl or C2-5 acyl.),

[0304] R19 is

[0305] (i) hydrogen,

[0306] (ii) C1-8 alkyl,

[0307] (iii) phenyl or

[0308] (iv) C1-8 alkyl substituted with phenyl,

[0309] R20 is

[0310] (i) hydrogen,

[0311] (ii) C1-8 alkyl or

[0312] (iii) —C(O)R28 (wherein R28 is C1-8 alkyl, C1-8 alkoxy, Cyc1 or NR29R30 (wherein R29 and R30 are each independently, hydrogen or C1-8 alkyl.).),

[0313] (iv) Cyc1 or

[0314] (v) C1-8 alkyl substituted with Cyc1 or cyano,

[0315] R21 is

[0316] (i) hydrogen,

[0317] (ii) C1-8 alkyl or

[0318] (iii) Cyc1,

[0319] Cyc1 is

[0320] (i) C3-15 mono-, bi- or tricyclic carbo ring or

[0321] (ii) 4-18 membered mono-, bi- or tricyclic hetero ring containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom,

[0322] the said carbocyclic ring or heterocyclic ring may be substituted with one or more of (i) C1-8 alkyl, (ii) C2-8 alkenyl, (iii) C2-8 alkynyl, (iv) oxo, (v) cyano, (vi) nitro, (vii) trihalomethyl, (viii) trihalomethoxy, (ix) halogen, (x) diphenylmethyl, (xi) triphenylmethyl, (xii) Cyc2, (xiii) —OR31, (xiv) —SR2, (xv) —NR33R34, (xvi) —SO2NR35R36, (xvii) —C(O)R37 or (xviii) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with Cyc2, hydroxy, halogen or —C(O)-Cyc2,

[0323] R31 and R32 are each independently, hydrogen, C1-8 alkyl or Cyc2,

[0324] R33 is hydrogen or C1-8 alkyl,

[0325] R34 is hydrogen, C1-8 alkyl or —C(O)-Cyc2,

[0326] R36 is hydrogen or C1-8 alkyl,

[0327] R36 is hydrogen, C1-8 alkyl or Cyc2,

[0328] R37 is hydrogen, C1-8 alkyl, —OR38, —NR39R40, Cyc2, or C1-8 alkyl substituted with Cyc2 or —C(O)—Cyc2,

[0329] R36, R39 and R40 are each independently, hydrogen, C1-8 alkyl, or C1-8 alkyl substituted with Cyc2,

[0330] Cyc2 is

[0331] (i) C3-15 mono-, bi- or tricyclic carbo ring or

[0332] (ii) 4-18 membered mono-, bi- or tricyclic hetero ring containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom,

[0333] the said carbocyclic ring or heterocyclic ring may be substituted with one or more of (i) C1-8 alkyl, (ii) C2-8 alkenyl, (iii) C2-8 alkynyl, (iv) oxo, (v) cyano, (vi) nitro, (vii) trihalomethyl, (viii) trihalomethoxy, (ix) halogen, (x) —OR41, (xi) —SR42, (xii) —NR43R44, (xiii) —SO2NR45R46, (xiv) —C(O)R47, (xv) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with hydroxy or halogen or (xvi) phenyl,

[0334] R41, R42, R43, R44, R45 and R46 are each independently, hydrogen or C1-8 alkyl, R47 is hydrogen, C1-8 alkyl or C1-8 alkoxy

[0335] each R2 of (R2q is independently,

[0336] (i) C1-8 alkyl,

[0337] (ii) C2-8 alkenyl,

[0338] (iii) C2-8 alkynyl,

[0339] (iv) —OR48,

[0340] (v) —NR49R50,

[0341] (vi) —C(O)R51,

[0342] (vii) nitro,

[0343] (viii) cyano,

[0344] (ix) halogen or

[0345] (x) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with —OR48, -NR49R50, —C(O)R51, halogen or Cyc3,

[0346] R48 is

[0347] (i) hydrogen,

[0348] (ii) C1-8 alkyl,

[0349] (iii) C2-8 alkenyl,

[0350] (iv) C2-8 alkynyl,

[0351] (v) Cyc3 or

[0352] (vi) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with halogen, —OR52, —

[0353] NR53R54, —C(O)R55 or Cyc3,

[0354] R49 and R51 are each independently, hydrogen, C1-8 alkyl or —COR59,

[0355] R51 is hydrogen, C1-8 alkyl, hydroxy, C1-8 alkoxy or —NR6“R6,

[0356] R52 is hydrogen, C1-8 alkyl, Cyc3, or C1-8 alkyl substituted with Cyc3,

[0357] R53 and R54 are each independently, hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl or —C(O)R56 (wherein R56 is C1-8 alkyl, C1-8 alkoxy, Cyc3, or C1-8 alkyl substituted with Cyc3),

[0358] R55 is hydroxy, C1-8 alkoxy, or —NR57R58 (wherein R57 and R58 are each independently, hydrogen, C1-8 alkyl, or C1-8 alkyl substituted with Cyc3),

[0359] R59 is C1-8 alkyl or C1-8 alkoxy,

[0360] R60 and R61 are each independently, hydrogen or C1-8 alkyl,

[0361] Cyc3 is

[0362] (i) C3-15 mono-, bi- or tricyclic carbo ring or

[0363] (ii) 4-18 membered mono-, bi- or tricyclic hetero ring containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom,

[0364] the said carbocyclic ring or heterocyclic ring may be substituted with one or more of (i) C1-8 alkyl, (ii) C1-8 alkoxy, (iii) nitro, (iv) halogen, (v) cyano, (vi) hydroxy, (vii) benzyloxy, (viii) —NR62R63, (ix) —COOR64, (x) trihalomethyl, (xi) trihalomethoxy, (xii) phenyl, (xiii) phenoxy, (xiv) phenylthio, (xv) C1-8 alkyl or C1-8 alkoxy substituted with phenyl, phenoxy, phenylthio, hydroxy, —NR62R63 or —COOR64,

[0365] R62 and R63 are each independently, hydrogen or C1-8 alkyl,

[0366] R64 is hydrogen or C1-8 alkyl,

[0367] with the proviso that when

[0368] (1) when A2 is (vi) —NR5C(O)—, (x) —NR7SO2—, (xiv) —NR13C(O)O— or (xv) —OC(O)O—,

[0369] then A3 is not hydrogen,

[0370] (2) when is a double bond and Y is hydrogen, then n is 1 or 2,

[0371] (3) when is a single bond, Y is 26

[0372] n is 2,

[0373] m is 0 or 2, p is O or an integer of 1-4, ring A and ring B are benzene ring, R1 is C1-8 alkyl, C1-8 alkoxy, halogen, carboxy, nitro or C1-8 alkyl substituted with halogen, then q is not 0,

[0374] (4) when is a single bond, Y is 27

[0375] n is 2,

[0376] m is 0 or 2, p is 0 or an integer of 1-4, ring A and ring B are benzene ring, R1 is C1-8 alkyl, C1-8 alkoxy, halogen, carboxy, nitro or C1-8 alkyl substituted with halogen, and q is an integer of 1-5, then R2 is not C1-8 alkyl, C1-8 alkoxy, halogen, carboxy, nitro or C1-8 alkyl substituted with halogen,

[0377] (5) when is a double bond, Y is hydrogen, n is 2, p is 1 and ring A is benzene ring, then R1 is not halogen, C1-8 alkyl, phenylsulfonylamino, 2-methylphenylsulfonylamino, 3-methylphenylsulfonylamino, 4-methylphenylsulfonylamino, hydroxy, C1-8 alkoxy, nitro, or C1-8 alkoxy substituted with carboxy, hydroxy, C1-8 alkoxycarbonyl or hydroxyaminocarbonyl,

[0378] (6) when is a double bond, Y is hydrogen, n is 2, p is 2 and ring A is benzene ring and one R1 is phenylsulfonylamino, 2-methylphenyisulfonylamino, 3-methylphenylsulfonylamino or 4-methylphenylsulfonylamino, then the other R1 is not C1-8 alkyl,

[0379] (7) when is a double bond, Y is hydrogen, n is 2, p is 2-3, ring A is benzene ring, one R1 is hydroxy, C1-8 alkoxy, or C1-8 alkoxy substituted with carboxy, hydroxy, C1-8 alkoxycarbonyl or hydroxyaminocarbonyl, then the other R1 is neither halogen nor C1-8 alkyl,

[0380] (8) when is a double bond, Y is hydrogen, n is 2, p is 3-4 and ring A is benzene ring, then two or three R1 are not t-butyl at the same time, and

[0381] (9) the following compounds (1)-(32) are excluded:

[0382] (1) 3-(thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,

[0383] (2) 6-nitro-3-(thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene,

[0384] (3) 3-(thiophen-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[blthiophene,

[0385] (4) 4,5-dimethyl-1,1-dioxidebenzo[b]thiophene,

[0386] (5) 4,6-dimethyl-1,1-dioxidebenzo[b]thiophene,

[0387] (6) 4,7-dimethyl-1,1-dioxidebenzo[b]thiophene,

[0388] (7) 5,6-dimethyl-1,1-dioxidebenzo[b]thiophene,

[0389] (8) 5,7-dimethyl-1,1-dioxidebenzo[b[thiophene,

[0390] (9) 6,7-dimethyl-1,1-dioxidebenzo[b]thiophene,

[0391] (10) 4-carboxymethyl-1,1-dioxidebenzo[b]thiophene,

[0392] (11) 6-(2,2-bis(ethoxycarbonyl)ethenyl)amino-1,1-ioxidebenzo[b]thiophene,

[0393] (12) 4-methylaminocarbonyloxy-1,1-dioxidebenzo[b]thiophene,

[0394] (13) 5-(2-(N-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-N-methylamino)ethyl)-1,1-dioxidebenzo[b]thiophene,

[0395] (14) 5-(2-hydroxyethyl)-1,1-dioxidebenzo[b]thiophene,

[0396] (15) 5-bromo-7-methyl-1,1-dioxidebenzo[b]thiophene,

[0397] (16) 7-bromo-5-methyl-1,1-dioxidebenzo[b]thiophene,

[0398] (17) 5-bromo-6-methyl-1,1-dioxidebenzo[b]thiophene,

[0399] (18) 5-bromo-4-methyl-1,1-dioxidebenzo[b]thiophene,

[0400] (19) 6-bromo-5-methyl-1,1-dioxidebenzo[b]thiophene,

[0401] (20) 4-bromo-5-methyl-1, -dioxidebenzo[b]thiophene,

[0402] (21) 6-amino-1,1-dioxidebenzo[b]thiophene,

[0403] (22) 6-acetylamino-1,1-dioxidebenzo[b]thiophene,

[0404] (23) 6-(4-diethylaminophenyl)-1,1-dioxidebenzo[b]thiophene,

[0405] (24) 1,1-dioxidethieno[2,3-b]pyridine,

[0406] (25) 1,1 -dioxidethieno[3,2-b]pyridine,

[0407] (26) 1,1-dioxidethieno[2,3-c]pyridine,

[0408] (27) 5-amino-1,1-dioxidebenzo[b]thiophene,

[0409] (28) 5-(3-methyl-5-oxo-4,5-dihydropyrazol-1-yl)-1,1-dioxidebenzo[b]thiophene,

[0410] (29) 4-(2-(1,1-dioxidebenzo[b]thiophen-3-yl)ethyl)-1,1-dioxidebenzo[b]thiophene,

[0411] (30) 7-methyl-1,1-dioxidethieno[2,3-c]pyridine,

[0412] (31) 1,1-dioxidebenzo[b]thiophene or

[0413] (32) 4-(4-methoxyphenyl)-1,1-dioxidethieno[3,2-c]pyridine.],

[0414] an N-oxide derivative thereof or a non-toxic salt thereof,

[0415] (3) a method for preparation of a fused thiophene derivative of the formula (IA), an N-oxide derivative thereof or a non-toxic salt thereof and

[0416] (4) a method for preparation of a compound of the formula (XI) 28

[0417] which is characterized by cyanization of a compound of the formula (XII) 29

[0418] to obtain a compound of the formula (XIII) 30

[0419] then by subjecting to dehydration of the said compound of the formula (XII) to obtain a compound of the formula (XIV) 31

[0420] and then by subjecting to hydrolysis of the said compound of the formula (XIV).

DETAILED EXPLANATION OF THE INVENTION

[0421] Unless otherwise specified, all isomers are included in the present invention. For example, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylene, alkenylene and alkynylene group include straight or branched ones. In addition, isomers on double bond, ring, fused ring (E—, Z—, cis-, trans-isomer), isomers generated from asymmetric carbon atom(s) (R—, S—, α—, β-isomer, enantiomer, diastereomer), optically active isomers (D—, L—, d-, I-isomer), polar compounds generated by chromatographic separation (more polar compound, less polar compound), equilibrium compounds, mixtures thereof at voluntary ratios and racemic mixtures are also included in the present invention.

[0422] In the present invention, an N-oxide derivative of a compound of the formula (I) and (IA) means a compound wherein nitrogen atom(s) in a compound containing nitrogen atom(s) of the formula (I) and (IA) is (are) oxidized.

[0423] In the present invention, C1-8 alkyl means methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl and the isomers thereof.

[0424] C2-8 alkenyl means vinyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, butadienyl, pentadienyl, hexadienyl, heptadienyl, octadienyl, hexatrienyl, heptatrienyl, octatrienyl and the isomers thereof.

[0425] C2-8 alkynyl means ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl and the isomers thereof.

[0426] C1-8 alkylene means methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, heptamethylene, octamethylene and the isomers thereof.

[0427] C2-8 alkenylene means ethenylene, propenylene, butenylene, pentenylene, hexenylene, heptenylene, octenylene and the isomers thereof.

[0428] C2-8 alkynylene means ethynylene, propynylene, butynylene, pentynylene, hexynylene, heptynylene, octynylene and the isomers thereof.

[0429] Halogen means chloride, bromide, fluoride and iodide.

[0430] C1-8 alkoxy means methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy and the isomers thereof.

[0431] Trihalomethyl means methyl substituted with three atoms selected from group consisting of chloride, bromide, fluoride and iodide atom.

[0432] Trihalomethoxyl means methoxyl substituted with three atoms selected from group consisting of chloride, bromide, fluoride and iodide atom.

[0433] C2-5 acyl means acetyl, propionyl, butyryl, valeryl and isomers thereof.

[0434] 6Membered monocyclic hetero aryl containing 1-2 nitrogen atom(s) includes, for example, pyridine, pyridine-N-oxide, pyrazine, pyrazine-N-monoxide, pyrazine-N-dioxide, pyrimizine, pyrimizine-N-monoxide, pyrimizine-N-dioxide, pyridazine, pyridazine-N-monoxide, pyridazine-N-dioxide ring etc.

[0435] C3-15 Mono-, bi- or tricyclic carbo ring includes, for example, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclopenten, cyclohexen, cyclopentadien, cyclohexadien, benzene, penthalene, indene, naphthalene, azulene, florene, phenanthrene, anthracene, acenaphthylene, biphenylene, perhydropentalene, perhydroindene, dihydronaphthalene, tetrahydronaphthalene, perhydronaphthalene, perhydroazulene, perhydrofluorene, perhydrophenanthrene, perhydroanthracene, perhydroacenaphthylene, perhydrobiphenylene ring etc.

[0436] 4-18 Membered mono-, bi- or tricyclic hetero ring containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom includes 4-18 membered mono-, bi- or tricyclic hetero aryl containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom or corresponding hetero ring in which ring is saturated partially or fully.

[0437] The said 4-18 membered mono-, bi- or tricyclic hetero aryl containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom includes, for example, pyrrole, pyrrole-N-oxide, imidazole, triazole, tetrazole, pyrazole, pyridine, pyridine-N-oxide, pyrazine, pyrazine-N-monoxide, pyrazine-N-dioxide, pyrimizine, pyrimizine-N-monoxide, pyrimizine-N-dioxide, pyridazine, pyridazine-N-monoxide, pyridazine-N-dioxide, azepine, diazepine, furan, pyran, oxepine, oxazepine, thiophene, thiain (thiopyran), thiepine, oxazole, isoxazole, thiazole, isothiazole, oxadiazole, oxazine, oxadiazine, oxazepine, oxadiazepine, thiadiazole, thiazine, thiadiazine, thiazepine, thiadiazepine, indole, isoindole, benzofuran, isobenzofuran, benzothiophene, isobenzothiophene, indazole, quinoline, quinoline-N-oxide, isoquinoline, isoquinoline-N-oxide, phthalazine, naphthyridine, naphthyridine-N-monoxide, naphthyridine-N-dioxide, quinoxaline, quinoxaline-N-monoxide, quinoxaline-N-dioxide, quinazoline, quinazoline-N-monoxide, quinazoline-N-dioxide, cinnoline, benzoxazole, benzothiazole, benzoimidazole, carbazole, acridine ring etc.

[0438] The said 4-18 membered mono-, bi- or tricyclic hetero ring containing 1-4 nitrogen atom(s), 1-2 oxygen atom(s) and/or one sulfur atom in which ring is saturated partially or fully includes, for example, pyrroline, pyrrolidine, pyrrolidine-N-oxide, imidazoline, imidazolidine, triazoline, triazolidine, tetrazoline, tetrazolidine, dihydropyridine, dihydropyridine-N-oxide, dihydropyrazine, dihydropyrazine-N-monoxide, dihydropyrazine-N-dioxide, dihydropyrimizine, dihydropyrimizine-N-monoxide, dihydropyrimizine-N-dioxide, dihydropyridazine, dihydropyridazine-N-monoxide, dihydropyridazine-N-dioxide, piperidine, piperidine-N-oxide, piperazine, piperazine-N-monoxide, piperazine-N-dioxide, tetrahydropyrimizine, tetrahydropyrimizine-N-monoxide, tetrahydropyrimizine-N-dioxide, tetrahydropyridazine, tetrahydropyridazine-N-monoxide, tetrahydropyridazine-N-dioxide, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrothiophene, tetrahydrothiophene, dihydrothiain (dihydrothiopyran), tetrahydrothiain (tetrahydrothiopyran), dihydroxazole, tetrahydroxazole, dihydroisoxazole, tetrahydroisoxazole, dihydrothiazole, tetrahydrothiazole, dihydroisothiazole, tetrahydroisothiazole, morpholine, morpholine-N-oxide, thiomorpholine, thiomorpholine-N-oxide, indoline, isoindoline, dihydrobenzofuran, perhydrobenzofuran, dihydroisobenzofuran, perhydroisobenzofuran, dihydrobenzothiophene, perhydrobenzothiophene, dihydroisobenzothiophene, perhydroisobenzothiophene, dihydroindazole, perhydroindazole, dihydroquinoline, dihydroquinoline-N-oxide, tetrahydroquinoline, tetrahydroquinoline-N-oxide, perhydroquinoline, perhydroquinoline-N-oxide, dihydroisoquinoline, dihydroisoquinoline-N-oxide, tetrahydroisoquinoline, tetrahydroisoquinoline-N-oxide, perhydroisoquinoline, perhydroisoquinoline-N-oxide, dihydrophthalazine, tetrahydrophthalazine, perhydrophthalazine, dihydronaphthyridine, dihydronaphthyridine-N-monoxide, dihydronaphthyridine-N-dioxide, tetrahydronaphthyridine, tetrahydronaphthyridine-N-monoxi de, tetrahydronaphthyridine-N-dioxide, perhydronaphthyridine, perhydronaphthyridine-N-monoxide, perhydronaphthyridine-N-dioxide, dihydroquinoxaline, dihydroquinoxaline-N-monoxide, dihydroquinoxaline-N-dioxide, tetrahydroquinoxaline, tetrahydroquinoxaline-N-monoxide, tetrahydroquinoxaline-N-dioxide, perhydroquinoxaline, perhydroquinoxaline-N-monoxide, perhydroquinoxaline-N-dioxide, dihydroquinazoline, dihydroquinazoline-N-monoxide, dihydroquinazoline-N-dioxide, tetrahydroquinazoline, tetrahydroquinazoline-N-monoxide, tetrahydroquinazoline-N-dioxide, perhydroquinazoline, perhydroquinazoline-N-monoxide, perhydroquinazoline-N-dioxide, dihydrocinnoline, tetrahydrocinnoline, perhydrocinnoline, dihydrobenzoxazole, perhydrobenzoxazole, dihydrobenzothiazole, perhydrobenzothiazole, dihydrobenzoimidazole, perhydrobenzoimidazole, benzoxazepine, benzoxadiazepine, benzothiazepine, benzothiadiazepine, benzoazepine, benzodiazepine, indroxoazepine, indrotetrahydroxazepine, indroxadiazepine, indrotetrahydroxadiazepine, indrothiazepine, indrotetrahydrothiazepine, indrothiadiazepine, indrotetrahydrothiadiazepine, indroazepine, indrotetrahydroazepine, indrodiazepine, indrotetrahydrodiazepine, benzofurazane, benzothiadiazole, benzotriazole, camphar, imidazothiazole, dihydrocarbazole, tetrahydrocarbazole, perhydrocarbazole, dihydroacridine, tetrahydroacridine, perhydroacridine, 1,3-dioxaindan, 1,4-dioxoindan ring etc.

[0439] In the present invention, m is, preferably, 0 or 2 and most preferably, 2.

[0440] n is, preferably, 0 or 2 and most preferably, 2.

[0441] p is, preferably, 1 or 2 and most preferably, 2.

[0442] q is, preferably, 0 or 1.

[0443] Z is, preferably, single bond or C1-8 alkylene, and most preferably, single bond. 32

[0444] is, preferably, pyridine or benzene ring, and most preferably, benzene ring. 33

[0445] is, preferably, C5-10 mono- or bicyclic carbo ring or 5-10 membered mono- or bicyclic hetero ring containing 1-3 nitrogen atom(s), one oxygen atom and/or one sulfur atom, more preferably, benzene, cyclohexane, thiophene, furan, pyridine, pyrimizine, imidazole ring, and most preferably, benzene or thiophene ring.

[0446] R1 is, preferably, C1-8 alkyl, nitro, cyano, halogen, Cyc1 or C1-8 alkyl substituted with halogen or Cyc1, or A1—A2—A3, and most preferably, C1-8 alkyl substituted with Cyc1 or A1—A2—A3.

[0447] A1 is, preferably, single bond, C1-8 alkylene, C2-8 alkenylene, and most preferably, single bond or C1-8 alkylene.

[0448] A2 is, preferably, —O—, —NR3—, —C(O)—, —C(O)NR4—, —NR5C(O)—, —C(O)O—, —NR13C(O)O—, and most preferably, O—, —NR3—, —C(O)—, —C(O)NR4—, —NR5C(O)—.

[0449] A3 is, preferably, C1-8 alkyl, Cyc1, or C1-8 alkyl or C2-8 alkenyl substituted with Cyc1, —C(O)R 7, —NR19R20 or —OR18, and most preferably, C1-8 alkyl substituted with Cyc1 or NR19R20.

[0450] Cyc1 is, preferably, C5-10 mono- or bicyclic carbo ring or 5-10 membered mono- or bicyclic hetero ring containing 1-3 nitrogen atom(s), one oxygen atom and/or one sulfur atom, and more preferably, C5-10 monocyclic carbo ring or 5-10 membered monocyclic hetero ring containing 1-2 nitrogen atom(s) and/or one oxygen atom, and most preferably, benzene, piperidine, piperazine, pyrrolidine, pyridine or morpholine ring.

[0451] R19, R20 is, preferably, hydrogen or C1-8 alkyl, and most preferably, methyl, ethyl, propyl or isopropyl.

[0452] [Salts]

[0453] In the present invention, non-toxic salts include all such salts, for example, ordinal salts, acid-addition salts and hydrate salts.

[0454] The compounds of the present invention of the formula (I) may be converted into the corresponding salts by known method. Non toxic and water-soluble salts are preferable. Suitable salts include the salts of alkalimetal (sodium, potassium etc.), alkaline-earth metal (calcium, magnesium etc.), ammonium salts, salts of organic amine which is pharmaceutically permitted (tetramethyl ammonium, triethylamine, methylamine, dimethylamine, cyclopentylamine, benzylamine, phenetylamine, piperidine, monoethanolamine, diethanolamine, tris(hydroxymethyl)amine, lysine, arginine, N-methyl-D-gulcamine etc.).

[0455] The compounds of the present invention of the formula (I) may be converted into the corresponding acid-addition salts by known method. Non toxic and water-soluble acid-addition are preferable. Suitable acid-addition salts include the salts with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfonic acid, phosphonic acid, nitric acid and the salts with organic acids such as acetic acid, trifluoroacetic acid, lactic acid, tartaric acid, oxalic acid, fumaric acid, maleic acid, citric acid, benzoic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, isethionic acid, glucuronic acid and gluconic acid.

[0456] The compounds of the present invention of the formula (I) or salts thereof may be converted into a corresponding hydrate by known methods.

[0457] In the compounds of the formula (I), preferred compounds are as follows: the compound of the formula (I-A) 34

[0458] (wherein all the symbols are the same meanings as hereinbefore described.), the compound of the formula (I-B) 35

[0459] (wherein all the symbols are the same meanings as hereinbefore described.), the compound of the formula (I-C) 36

[0460] (wherein all the symbols are the same meanings as hereinbefore described.), the compound of the formula (I-D) 37

[0461] (wherein all the symbols are the same meanings as hereinbefore described.), the compound of the formula (I-E) 38

[0462] (wherein all the symbols are the same meanings as hereinbefore described.), the compound of the formula (I-F) 39

[0463] (wherein all the symbols are the same meanings as hereinbefore described.), the compound of the formula (I-G) 40

[0464] (wherein all the symbols are the same meanings as hereinbefore described.), the compound of the formula (I-H) 41

[0465] (wherein all the symbols are the same meanings as hereinbefore described.), the compound of the formula (I-J) 42

[0466] (wherein all the symbols are the same meanings as hereinbefore described.), the compound of the formula (I-K) 43

[0467] (wherein all the symbols are the same meanings as hereinbefore described.), the compound of the formula (I-L) 44

[0468] (wherein all the symbols are the same meanings as hereinbefore described.), the compound of the formula (I-M) 45

[0469] (wherein all the symbols are the same meanings as hereinbefore described.), the compound of the formula (I-N) 46

[0470] (wherein all the symbols are the same meanings as hereinbefore described.), the compound of the formula (I-O) 47

[0471] (wherein all the symbols are the same meanings as hereinbefore described.), or the compound of the formula (I-P) 48

[0472] (wherein all the symbols are the same meanings as hereinbefore described.).

[0473] In the compounds of the formula (I-A), the compound of the formula (I-A′) 49

[0474] (wherein, R1′ is C1-8 alkyl substituted with Cyc1, or 50

[0475] (wherein, A1′ is single bond or C1-8 alkylene, A2′ is —O—, —NR3—, —C(O)—, —C(O)NR4— or NR5C(O)— and the other symbols are the same meanings as hereinbefore described.) and the other symbols are the same meanings as hereinbefore described.) is most preferable.

[0476] In the compound of the formula (I-N), the compound of the formula (I-N′) 51

[0477] (wherein all the symbols are the same meanings as hereinbefore described.) is most preferable.

[0478] The following compounds (1)-(4) are known and marketed ones, but their activities as inhibitor of producing IL-6 and/or IL-12 have not been known at all. The compounds (1)-(4) and non-toxic salts thereof are also preferable ones used in the present invention.

[0479] For example,

[0480] Compound (1): 3-(thiophene-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene (Maybridge, Catalog No. KM 08156): 52

[0481] Compound (2): 6-nitro-3-(thiophene-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene (Maybridge, Catalog No. KM 08165): 53

[0482] Compound (3): 3-(thiophene-2-yl)thio-2,3-dihydro-1,1 -dioxidebenzo[b]thiophene (Maybridge, Catalog No. KM 08138): 54

[0483] Compound (4): 3-phenylsulfonyl-2,3-dihydro-11-dioxidebenzo[b]thiophene (Maybridge, Catalog No. KM 08140): 55

[0484] More preferable compounds are the following known compounds and the compounds shown in the Tables 1 to 78 and described in Examples and non-toxic salts thereof.

[0485] In the following tables, 3-Py is pyridin-3-yl, Me is methyl, Et is ethyl, n-Pr is normalpropyl, i-Pr is isopropyl, t-Bu is t-butyl and the other symbols are the same meanings as hereinbefore described.

TABLE 1
	(I-A)
56
No.	p	position	R1	q	position	R2
1	1	4	—O—(CH2)2-(3-Py)	0	—	—
2	1	5	—O—(CH2)2-(3-Py)	0	—	—
3	1	6	—O—(CH2)2-(3-Py)	0	—	—
4	1	7	—O—(CH2)2-(3-Py)	0	—	—
5	1	4	—O—(CH2)2—N(CH3)2	0	—	—
6	1	5	—O—(CH2)2—N(CH3)2	0	—	—
7	1	6	—O—(CH2)2—N(CH3)2	0	—	—
8	1	7	—O—(CH2)2—N(CH3)2	0	—	—
9	0	—	—	1	2′	—O—(CH2)2-(3-Py)
10	0	—	—	1	3′	—O—(CH2)2-(3-Py)
11	0	—	—	1	4′	—O—(CH2)2-(3-Py)
12	0	—	—	2	3′, 5′	—O—(CH2)2-(3-Py)
13	0	—	—	1	2′	—O—(CH2)2—N(CH3)2
14	0	—	—	1	3′	—O—(CH2)2—N(CH3)2
15	0	—	—	1	4′	—O—(CH2)2—N(CH3)2
16	0	—	—	2	3′, 5′	—O—(CH2)2—N(CH3)2
17	1	4	—O—(CH2)2-(3-Py)	1	2′	—O—(CH2)2-(3-Py)
18	1	5	—O—(CH2)2-(3-Py)	1	3′	—O—(CH2)2-(3-Py)
19	1	6	—O—(CH2)2-(3-Py)	1	4′	—O—(CH2)2-(3-Py)
20	1	7	—O—(CH2)2-(3-Py)	2	3′, 5′	—O—(CH2)2-(3-Py)

[0486]

TABLE 2
	(I-B)
57
No.	p	position	R1	q	position	R2
1	1	5	—O—(CH2)2-(3-Py)	0	—	—
2	1	6	—O—(CH2)2-(3-Py)	0	—	—
3	1	7	—O—(CH2)2-(3-Py)	0	—	—
4	2	6, 7	—O—(CH2)2-(3-Py)	0	—	—
5	1	5	—O—(CH2)2—N(CH3)2	0	—	—
6	1	6	—O—(CH2)2—N(CH3)2	0	—	—
7	1	7	—O—(CH2)2—N(CH3)2	0	—	—
8	2	6, 7	—O—(CH2)2—N(CH3)2	0	—	—
9	0	—	—	1	2′	—O—(CH2)2-(3-Py)
10	0	—	—	1	3′	—O—(CH2)2-(3-Py)
11	0	—	—	1	4′	—O—(CH2)2-(3-Py)
12	0	—	—	2	3′, 5′	—O—(CH2)2-(3-Py)
13	0	—	—	1	2′	—O—(CH2)2—N(CH3)2
14	0	—	—	1	3′	—O—(CH2)2—N(CH3)2
15	0	—	—	1	4′	—O—(CH2)2—N(CH3)2
16	0	—	—	2	3′, 5′	—O—(CH2)2—N(CH3)2
17	1	5	—O—(CH2)2-(3-Py)	1	2′	—O—(CH2)2-(3-Py)
18	1	6	—O—(CH2)2-(3-Py)	1	3′	—O—(CH2)2-(3-Py)
19	1	7	—O—(CH2)2-(3-Py)	1	4′	—O—(CH2)2-(3-Py)
20	2	6, 7	—O—(CH2)2-(3-Py)	1	3′	—O—(CH2)2-(3-Py)

[0487]

TABLE 3
	(I-C)
58
No.	p	position	R1	q	position	R2
1	1	4	—O—(CH2)2-(3-Py)	0	—	—
2	1	5	—O—(CH2)2-(3-Py)	0	—	—
3	1	6	—O—(CH2)2-(3-Py)	0	—	—
4	2	4, 5	—O—(CH2)2-(3-Py)	0	—	—
5	1	4	—O—(CH2)2—N(CH3)2	0	—	—
6	1	5	—O—(CH2)2—N(CH3)2	0	—	—
7	1	6	—O—(CH2)2—N(CH3)2	0	—	—
8	2	4, 5	—O—(CH2)2—N(CH3)2	0	—	—
9	0	—	—	1	2′	—O—(CH2)2-(3-Py)
10	0	—	—	1	3′	—O—(CH2)2-(3-Py)
11	0	—	—	1	4′	—O—(CH2)2-(3-Py)
12	0	—	—	2	3′, 5′	—O—(CH2)2-(3-Py)
13	0	—	—	1	2′	—O—(CH2)2—N(CH3)2
14	0	—	—	1	3′	—O—(CH2)2—N(CH3)2
15	0	—	—	1	4′	—O—(CH2)2—N(CH3)2
16	0	—	—	2	3′, 5′	—O—(CH2)2—N(CH3)2
17	1	4	—O—(CH2)2-(3-Py)	1	2′	—O—(CH2)2-(3-Py)
18	1	5	—O—(CH2)2-(3-Py)	1	3′	—O—(CH2)2-(3-Py)
19	1	6	—O—(CH2)2-(3-Py)	1	4′	—O—(CH2)2-(3-Py)
20	2	4, 5	—O—(CH2)2-(3-Py)	1	3′	—O—(CH2)2-(3-Py)

[0488]

TABLE 4
	(I-D)
59
No.	p	position	R1	q	position	R2
1	1	4	—O—(CH2)2-(3-Py)	0	—	—
2	1	5	—O—(CH2)2-(3-Py)	0	—	—
3	1	6	—O—(CH2)2-(3-Py)	0	—	—
4	1	7	—O—(CH2)2-(3-Py)	0	—	—
5	1	4	—O—(CH2)2—N(CH3)2	0	—	—
6	1	5	—O—(CH2)2—N(CH3)2	0	—	—
7	1	6	—O—(CH2)2—N(CH3)2	0	—	—
8	1	7	—O—(CH2)2—N(CH3)2	0	—	—
9	0	—	—	1	3′	—O—(CH2)2-(3-Py)
10	0	—	—	1	4′	—O—(CH2)2-(3-Py)
11	0	—	—	1	5′	—O—(CH2)2-(3-Py)
12	0	—	—	1	6′	—O—(CH2)2-(3-Py)
13	0	—	—	1	3′	—O—(CH2)2—N(CH3)2
14	0	—	—	1	4′	—O—(CH2)2—N(CH3)2
15	0	—	—	1	5′	—O—(CH2)2—N(CH3)2
16	0	—	—	1	6′	—O—(CH2)2—N(CH3)2
17	1	4	—O—(CH2)2-(3-Py)	1	3′	—O—(CH2)2-(3-Py)
18	1	5	—O—(CH2)2-(3-Py)	1	4′	—O—(CH2)2-(3-Py)
19	1	6	—O—(CH2)2-(3-Py)	1	5′	—O—(CH2)2-(3-Py)
20	1	7	—O—(CH2)2-(3-Py)	1	6′	—O—(CH2)2-(3-Py)

[0489]

TABLE 5
	(I-E)
60
No.	p	position	R1	q	position	R2
1	1	4	—O—(CH2)2-(3-Py)	0	—	—
2	1	5	—O—(CH2)2-(3-Py)	0	—	—
3	1	6	—O—(CH2)2-(3-Py)	0	—	—
4	1	7	—O—(CH2)2-(3-Py)	0	—	—
5	1	4	—O—(CH2)2—N(CH3)2	0	—	—
6	1	5	—O—(CH2)2—N(CH3)2	0	—	—
7	1	6	—O—(CH2)2—N(CH3)2	0	—	—
8	1	7	—O—(CH2)2—N(CH3)2	0	—	—
9	0	—	—	1	2′	—O—(CH2)2-(3-Py)
10	0	—	—	1	4′	—O—(CH2)2-(3-Py)
11	0	—	—	1	5′	—O—(CH2)2-(3-Py)
12	0	—	—	1	6′	—O—(CH2)2-(3-Py)
13	0	—	—	1	2′	—O—(CH2)2—N(CH3)2
14	0	—	—	1	4′	—O—(CH2)2—N(CH3)2
15	0	—	—	1	5′	—O—(CH2)2—N(CH3)2
16	0	—	—	1	6′	—O—(CH2)2—N(CH3)2
17	1	4	—O—(CH2)2-(3-Py)	1	2′	—O—(CH2)2-(3-Py)
18	1	5	—O—(CH2)2-(3-Py)	1	4′	—O—(CH2)2-(3-Py)
19	1	6	—O—(CH2)2-(3-Py)	1	5′	—O—(CH2)2-(3-Py)
20	1	7	—O—(CH2)2-(3-Py)	1	6′	—O—(CH2)2-(3-Py)

[0490]

TABLE 6
	(I-F)
61
No.	p	position	R1	q	position	R2
1	1	4	—O—(CH2)2-(3-Py)	0	—	—
2	1	5	—O—(CH2)2-(3-Py)	0	—	—
3	1	6	—O—(CH2)2-(3-Py)	0	—	—
4	1	7	—O—(CH2)2-(3-Py)	0	—	—
5	1	4	—O—(CH2)2—N(CH3)2	0	—	—
6	1	5	—O—(CH2)2—N(CH3)2	0	—	—
7	1	6	—O—(CH2)2—N(CH3)2	0	—	—
8	1	7	—O—(CH2)2—N(CH3)2	0	—	—
9	0	—	—	1	2′	—O—(CH2)2-(3-Py)
10	0	—	—	1	3′	—O—(CH2)2-(3-Py)
11	0	—	—	2	2′, 5′	—O—(CH2)2-(3-Py)
12	0	—	—	2	2′, 6′	—O—(CH2)2-(3-Py)
13	0	—	—	1	2′	—O—(CH2)2—N(CH3)2
14	0	—	—	1	3′	—O—(CH2)2—N(CH3)2
15	0	—	—	2	2′, 5′	—O—(CH2)2—N(CH3)2
16	0	—	—	2	2′, 6′	—O—(CH2)2—N(CH3)2
17	1	4	—O—(CH2)2-(3-Py)	1	2′	—O—(CH2)2-(3-Py)
18	1	5	—O—(CH2)2-(3-Py)	1	3′	—O—(CH2)2-(3-Py)
19	1	6	—O—(CH2)2-(3-Py)	1	2′	—O—(CH2)2-(3-Py)
20	1	7	—O—(CH2)2-(3-Py)	1	3′	—O—(CH2)2-(3-Py)

[0491]

TABLE 7
	(I-G)
62
No.	p	position	R1	q	position	R2
1	1	5	—O—(CH2)2-(3-Py)	0	—	—
2	1	6	—O—(CH2)2-(3-Py)	0	—	—
3	1	7	—O—(CH2)2-(3-Py)	0	—	—
4	2	6, 7	—O—(CH2)2-(3-Py)	0	—	—
5	1	5	—O—(CH2)2—N(CH3)2	0	—	—
6	1	6	—O—(CH2)2—N(CH3)2	0	—	—
7	1	7	—O—(CH2)2—N(CH3)2	0	—	—
8	2	6, 7	—O—(CH2)2—N(CH3)2	0	—	—
9	0	—	—	1	3′	—O—(CH2)2-(3-Py)
10	0	—	—	1	4′	—O—(CH2)2-(3-Py)
11	0	—	—	1	5′	—O—(CH2)2-(3-Py)
12	0	—	—	1	6′	—O—(CH2)2-(3-Py)
13	0	—	—	1	3′	—O—(CH2)2—N(CH3)2
14	0	—	—	1	4′	—O—(CH2)2—N(CH3)2
15	0	—	—	1	5′	—O—(CH2)2—N(CH3)2
16	0	—	—	1	6′	—O—(CH2)2—N(CH3)2
17	1	5	—O—(CH2)2-(3-Py)	1	3′	—O—(CH2)2-(3-Py)
18	1	6	—O—(CH2)2-(3-Py)	1	4′	—O—(CH2)2-(3-Py)
19	1	7	—O—(CH2)2-(3-Py)	1	5′	—O—(CH2)2-(3-Py)
20	2	6, 7	—O—(CH2)2-(3-Py)	1	6′	—O—(CH2)2-(3-Py)

[0492]

TABLE 8
	(I-H)
63
No.	p	position	R1	q	position	R2
1	1	4	—O—(CH2)2-(3-Py)	0	—	—
2	1	5	—O—(CH2)2-(3-Py)	0	—	—
3	1	6	—O—(CH2)2-(3-Py)	0	—	—
4	2	4, 5	—O—(CH2)2-(3-Py)	0	—	—
5	1	4	—O—(CH2)2—N(CH3)2	0	—	—
6	1	5	—O—(CH2)2—N(CH3)2	0	—	—
7	1	6	—O—(CH2)2—N(CH3)2	0	—	—
8	2	4, 5	—O—(CH2)2—N(CH3)2	0	—	—
9	0	—	—	1	3′	—O—(CH2)2-(3-Py)
10	0	—	—	1	4′	—O—(CH2)2-(3-Py)
11	0	—	—	1	5′	—O—(CH2)2-(3-Py)
12	0	—	—	1	6′	—O—(CH2)2-(3-Py)
13	0	—	—	1	3′	—O—(CH2)2—N(CH3)2
14	0	—	—	1	4′	—O—(CH2)2—N(CH3)2
15	0	—	—	1	5′	—O—(CH2)2—N(CH3)2
16	0	—	—	1	6′	—O—(CH2)2—N(CH3)2
17	1	4	—O—(CH2)2-(3-Py)	1	3′	—O—(CH2)2-(3-Py)
18	1	5	—O—(CH2)2-(3-Py)	1	4′	—O—(CH2)2-(3-Py)
19	1	6	—O—(CH2)2-(3-Py)	1	5′	—O—(CH2)2-(3-Py)
20	2	4, 5	—O—(CH2)2-(3-Py)	1	6′	—O—(CH2)2-(3-Py)

[0493]

TABLE 9
	(I-J)
64
No.	p	position	R1	q	position	R2
1	1	5	—O—(CH2)2-(3-Py)	0	—	—
2	1	6	—O—(CH2)2-(3-Py)	0	—	—
3	1	7	—O—(CH2)2-(3-Py)	0	—	—
4	2	6, 7	—O—(CH2)2-(3-Py)	0	—	—
5	1	5	—O—(CH2)2—N(CH3)2	0	—	—
6	1	6	—O—(CH2)2—N(CH3)2	0	—	—
7	1	7	—O—(CH2)2—N(CH3)2	0	—	—
8	2	6, 7	—O—(CH2)2—N(CH3)2	0	—	—
9	0	—	—	1	2′	—O—(CH2)2-(3-Py)
10	0	—	—	1	4′	—O—(CH2)2-(3-Py)
11	0	—	—	1	5′	—O—(CH2)2-(3-Py)
12	0	—	—	1	6′	—O—(CH2)2-(3-Py)
13	0	—	—	1	2′	—O—(CH2)2—N(CH3)2
14	0	—	—	1	4′	—O—(CH2)2—N(CH3)2
15	0	—	—	1	5′	—O—(CH2)2—N(CH3)2
16	0	—	—	1	6′	—O—(CH2)2—N(CH3)2
17	1	5	—O—(CH2)2-(3-Py)	1	2′	—O—(CH2)2-(3-Py)
18	1	6	—O—(CH2)2-(3-Py)	1	4′	—O—(CH2)2-(3-Py)
19	1	7	—O—(CH2)2-(3-Py)	1	5′	—O—(CH2)2-(3-Py)
20	2	6, 7	—O—(CH2)2-(3-Py)	1	6′	—O—(CH2)2-(3-Py)

[0494]

TABLE 10
	(I-K)
65
No.	p	position	R1	q	position	R2
1	1	4	—O—(CH2)2-(3-Py)	0	—	—
2	1	5	—O—(CH2)2-(3-Py)	0	—	—
3	1	6	—O—(CH2)2-(3-Py)	0	—	—
4	2	4, 5	—O—(CH2)2-(3-Py)	0	—	—
5	1	4	—O—(CH2)2—N(CH3)2	0	—	—
6	1	5	—O—(CH2)2—N(CH3)2	0	—	—
7	1	6	—O—(CH2)2—N(CH3)2	0	—	—
8	2	4, 5	—O—(CH2)2—N(CH3)2	0	—	—
9	0	—	—	1	2′	—O—(CH2)2-(3-Py)
10	0	—	—	1	4′	—O—(CH2)2-(3-Py)
11	0	—	—	1	5′	—O—(CH2)2-(3-Py)
12	0	—	—	1	6′	—O—(CH2)2-(3-Py)
13	0	—	—	1	2′	—O—(CH2)2—N(CH3)2
14	0	—	—	1	4′	—O—(CH2)2—N(CH3)2
15	0	—	—	1	5′	—O—(CH2)2—N(CH3)2
16	0	—	—	1	6′	—O—(CH2)2—N(CH3)2
17	1	4	—O—(CH2)2-(3-Py)	1	2′	—O—(CH2)2-(3-Py)
18	1	5	—O—(CH2)2-(3-Py)	1	4′	—O—(CH2)2-(3-Py)
19	1	6	—O—(CH2)2-(3-Py)	1	5′	—O—(CH2)2-(3-Py)
20	2	4, 5	—O—(CH2)2-(3-Py)	1	6′	—O—(CH2)2-(3-Py)

[0495]

TABLE 11
(I-L)
66
No.	p	position	R1	q	position	R2
1	1	5	—O—(CH2)2-(3-Py)	0	—	—
2	1	6	—O—(CH2)2-(3-Py)	0	—	—
3	1	7	—O—(CH2)2-(3-Py)	0	—	—
4	2	6, 7	—O—(CH2)2-(3-Py)	0	—	—
5	1	5	—O—(CH2)2—N(CH3)2	0	—	—
6	1	6	—O—(CH2)2—N(CH3)2	0	—	—
7	1	7	—O—(CH2)2—N(CH3)2	0	—	—
8	2	6, 7	—O—(CH2)2—N(CH3)2	0	—	—
9	0	—	—	1	2′	—O—(CH2)2-(3-Py)
10	0	—	—	1	3′	—O—(CH2)2-(3-Py)
11	0	—	—	2	2′, 3′	—O—(CH2)2-(3-Py)
12	0	—	—	2	2′, 5′	—O—(CH2)2-(3-Py)
13	0	—	—	1	2′	—O—(CH2)2—N(CH3)2
14	0	—	—	1	3′	—O—(CH2)2—N(CH3)2
15	0	—	—	2	2′, 3′	—O—(CH2)2—N(CH3)2
16	0	—	—	2	2′, 5′	—O—(CH2)2—N(CH3)2
17	1	5	—O—(CH2)2-(3-Py)	1	2′	—O—(CH2)2-(3-Py)
18	1	6	—O—(CH2)2-(3-Py)	1	3′	—O—(CH2)2-(3-Py)
19	1	7	—O—(CH2)2-(3-Py)	2	2′, 3′	—O—(CH2)2-(3-Py)
20	2	6, 7	—O—(CH2)2-(3-Py)	2	2′, 5′	—O—(CH2)2-(3-Py)

[0496]

TABLE 12
(I-M)
67
No.	p	position	R1	q	position	R2
1	1	4	—O—(CH2)2-(3-Py)	0	—	—
2	1	5	—O—(CH2)2-(3-Py)	0	—	—
3	1	6	—O—(CH2)2-(3-Py)	0	—	—
4	2	4, 5	—O—(CH2)2-(3-Py)	0	—	—
5	1	4	—O—(CH2)2—N(CH3)2	0	—	—
6	1	5	—O—(CH2)2—N(CH3)2	0	—	—
7	1	6	—O—(CH2)2—N(CH3)2	0	—	—
8	2	4, 5	—O—(CH2)2—N(CH3)2	0	—	—
9	0	—	—	1	2′	—O—(CH2)2-(3-Py)
10	0	—	—	1	3′	—O—(CH2)2-(3-Py)
11	0	—	—	2	2′, 3′	—O—(CH2)2-(3-Py)
12	0	—	—	2	2′, 5′	—O—(CH2)2-(3-Py)
13	0	—	—	1	2′	—O—(CH2)2—N(CH3)2
14	0	—	—	1	3′	—O—(CH2)2—N(CH3)2
15	0	—	—	2	2′, 3′	—O—(CH2)2—N(CH3)2
16	0	—	—	2	2′, 5′	—O—(CH2)2—N(CH3)2
17	1	4	—O—(CH2)2-(3-Py)	1	2′	—O—(CH2)2-(3-Py)
18	1	5	—O—(CH2)2-(3-Py)	1	3′	—O—(CH2)2-(3-Py)
19	1	6	—O—(CH2)2-(3-Py)	2	2′, 3′	—O—(CH2)2-(3-Py)
20	2	4, 5	—O—(CH2)2-(3-Py)	2	2′, 5′	—O—(CH2)2-(3-Py)

[0497]

TABLE 13
(I-A-1)
68
No.	R1	No.	R1
1	69	11	70
2	71	12	72
3	73	13	74
4	75	14	76
5	77	15	78
6	79	16	80
7	81	17	82
8	83	18	84
9	85	19	86
10	87	20	88

[0498]

TABLE 14
(I-A-2)
89
No.	R1	No.	R1
1	90	11	91
2	92	12	93
3	94	13	95
4	96	14	97
5	98	15	99
6	100	16	101
7	102	17	103
8	104	18	105
9	106	19	107
10	108	20	109

[0499]

TABLE 15
(I-A-3)
110
No.	R1	No.	R1
1	111	11	112
2	113	12	114
3	115	13	116
4	117	14	118
5	119	15	120
6	121	16	122
7	123	17	124
8	125	18	126
9	127	19	128
10	129	20	130

[0500]

TABLE 16
(I-A-4)
131
No.	R1	No.	R1
1	132	11	133
2	134	12	135
3	136	13	137
4	138	14	139
5	140	15	141
6	142	16	143
7	144	17	145
8	146	18	147
9	148	19	149
10	150	20	151

[0501]

TABLE 17
(I-B-1)
152
No.	R1	No.	R1
1	153	11	154
2	155	12	156
3	157	13	158
4	159	14	160
5	161	15	162
6	163	16	164
7	165	17	166
8	167	18	168
9	169	19	170
10	171	20	172

[0502]

TABLE 18
(I-B-2)
173
No.	R1	No.	R1
1	174	11	175
2	176	12	177
3	178	13	179
4	180	14	181
5	182	15	183
6	184	16	185
7	186	17	187
8	188	18	189
9	190	19	191
10	192	20	193

[0503]

TABLE 19
(I-B-3)
194
No.	R1	No.	R1
1	195	11	196
2	197	12	198
3	199	13	200
4	201	14	202
5	203	15	204
6	205	16	206
7	207	17	208
8	209	18	210
9	211	19	212
10	213	20	214

[0504]

TABLE 20
(I-C-1)
215
No.	R1	No.	R1
1	216	11	217
2	218	12	219
3	220	13	221
4	222	14	223
5	224	15	225
6	226	16	227
7	228	17	229
8	230	18	231
9	232	19	233
10	234	20	235

[0505]

TABLE 21
    (I-C-2)
236
No. R1
1   237
2   238
3   239
4   240
5   241
6   242
7   243
8   244
9   245
10  246
11  247
12  248
13  249
14  250
15  251
16  252
17  253
18  254
19  255
20  256

[0506]

TABLE 22
    (I-C-3)
257
No. R1
1   258
2   259
3   260
4   261
5   262
6   263
7   264
8   265
9   266
10  267
11  268
12  269
13  270
14  271
15  272
16  273
17  274
18  275
19  276
20  277

[0507]

TABLE 23
    (I-D-1)
278
No. R1
1   279
2   280
3   281
4   282
5   283
6   284
7   285
8   286
9   287
10  288
11  289
12  290
13  291
14  292
15  293
16  294
17  295
18  296
19  297
20  298

[0508]

TABLE 24
    (I-D-2)
299
No. R1
1   300
2   301
3   302
4   303
5   304
6   305
7   306
8   307
9   308
10  309
11  310
12  311
13  312
14  313
15  314
16  315
17  316
18  317
19  318
20  319

[0509]

TABLE 25
    (I-D-3)
320
No. R1
1   321
2   322
3   323
4   324
5   325
6   326
7   327
8   328
9   329
10  330
11  331
12  332
13  333
14  334
15  335
16  336
17  337
18  338
19  339
20  340

[0510]

TABLE 26
    (I-D-4)
341
No. R1
1   342
2   343
3   344
4   345
5   346
6   347
7   348
8   349
9   350
10  351
11  352
12  353
13  354
14  355
15  356
16  357
17  358
18  359
19  360
20  361

[0511]

TABLE 27
    (I-E-1)
362
No. R1
1   363
2   364
3   365
4   366
5   367
6   368
7   369
8   370
9   371
10  372
11  373
12  374
13  375
14  376
15  377
16  378
17  379
18  380
19  381
20  382

[0512]

TABLE 28
    (I-E-2)
383
No. R1
1   384
2   385
3   386
4   387
5   388
6   389
7   390
8   391
9   392
10  393
11  394
12  395
13  396
14  397
15  398
16  399
17  400
18  401
19  402
20  403

[0513]

TABLE 29
    (I-E-3)
404
No. R1
1   405
2   406
3   407
4   408
5   409
6   410
7   411
8   412
9   413
10  414
11  415
12  416
13  417
14  418
15  419
16  420
17  421
18  422
19  423
20  424

[0514]

TABLE 30
    (I-E-4)
425
No. R1
1   426
2   427
3   428
4   429
5   430
6   431
7   432
8   433
9   434
10  435
11  436
12  437
13  438
14  439
15  440
16  441
17  442
18  443
19  444
20  445

[0515]

TABLE 31
446
No. R1
1   447
2   448
3   449
4   450
5   451
6   452
7   453
8   454
9   455
10  456
11  457
12  458
13  459
14  460
15  461
16  462
17  463
18  464
19  465
20  466

[0516]

TABLE 32
467
No. R1
1   468
2   469
3   470
4   471
5   472
6   473
7   474
8   475
9   476
10  477
11  478
12  479
13  480
14  481
15  482
16  483
17  484
18  485
19  486
20  487

[0517]

TABLE 33
488
No. R1
1   489
2   490
3   491
4   492
5   493
6   494
7   495
8   496
9   497
10  498
11  499
12  500
13  501
14  502
15  503
16  504
17  505
18  506
19  507
20  508

[0518]

TABLE 34
509
No. R1
1   510
2   511
3   512
4   513
5   514
6   515
7   516
8   517
9   518
10  519
11  520
12  521
13  522
14  523
15  524
16  525
17  526
18  527
19  528
20  529

[0519]

TABLE 35
530
No. R1
1   531
2   532
3   533
4   534
5   535
6   536
7   537
8   538
9   539
10  540
11  541
12  542
13  543
14  544
15  545
16  546
17  547
18  548
19  549
20  550

[0520]

TABLE 36
551
No. R1
1   552
2   553
3   554
4   555
5   556
6   557
7   558
8   559
9   560
10  561
11  562
12  563
13  564
14  565
15  566
16  567
17  568
18  569
19  570
20  571

[0521]

TABLE 37
572
No. R1
1   573
2   574
3   575
4   576
5   577
6   578
7   579
8   580
9   581
10  582
11  583
12  584
13  585
14  586
15  587
16  588
17  589
18  590
19  591
20  592

[0522]

TABLE 38
593
No. R1
1   594
2   595
3   596
4   597
5   598
6   599
7   600
8   601
9   602
10  603
11  604
12  605
13  606
14  607
15  608
16  609
17  610
18  611
19  612
20  613

[0523]

TABLE 39
614
No. R1
1   615
2   616
3   617
4   618
5   619
6   620
7   621
8   622
9   623
10  624
11  625
12  626
13  627
14  628
15  629
16  630
17  631
18  632
19  633
20  634

[0524]

TABLE 40
635
No. R1
1   636
2   637
3   638
4   639
5   640
6   641
7   642
8   643
9   644
10  645
11  646
12  647
13  648
14  649
15  650
16  651
17  652
18  653
19  654
20  655

[0525]

TABLE 41
656
No. R1
1   657
2   658
3   659
4   660
5   661
6   662
7   663
8   664
9   665
10  666
11  667
12  668
13  669
14  670
15  671
16  672
17  673
18  674
19  675
20  676

[0526]

TABLE 42
677
No. R1
1   678
2   679
3   680
4   681
5   682
6   683
7   684
8   685
9   686
10  687
11  688
12  689
13  690
14  691
15  692
16  693
17  694
18  695
19  696
20  697

[0527]

TABLE 43
698
No. R1
1   699
2   700
3   701
4   702
5   703
6   704
7   705
8   706
9   707
10  708
11  709
12  710
13  711
14  712
15  713
16  714
17  715
18  716
19  717
20  718

[0528]

TABLE 44
719
No. R1
1   720
2   721
3   722
4   723
5   724
6   725
7   726
8   727
9   728
10  729
11  730
12  731
13  732
14  733
15  734
16  735
17  736
18  737
19  738
20  739

[0529]

TABLE 45
740
No. R1
1   741
2   742
3   743
4   744
5   745
6   746
7   747
8   748
9   749
10  750
11  751
12  752
13  753
14  754
15  755
16  756
17  757
18  758
19  759
20  760

[0530]

TABLE 46
761
No. R1
1   762
2   763
3   764
4   765
5   766
6   767
7   768
8   769
9   770
10  771
11  772
12  773
13  774
14  775
15  776
16  777
17  778
18  779
19  780
20  781

[0531]

TABLE 47
782
No. R1
1   783
2   784
3   785
4   786
5   787
6   788
7   789
8   790
9   791
10  792
11  793
12  794
13  795
14  796
15  797
16  798
17  799
18  800
19  801
20  802

[0532]

TABLE 48
803
No. R1
1   804
2   805
3   806
4   807
5   808
6   809
7   810
8   811
9   812
10  813
11  814
12  815
13  816
14  817
15  818
16  819
17  820
18  821
19  822
20  823

[0533]

TABLE 49
824
No. R1
1   825
2   826
3   827
4   828
5   829
6   830
7   831
8   832
9   833
10  834
11  835
12  836
13  837
14  838
15  839
16  840
17  841
18  842
19  843
20  844

[0534]

TABLE 50
845
No. R1
1   846
2   847
3   848
4   849
5   850
6   851
7   852
8   853
9   854
10  855
11  856
12  857
13  858
14  859
15  860
16  861
17  862
18  863
19  864
20  865

[0535]

TABLE 51
(I-M-2)
866
No.	R1	No.	R1
1	867	11	868
2	869	12	870
3	871	13	872
4	873	14	874
5	875	15	876
6	877	16	878
7	879	17	880
8	881	18	882
9	883	19	884
10	885	20	886

[0536]

TABLE 52
(I-M-3)
887
No.	R1	No.	R1
1	888	11	889
2	890	12	891
3	892	13	893
4	894	14	895
5	896	15	897
6	898	16	899
7	900	17	901
8	902	18	903
9	904	19	905
10	906	20	907

[0537]

TABLE 53
(I-N-1)
908
No.	R1	No.	R1
1	909	11	910
2	911	12	912
3	913	13	914
4	915	14	916
5	917	15	918
6	919	16	920
7	921	17	922
8	923	18	924
9	925	19	926
10	927	20	928

[0538]

TABLE 54
(I-N-2)
929
No.	R1	No.	R1
1	930	11	931
2	932	12	933
3	934	13	935
4	936	14	937
5	938	15	939
6	940	16	941
7	942	17	943
8	944	18	945
9	946	19	947
10	948	20	949

[0539]

TABLE 55
(I-N-3)
950
No.	R1	No.	R1
1	951	11	952
2	953	12	954
3	955	13	956
4	957	14	958
5	959	15	960
6	961	16	962
7	963	17	964
8	965	18	966
9	967	19	968
10	969	20	970

[0540]

TABLE 56
(I-N-4)
971
No.	R1	No.	R1
1	972	11	973
2	974	12	975
3	976	13	977
4	978	14	979
5	980	15	981
6	982	16	983
7	984	17	985
8	986	18	987
9	988	19	989
10	990	20	991

[0541]

TABLE 57
(I-O-1)
992
No.	R1	No.	R1
1	993	11	994
2	995	12	996
3	997	13	998
4	999	14	1000
5	1001	15	1002
6	1003	16	1004
7	1005	17	1006
8	1007	18	1008
9	1009	19	1010
10	1011	20	1012

[0542]

TABLE 58
(I-O-2)
1013
No.	R1	No.	R1
1	1014	11	1015
2	1016	12	1017
3	1018	13	1019
4	1020	14	1021
5	1022	15	1023
6	1024	16	1025
7	1026	17	1027
8	1028	18	1029
9	1030	19	1031
10	1032	20	1033

[0543]

TABLE 59
(I-O-3)
1034
No.	R1	No.	R1
1	1035	11	1036
2	1037	12	1038
3	1039	13	1040
4	1041	14	1042
5	1043	15	1044
6	1045	16	1046
7	1047	17	1048
8	1049	18	1050
9	1051	19	1052
10	1053	20	1054

[0544]

TABLE 60
(I-P-1)
1055
No.	R1	No.	R1
1	1056	11	1057
2	1058	12	1059
3	1060	13	1061
4	1062	14	1063
5	1064	15	1065
6	1066	16	1067
7	1068	17	1069
8	1070	18	1071
9	1072	19	1073
10	1074	20	1075

[0545]

TABLE 61
    (I-P-2)
1076
No. R1
1   1077
2   1078
3   1079
4   1080
5   1081
6   1082
7   1083
8   1084
9   1085
10  1086
11  1087
12  1088
13  1089
14  1090
15  1091
16  1092
17  1093
18  1094
19  1095
20  1096

[0546]

TABLE 62
    (I-P-3)
1097
No. R1
1   1098
2   1099
3   1100
4   1101
5   1102
6   1103
7   1104
8   1105
9   1106
10  1107
11  1108
12  1109
13  1110
14  1111
15  1112
16  1113
17  1114
18  1115
19  1116
20  1117

[0547]

TABLE 63
    (I-A-1)
1118
No. R1
21  1119
22  1120
23  1121
24  1122
25  1123
26  1124
27  1125
28  1126
29  1127
30  1128
31  1129
32  1130
33  1131
34  1132
35  1133
36  1134
37  1135
38  1136
39  1137
40  1138
41  1139
42  1140
43  1141
44  1142

[0548]

TABLE 64
    (I-A-1)
1143
No. R1
45  1144
46  1145
47  1146
48  1147
49  1148
50  1149
51  1150
52  1151
53  1152
54  1153
55  1154
56  1155
57  1156
58  1157
59  1158
60  1159
61  1160
62  1161
63  1162
64  1163
65  1164
66  1165
67  1166

[0549]

TABLE 65
    (I-A-2)
1167
No. R1
21  1168
22  1169
23  1170
24  1171
25  1172
26  1173
27  1174
28  1175
29  1176
30  1177
31  1178
32  1179
33  1180
34  1181
35  1182
36  1183
37  1184
38  1185
39  1186
40  1187
41  1188
42  1189
43  1190
44  1191

[0550]

TABLE 66
    (I-A-2)
1192
No. R1
45  1193
46  1194
47  1195
48  1196
49  1197
50  1198
51  1199
52  1200
53  1201
54  1202
55  1203
56  1204
57  1205
58  1206
59  1207
60  1208
61  1209
62  1210
63  1211
64  1212
65  1213
66  1214
67  1215

[0551]

TABLE 67
    (I-A-3)
1216
No. R1
21  1217
22  1218
23  1219
24  1220
25  1221
26  1222
27  1223
28  1224
29  1225
30  1226
31  1227
32  1228
33  1229
34  1230
35  1231
36  1232
37  1233
38  1234
39  1235
40  1236
41  1237
42  1238
43  1239
44  1240

[0552]

TABLE 68
    (I-A-3)
1241
No. R1
45  1242
46  1243
47  1244
48  1245
49  1246
50  1247
51  1248
52  1249
53  1250
54  1251
55  1252
56  1253
57  1254
58  1255
59  1256
60  1257
61  1258
62  1259
63  1260
64  1261
65  1262
66  1263
67  1264

[0553]

TABLE 69
    (I-A-4)
1265
No. R1
21  1266
22  1267
23  1268
24  1269
25  1270
26  1271
27  1272
28  1273
29  1274
30  1275
31  1276
32  1277
33  1278
34  1279
35  1280
36  1281
37  1282
38  1283
39  1284
40  1285
41  1286
42  1287
43  1288
44  1289

[0554]

TABLE 70
    (I-A-4)
1290
No. R1
45  1291
46  1292
47  1293
48  1294
49  1295
50  1296
51  1297
52  1298
53  1299
54  1300
55  1301
56  1302
57  1303
58  1304
59  1305
60  1306
61  1307
62  1308
63  1309
64  1310
65  1311
66  1312
67  1313

[0555]

TABLE 71
	(I-N-1)
1314
No.	R1	No.	R1
21	1315	33	1316
22	1317	34	1318
23	1319	35	1320
24	1321	36	1322
25	1323	37	1324
26	1325	38	1326
27	1327	39	1328
28	1329	40	1330
29	1331	41	1332
30	1333	42	1334
31	1335	43	1336
32	1337	44	1338

[0556]

TABLE 72
	(I-N-1)
1339
No.	R1	No.	R1
45	1340	57	1341
46	1342	58	1343
47	1344	59	1345
48	1346	60	1347
49	1348	61	1349
50	1350	62	1351
51	1352	63	1353
52	1354	64	1355
53	1356	65	1357
54	1358	66	1359
55	1360	67	1361
56	1362

[0557]

TABLE 73
	(I-N-2)
1363
No.	R1	No.	R1
21	1364	33	1365
22	1366	34	1367
23	1368	35	1369
24	1370	36	1371
25	1372	37	1373
26	1374	38	1375
27	1376	39	1377
28	1378	40	1379
29	1380	41	1381
30	1382	42	1383
31	1384	43	1385
32	1386	44	1387

[0558]

TABLE 74
	(I-N-2)
1388
No.	R1	No.	R1
45	1389	57	1390
46	1391	58	1392
47	1393	59	1394
48	1395	60	1396
49	1397	61	1398
50	1399	62	1400
51	1401	63	1402
52	1403	64	1404
53	1405	65	1406
54	1407	66	1408
55	1409	67	1410
56	1411

[0559]

TABLE 75
	(I-N-3)
1412
No.	R1	No.	R1
21	1413	33	1414
22	1415	34	1416
23	1417	35	1418
24	1419	36	1420
25	1421	37	1422
26	1423	38	1424
27	1425	39	1426
28	1427	40	1428
29	1429	41	1430
30	1431	42	1432
31	1433	43	1434
32	1435	44	1436

[0560]

TABLE 76
	(I-N-3)
1437
No.	R1	No.	R1
45	1438	57	1439
46	1440	58	1441
47	1442	59	1443
48	1444	60	1445
49	1446	61	1447
50	1448	62	1449
51	1450	63	1451
52	1452	64	1453
53	1454	65	1455
54	1456	66	1457
55	1458	67	1459
56	1460

[0561]

TABLE 77
	(I-N-4)
1461
No.	R1	No.	R1
21	1462	33	1463
22	1464	34	1465
23	1466	35	1467
24	1468	36	1469
25	1470	37	1471
26	1472	38	1473
27	1474	39	1475
28	1476	40	1477
29	1478	41	1479
30	1480	42	1481
31	1482	43	1483
32	1484	44	1485

[0562]

TABLE 78
	(I-N-4)
1486
No.	R1	No.	R1
45	1487	57	1488
46	1489	58	1490
47	1491	59	1492
48	1493	60	1494
49	1495	61	1496
50	1497	62	1498
51	1499	63	1500
52	1501	64	1502
53	1503	65	1504
54	1505	66	1506
55	1507	67	1508
56	1509

[0563] [Methods for Preparation of the Compounds of the Present Invention]

[0564] The compounds of the present invention of the formula (I) of the present invention may be prepared by the following methods or the methods described in examples.

[0565] Among the compounds of the present invention of the formula (I), the compounds of the present invention of the formula (I-1) 1510

[0566] (wherein all the symbols are the same meanings as hereinbefore described.) may be prepared by the known methods or the following methods [1]˜14].

[0567] [1] The compounds of the present invention of the formula (I-1) in which n is 1 or 2 may be also prepared by the following methods (a)˜(b).

[0568] (a) The compounds of the present invention of the formula (I-1) in which n is 1, i.e., the compounds of the present invention of the formula (I-1-1a) 1511

[0569] (wherein all the symbols are the same meanings as hereinbefore described.) may be prepared by oxidation of the compounds of the formula (I-1-1c) 1512

[0570] (wherein all the symbols are the same meanings as hereinbefore described.)

[0571] The above oxidation is known per se. For example, it may be carried out in an adequate organic solvent (e.g., methylene chloride, chloroform, benzene, hexane, t-butyl alcohol etc.), in the presence of an 1-1.2 equivalent amount of oxidizing agent (e.g., hydrogen peroxide, sodium periodate, acyl nitrite, sodium perborate, peracid (e.g., 3-chloroperbenzoic acid, peracetic acid etc.), potassium peroxymonosulfate, potassium permanganate, chromic acid etc.), at -40° C.˜0° C.

[0572] (b) The compounds of the present invention of the formula (I-1) in which n is 2, i.e., the compounds of the present invention of the formula (I-1-1b) 1513

[0573] (wherein all the symbols are the same meanings as hereinbefore described.) may be prepared by oxidation of the said the compounds of the formula (I-1-1c).

[0574] The above oxidation is known per se. For example, it may be carried out in an adequate organic solvent (e.g., methylene chloride, chloroform, benzene, hexane, t-butyl alcohol etc.), in the presence of an excess amount of oxidizing agent (e.g., hydrogen peroxide, sodium periodate, acyl nitrite, sodium perborate, peracid (e.g., 3-chloroperbenzoic acid, peracetic acid etc.), potassium peroxymonosulfate, potassium permanganate, chromic acid etc.), at 20° C.˜60° C.

[0575] [2] The compounds of the present invention of the formula (I-1) in which at least one of R1 (s) is a substituted oxy group or a group containing substituted oxy, i.e., the compounds of the present invention of the formula (I-1-2) 1514

[0576] (wherein, R1-1-2 is the same meanings as hereinbefore described for R1, provided that at least one of R R1-1-2(s) is a substituted oxy group or a group containing substituted oxy and the other symbols are the same meaning as hereinbefore described.)

[0577] may be also prepared by the following methods (a)˜(b).

[0578] (a) The compounds of the present invention of the formula (I-1-2) may be prepared by etherification of the compounds of the formula (I-1 -2) in which at least one of R1(s) is a hydroxy or a group containing hydroxy, i.e., the compounds of the formula (I-1-2a) 1515

[0579] (wherein, R R1-1-2a is the same meanings as hereinbefore described for R1, provided that at least one of R R1-1-2a(s) is a hydroxy or a group containing hydroxy and the other symbols are the same meaning as hereinbefore described.) with the corresponding compounds containing a group which is removal (chloride, bromide, iodide, mesyl or tosyl etc.).

[0580] This etherification is well known. For example, it may be carried out in an organic solvent (dimethylformamide, dimethylsulfoxide, chloroform, methyhlene chloride, diethyl ether, tetrahydrofuran etc.) in the presence of hydroxide of an alkalimetal (sodium hydroxide, potassium hydroxide, lithium hydroxide etc.), hydroxide of an alkaline earth metal (barium hydroxide, calcium hydroxide etc.) or carbonate (sodium carbonate , potassium carbonate etc.) or an aqueous solution thereof or a mixture thereof at 0˜100° C.

[0581] (b) The compounds of the present invention of the formula (I-1-2) may be prepared by etherification of the compounds of the formula (1-1 -2) in which at least one of R1(s) is a hydroxy or a group containing hydroxy, i.e., the compounds of the formula (I-1-2b) 1516

[0582] (wherein, R R1-1-2b is the same meanings as hereinbefore described for R1, provided that at least one of R R1-1-2b(s) is a hydroxy or a group containing hydroxy and the other symbols are the same meaning as hereinbefore described.) with the corresponding compounds containing hydroxy.

[0583] This etherification is well known. For example, it may be carried out in an organic solvent (methylene chloride, diethyl ether, tetrahydrofuran, acetonitrile, benzene, toluene etc.) in the presence of azo compounds (diethyl azodicaroxylate, diisopropyl azodicaroxylate, 1,1′-(azodicarbonyl)dipiperidine, 1,1′-azobis(N,N-dimethylformamide) etc.) and phosphine compounds (triphenylphosphine , tributylphosphine , trimethylphosphine etc.), with the corresponding alcohol compounds at 0˜60° C.

[0584] [3] The compounds of the present invention of the formula (I-1) in which at least one of R1(s) is a substituted amino or a group containing substituted amino, i.e., the compounds of the present invention of the formula (I-1-3) 1517

[0585] (wherein, R1-1-3 is the same meanings as hereinbefore described for R1, provided that at least one of R R1-1-3(s) is a substituted amino or a group containing substituted amino and the other symbols are the same meaning as hereinbefore described.)

[0586] may be prepared by the following methods (a)˜(d).

[0587] (a) The compounds of the present invention of the formula (I-1-3) may be prepared by reacting the compounds of the formula (I-1-3) in which at least one of R1(s) is halogen (chloride, bromide, iodide) or a group containing halogen, i.e., the compounds of the formula (I-1-3a) 1518

[0588] (wherein, R R1-1-3 is the same meanings as hereinbefore described for R1, provided that at least one of R R1-1-3a(s) is a halogen (chloride, bromide, iodide) or a group containing halogen and the other symbols are the same meaning as hereinbefore described.)

[0589] and the corresponding compounds containing amino.

[0590] This reaction is well known. For example, it may be carried out in an organic solvent (dimethylformamide, dimethylsulfoxide, chloroform, methyhlene chloride, diethyl ether, tetrahydrofuran, acetonitrile etc.) in the presence or absence of base (triethylamine, pyridine etc.) at 0˜100° C.

[0591] (b) The compounds of the present invention of the formula (I-1-3) may be prepared by reacting the compounds of the formula (I-1-3) in which at least one of R1(s) is an amino or a group containing amino, i.e., the compounds of the formula (I-1-3b) 1519

[0592] (wherein, R R1-1-3b is the same meanings as hereinbefore described for R1, provided that at least one of R R1-1-3b(s) is an amino or a group containing amino and the other symbols are the same meaning as hereinbefore described.) and the corresponding compounds containing halogen (chloride, bromide, and iodide).

[0593] This reaction may be carried out by the same procedure for the preparation of the said compounds of the formula (I-1-3a).

[0594] (c) The compounds of the present invention of the formula (I-1-3) may be prepared by reductive amidation of the compounds of the formula (I-1-3) in which at least one of R1(s) is an amino or a group containing amino, i.e., the compounds of the formula (I-1-3c) 1520

[0595] (wherein, R R1-1-3c is the same meanings as hereinbefore described for R1, provided that at least one of R R1-1-3(s) is an amino or a group containing amino and the other symbols are the same meaning as hereinbefore described.) with the corresponding compounds containing carbonyl.

[0596] This reductive amidation is well known. For example, it may be carried out in an organic solvent (methanol, ethanol, dimethylformamide, dimethylsulfoxide etc,) in the presence of reductant (sodium cyanoborohydride, sodium triacetoxyborohydride, sodium borohydride, Pd-C etc.) and in the presence of acid (acetic acid, hydrochlolride solution etc.), if necessary, at −20˜60° C.

[0597] (d) The compounds of the present invention of the formula (I-1-3) may be prepared by reductive amidation of the compounds of the formula (I-1-3) in which at least one of R1(s) is a carbonyl or a group containing carbonyl, i.e., the compounds of the formula (I-1-3d) 1521

[0598] (wherein, R R1-1-3d is the same meanings as hereinbefore described for R1, provided that at least one of R R1-1-3d(s) is a carbonyl or a group containing carbonyl and the other symbols are the same meaning as hereinbefore described.)

[0599] with the corresponding compounds containing amino.

[0600] This reductive amidation may be carried out by the same procedure for preparation of the said compounds of the formula (I-1-3c).

[0601] [4] The compounds of the present invention of the formula (I-1) in which at least one of R1(s) is an amide or a group containing amide, i.e., the compounds of the present invention of the formula (I-1-4) 1522

[0602] (wherein, R1-1-4 is the same meanings as hereinbefore described for R1, provided that at least one of R R1-1-4(s) is an amide or a group containing amide and the other symbols are the same meaning as hereinbefore described.) may be prepared by the following methods (a)˜(b).

[0603] (a) The compounds of the present invention of the formula (I-1-4) may be prepared by amidation of the compounds of the formula (I-1) in which at least one of R1(s) is a —COOH or a group containing —COOH, i.e., the compounds of the formula (I-1-4a) 1523

[0604] (wherein, R R1-1-4a is the same meanings as hereinbefore described for R1, provided that at least one of R R1-1-4a(s) is a —COOH or a group containing —COOH and the other symbols are the same meaning as hereinbefore described.) with the corresponding compounds containing amino.

[0605] The amidation is well known. For example, it may be carried out

[0606] (1) by the method with using acid halide,

[0607] (2) by the method with using mixed acid anhydride,

[0608] (3) by the method with using conducing agent etc.

[0609] Concrete description of these methods are as follows:

[0610] (1) method with using acid halide may be carried out, for example; carboxylic acid is reacted with an acid halide (oxalyl chloride or thionyl chloride etc.) in an organic solvent (chloroform, methylene chloride, diethyl ether or tetrahydrofuran etc.) or without solvents at from −20° C. to a refluxing temperature to give an acid halide. The obtained acid halide and an amine are reacted in an organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran etc.) in the presence of tertiary amine (pyridine, triethylamine, dimethylaniline or dimethylaminopyridine etc.) at 0-40° C.

[0611] (2) method with using mixed acid anhydride may be carried out, for example; carboxylic acid is reacted with an acid halide (pivaloyl chloride, tosyl chloride, mesyl chloride etc.) or an acid derivative (ethyl chloroformate, isobutyl chloroformate etc.) in an organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran. etc.) or without solvents, in the presence of tertiary amine (pyridine, triethylamine, dimethylaniline or dimethylaminopyridine etc.), at 0-40° C.

[0612] (3) method with using condensing agent may be carried out, for example; a carboxylic acid and an amine are reacted in an organic solvent (chloroform, methylene chloride, dimethylformamide, diethyl ether or tetrahydrofuran. etc.) or without solvents in the presence or absence of tertiary amine (pyridine, triethylamine, dimethylaniline or dimethylaminopyridine etc.) using with condensing agent (1,3-dicyclohexylcarbodiimido (DCC), 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimido (EDC), 1,1′-carbonydimidazole (CDI), 2-chloro-1-methylpyridinium iodide, propane phosphate cyclic anhydride etc.) using or without 1-hydroxybenztriazole (HOBt) at 0-40° C. (etc.)

[0613] Preferably, the above reactions (1), (2) and (3) described above are carried out under an atmosphere of an inert gas (argon, nitrogen etc.) on anhydrous condition.

[0614] (b) The compounds of the present invention of the formula (I-1-4) may be prepared by amidation of the compounds of the formula (I-1) in which at least one of R1(s) is an amino or a group containing amino, i.e., the compounds of the formula (I-1-4b) 1524

[0615] (wherein, R R1-1-4b is the same meanings as hereinbefore described for R1, provided that at least one of R R1-1-4b(s) is an amino or a group containing amino and the other symbols are the same meaning as hereinbefore described.)with the corresponding compounds containing carboxy.

[0616] The above amidation may be carried out by the same procedure for preparation of the said compounds of the formula (I-1-4a).

[0617] [5] The compounds of the present invention of the formula (1-1) in which at least one of R1(s) is an ester or a group containing ester, i.e., the compounds of the present invention of the formula (I-1-5) 1525

[0618] (wherein, R1-1-5 is the same meanings as hereinbefore described for R1, provided that at least one of R1-1-5(s) is an ester or a group containing ester and the other symbols are the same meaning as hereinbefore described.) may be prepared by the following methods (a)˜(b).

[0619] (a) The compounds of the present invention of the formula (I-1-5) may be prepared by esterification of the compounds of the formula (I-1) in which at least one of R1(s) is a —COOH or a group containing —COOH, i.e., the compounds of the formula (I-1-5a) 1526

[0620] (wherein, R1-1-5a is the same meanings as hereinbefore described for R1, provided that at least one of R1-1-5a(s) is a —COOH or a group containing —COOH and the other symbols are the same meaning as hereinbefore described.) with the corresponding compounds containing hydroxy.

[0621] Esterification is well known. For example, it may be carried out

[0622] (1) by the method with using acid halide,

[0623] (2) by the method with using mixed acid anhydride,

[0624] (3) by the method with using conducing agent etc.

[0625] Concrete description of the above methods are as follows:

[0626] (1) method with using acid halide may be carried out, for example; carboxylic acid is reacted with an acid halide (oxalyl chloride or thionyl chloride -etc.) in an inert organic solvent (chloroform, methylene chloride, diethyl ether or tetrahydrofuran etc.) or without solvents at from −20° C. to a refluxing temperature to give an acid halide. The obtained acid halide and an alcohol are reacted in an inert organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran etc.) in the presence of tertiary amine (pyridine, triethylamine, dimethylaniline or dimethylaminopyridine etc.) at 0-40° C.

[0627] (2) method with using mixed acid anhydride may be carried out, for example; carboxylic acid is reacted with an acid halide (pivaloyl chloride, tosyl chloride, mesyl chloride etc.) or an acid derivative (ethyl chloroformate, isobutyl chloroformate etc.) in an inert organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran. etc.) or without solvents, in the presence of tertiary amine (pyridine, triethylamine, dimethylaniline or dimethylaminopyridine etc.), at 0-40° C. to give an acid halide. The obtained acid halide and an alcohol are reacted in an inert organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran etc.) at 0-40° C.

[0628] (3) method with using condensing agent may be carried out, for example; a carboxylic acid and an alcohol are reacted in an organic solvent (chloroform, methylene chloride, dimethylformamide, diethyl ether or tetrahydrofuran. etc.) or without solvents in the presence or absence of tertiary amine (pyridine, triethylamine, dimethylaniline or dimethylaminopyridine etc.) using with condensing agent (1,3-dicyclohexylcarbodiimido (DCC), 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimido (EDC), 1,1′-carbonydimidazole (CDI), 2-chloro-1-methylpyridinium iodide, propane phosphate cyclic anhydride etc.) using or without 1-hydroxybenztriazole (HOBt) at 0-40° C.

[0629] Preferably, the reactions (1), (2) and (3) described above are carried out under an atmosphere of inert gas (argon, nitrogen etc.) on anhydrous condition.

[0630] (b) The compounds of the present invention of the formula (1-1-5) may be prepared by esterification of the compounds of the formula (I-1) in which at least one of R1(s) is a hydroxy or a group containing hydroxy, i.e., the compounds of the formula (I-1-5b) 1527

[0631] (wherein, R1-1-5b is the same meanings as hereinbefore described for R1, provided that at least one of R1-1-5b(s) is a hydroxy or a group containing hydroxy and the other symbols are the same meaning as hereinbefore described.) with the corresponding compounds containing carboxy.

[0632] The esterification may be carried out by the same procedure for preparation of the said compounds of the formula (I-1-5a).

[0633] [6] The compounds of the present invention of the formula (1-1) in which at least one of R1(s) is a sulfonamide or a group containing sulfonamide, i.e., the compounds of the present invention of the formula (I-1-6) 1528

[0634] (wherein, R1-1-6 is the same meanings as hereinbefore described for R1, provided that at least one of R1-1-6(s) is a sulfonamide or a group containing sulfonamide and the other symbols are the same meaning as hereinbefore described.) may be prepared by the following methods (a)˜(b).

[0635] (a) The compounds of the present invention of the formula (I-1-6) may be prepared by sulfonamidation of the compounds of the formula (I-1) in which at least one of R1(s) is a —SO3H or a group containing —SO2H, i.e., the compounds of the formula (II) 1529

[0636] (wherein, R1-1-6a is the same meanings as hereinbefore described for R1, provided that at least one of R1-1-6a(s) is a —SO3H or a group containing —SO3H and the other symbols are the same meaning as hereinbefore described.) with the corresponding compounds containing amino.

[0637] The sulfonamidation is well known. For example, it may be carried out by reacting sulfonic acid with acid halide (oxazolyl chloride, thionyl chloride etc.) in an inert organic solvent (chloroform, methyhlene chloride, diethyl ether, tetrahydrofuran etc.) or without solvent, at −20° C. refluxing temperature to obtain sulfonylhalide and then by reacting the obtained sulfonylhalide with an amine in an inert organic solvent (chloroform, methyhlene chloride, diethyl ether, tetrahydrofuran etc.) in the presence of tertiary amine (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine etc.) at 0˜40° C.

[0638] (b) The compounds of the present invention of the formula (I-1-6) may be prepared by sulfonamidation of the compounds of the formula (1-1) in which at least one of R1(s) is an amino or a group containing amino, i.e., the compounds of the formula (I-1-6b) 1530

[0639] (wherein, R1-1-6b is the same meanings as hereinbefore described for R1, provided that at least one of R1-1-6b(s) is an amino or a group containing amino and the other symbols are the same meaning as hereinbefore described.) with the corresponding compounds containing sulfo.

[0640] The sulfonamidation may be carried out the same procedure for preparation of the said compounds of the formula (I-1-6a).

[0641] [7] The compounds of the present invention of the formula (I-1) in which at least one of R1(s) is a substituted aminocarbonyloxy or a group containing a substituted aminocarbonyloxy, i.e., the compounds of the present invention of the formula (I-1-7) 1531

[0642] (wherein, R R1-1-7 is the same meanings as hereinbefore described for R1, provided that at least one of R R1-1-7(s) is a substituted aminocarbonyloxy or a group containing a substituted aminocarbonyloxy and the other symbols are the same meaning as hereinbefore described.) may be prepared by reacting the compounds of the formula (I-1) in which at least one of R1(s) is a hydroxy or a group containing hydroxy, i.e., the compounds of the formula (I-1-7a) 1532

[0643] (wherein, R1-1-7a is the same meanings as hereinbefore described for R1, provided that at least one of R1-1-7a(s) is a hydroxy or a group containing hydroxy and the other symbols are the same meaning as hereinbefore described.) with the corresponding compounds containing isocyanate.

[0644] This reaction is well known. For example, it may be carried out in an organic solvent (tetrahydrofuran, methyhlene chloride, diethyl ether etc.) in the presence of base (1,8-diazabicyclo[5.4.0]undec-7-en (DBU), triethylamine, sodium hydride etc.) at 0˜100° C.

[0645] [8] The compounds of the present invention of the formula (I-1) in which at least one of R1(s) is a substituted aminocarbonylamino or a group containing a substituted aminocarbonylamino, i.e., the compounds of the present invention of the formula (I-1-8) 1533

[0646] (wherein, R1-1-8 is the same meanings as hereinbefore described for R1, provided that at least one of R1-1-8(s) is a substituted aminocarbonyl or a group containing a substituted aminocarbonyl and the other symbols are the same meaning as hereinbefore described.) may be prepared by reacting the compounds of the formula (I-1) in which at least one of R1(s) is an amino or a group containing amino, i.e., the compounds of the formula (I-1-8a) 1534

[0647] (wherein, R R1-1-8 is the same meanings as hereinbefore described for R1, provided that at least one of R R1-1-8a(s) is an amino or a group containing amino and the other symbols are the same meaning as hereinbefore described.) with the corresponding compounds containing isocyanate.

[0648] This reaction may be carried out by the same procedure for preparation of the said compounds of the formula (I-1-7).

[0649] [9] The compounds of the present invention of the formula (I-1) in which at least one of R1(s) is a substituted oxycarbonylamino or a group containing a substituted oxyocarbonylamino, i.e., the compounds of the present invention of the formula (I-1-9) 1535

[0650] (wherein, R R1-1-9 is the same meanings as hereinbefore described for R1, provided that at least one of R R1-1-9(s) is a substituted oxycarbonylamino or a group containing a substituted oxyocarbonylamino and the other symbols are the same meaning as hereinbefore described.) may be prepared by esterification of the compounds of the formula (I-1) in which at least one of R1(s) is an amino or a group containing amino, i.e., the compounds of the formula (I-1-9a) 1536

[0651] (wherein, R R1-1-9a is the same meanings as hereinbefore described for R1, provided that at least one of R1-1-9a(s) is an amino or a group containing amino and the other symbols are the same meaning as hereinbefore described.) with the corresponding halo formic acid ester.

[0652] This reaction is well known. For example, it may be carried out in an organic solvent (tetrahydrofuran, methyhlene chloride, diethyl ether etc.) in the presence of base (triethylamine, pyridine etc.) at −78˜40° C.

[0653] [10] The compounds of the present invention of the formula (I-1) in which at least one of R1(s) is a substituted oxycarbonyloxy or a group containing a substituted oxycarbonyloxy, i.e., the compounds of the present invention of the formula (I-1-10) 1537

[0654] (wherein, R1-1-10 is the same meanings as hereinbefore described for R1, provided that at least one of R1-1-10(s) is a substituted oxycarbonyloxy or a group containing a substituted oxycarbonyloxy and the other symbols are the same meaning as hereinbefore described.) may be prepared by esterification of the compounds of the formula (I-1) in which at least one of R1(s) is a hydroxy or a group containing hydroxy, i.e., the compounds of the formula (I-1-10a) 1538

[0655] (wherein, R1-1-10a is the same meanings as hereinbefore described for R1, provided that at least one of R1-1-10a(s) is a hydroxy or a group containing hydroxy and the other symbols are the same meaning as hereinbefore described.) with the corresponding halo formic acid ester.

[0656] This reaction may be carried out by the same procedure for preparation of the said compounds of the formula (I-1-9).

[0657] [11] The compounds of the present invention of the formula (I-1) in which at least one of R1(s) is a substituted (hydroxy)methyl or a group containing a substituted (hydroxy)methyl, i.e., the compounds of the present invention of the formula (I-1-11) 1539

[0658] (wherein, R1-1-11 is the same meanings as hereinbefore described for R1, provided that at least one of R1-1-11(s) is a substituted (hydroxy)methyl or a group containing a substituted (hydroxy)methyl and the other symbols are the same meaning as hereinbefore described.) may be prepared by the following methods (a)˜(b).

[0659] (a) The compounds of the present invention of the formula (I-1-11) in which n is 0, i.e., the compounds of the present invention of the formula (I-1-11a) 1540

[0660] (wherein all the symbols are the same meanings as hereinbefore described.) may be prepared by reacting the compounds of the formula (I-1) in which at least one of R1(s) is a formyl i.e., the compounds of the formula (1-1-11 aa) 1541

[0661] (wherein, R1-1-11aa is the same meanings as hereinbefore described for R1, provided that at least one of R1-1-11a(s) is a formyl and the other symbols are the same meaning as hereinbefore described.)

[0662] with the corresponding Grignard's reagents or corresponding derivatives containing lithium.

[0663] This reaction is well known. For example, it may be carried out in an organic solvent (tetrahydrofuran, diethyl ether etc.) at −78˜0° C.

[0664] (b) The compounds of the present invention of the formula (I-1-11) in which n is 1 or 2, i.e., the compounds of the present invention of the formula (I-1-11b) 1542

[0665] (wherein, n-1-11b is an integer of 1˜2 and the other symbols are the same meaning as hereinbefore described.)

[0666] may be prepared by oxidizing the said compounds of the formula (I-1-11a) as described in [1].

[0667] [12] The compounds of the present invention of the formula (I-1) in which at least one of R1(s) is a substituted carbonyl or a group containing substituted carbonyformyl, i.e., the compounds of the present invention of the formula (I-1-12) 1543

[0668] (wherein, R1-1-12 is the same meanings as hereinbefore described for R1, provided that at least one of R1-1-12(s) is an substituted carbonyl or a group containing substituted carbonyl and the other symbols are the same meaning as hereinbefore described.)

[0669] may be prepared by oxidizing the said compounds of the formula (I-1-11).

[0670] This oxidation is well known. For example, it may be carried out in an organic solvent (methyhlene chloride, chloroform etc.) using oxidant (manganese dioxide, oxazolyl chloride, pyridinium dichromate etc.) at −78˜40° C.

[0671] [13] The compounds of the present invention of the formula (I-1) in which at least one of R1(s) is an amino or a group containing amino, i.e., the compounds of the present invention of the formula (I-1 -13) 1544

[0672] (wherein, R1-1-13 is the same meanings as hereinbefore described for R1, provided that at least one of R1-1-13(s) is an amino or a group containing amino and the other symbols are the same meaning as hereinbefore described.) may be prepared by reducing nitro in the compounds of the formula of (I-1) in which at least one of R1(s) is a nitro or a group containing nitro, i.e., the compounds of the formula (I-1-13a) 1545

[0673] (wherein, R R1-1-13a is the same meanings as hereinbefore described for R1, provided that at least one of R1-1-13a(s) is a nitro or a group containing nitro and the other symbols are the same meaning as hereinbefore described.).

[0674] The reduction of nitro is well known. For example, it may be carried out by hydrogenolysis and reduction using organic metal.

[0675] This hydrogenolysis is well known. For example, it may be carried out in inert solvent [ethers (e.g., tetrahydrofuran, dioxane, dimethoxy ethane, diethyl ether etc.), alcohols (e.g., methanol , ethanol etc.), benzenes (e.g., benzene, toluene etc.), ketones (e.g., acetone, methyl ethyl ketone etc.), nitriles (e.g., acetonitrile etc.), amides (e.g., dimethylformamide etc.), water, ethyl acetate, acetic acid or mixture of the said two or more solvents etc.], in the presence of catalyst to hydrogenate (e.g., Pd-C, palladium black, Pd, palladium hydroxide, platinum oxide, Ni, Raney nickel, ruthenium chloride etc.), in the presence or absence of an inorganic acid (e.g., hydrochloric acid, sulfuric acid, hypochlorous acid, boric acid, tetrafluoroboric acid etc.) or an organic acid (e.g., acetic acid, p-toluenesulfonic acid, bromic acid, trifluoroacetic acid, formic acid etc.), at an ordinary or increased pressure under an atmosphere of hydrogen gas or in the presence of ammonium formate at 0˜200° C. When an acid is used, its salt may be used.

[0676] The reduction using an organic metal is well known. For example, it may be carried out in a water-admissible solvent (ethanol , methanol etc.) in the presence or absence of an aqueous hydrochloric acid solution, using an organic metal (Zn, Fe, Sn, SnCl2, FeCl2 etc.) at 50˜150° C.

[0677] [14] The compounds of the present invention of the formula (I-1) in which at least one of R1(s) is a —COOH, hydroxy or amino or a group containing —COOH, hydroxy or amino, i.e., the compounds of the present invention of the formula (I-1-14) 1546

[0678] (wherein, R1-1-14 is the same meanings as hereinbefore described for R1, provided that at least one of R R1-1-14(s) is a —COOH, hydroxy or amino or a group containing —COOH, hydroxy or amino and the other symbols are the same meaning as hereinbefore described.) may be prepared by removal of protecting group in the compounds of the formula (I-1) containing a protected COOH, hydroxy or amino, i.e., the compounds of the formula (I-1-14a) 1547

[0679] (wherein, R1-1-14a is the same meanings as hereinbefore described for R1, provided that at least one of R1-1-14a(s) is a protected COOH (e.g., it is protected by methyl, ethyl, t-butyl and benzyl etc.), protected hydroxy (e.g., it is protected by methoxymethyl, tetrahydropyranyl, t-butyldimethylsilyl, acetyl, benzyl etc.) or protected amino (e.g., it is protected by benzyloxycarbonyl, t-butoxycarbonyloxy, trifluoroacetyl etc.) or a group containing such a group, and the other symbols are the same meaning as hereinbefore described.) according to alkaline hydrolysis, removal of protecting group in an acidic condition, removal of silyl or hydrogenolysis.

[0680] The removal of a protecting group according to alkaline hydrolysis is well known. For example, it may be carried out in an organic solvent (methanol, tetrahydrofuran, dioxane etc.), using hydroxide of an alkaline metal (sodium hydroxide, potassium hydroxide , lithium hydroxide etc.), hydroxide of an alkaline earth metal (barium hydroxide, calcium hydroxide etc.) or carbonate (sodium carbonate , potassium carbonate etc.) or an aqueous solution thereof or a mixture thereof at 0˜40° C.

[0681] The removal of a protecting group in an acidic condition is well known. For example, it may be carried out in an organic solvent (methyhlene chloride, chloroform, dioxane, ethyl acetate, anisole etc.), organic acid (acetic acid, trifluoroacetic acid, methanesulfonic acid, trimethylsilyliodide etc.) or inorganic acid (hydrochloric acid, sulfuric acid etc.) or a mixture thereof (bromohydroacetic acid etc.) at 0˜100° C.

[0682] The removal of silyl is well known. For example, it may be carried out in a water-admissible organic solvent (tetrahydrofuran, acetonitrile etc.), using tetrabutylammonium fluoride at 0˜40° C.

[0683] The removal of protecting group according to hydrogenolysis may be carried out by the same procedure of hydrogenolysis described in [13].

[0684] Among the compounds of the formula (I), the compounds of the formula (I-2) 1548

[0685] may be prepared by the following methods [15]˜[17].

[0686] [15] The compounds of the present invention of the formula (I-2) in which m is 0, i.e., the compounds of the present invention of the formula (I-2-15) 1549

[0687] (wherein all the symbols are the same meanings as hereinbefore described.) may be prepared by the following methods (a)˜(b).

[0688] (a) The compounds of the present invention of the formula (I-2-15) in which n is 1 or 2, i.e., the compounds of the present invention of the formula (I-2-15a) 1550

[0689] (wherein, n-2-15a is an integer of 1˜2 and the other symbols are the same meanings as hereinbefore described.) may be prepared by reacting the said compounds of the formula (I-1-1a) or the compounds of the formula (I-1-1b) and the compounds of the formula (III) 1551

[0690] (wherein all the symbols are the same meanings as hereinbefore described.).

[0691] This reaction is known one (to see J. Am. Chem. Soc., 72, 1985 (1950), J. Org. Chem., 54, 4232 (1989). For example, it may be carried out in an inert organic solvent (tetrahydrofuran, diethyl ether, methylene chloride, chloroform, benzene, toluene, dimethylformamide, dimethylsulfoxide, acetonitrile etc.) using hydride of an alkaline metal, hydroxide of an alkaline metal (sodium hydroxide, potassium hydroxide, lithium hydroxide etc.), hydroxide of an alkaline earth metal (barium hydroxide, calcium hydroxide etc.) or tertiary amine (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine etc.) or an aqueous solution thereof, or a mixture thereof at 0˜40° C.

[0692] (b) The compounds of the present invention of the formula (I-2-15) in which n is 0, i.e., the compounds of the present invention of the formula (I-2-15b) 1552

[0693] (wherein all the symbols are the same meanings as hereinbefore described.) may be prepared by reduction of the compounds obtained by the. above mentioned method in which m is 0, n is 1, i.e., the compounds of the formula (I-2-15ab) 1553

[0694] (wherein all the symbols are the same meanings as hereinbefore described.).

[0695] This reduction reaction is well known. For example, this reaction may be carried out in an organic solvent (diethyl ether, tetrahydrofuran etc.) using reductant (lithium aluminum hydride, aluminum diisobutylhydride etc.) at 0˜80° C.

[0696] [16] The compounds of the present invention of the formula (I-2) in which m is 1, i.e., the compounds of the present invention of the formula (I-2-16) 1554

[0697] (wherein all the symbols are the same meanings as hereinbefore described.) may be prepared by oxidizing the said compounds of the formula (I-2-15).

[0698] This oxidation may be carried out by the same procedure for preparation of the compounds of the formula (I-1-1a) in [1].

[0699] [17] The compounds of the present invention of the formula (I-2) in which m is 2, i.e., the compounds of the present invention of the formula (I-2-17) 1555

[0700] (wherein all the symbols are the same meanings as hereinbefore described.) may be prepared by the following methods (a)˜(c).

[0701] (a) The compounds of the present invention of the formula (I-2-17) in which n is 1 or 2, i.e., the compounds of the present invention of the formula (I-2-17a) 1556

[0702] (wherein, n-2-17a is an integer of 1˜2 and the other symbols are the same meaning as hereinbefore described.)

[0703] may be prepared by reacting the said compounds of the formula (I-11-a) or the compounds of the formula (I-1-1b) and the compounds of the formula (IV) 1557

[0704] (wherein all the symbols are the same meanings as hereinbefore described.).

[0705] This reaction may be carried out by the same procedure described in the reaction of the compounds of the formula (I-2-15a) and the compounds of the formula (III) in [15].

[0706] (b) The compounds of the present invention of the formula (I-2-17) in which n is 0, i.e., the compounds of the formula (I-2-17b) 1558

[0707] (wherein all the symbols are the same meanings as hereinbefore described.) may be prepared by reduction of the compounds of the formula (V) 1559

[0708] (wherein all the symbols are the same meanings as hereinbefore described.).

[0709] This reduction is known one. For example, it may be carried out by hydrogenation or by the method using triethylsilane.

[0710] This hydrogenation is known reaction. For example, it may be carried out in inert solvent [ethers (e.g., tetrahydrofuran, dioxane, dimethoxy ethane, diethyl ether etc.), alcohols (e.g., methanol, ethanol etc.), benzenes (e.g., benzene, toluene etc.), ketones (e.g., acetone, methyl ethyl ketone etc.), nitrites (e.g., acetonitrile etc.), amides (e.g., dimethylformamide etc.), water, ethyl acetate, acetic acid or mixture of the said two or more solvents etc.], in the presence of catalyst to hydrogenate (e.g., Pd-C, palladium black, Pd, palladium hydroxide, platinum oxide, Ni, Raney nickel, ruthenium chloride etc.), in the presence or absence of an inorganic acid (e.g., hydrochloric acid, sulfuric acid, hypochlorous acid, boric acid, tetrafluoroboric acid etc.) or an organic acid (e.g., acetic acid, p-toluenesulfonici acid, bromic acid, trifluoroacetic acid, formic acid etc.), at an ordinary or increased pressure under an atmosphere of hydrogen gas, or in the presence of ammonium formate at 0˜200° C. When an acid is used, its salt may be used.

[0711] This reduction using triethylsilane is well known. For example, it may be carried out in trifluoroacetic acid, in the presence of triethylsilane at 0˜100° C.

[0712] (c) The compounds of the present invention of the formula (I-2-17) in which n is 2, i.e., the compounds of the present invention of the formula (I-2-17c) 1560

[0713] (wherein all the symbols are the same meanings as hereinbefore described.) may be prepared by oxidizing the compounds obtained by the above mentioned method in which m is 0 and n is 2, i.e., the compounds of the formula (I-2-15ac) 1561

[0714] (wherein all the symbols are the same meanings as hereinbefore described.).

[0715] This reaction may be carried out by the same procedure for preparation of the compounds of the formula (I-1-1b) in [1].

[0716] The compounds of the present invention of the formula (I-2) may be also prepared by not only the methods described in [15]˜[17] but also the following methods [18]˜[30].

[0717] [18] The compounds of the present invention of the formula (I-2) in which at least one of R1(s) or R2(s) is a substituted oxy or a group containing substituted oxy, i.e., the compounds of the present invention of the formula (I-2-18) 1562

[0718] (wherein, R1-2-18 and R2-2-18 are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-18(s) and R2-2-18(s) is a substituted oxy or a group containing substituted oxy and the other symbols are the same meaning as hereinbefore described.) may be prepared by the following methods (a)˜(b).

[0719] (a) The compounds of the present invention of the formula (I-2-18) may be prepared by eterification of the compounds of the formula (I-2) in which at least one of R1(s) or R2(s) is hydroxy or a group containing hydroxy, i.e., the compounds of the formula (I-2-18a) 1563

[0720] (wherein, R1-2-18a and R2-2-18a are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-18a(s) and R2-2-18a(s) is a hydroxy or a group containing hydroxy and the other symbols are the same meaning as hereinbefore described.)

[0721] and the corresponding compounds containing a group which is removal (chloride, bromide, iodide, mesyl or tosyl etc.).

[0722] This eterification may be carried out by the same procedure for preparation of the compounds of the formula (I-1-2a) in [2].

[0723] (b) The compounds of the present invention of the formula (I-2-18) may be prepared by eterification of the compounds of the formula (I-2) in which at least one of R1(s) is a hydroxy or a group containing hydroxy, i.e., the compounds of the formula (I-2-18b) 1564

[0724] (wherein, R1-2-18b and R2-2-18b are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-18b(s) and R2-2-18b(s) is a hydroxy or a group containing hydroxy and the other symbols are the same meaning as hereinbefore described.)

[0725] with corresponding compounds containing hydroxy.

[0726] This eterification may be carried out by the procedure for preparation of the compounds of the formula (I-1-2b) in [2].

[0727] [19] The compounds of the present invention of the formula (I-2) in which at least one of R1(s) or R2(s) is a substituted amino or a group containing substituted amino, i.e., the compounds of the present invention of the formula (I-2-19) 1565

[0728] (wherein, R1-2-19 and R2-2-19 are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-19(s) and R2-2-19(s) is a substituted amino or a group containing substituted amino and the other symbols are the same meaning as hereinbefore described.) may be prepared by the following methods (a)˜(d).

[0729] (a) The compounds of the present invention of the formula (I-2-19) may be prepared by reacting the compounds of the formula (I-2) in which at least one of R1(s) or R2(s) is a halogen (chloride, bromide, iodide) or a group containing halogen, i.e., the compounds of the formula (I-2-19a) 1566

[0730] (wherein, R1-2-19a and R2-2-19a are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-19a(s) and R2-2-19a(s) is a halogen (chloride, bromide, iodide) or a group containing halogen and the other symbols are the same meaning as hereinbefore described.)

[0731] and the compounds containing amino.

[0732] This reaction may be carried out by the same procedure for preparation of the compounds of the formula (I-1-3a) in [3].

[0733] (b) The compounds of the present invention of the formula (I-2-19) may be prepared by reacting the compounds of the formula (I-2) in which at least one of R1(s) or R2(s) is an amino or a group containing amino, i.e., the compounds of the formula (I-2-19b) 1567

[0734] (wherein, R1-2-19b and R2-2-19b are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-19b(s) and R2-2-19b(s) is an amino or a group containing amino and the other symbols are the same meaning as hereinbefore described.) and the corresponding compounds containing halogen (chloride, bromide, and iodide).

[0735] This reaction may be carried out by the same procedure for preparation of the compounds of the formula (I-1-3a) in [3].

[0736] (c) The compounds of the present invention of the formula (I-2-19) may be prepared by reacting the compounds of the formula (I-2) in which at least one of R1(s) or R2(s) is an amino or a group containing amino, i.e., the compounds of the formula (I-2-19c) 1568

[0737] (wherein, R1-2-19c and R2-2-19c are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-19c(s) and R2-2-19c(s) is an amino or a group containing amino and the other symbols are the same meaning as hereinbefore described.) and the corresponding compounds containing carbonyl.

[0738] This reaction may be carried out by the same procedure for preparation of the compounds of the formula (I-1-3c) in (3].

[0739] (d) The compounds of the present invention of the formula (I-2-19) may be prepared by reductive amidation of the compounds of the formula (I-2) in which at least one of R1(s) or R2(s) is a carbonyl or a group containing carbonyl, i.e., the compounds of the formula (I-2-19d) 1569

[0740] (wherein, R1-2-19d and R2-2-19d are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-19d(s) and R2-2-19d(s) is a carbonyl or a group containing carbonyl and the other symbols are the same meaning as hereinbefore described.) and the corresponding compounds containing amino.

[0741] This reductive amidation may be carried out by the same procedure for preparation of the compounds of the formula (I-1-3c) in [3].

[0742] [20] The compounds of the present invention of the formula (I-2) in which at least one of R1(s) or R2(s) is an amide or a group containing amide, i.e., the compounds of the present invention of the formula (I-2-20) 1570

[0743] (wherein, R1-2-20 and R2-2-20 are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-20(s) and R2-2-20(s) is an amide or a group containing amide and the other symbols are the same meaning as hereinbefore described.) may be prepared by the following methods (a)˜(b).

[0744] (a) The compounds of the present invention of the formula (I-2-20) may be prepared by amidation of the compounds of the formula (I-2) in which at least one of at least one of R1(s) or R2(s) is a —COOH or a group containing —COOH, i.e., the compounds of the formula (I-2-20a) 1571

[0745] (wherein, R1-2-20a and R2-2-20a are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-1-20a(s) and R2-2-20a(s) is a —COOH or a group containing —COOH and the other symbols are the same meaning as hereinbefore described.) and the corresponding compounds containing amino.

[0746] The amidation may be carried out by the same procedure for preparation of the compounds of the formula (I-1-4) in [4].

[0747] (b) The compounds of the present invention of the formula (I-2-20) may be prepared by amidation of the compounds of the formula (I-2) in which at least one of R1(s) or R2(s) is an amino or a group containing amino, i.e., the compounds of the formula (I-2-20b) 1572

[0748] (wherein, R1-2-20b and R2-2-20b are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-20b(s) and R2-2-20b(s) is an amino or a group containing amino and the other symbols are the same meaning as hereinbefore described.) and the corresponding compounds containing carboxy.

[0749] The amidation may be carried out by the same procedure for preparation of the compounds of the formula (I-1-4) in [4].

[0750] [21] The compounds of the present invention of the formula (I-2) in which at least one of R1(s) or R2(s) is an ester or a group containing ester, i.e., the compounds of the present invention of the formula (I-2-21) 1573

[0751] (wherein, R1-2-21 and R2-2-1 are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-2(s) and R2-2-21(s) is an ester or a group containing ester and the other symbols are the same meaning as hereinbefore described.) may be prepared by the following methods (a)˜(b).

[0752] (a) The compounds of the present invention of the formula (I-2-21) may be prepared by esterification of the compounds of the formula (I-2) in which at least one of R1(s) or R2(s) is a —COOH or a group containing —COOH, i.e., the compounds of the formula (I-2-21a) 1574

[0753] (wherein, R1-2-21a and R2-2-21a are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-21a(s) and R2-2-21a(s) is a —COOH or a group containing —COOH and the other symbols are the same meaning as hereinbefore described.) and the corresponding compounds containing hydroxy.

[0754] This esterification may be carried out by the same procedure for preparation of the compounds of the formula (I-1-5) in [5].

[0755] (b) The compounds of the present invention of the formula (I-2-21) may be prepared by esterification of the compounds of the formula (I-2) in which R1(s) or R2(s) is a hydroxy or a group containing hydroxy, i e., the compounds of the formula (I-2-21b) 1575

[0756] (wherein, R1-2-21 and R2-2-21b are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-21b(s) and R2-2-21b(s) is a hydroxy or a group containing hydroxy and the other symbols are the same meaning as hereinbefore described.) and the corresponding compounds containing carboxy.

[0757] This esterification may be carried out by the same procedure for preparation of the compounds of the formula (I-1-5) in [5].

[0758] [22] The compounds of the present invention of the formula (I-2) in which at least one of R1(s) or R2(s) is a sulfonamide or a group containing sulfonamide, i.e., the compounds of the present invention of the formula (I-2-22) 1576

[0759] (wherein, R1-2-22 and R2-2-22 are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-22(s) and R2-2-22(s) is a sulfonamide or a group containing sulfonamide and the other symbols are the same meaning as hereinbefore described.) may be prepared by the following methods (a)˜(b).

[0760] (a) The compounds of the present invention of the formula (I-2-22) may be prepared by sulfonamidation of the compounds of the formula (I-2) in which at least one of R1(s) or R2(s) is a —SO3H or a group containing —SO3H, i.e., the compounds of the formula (VI) 1577

[0761] (wherein, R1-2-22a and R2-2-22a are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-22a(s) and R2-2-22a(s) is a —SO3H or a group containing —SO3H and the other symbols are the same meaning as hereinbefore described.) and the corresponding compounds containing amino.

[0762] The sulfonamidation may be carried out by the same procedure for preparation of the compounds of the formula (I-1-6a) in [6].

[0763] (b) The compounds of the present invention of the formula (I-2-22) may be prepared by sulfonamidation of the compounds of the formula (I-2) in which at least one of R1(s) or R2(s) is an amino or a group containing amino, i.e., the compounds of the formula (I-2-22b) 1578

[0764] (wherein, R1-2-22b and R2-2-22b are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-22b(s) and R2-2-22b(s) is an amino or a group containing amino and the other symbols are the same meaning as hereinbefore described.) and the corresponding compounds containing sulfo.

[0765] The sulfonamidation may be carried out by the same procedure for preparation of the compounds of the formula (I-1-6a) in [6].

[0766] [23] The compounds of the present invention of the formula (I-2) in which at least one of R1(s) or R2(s) is a substituted aminocarbonyloxy or a group containing a substituted aminocarbonyloxy, i.e., the compounds of the present invention of the formula (I-2-23) 1579

[0767] (wherein, R1-2-23 and R2-2-23 are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-23(s) and R2-2-23(s) is a substituted aminocarbonyloxy or a group containing a substituted aminocarbonyloxy and the other symbols are the same meaning as hereinbefore described,) may be prepared by reacting the compounds of the formula (I-2) in which at least one of R1(s) or R2(s) is a hydroxy or a group containing hydroxy, i.e., the compounds of the formula (I-2-23a) 1580

[0768] (wherein, R1-2-23a and R2-2-23a are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-23a(s) and R2-2-23a(s) is a hydroxy or a group containing hydroxy and the other symbols are the same meaning as hereinbefore described.) and the corresponding compounds containing isocyanate.

[0769] This reaction may be carried out by the same procedure for preparation of the compounds of the formula (I-1-7) in [7].

[0770] [24] The compounds of the present invention of the formula (I-2) in which at least one of R1(s) or R2(s) is a substituted aminocarbonylamino or a group containing a substituted aminocarbonylamino, i.e., the compounds of the present invention of the formula (I-2-24) 1581

[0771] (wherein, R1-2-24 and R2-2-24 are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-24(s) and R2-2-24(s) is a substituted aminocarbonylamino or a group containing a substituted aminocarbonylamino and the other symbols are the same meaning as hereinbefore described.) may be prepared by reacting the compounds of the formula (I-2) in which at least one of R1(s) or R2(s) is an amino or a group containing amino, i.e., the compounds of the formula (I-2-24a) 1582

[0772] (wherein, R1-2-24a and R2-2-24a are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-24a(s) and R2-2-24a(s) is an amino or a group containing amino and the other symbols are the same meaning as hereinbefore described.) and the corresponding compounds containing isocyanate.

[0773] This reaction may be carried out by the same procedure for preparation of the compounds of the formula (I-1-7) in [7].

[0774] [25] The compounds of the present invention of the formula (I-2) in which at least one of R1(s) or R2(s) is a substituted oxycarbonylamino or a group containing a substituted oxyocarbonylamino, i.e., the compounds of the present invention of the formula (I-2-25) 1583

[0775] (wherein, R1-2-25 and R2-2-25 are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-25(s) and R2-2-25 (s) is a substituted oxycarbonylamino or a group containing a substituted oxyocarbonylamino and the other symbols are the same meaning as hereinbefore described.) may be prepared by reacting the compounds of the formula (I-2) in which at least one of R1(s) or R2(s) is an amino or a group containing amino, i.e., the compounds of the formula (I-2-25a) 1584

[0776] (wherein, R1-2-25a and R1-2-25a are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-25a(s) and R2-2-25a(s) is an amino or a group containing amino and the other symbols are the same meaning as hereinbefore described.) and the corresponding compounds containing haloformic acid ester.

[0777] This reaction may be carried out by the same procedure for preparation of the compounds of the formula (I-1-9) in [9].

[0778] [26] The compounds of the present invention of the formula (I-1) in which at least one of R1(s) or R2(s) is a substituted oxycarbonyloxy or a group containing a substituted oxycarbonyloxy, i.e., the compounds of the present invention of the formula (I-2-26) 1585

[0779] (wherein, R1-2-26 and R2-2-26 are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-26(s) and R2-2-26(s) is a substituted oxycarbonyloxy or a group containing a substituted oxycarbonyloxy and the other symbols are the same meaning as hereinbefore described.) may be prepared by reacting the compounds of the formula (I-2) in which at least one of R1(s) or R2(s) is a hydroxy or a group containing hydroxy, i.e., the compounds of the formula (I-2-26a) 1586

[0780] (wherein, R1-2-26a and R2-2-26a are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-26a(s) and R2-22-6a(s) is a hydroxy or a group containing hydroxy and the other symbols are the same meaning as hereinbefore described.) and the corresponding compounds containing haloformic acid ester.

[0781] This reaction may be carried out by the same procedure for preparation of the compounds of the formula (I-1-9) in [9].

[0782] [27] The compounds of the present invention of the formula (I-2) in which at least one of R1(s) or R2(s) is a substituted (hydroxy)methyl or a group containing substituted (hydroxy)methyl, i.e., the compounds of the present invention of the formula (I-2-27) 1587

[0783] (wherein, R1-2-27 and R2-2-27 are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-27(s) and R2-2-27(s) is a substituted (hydroxy)methyl or a group containing a substituted (hydroxy)methyl and the other symbols are the same meaning as hereinbefore described.) may be prepared by reacting the compounds of the formula (I-2) in which at least one of R1(s) or R2(s) is a formyl, i.e., the compounds of the formula (I-2-27a) 1588

[0784] (wherein, R1-2-27a and R2-2-27a are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-27a(s) and R2-2-27a(s) is a formyl and the other symbols are the same meaning as hereinbefore described.) and Grignard's reagents or corresponding derivatives containing lithium.

[0785] This reaction may be carried out by the same procedure for preparation of the compounds of the formula (I-1-11a) in (11].

[0786] [28] The compounds of the present invention of the formula (I-2) in which at least one of R1(s) or R2(s) is a substituted carbonyl or a group containing a substituted carbonyl, i.e., the compounds of the present invention of the formula (I-2-28) 1589

[0787] (wherein, R1-2-28 and R2-2-28 are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-28(s) and R2-2-28(s) is a substituted carbonyl or a group containing a substituted carbonyl and the other symbols are the same meaning as hereinbefore described.) may be prepared by oxidizing the said compounds of the formula (I-2-27).

[0788] This reaction may be carried out by the same procedure for preparation of the compounds of the formula (I-1-12) in [12].

[0789] [29] The compounds of the present invention of the formula (I-2) in which at least one of R1(s) or R2(s) is an amino or a group containing amino, i.e., the compounds of the present invention of the formula (I-2-29) 1590

[0790] (wherein, R1-2-29 and R2-22-29 are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-29(s) and R2-2-29(s) is an amino or a group containing amino and the other symbols are the same meaning as hereinbefore described.) may be prepared by reduce of nitro in the compounds of the formula (I-2) in which at least one of R1(s) or R2(s) is a nitro or a group containing nitro, i.e., the compounds of the formula (I-2-29a) 1591

[0791] (wherein, R2-2-29a and R2-2-29a are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-29a(s) and R2-2-29a(s) is a nitro or a group containing nitro and the other symbols are the same meaning as hereinbefore described.).

[0792] The reduction of nitro may be carried out by the same procedure for preparation of the compounds of the formula (I-1-13) in [13].

[0793] [30] The compounds of the present invention of the formula (I-2) in which at least one of R1(s) or R2(s) is a —COOH, hydroxy or amino or a group containing —COOH, hydroxy or amino, i.e., the compounds of the present invention of the formula (I-2-30) 1592

[0794] (wherein, R1-2-30 and R2-2-30 are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-30(s) and R2-2-30(s) is a —COOH, hydroxy or amino or a group containing —COOH, hydroxy or amino and the other symbols are the same meaning as hereinbefore described.) may be prepared by removal of protecting group in the compounds of the formula (I-2) in which —COOH, hydroxy or amino which is protected by a protecting group or a group containing —COOH, hydroxy or amino which is protected by a protecting group, i.e., the compounds of the formula (I-2-30a) 1593

[0795] (wherein, R1-2-30a and R2-2-30a are the same meanings as hereinbefore described for R1 and R2, respectively, provided that at least one of R1-2-30a(s) and R2-2-30a(s) is a protected —COOH (e.g., it is protected by methyl, ethyl, t-butyl and benzyl etc.), protected hydroxy (e.g., it is protected by methoxymethyl, tetrahydropyranyl, t-butyldimethylsilyl, acetyl, benzyl etc.) or protected amino (e.g., it is protected by benzyloxycarbonyl, t-butoxycarbonyloxy, trifluoroacetyl etc.) or a group containing such a group and the other symbols are the same meaning as hereinbefore described.) by an alkaline hydrolysis, by removal of protecting group in an acidic condition, by removal of silyl or by removal of protecting group based on hydrogenelysis. An alkaline hydrolysis, by removal of protecting group in an acidic condition, by removal of silyl or by hydrogenolysis may be carried out by same procedure for preparation of the compounds of the formula (I-1-14) in [14].

[0796] Reaction for removal of protecting group in the present invention means an ordinal one which is well known to the person in the art, for example, alkaline hydrolysis, removal of protecting group in an acidic condition and hydrogenolysis. The aimed compounds of the present invention may be prepared easily by choice of these reactions.

[0797] As well known to the person in the art, a protecting group of carboxy includes, for example, methyl, ethyl, t-butyl and benzyl. In addition, such a group includes the other protecting group which is removable selectively and easily, for example, one described in T. W. Greene, Protective Groups in Organic Synthesis, Wiley, New York, 1991.

[0798] A protecting group of hydroxy includes, for example, methoxymethyl, tetrahydropyranyl, t-butyidimethylsilyl, acetyl, and benzyl. In addition, such a group includes the other protecting group which is removable selectively and easily, for example, one described in T. W. Greene, Protective Groups in Organic Synthesis, Wiley, New York, 1991.

[0799] A protecting group of amino includes, for example, benzyloxycarbonyl, t-butoxycarbonyl, trifluoroacetyl. In addition, such a group includes the other protecting group which is removable selectively and easily, for example, one described in T. W. Greene, Protective Groups in Organic Synthesis, Wiley, New York, 1991.

[0800] The compounds of the formula (V) are known per se or may be prepared according to the following Reaction Scheme or by known methods easily.

[0801] In Reaction Scheme, X is halogen. 1594

[0802] The compounds of the formulae (III), (IV), (VI), (VII) or (VIII) used as starting materials have been known per se or may be prepared by known methods easily.

[0803] Further, the compounds of the formula (I-1-1 c) in which A is benzene, R1 is carboxy, p is 1 and R1 is bonded at 4-position, i.e., the compounds of the formula (XI) are important intermediates of the compounds of the formula (I) of the present invention. The methods for preparation of the compounds of the formula (XI) are shown in the mentioned Reaction Scheme 5. Next, each step is explained in detail.

[0804] The reaction to synthesis of the compounds of the formula (XIII) from the compounds of the formula (XII) is well known. For example, it may be carried out in an inert organic solvent (acetonitrile, benzene, toluene, xylene, methyhlene chloride, chloroform, dimethoxy ethane, tetrahydrofuran, tetrahydropyran, dioxane, diethyl ether, acetone etc.) or mixture thereof, in the presence of Lewis acid (Znl2, ZnCl2, aluminum chloride, TiCl2, lithium hypochloric acid, lithium borotetrafluoride, lithium hexafluoride etc.) and cyanide derivatives (trimethylsilylcyanide, diethyl aluminum cyanide, or diethyl cyanophosphonate etc.) at 0˜40°C.

[0805] The reaction to synthesis of the compounds of the formula (XIV) from the compounds of the formula (XIII) is well known. For example, it may be carried out in an inert organic solvent (benzene, toluene, ethyl acetate, dioxane, dimethoxy ethane, diethyl ether, tetrahydrofuran, tetrahydropyran, the mixture thereof etc.) in the presence of oxidant (2,3-dichloro-5,6-dicyano-1,4-benzoquinon, chloranil (2,3,5,6-tetrachloro-1,4-benzoquinon) etc.) at room temperature to refluxing temperature. Or it may be carried out, for example, in an organic solvent (ethylene glycol, oleic acid, diethylene glycol, dimethyl ether, toluene, benzene, xylene etc.) in the presence of hydrogen acceptor (nitrobenzene, maleic acid, cyclohexen, oleic acid, 1,5-cycloctadien, phenylacetylene, 2-butylic acid etc.) and in the presence of metal catalyst (Pd—C, palladium hydroxide, palladium black, Pd, platinum oxide, Ni, Raney nickel, ruthenium chloride etc.) at 60° C.˜refluxing temperature.

[0806] The reaction to synthesis of the compounds of the formula (XI) from the compounds of the formula (XIV) is well known. For example, it may be carried out in alcohol solvent (ethylene glycol, t-butanol, benzyl alcohol, methanol ethanol , propanol, isopropanol etc.) in the presence of alkali (sodium hydroxide, potassium hydroxide, lithium hydroxide etc.) at 60° C.˜refluxing temperature.

[0807] In each reaction in the present specification, obtained products may be purified by conventional techniques. For example, purification may be carried out by distillation at atmospheric or reduced pressure, by high performance liquid chromatography, by thin layer chromatography or by column chromatography using silica gel or magnesium silicate, by washing or by recrystallization. Purification may be carried out after each reaction, or after a series of reactions.

[0808] In addition, the optical isomers of the compounds of the present invention of the formula (I) may be obtained by an ordinal optical separation (e.g., separation by gas chromatography or by high performance liquid chromatography, separation by crystallization to diastermeric salt or clathrate compounds or separation by preferential crystallization etc.) or by ordinal method for preparation of racemic compound.

[0809] [Pharmacological Activities]

[0810] According to the following experiments, it has been proved that the compounds of the present invention of the formula (I) possess inhibitory activities of producing IL-6 and/or IL-12.

[0811] (1) Assaying Inhibitory Activity on IL-6 production and cellular toxicity

[0812] [Experimental Method]

[0813] 1.5×104 of A549 cells (human lung epithelial cell line) were suspended in dalbeco-modified eagle medium (DMEM) containing 0.5% fetus bovine serum (abbreviated as FBS) (100 μl) and incubated in 96 well-microplate over day and night. The test compound dissolved in various kinds of solvents at various concentrations (20 μl) and Tumor Necrosis Factor-α (TNF-α (Genzyme Co, Cat. No. TNF-H)) dissolved in DMEM at the concentration of 12.5 ng/ml (80 μl) were added thereto. After incubation for 24 hours, the supernatant (200 μl) was recovered to assay the quantity of IL-6 using Enzyme Linked Immuno Solvent Assay (ELISA) Method (R&D Systems Co., Cat. No. D6050), to calculate inhibitory activity of the test compound and determine 50 % inhibitory concentration (IC50). To the cells from which the supernatant was removed, a solution of brom 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolinium (abbreviated as MTT (Dojin Chemical Laboratory, Cat. No. 345-01821)) dissolved in DMEM containing 1 0% FBS at the concentration of 0.5mg/ml (100 μl) was added and incubated for 3 hours. After removing MTT solution, methanol (100 μl) was added thereto. After lyse the cells, the intensity of absorbance on 570 nm as a control of 690 nm was determined to assay cellular toxicity of the test compound. As a result, it has been proved that the compounds of the present invention possess an inhibitory activity on IL-6 production with an IC50 value of 20 μM or less. For example, free compound of the compound of

EXAMPLE 20(4) possessed an inhibitory activity on IL-6 production with an IC50 value of 4.4 μM and showed no cellular toxicity at 10 μM.

[0814] (2) Assaying Inhibitory Activity on IL-12 Production and Cellular Toxicity

[0815] [Experimental Method]

[0816] 2.0×105 of peripheral monocyte prepared from healthy human blood by Ficole gravity centrifugation method (Pharmacia Biotech Co, Cat. No. 17-1440-02) were suspended in RPMI1640 medium containing 10% FBS (170 μl). The test compound dissolved in various kinds of solvents at the various concentrations (10 μl) and 6000 units/ml of Interferon-γ (IFN-γ (Serotec Co, Cat. No. PHP050)) (10 μl) dissolved in RPMI1640 medium containing 10% FBS. After incubation for 24 hours in 96 well-microplate, lipopolysaccharide (6 μg/ml) dissolved in RPMI1640 medium containing 10% FBS (LPS (Difco Co., Cat. No. 3120-25-0)) (10 μl) was added thereto. After incubation for 20 hours, the supernatant (150 μl) was recovered to assay the quantity of IL-12 using ELISA Method (R&D Systems Co, Cat. No. D1200), calculate for inhibitory activity of the test compound and determine 50% inhibitory concentration (IC50) (see J. Exp. Med., 183, 147 (1996)). To the cells from which the supernatant (150 μl) was removed, a solution of MTT dissolved in RPMI1640 medium containing 10% FBS at 1 mg/ml (50 μl) was added and incubated for 3 hours. 2-Propanol containing 0.04N HCl (100 μl) was added thereto. After lyse the cells, the intensity of absorbance on 570 nm as a control of 690 nm was determined to assay cellular toxicity of the test compound. As a results, it has been proved that the compounds of the present invention possess an inhibitory activity on IL-12 production with an IC50 value of 10 μM or less. For example, hydrochloride of the compound of Example 20(4) possessed an inhibitory activity on IL-12 production with an IC50 of 0.11 μM and showed no cellular toxicity at 1 μM.

[0817] [Toxicity]

[0818] The toxicity of the compounds of the present invention is very low and therefore, it is confirmed that these compounds are safe for use as medicine.

[0819] [Application for Pharmaceuticals]

[0820] The compounds of the present invention possess an inhibitory activity of producing IL-6 and/or IL-12 in animal, especially human, so they are useful for prevention and/or treatment of, for example, various inflammatory diseases, sepsis, multiple myeloma, plasma cell leukemia, osteoporosis, cachexia, psoriasis, nephritis, renal cell carcinoma, Kaposi's sarcoma, rheumatoid arthritis, gammopathy, Castleman's disease, atrial myxoma, diabetes mellitus, autoimmune diseases, hepatitis, multiple sclerosis, colitis, graft versus host immune diseases, infectious diseases.

[0821] For the purpose above described, the compounds of the general formula (I) of the present invention, non-toxic salts, acid addition salts, or hydrates thereof may be normally administered systematically or locally, usually by oral or parenteral administration.

[0822] The doses to be administered are determined depending upon age, body weight, symptom, the desired therapeutic effect, the route of administration, and the duration of the treatment etc. In the human adult, the doses per person per dose are generally between 1 mg and 1000 mg, by oral administration, up to several times per day, and between 0.1 mg and 100 mg, by parenteral administration (preferred into vein) up to several times per day, or continuous administration between 1 and 24 hrs. per day into vein.

[0823] As mentioned above, the doses to be used depend upon various conditions. Therefore, there are cases in which doses lower than or greater than the ranges specified above may be used.

[0824] The compounds of the present invention may be administered as inner solid composition's or inner liquid compositions for oral administration, or as injections, liniments or suppositories etc. for parenteral administration.

[0825] Inner solid compositions for oral administration include compressed tablets, pills, capsules, dispersible powders, and granules. Capsules contain hard capsules and soft capsules.

[0826] In such inner solid compositions, one or more of the active compound(s) is or are, admixed with at least one inert diluent (lactose, mannitol, glucose, microcrystalline cellulose, starch etc.), connecting agents (hydroxypropyl cellulose, polyvinylpyrrolidone, magnesium metasilicate aluminate etc.), disintegrating agents (cellulose calcium glycolate etc.), lubricating agents (magnesium stearate), stabilizing agents, assisting agents for dissolving (glutamic acid, asparaginic acid etc.) etc. to prepare pharmaceuticals by known methods. The pharmaceuticals may, if desired, be coated with material such as sugar, gelatin, hydroxypropyl cellulose or hydroxypropyl cellulose phthalate etc., or be coated with two or more films. And further, coating may include containment within capsules of absorbable materials such as gelatin.

[0827] Inner liquid compositions for oral administration include pharmaceutically-acceptable water-agents, emulsions, syrups and elixirs etc. In such liquid compositions, one or more of the active compound(s) is or are comprised in inert diluent(s) commonly used in the art (purified water, ethanol or mixture thereof etc.). Besides inert diluents, such compositions may also comprise adjuvants such as wetting agents, suspending agents, sweetening agents, flavouring agents, perfuming agents and preserving agents.

[0828] Injections for parenteral administration include solutions, suspensions and emulsions, and solid injections. Aqueous solutions or suspensions include distilled water for injection and physiological salt solution. Non-aqueous solutions or suspensions include propylene glycol, polyethylene glycol, plant oil such as olive oil, alcohol such as ethanol, POLYSOLBATE80 (registered trade mark) etc. Such compositions may comprise additional diluents: e.g. preserving agents, wetting agents, emulsifying agents, dispersing agents, stabilizing agent, assisting agents such as assisting agents for dissolving (for example, glutamic acid, asparaginic acid). They may be sterilized for example, by filtration through a bacteria-retaining filter, by incorporation of sterilizing agents in the compositions or by irradiation. They may also be manufactured in the form of sterile solid compositions and which can be dissolved in sterile water or some other sterile diluent for injection immediately before use.

[0829] Other compositions for parenteral administration include liquids for external use, and endermic liniments, ointments, spray, suppositories and pessaries which comprise one or more of the active compound(s) and may be prepared by known methods.

[0830] Spray compositions may comprise additional substances other than inert diluents: e.g. stabilizing agents such as sodium hydrogen sulfate, stabilizing agents to give isotonicity, isotonic buffer such as sodium chloride, sodium citrate, citric acid. For preparation of such spray compositions, for example, the method described in the U.S. Pat. Nos. 2,868,691 or 3,095,355 may be used.

BEST MODE FOR CARRYING OUT THE INVENTION

[0831] The following reference Examples and Examples are intended to illustrate, but do not limit the present invention.

[0832] The solvents in parenthesis show the developing or eluting solvents and the ratios of the solvents used are by volume in chromatographic separations. The solvents in parentheses in NMR show the solvents used for measurement.

EXAMPLE 1

3-Phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0833] 1595

[0834] To asolution of benzothiophene-1,1-dioxide (1 g) in tetrahydrofuran (10 ml) were added triethylamine (1.55 ml) and thiophenol (798 mg). The reaction mixture was stirred for 4 hours at room temperature. To the reaction mixture was water added. The mixture was extracted with ethyl acetate. The extract was washed by water, a saturated aqueous solution of sodium chloride successively, dried over anhydrous sodium sulfate, and concentrated. The residue was purified with chromatography on silica gel (hexane:ethyl acetate=1:1). The obtained compound was then recrystallized from ethanol to give the title compound (1.18 g) having the following physical data.

[0835] TLC: Rf 0.46 (hexane:ethyl acetate=2:1);

[0836] NMR (CDCl3): δ 7.85-7.18 (9H, m), 4.98 (1H, t, J=7 Hz), 3.80 (1H, dd, J=14, 7 Hz), 3.51 (1H, dd, J=14, 7 Hz).

EXAMPLES 1(1)˜1(18)

[0837] By the same procedure as described in Example 1 using a corresponding thiol instead of thiophenol, the following compounds of the present invention were obtained.

EXAMPLE 1 (1)

3-(Thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0838] 1596

[0839] TLC: Rf 0.53 (hexane:ethyl acetate=1:1);

[0840] NMR (CDCl3):δ 7.81-7.66 (m, 3H), 7.58-7.51 (m, 1H), 7.42 (dd, J=5.4, 1.4 Hz, 1H), 7.14 (dd, J=3.6, 1.4 Hz, 1H), 7.00 (dd, J=5.4, 3.6 Hz, 1H), 4.78 (t-like, J=6.9 Hz, 1H), 3.80 (dd, J=14.0, 7.2 Hz, 1H), 3.51 (dd, J=14.0, 6.6 Hz, 1H).

EXAMPLE 1 (2)

3-(4-Methylphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0841] 1597

[0842] TLC: Rf 0.40 (hexane:ethyl acetate=2:1);

[0843] NMR (CDCl3): δ 7.85-7.57 (m, 4H), 7.42 (d, J=8.0 Hz, 2H), 7.21 (d, J=8.0 Hz, 2H), 4.80 (t-like, J=6.5 Hz, 1H), 3.85 (dd, J=14.0, 7.5 Hz, 1H), 3.38 (dd, J=14.0, 6.0 Hz, 1H).

EXAMPLE 1 (3)

3-(4-Methoxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0844] 1598

[0845] TLC: Rf 0.38 (hexane:ethyl acetate=2:1);

[0846] NMR (CDC3): δ 7.82-7.45 (4H, m), 7.36 (2H, d, J=7 Hz), 6.85 (2H, d, J=7 Hz), 4.83 (1 H, t, J=7 Hz), 3.83 (3H, s), 3.74 (1 H, dd, J=13, 7 Hz), 3.46 (1 H, dd, J=13, 7 Hz).

EXAMPLE 1 (4)

3-(4-Chlorophenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0847] 1599

[0848] TLC: Rf 0.37 (hexane ethyl acetate=2:1);

[0849] NMR (CDCl3): δ 7.88-7.67 (m, 4H), 7.32 (d, J=8.0 Hz, 2H), 7.25 (d, J=8.0 Hz, 2H), 4.83 (t-like, J=7.0 Hz, 1H), 3.83 (dd, J=14.5, 6.5 Hz, 1H), 3.52 (dd, J=14.5, 7.8 Hz, 1H).

EXAMPLE 1 (5)

3-(4-Fluorophenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0850] 1600

[0851] TLC Rf 0.36 (hexane:ethyl acetate=2:1);

[0852] NMR (CDCl3): δ 7.80-7.32 (m, 6H), 7.04 (t-like, J=8.8 Hz, 2H), 4.90 (t-like, J=6.6 Hz, 1H), 3.78 (dd, J=13.6, 7.6 Hz, 1H), 3.50 (dd, J=13.6, 6.4 Hz, 1H).

EXAMPLE 1 (6)

3-(4-Hydroxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0853] 1601

[0854] TLC: Rf 0.33 (hexane:ethyl acetate=1:1);

[0855] NMR (CDCl3): δ 3.45 (dd, J=15, 7.5Hz, 1H), 3.75 (dd, J15, 7.5Hz, 1H), 4.80 (t, J=7.5 Hz, 1H), 5.60 (s, 1H), 6.75 (d, J=7.5 Hz, 2H), 7.30 (d, J=7.5 Hz, 2H), 7.45-7.80 (m, 4H).

EXAMPLE 1 (7)

3-(3-Hydroxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0856] 1602

[0857] TLC: Rf 0.36 (hexane:ethyl acetate=1:1);

[0858] NMR (CDCl3): δ 3.50 (dd, J=15, 7.5 Hz, 1H), 3.85 (dd, J=15, 7.5 Hz, 1H), 5.00 (t, J=7.5 Hz, 1H), 5.65 (s, 1H), 6.75-7.00 (m, 3H), 7.10-7.30 (m, 1H), 7.50-7.80 (m, 4H).

EXAMPLE 1 (8)

3-(2-Hydroxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0859] 1603

[0860] TLC: Rf 0.33 (hexane ethyl acetate=1:1);

[0861] NMR (CDCl3): δ 3.45 (dd, J=12.5, 5.0 Hz, 1H), 3.70 (dd, J=12.5, 7.5 Hz, 1H), 4.80 (dd, J=7.5, 5.0 Hz, 1H), 6.65 (s, 1H), 6.90 (t, J=7.5 Hz, 1H), 7.00 (d, J=7.5 Hz, 1H), 7.30 -7.80 (m, 6H).

EXAMPLE 1 (9)

3-(Pyridin-4-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0862] 1604

[0863] TLC: Rf 0.45 (ethyl acetate)

[0864] NMR (CDCl3): δ 3.58 (dd, J=13, 6 Hz, 1H), 4.00 (dd, J=13, 6 Hz, 1H), 5.22 (t, J=6 Hz, 1H), 7.20 (m, 2H), 7.69 (m, 4H), 8.51 (m, 2H)

EXAMPLE 1 (10)

3-(Pyrimidin-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0865] 1605

[0866] TLC: Rf 0.55 (hexane:ethyl acetate=1:2);

[0867] NMR (CDCl3): δ 3.71 (dd, J=14, 7 Hz, 1H), 4.24 (dd, J=14, 7 Hz, 1H), 5.70 (t, J=7 Hz, 1H), 7.10 (t, J=5 Hz, 1H), 7.52-7.85 (m, 4H), 8.58 (d, J=5 Hz, 2H).

EXAMPLE 1 (11)

3-(Thiazol-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0868] 1606

[0869] TLC: Rf 0.52 (hexane:ethyl acetate=1:1);

[0870] NMR (CDCl3): δ 3.55 (dd, J=13.4 Hz, 1H), 3.81 (dd, J=13, 7 Hz, 1H), 5.60 (dd, J=7, 4 Hz, 1H), 7.57-7.80 (m, 6H).

EXAMPLE 1 (12)

3-(3-Methylfuran-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0871] 1607

[0872] TLC: Rf 0.45 (hexane ethyl acetate=4:1);

[0873] NMR (CDCl3): δ 2.27 (s, 3H), 3.39 (dd, J=14.0 Hz, 6.0 Hz, 1H), 3.75 (dd, J=14.0 Hz, 6.0 Hz, 1H), 4.69 (t, J=6.0 Hz, 1H), 6.07 (d, J=2.0 Hz, 1H), 7.25 (d, J=2.0 Hz, 1H), 7.48-7.77 (m, 4H).

EXAMPLE 1 (13)

3-(3-Methoxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0874] 1608

[0875] TLC: Rf 0.44 (hexane:ethyl acetate=1:1);

[0876] NMR (CDCl3): δ 3.50 (dd, J=12.5, 7.5 Hz, 1H), 3.75 (s, 3H), 3.80 (dd, J=12.5, 7.5 Hz, 1H), 5.00 (t, J=7.5 Hz, 1H), 6.85-7.05 (m, 3H), 7.20-7.30 (m, 1H), 7.50-7.80 (m, 4H).

EXAMPLE 1 (14)

3-(2-Methoxycarbonylphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0877] 1609

[0878] TLC: Rf 0.40 (hexane ethyl acetate=1:1);

[0879] NMR (CDCl3): δ 3.60 (dd, J=15, 7.5 Hz, 1H), 3.90 (s, 3H), 3.95 (dd, J=15, 7.5 Hz, 1H), 5.25 (t, J=7.5 Hz, 1H), 7.30-7.80 (m, 7H), 7.95-8.05 (m, 1H).

EXAMPLE 1 (15)

3-Cyclohexylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0880] 1610

[0881] TLC: Rf 0.32 (hexane:ethyl acetate=3:1);

[0882] NMR (CDCl3): δ 1.26-2.10 (m, 10H), 2.80-2.93 (m, 1H), 3.52 (dd, J=13.4, 7.4 Hz, 1H), 3.92 (dd, J=13.4, 7.4 Hz, 1H), 4.68 (t, J=7.4 Hz, 1H), 7.47-7.54 (m, 1H), 7.59-7.67 (m, 1H), 7.70-7.75 (m, 2H).

EXAMPLE 1 (16)

3-(Naphthalen-1-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0883] 1611

[0884] TLC: Rf 0.36 (hexane:ethyl acetate=2:1);

[0885] NMR (CDCl3): δ 3.51 (dd, J=13.6, 5.8 Hz, 1H), 3.64 (dd, J=13.6 Hz, 7.3 Hz, 1H), 5.01 (t-like, J=6.4 Hz, 1H), 7.40-7.79 (m, 8H), 7.90-7.94 (m, 2H), 8.52-8.56 (m, 1H).

EXAMPLE 1 (17)

3-(2-Methoxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0886] 1612

[0887] TLC: Rf 0.49 (hexane:ethyl acetate=1:1);

[0888] NMR (CDCl3): δ 3.55 (dd, J=12.5, 7.5 Hz, 1H), 3.75 (dd, J=12.5, 7.5 Hz, 1H), 3.90 (s, 3H), 5.10 (t, J=7.5 Hz, 1H), 6.90-7.00 (m, 2H), 7.30-7.80 (m, 6H).

EXAMPLE 1 (18)

3-(1-Methylimidazol-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0889] 1613

[0890] TLC: Rf 0.50 (hexane:ethyl acetate=1:2); NMR (CDCl3):5 3.54 (dd, J=14, 3 Hz, 1H), 3.65 (s, 3H), 4.04 (dd, J=14, 9 Hz, 1H), 6.58 (d, J=2.7 Hz, 1H), 6.65 (d, J=2.7 Hz, 1H), 6.95 (dd, J=9,3 Hz, 1H), 7.56 (m, 1H), 7.67 (m, 2H), 7.85 (m, 1H).

EXAMPLE 2

3-Phenylsulfinyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0891] 1614

[0892] To potassium peroxymonosulfate (“OXONE” (trade name) marketed from Aldrich Co., abbreviated as OXONE®; 2.14 g), water (10 ml) was added. To a solution of a compound prepared in Example 1 (0.961 g) in methanol (50 ml), thus obtained aqueous solution of OXONE® (5.5 ml) was added at 0° C. The reaction mixture was stirred at 0° C. for 30 minutes. To the reaction mixture, water was added. The mixture was extracted by ethyl acetate. The extract was washed by water (twice) and a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate and concentrated. The residue was recrystallized from ethanol to give the title compound (361 mg) having the following physical data.

[0893] TLC: Rf 0.13 (hexane:ethyl acetate=1:1);

[0894] NMR (CDCl3): δ 7.85-7.45 (9H, m), 4.57 (1H, t, J=7 Hz), 3.98 (1H, dd, J=14, 7 Hz), 3.19 (1H, dd, J=14, 7 Hz).

EXAMPLES 2 (1)˜2 (2)

[0895] By the same procedure as described in Example 2 using the compounds prepared in Example 1 (1) and Example 1 (14) instead of the compound prepared in Example 1, the following compounds of the present invention were obtained.

EXAMPLE 2 (1)

3-(Thiophen-2-yl)sulfinyl-2,3-dihydro-1,1 -dioxidebenzo[b]thiophene

[0896] 1615

[0897] TLC: Rf 0.01 (hexane:ethyl acetate=1:1);

[0898] NMR (CDCl3): δ 7.95-7.50 (4.5H m), 7.50-7.25 (1.5H, m), 7.25-7.10 (1H, m), 4.99 (0.5H, dd, J=8.4, 4 Hz), 4.81(0.5H, dd, J=8.4, 4 Hz), 4.02 (0.5H, dd, J=14.2, 4.4 Hz), 3.72-3.40 (1.5H, m).

EXAMPLE 2 (2)

3-(2-Methoxycarbonylphenyl)sulfinyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0899] 1616

[0900] TLC: Rf 0.33 (hexane:ethyl acetate=1:1);

[0901] NMR (CDCl3): δ 2.90 (dd, J=12.5, 7.5 Hz, 1H), 4.00 (s, 3H), 4.00(dd, J=12.5, 7.5 Hz, 1H), 5.05 (t, J=7.5 Hz, 1H), 7.55-7.90 (m, 5H), 8.10-8.25 (m, 3H).

EXAMPLE 3

3-Phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0902] 1617

[0903] To OXONE® (2.14 9), water (10 ml) was added. To a solution of the compound prepared in Example 1 (0.961 g) in methanol (50 ml),was added thus obtained aqueous solution of OXONE® at room temperature. The reaction mixture was stirred for 2 hours at room temperature. To the reaction mixture, water was added. The mixture was extracted by ethyl acetate. The extract was washed by water (twice) and a saturated aqueous solution of sodium chloride successively, dried over anhydrous sodium sulfate, and concentrated. The residue was recrystallized from ethanol to give the compound of the present invention (1.54 g) having the following physical data.

[0904] TLC: Rf 0.45 (hexane:ethyl acetate=1:1);

[0905] NMR (CDCl3): δ 3.65-3.85 (m, 2H), 5.10 (dd, J=10, 5.0 Hz, 1H), 7.40-7.80 (m, 8H), 8.05 (d, J=10 Hz, 1H).

EXAMPLES 3 (1)˜3 (17)

[0906] By the same procedure as described in Example 3 using the compounds prepared in Examples 1 (1)˜1 (17) instead of the compound prepared in Example 1, or using 3-chloroperbenzoic acid instead of OXONE® as an oxidant, the following compounds of the present invention were obtained.

EXAMPLE 3 (1)

3-(Thiophen-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0907] 1618

[0908] TLC: Rf 0.18 (hexane:ethyl acetate=2:1);

[0909] NMR (CDCl3): δ 8.08 (d, J=5.0 Hz, 1H), 7.82-7.66 (m, 5H), 7.20 (dd, J=5.0, 3.8Hz, 1H), 5.82 (dd, J=9.4, 3.1 Hz, 1H), 4.07 (dd, J=15.4, 9.4 Hz, 1H), 3.83 (dd, J=15.4, 3.1 Hz, 1H).

EXAMPLE 3 (2)

3-(4-Methylphenyl)sulfonyl-2,3-dihidro-1,1 -dioxidebenzo[b]thiophene

[0910] 1619

[0911] TLC. Rf 0.11 (hexane:ethyl acetate=2:1);

[0912] NMR (CDCl3): δ 8.04 (1H, d, J=8 Hz), 7.82-7.58 (3H, m), 7.53 (2H, d, J=9 Hz), 7.28 (2H, d, J=9 Hz), 5.08 (1 H, dd, J=1H, 8 Hz), 3.86-3.55 (2H, m), 2.42 (3H, s).

EXAMPLE 3 (3)

3-(4-Methoxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0913] 1620

[0914] TLC: Rf 0.23 (hexane:ethyl acetate=1:1);

[0915] NMR (CDCl3): δ 8.04 (1H, d, J=8 Hz), 7.88-7.60 (3H, m), 7.54 (2H, d, J=7 Hz), 6.91 (2H, d, J=7 Hz), 5.06 (1 H, t, J=7 Hz), 3.85 (3H, s), 3.80-3.60 (2H, m).

EXAMPLE 3 (4)

3-(4-Chlorophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0916] 1621

[0917] TLC: Rf 0.26 (hexane:ethyl acetate=2:1);

[0918] NMR (CDCl3): δ 8.02 (1H, d, J=8 Hz), 7.85-7.58 (3H, m), 7.58-7.32 (4H, m), 5.09 (1 H, t, J=7 Hz), 3.90-3.65 (2H, m).

EXAMPLE 3 (5)

3-(4-Fluorophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0919] 1622

[0920] TLC: Rf 0.41 (hexane:ethyl acetate=1:1)

[0921] NMR (CDCl3): δ 8.03 (1H, d, J=8 Hz), 7.90-7.45 (5H, m), 7.20-7.00 (2H, m), 5.08 (1H, t, J=7 Hz), 3.80-3.75 (2H, m).

EXAMPLE 3 (6)

3-(4-Hydroxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0922] 1623

[0923] TLC: Rf 0.27 (hexane:ethyl acetate=1:1);

[0924] NMR (CD3OD+CDCl3): δ 7.97 (1 H, d, J=7 Hz), 7.85-7.55 (3H, m), 7.46 (2H, d, J=9 Hz), 6.84 (2H, d, J=9 Hz), 5.09 (1H, t, J=7 Hz), 3.90-3.60 (2H, m).

EXAMPLE 3(7)

3-(3-Hydroxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0925] 1624

[0926] TLC: Rf 0.22 (hexane:ethyl acetate=1:1);

[0927] NMR (CDCl3+DMSO-d6): δ 9.83 (1H, brs), 7.90-7.78 (1 H, m), 7.78-7.50 (3H, m), 7.42-7.08 (4H, m), 5.28-5.10 (1H, m), 3.90-3.58 (2H, m).

EXAMPLE 3 (8)

3-(2-Hydroxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0928] 1625

[0929] TLC: Rf 0.15 (hexane:ethyl acetate=1:1);

[0930] NMR (CDCl3+DMSO-d6): δ 7.90-7.42 (6H, m), 7.13 (1H, d, J=8 Hz), 6.98 (1H, t, J=7 Hz), 5.71 (1H, dd, J=9, 5 Hz), 3.86 (1H, dd, J=14, 5 Hz), 3.65 (1H, dd, J=14, 9 Hz).

EXAMPLE 3 (9)

3-(Pyridin-4-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0931] 1626

[0932] TLC: Rf 0.25 (hexane:ethyl acetate=1:2);

[0933] NMR (DMSO-d6): δ 3.87 (dd, J=15, 3 Hz, 1H), 4.03 (dd, J=15, 9Hz, 1H), 5.94 (dd, J=9, 3 Hz, 1H), 7.70 (dd, J=4, 2 Hz, 2H), 7.81 (m, 4H), 8.88 (dd, J=4, 2 Hz, 2H).

EXAMPLE 3 (10)

3-(Pyrimidin-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0934] 1627

[0935] TLC: Rf 0.15 (methylene chloride);

[0936] NMR (DMSO-d6): δ 4.00 (dd, J=16, 4 Hz, 1H), 4.12 (dd, J=16, 9 Hz, 1H), 6.17 (dd, J=9, 4 Hz, 1H), 7.78 (m, 3H), 7.90 (m, 2H), 9.09 (dd, J=5, 1 Hz, 2H).

EXAMPLE 3 (11)

3-(Thiazol-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0937] 1628

[0938] TLC: Rf 0.40 (hexane:ethyl acetate=1:1);

[0939] NMR (CDCl3): δ 3.87 (dd, J=15, 9 Hz, 1H), 4.20 (dd, J=15, 5 Hz, 1H), 5.39 (dd, J=9, 5 Hz, 1H), 7.61-7.81 (m, 4H), 7.99-8.08 (m, 2H).

EXAMPLE 3 (12)

3-(3-Methylfuran-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]furan

[0940] 1629

[0941] TLC: Rf 0.50 (hexane:ethyl acetate=3:2);

[0942] NMR (CDCl3): δ 2.39 (s, 3H), 3.78 (dd, J=15, 4 Hz, 1H), 3.88 (dd, J=15, 8 Hz, 1H), 5.00 (dd, J=8, 4 Hz, 1H), 5.98 (d, J=2 Hz, 1H), 7.18 (d, J=2 Hz, 1H), 7.60-7.80 (m, 3H), 8.02 (m, 1H).

EXAMPLE 3 (13)

3-(3-Methyoxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0943] 1630

[0944] TLC: Rf 0.33 (hexane:ethyl acetate=1:1);

[0945] NMR (CDCl3): δ 3.65-3.90 (m, 2H), 3.75 (s, 3H), 5.10 (dd, J=10, 5.0Hz, 1H), 7.10-7.50 (m, 4H), 7.60-7.80 (m, 3H), 8.00 (d, J=7.5 Hz, 1H).

EXAMPLE 3 (14)

3-(2-Methoxycarbonylphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0946] 1631

[0947] TLC: Rf 0.59 (methylene chloride:ethyl acetate=9:1);

[0948] NMR (CDCl3): δ 8.01-7.97 (m, 1H), 7.84-7.63 (m, 7H), 6.06 (dd, J=9.0, 4.5 Hz, 1H), 4.04 (s, 3H), 3.92 (dd, J=14.0, 4.5 Hz, 1H), 3.63 (dd, J=14.0, 9.0 Hz, 1H).

EXAMPLE 3 (15)

3-Cyclohexylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0949] 1632

[0950] TLC: Rf 0.37 (hexane:ethyl acetate=1:1);

[0951] NMR (CDCl3): δ 1.13-1.68 (m, 8H), 1.90-1.96 (m, 1H), 2.15-2.19 (m, 1H), 3.07-3.23 (m, 1H), 3.87 (dd, J=14.5, 8.2 Hz, 1H), 3.95 (dd, J=14.5, 5.2 Hz, 1H), 4.96 (dd, J=8.2, 5.2 Hz, 1H), 7.63-7.83 (m, 3H), 7.96-8.00 (m, 1H).

EXAMPLE 3 (16 )

3-(Naphthalen-1-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0952] 1633

[0953] TLC: Rf 0.40 (hexane:ethyl acetate=1:1);

[0954] NMR (CDCl3): δ 3.38 (dd, J=14.4, 8.8 Hz, 1H), 3.77 (dd, J=14.4, 5.0 Hz, 1H), 5.31 (dd, J=8.8, 5.0 Hz, 1H), 7.60-7.81 (m, 7H), 8.00-8.05 (m, 1H), 8.22-8.28 (m, 2H), 8.72-8.77 (m, 1H).

EXAMPLE 3 (17)

3-(2-Methoxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0955] 1634

[0956] TLC: Rf 0.20 (hexane:ethyl acetate=1:1);

[0957] NMR (CDCl3+DMSO-d6): δ 3.65 (dd, J=15, 10 Hz, 1H), 3.80 (dd, J=15, 5.0 Hz, 1H), 4.00 (s, 3H), 5.55 (dd, J=10, 5.0 Hz, 1H), 7.05-7.20 (m, 2H), 7.60-7.95 (m, 6H).

EXAMPLE 4

3-(4-(2-(Piperidin-1-yl)ethoxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0958] 1635

[0959] To a solution of the compound prepared in Example 3 (6) (283 mg) in dimetyhylformamide (5 ml) were added N-chloroethylpiperidine (193 mg) and cesium carbonate (1.0 g). The reaction mixture was stirred at room temperature overnight. To the reaction mixture, water was added. The mixture was extracted by ethyl acetate. The extract was washed by water (three times), a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and concentrated. The residue was purified with column chromatography on silica gel (hexane:ethyl acetate=1:1) to give the compound of the present invention (186 mg) having the following physical data.

[0960] TLC: Rf 0.54 (ethyl acetate:methanol:28% ammonia water=100:10:1);

[0961] NMR (CDCl3):δ 8.03 (1H, d, J=7 Hz), 7.85-7.55 (3H, m), 7.53 (2H, d, J=9 Hz), 6.92 (2H, d, J=9 Hz), 5.05 (1H, t, J=7 Hz), 4.13 (2H, t, J=6 Hz), 3.85-3.60 (2H, m), 2.76 (2H, t, J=6 Hz), 2.49 (4H, brt, J=6 Hz), 1.68-1.45 (6H, m).

EXAMPLES 4 (1)˜4 (4)

[0962] By the same procedure as described in Example 4 by using the compounds prepared in Examples 3 (6)˜3 (8) and corresponding halogenated compounds, the following compounds of the present invention were obtained.

EXAMPLE 4 (1)

3-(4- (2-(pyrrolidin-1-yl)ethoxy) phenyl)sulfonyl)-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0963] 1636

[0964] TLC: Rf 0.35 (ethyl acetate:methanol:28% ammonia water=100:10:1);

[0965] NMR (CDCl3): δ 8.03 (1H, d, J=7 Hz), 7.90-7.40 (5H, m), 6.93 (2H, d, J=7 Hz), 5.18-4.95 (1H, m), 4.14 (2H, t, J=6 Hz), 3.90-3.60 (2H, m), 2.91 (2H, t, J=6 Hz), 2.75-2.40 (4H, m), 1.84-1.74 (4H, m).

EXAMPLE 4 (2)

3-(4-(2-(Morpholine-1-yl)ethoxy) phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0966] 1637

[0967] TLC: Rf 0.44 (ethyl acetate:methanol:28% ammonia water=100:10:1);

[0968] NMR (CDCl3): δ 8.05 (1H, d, J=7 Hz), 7.85-7.40 (5H, m), 6.91 (2H, d, J=7 Hz), 5.06 (1H, t, J=7 Hz), 4.13 (2H, t, J=6 Hz), 3.95-3.50 (6H, m), 2.80 (2H, t, J=6 Hz), 2.70-2.40 (4H, m).

EXAMPLE 4 (3)

3-(3-Benzyloxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0969] 1638

[0970] TLC: Rf 0.55 (hexane:ethyl acetate=1:1);

[0971] NMR (CDCl3): δ 8.02 (1H, d, J=7 Hz), 7.85-7.52 (3H, m), 7.52-7.10 (9H, m), 5.15-4.85 (3H, m), 3.80-3.45 (2H, m).

EXAMPLE 4 (4)

3-(2-Benzyloxyohenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0972] 1639

[0973] TLC: Rf 0.37 (hexane ethyl acetate=1:1);

[0974] NMR (CDCl3): δ 7.93 (1H, dd, J=8, 2 Hz), 7.85-7.30 (10 H, m), 7.25-7.08 (2H, m), 5.52 (1H, dd, J=9, 5 Hz), 5.28 (2H, s), 3.79 (1H, dd, J=14, 5 Hz), 3.48 (1H, dd, J=14, 9 Hz).

EXAMPLE 5

3-(4-(Pyridin-2-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0975] 1640

[0976] By the same procedure as described in Example 4 using the compound prepared in Example 1 (6) instead of the compound prepared in Example 3 (6), and using a corresponding halogenated compound instead of N-chloroethylpiperidine, the compound of the present invention having the following physical data was obtained.

[0977] TLC: Rf 0.58 (ethyl acetate)

[0978] NMR (CDCl3): δ 8.65-8.55 (1H, m), 7.80-7.20 (9H, m), 7.00-6.90 (2H, m), 5.20 (2H, s), 4.85 (1H, t, J=7.5 Hz), 3.75 (1H, dd, J=12.5, 7.5 Hz), 3.45 (1H, dd, J=12.5, 7.5 Hz).

EXAMPLES 5 (1)˜5 (9)

[0979] By the same procedure as described in Example 5 using the compounds prepared in Examples 1 (6)˜1 (8), the following compounds of the present invention were obtained.

EXAMPLE 5 (1)

3-(4-Pyridin-3-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0980] 1641

[0981] TLC: Rf 0.42 (ethyl acetate);

[0982] NMR (CDCl3): δ 8.70-8.60 (2H, m), 7.80-7.30 (8H, m), 7.00-6.90 (2H, m), 5.05 (2H, s), 4.85 (1H, t, J=5 Hz), 3.75 (1H, dd, J=15, 5 Hz), 3.45 (1H, dd, J=15, 5 Hz).

EXAMPLE 5 (2)

3-(4-(Pyridin-4-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0983] 1642

[0984] TLC: Rf 0.33 (ethyl acetate);

[0985] NMR (CDCl3): δ 8.65-8.60 (2H, m), 7.80-7.30 (8H, m), 7.00-6.90 (2H, m), 5.10 (2H, s), 4.85 (1H, t, J=5 Hz), 3.75 (1H, dd, J=15, 5 Hz), 3.45 (1H; dd, J=15, 5 Hz)

EXAMPLE 5 (3)

3-(4-(3-Hydroxypropyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0986] 1643

[0987] TLC: Rf 0.14 (hexane:ethyl acetate=1:1);

[0988] NMR (CD3OD): δ 1.90-2.10 (m, 2H), 3.30-3.50 (m, 1H), 3.50-4.00 (m, 3H), 4.00-4.20 (m, 2H), 4.90-5.10 (m, 1H), 6.80-7.00 (m, 2H), 7.30-7.50 (m, 2H), 7.50-7.80 (m, 4H).

EXAMPLE 5(4)

3-(3-(Pyridin-3-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo [b] thiophene

[0989] 1644

[0990] TLC: Rf 0.44 (ethyl acetate);

[0991] NMR (CDCl3): δ 3.50 (dd, J=12.5, 7.5 Hz, 1H), 3.80 (dd, J=12.5, 7.5 Hz, 1H), 4.95-5.10 (m, 1H), 5.00 (s, 2H), 6.90-7.10 (m, 3H), 7.20-7.40 (m, 2H), 7.50-7.80 (m, 5H), 8.50-8.70 (m, 2H).

EXAMPLE 5(5)

3-(3-(3-Hydroxypropyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0992] 1645

[0993] TLC: Rf 0.17 (hexane:ethyl acetate=1:1);

[0994] NMR (CDCl3): δ 1.95-2.05 (m, 2H), 3.50 (dd, J=12.5, 7.5 Hz, 1H), 3.80 (dd, J=12.5,7.5 Hz, 1H), 3.85 (t, J=7.5 Hz, 2H), 4.05 (t, J=7.5 Hz, 2H), 5.00 (t, J=7.5 Hz, 1H), 6.80-7.05 (m, 3H), 7.20-7.30 (m, 1H), 7.50-7.80 (m, 4H)).

EXAMPLES 5 (6)

3-(2-(Pyridin-3-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0995] 1646

[0996] TLC: Rf 0.16 (hexane:ethyl acetate=1:1);

[0997] NMR (CD3OD): δ 3.50 (dd, J=15, 5.0 Hz, 1H), 3.85 (dd, J=15, 7.5 Hz, 1H), 5.20 (dd, J=7.5, 5.0 Hz, 1H), 5.25 (s, 2H), 7.00 (t, J=7.5 Hz, 1H), 7.20 (d, J=7.5 Hz, 1H), 7.35-7.70 (m, 7H), 8.00 (d, J=7.5 Hz, 1H), 8.50 (dd, J=5.0, 2.5 Hz, 1H), 8.70 (d, J=2.5 Hz, 1H).

EXAMPLES 5 (7)

3-(2-(3-Hydroxypropyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[0998] 1647

[0999] TLC: Rf 0.30 (hexane:ethyl acetate=1:2);

[1000] NMR (CDCl3): δ 2.05-2.10 (m, 2H), 2.30-2.60 (m, 1H), 3.50 (dd, J=15, 5.0 Hz, 1H), 3.70 (dd, J=5, 7.5 Hz, 1H), 3.90 (t, J=5.0 Hz, 2H), 4.20-4.40 (m, 2H), 5.10 (dd, J=7.5, 5.0 Hz, 1H), 6.90-7.00 (m, 2H), 7.30 -7.80 (m, 6H).

EXAMPLE 5 (8)

3-(4-(2-(t-Butoxycarbonylamino)ethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1001] 1648

[1002] TLC: Rf 0.30 (toluene:ethyl acetate=4:1);

[1003] NMR (CDCl3): δ 7.80-7.10 (6H, m), 6.80 (2H, d, J=10 Hz), 5.10-4.70 (2H, m), 4.00 (2H, t, J=5 Hz), 3.75 (1H, dd, J=15, 7.5 Hz), 3.60-3.40 (3H, m), 1.45 (9H, s).

EXAMPLE 5 (9)

3-(3-(2-(t-Butoxycarbonylamino)ethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1004] 1649

[1005] TLC: Rf 0.40 (hexane ethyl:acetate=1:1);

[1006] NMR (CDCl3): δ 7.80-7.50 (4H, m), 7.40-7.20 (1H, m), 7.05-6.70 (3H, m), 5.05-4.90 (2H, m), 3.95 (2H, t, J=5 Hz), 3.80 (1H, dd, J=15, 5 Hz), 3.60-3.40 (3H, m), 1.45 (9H, s).

EXAMPLE 6

3-(4-(Pyridin-2-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1007] 1650

[1008] By the same procedure as described in Example 3 using the compound prepared in Example 5 instead of the compound prepared in Example 1, and then by converting into the corresponding hydrochloride by a known method, the compound of the present invention having the following physical data was obtained.

[1009] Free Compound:

[1010] TLC: Rf 0.44 (ethyl acetate);

[1011] NMR (DMSO-d6): δ 8.60-8.55 (1H, m), 7.90-7.60 (7H, m), 7.50 (1H, d, J=7.5 Hz), 7.40-7.30 (1H, m), 7.20 (2H, d, J=7.5 Hz), 5.70 (1H, dd, J=10, 2.5 Hz), 5.30 (2H, s), 4.00 (1H, dd, J=15, 10 Hz), 3.75 (1H, dd, J=15, 2.5 Hz).

[1012] Hydrochloride:

[1013] TLC: Rf 0.49 (ethyl acetate:triethylamine=19:1);

[1014] NMR (CD3OD): δ 3.80 (dd, J=15, 25 Hz, 1H), 3.95 (dd J-15, 10 Hz, 1H), 5.50 (dd, J=10, 2.5 Hz, 1H), 5.60 (s, 2H), 7.20 (d, J=7.5 Hz, 2H), 7.55-8 00 (m, 4H), 7.70 (d, J=7.5 Hz, 2H), 8.05-8.25 (m, 2H), 8.60-8.95 (m, 2H).

EXAMPLES 6 (1)˜6 (9)

[1015] Using the compounds prepared in Examples 5 (1)˜5 (9) instead of the compound prepared in Example 5, by the same procedure as described in Example 5, or by the same reaction using 3-chloroperbenzoic acid instead of OXONE® as an oxidant, and if necessary, by converting into corresponding salts, the following compounds of the present invention were obtained.

EXAMPLE 6 (1)

3-(4-(Pyridin-3-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1016] 1651

[1017] Free Compound:

[1018] TLC: Rf 0.27 (ethyl acetate);

[1019] NMR (CDCl3): δ 8.70-8.55 (2H, m), 8.10-8.00 (1H, m), 7.80-7.50 (6H, m), 7.40-7.30 (1H, m), 7.10-6.90 (2H, m), 5.15 (2H, s), 5.20-5.00 (1H, m), 3.90-3.70 (2H, m).

[1020] Hydrochloride:

[1021] TLC: Rf 0.38 (ethyl acetate:triethylamine=19:1);

[1022] NMR (CD3OD): δ 3.80 (dd,J=15,2.5 Hz, 1H), 3.95 (dd, J=15, 10 Hz, 1H), 5.45 (s, 2H), 5.45-5.55 (m, 1H), 7.20 (d, J=10 Hz, 2H), 7.60-8.00 (m, 4H), 7.60(d, J=10 Hz, 2H), 8.10-8.20 (m, 1H), 8.70-9.00 (m, 3H).

EXAMPLE 6 (2)

3-(4-(Pyridin-4-ylmethyloxy)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1023] 1652

[1024] Free Compound:

[1025] TLC: Rf 0.22 (ethyl acetate);

[1026] NMR (DMSO-d6): δ 8.60 (2H, d, J=5 Hz), 7.90-7.65 (6H, m), 7.45 (2H, d, J=5 Hz), 7.20 (2H, d, J=7.5 Hz), 5.75 (1 H, dd, J=7.5, 2.5 Hz), 5.30 (2H, s), 4.00 (1 H, dd, J=15, 7.5 Hz), 3.80 (1 H, dd, J=15, 2.5 Hz).

[1027] Hydrochloride:

[1028] TLC: Rf 0.35 (ethyl acetate:triethylamine=19:1);

[1029] NMR (DMSO-d6): δ 3.80 (dd, J=15, 2.5 Hz, 1H), 4.00 (dd, J=15, 10 Hz, 1H), 5.55 (s, 2H), 5.75 (dd, J=10, 2.5 Hz, 1H), 7.25 (d, J=10 Hz, 2H), 7.65-7.90 (m, 4H), 7.70 (d, J=10 Hz, 2H), 7.95 (d, J=7.5 Hz, 2H), 8.90 (d, J=7.5 Hz, 2H).

EXAMPLE 6 (3)

3-(4-(3-Hydroxypropylpxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1030] 1653

[1031] TLC: Rf 0.33 (ethyl acetate );

[1032] NMR (CDCl3): δ 2.05 (quint., J=5.0 Hz, 2H), 3.70-3.90 (m, 2H), 3.85 (t, J=5.0 Hz, 2H), 4.15 (t, J=5.0 Hz, 2H), 5.05 (t, J=7.5 Hz, 1H), 6.90 (d, J=10 Hz, 2H), 7.50 (d, J=10 Hz, 2H), 7.60-7.80 (m, 3H), 8.05 (d, J=7.5 Hz, 1H).

EXAMPLE 6 (4)

3-(3-(Pyridin-3-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1033] 1654

[1034] TLC: Rf 0.60 (ethyl acetate methanol:triethylamine=16:2:1);

[1035] NMR (CD3OD): δ 3.85 (dd, J=15, 5.0 Hz, 1H), 3.95 (dd, J=15, 10 Hz, 1H), 5.35 (d, J=12.5 Hz, 1H), 5.45 (d, J=12.5 Hz, 1H), 5.55 (dd, J=10, 5.0 Hz, 1H), 7.20-7.85 (m, 7H), 7.95 (d, J=7.5 Hz, 1H), 8.15 (dd, J=10, 7.5 Hz, 1H), 8.75 (d, J=7.5 Hz, 1H), 8.85 (d, J=5.0 Hz, 1H), 9.00 (s, 1H).

EXAMPLE 6 (5)

3-(3-(3-Hydroxypropyloxy) phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1036] 1655

[1037] TLC: Rf 0.33 (ethyl acetate );

[1038] NMR (CDCl3): δ 1.90-2.20 (m, 2H), 3.65-3.90 (m, 4H), 3.95-4.20 (m, 2H), 5.10 (dd, J=10, 5.0 Hz, 1H), 7.10-7.30 (m, 3H), 7.30-7.45 (m, 1H), 7.60-7.80 (m, 3H), 8.00 (d, J=5.0 Hz, 1H).

EXAMPLE 6 (6)

3-(2-(Pyridin-3-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1039] 1656

[1040] TLC: Rf 0.51 (ethyl acetate:methanol triethylamine=16:2:1);

[1041] NMR (DMSO-d6): δ 3.70 (dd, J=15, 2.5 Hz, 1H), 3.95 (dd, J=15, 10 Hz, 1H), 5.60 (s, 2H) 5.75 (dd, J=10, 2.5 Hz, 1H), 7.20-7.35 (m, 1H), 7.40-7.60 (m, 2H), 7.60-7.90 (m, 5H), 7.95-8.10 (m, 1H), 8.60 (d, J=7.5 Hz, 1H), 8.90 (d, J=5.0 Hz, 1H), 9.05 (s, 1H).

EXAMPLE 6 (7)

3-(2-(3-Hydroxypropylpxy)phenyl)sulfonyl-2,3-dyhydro-1,1-dioxidebenzo[b]thiophene

[1042] 1657

[1043] TLC: Rf 0.37 (ethyl acetate);

[1044] NMR (CDCl3): δ 5 2.00-2.30 (m, 2H), 2.50-2.80 (m, 1H), 3.55 (dd, J=15, 10 Hz, 1H), 3.80 (dd, J=15, 5.0 Hz, 1H), 3.95 (t, J=5.0 Hz, 2H), 4.25-4.50 (m, 2H), 5.65 (dd, J=10, 5.0 Hz, 1H), 7.10-7.20 (m, 2H), 7.60-7.80 (m, 4H), 7.80-7.95 (m, 2H).

EXAMPLE 6 (8)

3-(4-(2-(t-Butoxycarbonylamino)ethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1045] 1658

[1046] TLC: Rf 0.40 (hexane ethyl:acetate=1:2);

[1047] NMR (DMSO-d6): δ 1.40 (s, 9H), 3.80 (dd, J=15, 2.5 Hz, 1H), 3.90-4.15 (m, 5H), 5.75 (dd, J=10, 2.5 Hz, 1H), 6.90-7.10 (m, 1H), 7.10 (d, J=7.5 Hz, 2H), 7.60-7.85 (m, 4H), 7.65 (d, J=7.5 Hz, 2H).

EXAMPLE 6 (9)

3-(3-(2-(t-Butoxycarbonylamino)ethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1048] 1659

[1049] TLC: Rf 0.13 (hexane:ethyl acetate=1:1); NMR (CDCl3): δ 1.45 (s, 9H), 3.45-3.55 (m, 2H), 3.70-4.00 (m, 4H), 4.85-5.00 (m, 1H), 5.10 (dd, J=10, 5.0 Hz, 1H), 7.00-7.50 (m, 4H), 7.60-7.80 (m, 3H), 8.05 (d, J=7.5 Hz, 1H).

EXAMPLE 7

3-(4-(2-Aminoethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1050] 1660

[1051] To a solution of the compound prepared in Example 6 (8) (200 mg) in dioxane (25 ml) and methanol (5 ml), was added a solution of 4N hydrochloric acid in dioxane (10 ml) at room temperature. The reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated to give the compound of the present invention (160 mg) having the following physical data.

[1052] TLC: Rf 0.16 (ethyl acetate:methanol:triethylamine=16:3:1);

[1053] NMR (CD3OD): δ 3.35 (t, J=5.0 Hz, 2H), 3.80 (dd, J=15, 5.0 Hz, 1H), 3.95 (dd, J=15, 10 Hz, 1H), 4.30 (t, J=5.0 Hz, 2H), 5.45 (dd, J=10, 5.0 Hz, 1H), 7.10 (d, J=7.5 Hz, 2H), 7.60 (d, J=7.5 Hz, 2H), 7.60-8.00 (m, 4H).

EXAMPLE 7 (1)

3-(3-(2-Aminoethyloxy) phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1054] 1661

[1055] By the same procedure as described in Example 7 using the compound prepared in Example 6 (9) instead of the compound prepared in Example 6 (8), the compound of the present invention having the following physical data was obtained.

[1056] TLC: Rf 0.60 (ethyl acetate:methanol triethylamine=14:3:1);

[1057] NMR (CD3OD): δ 3.25-3.45 (m, 2H), 3.80-4.00 (m, 2H), 4.15-4.35 (m, 2H), 5.55 (dd, J=7.5, 2.5 Hz, 1H), 7.20-7.50 (m, 4H), 7.60-8.00 (m, 4H).

EXAMPLE 8

3-(4-(2-(N,N-Dimethylamino)ethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1058] 1662

[1059] To a solution of the compound prepared in Example 7 (105 mg) and 90% paraformaldehyde (87 mg) in a mixture of acetic acid (3 ml) and methanol (3 ml), was added sodium cyanoborohydride (86 mg) at 0° C. The reaction mixture was stirred at room temperature overnight. To the reaction mixture, a saturated aqueous solution of sodium bicarbonate was added. The mixture was extracted by ethyl acetate. The extract was washed by water, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified with column chromatography on silica gel (ethyl acetate:methanol:triethylamine=16:3:1). Then to a solution of the obtained compound in dioxane (25 ml) and methanol (5 ml), was added a solution of 4N hydrochloric acid-dioxane (10 ml) at room temperature. The reaction mixture was stirred for 30 minutes and concentrated to give the compound of the present invention (35 mg) having the following physical data.

[1060] TLC: Rf 0.40 (ethyl acetate:methanol:triethylamine=16:3:1); NMR (CD3OD): δ 3.10(s, 6H), 3.60 (t, J=5.0 Hz, 2H), 3.80 (dd, J=15, 2.5 Hz, 1H), 3.95 (dd, J=15, 10 Hz, 1H), 4.45 (t, J=5.0 Hz, 2H), 5.50 (dd, J=10, 2.5 Hz, 1H), 7.10 (d, J=7.5 Hz; 2H), 7-60 (d, J=7.5 Hz, 2H), 7.60-8.00 (m, 4H).

EXAMPLE 8 (1)

3-(3-(2-(N,N-Dimethylamino)ethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1061] 1663

[1062] By the same procedure as described in Example 8 using the compound prepared in Example 7 (1) instead of the compound prepared in Example 7, the compound of the present invention having the following physical data was obtained.

[1063] TLC: Rf 0.44 (ethyl acetate:methanol:triethylamine=16:2:1);

[1064] NMR (DMSO-d6): δ 2.80 (s, 6H), 3.50 (t, J=5.0 Hz, 2H), 3.85 (dd, J=15, 2.5 Hz, 1H), 4.00 (dd, J=15, 10 Hz, 1H), 4.30-4.55 (m, 2H), 5.90 (dd, J=10, 2.5 Hz, 1H), 7.30-7.60 (m, 4H), 7.70-7.90 (m, 4H).

EXAMPLE 9

5-Nitro-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1065] 1664

[1066] By the same procedure as described in Example 1 using 5-nitrobenzothiophene-1,1-dioxide instead of benzothiophene-1,1-dioxide, the compound of the present invention having the following physical data was obtained.

[1067] TLC: Rf 0.35 (hexane:ethyl acetate=2:1);

[1068] NMR (CDCl3): δ 8.52 (1 H, d, J=2 Hz), 8.38 (1 H, dd. J=8.4, 2.0 Hz), 7.89 (1 H, d, J=8.4 Hz), 7.48-7.36 (5H, m), 4.97 (1H, dd, J=7.2, 6.8 Hz), 3.92 (1H, dd, J=13.6, 7.2 Hz), 3.60 (1H, dd, J=13.6, 6.8 Hz).

EXAMPLES 9 (1)˜9 (17)

[1069] By the same procedure as described in Example 9 using a corresponding benzothiophene-1,1-dioxide instead of 5-nitrobenzothiophene-1,1-dioxide, the following compounds were obtained.

EXAMPLE 9 (1)

[1070] 6-Methoxy-3-phenylthio-2,3-dihydro-1,1-di oxidebenzo[b]thiophene 1665

[1071] TLC: Rf 0.60 (hexane:ethyl acetate=1:1);

[1072] NMR (CDCl3): δ 3.52 (dd, J=13.6 Hz, 6.8 Hz, 1H), 3.81 (dd, J=13.6 Hz, 6.8 Hz, 1H), 3.86 (s, 3H), 4.92 (t, J=6.8 Hz, 1H), 7.14-7.21 (m, 2H), 7.32-7.40 (m, 3H), 7.40-7.43 (m, 2H), 7.57-7.61 (m, 1H).

EXAMPLE 9 (2)

4-Methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo [b]thiophene

[1073] 1666

[1074] TLC: Rf 0.21 (hexane:methylene chloride=1:4);

[1075] NMR (CDCl3): δ 3.60 (dd, J=14.0 Hz, 1.8 Hz, 1H), 3.71 (dd, J=14.0 Hz, 6.9 Hz, 1H), 3.91 (s, 3H), 5.05 (dd, J=6.9 Hz, 1.8 Hz, 1H), 7.07 (dd, J=8.1 Hz, 0.7 Hz, 1H), 7.29-7.37 (m, 4H), 7.48-7.56 (m, 3H).

EXAMPLE 9 (3)

5-Methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1076] 1667

[1077] TLC: Rf 0.62 (hexane:ethyl acetate=1:1);

[1078] NMR (CDCl3): δ 3.51 (dd, 1H, J=14, 5 Hz), 3.79 (dd, 1H, J=14, 5 Hz), 3.88 (s, 3H), 4.92 (t, 1H, J=5 Hz), 7.04 (dd, 1H, J=5 Hz, 2 Hz), 7.13 (d, 1H, J=2 Hz), 7.35 (m, 3H), 7.44 (m, 2H), 7.63 (d, 1 H, J=5 Hz).

EXAMPLE 9 (4)

7-Methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1079] 1668

[1080] TLC: Rf 0.42 (hexane:ethyl acetate=1:1);

[1081] NMR (CDCl3): δ 7.62-7.38 (1H, m), 7.58-7.28 (6H, m), 6.79 (1H, d, J=8.4 Hz), 4.89 (1H, t, J=7.6 Hz), 3.97 (3H, s), 3.78 (1H, dd, J=13.5, 7.6 Hz), 3.52 (1H, dd, J=13.5, 7.6 Hz).

EXAMPLE 9 (5)

4-Chloro-3-phenylthin-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1082] 1669

[1083] TLC: Rf 0.31 (hexane:ethyl acetate=2:1);

[1084] NMR (CDCl3): δ 3.68 (dd, J=14.2, 3.0 Hz, 1H), 3.75 (dd, J=14.2, 5.6 Hz, 1H), 5.00 (dd, J=5.6, 3.0 Hz, 1H), 7.35-7.40 (m, 3H), 7.49-7.59 (m, 3H), 7.64-7.69 (m, 2H).

EXAMPLE 9 (6)

5-(t-Butoxycarbonylamino)methyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1085] 1670

[1086] TLC: Rf 0.44 (hexane:ethyl acetate=1:1);

[1087] NMR (CDCl3): δ 1.45 (s, 9H), 3.60 (dd, J=12.5, 2.5 Hz, 1H), 3.75 (dd, J=12.5 Hz, 7.5 Hz, 1H), 4.50 (dd, J=15, 5.0 Hz, 1H), 4.85 (dd, J=15, 7.5 Hz, 1H), 5.00-5.20 (m, 2H) 7.30-7.45 (m, 3H), 7.50-7.75 (m, 5H).

EXAMPLE 9 (7)

4,7-Dimethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1088] 1671

[1089] TLC: Rf 0.45 (hexane:ethyl acetate=2:1);

[1090] NMR (CDCl3): δ 7.50-7.30 (5H, m), 7.20 (1H, d, J=7.8 Hz), 4.89 (1H, dd, J=5.8, 2.2Hz), 3.75-3.55 (2H, m), 2.60 (3H, s), 2.54 (3H, s).

EXAMPLE 9 (8) 4,6-Dimethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1091] 1672

[1092] TLC: Rf 0.50 (hexane:ethyl acetate=2:1);

[1093] NMR (CDCl3): δ 5 7.56-7.24 (7H, m), 4.90 (1H, dd, J=6.0, 1.8 Hz), 3.80-3.66 (2H, m 2.56 (3H, s), 2.42 (3H, s).

EXAMPLE 9 (9)

4-Ethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1094] 1673

[1095] TLC: Rf 0.44 (hexane:ethyl acetate=2:1);

[1096] NMR (CDCl3): δ 5 7.65-7.30 (8H, m), 4.99 (1H, dd, J=5.9, 2.4 Hz), 3.75-3.57 (2H, m 2.98 (2H, q, J=7.6 Hz), 1.37 (3H, t, J=7.6 Hz).

EXAMPLE 9 (10)

4-Methoxy-5-ethoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1097] 1674

[1098] TLC: Rf 0.44 (hexane:ethyl acetate=2:1);

[1099] NMR (CDCl3): δ 7.99 (1H, d, J=8.0 Hz), 7.60-7.50 (3H, m), 7.45-7.35 (3H, m), 5.11 (1H, dd, J=5.9, 2.8 Hz), 4.45 (2H, q, J=7.0 Hz), 4.09 (3H, s), 3.75-3.60 (2H, m), 1.44 (3H, t, J=7.0 Hz).

EXAMPLE 9 (11)

4-Bromo-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1100] 1675

[1101] TLC: Rf 0.20 (hexane:ethyl acetate=3:1);

[1102] NMR (CDCl3): δ 3.69 (dd, J=13.9, 2.8Hz, 1H), 3.74 (dd, J=13.9, 5.3Hz, 1H), 4.94 (dd, J=5.3, 2.8 Hz, 1H), 7.37-7.39 (m, 3H), 7.45 (t, J=7.8 Hz, 1H), 7.57-7.60 (m, 2H), 7.71 (d, J=7.8 Hz, 1H), 7.84 (dd, J=7.8, 0.9 Hz, 1H).

EXAMPLE 9 (12)

4-Hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1103] 1676

[1104] TLC: Rf 0.21 (hexane:ethyl acetate=1:1);

[1105] NMR (CDCl3): δ 3.49 (dd, J=13.9, 5.9 Hz, 1H), 3.81 (dd, J=13.9, 7.5 Hz, 1H), 4.93 (dd, J=7.5, 5.9 Hz, 1H), 7.17 (dd, J=8.0, 0.5 Hz, 1H), 7.25-7.51 (m, 7H).

EXAMPLE 9 (13)

5-Hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1106] 1677

[1107] TLC: Rf 0.50 (hexane:ethyl acetate=1:1);

[1108] NMR (CDCl3): δ 3.51 (dd, J=14.0, 7.0 Hz, 1H), 3.78 (dd, J=14.0, 7.0 Hz, 1H), 4.89 (t, J=7.0 Hz, 1H), 6.32 (s, 1H), 6.94 (dd, J=5.0 Hz, 2.0 Hz, 1H), 7.12 (d, J=2.0 Hz, 1H), 7.35 (m, 3H), 7.43 (m, 2H), 7.58 (d, J=5.0 Hz, 1H).

EXAMPLE 9 (14)

6-Hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1109] 1678

[1110] TLC: Rf 0.28 (hexane:ethyl acetate=1:1);

[1111] NMR (CDCl3): δ 3.54 (dd, J=13.8, 5.9 Hz, 1H), 3.83 (dd, J=13.8, 7.4 Hz, 1H), 4.91 (t-like, J=6.6 Hz, 1H), 7.10-7.15 (m, 2H), 7.31-7.42 (m, 5H), 7.51-7.56 (m, 1H).

EXAMPLE 9 (15)

7-Hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1112] 1679

[1113] TLC: Rf 0.52 (hexane:ethyl acetate=2:1);

[1114] NMR (CDCl3): δ 7.50-7.20 (5H, m), 7.11 (1 H, d, J=8.0 Hz), 6.85 (1 H, d, J=8.0 Hz), 6.68 (1H, dd, J=32.6, 6.6 Hz), 4.91 (1H, t, J=7.5 Hz), 3.79 (1H, dd, 14, 7.5 Hz), 3.50 (1H, dd, J=14, 7.5 Hz).

EXAMPLE 9 (16)

3-Phenylthio-2,3-dihydro-1,1-dioxidethieno[2,3-b]pyridine

[1115] 1680

[1116] TLC: Rf 0.50 (hexane: ethyl acetate=1:1);

[1117] NMR (CDCl3): δ 3.49 (dd, J=14.0, 7.0 Hz, 1H), 3.85 (dd, J=14.0, 8.0 Hz, 1H), 4.91 (dd, J=8.0, 7.0 Hz, 1H), 7.40 (m, 5H), 7.58 (dd, J=8.0, 5.0 Hz, 1H), 8.08 (m, 1H), 8.76 (m, 1H).

EXAMPLE 9 (17)

4,7-dihydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1118] 1681

[1119] TLC: Rf 0.33 (methylene chloride:ethyl acetate=1:1);

[1120] NMR (CDCl3): δ 9.25 (2H, brs), 7.55-7.45 (2H, m), 7.40-7.30 (3H, m), 6.96 (1H, d, J=8.8 Hz), 6.85 (1H, d, J=8.8 Hz), 5.09 (1 H, dd, J=7.4, 1.6 Hz), 3.71 (1H, dd, 13.9, 7.4 Hz), 3.50 (1H, dd, J=13.9, 1.6 Hz).

EXAMPLE 10

5-Nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1121] 1682

[1122] To a solution of the compound prepared in Example 9 (790 mg) in chloroform (45 ml) was added 3-chloroperbenzoic acid (70 % purity, 1.21 g). The reaction mixture was stirred at room temperature for 2 hours. To the reaction mixture, water was added. The mixture was extracted by ethyl acetate. The extract was washed by 2N aqueous solution of sodium hydroxide, water, a saturated aqueous solution of sodium chloride successively, dried over anhydrous magnesium sulfate and concentrated. The residue was purified with column chromatography on silica gel (hexane:ethyl acetate=3:2) to give the compound of the present invention (497 mg) having the following physical data.

[1123] TLC: Rf 0.39 (hexane:ethyl acetate=1:1);

[1124] NMR (CDCl3): δ 3.98 (dd, J=15.5, 3.0 Hz, 1H), 4.19 (dd, J=15.5, 9.3 Hz, 1H), 5.95 (dd, J=9.3, 3.0 Hz, 1H), 7.59-7.67 (m 2H), 7.78-7.84 (m, 3H), 8.11 (d, J=8.6 Hz, 1H), 8.41 (d, J=2.0 Hz, 1H), 8.51 (dd, J=8.6, 2.0 Hz, 1H).

EXAMPLES 10 (1)˜10 (16)

[1125] Using the compounds prepared in Examples 9 (1)˜9 (16) instead of the compound prepared in Example 9, by the same procedure as described in Example 10, or by the same reaction using 3-chloroperbenzoic acid instead of OXONE@, the following compounds of the present invention were obtained.

EXAMPLE 10 (1)

6-Methoxy-3-phenylsulfonyl-2,3-dihydro-1,1 -dioxidebenzo[b]thiophene

[1126] 1683

[1127] TLC: Rf 0.34 (hexane:ethyl acetate=1:1);

[1128] NMR (CDCl3): δ 3.66-3.82 (m, 2H), 3.87 (s, 3H), 5.00 (dd, J=7.5, 5.5 Hz, 1H), 7.06 (d, J=2.4 Hz, 1H), 7.24 (dd, J=8.8, 2.4 Hz, 1H), 7.46-7.54 (m, 2H), 7.63-7.71 (m, 3H), 7.86 (d, J=8.8 Hz, 1H).

EXAMPLE 10 (2)

4-Methoxy-3-phenylsulfonyl-2,3-dihydro-1,1 -dioxidebenzo[b]thiophene

[1129] 1684

[1130] TLC: Rf 0.17 (hexane:ethyl acetate=1:1);

[1131] NMR (CDCl3): δ 3.49 (s, 3H), 3.76 (dd, J=14.9, 9.2 Hz, 1H), 4.31 (dd, J=14.9, 1.3 Hz, 1H), 5.23 (dd, J=9.2, 1.3 Hz, 1H), 6.90 (d, J=8.0 Hz, 1H), 7.31 (d, J=7.8 Hz; 1H) 745-7.54 (m, 3H), 7.58-7.68 (m, 1H), 7.72-7.77 (m, 2H).

EXAMPLE 10 (3)

5-Methoxy-3-phenylsulfonyl-2,3-dihydro-1, 1 -dioxidebenzo[b]thiophene

[1132] 1685

[1133] TLC: Rf 0.50 (hexane:ethyl acetate=1:1);

[1134] NMR (CDCl3): δ 3.70(dd, J=12, 8 Hz, 1H), 3.77(dd, J=12, 4 Hz, 1H), 3.94(s, 3H), 5.01 (dd, J=8, 4 Hz, 1H), 7.12(d, J=8 Hz, 1H), 7.44(s, 1H), 7.53(m, 3H), 7.68(m, 3H).

EXAMPLE 10 (4)

7-Methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1135] 1686

[1136] TLC: Rf 0.40 (hexane:ethyl acetate=1:2);

[1137] NMR (DMSO-d6): δ 7.80-7.55 (6H, m), 7.27 (1H, d, J=8.2 Hz), 7.15 (1H, d, J=8.2 Hz), 5.73(1H, dd, J=9.5, 3.4 Hz), 3.91 (1H, dd, J=15, 9.5 Hz), 3.87 (3H, s), 3.69 (1H, dd, J=15, 3.4 Hz).

EXAMPLE 10 (5)

4-Chioro-3-phenylsufonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1138] 1687

[1139] TLC: Rf 0.43 (methylene chloride:ethyl acetate=15:1);

[1140] NMR (CDCl3): δ 3.79 (dd, J=15.0, 9.2 Hz, 1H), 4.24 (dd, J=15.0, 1.0 Hz, 1H), 5.26 (dd, J=9.2, 1.0 Hz, 1H), 7.46-7.66 (m, 6H), 7.77-7.81 (m, 2H).

EXAMPLE 10 (6)

4-(t-Butoxycarbonylamino)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1141] 1688

[1142] TLC: Rf 0.26 (hexane:ethyl acetate=1:1);

[1143] NMR (CDCl3): δ 1.45 (s, 9H), 3.75 (dd, J=15, 10 Hz, 1H), 3.85 (dd, J=15, 2.5 Hz, 1H), 4.40 (dd, J=5, 5.0 Hz, 1H), 4.95 (dd, J=15, 7.5 Hz, 1H), 5.35 (m, 2H), 7.45-7.90 (m, 8H).

EXAMPLE 10 (7)

4,7-Dimethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1144] 1689

[1145] TLC: Rf 0.18 (hexane:ethyl acetate=2:1);

[1146] NMR (DMSO-d6): δ 7.81-7.70 (3H, m), 7.70-7.55 (2H, m), 7.48 (1 H, d, J=7.8 Hz), 7.38 (1H, d, J=7.8 Hz), 5.73 (1H, t, J=5.2 Hz), 3.84 (2H, d-like, J=5.2 Hz), 2.40 (3H, s), 2.36 (3H, s).

EXAMPLE 10 (8)

4,6-Dimethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1147] 1690

[1148] TLC: Rf 0.18 (hexane:ethyl acetate=2:1);

[1149] NMR (DMSO-d6): δ 7.82-7.70 (3H, m), 7.70-7.55 (2H, m), 7.42 (2H, d, J=5.4 Hz), 5.73 (1 H, t, J=4.8 Hz), 3.86-3.80 (2H, m), 2.38 (6H, s).

EXAMPLE 10 (9)

4-Ethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1150] 1691

[1151] TLC: Rf 0.22 (hexane:ethyl acetate=2:1);

[1152] NMR (CDCl3): δ 7.68-7.40 (8H, m), 5.22 (1H, d, J=9.2 Hz), 3.99 (1H, d, J=15.2 Hz), 3.76 (1 H, dd, J=15.2, 9.2 Hz), 3.07 (2H, dd, J=7.6, 2.2 Hz), 1.33 (3H, t, J=7.6 Hz).

EXAMPLE 10 (10)

4-Methoxy-5-ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1153] 1692

[1154] TLC: Rf 0.38 (hexane:ethyl acetate=1:1);

[1155] NMR (CDCl3): δ 7.91 (1H, d, J=8.0 Hz), 7.83-7.45 (5H, m), 7.41 (1H, d, J=8.0 Hz), 5.28 (1H, d-like, J=8.0 Hz), 4.42 (2H, q, J=7.0 Hz), 4.17 (1H, dd, J=15, 1.6 Hz), 3.86 (3H, s), 3.75 (1H, dd, J=15, 8.0 Hz), 1.43 (3H, t, J=7.0 Hz).

EXAMPLE 10 (11)

4-Bromo-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1156] 1693

[1157] TLC: Rf 0.35 (hexane:ethyl acetate=1:1);

[1158] NMR (CDCl3): δ 3.79 (dd, J=15.0, 9.2 Hz, 1H), 4.23 (dd, J=15.0, 1.1 Hz, 1H), 5.23 (d-like, J=8.8 Hz, 1H), 7.44-7.54 (m, 3H), 7.62-7.70 (m, 2H), 7.78-7.83 (m, 3H).

EXAMPLE 10 (12)

4-Hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1159] 1694

[1160] TLC: Rf 0.22 (hexane:ethyl acetate=1:2);

[1161] NMR (DMSO-d6): δ 3.96 (dd, J=15.0, 8.4 Hz, 1H), 4.08 (dd, J=15.0, 1.8 Hz, 1H), 5.51 (dd, J=8.4, 1.8 Hz, 1H), 7.00 (d-like, J=8.0 Hz, 1H), 7.16 (d, J=7.0 Hz, 1H), 7.47 (t, J=8.0 Hz, 1H), 7.56-7.63 (m, 2H), 7.71-7.81 (m, 3H).

EXAMPLE 10 (13)

5-Hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1162] 1695

[1163] TLC: Rf 0.30 (hexane:ethyl acetate=1:1);

[1164] NMR (DMSO-d6): δ 3.66 (dd, J=14, 4 Hz, 1H), 3.90 (dd, J=14, 9 Hz, 1H), 5.71 (dd, J=9, 4 Hz, 1H), 7.07 (m, 2H), 7.55-7.82 (m, 6H), 10.80 (brs, 1H).

EXAMPLE 10 (14)

6-Hydroxy-3-phenylsulfonyl-2,3-dyhydro-1,1-dioxidebenzo[b]thiophene

[1165] 1696

[1166] TLC: Rf 0.37 (hexane:ethyl acetate=1:2);

[1167] NMR (DMSO-d6): δ 3.73 (dd, J=15.2, 3.2 Hz, 1H), 3.96 (dd, J=15.2, 9.2 Hz, 1H), 5.60 (dd, J=9.2, 3.2 Hz, 1H), 6.94 (s-like, 1H), 7.16 (d-like, J=8.4 Hz, 1H), 7.50 (d, J=8.4 Hz, 1H), 7.57-7.64 (m, 2H), 7.71-7.76 (m, 3H).

EXAMPLE 10 (15)

7-Hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1168] 1697

[1169] TLC: Rf 0.31 (hexane:ethyl acetate 1:2);

[1170] NMR (DMSO-d6): δ 7.80-7.45 (6H, m), 6.98 (2H, d, J=8.4 Hz), 5.66 (1H, dd, J=9.6, 3.2 Hz), 3.85 (1H, dd, J=15, 9.6 Hz), 3.68-3.58 (1H, m).

EXAMPLE 10 (16)

3-Phenylsulfonyl-2,3-dihydro-1,1-dioxidethieno[2,3-b]pyridine

[1171] 1698

[1172] TLC: Rf 0.20 (hexane:ethyl acetate=1:1);

[1173] NMR (CDCl3): δ 3.65 (dd, J=15, 8 Hz, 1H), 3.74 (dd, J=15, 6 Hz, 1H), 5.04 (dd, J=8, 6 Hz, 1H), 7.58 (m, 2H), 7.69 (m, 4H), 8.48 (m, 1H), 8.86 (m, 1H).

EXAMPLE 11

5-Amino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1174] 1699

[1175] Under an atmosphere of argon, to a solution of the compound prepared in Example 10 (110 mg) in ethanol (7.5 ml) and ethyl acetate (7.5 ml), was added 5% palladium-carbon (20 mg). The reaction mixture was stirred at room temperature for 2 hours under an atmosphere of hydrogen. The reaction mixture was filtrated through celite (trade name). The filtrate was concentrated. The residue was purified with column chromatography on silica gel (methylene chloride:ethyl acetate=2:1) to give the compound of the present invention (94 mg) having the following physical data. Then, it was converted into a corresponding salt by a known method to give the compound of the present invention having the following physical data.

[1176] Free Compound:

[1177] TLC: Rf 0.29 (hexane:ethyl acetate=1:2);

[1178] NMR (CDCl3): δ 3.61 (dd, J=14.6, 8.3 Hz, 1H), 3.70 (dd, J=14.6, 5.6 Hz, 1H), 4.34 (brs, 2H), 4.94 (dd, J=8.3, 5.6 Hz, 1H), 6.79 (dd, J=8.0, 2.0 Hz, 1H), 7.21 (d, J=2.0 Hz, 1H), 7.40 (d, J=8.0 Hz, 1H), 7.49-7.55 (m, 2H), 7.63-7.74 (m, 3H).

[1179] Hydrochloride:

[1180] TLC: Rf 0.47 (methylene chloride:methanol=18:1);

[1181] NMR (DMSO-d6): δ 3.53 (dd, J=14.9, 3.8 Hz, 1H), 3.75 (dd, J=14.9, 9.4 Hz, 1H), 5.58 (dd, J=9.4, 3.8 Hz, 1H), 6.76 (dd, J=8.6, 2.1 Hz, 1H), 6.90 (d, J=2.1 Hz, 1H), 7.31 (d, J=8.6 Hz, 1H), 7.57-7.65 (m, 2H), 7.72-7.79 (m, 3H).

EXAMPLE 12

5-Acetylamino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1182] 1700

[1183] To a solution of the compound prepared in Example 11 (91 mg) in pyridine (2 ml), was added acetic anhydride (1 ml). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated. The residue was purified with column chromatography on silica gel (hexane:ethyl acetate=1:1) to give the compound of the present invention (86 mg) having the following physical data.

[1184] TLC: Rf 0.20 (hexane:ethyl acetate=1:2);

[1185] NMR (CDCl3): δ 2.24 (s, 3H), 3.66 (dd, J=14.8, 8.3 Hz, 1H), 3.75 (dd, J=14.8, 5.2 Hz, 1H), 5.04 (dd, J=8.3, 5.2 Hz, 1H), 7.49-7.59 (m, 3H), 7.66-7.75 (m, 3H), 7.87-7.94 (m, 2H), 8.04 (s-like, 1H).

EXAMPLE 13

5-Aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1186] 1701

[1187] By the same procedure as described in Example 7 using the compound prepared in Example 10 (6) instead of the compound prepared in Example 6 (8), the compound of the present invention having the following physical data was obtained.

[1188] TLC: Rf 0.16 (ethyl acetate:methanol:triethylamine=16:2:1);

[1189] NMR (DMSO-d6): δ 3.80-4.00 (m, 2H), 4.35 (d, J=15 Hz, 1H), 4.55 (d, J=15 Hz, 1H), 6.30-6.40 (m, 1H), 7.60-7.70 (m, 2H), 7.75-7.95 (m, 5H), 8.00-8.15 (m, 1H), 8.30-8.65 (m, 2H).

EXAMPLE 14

4-(N,N-dimethylamino)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1190] 1702

[1191] By the same procedure as described in Example 8 using the compound prepared in Example 13 instead of the compound prepared in Example 7, the compound of the present invention having the following physical data was obtained.

[1192] TLC: Rf 0.50 (ethyl acetate:methanol:triethylamine=16:2:1);

[1193] NMR (DMSO-d6): δ 2.65 and 2.70 (both s, total 3H), 2.85 and 2.90 (both s, total 3H), 3.80 (d, J=12.5 Hz, 1H), 4.05 (dd, J=12.5, 7.5 Hz, 1H), 4.50-4.70 (m, 1H), 4.70-4.90 (m, 1H), 6.35 (d, J=7.5 Hz, 1H), 7.60-8.00 (m, 7H), 8.20-8.35 (m, 1H), 10.85 (brs, 1H).

EXAMPLE 15

4-Methoxy-5-formyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1194] 1703

[1195] To a suspension of lithium aluminum hydride (54 mg) in tetrahydrofuran (10 ml), was added a solution of the compound prepared in Example 10 (10) (300 mg) in tetrahydrofuran (10 ml) at −78° C. dropwise. The reaction mixture was stirred at −78° C. for 1 hour. The reaction mixture was poured into ice-water. The mixture was extracted by ethyl acetate. The extract was washed by water, a saturated aqueous solution of sodium chloride, successively, dried over anhydrous sodium sulfate, and concentrated. The residue was purified with column chromatography on silica gel (hexane:ethyl acetate=1:1) to give the compound of the present invention (51 mg) having the following physical data.

[1196] TLC: Rf 0.27 (hexane:ethyl acetate=1:2);

[1197] NMR (CDCl3): δ 3.80 (dd, J=15.2, 9.3 Hz, 1H), 4.05 (s, 3H), 4.14 (dd, J=15.2, 1.4 Hz, 1H), 5.28 (dd, J=9.3, 1.4 Hz, 1H), 7.46-7.54 (m, 3H), 7.63-7.78 (m, 3H), 8.05 (d, J=8.0 Hz, 1H), 10.33 (d, J=0.6 Hz, 1H).

EXAMPLE 16

4-Methoxy-3-(thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1198] 1704

[1199] By the same procedure as described in Example 1 using 2-thiophenthiol and 4-methoxybenzothiophen-1,1-diol, the compound of the present invention having the following physical data was obtained.

[1200] TLC: Rf 0.27 (methylene chloride:hexane=4:1);

[1201] NMR (CDCl3): δ 3.66 (d, J=5.5, 5.4 Hz, 1H), 3.73 (dd, J=15.5, 4.2 Hz, 1H), 3.95 (s, 3H), 4.88 (dd, J=5.4, 4.2 Hz, 1H), 7.01 (dd, J=5.4, 3.6 Hz, 1H), 7.09 (d, J=8.0 Hz, 1H), 7.19 (dd, J=3.6, 1.2 Hz, 1H), 7.27 (d, J=8.0 Hz, 1H), 7.44 (dd, J=5.4, 1.2 Hz, 1H), 7.53 (t, J=8.0 Hz, 1H).

EXAMPLE 17

4-Methoxy-3-(thioiphen-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1202] 1705

[1203] By the same procedure using the compound prepared in Example 16 instead of the compound prepared in Example 9, the compound of the present invention having the following physical data was obtained.

[1204] TLC: Rf 0.46 (methylene chloride:ethyl acetate=10:1);

[1205] NMR (CDCl3): δ 3.73 (s, 3H), 3.79 (dd, J=15.0, 9.2 Hz, 1H), 4.23 (dd, J=15.0, 1.2 Hz, 1H), 5.32 (dd, J=9.2, 1.2 Hz, 1H), 7.04 (d, J=8.0 Hz, 1H), 7.11 (dd, J=4.9, 3.8 Hz, 1H), 7.30 (d, J=8.0 Hz, 1H), 7.53 (dd, J=3.8, 1.4 Hz, 1H), 7.59 (t, J=8.0 Hz, 1H), 7.73 (dd, J=4.9, 1.4 Hz, 1H).

EXAMPLE 18

4-(4-Nitrophenylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1206] 1706

[1207] To a solution of a compound prepared in Example 9 (12) (1.0 g) in dimethylformamide (30 ml), were added 4-nitrobenzylbromide (947 mg) and potassium carbonate (1.0 g). The reaction mixture was stirred at room temperature overnight. To the reaction mixture, water was added. The mixture was extracted by ethyl acetate. The extract was washed by water (three times), a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and concentrated. The residue was purified with column chromatography on silica gel (hexane:ethyl acetate=1:1) to give the compound of the present invention (1.1 g) having the following physical data.

[1208] TLC: Rf 0.29 (hexane:ethyl acetate=1:1);

[1209] NMR (CDCl3): δ 8.25 (2H, d, J=8.5 Hz), 7.71 (2H, d, J=8.5 Hz), 7.60-7.20 (7H, m), 7.10 (1H, d, J=8 Hz), 5.32 (2H, s), 5.11 (1H, dd, J=7, 2 Hz), 3.85-3.55 (2H, m).

EXAMPLES 18 (1)˜18 (40)

[1210] By the sane procedure as described in Example 18 using compounds prepared in Examples 9 (12)˜9 (15) or Example 9 (17) and a corresponding halogenated compound, the following compounds of the present invention were obtained.

EXAMPLE 18 (1)

4-(3-Phenyloxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1211] 1707

[1212] TLC: Rf 0.27 (hexane ethyl acetate 2:1);

[1213] NMR (CDCl3): δ 7.54-7.42 (3H, m), 7.32-7.19 (6H, m), 7.10 (1H, d, J=8.0 Hz), 6.95-6.84 (3H, m), 5.01 (1H, dd, J=6.6, 2.2 Hz), 4.31 (2H, t, J=6.0 Hz), 4.20 (2H, t, J=6.0 Hz), 3.69 (1H, dd, J=13.9, 6.6 Hz), 3.59 (1H, dd, J=13.9, 2.2 Hz), 2.31 (2H, quint, J=6.0 Hz).

EXAMPLE 18 (2)

4-Benzyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1214] 1708

[1215] TLC: Rf 0.45 (hexane:ethyl acetate=2:1);

[1216] NMR (CDCl3): δ 7.54-7.26 (12H, m), 7.13 (1H, d, J=9.0 Hz), 5.22 (2H, s), 5.03 (1H, dd, J=6.0, 2.6 Hz), 3.71 (1H, dd, J=13.8, 6.0 Hz), 3.63 (1H, dd, J=13.8, 2.6 Hz).

EXAMPLE 18 (3)

4-(3-Benzyloxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1217] 1709

[1218] TLC: Rf 0.47 (hexane:ethyl acetate=1:1);

[1219] NMR (CDCl3): δ 2.13 (quint, J=6.0 Hz, 2H), 3.58 (dd, J=14.0, 2.4 Hz, 1H), 3.67 (dd, J=14.0, 6.6 Hz, 1H), 3.69 (t, J=6.0 Hz, 2H), 4.22 (t, J=6.0 Hz, 2H), 4.44 (d, J=12.0 Hz, 1H), 4.52 (d, J=12.0 Hz, 1H), 4.92 (dd, J=6.6, 2.4 Hz, 1H), 7.08 (d-like, J=7.4 Hz, 1H), 7.26 (s, 5H), 7.30-7.35 (m, 4H), 7.43-7.54 (m, 3H).

EXAMPLE 18 (4)

4-(Pyridin-3-ylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1220] 1710

[1221] TLC: Rf 0.46 (ethyl acetate);

[1222] NMR (CDCl3): δ 3.62 (dd, J=14.0, 2.2Hz, 1H), 3.72 (dd, J=14.0, 6.2Hz, 1H), 5.04 (dd, J=6.2, 2.2 Hz, 1H), 5.23 (s, 2H), 7.15 (dd, J=8.0, 1.0 Hz, 1H), 7.26-7.45 (m, 7H), 7.54 (t, J=8.0 Hz, 1H), 7.85-7.92 (m, 1H), 8.63 (dd, J=4.7, 2.0 Hz, 1H), 8.76 (dd, J=2.0, 0.6 Hz, 1H).

EXAMPLE 18 (5)

4-(Quinolin-2-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1223] 1711

[1224] TLC: Rf 0.25 (hexane:ethyl acetate=1:1);

[1225] NMR (CDCl3): δ 8.18 (1H, d, J=8 Hz), 8.10 (1H, d, J=8 Hz), 7.92-7.68 (3H, m), 7.68-7.40 (4H, m), 7.40-7.22 (4H, m), 7.16 (1H, d, J=8 Hz), 5.53 (2H, s), 5.18 (1H, dd, J=7, 2 Hz), 3.76 (1H, dd, J=14, 7 Hz), 3.66 (1H, dd, J=14, 2 Hz).

EXAMPLE 18 (6)

4-(Pyridin-2-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1226] 1712

[1227] TLC: Rf 0.33 (ethyl acetate);

[1228] NMR (CDCl3): δ 8.62 (1H, d, J=5 Hz), 7.80-7.58 (2H, m), 7.58-7.38 (3H, m), 7.38-7.18 (5H, m), 7.11 (1H, d, J=8 Hz), 5.35 (2H, s), 5.15 (1H, dd, J=7, 2 Hz), 3.85-3.58 (2H, m).

EXAMPLE 18 (7)

4-(Pyridin-4-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1229] 1713

[1230] TLC: Rf 0.15 (ethyl acetate);

[1231] NMR (CDCl3): δ 8.78-8.55 (2H, m), 7.65-7.18 (9H, m), 7.07 (1H, d, J=8 Hz), 5.23 (2H, s), 5.11 (1H, dd, J=7, 2 Hz), 3.82-3.53 (2H, m).

EXAMPLE 18 (8)

4-(3-(Pyridin-3-yl)propyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1232] 1714

[1233] TLC: Rf 0.18 (ethyl acetate);

[1234] NMR (CDCl3): δ 8.48-8.35 (m, 2H), 7.67-7.33 (m, 9H), 6.95 (d, J=8.0 Hz, 1H), 5.01 (d-like, J=8.5 Hz, 1H), 4.15-3.86 (m, 4H), 2.81 (t, J=7.0 Hz, 2H), 2.21-2.01 (m, 2H).

EXAMPLE 18 (9)

4-(3-Hydroxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1235] 1715

[1236] TLC: Rf 0.24 (hexane:ethyl acetate=1:2);

[1237] NMR (CDCl3): δ 2.06-2.17 (m, 2H), 3.57 (dd, J=14.0, 2.2 Hz, 1H), 3.67 (dd, J=14.0, 6.6 Hz, 1H), 3.91 (br, 2H), 4.27 (t, J=5.8 Hz, 2H), 5.05 (dd, J=6.6, 2.2 Hz, 1H), 7.11 (d, J=8.0 Hz, 1H), 7.30-7.38 (m, 4H), 7.49-7.56 (m, 3H).

EXAMPLE 18 (10)

5-Pentoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1238] 1716

[1239] TLC: Rf 0.70 (hexane:ethyl acetate=2:1);

[1240] NMR (CDCl3): δ 0.95 (t, J=7.0 Hz, 3H), 1.38-1.47 (m, 4H), 1.82 (quint, J=6.8 Hz, 2H), 3.51 (dd, J=15, 7 Hz, 1H), 3.79 (dd, J=15, 7 Hz, 1H), 4.00 (t, J=6.8 Hz, 2H), 4.89 (t, J=7.0 Hz, 1H), 7.01 (dd, J=8, 2 Hz, 1H), 7.12 (d, J=2 Hz, 1H), 7.36-7.38 (m, 3H), 7.41-7.43 (m, 2H), 7.61 (d, J=8 Hz, 1H).

EXAMPLE 18 (11)

5-(2-Phenyloxyethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1241] 1717

[1242] TLC: Rf 0.75 (hexane:ethyl acetate=1:1);

[1243] NMR (CDCl3): δ 7.65 (1H, d, J=8.5 Hz), 7.45-7.42 (2H, m), 7.34-7.29 (5H, m), 7.21 (1H, d, J=2.2 Hz), 7.09 (1 H, dd, J=8.5, 2.2 Hz), 7.00 (1 H, t, J=7.0 Hz), 6.95 (1 H, d, J=8.5 Hz), 4.93 (1H, t, J=7.0 Hz), 4.38 (4H, m), 3.78 (1H, dd, J=14.0, 7.0 Hz), 3.52 (1H, dd, J=14.0, 7.0 Hz).

EXAMPLE 18 (12)

5-(3-Hydroxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1244] 1718

[1245] TLC: Rf 0.25 (hexane:ethyl acetate=1:1);

[1246] NMR (CDCl3): δ 2.10 (quint, J=6.5 Hz, 2H), 3.60 (dd, J=14, 6.7Hz, 1H), 3.82 (dd, J=14, 6.7 Hz, 1H), 3.89 (t, J=6.5 Hz, 2H), 4.20 (t, J=6.5 Hz, 2H), 4.98 (t, J=6.7 Hz, 1H), 7.20 (dd, J=8.5, 2.2 Hz, 1H), 7.35-7.47 (m, 6H), 7.61 (d, J=8.5 Hz, 1H).

EXAMPLE 18 (13)

5-(Pyridin-3-ylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1247] 1719

[1248] TLC: Rf 0.40 (ethyl acetate);

[1249] NMR (CDCl3): δ 3.51 (dd, J=9.0, 4.5 Hz, 1H), 3.79 (dd, J=9.0, 5.0 Hz, 1H), 4.91 (t-like, J=4.7 Hz, 1H), 5.14 (s, 2H), 7.11 (dd, J=5.6, 1.6 Hz, 1H), 7.21 (d, J=1.6 Hz, 1H), 7.33-7.42 (m, 6H), 7.65 (d, J=5.6 Hz, 1H), 7.77 (dt, J=5.4, 1.3 Hz, 1H), 8.63 (dd, J=3.2, 1.3 Hz, 1H), 8.70 (d, J=1.3 Hz, 1H).

EXAMPLE 18 (14)

5-(3-(Pyridin-3-yl)propyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1250] 1720

[1251] TLC: Rf 0.16 (ethyl acetate);

[1252] NMR (CDCl3): δ 8.36-8.28 (m, 2H), 7.78-7.55 (m, 4H), 7.42-7.36 (m, 5H), 7.01 (d, J=8.0 Hz, 1H), 5.11 (d-like, J=9.0 Hz, 1H), 4.12 (t, J=7.0 Hz, 2H), 3.88-3.64 (m, 2H), 3.05 (t, J=7.0 Hz, 2H), 2.35-2.26 (m, 2H).

EXAMPLE 18 (15)

6-(3-Phenyloxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1253] 1721

[1254] TLC: Rf 0.42 (hexane:ethyl acetate=2:1);

[1255] NMR (CDCl3): δ 7.61-7.56 (1H, m), 7.43-7.25 (7H, m), 7.19-7.15 (2H, m), 6.95-6.89 (3H, m), 4.91 (1H, t-like, J=6.6 Hz), 4.22 (2H, t, J=6.0 Hz), 4.15 (2H, t, J=6.0 Hz), 3.80 (1H, dd, J=13.8, 7.3 Hz), 3.51 (1H, dd, J=13.8, 7.3 Hz), 2.28 (2H, quint, J=6.0 Hz).

EXAMPLE 18 (16)

6-Benzyloxy-3-phenylthio-2,3-dihydro-1,1-di oxidebenzo[b]thiophene

[1256] 1722

[1257] TLC: Rf 0.58 (hexane:ethyl acetate=2:1);

[1258] NMR (CDCl3): δ 7.63-7.58 (1 H, m), 7.45-7.31 (10H, m), 7.27-7.23 (2H, m), 5.10 (2H, s), 4.92 (1H, t-like, J=6.7 Hz), 3.81 (1H, dd, J=13.7, 7.5 Hz), 3.52 (1H, dd, J=13.7, 6.1 Hz).

EXAMPLE 18 (17)

6-pentoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1259] 1723

[1260] TLC: Rf 0.51 (hexane:ethyl acetate=2:1);

[1261] NMR (CDCl3): 7.60-7.55 (1H, m), 7.43-7.31 (5H, m), 7.19-7.12 (2H, m), 4.91 (1H, t, J=6.8 Hz), 3.99 (2H, t, J=6.6 Hz), 3.80 (1H, dd, J=13.8, 7.3 Hz), 3.51 (1H, dd, J=13.8, 6.2 Hz), 1.80 (2H, quint, J=7.0 Hz), 1.50-1.30 (4H, m), 0.92 (3H, t, J=7.0 Hz).

EXAMPLE 18 (18)

6-(2-(Morpholin-4-yl)ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1262] 1724

[1263] TLC: Rf 0.41 (hexane:ethyl acetate: triethylamine=2:4:1);

[1264] NMR (CDCl3): δ 7.60 (1H, d, J=8.4 Hz), 7.42-7.32 (5H, m), 7.22-7.16 (2H, m), 4.92 (1H, t-like, J=6.8 Hz), 4.15 (2H, t, J=5.8 Hz), 3.81 (1H, dd, J=13.8, 7.2 Hz), 3.73 (4H, t-like, J=4.6 Hz), 3.52 (1H, dd, J=13.8, 6.1 Hz), 2.82 (2H, t, J=5.8 Hz), 2.57 (4H, t-like, J=4.6 Hz).

EXAMPLE 18 (19)

6-(3-Hydroxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1265] 1725

[1266] TLC: Rf 0.33 (hexane:ethyl acetate 1:2);

[1267] NMR (CDCl3): δ 2.06 (quint, J=6.1 Hz, 2H), 3.51 (dd, J=13.6, 6.2 Hz, 1H), 3.80 (dd, J=13.6, 7.4 Hz, 1H), 3.85 (t, J=6.1 Hz, 2H), 4.17 (t, J=6.1 Hz, 2H), 4.92 (t-like, J=6.8 Hz, 1H), 7.16-7.21 (m, 2H), 7.32-7.45 (m, 5H), 7.57-7.61 (m, 1H).

EXAMPLE 18 (20)

6-(Pyridin-3-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1268] 1726

[1269] TLC: Rf 0.31 (methylene chloride: ethyl acetate=2:1);

[1270] NMR (CDCl3): “ 3.53 (dd, J=13.6, 6.2 Hz, 1H), 3.82 (dd, J=13.6, 7.2 Hz, 1H), 4.93 (t-like, J=6.6 Hz, 1H), 5.12 (s, 2H), 7.23-7.28 (m, 2H), 7.33-7.46 (m, 6H), 7.61-7.65 (m, 1H), 7.75-7.79 (m, 1H), 8.63 (dd, J=5.0, 1.6 Hz, 1H), 8.70 (d, J=1.6 Hz, 1H).

EXAMPLE 18 (21)

6-(3-Nitrophenylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1271] 1727

[1272] TLC: Rf 0.49 (hexane:ethyl acetate=1:1),

[1273] NMR (CDCl3): δ 8.33 (1H, brs), 8.22 (1H, dd, J=8, 2 Hz), 7.76 (1H, d, J=7.8 Hz), 7.70-7.48 (2H, m), 7.48-7.16 (7H, m), 5.21 (2H, s), 4.93 (1H, t-like, J=6.8 Hz), 3.83 (1H, dd, J=13.6, 7.6 Hz), 3.54 (1H, dd, J=13.6, 6.2 Hz).

EXAMPLE 18 (22)

6-(3-Bromopropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1274] 1728

[1275] TLC: Rf 0.48 (hexane:ethyl acetate=3:1);

[1276] NMR (CDCl3). δ 2.35 (quint, J=7.5 Hz, 2H), 3.55 (t, J=7.5 Hz, 2H), 3.59 (dd, J=15, 7 Hz, 1H), 3.80 (dd, J=15, 7 Hz, 1H), 4.18 (t, J=7.5 Hz, 2H), 4.92 (t, J=7 Hz, 1H), 7.20 (dd, J=9, 2 Hz, 1H), 7.34-7.43 (m, 6H), 7.60 (d, J=9 Hz, 1H).

EXAMPLE 18 (23)

7-Pentoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1277] 1729

[1278] TLC: Rf 0.80 (hexane:ethyl acetate=1:1);

[1279] NMR (CDCl3): δ 5 7.54 (1H, t, J=7.8 Hz), 7.45-7.21 (6H, m), 6.91 (1H, d, J=8.6 Hz), 4.88 (1H, t, J=7.6 Hz), 4.11 (2H, t, J=7.0 Hz), 3.77 (1H, dd, J=13.6, 7.6 Hz), 3.50 (1H, dd, J=13.6, 7.6 Hz), 1.87 (2H, quint, J=7.0 Hz), 1.50-1.30 (4H, m), 0.92 (3H, t, J=7.2 Hz).

EXAMPLE 18 (24)

7-(2-Phenyloxyethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1280] 1730

[1281] TLC: Rf 0.55 (hexane:ethyl acetate=1:1);

[1282] NMR (CDCl3): δ 7.58 (1H, t, J=7.8 Hz), 7.45-7.25 (8H, m), 7.06 (1H, d, J=8.4 Hz), 7.05-6.90 (3H, m), 4.89 (1 H, t, J=7.6 Hz), 4.58 -4.45 (2H, m), 4.45-4.35 (2H, m), 3.78 (1 H, dd, J=13.6, 7.6 Hz), 3.52 (1H, dd, J=13.6, 7.6 Hz).

EXAMPLE 18 (25)

7-(3-Hydroxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1283] 1731

[1284] TLC: Rf 0.25 (hexane:ethyl acetate=1:2);

[1285] NMR (CDCl3): δ 7.60-6.60 (8H, m), 4.90 (1 H, t, J=6.8 Hz), 4.36-4.26 (2H, m), 3.90 (2H, br) 3.79 (1H, d, J=13.8, 6.8 Hz), 3.52 (1H, dd, J=13.8, 6.8 Hz), 2.50-2.05 (2H, m).

EXAMPLE 18 (26)

7-(Pyridin-3-ylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1286] 1732

[1287] TLC: Rf 0.12 (hexane:ethyl acetate=1:2);

[1288] NMR (CDCl3): δ 8.66 (1H, d, J=2.2 Hz), 8.57 (1H, dd, J=4.8, 1.8 Hz), 7.93 (1H, d, J=8.2 Hz), 7.56 (1H, t, J=8.2 Hz), 7.45-7.30 (4H, m), 6.97 (1H, d, J=8.2 Hz), 5.30 (2H, s), 4.92 (1H, t, J=7.0 Hz), 3.82 (1H, dd, J=13.8, 7.8 Hz), 3.54 (1H, dd, J=13.8, 7.8 Hz).

EXAMPLE 18 (27)

4-(t-Butoxycarbonylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1289] 1733

[1290] TLC: Rf 0.33 (hexane:ethyl acetate=2:1);

[1291] NMR (CDCl3): δ 7.57-7.46 (3H, m), 7.37-7.32 (4H, m), 6.93 (1H, d-like, J=8.0 Hz), 5.16 (1H, dd, J=6.6, 2.0 Hz), 4.61 (2H, s), 3.72 (1H, dd, J=13.9, 6.6 Hz), 3.61 (1H, dd, J=13.9, 2.0 Hz), 1.49 (9H, s).

EXAMPLE 18 (28)

5-(t-Butoxycarbonylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1292] 1734

[1293] TLC: Rf 0.52 (hexane:ethyl acetate=2:1);

[1294] NMR (CDCl3): δ 1.50 (s, 9H), 3.48 (dd, J=14, 6.7 Hz, 1H), 3.82 (dd, J=14, 6.7 Hz, 1H), 4.66 (s, 2H), 4.95 (t, J=6.7 Hz, 1H), 7.18 (dd, J=9, 2.3 Hz, 1H) 7.40-7.53 (m, 6H), 7.62 (d, J=9 Hz, 1H).

EXAMPLE 18 (29)

6-(t-Butoxycarbonylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1295] 1735

[1296] TLC: Rf 0.44 (hexane:ethyl acetate 2:1);

[1297] NMR (CDCl3): δ 7.61 (1H, d, J=8.7 Hz), 7.44-7.32 (5H, m), 7.24 (1H, dd, J=8.7, 2.6 Hz), 7.08 (1H, d, J=2.6 Hz), 4.91 (1H, t-like, J=6.7 Hz), 4.56 (2H, s), 3.80 (1H, dd, J=13.7, 7.3 Hz), 3.51 (1H, dd, J=13.7, 6.1 Hz), 1.49 (9H, s).

EXAMPLE 18 (30)

7-(t-Butoxycatbonylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1298] 1736

[1299] TLC: Rf 0.55 (hexane:ethyl acetate=1:1);

[1300] NMR (CDCl3): δ 7.54 (1H, t, J=7.6 Hz), 7.45-7.27 (6H, m), 6.80 (1H, d, J=8.0 Hz), 4.90 (1H, t, J=7.6 Hz), 4.69 (2H, s), 3.79 (1H, dd, J=13.6, 7.6 Hz), 3.52 (1H, dd, J=13.6, 7.6 Hz), 1.46 (9H, s).

EXAMPLE 18 (31)

4-(2-(t-Butoxycarbonylamino)ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1301] 1737

[1302] TLC: Rf 0.35 (hexane:ethyl acetate=1:2);

[1303] NMR (CDCl3): δ 1.35 (s, 9H), 3.46-3.66 (m, 2H), 3.62 (dd, J=14.2, 2.2 Hz, 1H), 3.73 (dd, J=14.2, 6.8 Hz, 1H), 4.11-4.25 (m, 2H), 5.06 (dd, J=6.8, 2.2 Hz, 1H), 5.39 (br, 1H), 7.08 (d, J=7.6 Hz, 1H), 7.31-7.39 (m, 4H), 7.44-7.57 (m, 3H).

EXAMPLE 18 (32)

4-(3-(t-Butoxycarbonylamino)propyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1304] 1738

[1305] TLC: Rf 0.28 (hexane:ethyl acetate=1:1);

[1306] NMR (CDCl3): δ 1.38 (s, 9H), 2.00-2.11 (m, 2H), 3.33-3.44 (m, 2H), 3.59 (dd, J=14.0, 2.2 Hz, 1H), 3.69 (dd, J=14.0, 6.6 Hz, 1H), 4.17 (t, J=5.9 Hz, 2H), 4.90 (br, 1H), 5.08 (dd, J=6.6, 2.2 Hz, 1H), 7.08 (dd, J=8.1, 0.7 Hz, 1H), 7.29-7.38 (m, 4H), 7.48-7.56 (m, 3H).

EXAMPLE 18 (33)

5-(2-(t-Butoxycarbonylamino)ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1307] 1739

[1308] TLC: Rf 0.40 (hexane:ethyl acetate=2:1);

[1309] NMR (CDCl3): δ 1.46 (s, 9H), 3.52 (dd, J=15, 6 Hz, 1H), 3.56 (t, J=7.5 Hz, 2H), 3.80 (dd, J=15, 6 Hz, 1H), 4.10 (t, J=7.5 Hz, 2H), 4.88 (t, J=6 Hz, 1H), 4.99 (br, 1H), 7.03 (dd, J=9, 2 Hz, 1H), 7.12 (d, J=2 Hz, 1H), 7.35-7.47 (m, 5H), 7.64 (d, J=9 Hz, 1H).

EXAMPLE 18(34)

6-(3-(t-Butoxycarbonylamino)propyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1310] 1740

[1311] TLC: Rf 0.43 (hexane:ethyl acetate=1:1);

[1312] NMR (CDCl3): δ 5 1.44 (s, 9H), 2.01 (quint, J=6.2 Hz, 2H), 3.32 (q, J=6.2 Hz, 2H), 3.51 (dd, J=13.6, 6.0 Hz, 1H), 3.80 (dd, J=13.6, 7.4 Hz, 1H), 4.06 (t, J=6.2 Hz, 2H), 4.69 (br, 1H), 4.91 (t-like, J=6.8 Hz, 1H), 7.14-7.21 (m, 2H), 7.32-7.45 (m, 5H), 7.59 (d, J=8.4 Hz, 1H).

EXAMPLE 18(35)

6-(2-(t-Butoxycarbonylamino)ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1313] 1741

[1314] TLC: Rf 0.47 (hexane:ethyl acetate=1:1);

[1315] NMR (CDCl3): δ 1.46 (s, 9H), 3.51 (dd, J=13.8, 6.2 Hz, 1H), 3.55 (q, J=5.2 Hz, 2H), 3.81 (dd, J=13.8, 7.4 Hz, 1H), 4.06 (t, J=5.2 Hz, 2H), 4.92 (t-like, J=6.4 Hz, 1H), 4.96 (br, 1H), 7.13 (d, J=2.4 Hz, 1H), 7.18 (dd, J=8.5, 2.4 Hz, 1H), 7.32-7.45 (m, 5H), 7.60 (d, J=8.5 Hz, 1H).

EXAMPLE 18(36)

7-(2-(t-Butoxycarbonylamino)ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1316] 1742

[1317] TLC: Rf 0.60 (hexane ethyl acetate=1:2);

[1318] NMR (CDCl3): “ 7.60-7.24 (7H, m), 6.94 (1H, d, J=8.4 Hz), 5.38 (1H, bs), 4.90 (1H, t, J=7.4 Hz), 4.30-4.05 (2H, m), 3.79 (1H, dd, J=13.7, 7.4 Hz), 3.60-3.40 (3H, m), 1.42 (9H, s).

EXAMPLE 18(37)

4-(N-(t-Butoxycarbonyl)piperidin-4-yl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1319] 1743

[1320] TLC: Rf 0.41 (hexane:ethyl acetate=1:1);

[1321] NMR (CDCl3): δ 7.60-7.42 (3H, m), 7.42-7.25 (4H, m), 7.04 (1 H, d, J=8.2 Hz), 5.05 (1 H, dd, J=6.6, 2.2 Hz), 4.80-4.60 (1H, m), 3.85-3.32 (6H, m), 2.15-1.65 (4H, m), 1.48 (9H, s).

EXAMPLE 18(38)

4,7-B is [(2-(t-butoxycarbonylamino)ethyl) oxy]-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1322] 1744

[1323] TLC: Rf 0.35 (hexane:ethyl acetate=1:2);

[1324] NMR (CDCl3): δ 7.53-7.30 (5H, m), 7.20-6.85 (2H, m), 5.40 (2H, brs), 5.03-4.85 (1H, m), 4.25-4.00 (4H, m), 3.90-3.40 (6H, m), 1.43 (18H, s).

EXAMPLE 18(39)

4-(3-Nitrophenylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1325] 1745

[1326] TLC: Rf 0.29 (hexane:ethyl acetate=1:1);

[1327] NMR (CDCl3): δ 8.44 (1H, s), 8.24 (1 H, d, J=8.4 Hz), 7.86 (1H, d, J=8.0 Hz), 7.65-7.20, (8H, m), 7.14 (1H, d, J=7.2 Hz), 5.31 (2H, s), 5.13 (1H, dd, J=2.6 Hz, 6.6 Hz), 3.80-3.56 (2H, m).

EXAMPLE 18(40)

4,7-Bis(pyridin-3-ylmethyloxy)-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1328] 1746

[1329] TLC: Rf 0.20 (ethyl acetate:methanol=10:1);

[1330] NMR (CDCl3): δ 8.75-8.72 (1H, m), 8.70-8.50 (4H, m), 7.96-7.82 (2H, m), 7.46-7.24 (6H, m), 7.05 (1H, d, J=9.0 Hz), 6.93 (1H, d, J=9.0 Hz), 5.25 (2H, s), 5.15 (2H, s), 5.01-4.95 (1H, m), 3.81-3.59 (2H, m).

EXAMPLE 19

4-(3-Hydroxypropyl)oxy-3-phenylsulfynyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1331] 1747

[1332] By the same procedure as described in Example 2 using the compound prepared in Example 18 (9) instead of the compound prepared in Example 1, the compound of the present invention having the following physical data was obtained.

[1333] TLC: Rf 0.18 (hexane:ethyl acetate=1:1);

[1334] NMR (CDCl3): δ 2.17 (quint, J=6.0 Hz, 2H), 3.08 (dd, J=14.0, 8.6 Hz, 1H), 3.94 (t, J=6.0 Hz, 2H), 3.98 (dd, J=14.0, 4.8 Hz, 1H), 4.32 (t, J=6.0 Hz, 2H), 4.15 (dd, J=8.6, 4.8 Hz, 1H), 7.18 (d, J=7.9 Hz, 1H), 7.35 (d, J=7.9 Hz, 1H), 7.55-7.66 (m, 6H).

EXAMPLE 20

4-(4-Nitrophenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1335] 1748

[1336] By the same procedure as described in Example 10 using the compound prepared in Example 18 instead of the compound prepared in Example 9, the compound of the present invention having the following physical data was obtained.

[1337] TLC: Rf 0.67 (ethyl acetate:methanol:28% ammonia water=100:10:1);

[1338] NMR (DMSO-d6): δ 8.25 (2H, d, J=9 Hz), 7.78-7.52 (6H, m), 7.52-7.20 (4H, m), 5.74 (1H, d, J=9 Hz), 5.26 (1H, d, J=14 Hz), 4.99 (1H, d, J=14 Hz), 4.19 (1H, d, J=15 Hz), 4.00 (1H, dd, J=15, 9 Hz).

EXAMPLES 20 (1)˜20 (39)

[1339] Using the compounds prepared in Examples 18 (1)˜18 (39) instead of the compound prepared in Example 18 by the same procedure as described in Example 20, or by the same reaction using 3-chloroperbenzoic acid instead of OXONEO as an oxidizer, and, if necessary, by converting into the corresponding salts by known methods, the following compounds of the present invention were obtained.

EXAMPLE 20 (1)

4-(3-Phenyloxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1340] 1749

[1341] TLC: Rf 0.33 (hexane:ethyl acetate=1:1);

[1342] NMR (CDCl3): δ 2.20 (quint, J=6.0 Hz, 2H), 3.70 (dd, J=14.8, 9.3 Hz, 1H), 3.99-4.28 (m, 4H), 4.20 (dd, J=14.8, 1.2 Hz, 1H), 5.19 (dd, J=9.3, 1.2 Hz, 1H), 6.89-7.01 (m, 4H), 7.21-7.50 (m, 6H), 7.52-7.60 (m, 1H), 7.65-7.70 (m, 2H).

EXAMPLE 20 (2)

4-Benzyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1343] 1750

[1344] TLC: Rf 0.39 (hexane:ethyl=11);

[1345] NMR (CDCl6): δ 3.73 (dd, J=15.0, 9.0 Hz, 1H), 4.22 (d, J=15.0 Hz, 1H), 4.88 (d, J=11.7 Hz, 1H), 4.99 (d, J=11.7 Hz, 1H), 5.28 (d, J=9.0 Hz, 1H), 7.04 (d, J=7.8 Hz, 1H), 7.26-7.40 (m, 8H), 7.49-7.58 (m, 2H), 7.64-7.69 (m, 2H).

EXAMPLE 20 (3)

4-(3-Benzyloxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1346] 1751

[1347] TLC: Rf 0.26 (hexane:ethyl acetate=1:1);

[1348] NMR (CDCl3): δ 1.96 (quint, J=6.1 Hz, 2H), 3.57-3.67 (m, 2H), 3.67 (dd, J=14.9, 9.2 Hz, 1H), 3.82-3.92 (m, 1H), 3.98-4.09 (m, 1H), 4.21 (dd, J=14.9, 0.5 Hz, 1H), 4.46 (d, J=12.1 Hz, 1H), 4.56 (d, J=12.1 Hz, 1H). 5.05 (dd, J=9.2, 0.5 Hz, 1H), 6.94 (d, J=8.4 Hz, 1H), 7.22-7.27 (m, 6H), 7.35-7.60 (m, 4H), 7.65-7.69 (m, 2H).

EXAMPLE 20 (4)

4-(Pyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1349] 1752

[1350] free compound:

[1351] TLC: Rf 0.17 (ethyl acetate);

[1352] NMR (DMSO-d6): δ 3.95 (dd, J=15.0, 8.8 Hz, 1H), 4.16 (dd, J=15.0, 1.2 Hz, 1H), 4.93 (d, J=12.5 Hz, 1H), 5.15 (d, J=12.5 Hz, 1H), 5.66 (d-like, J=8.0 Hz, 1H), 7.35-7.45 (m, 5H), 7.55-7.72 (m, 4H), 7.80 (dt, J=8.0, 1.4 Hz, 1H), 8.56 (dd, J=5.0, 1.4 Hz, 1H), 8.61 (d, J=1.4 Hz, 1H).

[1353] Hydrochloride:

[1354] TLC: Rf 0.17 (ethyl acetate);

[1355] NMR (DMSO-d6): δ 3.98 (dd, J=15.2, 8.6 Hz, 1H), 4.16 (d, J=15.2 Hz, 1H), 5.10 (d, J=12.8 Hz, 1H), 5.29 (d, J=12.8 Hz, 1H), 5.85 (d, J=8.6 Hz, 1H), 7.38-7.59 (m, 5H), 7.66-7.75 (m, 3H), 7.94 (dd, J=8.0, 5.4 Hz, 1H), 8.38 (d, J=8.0 Hz, 1H), 8.84 (d, J=5.4 Hz, 1H), 8.88 (s, 1H).

[1356] Methanesulfonic Acid Salt:

[1357] TLC: Rf 0.31 (ethyl acetate:methanol=9:1);

[1358] NMR (DMSO-d6): δ 2.37 (3H, s), 4.00 (dd, J=15.0, 8.8 Hz, 1H), 4.17 (d-like, J=15.4 Hz, 1H), 5.13 (d, J=13.0 Hz, 1H), 5.32 (d, J=13.0 Hz, 1H), 5.85 (d-like, J=8.0 Hz, 1H), 7.39-7.45 (m, 4H), 7.52-7.59 (m, 1H), 7.66-7.77 (m, 3H), 8.05 (dd, J=8.2, 5.8 Hz, 1H), 8.49 (d, J=8.2 Hz, 1H), 8.89-8.92 (m, 2H).

EXAMPLE 20 (5)

4-(N-Oxidequinolin-2-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1359] 1753

[1360] TLC: Rf 0.38 (ethyl acetate:methanol: 28% ammonia water=100:10:1);

[1361] NMR (CDCl3): “ 8.77 (1H, d, J=8 Hz), 8.00-7.75 (4H, m), 7.75-7.63 (3H, m), 7.63-7.45 (2H, m), 7.45-7.22 (3H, m), 7.17 (1H, d, J=8 Hz), 5.72-5.25 (3H, m), 4.28 (1H, d, 15 Hz), 3.84 (1H, dd, J=15, 9 Hz).

EXAMPLE 20 (6a)

4-(Pyridin-2-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1362] 1754

[1363] TLC: Rf 0.43 (ethyl acetate:methanol:28% ammonia water=100:10:1);

[1364] NMR (CDCl3): “ 8.61 (1H, d, J=4 Hz), 7.88-7.18 (10H, m), 7.04 (1H, d, J=8 Hz), 5.37 (1H, d, J=9 Hz), 5.11 (1 H, d, J=14 Hz), 4.98 (1 H, d, J=14 Hz), 4.24 (1 H, d, J=15 Hz), 3.78 (1H, dd, J=15, 9 Hz).

EXAMPLE 20 (6b)

4-(N-Oxidepyridin-2-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1365] 1755

[1366] TLC: Rf 0.09 (ethyl acetate:methanol:28% ammonia water=100:10:1);

[1367] NMR (CDCl3+DMSO-d6): δ 8.42-8.22 (1H, m), 7.90-7.20 (11H, m), 5.83 (1H, d, J=8.5 Hz), 5.18 (1H, d, J=15 Hz), 4.93 (1H, d, J=15 Hz), 4.21 (1H, d, J=15 Hz), 4.03 (1H, dd, J=15, 8.5 Hz).

EXAMPLE 20 (7)

4-(Pyridin-4-ylmethyl)oxy-3-phenylsulfonyl-2,3-di hydro-1,1-dioxidebenzo[b]thiophene

[1368] 1756

[1369] Free Compound:

[1370] TLC: Rf 0.26 (ethyl acetate:methanol:28% ammonia water=100:10:1);

[1371] NMR (CDCl3+DMSO-d6): δ 8.57 (2H, d, J=6 Hz), 7.80-7.15 (10H, m), 5.75 (1H, d, J=9 Hz), 5.15 (1H, d, J=14 Hz), 4.90 (1H, d, J=14 Hz), 4.19 (1H, d, J=15 Hz), 4.00 (1H, dd, J=15, 9 Hz).

[1372] Hydrochloride:

[1373] TLC: Rf 0.31 (ethyl acetate:methanol=9:1);

[1374] NMR (DMSO-d6): δ 8.93 (d, J=6.5 Hz, 2H), 8.00 (d, J=6.5 Hz, 2H), 7.74-7.68 (m, 3H), 7.60-7.54 (m, 1H), 7.47-7.42 (m, 3H), 7.33 (d, J=8.0 Hz, 1H), 5.93 (d, J=9.0 Hz, 1H), 5.46 (d, J=16.0 Hz, 1H), 5.18 (d, J=16.0 Hz, 1H), 4.19 (d, J=15.0 Hz, 1H), 4.03 (dd, J=15.0, 9.0 Hz, 1H).

[1375] Methanesulfonic Acid Salt:

[1376] TLC: Rf 0.31 (ethyl acetate:methanol=9:1);

[1377] NMR (DMSO-d6): δ 8.94 (d, J=6.3 Hz, 2H), 8.03 (d, J=6.3 Hz, 2H), 7.74-7.68 (m, 3H), 7.60-7.55 (m, 1H), 7.47-7.42 (m, 3H), 7.34 (d, J=8.0 Hz, 1H), 5.92 (d, J=9.0 Hz, 1H), 5.46 (d, J=16.0 Hz, 1H), 5.19 (d, J=16.0 Hz, 1H), 4.19 (d, J=15.0 Hz, 1H), 4.03 (dd, J=15.0, 9.0 Hz, 1H), 2.38 (s, 3H).

EXAMPLE 20 (8)

4-(3-(Pyridin-3-yl)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-di oxidebenzo[b]thiophene

[1378] 1757

[1379] TLC: Rf 0.41 (ethyl acetate:methanol:28% ammonia water=100:10:1);

[1380] NMR (CDCl3+CD3OD): δ 8.50-8.36 (2H. m), 7.80-7.23 (9H, m), 7.00 (1H, d, J=8 Hz), 5.27 (1H, d, J=9 Hz), 4.26-3.68 (4H, m), 2.88 (2H, t, J=7 Hz), 2.20-1.90 (2H, m).

EXAMPLE 20 (9)

4-(3-Hydroxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1381] 1758

[1382] TLC: Rf 0.26 (hexane:ethyl acetate=1:1);

[1383] NMR (CDCl3): δ 2.02 (quint, J=5.6 Hz, 2H), 2.28 (t, J=5.6 Hz, 1H), 3.71 (dd, J=14.8, 9.2 Hz, 1H), 3.91 (m, J=5.6 Hz, 2H), 4.05 (dd, J=14.8, 1.0 Hz, 1H), 4.10-4.17 (m, 2H), 5.28 (d-like, J=8.8 Hz, 1H), 7.08 (d, J=8.4 Hz, 1H), 7.23 (d, J=7.8 Hz, 1H), 7.42-7.62 (m, 4H), 7.66-7.73 (m, 2H).

EXAMPLE 20 (10)

5-Pentoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1384] 1759

[1385] TLC: Rf 0.40 (hexane:ethyl acetate=2:1);

[1386] NMR (CDCl3): δ 0.96 (t, J=8 Hz, 3H), 1.42 (m, 4H), 1.86 (m, 2H), 3.70 (dd, J=14, 8 Hz, 1H), 3.80 (dd, J=14,6 Hz, 1H), 4.07 (m, 2H), 5.00 (dd, J=8,6 Hz, 1H), 7.10 (dd, J=8,2 Hz, 1H), 7.44 (d, J=2 Hz, 1H), 7.46-7.77 (m, 6H).

EXAMPLE 20 (11)

5-(2-Phenyloxyethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1387] 1760

[1388] TLC: Rf 0.25 (hexane:ethyl acetate=1:1);

[1389] NMR (CDCl3): (3.70 (dd, J=14, 8 Hz, 1H), 3.77 (dd, J=14, 6 Hz, 1H), 4.41 (m, 4H), 5.02 (dd, J=8, 6 Hz, 1H), 7.00 (m, 3H), 7.19 (dd, J=8, 2 Hz, 1H), 7.30-7.77 (m, 9H).

EXAMPLE 20 (12)

5-(3-Hydroxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1390] 1761

[1391] TLC: Rf 0.15 (hexane:ethyl acetate=1:1);

[1392] NMR (CDClo3): δ 2.11 (m, 2H), 3.65 (dd, J=14, 8 Hz, 1H), 3.78 (dd, J=14, 5 Hz, 1H), 3.89 (m, 2H), 4.25 (m, 2H), 5.01 (dd, J=8, 5 Hz, 1H), 7.12 (dd, J=9, 2 Hz, 1H), 7.45-7.77 (m, 7H).

EXAMPLE 20 (13)

5-(Pyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1393] 1762

[1394] Free Compound:

[1395] TLC: Rf 0.30 (ethyl acetate);

[1396] NMR (DMSC-d6): δ 3.79 (dd, J=15.1, 3.2 Hz, 1H), 4.00 (dd, J=15.1, 9.4 Hz, 1H), 5.27 (s, 2H), 5.74 (dd, J=9.4, 3.2 Hz, 1H), 7.20 (d, J=2.2 Hz, 1H), 7.36 (dd, J=8.7, 2.2 Hz, 1H), 7.47 (dd, J=7.8, 4.9 Hz, 1H), 7.57-7.65 (m, 2H), 7.71-7.82 (m, 4H), 7.91 (dt, J=7.8, 2.0 Hz, 1H), 8.58 (dd, J=4.9, 2.0 Hz, 1H), 8.71 (d, J=2.0 Hz, 1H).

[1397] Hydrochloride:

[1398] TLC: Rf 0.65 (ethyl acetate:triethylamine=10:1);

[1399] NMR (DMSO-d6): δ 3.77 (dd, J=15.0, 3.4 Hz, 1H), 3.99 (dd, J=15.0, 9.6 Hz, 1H), 5.43 (s, 2H), 5.77 (dd, J=9.6, 3.4 Hz, 1H), 7.30 (d, J=2.0 Hz, 1H), 7.41 (dd, J=8.8, 2.2 Hz, 1H), 7.59-7.66 (m, 2H), 7.74-7.82 (m, 4H), 8.02 (dd, J=8.4, 5.6 Hz, 1H), 8.57 (d-like, J=8.4 Hz, 1H), 8.88 (d-like, J=5.6 Hz, 1H), 9.04 (s-like, 1H).

[1400] Methanesulfonic Acid Salt:

[1401] TLC: Rf 0.30 (ethyl acetate);

[1402] NMR (DMSO-d6): δ 2.37 (3H, s), 3.77 (dd, J=15.0, 3.3 Hz, 1H), 4.00 (dd, J=15.0, 9.3 Hz, 1H), 5.77 (dd, J=9.3, 3.3 Hz, 1H), 7.31 (d, J=2.2 Hz, 1H), 7.41 (dd, J=8.7, 2.2 Hz, 1H), 7.59-7.66 (m, 2H), 7.74-7.83 (m, 4H), 8.06 (dd, J=8.0, 5.6 Hz, 1H), 8.61 (d-like, J=8.0 Hz, 1H), 8.91 (dd, J=5.6, 1.0 Hz, 1H), 9.07 (d, J=1.6 Hz, 1H).

EXAMPLE 20 (14)

5-(3-(Pyridin-3-yl)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1403] 1763

[1404] TLC: Rf 0.32 (ethyl acetate:methanol=10:1);

[1405] NMR (CD3OD): δ 8.80 (1H, s), 8.71 (1H, d, J=6 Hz), 8.56 (1H, d, J=8 Hz), 8.02 (1H, t, J=7 Hz), 7.85-7.42 (6H, m), 7.27 (1H, d, J=10 Hz), 7.14 (1H, s), 5.50-5.32 (1H, m), 4.16 (2H, t, J=6 Hz), 3.98-3.65 (2H, m), 3.10 (2H, t, J=7 Hz), 2.40-2.10 (2H, m).

EXAMPLE 20 (15)

6-(3-Phenyloxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1406] 1764

[1407] TLC: Rf 0.43 (hexane:ethyl acetate=1:1);

[1408] NMR (CDCl3): δ 2.29 (quint, J=6.0 Hz, 2H), 3.65-3.81 (m, 2H), 4.15 (t, J=6.0 Hz, 2H), 4.21 (t, J=6.0 Hz, 2H), 4.99 (dd, J=7.3, 5.9 Hz, 1H), 6.89-6.99 (m, 3H), 7.08 (d, J=2.2 Hz, 1H), 7.23 (dd, J=8.8, 2.2 Hz, 1H), 7.25-7.33 (m, 2H), 7.45-7.52 (m, 2H), 7.62-7.70 (m, 3H), 7.85 (d, J=8.8 Hz, 1H).

EXAMPLE 20 (16)

6-Benzyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1409] 1765

[1410] TLC: Rf 0.50 (hexane:ethyl acetate=1:1);

[1411] NMR (CDCl3): δ 3.71 (dd, J=14.7, 7.7 Hz, 1H), 3.80 (dd, J=14.7, 5.5 Hz, 1H), 5.00 (dd, J=7.7, 5.5 Hz, 1H), 5.10 (s, 2H), 7.15 (d, J=2.5 Hz, 1H), 7.30 (dd, J=8.5, 2.5 Hz, 1H), 7.40-7.53 (m, 7H), 7.63-7.71 (m, 3H), 7.87 (d, J=8.5 Hz, 1H).

EXAMPLE 20 (17)

6-Pentoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1412] 1766

[1413] TLC: Rf 0.26 (hexane:ethyl acetate 2:1);

[1414] NMR (CDCl3): δ 0.94 (t, J=6.4 Hz, 3H), 1.42 (m, 4H), 1.81 (m, 2H), 3.70 (dd, J=14.9, 7.6 Hz, 1H), 3.79 (dd, J=14.9, 5.7 Hz, 1H), 3.99 (t, J=6.4 Hz, 2H), 5.00 (dd, J=7.6, 5.7 Hz, 1H), 7.04 (d, J=2.4 Hz, 1H), 7.23 (dd, J=8.8, 2.4 Hz, 1H), 7.46-7.54 (m, 2H), 7.64-7.72 (m, 3H), 7.84 (d, J=8.8 Hz, 1H).

EXAMPLE 20 (18)

6-(2-(Morpholin-4-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1415] 1767

[1416] Free Compound:

[1417] TLC: Rf 0.27 (hexane:ethyl acetate: triethylamine=2:4:1);

[1418] NMR (CDCl3): δ 2.56 (t, J=4.5 Hz, 4H), 2.81 (t, J=5.6 Hz, 2H), 3.70-3.77 (m, 6H), 4.14 (t, J=5.6 Hz, 2H), 5.01 (dd, J=7.5, 5.7 Hz, 1H), 7.08 (d, J=2.3 Hz, 1H), 7.25 (dd, J=8.7, 2.3 Hz, 1H), 7.47-7.54 (m, 2H), 7.64-7.72 (m, 3H), 7.83 (d, J=8.7 Hz, 1H).

[1419] Hydrochloride:

[1420] TLC: Rf 0.27 (hexane ethyl acetate:triethylamine=4:8:1);

[1421] NMR (CD3OD): δ 3.43-3.53 (m, 4H), 3.68 (t, J=4.8 Hz, 2H), 3.80 (dd, J=15.4, 8.4 Hz, 1H), 3.95 (dd, J=15.4, 4.0 Hz, 1H), 3.92-4.02 (m, 4H), 4.51 (t, J=4.8 Hz, 2H), 5.45 (dd, J=8.4, 4.0 Hz, 1H), 7.33 (d, J=2.6 Hz, 1H), 7.42 (dd, J=8.8, 2.6 Hz, 1H), 7.55-7.63 (m, 2H), 7.71-7.81 (m, 4H).

EXAMPLE 20 (19)

6-(3-Hydroxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1422] 1768

[1423] TLC: Rf 0.22 (hexane:ethyl acetate=1:2);

[1424] NMR (CDCl3): δ 2.06 (quint, J=6.0 Hz, 2H), 3.71 (dd, J=14.6, 7.5 Hz, 1H), 3.79 (dd, J=14.6, 5.6 Hz, 1H), 3.85 (t, J=6.0 Hz, 2H), 4.16 (t, J=6.0 Hz, 2H), 5.00 (dd, J=7.5, 5.6 Hz, 1H), 7.08 (d, J=2.4 Hz, 1H), 7.24 (dd, J=8.8, 2.4 Hz, 1H), 7.47-7.55 (m, 2H), 7.64-7.71 (m, 3H), 7.84 (d, J=8.8 Hz, 1H).

EXAMPLE 20 (20)

6-(Pyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1425] 1769

[1426] Free Compound:

[1427] TLC: Rf 0.39 (ethyl acetate);

[1428] NMR (DMSO-d6): δ 3.78 (dd, J=15.2, 3.1 Hz, 1H), 4.01 (dd, J=15.2, 9.2 Hz, 1H), 5.29 (s, 2H), 5.69 (dd, J=9.2, 3.1 Hz, 1H), 7.42-7.47 (m, 3H), 7.58-7.66 (m, 3H), 7.74-7.82 (m, 3H), 7.89 (dt, J=8.0, 1.0 Hz, 1H), 8.57 (dd, J=4.8, 1.6 Hz, 1H), 8.69 (d, J=1.6 Hz, 1H).

[1429] Hydrochloride:

[1430] TLC: Rf 0.39 (ethyl acetate);

[1431] NMR (DMSO-d6): δ 3.78 (dd, J=15.2, 3.0 Hz, 1H), 4.01 (dd, J=15.2, 9.4 Hz, 1H), 5.72 (dd, J=9.4, 3.0 Hz, 1H), 7.46-7.51 (m, 2H), 7.59-7.66 (m, 3H), 7.75-7.83 (m, 3H), 7.99 (dd, J=8.0, 5.4 Hz, 1H), 8.52 (d, J=8.0 Hz, 1H), 8.87 (dd, J=5.4, 1.2 Hz, 1H), 8.99 (d, J=1.2 Hz, 1H).

EXAMPLE 20 (21)

6-(3-Nitrophenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1432] 1770

[1433] TLC: Rf 0.55 (hexane:ethyl acetate=1:2);

[1434] NMR (DMSO-d6): δ 8.36-8.34 (m, 1H), 8.25-8.20 (m, 1H), 7.93 (d-like, J=7.6 Hz, 1H), 7.82-7.72 (m, 4H), 7.68-7.58 (m, 3H), 7.50-7.43 (m, 2H), 5.70 (dd, J=9.4, 3.0 Hz, 1H), 5.40 (s, 2H), 4.02 (dd, J=15.2, 9.4 Hz, 1H), 3.79 (dd, J=15.2, 3.0 Hz, 1H).

EXAMPLE 20 (22)

6-(3-Bromopropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1435] 1771

[1436] TLC: Rf 0.60 (hexane:ethyl acetate=1:1);

[1437] NMR (CDCl3): δ 2.35 (m, 2H), 3.60 (t, J=6.0 Hz, 2H), 3.70-3.91 (m, 2H), 4.17 (t, J=6.0 Hz, 2H), 5.01 (dd, J=14, 7 Hz, 1H), 7.09 (d, J=3.0 Hz, 1H), 7.25 (m, 1H), 7.53 (m, 2H), 7.67 (m, 3H), 7.89 (m, 1H).

EXAMPLE 20 (23)

7-Pentoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1438] 1772

[1439] TLC: Rf 0.48 (hexane:ethyl acetate=1:1);

[1440] NMR (CDCl3): δ 7.70-7.43 (7H, m), 6.99 (1H, d, J=8.2 Hz), 5.01 (1H, dd, J=8.6, 5.4 Hz), 4.07 (2H, t, J=6.8 Hz), 3.73-3.68 (2H, m), 1.80 (2H, quint., J=6.8 Hz), 1.50-1.20 (4H, m), 0.89 (3H, t, J=6.8 Hz).

EXAMPLE 20 (24)

7-(2-Phenyloxyethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1441] 1773

[1442] TLC: Rf 0.27 (hexane:ethyl acetate=1:1)

[1443] NMR (CDCl3): δ7.70-6.88 (13H, m), 5.01 (1H, dd, J=8.1, 5.4 Hz), 4.50-4.40 (2H, m), 4.40-4.31 (2H, m), 3.76-3.70 (2H, m).

EXAMPLE 20 (25)

7-(3-Hydroxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1444] 1774

[1445] TLC: Rf 0.46 (ethyl acetate);

[1446] NMR (CDCl3): δ 7.75-7.40 (7H, m), 7.07 (1H, d, J=8.0 Hz), 5.05 (1H, dd, J=8.4,5.4 Hz), 4.26 (2H, t, J=5.8 Hz), 3.85-3.65 (4H, m), 2.03 (2H, quint, J=5.8 Hz).

EXAMPLE 20 (26a)

7-(Pyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1447] 1775

[1448] TLC: Rf 0.30 (ethyl acetate:triethylamine=20:1);

[1449] NMR (DMSO-d6): δ 8.85-8.75 (2H, m), 8.27 (1H, d, J=7.6 Hz), 7.92-7.55 (7H, m), 7.43 (1H, d, J=8.2 Hz), 7.26 (1H, d, J=7.6 Hz), 5.80 (1H, dd, J=9.4, 3.2 Hz), 5.51 (2H, s), 3.99 (1H, dd, J=15.3, 9.4 Hz), 3.77 (1H, dd, J=15.3, 3.2 Hz).

EXAMPLE 20 (26b)

7-(N-Oxidepyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1450] 1776

[1451] TLC: Rf 0.26 (ethyl acetate: methanol triethylamine 16 3 1);

[1452] NMR (DMSO-d6): δ 5.38 (1H, s), 8.30 (1H, d, J=5.4 Hz), 7.90-7.42 (8H, m), 7.39 (1H, d, J=7.8 Hz), 7.23 (1H, d, J=7.8 Hz), 5.78 (1H, dd, J=9.7, 3.4 Hz), 5.39 (2H, s), 3.99 (1 H, dd, J=15, 9.7 Hz), 3.78 (1H, dd, J=15, 3.4 Hz).

EXAMPLE 20 (27)

4-(t-Butoxycarbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1453] 1777

[1454] TLC: Rf 0.28 (hexane:ethyl acetate=1:1);

[1455] NMR (CDCl3): δ 1.48 (s, 9H), 3.76 (dd, J-14.9, 9.2 Hz, 1H), 4.16 (d, J=16.0 Hz, 1H), 4.25 (dd, J=1.9, 1.2 Hz, 1H), 4.31 (d, J=16.0 Hz, 1H), 5.36 (dd, J=9.2, 1.2 Hz, 1H), 6.82 (dd, J=8.1, 0.7 Hz, 1H), 7.35 (d, J=7.4 Hz, 1H), 7.44-7.57 (m, 3H), 7.59-7.67 (m, 1H), 7.78-7.83 (m, 2H).

EXAMPLE 20 (28)

5-(t-Butoxycarbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1456] 1778

[1457] TLC: Rf 0.50 (hexane:ethyl acetate=1:1);

[1458] NMR (CDCl3): δ 1.53 (s, 9H), 3.74 (d-like, J=6 Hz, 2H), 4.67 (m, 2H), 5.00 (t, J=6 Hz, 1H), 7.17 (dd, J=8, 2Hz, 1H), 7.45 (d, J=2 Hz, 1H), 7.50 (m, 2H), 7.55 (d, J=8 Hz, 1H), 7.66 (m, 3H).

EXAMPLE 20 (31)

6-(t-Butoxycarbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1459] 1779

[1460] TLC: Rf 0.42 (hexane:ethyl acetate=1:1);

[1461] NMR (CDCl3): δ 1.48 (s, 3H), 3.67-3.83 (m, 2H), 4.56 (s, 2H), 5.00 (dd, J=7.4, 5.6 Hz, 1H), 6.99 (d, J=2.6 Hz, 1H), 7.29 (dd, J=8.8, 2.6 Hz, 1H), 7.46-7.53 (m, 2H), 7.61-7.70 (m 2H), 7.89 (d, J=8.8 Hz, 1H).

EXAMPLE 20 (30)

7-(t-Butoxycarbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1462] 1780

[1463] TLC: Rf 0.28 (hexane:ethyl acetate=1:1);

[1464] NMR (CDCl3): δ 7.70-7.47 (7H, m), 6.91-6.86 (lH, m), 5.02 (1H, dd, J=8.3, 5.6 Hz), 4.64 (2H, s), 3.76-3.72 (2H, m), 1.44 (9H, s).

EXAMPLE 20 (31)

4-(2-(t-Butoxycarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1465] 1781

[1466] TLC: Rf 0.35 (hexane:ethyl acetate=1:2);

[1467] NMR (CDCl3): 3.42-3.56 (m, 1H), 3.63-3.76 (m, 1H), 3.73 (dd, J=15.2, 9.6 Hz, 1H), 4.02-4.34 (m, 2H), 4.10 (dd, J=15.2, 1.2 Hz, 1H), 5.29 (dd, J=9.6, 1.2 Hz, 1H), 5.78 (br, 1H), 7.02 (d-like, J=7.5 Hz, 1H), 7.22 (d, J=7.5 Hz, 1H), 7.40-7.64 (m, 4H), 7.21-7.76 (m, 2H).

EXAMPLE 20 (32)

4-(3-(t-Butoxycarbonylamino)propyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1468] 1782

[1469] TLC: Rf 0.30 (hexane:ethyl acetate 1:2);

[1470] NMR (CDCl3): δ 1.41 (s, 9H), 1.93 (m, 2H), 3.35 (m, 2H), 3.72 (dd, J=15.0, 9.0 Hz, 1H), 3.99 (t, J=6.1 Hz, 2H), 4.09 (d, J=15.0 Hz, 2H), 4.95 (br, 1H), 5.35 (d, J=9.0 Hz, 1H), 7.02 (d, J=7.5 Hz, 1H), 7.25 (d, J=7.5 Hz, 1H), 7.43-7.67 (m, 4H), 7.70-7.75 (m, 2H).

EXAMPLE 20 (33)

5-(2-(t-Butoxycarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1471] 1783

[1472] TLC: Rf 0.40 (hexane:ethyl acetate=1:1);

[1473] NMR (CDCl3): δ 1.47 (s, 9H), 3.54 (m, 2H), 3.66 (dd, J=15, 8Hz, 1H), 3.80 (dd, J=15,5 Hz, 1H), 4.13 (t, J=5 Hz, 2H), 5.00 (dd, J=8, 5 Hz, 1H), 5.00 (br, 1H), 7.12 (dd, J=8, 2 Hz, 1H), 7.44 (d, J-2 Hz, 1H), 7.55 (m, 3H), 7.72 (m, 3H).

EXAMPLE 20 (34)

6-(3-(t-Butoxycarbonylamino)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1474] 1784

[1475] TLC: Rf 0.41 (hexane:ethyl acetate=1:2);

[1476] NMR (CDCl3): δ 1.44 (s, 9H), 2.01 (quint, J=6.2 Hz, 2H), 3.32 (q, J=6.2 Hz, 2H), 3.71 (dd, J=14.6, 7.7 Hz, 1H), 3.79 (dd, J=14.6, 5.5 Hz, 1H), 4.06 (t, J=6.2 Hz, 2H), 4.68 (br, 1H), 5.00 (dd, J=7.7, 5.5 Hz, 1H), 7.05 (d, J=2.4 Hz, 1H), 7.23 (dd, J=8.8, 2.4 Hz, 1H), 7.47-7.54 (m, 2H), 7.64-7.72 (m, 3H), 7.85 (d, J=8.8 Hz, 1H).

EXAMPLE 20 (35)

6-(2-(t-Butoxycarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1477] 1785

[1478] TLC: Rf 0.24 (hexane ethyl acetate=1:1);

[1479] NMR (CDCl3): δ 1.46 (s, 9H), 3.56 (q, J=5.4 Hz, 2H), 3.71 (dd, J=14.8, 7.7 Hz, 1H), 3.79 (dd, J=14.8, 5.6 Hz, 1H), 4.06 (t, J=5.4 Hz, 2H), 4.97 (br, 1H), 5.00 (dd, J=7.7, 5.6 Hz, 1H), 7.05 (d, J=2.6 Hz, 1H), 7.24 (dd, J=8.8, 2.6 Hz, 1H), 7.47-7.55 (m, 2H), 7.65-7.72 (m, 3H), 7.88 (d, J=8.8 Hz, 1H).

EXAMPLE 20 (36)

7-(2-(t-Butoxycarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1480] 1786

[1481] TLC: Rf 0.36 (hexane:ethyl acetate=2:1);

[1482] NMR (CDCl3): δ 7.72-7.40 (7H, m), 7.04 (1H, d, J=8.2 Hz), 5.22 (1H, bs), 5.02 (1H, dd, J=8.7, 5.0 Hz), 4.25-4.10 (2H, m), 3.85-3.65 (2H, m), 3.60-3.46 (2H, m), 1.42 (9H, s).

EXAMPLE 20 (37)

4-(N-(t-Butoxycarbonyl)piperidin-4-yl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1483] 1787

[1484] TLC: Rf 0.19 (hexane:ethyl acetate=1:1);

[1485] NMR (CDCl3): δ 7.80-7.38 (6H, m), 7.23 (1H, d, J=8 Hz), 7.05 (1H, d, J=8 Hz), 5.23 (1H, d, J=9 Hz), 4.70 -4.45 (1H, m), 4.08 (1H, d, J=15 Hz), 3.95-3.60 (2H, m), 3.72 (1H, dd, J=15, 9 Hz), 3.50-3.22 (2H, m), 2.15-1.58 (4H, m), 1.48 (9H, s).

EXAMPLE 20 (38)

4,7-Bis[(2-(t-butoxycarbonylamino)ethyl)oxy]-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1486] 1788

[1487] TLC: Rf 0.25 (hexane:ethyl acetate=1:3);

[1488] NMR (CDCl3): δ 7.77 (2H, d, J=8.2 Hz), 7.70-7.55 (1H, m), 7.55-7.40 (2H, m), 6.95 (2H, s), 5.71 (1H, brs), 5.40-5.15 (2H, m), 4.20-3.30 (10H, m), 1.43 (18H, s).

EXAMPLE 20 (39)

4-(3-Nitrophenylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1489] 1789

[1490] TLC: Rf 0.13 (hexane ethyl acetate=1:1);

[1491] NMR (CDCl3+CD30D): δ 8.35 (1H, s), 8.27 (1H, d, J=8 Hz), 7.87 (1H, d, J=8 Hz), 7.80-7.50 (5H, m), 7.50-7.25 (3H, m), 7.13 (1H, d, J=8 Hz), 5.36 (1H, d-like, J=9 Hz), 5.25-4.98 (2H, m), 4.11 (1H, dd, J=15, 1 Hz), 3.76 (1H, dd, J=15, 9 Hz).

EXAMPLE 21

4-Carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1492] 1790

[1493] To a solution of the compound prepared in Example 20 (27) (105 mg) in methylene chloride (5 ml), was added trifluoroacetic acid (5 ml) at 0° C. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated. The residue was recrystallized from diethyl ether to give the compound of the present invention (63 mg) having the following physical data.

[1494] TLC: Rf 0.20 (chloroform:methanol=4:1);

[1495] NMR (CDCl3+CD3OD): δ 3.79 (dd, J=14.9, 9.0 Hz, 1H), 4.23 (dd, J=14.9, 1.0 Hz, 1H), 4.26 (d, J=16.1 Hz, 1H), 4.43 (d, J=16.1 Hz, 1H), 5.45 (dd, J=9.0, 1.0 Hz, 1H), 6.91 (d, J=8.0 Hz, 1H), 7.36 (d, J=7.6 Hz, 1H), 7.45-7.59 (m, 3H), 7.62-7.70 (m, 1H), 7.77-7.81 (m, 2H).

EXAMPLES 21 (1)˜21 (3)

[1496] By the same procedure as described in Example 21 using the compounds prepared in Examples 20 (28)˜20 (30) instead of the compound prepared in Example 20 (27), the following compounds of the present invention were obtained.

EXAMPLE 21 (1)

5-Carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1497] 1791

[1498] TLC: Rf 0.30 (chloroform:methanol=4:1);

[1499] NMR (CDCl3+CD3OD): δ 3.79 (d-like, J=6 Hz, 2H), 4.76 (s, 2H), 5.10 (t, J=6 Hz, 1H), 7.20 (dd, J=8, 2 Hz, 1H), 7.39 (d, J=2 Hz, 1H), 7.51 (d, J=8 Hz, 1H), 7.55 (m, 2H), 7.69 (m, 3H).

EXAMPLE 21 (2)

6-Carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1500] 1792

[1501] TLC: Rf 0.25 (chloroform:methanol=4:1);

[1502] NMR (CDCl3+CD3OD): δ 3.70-3.85 (m, 2H), 4.68 (s, 2H), 5.07 (t-like, J=6.6 Hz, 1H), 7.07 (d, J=2.5 Hz, 1H), 7.32 (dd, J=8.8, 2.5 Hz, 1H), 7.47-7.55 (m, 2H), 7.63-7.73 (m, 3H), 7.83 (d, J=8.8 Hz, 1H).

EXAMPLE 21 (3)

7-Carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1503] 1793

[1504] TLC: Rf 0.29 (ethyl acetate:acetic acid=10:1);

[1505] NMR (CDCl3+DMSO-d6): δ 7.52-7.26 (6H, m), 7.20 (1H, d, J=7.8 Hz), 6.77 (1H, d, J=8.2 Hz), 4.98 (1H, dd, J=7.8, 5.6 Hz), 4.52 (2H, s), 3.58-3.54 (2H, m).

EXAMPLE 22

4-(N-Pyridin-3-ylmethyl)carbamoylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1506] 1794

[1507] A suspension of the compound prepared in Example 21 (480 mg) in thionyl chloride (10 ml) was refluxed for 15 minutes. After removing thionylchloride, the residue was dissolved in methylene chloride (5 ml). Thereto was added dropwise a solution of 3-(aminomethyl)pyridine (0.15 ml) and triethylamine (1 ml) in methylene chloride (10 ml) under cooling with ice. The reaction mixture was stirred at room temperature for 2 hours. To the reaction mixture was added water. The mixture was extracted by ethyl acetate. The extract was washed by water, a saturated aqueous solution of sodium chloride successively, dried over anhydrous sodium sulfate and concentrated. The residue was purified with column chromatography on silica gel (ethyl acetate:triethylamine=100:1) to give the compound of the present invention (421 mg) having the following physical data.

[1508] Free Compound:

[1509] TLC: Rf 0.49 (ethyl acetate:methanol:triethylamine=8:1:1);

[1510] NMR (DMSO-d6): δ 4.03 (dd, J=14.9, 8.4 Hz, 1H), 4.11 (d, J=14.5 Hz, 1H), 4.12 (dd, J=14.9, 1.6 Hz, 1H), 4.33 (dd, J=15.3, 6.0 Hz, 1H), 4.44 (dd, J=15.3, 6.0 Hz, 1H), 4.57 (d, J=14.5 Hz, 1H), 6.00 (dd, J=8.4, 1.6 Hz, 1H), 7.24 (d, J=8.0 Hz, 1H), 7.34 (dd, J=8.0, 4.7 Hz, 1H), 7.40 (d, J=8.0 Hz, 1H), 7.49-7.54 (m, 2H), 7.63-7.73 (m, 5H), 8.39 (t, J=6.0 Hz, 1H), 8.46 (dd, J=4.7, 1.7 Hz, 1H), 8.51 (d, J=1.7 Hz, 1H).

[1511] Hydrochloride:

[1512] TLC: Rf 0.49 (ethyl acetate:methanol:triethylamine=8:1:1);

[1513] NMR (DMSO-d6): δ 4.04 (dd, J=15.0, 8.7 Hz, 1H), 4.12 (d, J=14.7 Hz, 1H), 4.13 (dd, J=1 5.0, 1.5 Hz, 1H), 4.49 (dd, J=1 5.8, 6.2 Hz, 1H), 4.57 (dd, J=15.8, 6.2 Hz, 1H), 4.60 (d, J=14.7 Hz, 1H), 6.15 (dd, J=8.7, 1.5 Hz, 1H), 7.25 (d, J=8.2 Hz, 1H), 7.40 (d, J=7.6 Hz, 1H), 7.52-7.57 (m, 2H), 7.64 (d, J=8.2 Hz, 1H), 7.68-7.74 (m, 3H), 7.93 (dd, J=8.0, 5.5 Hz, 1H), 8.37 (d, J=8.0 Hz, 1H), 8.68 (t, J=6.2 Hz, 1H), 8.78 (d, J=5.4 Hz, 1H), 8.81 (s 1H).

EXAMPLES 22 (1) And 22 (2)

[1514] By the same procedure as described in Example 22 using a corresponding amine compound instead of 3-(aminomethyl)pyridine, and if necessary, by converting into the corresponding salt by a known method, the following compounds of the present invention were obtained.

EXAMPLE 22 (1)

4-((2-(N,N-Dimethylamino)ethylamino)carbonylmethyl)oxy-3-phenylsuifonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1515] 1795

[1516] Free Compound:

[1517] TLC: Rf 0.29 (ethyl acetate:methanol: triethylamine=8:1:1);

[1518] NMR (CDCl3): δ 2.24 (s, 6H), 2.51 (t-like, J=6.0 Hz, 2H), 3.49 (m, J=6.0 Hz, 2H), 3.77 (dd, J=15.3, 9.6 Hz, 1H), 4.05 (dd, J=15.3, 1.3 Hz, 1H), 4.53 (d, J=14.2 Hz, 1H), 4.64 (d, J=14.2 Hz, 1H), 5.39 (d-like, J=9.0 Hz, 1H); 7.04 (d, J=8.0 Hz, 1H), 7.27 (d, J=8.0 Hz, 1H), 7.42-7.48 (m, 2H), 7.57 (t, J=8.0 Hz, 1H), 7.59-7.65 (m, 1H), 7.70-7.74 (m, 2H), 7.94 (br, 1H).

[1519] hydrochloride:

[1520] TLC: Rf 0.29 (ethyl acetate:methanol:triethylamine=8:1:1);

[1521] NMR (DMSO-d6): δ 2.76 (s, 6H), 3.14-3.18 (m, 2H), 3.44-3.56 (m, 2H), 4.00 (dd, J=15.0, 9.3 Hz, 1H), 4.03 (d, J=14.4 Hz, 1H), 4.17 (d, J=15.0 Hz, 1H), 4.50 (d, J=14.4 Hz, 1H), 6.24 (d-like, J=8.7 Hz, 1H), 7.25 (d, J=8.0 Hz, 1H), 7.39 (d, J=8.0 Hz, 1H), 7.56-7.62 (m, 2H), 7.64 (t, J=8.0 Hz, 1H), 7.70-7.77 (m, 3H), 8.23 (t, J=5.5 Hz, 1H).

EXAMPLE 22 (2)

4-((N-Benzyl-2-(N′,N′-dimethylamino)ethylamino)carbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1522] 1796

[1523] TLC: Rf 0.52 (ethyl acetate:methanol:triethylamine=9:1:1);

[1524] NMR (CDCl3): δ 2.22 (s, 3H), 2.29 (s, 3H), 2.44-2.55 (m, 2H), 3.29-3.35 (m, 1H), 3.56-3.60 (m, 1H), 3.73-3.75 (m, 2H), 4.60 (d, J=15.0 Hz, 0.5H), 4.67 (s-like, 1H), 4.76 (d, J=15.0 Hz, 0.5H), 4.88 (s, 1H), 4.94-5.00 (m, 1H), 5.05 (d, J=15.0 Hz, 0.5H), 5.18 (d, J=15.0 Hz, 0.5H), 7.10-7.36 (m, 6H), 7.41-7.53 (m, 4H), 7.61-7.68 (m, 3H).

EXAMPLE 23

4-(2-Aminoethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene hydrochloride

[1525] 1797

[1526] By the same procedure as described in Example 7 using the compound prepared in Example 20 (31) instead of the compound prepared in Example 6 (8), the compound of the present invention having the following physical data was obtained.

[1527] TLC: Rf 0.21 (ethyl acetate: methanol: triethylamine=8:2:1);

[1528] NMR (DMSO-d6): δ 2.66-2.78 (m, 1H), 3.02-3.12 (m, 1H), 3.83-4.18 (m, 4H), 6.23 (d-like, J=6.6 Hz, 1H), 7.27 (d, J=8.0 Hz, 1H), 7.39 (d, J=7.6 Hz, 1H), 7.58-7.68 (m, 3H), 7.72-7.79 (m, 3H), 8.02 (br, 2H).

EXAMPLES 23 (1)˜23 (7)

[1529] By the same procedure as described in Example 23 using the compounds prepared in Examples 20 (32)˜20 (38) instead of the compound prepared in Example 20 (31), the following compounds of the present invention were obtained.

EXAMPLE 23 (1)

4-(3-Aminopropyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1530] 1798

[1531] TLC: Rf 0.12 (ethyl acetate:methanol: triethylamine=8:4:1);

[1532] NMR (DMSO-d6): δ 1.85-1.93 (m, 2H), 2.93 (q, J=6.4 Hz, 2H), 3.87-4.08 (m, 2H), 3.97 (dd, J=15.0, 8.4 Hz, 1H), 4.11 (dd, J=15.0, 1.4 Hz, 1H), 5.65 (dd, J=8.4, 1.4 Hz, 1H), 7.26 (d, J=7.8 Hz, 1H), 7.33 (d, J=7.8 Hz, 1H), 7.59-7.78 (m, 6H), 8.15 (br, 3H).

EXAMPLE 23 (2)

5-(2-Aminoethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1533] 1799

[1534] TLC: Rf 0.25 (ethyl acetate methanol triethylamine 8:2:1);

[1535] NMR (DMSO-d6): δ 7.81-7.72 (m, 4H), 7.66-7.59 (m, 2H), 7.32-7.27 (m, 2H), 5.77 (dd, J=9, 3.5 Hz, 1H), 4.27 (m, 2H), 3.94 (dd, J=15, 9 Hz, 1H), 3.71 (dd, J=15, 3.5 Hz, 1H), 3.38-3.32 (m, 2H).

EXAMPLE 23 (3)

6-(3-Aminopropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1536] 1800

[1537] TLC: Rf 0.40 (ethyl acetate:methanol:triethylamine=8:2 :1);

[1538] NMR (DMSO-d6): 5 2.05 (quint, J=6.8 Hz, 2H), 2.95 (t, J=6.8 Hz, 2H), 3.76 (dd, J=15.2, 3.0 Hz, 1H), 4.00 (dd, J=15.2, 9.4 Hz, 1H), 4.18 (t, J=6.8 Hz, 2H), 5.70 (dd, J=9.4, 3.0 Hz, 1H), 7.29-7.38 (m, 2H), 7.56-7.67 (m, 3H), 7.76-7.79 (m, 3H), 8.08 (br, 2H).

EXAMPLE 23 (4)

6-(2-Aminoethyl)oxy-3-phenylsulfonyl-1,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1539] 1801

[1540] TLC: Rf 0.16 (ethyl acetate:methanol:triethylamine=9:1:1);

[1541] NMR (DMSO-d6): δ 3.22 (t, J=4.9 Hz, 2H), 3.79 (dd, J=15.1, 3.0 Hz, 1H), 4.01 (dd, J=15.1, 9.4 Hz, 1H), 4.32 (t, J=4.9 Hz, 2H), 5.73 (dd, J=9.4, 3.0 Hz, 1H), 7.35 (d, J=2.4 Hz, 1H), 7.40 (dd, J=8.8, 2.4 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.64-7.66 (m, 2H), 7.76-7.81 (m, 3H), 8.35 (br, 3H).

EXAMPLE 23 (5)

7-(2-Aminoethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[1542] 1802

[1543] TLC: Rf 0.38 (ethyl acetate:acetic acid:water=3:1:1);

[1544] NMR (DMSO-d6): δ 8.18 (3H, brs), 7.83-7.60 (6H, m), 7.40 (1H, d, J=8 Hz), 7.22 (1H, d, J=8 Hz), 5.81 (1 H, dd, J=9.6, 3.2 Hz), 4.44-3.30 (2H, m), 3.96 (1 H, dd, J=15, 9.6 Hz), 3.76 (1H, dd, J=15, 3.2 Hz), 3.18 (2H, t, J=6 Hz).

EXAMPLE 23 (6)

4-(Piperidin-4-yl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene hydrochloride

[1545] 1803

[1546] TLC: Rf 0.47 (ethyl acetate:acetic acid:water=3:1:1);

[1547] NMR (DMSO-d6): δ 8.91 (2H, brs), 7.90-7.52 (6H, m), 7.41 (1H, d, J=8 Hz), 7.33 (1H, d, J=8 Hz), 5.71 (1H, d, J=7 Hz), 4.95-4.70 (1H, m), 4.20-3.80 (2H, m), 3.50-2.95 (4H, m), 2.30-1.60 (4H, m).

EXAMPLE 23 (7)

4,7-Bis[(2-aminoethyl)oxy]-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[1548] 1804

[1549] TLC: Rf 0.22 (ethyl acetate:methanol:triethylamine=4:1:1);

[1550] NMR (DMSO-d6): δ 8.10 (6H, brs), 7.85-7.70 (3H, m), 7.70-7.50 (2H, m), 7.37 (1H, d, J=8.6 Hz), 7.23 (1H, d, J=8.6 Hz), 6.14 (1H, d, J=6.0 Hz), 4.50-4.15 (2H, m), 4.15-3.90 (4H, m), 3.85-3.65 (1H, m), 3.25-3.15 (2H, m), 3.15-2.90 (1H, m).

EXAMPLE 24

4-(2-(N,N-Dimethylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1551] 1805

[1552] By the same procedure as described in Example 8 using the compound prepared in Example 23 instead of the compound prepared in Example 7, the compounds of the present invention having the following physical data were obtained.

[1553] Free Compound:

[1554] TLC: Rf 0.47 (ethyl acetate:methanol:triethylamine=8:2:1);

[1555] NMR (CDCl3): δ 2.33 (s, 6H), 2.52-2.77 (m, 2H), 3.72 (dd, J=15.0, 9.4 Hz, 1H), 3.79-3.89 (m, 1H), 4.00-4.12 (m, 1H), 4.18 (dd, J=15.0, 1.1 Hz, 1H), 5.35 (d-like, J=8.8 Hz, 1H), 6.99 (d, J=8.2 Hz, 1H), 7.28 (d, J=7.2 Hz, 1H), 7.43-7.66 (m, 4H), 7.72-7.77 (m, 2H).

[1556] Hydrochloride:

[1557] TLC: Rf 0.47 (ethyl acetate:methanol:triethylamine=8:2:1);

[1558] NMR (CD3OD): δ 3.05 (s, 6H), 3.52-3.76 (m, 2H), 3.83-3.99 (m, 2H), 4.38-4.63 (m, 2H), 5.89 (t, J=5.4 Hz, 1H), 7.30 (d, J=7.7 Hz, 1H), 7.39 (d, J=7.7 Hz, 1H), 7.51-7.59 (m, 2H), 7.66-7.78 (m, 4H).

EXAMPLES 24 (1)˜24 (5)

[1559] By the same procedure as described in Example 14 using the compounds prepared in Examples 23 (1)˜23 (5) instead of the compound prepared in Example 23, and if necessary, by converting into the corresponding salts by known methods, the following compounds of the present invention were obtained, with the proviso that when compounds of Example 23 (1) and Example 23 (3) were used, compounds of Example 24 (1b) and Example 24 (3b) were also generated respectively.

EXAMPLE 24 (1a)

4-(3-(N,N-Dimethylamino)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1560] 1806

[1561] Free Compound:

[1562] TLC: Rf 0.35 (ethyl acetate:methanol:triethylamine=8:2:1);

[1563] NMR (CDCl3): δ 1.86 (quint, J=7.0 Hz, 2H), 2.26 (s, 6H), 2.47 (t, J=7.0 Hz, 2H), 3.74 (dd, J=5.0, 9.2 Hz, 1H), 3.83-4.03 (m, 2H), 4.21 (dd, J=15.0, 1.2 Hz, 1H), 5.25 (d-like, J=8.8 Hz, 1H), 6.99 (d, J=7.8 Hz, 1H), 7.24 (d, J=7.8 Hz, 1H), 7.48-7.74 (m, 6H).

[1564] Hydrochloride:

[1565] TLC: Rf 0.35 (ethyl acetate:methanol:triethylamine=8:2:1);

[1566] NMR (DMSO-d6): δ 2.15 (m, 2H), 2.80 (s, 6H), 3.31 (t, J=7.5 Hz, 2H), 3.75 (dd, J=15.2, 9.2 Hz, 1H), 4.15 (t, J=6.2 Hz, 2H), 4.31 (dd, J=15.2, 1.1 Hz, 1H), 5.69 (dd, J=9.2, 1.1 Hz, 1H), 7.32-7.39 (m, 2H), 7.55-7.72 (m, 3H), 7.80-7.85 (m, 3H).

EXAMPLE 24 (1b)

4-(3-(N-Cyanomethyl-N-methylamino)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1567] 1807

[1568] TLC: Rf 0.36 (ethyl acetate:triethylamine=9:1);

[1569] NMR (CDCl3): δ 1.88 (quint, J=6.6 Hz, 2H), 2.38 (s, 3H), 2.69 (m, 2H), 3.51 (d, J=17.0 Hz, 1H), 3.61 (d, J=17.0 Hz, 1H), 3.73 (dd, J=15.0, 9.4 Hz, 1H), 3.96 (m, 2H), 4.13 (dd, J=15.0, 1.0 Hz, 1H), 5.28 (d-like, J=8.4 Hz, 1H), 7.00 (d, J=7.8 Hz, 1H), 7.24 (d, J=7.8 Hz, 1H), 7.42-7.74 (m, 6H).

EXAMPLE 24 (2)

5-(2-(N,N-Dimethylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydeo-1,1-dioxidebenzo[b]thiophene

[1570] 1808

[1571] Free Compound:

[1572] TLC: Rf 0.55 (ethyl acetate: methanol: triethylamine 8:2:1);

[1573] NMR (DMSO-d6): δ 2.23 (s, 6H), 2.66 (t, J=6 Hz, 2H), 3.77 (dd, J=15, 3 Hz, 1H), 3.98 (dd, J=15, 10 Hz, 1H), 4.10 (m, 2H), 5.71 (dd, J=10, 3 Hz, 1H), 7.05 (d, J=2 Hz, 1H), 7.25 (dd, J=9, 2 Hz, 1H), 7.58-7.84 (m, 6H).

[1574] Hydrochloride:

[1575] TLC: Rf 0.55 (ethyl acetate:methanol:triethylamine=8:2:1);

[1576] NMR (DMSO-d6): δ 2.84 (s, 6H), 3.56 (m, 2H), 3.75 (dd, J=15, 4 Hz, 1H), 3.97 (dd, J=15, 9 Hz, 1H), 4.45 (m, 2H), 5.76 (dd, J=9, 4 Hz, 1H), 7.22 (d, J=2 Hz, 1H), 7.33 (dd, J=9, 2 Hz, 1H), 7.64 (m, 2H), 7.79 (m, 4H).

EXAMPLE 24 (3a)

6-(3-(N,N-Dimethylamino) propyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1577] 1809

[1578] Free Compound:

[1579] TLC: Rf 0.53 (ethyl acetate:methanol:triethylamine=8:2:1);

[1580] NMR (CDCl3): δ 1.97 (quint, J=6.6 Hz, 2H), 2.25 (s, 6H), 2.44 (t, J=6.6 Hz, 2H), 3.71 (dd, J=14.6, 7.6 Hz; 1H), 3.79 (dd, J=14.6, 5.6 Hz, 1H), 4.07 (t, J=6.6 Hz, 2H), 5.00 (dd, J=7.6, 5.6 Hz, 1H), 7.08 (d, J=2.6 Hz, 1H), 7.23 (dd, J=8.8, 2.6 Hz, 1H), 7.46-7.54 (m, 2H), 7.63-7.72 (m, 3H), 7.85 (d, J=8.8 Hz, 1H).

[1581] Hydrochloride:

[1582] TLC: Rf 0.53 (ethyl acetate:methanol:triethylamine=8:2:1);

[1583] NMR (DMSO-d6): δ 2.17 (m, 2H), 2.78 (s, 6H), 3.20 (t, J=7.9 Hz, 2H), 3.77 (dd, J=15.4, 3.2 Hz, 1H), 4.00 (dd, J=15.4, 9.4 Hz, 1H), 4.18 (t, J=6.0 Hz, 2H), 5.71 (dd, J=9.4, 3.2 Hz, 1H), 7.30-7.38 (m, 2H), 7.58-7.67 (m, 3H), 7.75-7.79 (m, 3H).

EXAMPLE 24 (3b)

6-(3- (N-Cyanomethyl-N-methylamino)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1584] 1810

[1585] TLC: Rf 0.33 (ethyl acetate:hexane:triethylamine=6:3:1);

[1586] NMR (CDCl3): δ 1.97 (quint, J=6.5 Hz, 2H), 2.38 (s, 3H), 2.65 (t, J=6.5 Hz, 2H), 3.54 (s, 2H), 3.71 (dd, J=14.8, 7.8 Hz, 1H), 3.79 (dd, J=14.8, 5.2 Hz, 1H), 4.06 (t, J=6.5 Hz, 2H), 5.00 (dd, J=7.8, 5.2 Hz, 1H), 7.07 (d, J=2.6 Hz, 1H), 7.23 (dd, J=9.0, 2.6 Hz, 1H), 7.47-7.55 (m, 2H), 7.65-7.72 (m, 3H), 7.84 (d, J=9.0 Hz, 1H).

EXAMPLE 24 (4)

6-(2-(N,N-Dimethylamino)ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1587] 1811

[1588] Free Compound:

[1589] TLC: Rf 0.47 (ethyl acetate:methanol:triethylamine 9:1:1);

[1590] NMR (CDCl3): δ 2.34 (s, 6H), 2.75 (t, J=5.4 Hz, 2H), 3.74 (dd, J=14.8, 7.8 Hz, 1H), 3.79 (dd, J=14.8, 5.4Hz, 1H), 4.09 (t, J=5.4 Hz, 2H), 5.00 (dd, J=7.8, 5.4Hz, 1H), 7.06 (d, J=2.4 Hz, 1H), 7.28 (dd, J=8.8, 2.4 Hz, 1H), 7.47-7.52 (m, 2H), 7.62-7.69 (m, 3H), 7.84 (d, J=8.8 Hz, 1H).

[1591] Hydrochloride:

[1592] TLC: Rf 0.47 (ethyl acetate:methanol:triethylamine=9:1:1);

[1593] NMR (DMSO-d6): δ 2.83 (d, J=4.5 Hz, 6H), 3.50-3.54 (m, 2H), 3.78 (dd, J=15.0, 3.0 Hz, 1H), 4.01 (dd, J=15.0, 9.4 Hz, 1H), 4.49 (t, J=5.1 Hz, 2H), 5.73 (dd, J=9.4, 3.0 Hz, 1H), 7.41-7.44 (m, 2H), 7.60-7.67 (m, 3H), 7.77-7.80 (m, 3H), 10.83 (br, 1H).

EXAMPLE 24 (5)

7-(2-(N,N-Dimethylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzp[b]thiophene hydrochloride

[1594] 1812

[1595] TLC: Rf 0.32 (ethyl acetate:methanol:triethylamine=16:3:1);

[1596] NMR (DMSO-d6): δ 7.85-7.60 (6H, m), 7.37 (1H, d, J=8.2 Hz), 7.22 (1H, d, J=8.2 Hz), 5.81 (1 H, dd, J=9.4, 3.2 Hz), 4.65-4.56 (2H, m), 3.97 (1H, dd, J=15, 9.4 Hz), 3.75 (1 H, dd, J=15, 3.2 Hz), 3.56-3. 45 (2H, m), 2.82 (6H, s).

EXAMPLE 25

4-(3-Aminophenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1597] 1813

[1598] By the same procedure as described in Example 11 using the compound prepared in Example 20 (39) instead of the compound prepared in Example 10, the compound of the present invention having the following physical data was obtained.

[1599] TLC: Rf 0.34 (chloroform:tetrahydrofuran:28% ammonia water=100:50:1);

[1600] NMR (DMSO-d6): δ 7.80-7.55 (4H, m), 7.49 (2H, t, J=8 Hz), 7.31 (2H, dd, J=12, 8 Hz), 7.02 (1H, t, J=8 Hz), 6.60-6.45 (2H, m), 5.54 (1H, d, J=9 Hz), 5.10 (2H, bs), 4.91 (1H, d, J=12 Hz), 4.69 (1H, d, J=12 Hz), 4.20 (1H, d, J=15 Hz), 3.98 (1H, dd, J=15, 9 Hz).

EXAMPLE 26

4-(3-(Pyridin-3-ylcarbonylamino)phenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1601] 1814

[1602] To a solution of the compound prepared in Example 25 (143 mg) in pyridine (6 ml) was added nicotinyl chloride-hydrochloride (77 mg). The mixture was stirred at room temperature for 1.5 hours. To the reaction mixture, water was added. The mixture was extracted by ethyl acetate. The extract was washed by water, a saturated aqueous solution of sodium chloride successively, dried over anhydrous sodium sulfate and concentrated. The residue was recrystallized from ethanol to give the compound of the present invention (127 mg) having the following physical data.

[1603] TLC: Rf 0.34 (ethyl acetate:methanol:28% ammonia water=100:10:1);

[1604] NMR (DMSO-d6): δ 9.12 (1H, d, J=2 Hz), 8.77 (1H, dd, J=5,2 Hz), 8.31 (1H, d, J=8 Hz), 7.82 (1H, s), 7.78-7.52 (7H, m), 7.52-7.25 (5H, m), 7.19 (1H, d, J=7 Hz), 5.59 (1H, d, J=8.5 Hz), 5.11 (1H, d, J=12 Hz), 4.86 (1H, d, J=12 Hz), 4.20 (1H, d, J=15 Hz), 4.01 (1H, dd, J=15, 8.5 Hz).

EXAMPLE 26 (1)

4-(2-(Pyridin-3-ylcarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1605] 1815

[1606] By the same procedure as described in Example 26 using the compound prepared in Example 23 instead of the compound prepared in Example 25, and if necessary, by converting into the corresponding salt by known methods, the compounds of the present invention having the following physical data were obtained.

[1607] Free Compound:

[1608] TLC: Rf 0.43 (ethyl acetate:methanol:triethylamine=8:1:1);

[1609] NMR (DMSO-d6): δ 3.36-3.55 (m, 2H), 3.81-3.88 (m, 1H), 4.02 (dd, J=15.0, 8.7 Hz, 1H), 4.04-4.10 (m, 1H), 4.13 (dd, J=15.0, 1.3 Hz, 1H), 5.61 (d-like, J=7.5 Hz, 1H), 7.31 (d, J=8.1 Hz, 1H), 7.35 (d, J=7.2 Hz, 1H), 7.48 (dd, J=8.1, 4.8 Hz, 1H), 7.56-7.68 (m, 3H), 7.71-7.77 (m, 3H), 8.15 (dt, J=8.1, 1.8 Hz, 1H), 8.65-8.68 (m, 1H), 8.68 (dd, J=4.8, 1.8 Hz, 1H), 8.98 (d, J=1.8 Hz, 1H).

[1610] Hydrochloride:

[1611] TLC: Rf 0.43 (ethyl acetate:methanol:triethylamine=8:1:1);

[1612] NMR (DMSO-d6): δ 3.41-3.56 (m, 2H), 3.83-3.89 (m, 1H), 4.01 (dd, J=15.0, 8.7 Hz, 1H), 4.07-4.12 (m, 1H), 4.12 (dd, J=15.0, 1.2 Hz, 1H), 5.67 (d-like, J=7.5 Hz, 1H), 7.31 (d, J=8.0 Hz, 1H), 7.34 (d, J=8.0 Hz, 1H), 7.56-7.61 (m, 2H), 7.65 (t, J=8.0 Hz, 1H), 7.71-7.76 (m, 3H), 7.83 (dd, J=8.1, 5.4 Hz, 1H), 8.59 (dt, J=8.1, 1.6 Hz, 1H), 8.87 (dd, J=5.4, 1.6 Hz, 1H), 9.10 (t, J=5.4 Hz, 1H), 9.19 (d, J=1.6 Hz, 1H).

EXAMPLE 27

5-Methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1613] 1816

[1614] To a solution of 5-methyl-1,1-dioxidebenzo[b]thiophene (353 mg) in ethanol (19.5 ml), were added water (0.5 ml), acetic acid (0.4 ml) and benzenesulfonic acid sodium salt (940 mg) successively. The reaction mixture was refluxed for 7 hours. The reaction mixture was cooled to room temperature. The crystals that appeared were separated by filtration. The crystals were washed by water, ethanol and hexane, sucessively, to give the compound of the present invention (381 mg) having the following physical data.

[1615] TLC: Rf 0.32 (hexane:ethyl acetate=1:1);

[1616] NMR (CDCl3): δ 2.52 (s, 3H), 3.66 (dd, J=14.6, 8.7 Hz, 1H), 3.77 (dd, J=14.6, 4.9 Hz, 1H), 5.02 (dd, J=8.7, 4.9 Hz, 1H), 7.41-7.57 (m, 4H), 7.64-7.69 (m, 3H), 7.80 (s-like, 1H).

EXAMPLES 27 (1)˜27 (5)

[1617] By the same procedure as described in Example 27 using corresponding benzo[b]thiophene compounds instead of 5-methyl-1,1-dioxidebenzo[b]thiophene, the following compounds of the present invention were obtained.

EXAMPLE 27 (1)

5-(4-Chlorophenylcarbonyl)amino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1618] 1817

[1619] TLC: Rf 0.27 (methylene chloride ethyl acetate 8:1);

[1620] NMR (DMSO-d6): δ 3.74 (dd, J=15.1, 3.7 Hz, 1H), 3.95 (dd, J=15.1, 9.3 Hz, 1H), 5.83 (dd, J=9.3, 3.7 Hz, 1H), 7.58-7.65 (m, 2H), 7.66 (d, J=8.7 Hz, 2H), 7.73-7.83 (m, 4H), 8.04 (d, J=8.7 Hz, 2H), 8.10 (dd, J=8.8, 2.0 Hz, 1H), 8.40 (d, J=2.0 Hz, 1H), 10.86 (s, 1H).

EXAMPLE 27 (2)

4-Cyano-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b][thiophene

[1621] 1818

[1622] TLC: Rf 0.60 (methylene chloride:ethyl acetate=8:1);

[1623] NMR (DMSO-d6): δ 3.95 (dd, J=15, 10 Hz, 1H), 4.15 (d, J=15 Hz, 1H), 5.80 (d, J=10 Hz, 1H), 7.60-7.80 (m, 2H), 7.80-7.90 (m, 3H), 7.95 (t, J=7.5 Hz, 1H), 8.20 (d, J=7.5 Hz, 1H), 8.35 (d, J=7.5 Hz, 1H).

EXAMPLE 27 (3)

6-Nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1624] 1819

[1625] TLC: Rf 0.44 (hexane ethyl acetate=1:1);

[1626] NMR (DMSO-d6): δ 3.97 (dd, J=15.3, 3.0 Hz, 1H), 4.16 (dd, J=15.3, 9.3 Hz, 1H), 6.00 (dd, J=9.3, 3.0 Hz, 1H), 7.62-7.67 (m, 2H), 7.79-7.83 (m, 3H), 8.02 (d, J=8.4 Hz, 1H), 8.61 (s-like, 1H), 8.62 (dd, J=8.4, 2.1 Hz, 1H).

EXAMPLE 27 (4)

4,7-Dimethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1627] 1820

[1628] TLC: Rf 0.48 (ethyl acetate );

[1629] NMR (DMSO-d6): δ 3.27 (s, 3H), 3.85 (s, 3H), 3.96 (dd, J=15.2, 8.8 Hz, 1H), 4.12 (dd, J=15.2, 1.5 Hz, 1H), 5.49 (dd, J=8.8, 1.5 Hz, 1H), 7.12 (d, J=9.0 Hz, 1H), 7.21 (d, J=9.0 Hz, 1H), 7.60-7.78 (m, 5H).

EXAMPLE 27 (5)

4,7-Bis(3-hydroxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1630] 1821

[1631] TLC: Rf 0.34 (ethyl acetate:methanol=9:19;

[1632] NMR (DMSO-d6): 5 1.52-1.57 (m, 2H), 1.83 (quint, J_6.3 Hz, 2H), 3.43 (q, J=6.3 Hz, 2H), 3.55 (q, J=5.8 Hz, 2H), 3.60-3.67 (m, 1H), 3.80-3.87 (m, 1H), 3.96 (dd, J=14.8, 9.0 Hz, 1H), 4.09 (d-like, J=14.8 Hz, 1H), 4.08-4.21 (m, 2H), 4.46 (t, J=5.1 Hz, 1H), 4.52 (t, J=5.1 Hz, 1H), 5.45 (d-like, J=7.8 Hz, 1H), 7.14 (d, J=9.0 Hz, 1H), 7.20 (d, J=9.0 Hz, 1H), 7.58-7.63 (m, 2H), 7.72-7.77 (m, 3H).

EXAMPLE 28

4-(Pyridin-3-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1633] 1822

[1634] To 4-carboxy-1,1-dioxidebenzo[b]thiophene (prepared by the method described in Example 107 hereafter) (270 mg), was added thionyl chloride (2.0 ml). The mixture was refluxed for 2 hours, and concentrated. To a solution of (pyridin-3-ylmethyl)amine (154 mg) dissolved in methylene chloride (6.0 ml) and triethylamine (260 mg), a solution of the said chloride in methylene chloride (4.0 ml) were added dropwise. The mixture was stirred for 2 hours at room temperature. To the reaction mixture, ice-water and a 1N aqueous solution of sodium hydroxide (1.5 ml) were added dropwise. The mixture was extracted by ethyl acetate (40 ml). The extract was washed by a saturated sodium chloride, dried over anhydrous magnesium sulfate, and concentrated. The residue was recrystallized from a mixed solvent of ethyl acetate and hexane to give the compound of the present invention (330 mg) having the following physical data.

[1635] TLC: Rf 0.48 (methylene chloride: methanol=10:1);

[1636] NMR (CDCl3): δ 8.56 (d, J=2.1 Hz, 1H), 8.53 (dd, J=4.5, 2.1 Hz, 1H), 7.93 (dd, J=7.2, 0.6 Hz, 1H), 7.79-7.72 (m, 2H), 7.70 (dd, J=7.5, 0.6 Hz, 1H), 7.55 (t, J=7.8 Hz, 1H), 7.31 (dd, J=7.8, 4.5 Hz, 1H), 6.86 (t, J=6.3 Hz, 1H), 6.77 (d, J=7.2 Hz, 1H), 4.65 (d, J=6.3 Hz, 2Hz.

EXAMPLES 28 (1)˜28 (33)

[1637] By the same procedure as described in Example 28 using carboxylic acid corresponding to 4-carboxy-1,1-dioxidebenzo[b]thiophene and amine derivative corresponding to (pyridin-3-ylmethyl)amine, and if necessary, by converting into the corresponding salt by a known method, the compounds of the present invention were obtained.

[1638] In the preparation of a compound of Example 28 (33), 4-aminomethyl-1,1-dioxidebenzo[b]thiophene and pyridin-3-ylcarboxylic acid were subjected to reaction.

EXAMPLE 28 (1)

4-(4-Benzylpiperazin-1-yl) carbonyl-1,1-dioxidebenzo[b]thiophene

[1639] 1823

[1640] TLC: Rf 0.30 (ethyl acetate:methanol=50:1);

[1641] NMR (CDCl3): δ 7.75 (d, J=7.4 Hz, 1H), 7.56 (t, J=7.4 Hz, 1H), 7.47 (d, J=7.4 Hz, 1H), 7.40-7.20 (m, 6H), 6.78 (d, J=7.0 Hz, 1H), 3.83 (m, 2H), 3.55 (s, 2H), 3.34 (m, 2H), 2.55 (m, 2H), 2.37 (m, 2H).

EXAMPLE 28 (2)

4-(N-(2-(Pyridin-3-yl)ethyl)-N-methylcarbamoyl)-1,1-dioxidebenzo[b]thiophene

[1642] 1824

[1643] MS (APCI, Pos.): m/z 361 (M+MeOH+H)+, 329 (M+H)+.

EXAMPLE 28 (3)

4-(2-(2-Hydroxyethoxy)ethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1644] 1825

[1645] MS (APCI, Pos.): m/z 330 (M+MeOH+H)+, 298 (M+H)+.

EXAMPLE 28 (4)

4-(2,4-Dimethoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1646] 1826

[1647] TLC: Rf 0.68 (ethyl acetate);

[1648] NMR (CDCl3): δ 7.90 (d, J=7.5 Hz, 1H), 7.75 (d, J=7.5 Hz, 1H), 7.60 (d, J=7.5 Hz, 1H), 7.55 (t, J=7.5 Hz, 1H), 7.25 (d, J=10 Hz, 1H), 6.75 (d, J=7.5 Hz, 1H), 6.60-6.40 (m, 3H), 4.55 (d, J=7.5 Hz, 2H), 3.85 (s, 3H), 3.80 (s, 3H).

EXAMPLE 28 (5)

4-(1-Benzylpiperidin-4-yl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1649] 1827

[1650] Free Aicd:

[1651] TLC: Rf 0.50 (ethyl acetate:methanol=8:1.5);

[1652] NMR (CDCl3): δ 7.90 (d, J=7.5 Hz, 1H), 7.80 (d, J=7.5 Hz, 1H), 7.60 (d, J=7.5 Hz, 1H), 7.55 (t, J=7.5 Hz, 1H), 7.50-7.20 (m, 5H), 6.75 (d, J=7.5 Hz, 1H), 6.05-5.95 (m, 1H), 4.10-3.90 (m, 1H), 3.55 (s, 2H), 3.00-2.90 (m, 2H), 2.30-2.10 (m, 2H), 2.10-1.90 (m, 2H), 1.70-1.50 (m, 2H).

[1653] Hydrochloride:

[1654] TLC: Rf 0.44 (methanol:ethyl acetate=1:10);

[1655] NMR (CD3OD): δ 7.90-7.75 (m, 3H), 7.75-7.45 (m, 6H), 7.08 (d, J=7.0 Hz, 1H), 4.34 (s, 2H), 4.27-4.05 (m, 1H), 3.61-3.42 (m, 2H), 3.33-3.10 (m, 2H), 2.34-2.15 (m, 2H), 2.12-1.81 (m, 2H).

[1656] Methanesulfonic Acid Salt:

[1657] TLC: Rf 0.44 (methanol:ethyl acetate=1:10);

[1658] NMR (CD3OD): δ 7.89-7.74 (m, 3H), 7.73-7.60 (m, 1H), 7.60-7.45 (m, 5H), 7.08 (d, J=7.0 Hz, 1H), 4.34 (s, 2H), 4.27-4.03 (m, 1H), 3.68-3.38 (m, 2H), 3.38-3.06 (m, 2H), 2.67 (s, 3H), 2.38-1.72 (m, 4H).

EXAMPLE 28 (6)

4-(Pyridin-4-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1659] 1828

[1660] TLC: Rf 0.29 (ethyl acetate:methanol=19:1);

[1661] NMR (CDCl3+CD3OD): δ 8.50 (d, J=7 Hz, 2H), 8.25 (broad-t, J=7 Hz, 1H), 7.95 (d, J=7 Hz, 1H), 7.80 (d, J=8 Hz, 2H), 7.60 (t, J=8 Hz, 1H), 7.30 (d, J=7Hz, 2H), 6.80 (d, J=7 Hz, 1H), 4.60 (d, J=7 Hz, 2H).

EXAMPLE 28 (7)

4-(2-t-Butoxycarbonylethyl) carbamoyl-1,1-dioxidebenzo[b]thiophene

[1662] 1829

[1663] TLC: Rf 0.40 (ethyl acetate:hexane=3:2);

[1664] NMR (CDCl3): δ 8.00 (d, J=7 Hz, 1H), 7.80 (d, J=8 Hz, 1H), 7.70 (d, J=8 Hz, 1H), 7.60 (t, J=8 Hz, 1H), 6.95 (broad-s, 1H), 6.80 (d, J=7 Hz, 1H), 3 70 (q, J=7 Hz, 7H), 2.60 (t, J=7 Hz, 2H), 1.45 (s, 9H).

EXAMPLE 28 (8)

4-(Thiophen-2-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1665] 1830

[1666] TLC: Rf 0.48 (chloroform:methanol=9:1);

[1667] NMR (CDCl3+DMSO-d6): δ 8.50 (t, J=7 Hz, 1H), 7.95 (d, J=6 Hz, 1H), 7.85 (d, J=8 Hz, 1H), 7.75 (d, J=8 Hz, 1H), 7.55 (t, J=8 Hz, 1H), 7.25 (d, J=6 Hz, 1H), 7.05 (d, J=3 Hz, 1H), 6.95 (dd, J=3 Hz and 6 Hz, 1H), 6.80 (d, J=6 Hz, 1H), 4.75 (d, J=7 Hz, 2H).

EXAMPLE 28 (9)

4-Benzylcarbamoyl-1,1-dioxidebenzo[b]thiophene

[1668] 1831

[1669] TLC: Rf 040 (ethyl acetate hexane=1:1);

[1670] NMR (CDCl3+DMSO-d6): δ 7.99 (d, J=7.2 Hz, 1H), 7.81-7.75 (m, 2H), 7.56 (t, J=7.5 Hz, 1H), 7.43 (t, J=5.7 Hz, 1H), 7.40-7.27 (m, 5H), 6.78 (d, J=7.2 Hz, 1H), 4.63 (d, J=5.7 Hz, 2H).

EXAMPLE 28 (10)

4-(Pyridin-2-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1671] 1832

[1672] TLC: Rf 0.30 (ethyl acetate:hexane=1:1);

[1673] NMR (CDCl3): δ 8.56 (d, J=5.1 Hz, 1H), 8.05 (dd, J=7.2, 0.9 Hz, 1H), 7.84 (t, J=7.2 Hz, 1H), 7.73 (dt, J=0.9, 7.8 Hz, 1H), 7.68 (t, J=5.1 Hz, 1H), 7.61 (t, J=7.8 Hz, 1H), 7.33 (d, J=7.8 Hz, 1H), 7.59-7.23 (m, 2H), 6.78 (d, J=6.9 Hz, 1H), 4.76 (d, J=5.1 Hz, 2H).

EXAMPLE 28 (11)

4-(2-(Piperidin-1-yl)ethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1674] 1833

[1675] Free Aicd:

[1676] TLC: Rf 0.35 (methylene chloride:methanol=10:1);

[1677] NMR (CDCl3): δ 8.04 (dd, J=7.2, 0.9 Hz, 1H), 7.80 (dt, J=7.8. 0.9 Hz, 1H), 7.72 (dd. J=7.8, 0.9 Hz, 1H), 7.59 (t, J=7.8 Hz, 1H), 7.02 (bs, 1H), 6.77 (d, J=7.2 Hz, 1H), 3.54 (q, J=5.7 Hz, 2H), 2.58 (t, J=5.7 Hz, 2H), 2.50-2.40 (m, 4H), 1.76-1.43 (m, 6H).

[1678] Hydrochloride:

[1679] TLC: Rf 0.60 (methylene chloride:methanol:triethylamine=8:1.5:0.5);

[1680] NMR (DMSO-d6): δ 10.20 (br. s, 1H), 9.25-9.10 (m, 1H), 8.01 (d, J=7.0 Hz, 1H), 7.99 (d, J=7.0 Hz, 1H), 7.93 (d, J=6.9 Hz, 1H), 7.73 (t, J=7.0 Hz, 1H), 7.47 (d, J=6.9 Hz, 1H), 3.80-3.60 (m, 2H), 3.60-3.50 (m, 2H), 3.45-3.15 (m, 2H), 3.10-2.80 (m, 2H), 2.00-1.70 (m, 5H), 1.55-1.30 (m, 1H).

EXAMPLE 28 (12)

4-((1S)-1-t-Butoxycarbonyl-2-methylpropyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1681] 1834

[1682] TLC: Rf 0.48 (hexane:ethyl acetate=1:1);

[1683] NMR (CDCl3): δ 7.95 (d, J=7.2 Hz, 1H), 7.81 (d, J=7.8 Hz, 1H), 7.77 (d, J=7.8 Hz, 1H), 7.59 (t, J=7.8 Hz, 1H), 6.78 (d, J=7.2 Hz, 1H), 6.56 (d, J=8.4 Hz, 1H), 4.64 (dd, J=8.4, 4.2 Hz, 1H), 2.36-2.27 (m, 1H), 1.51 (s, 9H), 1.02 (d, J=6.9 Hz, 3H), 0.98 (d, J=6.9 Hz, 3H).

EXAMPLE 28 (13)

4-(2-Fluorophenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1684] 1835

[1685] TLC: Rf 0.60 (chloroform:methanol=9:1);

[1686] NMR (CDCl3+DMSO-d6): δ 7.95 (broad peak, 1H), 7.95 (d, J=7 Hz, 1H), 7.80 (d, J=8 Hz, 1H), 7.78 (d, J=8 Hz, 1H), 7.55 (t, J=8 Hz, 1H), 7.50-7.20 (m, 2H), 7.20-7.00 (m, 2H), 6.77 (d, J=7 Hz, 1H), 4.62 (d, J=7 Hz, 2H).

EXAMPLE 28 (14)

4-(3-Fluorophenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1687] 1836

[1688] TLC: Rf 0.50 (chloroform:methanol=9:1);

[1689] NMR (CDCl3+DMSO-d6): δ 8.40 (broad peak, 1H), 7.98 (d, J=7 Hz, 1H), 7.85 (d, J=8 Hz, 1H), 7.80 (d, J=8 Hz, 1H), 7.55 (t, J=8 Hz, 1H), 7.40-7.25 (m, 1H), 7.20-6.90 (m, 3H), 6.80 (d, J=7 Hz, 1H), 4.60 (d, J=7 Hz, 2H).

EXAMPLE 28 (15)

4-(3-Methylphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1690] 1837

[1691] TLC: Rf 0.60 (chloroform: methanol=9:1); NMR (CDCl3): δ 7.95 (d, J=7 Hz, 1H), 7.75 (d, J=8 Hz, 1H), 7.65 (d, J=8 Hz, 1H), 7.52 (t, J=8 Hz, 1H), 7.30-7.20 (m, 1H), 7.20-7.10 (m, 3H), 6.75 (d, J=7 Hz, 1H), 6.40 (broad peak, 1H), 4.60 (d, J=7 Hz, 2H), 2.40 (s, 3H).

EXAMPLE 28 (16)

4-(2-Methoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1692] 1838

[1693] TLC: Rf 0.64 (chloroform:methanol=9:1);

[1694] NMR (CDCl3+DMSO-d6): δ 7.93 (d, J=7 Hz, 1H), 7.85-7.70 (m, 3H), 7.55 (t, J=8 Hz, 1H), 7.30 (m, 2H), 6.92 (m, 2H), 6.78 (d, J=7 Hz, 1H), 4.60 (d, J=7 Hz, 2H), 3.90 (s, 3H).

EXAMPLE 28 (17)

4-(2,3-dimethoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1695] 1839

[1696] TLC: Rf 0.63 (chloroform:methanol=9:1);

[1697] NMR (CDCl3+DMSO-d6): δ 7.97 (d, J=7.2 Hz, 1H), 7.77 (d, J=7.6 Hz, 1H), 7.76 (d, J=7.6 Hz, 1H), 7.73 (broad peak, 1H), 7.54 (t, J=7.6 Hz, 1H), 7.06 (t, J=7.8 Hz, 1H), 7.00-6.85 (m, 2H), 6.77 (d, J=7.2 Hz, 1H), 4.63 (d, J=5.6 Hz, 2H), 3.90 (s, 3H), 3.88 (s, 3H).

EXAMPLE 28 (18)

4-(3,4-Dimethoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1698] 1840

[1699] TLC: Rf 0.53 (chloroform:methanol=9:1);

[1700] NMR (CDCl3+DMSO-d6): δ 8.57 (t-like, J=5.8 Hz, 1H), 7.97 (d, J=7.2 Hz, 1H), 7.86 (d, J=7.8 Hz, 1H), 7.77 (d, J=7.8 Hz,1H), 7.57 (t, J=7.8 Hz,1H), 7.00-6.80 (m, 4H), 4.53 (d, J=5.8 Hz, 2H), 3.88 (s, 3H), 3.87 (s, 3H).

EXAMPLE 28 (19)

4-(2,5-Difluorophenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1701] 1841

[1702] TLC: Rf 0.45 (chloroform:methanol 9:1);

[1703] NMR (CDCl3+DMSO-d6): δ 8.78 (t, J=6.0 Hz, 1H), 7.97 (dd, J=7.0 Hz and 1.0 Hz, 1H), 7.89 (dd, J=7.6 Hz and 1.0 Hz, 1H), 7.79 (d, J=7.6 Hz, 1H), 7.59 (t, J=7.6 Hz, 1H), 7.20-6.90 (m, 3H), 6.82 (d, J=7.0 Hz, 1H), 4.60 (d, J=6.0 Hz, 1H).

EXAMPLE 28 (20)

4-(3,4,5-Trimethoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1704] 1842

[1705] TLC: Rf 0.33 (chloroform:methanol=9:1);

[1706] NMR (CDCl3, DMSO-d6): δ 8.00 (broad peak, 1H), 7.98 (dd, J=7.2 Hz and 1.0 Hz, 1H), 7.82 (dd, J=7.6 Hz and 1.0 Hz, 1H), 7.78 (d, J=7.6 Hz, 1H), 7.56 (t, J=7.6 Hz, 1H), 6.79 (d, J=7.2 Hz, 1H), 6.61 (s, 2H), 4.54 (d, J=5.8 Hz, 2H), 3.86 (s, 6H), 3.83 (s, 3H).

EXAMPLE 28 (21)

4-(Benzimidazol-2-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1707] 1843

[1708] TLC: Rf 0.28 (chloroform:methanol=9:1);

[1709] NMR (CDCl3+DMSO-d6): δ 8.97 (t, J=5.6 Hz, 1H), 8.08 (d, J=7.2 Hz, 1H), 7.94 (dd, J=7.8 Hz and 1.0 Hz, 1H), 7.79 (dd, J=7.8 Hz and 1.0 Hz, 1H), 7.62-7.50 (m, 3H), 7.30-7.15 (m, 2H), 6.81 (d, J=7.2 Hz, 1H), 4.85 (d, J=5.6 Hz, 2H).

EXAMPLE 28 (22)

4-(3,5-Difluorophenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1710] 1844

[1711] TLC: Rf 0.57 (chloroform:methanol=9:1);

[1712] NMR (CDCl3+DMSO-d6): δ 9.11 (t, J=5.8 Hz, 1H), 7.98 (dd, J=7.2 Hz and 1.0 Hz, 1H), 7.93 (dd, J=7.6 Hz and 1.0 Hz, 1H), 7.81 (d, J=7.6 Hz, 1H), 7.62 (t, J=7.6 Hz, 1H), 7.00-6.90 (m, 2H), 6.90 (d, J=7.2 Hz, 1H), 6.80-6.68 (m, 1H), 4.55 (d, J=5.8 Hz, 2H).

EXAMPLE 28 (23)

4-(N-Benzyl-N-methylcarbamoyl)-1,1-dioxidebenzo[b]thiophene

[1713] 1845

[1714] TLC: Rf 0.69 (chloroform:methanol=9:1);

[1715] NMR (CDCl3): δ 7.80-7.70 (m, 1H), 7.65-7.47 (m, 2H), 7.47-7.25 (m, 5H), 7.15-7.00 (m, 1H), 6.80-6.72 (m, 1H), 4.78 and 4.44 (each s, total 2H), 3.12 and 2.84 (each s, total 3H).

EXAMPLE 28 (24)

4-(4-Nitrophenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1716] 1846

[1717] TLC: Rf 0.44 (chloroform:methanol 9:1);

[1718] NMR (CDCl3+DMSO-d6): δ 9.20 (t, J=5.8 Hz, 1H), 8.20 (d, J=8 Hz, 2H), 7.98 (d, J=7 Hz, 1H), 7.93 (d, J=7.5 Hz, 1H), 7.81 (d, J=7.5 Hz, 1H), 7.62 (t, J=7.5 Hz, 1H), 7.57 (d, J=8 Hz, 2H), 6.89 (d, J=7 Hz, 1H), 4.67 (d, J=5.8 Hz, 2H).

EXAMPLE 28 (25)

5-(2-Hydroxyethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[1719] 1847

[1720] TLC: Rf 0.38 (ethyl acetate);

[1721] NMR (CDCl3+CD3OD): δ 7.98 (dd, J=8.0 Hz, 1.2 Hz, 1H), 7.88 (d, J=1.2 Hz, 1H), 7.77 (d, J=8.0 Hz, 1H), 7.31 (d, J=6.8 Hz, 1H), 6.81 (d, J=6.8 Hz, 1H), 3.78 (t, J=4.8 Hz, 2H), 3.57 (t, J=4.8 Hz, 2H).

EXAMPLE 28 (26)

5-(Pyridin-3-ylmethyl)carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[1722] 1848

[1723] MS (APCI, Pos.): m/z 363 (M+MeOH+H)+, 331 (M+H)+.

EXAMPLE 28 (27)

5-(2-Dimethylaminoethyl)carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[1724] 1849

[1725] TLC: Rf 0.27 (methylene chloride:methanol=10:1);

[1726] NMR (CDCl3): δ 8.23 (d, J=8.1 Hz,1H), 8.03 (t, J=5.7 Hz, 1H), 7.55 (d, J=8.1 Hz, 1H), 7.41 (d, J=6.9 Hz, 1H), 6.76 (d, J=6.9 Hz, 1H), 3.94 (s, 3H), 3.57 (q, J=5.7 Hz, 2H), 2.53 (t, J=5.7 Hz, 2H), 2.30 (s, 6H).

EXAMPLE 28 (28)

5-Dimethylcarbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[1727] 1850

[1728] TLC: Rf 0.35 (methanol:ethyl acetate=5:95);

[1729] NMR (CDCl3): δ 7.52-7.38 (m, 3H), 6.75 (d, J=7.4 Hz, 1H), 3.93 (s, 3H), 3.15 (s, 3H), 2.88 (s, 3H).

EXAMPLE 28 (29)

5-(2,3,4,5,6,7-Hexahydro-1H-azepin-1-yl)carbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[1730] 1851

[1731] TLC: Rf 0.60 (methylene chloride:methanol=10:1);

[1732] NMR (CDCl3): δ 7.48 (dd, J=7.5,0.9Hz, 1H), 7.42 (dd, J=6.9, 0.9 Hz, 1H), 7.38 (d, J=7.5 Hz, 1H), 6.74 (d, J=6.9 Hz, 1H), 3.95 (s, 3H), 3.80-3.56 (m, 2H), 3.30-3.20 (m, 2H), 1.90-1.75 (m, 2H), 1.75-1.40 (m, 6H).

EXAMPLE 28 (30)

5-(2,3-Dihydroindol-1-yl)carbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[1733] 1852

[1734] TLC: Rf 0.82 (methylene chloride:methanol=10:1);

[1735] NMR (CDCl3): δ 8.31 (d, J=7.8 Hz, 1H), 7.54 (s, 2H), 7.45 (d, J=6.9 Hz, 1H), 7.33-7.20 (m, 2H), 7.20-7.07 (m, 1H), 6.77 (d, J=6.9 Hz, 1H), 3.97 (s, 3H), 3.90-3.66 (m, 2H), 3.25-3.10 (m, 2H).

EXAMPLE 28 (31)

5-(4-(2-Chlorophenyl)piperazin-1-yl)carbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[1736] 1853

[1737] TLC: Rf 0.30 (ethyl acetate:hexane=1:1);

[1738] NMR (CDCl3): δ 7.51 (d, J=7.8 Hz, 1H), 7.46 (d, J=7.8 Hz, 1H), 7.43-7.35 (m, 2H), 7.30-7.20 (m, 1H), 7.06-6.99 (m, 2H), 6.76 (d, J=6.9 Hz, 1H), 4.10-3.90 (m, 2H), 3.98 (s, 3H), 3.54-3.37 (m, 2H),3.20-2.90 (m, 4H).

EXAMPLE 28 (32)

5-(4-(2-(2-Trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[1739] 1854

[1740] TLC: Rf 0.33 (ethyl acetate);

[1741] NMR (CDCl3): δ 7.63 (d, J=7.8 Hz, 1H), 7.49 (d, J=7.5 Hz, 2H), 7.46-7.40 (m, 2H), 7.40-7.27 (m, 2H), 6.75 (d, J=7.5 Hz, 1H), 3.94 (s, 3H), 3.90-3.80 (m, 2H), 3.35-3.20 (m, 2H), 3.04-2.94 (m, 2H), 2.68-2.60 (m, 4H), 2.58-2.40 (m, 2H).

EXAMPLE 28 (33)

4-(Pyridin-3-ylcarbonyl)aminomethyl-1,1-dioxidebenzo[b]thiophene

[1742] 1855

[1743] MS (APCI, Pos.): m/z 333 (M+MeOH+H)+, 301 (M+H)+.

EXAMPLE 29

4-(3-(Pyrrol-1-yl)-propyl) oxy-1,1-dioxidebenzo[b]thiophene

[1744] 1856

[1745] 4-Hydroxy-1,1-dioxidebenzo[b]thiophene (370 mg), triphenylphosphine (630 mg) and 1-(3-hydroxypropyl)pyrrole (300 mg) were dissolved in anhydrous tetrahydrofuran (15 ml). Under an atmosphere of argon to the mixture, was added a solution of diethylazodicarboxylate (323 mg) in anhydrous tetrahydrofuran (4 ml) dropwise. The mixture was stirred at room temperature for 2 hours. To the reaction mixture methanol was added. The mixture was stirred for 10 minutes. The reaction mixture was concentrated. The residue was purified with column chromatography on silica gel (hexane:ethyl acetate=2:1) to give the compound of the present invention (473 mg) having the following physical data.

[1746] TLC: Rf 0.47 (hexane:ethyl acetate=1:1);

[1747] NMR (CDCl3): δ 7.55-7.35 (m, 2H), 7.30 (d, J=8 Hz, 1H), 6.97 (d, J=8 Hz, 1H), 6.75-6.54 (m, 3H), 6.16 (t, J=2 Hz, 2H), 4.12 (t, J=6 Hz, 2H), 4.00 (t, J=6 Hz, 2H), 2.27 (q, J=6 Hz, 2H).

EXAMPLES 30˜30 (13)

[1748] By the same procedure as described in Example 18 using alcohol derivative corresponding to the compound prepared in Example 9 (12) and halogenated compound corresponding to 4-nitrobenzylbromide, or by the same procedure as described in Example 29 using alcohol derivative corresponding to 4-hydroxy-1,1-dioxidebenzo[b]thiophene and alcohol derivative corresponding to 1-(3-hydroxypropyl)pyrrole, the following compounds of the present invention were obtained.

EXAMPLE 30

4-(Quinolin-2-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[1749] 1857

[1750] TLC: Rf 0.27 (hexane:ethyl acetate=1:1);

[1751] NMR (CDCl3): δ 8.23 (d, J=8 Hz, 1H), 8.09 (d, J=8Hz, 1H), 7.95-7.68 (m, 2H), 7.68-7.50 (m, 3H), 7.50-7.22 (m, 2H), 7.14 (d, J=8 Hz, 1H), 6.66 (d, J=7 Hz, 1H), 5.49 (s, 2H).

EXAMPLE 30 (1)

4-(2-(Pyrrol-1-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene

[1752] 1858

[1753] TLC: Rf 0.50 (ethyl acetate:hexane=2:1);

[1754] NMR (CDCl3): δ 7.55-7.22 (m, 3H), 6.94 (d, J=8 Hz, 1H), 6.73 (t, J=2 Hz, 2H), 6.62 (d, J=7 Hz, 1H), 6.19 (t, J=2 Hz, 2H), 4.32 (s, 4H).

EXAMPLE 30 (2)

4-(2-(4-Methylazol-5-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene

[1755] 1859

[1756] TLC: Rf 0.15 (ethyl acetate:hexane=2:1);

[1757] NMR (CDCl3): δ 8.63 (s, 1H), 7.58-7.37 (m, 2H), 7.31 (d, J=8 Hz, 1H), 7.03 (d, J=8 Hz,1H), 6.64 (d, J=8 Hz, 1H), 4.26 (t, J=6 Hz, 2H), 3.31 (t, J=6 Hz, 2H), 2.46 (s, 3H).

EXAMPLE 30 (3)

4-(3-(Pyridin-4-yl)propyl)oxy-1,1-dioxidebenzo[b]thiophene

[1758] 1860

[1759] TLC: Rf 0.36 (ethyl acetate:methanol=10:1);

[1760] NMR (CDCl3): δ 8.53 (dd, J=1.6, 4.5 Hz, 2H), 7.60-7.22 (m, 3H), 7.14 (d, J=5.8 Hz, 2H), 7.00 (d, J=8.0 Hz, 1H), 6.62 (d, J=7.4 Hz, 1H), 4.09 (t, J=6.2 Hz, 2H), 2.84 (t, J=7.4 Hz, 2H), 2.19 (quint, J=6.2 Hz, 2H).

EXAMPLE 30 (4)

4-(1-t-Butoxycarbonylpiperidin-3-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[1761] 1861

[1762] TLC: Rf 0.46 (hexane:ethyl acetate=1:1);

[1763] NMR (CDCl3): δ 7.58-7.38 (m, 2H), 7.30 (d, J=7.6 Hz, 1H), 7.04 (d, J=8.2 Hz, 1H), 6.61 (d, J=7.0 Hz, 3.15-2.50 (m, 4H), 1.45 (s, 9H).

EXAMPLE 30 (5)

4-(2-(Pyrrolidin-1-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene

[1764] 1862

[1765] TLC: Rf 0.36 (ethyl acetate:acetic acid:water=3:1:1);

[1766] NMR (CDCl3): δ 7.55-7.35 (m, 2H), 7.29 (d, J=7 Hz, 1H), 7.06 (d, J=8 Hz, 1H), 6.61 (d, J=7 Hz, 1H), 4.22 (t, J=6 Hz, 2H), 2.94 (t, J=6 Hz, 2H), 2.64 (t, J=6 Hz, 4H), 2.20-1.65 (m, 4H).

EXAMPLE 30 (6)

4-(2-(Piperidin-1-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene

[1767] 1863

[1768] TLC: Rf 0.44 (ethyl acetate:acetic acid:water=3:1:1);

[1769] NMR (CDCl3): δ 7.60-7.58 (m, 2H), 7.29 (d, J=8 Hz, 1H), 7.07 (d, J=8 Hz, 1H), 6.61 (d, J=7 Hz, 1H), 4.21 (t, J=6 Hz, 2H), 2.80 (t, J=6 Hz, 2H), 2.51 (t, J=6 Hz, 4H), 1.90-1.35 (m 6H).

EXAMPLE 30 (7)

4-(2-(2-Acetyloxyethoxy)ethyl)oxy-1,1-dioxidebenzo[b]thiophene

[1770] 1864

[1771] TLC: Rf 0.46 (ethyl acetate:hexane=2:1);

[1772] NMR (CDCl3): δ 5 7.58-7.38 (m, 2H), 7.31 (d, J=7 Hz, 1H), 7.08 (d, J=9 Hz, 1H), 6.62 (d, J=7 Hz, 1H), 4.25 (t, J=5 Hz, 4H), 3.88 (t, J=5 Hz, 2H), 3.76 (t, J=5 Hz, 2H), 2.07 (s, 3H).

EXAMPLE 30 (8)

4-(2-(4-Benzylpiperazin-1-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene

[1773] 1865

[1774] TLC: Rf 0.57 (chloroform:methanol 5:1);

[1775] NMR (CDCl3): δ 7.58-7.38 (m, 2H), 7.38-7.18 (m, 6H), 7.05 (d, J=8 Hz, 1H), 6.60 (d, J=7 Hz,1H), 4.35-4.05 (m, 2H), 3.52 (s, 2H), 2.85 (t, J=6 Hz, 2H), 2.78-2.35 (m, 8H).

EXAMPLE 30 (9)

4-Diethylcarbamoylmethyloxy-1,1-dioxidebenzo[b]thiophene

[1776] 1866

[1777] TLC: Rf 0.25 (hexane:ethyl acetate=1:2);

[1778] NMR (CDCl3): δ 7.52 (d, J=7.0 Hz,1H), 7.46 (t, J=8.0 Hz, 1H), 7.32 (d, J=8.0 Hz, 1H), 7.05 (d, J=8.0 Hz, 1H), 6.63 (d, J=7.0 Hz, 1H), 4.80 (s, 2H), 3.41 (q, J=7.2 Hz, 2H), 3.36 (q, J=7.2 Hz, 2H), 1.23 (t, J=7.2 Hz, 3H), 1.15 (t, J=7.2 Hz, 3H).

EXAMPLE 30 (10)

4-Cyanomethyloxy-1,1-dioxidebenzo[b]thiophene

[1779] 1867

[1780] TLC: Rf 0.30 (hexane:ethyl acetate=1:1);

[1781] NMR (CDCl3): δ 7.65-7.35 (m, 3H), 7.15 (d, J=7.5 Hz, 1H), 6.70 (d, J=7.5 Hz, 1H), 4.90 (s, 2H).

EXAMPLE 30 (11)

5-(Pyridin-3-yloxy)methyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[1782] 1868

[1783] MS (APCI, Pos.): m/z 336 (M+MeOH+H)+, 304 (M+H)+.

EXAMPLE 30 (12)

5-(2-t-Butoxycarbonylaminoethyl)oxy-4-nitro-1,1-dioxidebenzo[b]thiophene

[1784] 1869

[1785] TLC: Rf 0.32 (hexane:ethyl acetate=1:1);

[1786] NMR (CDCl3) δ 7.80 (d, J=8.6 Hz, 1H), 7.33 (d, J=7.0 Hz, 1H), 7.18 (d, J=8.6 Hz, 1H), 6.93 (d, J=7.0 Hz, 1H), 5.00 (br, 1H), 4.24 (t, J=5.2 Hz, 2H), 3.57 (q, J=5.2 Hz, 2H), 1.45 (s, 9H).

EXAMPLE 30 (13)

5-((2E)-3-Ethoxycarbonyl-2-propenyl) oxy-1,1-dioxidebenzo[b]thiophene

[1787] 1870

[1788] TLC: Rf 0.51 (hexane:ethyl acetate=1:1);

[1789] NMR (CDCl3): δ 7.65 (d, J=8.8 Hz, 1H), 7.14 (d, J=6.8 Hz, 1H), 7.12-6.85 (m, 4H), 6.74 (d, J=6.8 Hz, 1H), 6.23-6.10 (m, 1H), 4.82-4.73 (m, 2H), 4.23 (q, J=7.0 Hz, 2H), 1.31 (t, J=7.0 Hz, 3H).

EXAMPLE 31

4-(2,4-Dimethoxyphenylmethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene

[1790] 1871

[1791] 4-Bromomethyl-1,1-dioxidebenzo[b]thiophene (198 mg) was dissolved in acetonitrile (10 ml). Thereto was added a solution of 2,4-dimethoxybenzylamine, hydrochloride (188 mg) and triethylamine (0.26 ml) in acetonitrile (6 ml). The mixture was stirred at room temperature for 1 hour. To the reaction mixture a saturated aqueous solution of sodium bicarbonate was added. The mixture was extracted by ethyl acetate. The extract was washed by a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated. The residue was purified with column chromatography on silica gel (ethyl acetate:hexane 1:1→2:1) to give the compound of the present invention (113 mg) having the following physical data.

[1792] TLC: Rf 0.29 (ethyl acetate);

[1793] NMR (CDCl3): δ 7.63-7.39 (m, 4H), 7.07 (d, J=8.0 Hz,1H), 6.66 (d, J=7.0 Hz,1H), 6.49-6.39 (m, 2H), 3.83 (s, 2H), 3.81 (s, 3H), 3.79 (s, 3H), 3.72 (s, 2H), 1.98 (s, 1H).

EXAMPLES 31 (1)˜31 (12)

[1794] By the same procedure as described in Example 31 using 4-bromomethyl-1,1-dioxidebenzo[b]thiophene and an amine derivative corresponding to 2,4-dimethoxybenzylamine-hydrochloride, and if necessary, by converting into the corresponding salt by a known method, the following compounds of the present invention were obtained.

EXAMPLE 31 (1)

4-(Pyridin-3-ylmethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene-2hydrochloride

[1795] 1872

[1796] TLC: Rf 0.37 (ethyl acetate:methanol=5:1);

[1797] NMR (CD3OD): δ 9.11 (d, J=1.7 Hz, 1H), 8.92 (dd, J=5.5, 1.7 Hz, 1H), 8.73 (dt, J=8.2, 1.7 Hz, 1H), 8.10 (dd, J=8.2, 5.5 Hz, 1H), 7.94-7.90 (m, 2H), 7.84 (d, J=7.4 Hz, 1H), 7.20 (t, J=7.4 Hz,. 1H), 7.18 (d, J=7.4 Hz, 1H), 4.68 (s, 2H), 4.63 (s, 2H).

EXAMPLE 31 (2)

4-(2-(Dimethylamino)ethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene

[1798] 1873

[1799] MS (APCI, Pos.): mlz 299 (M+MeOH+H)+, 267 (M+H)+.

EXAMPLE 31 (3)

4-(N,N-Bis(2-hydroxyethyl)amino)methyl-1,1-dioxidebenzo[b]thiophene

[1800] 1874

[1801] MS (APCI, Pos.): m/z 316 (M+MeOH+H)+, 284 (M+H)+.

EXAMPLE 31 (4)

4-(2-(2-Hydroxyethoxy)ethyl)aminoethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene

[1802] 1875

[1803] MS (APCI, Pos.): m/z 599 (2M+MeOH+H)+, 567 (2M+H)+, 316 (M+MeOH+H)+, 284 (M+H)+.

EXAMPLE 31 (5)

4-(4-Benzylpiperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene

[1804] 1876

[1805] Free Compound:

[1806] TLC: Rf 0.27 (ethyl acetate:hexane=1:1);

[1807] NMR (CDCl3): δ 7.71 (d, J=7.0 Hz, 1H), 7.62 (t, J=4.6 Hz, 1H), 7.44 (d, J=4.6 Hz, 2H), 7.35-7.25 (m, 5H), 6.68 (d, J=7.0 Hz, 1H), 3.60 (s, 2H), 3.51 (s, 2H), 2.46 (brs, 8H).

[1808] 2hydrochloride:

[1809] TLC: Rf 0.32 (ethyl acetate);

[1810] NMR (CD3OD): δ 7.86 (d, J=7.2 Hz, 1H), 7.76-7.70 (m, 2H), 7.63 (d, J=7.8 Hz, 1H), 7.58-7.47 (m, 5H), 7.07 (d, J=7.2 Hz, 1H), 4.38 (s, 2H), 4.13 (s, 2H), 3.41 (br, 4H), 3.13 (br, 4H).

EXAMPLE 31 (6)

4-(4-(Pyridin-2-yl)piperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene

[1811] 1877

[1812] MS (APCI, Pos.): m/z 374 (M+MeOH+H)+, 342 (M+H)+.

EXAMPLE 31 (7)

4-(4-Ethoxycarbonylpiperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene

[1813] 1878

[1814] MS (APCI, Pos.): m/z 369 (M+MeOH+H)+, 337 (M+H)+.

EXAMPLE 31 (8)

4-(4-(2-Hydroxyethyl)piperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene

[1815] 1879

[1816] MS (APCI, Pos.): m/z 649 (2M+MeOH+H)+, 617 (2M+H)+, 341 (M+MeOH+H)+, 309 (M+H)+.

EXAMPLE 31 (9)

4-(4-(Pyridin-4-yl)piperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene

[1817] 1880

[1818] MS (APCI, Pos.): m/z 374 (M+MeOH+H)+, 342 (M+H)+.

EXAMPLE 31 (10)

4-Benzylaminomethyl-1,1-dioxidebenzo[b]thiophene

[1819] 1881

[1820] Free Compound:

[1821] TLC: Rf 0.66 (ethyl acetate);

[1822] NMR (CDCl3): δ 7.62 (d, J=7.2 Hz, 1H), 7.56 (d, J=7.5 Hz, 1H), 7.52 (d, J=7.5 Hz, 1H), 7.46 (t, J=7.5 Hz, 1H), 7.39-7.24 (m, 5H), 6.69 (d, J=7.2 Hz, 1H), 3.89 (s, 2H), 3.81 (s, 2H), 1.59 (s, 1H).

[1823] Hydrochloride:

[1824] TLC: Rf 0.47 (ethyl acetate:hexane 2:1);

[1825] NMR (CD3OD): δ 7.95-7.18 (m, 8H), 7.15 (d, J=7 Hz, 1H), 6.98 (d, J=7 Hz, 1H), 4.48 (s, 2H), 4.36 (s, 2H).

EXAMPLE 31 (11)

4-(1-Benzylpiperidin-4-yl)aminomethyl-1,1-dioxidebenzo[b]thiophene

[1826] 1882

[1827] Free Compound:

[1828] TLC: Rf 0.27 (ethyl acetate:methanol=4:1);

[1829] NMR (CDCl3): δ 7.65 (d, J=7.0 Hz, 1H), 7.61 (d, J=6.8 Hz, 1H), 7.56-7.40 (m, 2H), 7.34-7.22 (m, 5H), 6.68 (d, J=7.0 Hz, 1H), 3.91 (s, 2H), 3.50 (s, 2H), 2.91-2.77 (m, 2H), 2.60-2.43 (m, 1H), 2.12-1.95 (m, 2H), 1.95-1.80 (m, 2H), 1.60-1.32 (m, 3H).

[1830] 2hydrochloride:

[1831] TLC: Rf 0.30 (ethyl acetate:methanol:triethylamine=8:1.5:0.5);

[1832] NMR (DMSO-d6+CD3OD): δ 7.97 (d, J=7.2 Hz, 1H), 7.95 (d, J=7.8 Hz, 1H), 7.88 (d, J=7.5 Hz,1H),7.65-7.55 (m, 3H), 7.50-7.40 (m, 4H), 4.42 (s, 2H), 4.33 (s, 2H), 3.80-3.40 (m, 3H), 3.10-2.95 (m, 2H), 2.50-2.35 (m, 2H), 2.35-2.05 (m, 2H).

EXAMPLE 31 (12)

4-(Morpholin-4-yl)methyl-1,1-dioxidebenzo[b]thiophene

[1833] 1883

[1834] TLC: Rf 0.31 (ethyl acetate:methylene chloride=1:1);

[1835] NMR (CDCl3): δ 7.69 (d, J=7.2 Hz, 1H), 7.64 (t, J=4.8 Hz, 1H), 7.46 (d, J=4.8 Hz, 2H), 6.71 (d, J=7.2 Hz, 1H), 3.68 (t, J=4.5 Hz, 4H), 3.60 (s, 2H), 2.44 (t, J=4.5 Hz, 4H).

EXAMPLE 32

4-Ethoxycarbonyl-1,1-dioxidebenzo[b]thiophene

[1836] 1884

[1837] To a solution of 4-Carboxy-1,1-dioxidebenzo[b]thiophene (2.42 g) in dimethylformamide (50 ml), were added potassium carbonate (3.10 g) and bromoethane (44.3 g). The mixture was stirred at room temperature overnight. To a reaction mixture, water was added. The mixture was extracted by ethyl acetate. The extract was washed by water and a saturated aqueous solution of sodium chloride sucessively, dried over anhydrous sodium sulfate and concentrated to give the compound of the present invention (2.08 g) having the following physical data.

[1838] TLC: Rf 0.24 (ethyl acetate:hexane=1:4);

[1839] NMR (CDCl3). δ 8.25 (d, J=7.4 Hz, 1H), 8.20 (d, J=7.8 Hz, 1H), 7.88 (d, J=7.8 Hz, 1H), 7.61 (t, J=7.8 Hz, 1H), 6.84 (d, J=7.4 Hz, 1H), 4.44 (q, J=7.2 Hz, 2H), 1.44 (t, J=7.2 Hz, 3H).

EXAMPLE 32 (1)

4-Benzyloxycarbonyl-1,1-dioxidebenzo[b]thiophene

[1840] 1885

[1841] By the same procedure as described in Example 32 using 4-carboxy-1,1-dioxidebenzo[b]thiophene and benzylbromide instead of bromoethane, the compound of the present invention having the following physical data was obtained.

[1842] MS (APCI, Pos.): m/z 301 (M+H)+.

EXAMPLE 33

4-(Pyridin-3-yl)-1,1-dioxidebenzo[b]thiophene

[1843] 1886

[1844] To a solution of 4-bromo-1,1-dioxidebenzo[b]thiophene (492 mg) in dimethylformamide (5.0 ml), were added diethyl(3-pyridyl)boran (440 mg) and trispotassium phosphate (637 mg) and tetrakis(triphenylphosphine)palladium (0) (116 mg). The mixture was stirred at 80° C. for 2 hours. The reaction mixture was poured into water. The mixture was extracted by ethyl acetate. The extract was washed by a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue was purified with column chromatography on silica gel (chloroform:methanol=50:1) to give the compound of the present invention (490 mg) having the following physical data.

[1845] TLC: Rf 0.59 (chloroform:methanol=9:1);

[1846] MS (APCI, Pos.): m/z 276 (M+MeOH+H)+, 244 (M+H)+.

EXAMPLE 33 (1)

6-(Pyridin-3-yl)-1,1-dioxidebenzo[b]thiophene

[1847] 1887

[1848] By the same procedure as described in Example 33, using 6-bromo-1,1-dioxidebenzo[b]thiophene instead of 4-bromo-1,1-dioxidebenzo[b]thiophene, and diethyl(3-pyridyl)borane, the compound of the present invention having the following physical data was obtained.

[1849] MS (APCI, Pos.): m/z 276 (M+MeOH+H)+, 244 (M+H)+.

EXAMPLE 34

4-(4,4-Dimethyl-4,5-dihydroxazol-2-yl)-1,1-dioxidebenzo[b]thiophene

[1850] 1888

[1851] To the compound prepared in the following Example 72 (519 mg), was added thionyl chloride (2.1 ml). The mixture was stirred at room temperature for 1 hour. To the reaction mixture was added ethyl acetate. The extract was washed by a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, concentrated to give the compound of the present invention (392 mg) having the following physical data.

[1852] TLC: Rf 0.42 (ethyl acetate:hexane=1:1);

[1853] NMR (CDCl3): δ 8.43 (d, J=7.0 Hz, 1H), 8.08 (d, J=7.8 Hz, 1H), 7.78 (d, J=7.8 Hz, 1H), 7.56 (t, J=7.8 Hz, 1H), 6.76 (d, J=7.0 Hz, 1H), 4.13 (s, 2H), 1.40 (s, 6H).

EXAMPLES 35˜35 (68)

[1854] By the same procedure as described in Example 27, using the compounds prepared in Examples 28˜28 (33), 29, 30˜30 (13), 31˜31 (12), 32˜32 (1), 33˜33 (1), 34 or corresponding compounds instead of 5-methyl-1,1-dioxidebenzo[b]thiophene, and if necessary, by converting into the corresponding salt by a known method, the compounds of the present invention having the following physical data were obtained.

EXAMPLE 35

4-(Pyridin-3-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1855] 1889

[1856] Free Acid:

[1857] TLC: Rf 0.44 (methylene chloride:methanol=10:1);

[1858] NMR (DMSO-d6): δ 9.41 (t, J=5.7 Hz, 1H), 8.67 (d, J=1.8 Hz, 1H), 8.46 (dd. J=4.8, 1.8 Hz,1H), 8.06 (d, J=6.3 Hz,1H), 7.96 (d, J=6.9 Hz, 1H), 7.90-7.67 (m, 5H), 7.66-7.58 (m, 2H), 7.36 (dd, J=8.1, 5.1 Hz, 1H), 6.27 (d, J=6.9 Hz, 1H), 4.54 (d, J=5.7 Hz, 2H), 4.10 (dd, J=15.6, 9.3 Hz, 1H), 3.98 (dd, J=15.6,1.5 Hz, 1H). hydrochloride:

[1859] TLC: Rf 0.45 (chloroform:methanol 9:1);

[1860] NMR (DMSO-d6): δ 9.70-9.62 (br, 1H), 8.95 (s, 1H), 8.75 (d, J=5.4 Hz, 1H), 8.55 (d, J=7.5 Hz, 1H), 8.13 (d, J=7.5 Hz, 1H), 7.98 (d, J=6.9 Hz, 1H), 7.94 (d, J=7.5 Hz, 1H), 7.91-7.85 (m, 1H), 7.81-7.72 (m, 1H), 7.67-7.58 (m, 4H), 6.21 (d, J=9.0 Hz, 1H), 4.76 (dd, J=15.6, 6.0 Hz, 1H), 4.62 (dd, J=15.6, 5.1 Hz, 1H), 4.07 (dd, J=15.0, 9.0 Hz, 1H), 3.93 (d, J=15.0Hz, 1H).

EXAMPLE 35 (1)

4-(4-Benzylpiperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene hydrochloride

[1861] 1890

[1862] TLC: Rf 0.46 (chloroform:methanol=19:1);

[1863] NMR (DMSO-d6): δ 11.60-11.40 and 11.40-11.20 (each br, total 1H), 8.05-7.52 (m, 10H), 7.51-7.23 (m, 3H), 5.88 and 5.81 (each d, J=9.3 Hz, total 1H), 4.80-3.85 (m, 6H), 3.70-2.78 (m, 6H).

EXAMPLE 35 (2)

4-(N-(2-(Pyridin-3-yl)ethyl)-N-methylcarbamoyl)-3-phenylsulfonyl-2,3-dihydro-2,2-dioxidebenzo[b]thiophene.hydrochloride

[1864] 1891

[1865] TLC: Rf 0.27 (chloroform: methanol=19:1);

[1866] NMR (DMSO-d6): δ 8.96 and 8.81 (each s, total 1H), 8.75 and 8.73 (each d, J=5.4 Hz, total 1H), 8.55 and 8.32 (each d, J=7.5 Hz, total 1H), 7.95-7.62 (m, 9H), 5.81 and 5.79 (each d, J=8.4 Hz, total 1H), 4.15-3.84 and 3.73-3.62 (each m, total 4H), 3.50-3.05 (m, 2H), 3.16 and 3.13 (each s, total 3H).

EXAMPLE 35 (3)

4-(2-(2-Hydroxyethoxy)ethyl)carbamoyl-3-phenylSulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1867] 1892

[1868] TLC: Rf 0.55 (methylene chloride:methanol=9:1);

[1869] NMR (DMSO-d6): δ 8.84 (t, J=5.4 Hz, 1H), 7.98-7.90 (m, 2H), 7.84 (d, J=7.5 Hz, 1H), 7.81-7.73 (m, 3H), 7.69-7.60 (m, 2H), 6.36 (d, J=8.9 Hz, 1H), 4.58 t, J=5.1 Hz, 1H), 4.09 (dd, J=15.3, 8.9 Hz, 1H), 3.9 6 (d, J=15.3 Hz, 1H), 3.67-3.53 (m, 2H), 3.53-3.35 (m, 6H).

EXAMPLE 35 (4)

4-(2,4-Dimethoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1870] 1893

[1871] TLC: Rf 0.48 (methylene chloride:methanol=95:5);

[1872] NMR (DMSO-d6): δ 5 9.04 (t, J=5 Hz, 1H), 8.03 (d, J=7.2 Hz, 1H), 7.92 (d, J=7.2 Hz, 1H), 7.90-7.70 (m, 5H), 7.62 (t, J=7.2 Hz, 1H), 7.32 (d, J=8.4 Hz, 1H), 6.57 (d, J=2.4 Hz, 1H), 6.47 (dd , J=8.4, 2.4 Hz, 1H), 6.27 (d, J=8.5 Hz, 1H), 4.47 (dd, J=15, 5 Hz, 1H), 4.29 (dd, J=15, 5Hz, 1H), 4.08 (dd, J=15, 8.5 Hz, 1H), 3.97 (d, J=15 Hz, 1H), 3.83 (s, 3H), 3.74 (s, 3H).

EXAMPLE 35 (5)

4-(1-Benzylpiperidin-4-yl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1873] 1894

[1874] Free Compound:

[1875] TLC: Rf 0.30 (methylene chloride:methanol=9:1);

[1876] NMR (CDCl3+CD3OD). δ 8.00-7.50 (m, 8H), 7.45-7.20 (m, 1H), 6.25 (dd, J=7.5, 2.5 Hz, 1H), 4.10-3.90 (m, 1H), 3.8 0 (dd, J=15, 2.5 Hz, H), 3.70-3.60 (m, H), 3.55 (s, 2H), 3.10-2.90 (m H, ), 2.30-1.95 (m, 4H), 1.90-1.70 (m, 2H).

[1877] Hydrochloride:

[1878] TLC: Rf 0.40 (methanol:ethyl acetate=1:10);

[1879] NMR (CD3OD): δ 8.04-7.43 (m, 13H), 6.15 (dd, J=8.2 Hz, 2.6 Hz, 1H), 4.35 (s, 2H), 4.34-4.06 (m,1H), 3.94 (dd, J=15.2 Hz, 8.2 Hz,1H), 3.83 (dd, J=15.2 Hz, 2.6 Hz,1H), 3.74-3.08 (m, 4H), 2.56-1.56 (m, 4H).

[1880] Methanesulfonic Acid Salt:

[1881] TLC: Rf 0.40 (methanol:ethyl acetate=1:10);

[1882] NMR (CD3OD): δ 8.06-7.44 (m, 13H), 6.14 (dd, J=8.2 Hz, 2.6 Hz, 1H), 4.34 (s, 2H), 4.32-4.12 (m,1H), 4.01-3.77 (m, 2H), 3.68-3.08 (m, 4H), 2.69 (s, 3H), 2.54-1.74 (m, 4H).

EXAMPLE 35 (6)

4-(Pyridin-4-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1883] 1895

[1884] TLC: Rf 0.35 (chloroform:methanol=9:1);

[1885] NMR (DMSO-d6). δ 9.45 (t. J=7 Hz, 1H), 8.50 (d, J=8 Hz, 2H), 8.10 (d, J=8 Hz, 1H), 8.00 (d, J=8 Hz, 1H), 7.90 (t, J=8 Hz,1H), 7.80-7.55 (m, 5H), 7.45 (d, J=8 Hz, 2H), 6.30 (dd, J=1 Hz and 7 Hz, 1H), 4.55 (m, 2H), 4.10 (dd, J=7 Hz and 15 Hz, 1H), 4.00 (dd, J=1 Hz and 15 Hz, 1H).

EXAMPLE 35 (7)

4-(2-t-Butoxycarbonylethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1886] 1896

[1887] TLC: Rf 0.37 (ethyl acetate:hexane=3:2);

[1888] NMR (DMSO-d6): δ 8.90 (t, J=7 Hz, 1H), 8.00-7.55 (m, 8H), 6.25 (dd, J=1 Hz and 7Hz, 1H), 4.10 (dd, J=7Hz and 15Hz, 1H), 3.95 (dd, J=1 Hz and 15 Hz, 1H), 3.45 (m, 2H), 2.60 (t, J=7 Hz, 2H).

EXAMPLE 35 (8)

4-(Thiophen-2-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1889] 1897

[1890] TLC: Rf 0.67 (chloroform:methanol=4:1);

[1891] NMR (DMSO-d6): δ 9.40 (t, J=7 Hz, 1H), 8.00-7.60 (m, 8H), 7.40 (d, J=6 Hz, 1H), 7.10 (d, J=4 Hz, 1H), 7.00 (dd, J=4 Hz and6 Hz, 1H), 6.30 (dd, J=1 Hz and7 Hz, 1H), 4.75 (dd, J=7 Hz and 16 Hz, 1H), 4.55 (dd, J=7 Hz and 16 Hz, 1H),4.10 (dd, J=7 Hz and 12 Hz, 1H), 4.00 (dd, J=1 Hz and 12 Hz, 1H).

EXAMPLE 35 (9)

4-Benzylcarbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1892] 1898

[1893] TLC: Rf 0.58 (methylene chloride:methanol=10:1);

[1894] NMR (CDCl3+DMSO-d6): δ 8.74 (t, J=5.7 Hz,1H), 8.03 (dd, J=7.8, 0.9 Hz, 1H), 7.93-7.80 (m, 3H), 7.78-7.68 (m, 2H), 7.59 (t, J=7.8 Hz, 2H), 7.50 (d, J=6.9 Hz, 2H), 7.39-7.20 (m, 3H), 6.36 (d, J=7.8 Hz, 1H), 4.71 (dd, J=14.9, 5.7 Hz, 1H), 4.62 (dd, J 14.9, 5.7 Hz, 1H), 3.86 (d, J=15.0 Hz, 1H), 3.69 (dd, J=15.0, 7.8 Hz, 1H).

EXAMPLE 35 (10)

4-(Pyridin-2-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1895] 1899

[1896] TLC: Rf 0.56 (methylene chloride:methanol=10:1);

[1897] NMR (DMSO-d6): δ 9.42 (t, J=6.3 Hz, 1H), 8.54 (d, J=5.1 Hz, 1H), 8.11 (d, J=7.5 Hz, 1H), 7.97 (d, J=8.1 Hz, 1H), 7.95-7.82 (m, 1H), 7.80-7.70 (m, 4H). 7.62 (t, J=8.1 Hz, 2H), 7.55 (d, J=8.1 Hz, 1H), 7.30-7.24 (m, 1H), 6.30 (d, J=8.7 Hz, 1H), 4.65 (dd, J=16.0,4.8 Hz, 1H), 4.54 (dd, J=16.0, 4.8 Hz, 1H), 4.10 (dd, J=15.6,4.8 Hz, 1H), 4.00 (d, J=15.6, 9.3 Hz, 1H).

EXAMPLE 35 (11)

4-(2-(Piperidin-1-yl) ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1898] 1900

[1899] Free Compound:

[1900] TLC: Rf 0.10 (methylene chloride:methanol=10:1);

[1901] NMR (CDCl3): δ 7.90-7.78 (m, 4H), 7.75-7.64 (m, 2H), 7.62-7.51 (m, 2H), 7.42 (bs, 1H), 6.29 (d, J=8.1 Hz, 1H), 3.84 (dd, J=15.0, 1.5 Hz, 1H), 3.75-3.60 (m, 2H), 3.58-3.45 (m, 1H), 2.77-2.60 (m , 2H), 2.55-2.40 (m, 4H), 1.80-1.40 (m, 6H).

[1902] Hydrochloride:

[1903] TLC: Rf 0.30 (ethyl acetate:methanol:triethylamine=8:1.5:0.5);

[1904] NMR (DMSO-d6): δ 10.25 (br. s, 1H), 9.32 (t, J=5.4 Hz, 1H),8.10 (dd, J=7, 1.4 Hz, 1H), 8.00-7.80 (m, 2H),7.80-7.70 (m, 3H), 7.70-7.55 (m, 2H),6.30 (d, J=8 Hz, 1H), 4.14 (dd, J=15, 8 Hz, 1H ), 3.97 (d, J=15 Hz, 1H), 3.90-3.70 (m, 2H),3.70-3.50 (m, 2H), 3.50-3.10 (m, 3H), 3.10-2.80(m, 2H), 2.00-1.60 (m, 4H), 1.60-1.20 (m, 1H).

[1905] Methanesulfonic Acid Salt:

[1906] TLC: Rf 0.30 (ethyl acetate:methanol:triethylamine=8:1.5:0.5);

[1907] NMR (DMSO-d6): δ 9.13 (t, J=5 Hz, 1H), 9.00 (br. s, 1H), 8.05 (dd, J=7, 1.4 Hz, 1H), 8.00-7.80 (m, 2H), 7.80-7.70 (m, 3H), 7.70-7.55 (m, 2H), 6.28 (d, J=8.2 Hz, 1H), 4.12 (dd, J=16, 8.2 Hz, 1H), 3.94 (d, J=16 Hz, 1H), 3.90-3.50 (m, 5H), 3.50-3.20 (m, 2H), 3.15-2.90 (m, 2H), 2.00-1.60 (m, 4H), 1.60-1.30 (m, 1H).

EXAMPLE 35 (12a)

4-((1S)-1-t-Butoxycarbonyl-2-methylpropyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1908] 1901

[1909] TLC: Rf 0.34 (hexane:ethyl acetate=1:1);

[1910] NMR (CDCl3): δ 7.99 (dd, J=7.5, 0.9 Hz, 1H), 7.87-7.84 (m, 3H), 7.75 (t, J=7.5 Hz, 1H), 7.72-7.67 (m, 1H), 7.60-7.55 (m, 2H), 6.80 (d, J=8.8 Hz, 1H), 6.25 (d, J=8.7 Hz, 1H), 4.67 (dd, J=8.8, 3.9 Hz, 1H), 3.80 (d-like, J=15.0 Hz, 1H), 3.65 (dd, J=15.0, 8.7 Hz, 1H), 2.47-2.41 (m, 1H), 1.54 (s, 9H), 1.12 (d, J=7.0 Hz, 3H), 1.06 (d, J=7.0 Hz, 3H).

[1911] (The determination of the absolute configuration of the carbon atom to which phenylsulfonyl is bonded is not performed, but this compound is a single isolated one.)

EXAMPLE 35 (12b)

4-((1S)-1-t-Butoxycarbonyl-2-methypropyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1912] 1902

[1913] TLC: Rf 0.34 (hexane:ethyl acetate=1:1);

[1914] NMR (CDCl3): δ 7.98 (d, J=7.8 Hz, 0.5H), 7.91-7.80 (m, 3.5H), 7.76-7.67 (m, 2H), 7.60-7.55 (m, 2H), 6.92 (d, J=8.1 Hz, 0.5H), 6.84 (d, J=8.7 Hz, 0.5H), 6.25 (dd, J=9.3, 1.5 Hz, 0.5H), 6.18 (dd, J=9.3, 1.5 Hz, 0.5H), 4.66 (dd, J=8.7, 3.9 Hz, 0.5H), 4.62 (dd, J=8.1, 5.3 Hz, 0.5H), 3.87 (dd, J=15.0, 1.5 Hz, 0.5H), 3.80 (dd, J=15.0, 1.5 Hz, 0.5H), 3.67 (dd, J=15.0, 9.3 Hz, O.SH), 2.41-2.36 (m, 0.5H), 2.33-2.24 (m, 0.5H), 1.54 (s, 4.5H), 1.46 (s, 4.5H), 1.11 (d, J=6.9 Hz, 1.5H), 1.07 (d, J=6.9 Hz, 1.5H), 1.06 (d, J=6.9 Hz, 1.5H), 1.05 (d, J=6.9 Hz, 1.5H).

EXAMPLE 35 (13)

4-(2-Fluorophenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1915] 1903

[1916] TLC: Rf 0.60 (chloroform:methanol=9:1);

[1917] NMR (DMSO-d6): δ 9.35 (t, J=7Hz, 1H), 8.05 (d, J=8Hz, 1H), 7.95 (d, J=8Hz, 1H), 7.85 (t, J=8 Hz, 1H), 7.80-7.50 (m, 6H), 7.40-7.10 (m, 3H), 6.25 (d, J=10 Hz, 1H), 4.60 (dd, J=16 Hz and 7Hz, 1H),4.45 (dd, J=16 Hz and 7Hz, 1H),4.10 (dd, J=16Hz and 10 Hz, 1H), 4.00 (d, J=16 Hz, 1H).

EXAMPLE 35 (14)

4-(3-Fluorophenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1918] 1904

[1919] TLC: Rf 0.60 (chloroform:methanol=9:1);

[1920] NMR (DMSO-d6): δ 9.40 (t, J=7 Hz, 1H), 8.05 (d, J=8 Hz, 1H), 7.95 (d, J=8 Hz, 1H), 7.85 (t, J=8 Hz, 1H), 7.80-7.70 (m, 3H), 7.70-7.55 (m, 2H), 7.45-7.20 (m, 3H), 7.05 (m, 1H), 6.25 (d, J=10 Hz, 1H), 4.55 (d, J=7 Hz, 2H), 4.10 (dd, J=16 Hz and 10 Hz, 1H), 3.97 (dd, J=16 Hz, 1H).

EXAMPLE 35 (15)

4-(3-Methylphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1921] 1905

[1922] TLC: Rf 0.69 (chloroform:methanol=9:1);

[1923] NMR (DMSO-d6): δ 9.31 (t, J=6.0 Hz, 1H), 8.06 (d, J=7.6 Hz, 1H), 7.96 (d, J=7.6 Hz, 1H), 7.85 (t, J=7.6 Hz, 1H), 7.80-7.70 (m, 3H), 7.70-7.55 (m, 2H), 7.30-7.15 (m, 3H), 7.15-7.00 (m, 1H), 6.31 (dd, J=8.6 Hz and 2.0 Hz, 1H), 4.48 (m, 2H), 4.10 (dd, J=15 Hz and 8.6 Hz, 1H), 3.98 (dd, J=15 Hz and 2.0 Hz, 1H), 2.27 (s, 3H).

EXAMPLE 35 (16)

4-(2-Methoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1924] 1906

[1925] TLC: Rf 0.70 (chloroform:methanol=9:1);

[1926] NMR (DMSO-d6): δ 9.15 (t-like, J=6 Hz, 1H), 8.08 (d, J=7.5 Hz, 1H), 7.95 (d, J 7.5 Hz,1H), 7.85 (t, J=7.5 Hz,1H), 7.80-7.70 (m, 3H), 7.70-7.55 (m, 2H), 7.50-7-35 (m, 1H), 7.35-7.20 (m, 1H), 7.10-6.80 (m, 2H), 6.28 (d, J=8 Hz, 1H), 4.57 (dd, J=16 Hz and 6 Hz, 1H), 4.35 (dd, J=16 Hz and 6 Hz, 1H), 4.10 (dd, J=15.5 Hz and 8 Hz, 1H), 4.00 (d, J=15.5 Hz, 1H), 3.85 (s, 3H).

EXAMPLE 35 (17)

4-(2,3-Dimethoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1927] 1907

[1928] TLC: Rf 0.52 (chloroform:methanol=9:1);

[1929] NMR (DMSO-d6): δ 9.22 (t, J=5.5 Hz, 1H), 8.05 (d, J=7.0 Hz, 1H), 7.95 (d, J=7.0 Hz, 1H), 7.85 (t, J=7.0 Hz, 1H), 7.80-7.70 (m, 3H), 7.70-7.57 (m, 2H), 7.15-6.90 (m, 3H), 6.29 (dd, J=8.5 Hz and 2.0 Hz, 1H), 4.62 (dd, J=15.0 Hz and 5.5 Hz, 1H), 4.38 (dd, J=15.0 Hz and 5.5 Hz, 1H), 4.11 (dd, J=15.5 Hz and 8.5 Hz, 1H), 3.99 (dd, J=15.5 Hz and 2.0 Hz, 1H), 3.82 (s, 6H).

EXAMPLE 35 (18)

4-(3,4-Dimethoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1930] 1908

[1931] TLC: Rf 0.48 (chloroform:methanol=9:1);

[1932] NMR (DMSO-d6): δ 9.27 (t, J=6.0 Hz, 1H), 8.04 (d, J=7.5 Hz, 1H), 7.95 (d, J=7.5 Hz, 1H), 7.85 (t, J=7.5 Hz, 1H), 7.80-7.70 (m, 3H), 7.70-7.57 (m, 2H), 7.44 (s, 1H), 7.00-6.85 (m, 2H), 6.31 (dd, J=8.6 Hz and 1.4 Hz, 1H), 4.45 (m, 2H), 4.11 (dd, J=15.0 Hz and 8.6 Hz, 1H), 3.99 (dd, J=15.0 Hz and 1.4 Hz, 1H), 3.73 (s, 3H), 3.72 (s, 3H).

EXAMPLE 35(19)

4-(2,5-Difluorophenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1933] 1909

[1934] TLC: Rf 0.59 (chloroform:methanol=9:1);

[1935] NMR (DMSO-d6): δ 9.41 (t, J=5.8Hz, 1H), 8.09 (dd, J=7.6Hz and 1.5 Hz, 1H), 7.98 (dd, J=7.6 Hz and 1.5 Hz, 1H), 7.87 (t, J=7.6 Hz,1H), 7.80-7.70 (m, 3H), 7.70-7.57 (m, 2H), 7.50-7.35 (m, 1H), 7.35-7.07 (m, 2H), 6.26 (dd, J=15 Hz and 8.4 Hz,1H), 4.54 (d, J=5.8 Hz, 2H), 4.10 (dd, J=15 Hz and 8.4 Hz, 1H), 3.97 (dd, J=15 Hz and 2.0 Hz,1H).

EXAMPLE 35 (20)

4-(3,4,5-Trimethoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1—dioxidebenzo[b]thiophene

[1936] 1910

[1937] TLC: Rf 0.58 (chloroform:methanol=9:1);

[1938] NMR (DMSO-d6): δ 9.31 (m, 1H), 8.06 (d, J=7.6 Hz, 1H), 7.95 (d, J=7.6 Hz, 1H), 7.85 (t, J=7.6 Hz, 1H),7.80-7.70 (m, 3H), 7.70-7.55 (m, 2H), 6.79 (s, 2H), 6.32 (d, J=8.4 Hz, 1H), 4.61 (dd, J=15.2 Hz and 6.6 Hz, 1H), 4.37 (dd, J=15.2 Hz and 4.6 Hz, 1H), 4.12 (dd, J=15 Hz and 8.4 Hz, 1H), 3.99(d, J=15 Hz, 1H), 3.73 (s, 6H), 3.61 (s, 3H).

EXAMPLE 35 (21)

4-(Benzimidazol-2-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1939] 1911

[1940] TLC: Rf 0.27 (chloroform:methanol=9:1);

[1941] NMR (DMSO-d6): δ 12.23 (broad-s, 1H), 9.48 (m, 1H), 8.17 (d, J=7 Hz, 1H), 8.00-7.80 (m, 2H), 7.80-7.70 (m, 3H), 7.70-7.45 (m, 4H), 7.20-7.10 (m, 2H), 6.29 (d, J=8 Hz, 1H), 4.89 (dd, J=16 Hz and 6 Hz, 1H), 4.51 (dd, J=16 Hz and 5 Hz, 1H), 4.13 (dd, J=15 Hz and 8 Hz, 1H), 3.99 (d, J=15 Hz, 1H).

EXAMPLE 35 (22)

4-(3,5-Difluorophenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1942] 1912

[1943] TLC: Rf 0.63 (chloroform:methanol=9:1);

[1944] NMR (DMSO-d6): δ 9.44 (t, J=5.6 Hz, 1H), 8.11 (d, J=7.4 Hz, 1H), 7.98 (d, J=7.4 Hz,1H), 7.88 (t, J=7.4 Hz,1H), 7.80-7.70 (m, 3H), 7.70-7.55 (m, 2H), 7.30-7.00 (m, 3H), 6.29 (dd, J=8.5 Hz and 2 Hz, 1H), 4.55 (m, 2H), 4.11 (dd, J=15 Hz and 8.5 Hz, 1H), 3.98 (dd, J=15 Hz and 2 Hz,1H).

EXAMPLE 35 (23)

4-(N-Benzyl-N-methylcarbamoyl)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1945] 1913

[1946] NMR (CDCl3): δ 8.00-7.25 (m, 13H), 6.00-5.90 (m, 1H), 5.19 (d, J=15 Hz) and 5.03 (d, J=18 Hz, total 1H), 4.49 (d, J=15 Hz) and 4.40 (d, J=18 Hz, total 1H), 3.75 (dd, J=2 Hz and 15 Hz, 1H), 3.63 (dd, J=8.5 Hz and 15 Hz, 1H), 3.18 and 3.12 (each s, total 3H).

EXAMPLE 35 (24)

4-(4-Nitrophenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1947] 1914

[1948] TLC: Rf 0.50 (chloroform:methanol=9:1);

[1949] NMR (DMSO-d6): δ 9.52 (m, 1H), 8.30-7.55 (m, 13H), 6.27 (d, J=6.4 Hz, 1H), 4.65 (m, 2H), 4.10 (dd, J=15.5 Hz and 6.4 Hz, 1H), 3.97 (d, J=15.5 Hz, 1H).

EXAMPLE 35 (25)

5-(2-Hydroxyethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1950] 1915

[1951] TLC: Rf 0.39 (ethyl acetate:methanol=95:5);

[1952] NMR (DMSO-d6): δ 8.79 (t, J=5.7 Hz, 1H), 8.18 (brs,1H), 8.14 (d, J=8.1 Hz,1H), 7.91 (d, J=8.1 Hz,1H), 7.82-7.75 (m, 3H), 7.68-7.58 (m, 2H), 5.83 (dd, J=9.4 Hz, 8.0 Hz, 1H), 4.77 (t, J=5.7 Hz, 1H), 4.03 (dd, J=15.0 Hz, 9.6 Hz, 1H), 3.84 (dd, J=15.0 Hz, 3.0 Hz, 1H), 3.54 (q, J=5.7 Hz, 2H), 3.36 (q, J=5.7 Hz, 2H).

EXAMPLE 35 (26)

5-(Pyridin-3-ylmethyl)carbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1953] 1916

[1954] Free Compound:

[1955] TLC: Rf 0.32 (ethyl acetate:methanol=9:1);

[1956] NMR (CDCl3): δ 8.59-8.56 (m, 2H), 8.04 (d, J=8.5 Hz, 1H), 7.74-7.68 (m, 3H), 7.58-7.53 (m, 1H), 7.47-7.31 (m, 5H), 5.16 (d, J=8.5 Hz, 1H), 4.68 (dd, J=15.0, 6.0 Hz, 1H), 4.59 (dd, J=15.0, 6.0 Hz, 1H), 4.11 (d, J=15.0 Hz, 1H), 3.77 (dd, J=15.0, 8.5 Hz, 1H), 3.67 (s, 3H).

[1957] Hydrochloride:

[1958] TLC: Rf 0.32 (ethyl acetate:methanol=9:1);

[1959] NMR (DMSO-d6): δ 9.37 (t, J=5.5 Hz, 1H), 8.90 (s, 1H), 8.84 (d, J=5.5 Hz, 1H), 8.49 (d, J=8.0 Hz, 1H), 8.02 (dd, J=8.0, 5.5 Hz, 1H), 7.85-7.75 (m, 4H), 7.67-7.56 (m, 3H), 5.70 (d, J=9.0 Hz, 1H), 4.72-4.60 (m, 2H), 4.15 (d, J=15.0 Hz, 1H), 4.02 (dd, J=15.0, 9.0 Hz, 1H), 3.56 (s, 3H).

EXAMPLE 35 (27)

5-(2-Dimethylaminoethyl)carbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1960] 1917

[1961] Free Compound:

[1962] TLC: Rf 0.24 (ethyl acetate:methanol:triethylamine=8:1:1);

[1963] NMR (CDCl3): δ 8.00 (d, J=8.0 Hz, 1H), 7.76-7.73 (m, 2H), 7.67-7.61 (m, 1H), 7.51-7.41 (m, 3H), 7.32 (bt, J=5.0 Hz, 1H), 5.23 (t, J=9.0 Hz, 1H), 4.19 (d, J=15.0 Hz, 1H), 3.81 (dd, J=15.0, 9.0 Hz, 1H), 3.77 (s, 3H), 3.64-3.42 (m, 2H), 2.51 (t, J=6.0 Hz, 1H), 2.28 (s, 6H).

[1964] Hydrochloride:

[1965] TLC: Rf 0.24 (ethyl acetate:methanol:triethylamine=8:1:1);

[1966] NMR (DMSO-d6): δ 10.47 (br, 1H), 8.90 (t, J=5.5 Hz, 1H), 7.86-7.76 (m, 4H), 7.69-7.64 (m, 2H), 7.56 (d, J=8.0 Hz, 1H), 5.69 (d, J=8.5 Hz, 1H), 4.13 (d, J=15.0 Hz, 1H), 4.00 (d, J=15.0, 8.5 Hz, 1H), 3.65-3.60 (m, 2H), 3.63 (s, 3H), 3.25 (t, J=6.0 Hz, 2H), 2.82 (s, 6H).

EXAMPLE 35 (28)

5-Dimethylcarbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1967] 1918

[1968] TLC: Rf 0.35 (ethyl acetate);

[1969] NMR (DMSO-d6): δ 7.83 (d, J=8.0 Hz, 2H), 7.44 (t, J=7.5 Hz, 1H), 7.63 (dd, J=8.0 Hz, 7.5 Hz, 2H), 7.49 (d, J=8.0 Hz,1H), 7.46 (d, J=7.5 Hz,1H), 5.63 (d, J=8.5 Hz, 1H), 4.13 (d, J=14.5 Hz, 1H), 4.02 (dd, J=14.5 Hz, 8.5 Hz, 1H), 3.59 (s, 3H), 3.01 (s, 3H), 2.78 (s, 3H).

EXAMPLE 35 (29)

5-(2,3,4,5,6,7-Hexahydro-1H-azepin-1-yl)carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1970] 1919

[1971] TLC: Rf 0.21 (ethyl acetate:hexane=2:1);

[1972] NMR (DMSO-d6): δ 7.87-7.70 (m, 3H), 7.70-7.60 (m, 2H), 7.60-7.53 (m, 2H),5.67 (d, J=8.7 Hz, 1H), 4.26 (d, J=15.0 Hz, 1H), 4.05 (dd, J=15.0, 8.7 Hz, 1H), 3.70-3.54 (m, 2H), 3.48 (s, 3H), 3.20-3.15 (m, 2H),1.85-1.40 (m, 8H).

EXAMPLE 35 (30)

5-(2,3-Dihydroindol-1-yl)carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1973] 1920

[1974] TLC: Rf 0.54 (ethyl acetate:hexane=2:1);

[1975] NMR (DMSO-d6): δ 8.13 (d, J=7.8 Hz, 1H), 7.87 (d, J=7.5 Hz, 1H), 7.83-7.70 (m, 2H), 7.70-7.56 (m, 2H), 7.66 (t, J=7.8 Hz, 2H), 7.31 (d, J=7.5 Hz,1H), 7.25 (t, J=7.5 Hz, 1H), 7.12 (t, J=7.5 Hz, 1H), 5.72 (d, J=8.7 Hz, 1H), 4.39-3.97 (m, 2H), 3.76 (dd, J=18.6, 8.7 Hz, 1H), 3.70-3.50 (m, 1H), 3.57 (s, 3H), 3.21-3.08 (m, 2H).

EXAMPLE 35 (31)

5-(4-(2-Chlorophenyl)piperazin-1-yl)carbonyl-4-methoxy-3-phenyisulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1976] 1921

[1977] TLC: Rf 0.78 (methylene chloride:methanol=10:1);

[1978] NMR (CDCl3+DMSO-d6): δ 7.94-7.86 (m, 1H), 7.77-7.66 (m, 2H), 7.64-7.50 (m, 4H), 7.44-7.16 (m, 2H), 7.10699 (m, 2H),5.38-5.27 (m, 1H), 4.26-4.00 (m, 2H), 3.95 and 3.78 (each s, total 3H), 3.90-3.65 (m, 2H),3.50-2.80 (m, 6H).

EXAMPLE 35 (32)

5-(4-(2-(2-Trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1979] 1922

[1980] TLC: Rf 0.51 (methylene chloride:methanol=10:1);

[1981] NMR (CDCl3): δ 7.93-7.86 (m, 1H), 7.74-7.43 (m, 7H), 7.40-7.30 (m, 3H), 5.31-5.20 (m, 1H), 4.24-3.64 (m, 7H), 3.34-3.10 (m, 2H), 3.06-2.90 (m, 2H), 2.70-2.30 (m, 6H).

EXAMPLE 35 (33)

4-(Pyridin-3-ylcarbonyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1982] 1923

[1983] Free Compound:

[1984] TLC: Rf 0.38 (ethyl acetate:methanol=9:1);

[1985] NMR (DMSO-d6): δ 9.31 (t, J=6.0 Hz, 1H), 9.05 (d, J=1.5 Hz, 1H), 8.72 (dd, J 5.0, 1.5 Hz, 1H), 8.23 (dt, J=8.0, 1.5 Hz. 1H); 7.87-7.63 (m, 8H), 7.52 (dd, J=8.0, 5.0 Hz, 1H), 6.05 (d, J=8.5 Hz, 1H), 5.01 (dd, J=16.0, 6.0 Hz, 1H), 4.78 (dd, J=16.0, 6.0 Hz, 1H), 4.02 (dd, J=15.3, 8.5 Hz, 1H), 3.86 (d, J=15.3 Hz, 1H).

[1986] Hydrochloride:

[1987] TLC: Rf 0.38 (ethyl acetate:methanol=9:1);

[1988] NMR (DMSO-d6): δ 9.63-9.59 (m, 1H), 9.20 (s, 1H), 8.86 (d, J=5.0 Hz, 1H), 8.57-8.54 (m, 1H), 7.87-7.63 (m, 9H), 6.11 (d, J=8.5 Hz, 1H), 5.02 (dd, J=15.8, 5.7 Hz, 1H), -4.80 (dd, J=15.8, 5.7 Hz, 1H), 4.00 (dd, J=15.5, 8.5 Hz, 1H), 3.86 (d, J=15.5 Hz, 1H).

EXAMPLE 35 (34)

4-(3-Pyrrol-1-yl)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1989] 1924

[1990] TLC: Rf 0.20 (ethyl acetate:hexane=1:1);

[1991] NMR (CDCl3): δ 7.75-7.35 (m, 6H), 7.24 (d, J=8 Hz, 1H), 6.93 (d, J=8 Hz, 1H), 6.68 (t, J=2 Hz, 2H), 6.15 (t, J=2 Hz, 2H), 5.21 (d, J=9 Hz, 1H), 4.53-4.00 (m, 2H), 4.10 (d, J=15 Hz, 1H), 4.00-3.65 (m, 2H), 3.73 (dd, J=9, 15 Hz, 1H), 2.19 (quint, J=5 Hz, 2H).

EXAMPLE 35 (35)

4-(Quinolin-2-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1992] 1925

[1993] Free Compound:

[1994] TLC: Rf 0.21 (benzene:ethyl acetate=2:1);

[1995] NMR (CDCl3): δ 8.42 (d, J=9 Hz, 1H), 8.03 (d, J=8 Hz, 2H), 7.90-7.20 (m, 11H), 5.80 (d, J=8 Hz, 1H), 5.31 (d, J=13 Hz, 1H), 5.09 (d, J=13 Hz, 1H), 4.24 (d, J=15 Hz, 1H), 4.02 (dd, J=8, 15 Hz, 1H). hydrochloride:

[1996] TLC: Rf 0.30 (hexane:ethyl acetate=1:2);

[1997] NMR (DMSO-d6): δ 8.64 (d, J=8.5 Hz, 1H), 8.20 (d, J=8.5 Hz, 1H), 8.13 (d, J=8.5 Hz, 1H), 7.92 (t-like, J=8.5 Hz, 1H), 7.81-7.65 (m, 5H), 7.48-7.31 (m, 5H), 5.91 (d, J=9.0 Hz, 1H), 5.42 (d, J=13.5 Hz, 1H), 5.21 (d, J=13.5 Hz, 1H), 4.22 (d, J=15.0 Hz, 1H), 4.02 (dd, J=9.0 Hz, 1H).

EXAMPLE 35 (36)

4-(2-(Pyrrol-1-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[1998] 1926

[1999] TLC: Rf 0.36 (hexane:ethyl acetate=1:2);

[2000] NMR (CDCl3+CD3OD): δ 7.85-7.58 (m, 3H), 7.58-7.42 (m, 3H), 7.28 (d, J=8 Hz, 1H), 6.92 (d, J=8 Hz, 1H), 6.74 (t, J=2 Hz, 2H), 6.18 (t, J=2 Hz, 2H), 5.16 (d, J=9 Hz, 1H), 4.30-4.05 (m, 5H), 3.73 (dd, J=9,15 Hz, 1H).

EXAMPLE 35 (37)

4-(2-(4-Methylthiazol-5-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2001] 1927

[2002] TLC: Rf 0.25 (ethyl acetate);

[2003] NMR (CD3OD): δ 9.88 (s, 1H), 7.80-7.40 (m, 6H), 7.26 (d, J=8 Hz, 1H), 7.25 (d, J=8Hz, 1H), 5.48 (d, J=9 Hz, 1H), 4.42-4.18 (m, 2H), 4.08 (d, J=15 Hz, 1H), 3.92 (dd, J=9,15 Hz, 1H), 3. 55-3.15 (m, 2H), 2.60 (s, 3H).

EXAMPLE 35 (38)

4-(3-(Pyridin-4-yl)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2004] 1928

Free Compound:

[2005] TLC: Rf 0.26 (ethyl acetate:methanol=10:1);

[2006] NMR (CDCl3): δ 8.53 (dd, J=1, 5 Hz, 2H), 7.78-7.35 (m. 6H), 7.25 (d, J=7 Hz, 1H), 7.17 (d, J=6 Hz, 2H), 6.95 (d, J=8 Hz, 1H), 5.17 (d, J=9 Hz, 1H), 4.14 (d, J=15 Hz, IH), 4.05-3.82 (m , 2H), 3.74 (dd, J=9, 15 Hz, 1H), 2.87 (t, J=6 Hz, 2H), 2.10 (quint, J=6 Hz, 2H).

[2007] Hydrochloride:

[2008] TLC: Rf 0.39 (ethyl acetate:methanol:ammonia water=100:10:1);

[2009] NMR (DMSO-d6): δ 8.83 (d, J=6 Hz, 2H), 7.90 (d, J=5 Hz, 2H), 7.85-7.52 (m, 6H), 7.34 (d, J=8 Hz, 1H), 7.24 (d, J=8 Hz, 1H), 5.64 (d, J=9 Hz, 1H), 4.18 (d, J=15 Hz, 1H), 4.00 (dd, J=9,15 Hz, 1H), 3.10-2.80 (m, 2H), 2.10-1.60 (m, 2H).

EXAMPLE 35 (39)

4-(1-t-Butoxycarbonylpiperidin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2010] 1929

[2011] TLC: Rf 0.23 (hexane:ethyl acetate=1:1);

[2012] NMR (CD3OD): δ 7.95-7.45 (m, 6H), 7.40-7.05 (m, 2H), 5.53 (d, J=9 Hz, 1H), 4.15 (d, J=15 Hz, 1H), 3.92 (dd, J=9,15 Hz, 1H), 4.05-3.55 (m, 4H), 3.20-2.40 (m, 2H), 2.00-1.20 (m, 5H), 1.47 and 1.44 (each s, 9H).

EXAMPLE 35 (40)

4-(2-(Pyrrolidin-1-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2013] 1930

Free Compound:

[2014] TLC: Rf 0.17 (chloroform:methanol=10:1);

[2015] NMR (CDCl3): δ 7.85-7.68 (m, 2H), 7.68-7.35 (m, 4H), 7.28 (d, J=8 Hz, 1H), 6.97 (d, J=8 Hz, 1H), 5.30 (d, J=9 Hz, 1H), 4.23 (d, J=15 Hz, 1H), 4.15-3.95 (m, 1H), 3.95-3.70 (m, 1H), 3.74 (dd, J=9, 15 Hz,1H), 2.78 (t, J=6 Hz, 2H), 2.70-2.45 (m, 4H), 1.95-1.60 (m, 4H).

[2016] Hydrochloride:

[2017] TLC: Rf 0.36 (ethyl acetate:acetic acid:water=3:1:1);

[2018] NMR (CDCl3+CD3OD): δ 7.98-7.82 (m,2H), 7.80-7.45 (m, 4H), 7.34 (d, J=8 Hz, 1H), 7.26 (d, J=8 Hz, 1H), 6.20-6.05 (m, 1H), 4.75-4.50 (m, 1H), 4.50-4.25 (m, 1H), 4.10-3.85 (m, 2H), 3.85-3.45 (m, 4H), 3.30-2.90 (m, 2H), 2.40-2.00 (m, 4H).

EXAMPLE 35 (41)

4-(2-(Piperidin-1-yl) ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2019] 1931

[2020] Free Compound:

[2021] TLC: Rf 0.24 (chloroform:methanol=10:1);

[2022] NMR (CDCl3): δ 7.85-7.67 (m, 2H), 7.67-7.36 (m, 4H), 7.27 (d, J=8 Hz, 1H), 6.97 (d, J=8 Hz, 1H), 5.29 (d, J=9 Hz, 1H), 4.25 (d, J=15 Hz, 1H), 4.18-3.92 (m, 1H), 3.92-3.65 (m, 1H), 3.74 (dd, J=9, 15 Hz, 1H), 2.62 (t, J=6 Hz, 2H), 2.46 (t, J=6 Hz, 4H), 1.90-1.35 (m, 6H).

[2023] Hydrochloride:

[2024] TLC: Rf 0.40 (ethyl acetate:acetic acid:water=3:1:1);

[2025] NMR (CDCl3+CD3OD): δ 7.95-7.75 (m, 2H), 7.75-7.45 (m, 4H), 7.32 (d, J=8 Hz, 1H), 7.30 (d, J=8 Hz, 1H), 6.05-5.85 (m, 1H), 4.75-4.38 (m,2H), 3.95-3.42 (m, 6H), 3.15-2.85 (m, 2H), 2.35-1.35 (m, 6H).

EXAMPLE 35 (42)

4-(2-(2-Acetyloxyethoxy)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2026] 1932

[2027] TLC: Rf 0.17 (ethyl acetate:hexane=2:1);

[2028] NMR (CDCl3): δ 7.82-7.70 (m, 2H), 7.65-7.35 (m, 4H), 7.27 (d, J=8 Hz, 1H), 7.00 (d, J=8 Hz, 1H), 5.30 (d, J=9 Hz, 1H), 4.32-4.05 (m, 4H), 4.05-3.88 (m, 1H), 3.84-3.75 (m, 5H), 2.05 (s, 3H).

EXAMPLE 35 (43)

4-(2-(4-Benzylpiperazin-1-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2029] 1933

[2030] Free Compound:

[2031] TLC: Rf 0.42 (chloroform:methanol=5:1);

[2032] NMR (CDCl3): δ 7.80-7.68 (m, 2H), 7.68-7.37 (m, 4H), 7.37-7.18 (m, 6H), 6.96 (d, J=8 Hz, 1H), 5.27 (d, J=9 Hz, 1H), 4.22 (d, J=15 Hz, 1H), 4.15-3.94 (m, 1H), 3.94-3.70 (m, 1H), 3.72 (dd , J=9, 15 Hz, 1H), 3.52 (s, 2H), 2.68 (t, J=6 Hz, 2H), 2.63-2.35 (m, 8H).

[2033] 2hydrochloride:

[2034] TLC: Rf 0.28 (ethyl acetate:acetic acid:water=3:1:1);

[2035] NMR (CD3OD): δ 7.907-7.22 (m, 13H), 6.13-6.00 (m, 1H), 4.68-4.35 (m, 2H), 4.46 (S, 2H), 4.10-3.40 (m, 12H).

EXAMPLE 35 (44)

4-Diethylcarbamoylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2036] 1934

[2037] TLC: Rf 0.40 (ethyl acetate);

[2038] NMR (CDCl3): δ 7.83-7.77 (m, 2H), 7.68-7.59 (m, 1H), 7.56-7.45 (m, 3H), 7.32 (d, J=7.6 Hz, 1H), 7.01 (d, J=7.6 Hz, 1H), 5.44 (d, J=8.8Hz, 1H), 4.59 (d, J=14.5 Hz, 1H), 4.51 (d, J=14.5 Hz, 1H), 4.15 (d, J=15.0 Hz, 1H), 3.74 (dd, J=15.0, 8.8 Hz, 1H), 3.39 (q, J=7.0 Hz, 2H), 3.30 (q, J=7.0 Hz, 2H), 1.22 (t, J=7.0 Hz, 3H), 1.14 (t, J=7.0 Hz, 3H).

EXAMPLE 35 (45)

4-Cyanomethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2039] 1935

[2040] TLC: Rf 0.27 (hexane:ethyl acetate=1:2);

[2041] NMR (DMSO-d6): δ 7.82-7.72 (m, 4H), 7.68-7.60 (m, 2H), 7.50 (d, J=8.0 Hz, 1H), 7.41 (d, J=8.0 Hz, 1H), 5.60 (dd, J=9.0, 1.2 Hz, 1H), 5.04 (d, J=16.0 Hz, 1H), 4.90 (d, J=16.0 Hz, 1H), 4.20 (dd, J=15.2, 1.2 Hz, 1H), 4.00 (dd, J=15.2, 9.0 Hz, 1H).

EXAMPLE 35 (46)

5-(Pyridin-3-yloxy) methyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2042] 1936

[2043] Free Compound:

[2044] TLC: Rf 0.27 (ethyl acetate);

[2045] NMR (CDCl3): δ 8.37-8.36 (m, 1H), 8.31-8.29 (m, 1H), 7.76-7.71 (m, 3H), 7.66-7.61 (m, 1H), 7.49-7.43 (m, 3H), 7.27-7.25 (m, 2H), 5.25 (dd, J=9.5,1.0 Hz, 1H), 5.16 (d, J=12.5 Hz, 1H), 5.12 (d, J=12.5 Hz, 1H), 4.15 (dd, J=15.0,1.0 Hz, 1H), 3.90 (s, 3H), 3.81 (dd, J=15.0, 9.5 Hz, 1H)

[2046] Hydrochloride:

[2047] TLC: Rf 0.27 (ethyl acetate);

[2048] NMR (DMSO-d6): δ 8.76 (d, J=2.5 Hz, 1H), 8.52 (d, J=5.0 Hz, 1H), 8.15 (dd, J=8.5, 2.5 Hz, 1H), 7.93-7.74 (m, 5H), 7.65-7.60 (m, 3H), 5.78 (d, J=8.5 Hz, 1H), 5.35 (s, 2H), 4.17 (d, J=15.0 Hz, 1H), 4.06 (dd, J=15.0, 8.5 Hz, 1H), 3.69 (s, 3H).

EXAMPLE 35 (47)

5-(2-(t-Butoxycarbonyl amino)ethyl)oxy-4-nitro-3-phenylsufonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2049] 1937

[2050] TLC: Rf 0.34 (hexane:ethyl acetate=1:2);

[2051] NMR (CDCl3): δ 7.86-7.70 (m, 4H), 7.63-7.54 (m, 2H), 7.41 (d, J=8.8 Hz, 1H), 5.69 (dd, J=9.0, 1.8 Hz, 1H), 5.07 (br, 1H), 4.38-4.22 (m, 2H), 3.90 (dd, J=15.0, 1.8 Hz, 1H), 3.75 (dd, J=15.0, 9.0 Hz, 1H), 3.68-3.52 (m, 2H), 1.46 (s, 9H).

EXAMPLE 35 (48)

5-((2E)-3-Ethoxycarbonyl-2-propenyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2052] 1938

[2053] TLC: Rf 0.41 (hexane:ethyl acetate=1:1);

[2054] NMR (CDCl3): δ 5 7.72-7.65 (m, 3H), 7.62-7.46 (m, 4H), 7.15 (dd, J=8.7,2.1 Hz,1H), 7.08 (dt, J=15.6, 4.2 Hz, 1H), 6.20 (dt, J=15.6, 2.1 Hz, 1H), 5.01 (dd, J=8.7, 4.8 Hz, 1H), 4.87-4.81 (m, 2H), 4.24 (q, J=7.2 Hz, 2H), 3.77 (dd, J=14.7,4.8 Hz, 1H), 3.70 (dd, J=14.7, 8.7 Hz, 1H), 1.31 (t, J=7.2 Hz, 3H).

EXAMPLE 35 (49)

4-(2,4-Dimethoxyphenylmethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2055] 1939

[2056] Free Compound:

[2057] TLC: Rf 0.35 (ethyl acetate);

[2058] NMR (CDCl3): δ 7.69 (dd, J=6.9, 1.5 Hz, 1H), 7.64-7.50 (m, 5H), 7.46-7.41 (m, 2H), 7.01 (d, J=8.0 Hz, 1H), 6.45 (d, J=2.5 Hz,1H), 6.43 (dd, J=8.0,2.5 Hz,1H), 6.05 (dd, J=9.3, 1.2 Hz, 1H), 4.51 (d, J=14.1 Hz, 1H), 3.91 (d, J=14.1 Hz, 1H), 3.85 (dd, J=15.0, 1.2 Hz, 1H), 3.81 (s, 3H), 3.78 (s, 3H), 3.73 (d, J=13.0 Hz, 1H), 3.66 (d, J=13.0 Hz, 1H), 3.65 (dd, J=15.0, 9.3 Hz, 1H).

[2059] Hydrochloride:

[2060] TLC: Rf 0.35 (ethyl acetate);

[2061] NMR (DMSO-d6): δ 9.40 (br, 2H), 8.20-8.11 (m, 1H), 7.86-7.59 (m, 7H), 7.42 (d, J 8.4 Hz, 1H), 6.61-6.56 (m, 2H), 6.09 (dd, J=6.8, 3.0 Hz, 1H), 4.65 (d, J=13.8 Hz, 1H), 4.38 (d, J=13.8 Hz, 1H), 4.22-4.06 (m, 2H), 3.88-3.85 (m, 2H), 3.80 (s, 3H), 3.79 (s, 3H).

EXAMPLE 35 (50)

4-(Pyridin-3-ylmethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene 2hydrochloride

[2062] 1940

[2063] TLC: Rf 0.44 (chloroform:methanol=9:1);

[2064] NMR (CD3OD): δ 9.21 (s, 1H), 8.95 (d, J=5.6 Hz, 1H), 8.92-8.84 (m, 1H), 8.22 (dd, J=6.6, 2.2 Hz, 1H), 8.16 (dd, J=8.0, 5.6 Hz, 1H), 7.93-7.74 (m, 5H), 7.68-7.58 (m, 2H), 6.20 (dd, J=8.6, 1.6 Hz, 1H), 4.96 (d, J=13.2 Hz, 1H), 4.83-4.70 (m, 3H), 3.92 (dd, J=15.4, 8.6 Hz, 1H), 3.77 (dd, J=15.4, 1.6 Hz, 1H).

EXAMPLE 35 (51)

4-(2-Dimethylaminoethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene-2hydrochloride

[2065] 1941

[2066] TLC: Rf 0.51 (chloroform:methanol:triethylamine=9:1:1);

[2067] NMR (DMSO-d6): δ 10.85-10.50 (br, 1H), 10.10-9.75 (br, 1H), 9.72-9.40 (br, 1H), 8.22 (dd, J=5.4, 3.0 Hz, 1H), 7.90-7.85 (m, 2H), 7.82-7.75 (m, 3H), 7.67-7.59 (m, 2H), 6.47 (t like, J=1.5 Hz, 1H), 4.72 (brd, J=12.0 Hz, 1H), 4.51 (brd, J=12.0 Hz, 1H), 3.91-3.84 (m, 2H), 3.70-3.30 (m, 4H), 2.85 (s, 6H).

EXAMPLE 35 (52)

4-(N,N-Bis(2-hydroxyethyl)amino)methyl-3-phenylsulfonyl-2,3-dlhydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2068] 1942

[2069] TLC: Rf 0.53 (chloroform:methanol=9:1);

[2070] NMR (DMSO-d6): δ 10.15-9.90 (br, 1H), 8.24 (d, J=6.6 Hz, 1H), 7.95-7.72 (m, 5H), 7.69-7.58 (m, 2H), 6.16 (d, J=8.7 Hz, 1H), 5.80-5.10 (br, 2H), 5.11 (brd, J=13.8 Hz, 1H), 4.70 (brd, J=13.8 Hz, 1H), 4.02 (dd, J=15.0, 8.7 Hz, 1H), 3.94-3.70 (m, 4H), 3.82 (d, J=15.0 Hz, 1H), 3.47-3.18 (m, 3H), 3.12-2.92 (m, 1H).

EXAMPLE 35 (53)

4-(2-(2-Hydroxyethoxy)ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2071] 1943

[2072] TLC: Rf 0.46 (methylene chloride:methanol=9:1);

[2073] NMR (DMSO-d6): δ 9.40-9.10 (br, 2H), 8.16 (dd, J=6.3, 2.4 Hz, 1H), 7.91-7.75 (m, 5H), 7.68-7.59 (m, 2H), 6.29 (dd, J=7.5, 2.4 Hz, 1H), 4.90-4.30 (br, 1H), 4.75-4.63 (m, 1H), 4.50-4.35 (m, 1H), 3.90 (dd, J=15 .6, 7.5 Hz, 1H), 3.84 (dd, J=15.6, 2.4 Hz, 1H), 3.74 (t, J=5.1 Hz, 2H), 3.58-3.47 (m, 4H), 3.28-3 15 (m, 2H).

EXAMPLE 35 (54)

4-(4-Benzylpiperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2074] 1944

[2075] Free Compound:

[2076] TLC: Rf 0.29 (chloroform:methanol=19:1);

[2077] NMR (CDCl3): δ 7.68-7.57 (m, 4H), 7.56-7.50 (m, 2H), 7.50-7.42 (m, 2H), 7.36-7.20 (m, 5H), 6.33 (d, J=9.0 Hz, 1H), 4.69 (d, J=14.1 Hz, 1H), 3.90 (d, J=15.0 Hz, 1H), 3.72 (dd, J=15.0, 9.0 Hz, 1H), 3.51 (s, 2H), 3.41 (d, J=14.1 Hz,1H), 2.70-2.25 (m, 8H).

[2078] 2hydrochloride:

[2079] TLC: Rf 0.29 (chloroform:methanol=19:1); NMR (DMSO-d6): δ 8.30-7.95 (br, 1H), 7.93-7.72 (m, 5H), 7.70-7.55 (m, 4H), 7.50-7.40 (m, 3H), 6.65-6.20 (br, 1H), 5.40-4.20 (br, 4H), 4.50-4.10 (br, 2H), 3.98 (dd, J=15.6, 9.0 Hz, 1H), 3.84 (d, J=15.6 Hz, 1H), 3.70-2.80 (m, 6H).

EXAMPLE 35 (55)

4-(4-(Pyridin-2-yl)piperazi n-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2080] 1945

[2081] Free Compound:

[2082] TLC: Rf 0.43 (chloroform:methanol 19:1);

[2083] NMR (CDCl3): δ 8.23-8.16 (m, 1H), 7.71-7.52 (m, 6H), 7.52-7.42 (m, 3H), 6.68-6.62 (m, 2H), 6.30 (d, J=9.0 Hz, 1H), 4.76 (d, J=14.1 Hz, 1H), 3.89 (d, J=15.0 Hz, 1H), 3.73 (dd, J=15.0, 9.0 Hz, 1H), 3.62-3. 45 (m, 4H), 3.49 (d, J=14.1 Hz, 1H), 2.73-2.61 (m, 2H), 2.58-2.44 (m, 2H). 3hydrochloride:

[2084] TLC: Rf 0.43 (chloroform:methanol=19:1);

[2085] NMR (DMSO-d6): δ 12.05-11.70 (br, 1H), 8.35 (d, J=6.3 Hz, 1H), 8.15-8.09 (m, 1H), 7.96-7.84 (m, 3H), 7.83-7.75 (m, 3H), 7.68-7.58 (m, 2H), 7.24 (d, J=8.7 Hz,1H), 6.93 (t, J=6.3 Hz, 1H), 6.46 (d, J=8.7 Hz,1H), 4.87 (d, J=13.8 Hz, 1H), 4.62 (d, J=13.8 Hz, 1H), 4.55-4.30 (m, 2H), 4.00 (dd, J=15.0, 8.7 Hz, 1H), 3.83 (d, J=15.0 Hz, 1H), 3.72-3.50 (m, 2H), 3.50-3.15 (m, 4H).

EXAMPLE 35 (56)

4-(4-Ethoxycarbonylpiperazin-1-yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2086] 1946

[2087] Free Compound:

[2088] TLC: Rf 0.45 (chloroform:methanol 19:1);

[2089] NMR (CDCl3): δ 7.69-7.52 (m, 6H), 7.51-7.41 (m, 2H), 6.16 (d, J=9.0 Hz, 1H), 4.71 (d, J=14.4 Hz, 1H), 4.15 (q, J=7.2 Hz, 2H), 3.91 (d, J=15.0 Hz, 1H), 3.74 (dd, J=15.0, 9.0 Hz, 1H), 3.54-3.39 (m, 5H), 2.55-2.46 (m, 2H), 2.41-2.29 (m, 2H), 1.27 (t, J=7.2 Hz, 3H).

[2090] Hydrochloride:

[2091] TLC: Rf 0.45 (chloroform:methanol=19:1);

[2092] NMR (DMSO-d6): δ 11.60-11.30 (br, 1H), 8.40-8.20 (br, 1H), 8.00-7.74 (m, 5H), 7.68-7.58 (m, 2H), 6.31 (brd, J=8.1 Hz, 1H), 4.98-4.70 (m, 1H), 4.70-4.52 (m, 1H), 4.20-3.89 (m, 2H), 4.07 (q, J=7.2 Hz, 2H), 3.82 (d, J=15.3 Hz, 1H), 3.77-3.60 (m, 1H), 3.52-2.90 (m, 6H), 1.18 (t, J=7.2 Hz, 3H).

EXAMPLE 35 (57)

4-(4-(2-Hydroxyethyl)piperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2093] 1947

[2094] Free Compound:

[2095] TLC: Rf 0.31 (chloroform:methanol=9:1);

[2096] NMR (CDCl3): δ 7.70-7.50 (m, 6H), 7.50-7.41 (m, 2H), 6.29 (d, J=9.0 Hz, 1H), 4.72 (d, J=14.1 Hz, 1H), 3.91 (d, J=15.0 Hz, 1H), 3.73 (dd, J=15.0, 9.0 Hz, 1H), 3.63 (t, J=5.1 Hz, 2H), 3.43 (d, J=14.1 Hz, 1H), 2.80-2.30 (m, 10H).

[2097] 2hydrochloride:

[2098] TLC. Rf 0.31 (chloroform:methanol=9:1);

[2099] NMR (DMSO-d6): δ 11.50-10.60 (br, 1H), 8.30-8.00 (br, 1H), 7.88-7.73 (m, 5H), 7.67-7.58 (m, 2H), 6.60-6.30 (br, 1H), 5.80-4.92 (br, 2H), 4.92-4.10 (br, 1H), 3.99 (dd, J=15.0, 8.7 Hz, 1H), 3.86 (d, J=15.0 Hz, 1H), 3.81-3.74 (m, 2H), 3.73-2.80 (m, 10H).

EXAMPLE 35 (58)

4-(4-(Pyridin-4-yl)piperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2100] 1948

[2101] free compound:

[2102] TLC: Rf 0.36 (chloroform:methanol=9:1);

[2103] NMR (DMSO-d6): δ 8.14 (d, J=6.6 Hz, 2H), 7.88-7.81 (m, 1H), 7.81-7.74 (m, 3H), 7.74-7.68 (m, 2H), 7.67-7.59 (m, 2H), 6.78 (d, J=6.6 Hz, 2H), 6.21 (d, J=9.0 Hz, 1H), 4.16 (d, J=14.4 Hz, 1H), 4.05 (dd, J=15.0, 9.0 Hz, 1H), 3.86 (d, J=15.0 Hz, 1H), 3.57 (d, J=14.4 Hz, 1H), 3.42-3.18 (m, 4H), 2.43 (t, J=4.8 Hz, 4H). 3hydrochloride:

[2104] TLC: Rf 0.36 (chloroform:methanol=9:1);

[2105] NMR (DMSO-d6): δ 14.20-13.80 (br, 1H), 12.30-11.90 (br, 1H), 8.46-8.20 (br, 1H), 8.35 (d, J=6.9 Hz, 2H), 7.98-7.82 (m, 2H), 7.82-7.74 (m, 3H), 7.67-7.57 (m, 2H), 7.25 (d, J=6.9 Hz, 2H), 6.48 (brd, J=8.7 Hz,1H), 5.05-4.75 (m, 1H), 4.75-4.52 (m,1H), 4.52-4.15 (m, 2H), 3.98 (dd, J=15.3, 8.7 Hz, 1H), 3.95-3.55 (m, 6H), 3.84 (d, J=15.3 Hz, 1H).

EXAMPLE 35 (59)

4-Benzylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2106] 1949

[2107] Free Compound:

[2108] TLC: Rf 0.46 (ethyl acetate);

[2109] NMR (CDCl3): δ 7.74 (dd, J=7.2, 1.5 Hz, 1H), 7.65-7.51 (m, 5H), 7.45-7.40 (m, 2H), 7.36-7.25 (m, 5H), 5.84 (dd, J=9.3, 1.0 Hz, 1H), 4.49 (d, J=14.1 Hz, 1H), 3.98 (d, J 14.1 Hz, 1H), 3.85 (d, J=12.7 Hz, 1H), 3.84 (dd, J=15.0, 1.0 Hz, 1H), 3.77 (d, J=12.7, 1H), 3.65 (dd, J=15.0, 9.3 Hz, 1H).

[2110] Hydrochloride:

[2111] TLC: Rf 0.49 (ethyl acetate:triethylamine=6:0.5);

[2112] NMR (DMSO-d6): δ 9.87 (brs, 1H), 9.57 (brs, 1H), 8.16 (d, J=6.6 Hz, 1H), 7.90-7.75 (m, 3H), 7.75-7.57 (m, 6H), 7.50-7.41 (m, 3H), 6.33-6.25 (m, 1H), 4.67 (d, J=13.5 Hz, 1H), 4.40 (d, J=13.5 Hz, 1H), 4.30 (s, 2H), 3.93-3.80 (m, 2H).

EXAMPLE 35 (60)

4-(1-benzylpiperidin-4-yl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2113] 1950

[2114] Free Compound:

[2115] TLC: Rf 0.30 (ethyl acetate:methanol=2:1);

[2116] NMR (CDCl3): δ 7.70 (dd, J=7.3, 1.3 Hz, 1H), 7.65-7.41 (m, 7H), 7.32-7.24 (m, 5H), 6.09 (dd, J=9.3, 1.0 Hz, 1H), 4.61 (d, J=14.0 Hz, 1H), 3.98 (d, J=14.0 Hz, 1H), 3.87 (dd, J=15.0, 1.0 Hz, 1H), 3.72 (dd, J=15.0, 9.3 Hz, 1H), 3.50 (s, 2H), 2.90-2.81 (m, 2H), 2.58-2.51 (m, 1H), 2.09-1.96 (m, 3H), 1.83-1.79 (m, 1H), 1.52-1.38 (m, 2H).

[2117] 2hydrochloride:

[2118] TLC: Rf 0.30 (ethyl acetate:methanol=2:1);

[2119] NMR (CD3OD): δ 8.16-8.12 (m, 1H), 7.91-7.74 (m, 5H), 7.65-7.49 (m, 7H), 6.06 (dd, J=8.4, 1.8 Hz, 1H), 4.84-4.68 (m, 2H), 4.36 (br, 2H), 3.90 (dd, J=15.4, 8.4 Hz, 1H), 3.77 (dd, J=15.4, 1.8 Hz, 1H), 3.80-3.60 (m, 3H), 3.30-3.15 (m, 2H), 2.58-2.43 (m, 2H), 2.35-2.13 (m, 2H).

EXAMPLE 35 (61)

4-(Morpholin-4-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2120] 1951

[2121] Free Compound:

[2122] TLC: Rf 0.34 (hexane:ethyl acetate=1:2);

[2123] NMR (CDCl3): δ 7.68-7.51 (m, 6H), 7.48-7.42 (m, 2H), 6.21 (dd, J=9.3, 0.9 Hz, 1H), 4.68 (d, J=14.3 Hz, 1H), 3.91 (dd, J=15.0, 0.9 Hz, 1H), 3.74 (dd, J=15.0, 9.3 Hz, 1H), 3.74-3.64 (m, 4H), 3.45 (d, J=14.3 Hz, 1H), 2.58-2.52 (m, 2H), 2.40-2.33 (m, 2H).

[2124] Hydrochloride:

[2125] TLC: Rf 0.34 (hexane:ethyl acetate=1:2);

[2126] NMR (DMSO-d6): δ 11.48 (br, 1H), 8.31 (d, J=7.2 Hz, 1H), 7.94-7.79 (m, 5H), 7.68-7.62 (m, 2H), 6.44 (d, J=8.1 Hz, 1H), 4.85-4.79 (m, 1H), 4.62-4.57 (m, 1H), 4.05-3.81 (m, 6H), 3.50-3.13 (m, 4H).

EXAMPLE 35 (62)

4-Ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2127] 1952

[2128] TLC: Rf 0.18 (methylene chloride);

[2129] NMR (CDCl3): δ 8.24 (dd, J=7.8 Hz, 1.5 Hz, 1H), 7.86 (dd, J=7.8 Hz, 1.5 Hz, 1H), 7.75 (t, J=7.8 Hz, 1H), 7.71-7.64 (m, 3H), 7.56-7.47 (m, 2H), 6.19 (dd, J=9.3 Hz, 1.5 Hz, 1H), 4.53-4.40 (m, 2H), 3.94 (dd, J=15.0 Hz, 1.5 Hz, 1H), 3.77 (dd, J=15.0 Hz, 9.3 Hz, 1H), 1.47 (t, J=7.2 Hz, 3H).

EXAMPLE 35 (63)

4-Benzyloxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2130] 1953

[2131] TLC: Rf 0.37 (chloroform:ethyl acetate=19:1);

[2132] NMR (CDCl3): δ 8.26 (dd, J=7.5, 1.2 Hz, 1H), 7.85 (dd, J=7.8, 1.2 Hz, 1H), 7.78-7.70 (m, 1H), 7.69-7.60 (m, 3H), 7.55-7.47 (m, 4H), 7.47-7.35 (m, 3H), 6.13 (dd, J=9.3, 1.2 Hz, 1H), 5.45 (d, J=12.3 Hz, 1H), 5.40 (d, J=12.3 Hz, 1H), 3.91 (dd, J=15.0, 1.2 Hz, 1H), 3.73 (dd, J=15.0, 9.3 Hz, 1H).

EXAMPLE 35 (64)

4-(Pyridin-3-yl)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2133] 1954

[2134] TLC: Rf 0.55 (chloroform:methanol=9:1);

[2135] NMR (DMSO-d6): δ 9.11 (s, 1H), 8.86 (d, J=5.4 Hz, 1H), 8.57 (d, J=5.4 Hz, 1H), 7.99-7.84 (m, 4H), 7.73-7.64 (m, 1H), 7.53-7.43 (m, 2H), 7.42-7.35 (m, 2H), 5.99 (dd, J=7.2, 3.0 Hz, 1H), 4.07 (dd, J=15.3, 7.2 Hz, 1H), 4.01 (dd, J=15.3, 3.0 Hz, 1H).

EXAMPLE 35 (65)

6-(Pyridin-3-yl)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2136] 1955

[2137] TLC: Rf 0 60 (chloroform:methanol 9:1);

[2138] NMR (DMSO-d6): δ 9.29 (d, J=2.1 Hz, 1H), 8.85 (d, J=5.1 Hz, 1H), 8.76 (d, J=7.8 Hz, 1H), 8.37 (s, 1H), 8.29 (dd, J=8.4, 2.1 Hz, 1H), 7.96 (dd, J=8.4, 5.1 Hz, 1H), 7.89-7.75 (m, 4H), 7.71-7.60 (m, 2H), 5.93 (dd, J=9.3, 3.0 Hz, 1H), 4.06 (dd, J=15.0, 9.3 Hz, 1H), 3.85 (dd, J=15.0, 3.0 Hz, 1H).

EXAMPLE 35 (66)

4-(4,4-Dimethyl-4,5-dihydroxazol-2-yl)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2139] 1956

[2140] TLC: Rf 0.22 (ethyl acetate:hexane=1:1);

[2141] NMR (CDCl3): δ 8.23 (d, J=6.0 Hz, 1H), 7.73-7.67 (m, 2H), 7.67-7.54 (m, 3H), 7.48-7.40 (m, 2H), 6.36 (dd, J=9.0 Hz, 1.8 Hz, 1H), 4.26 (d, J=7.5 Hz, 1H), 4.22 (d, J=7.5 Hz, 1H), 3.89 (dd, J=15.0 Hz, 1.8 Hz, 1H), 3.78 (dd, J=15.0 Hz, 9.0 Hz, 1H), 1.50 (s, 3H), 1.45 (s, 3H).

EXAMPLE 35 (67)

6-Bromo-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2142] 1957

[2143] TLC: Rf 0.24 (methylene chloride);

[2144] NMR (DMSO-d6): δ 8.13 (d, J=2.0 Hz, 1H), 8.02 (dd, J=8.5, 2.0 Hz, 1H), 7.83-7.76 (m, 3H), 7.67-7.60 (m, 3H), 5.79 (dd, J=9.5, 3.0 Hz, 1H), 4.05 (dd, J=15.5, 9.5 Hz, 1H), 3.85 (dd, J=15.5, 3.0 Hz, 1H).

EXAMPLE 35 (68) 6-Amino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2145] 1958

[2146] TLC: Rf 0.34 (hexane:ethyl acetate=1:2);

[2147] NMR (DMSO-d6): δ 7.79-7.71 (m, 3H), 7.64-7.56 (m, 2H), 7.28 (d, J=8.5 Hz, 1H), 6.89 (dd, J=8.5, 2.2 Hz, 1H), 6.68 (d, J=2.2 Hz, 1H), 6.00 (s, 2H), 5.47 (dd, J=9.2,3.0 Hz, 1H), 3.89 (dd, J=15.2, 9.2 Hz, 1H), 3.64 (dd, J=15.2, 3.0 Hz, 1H).

EXAMPLES 36˜36 (3)

[2148] By the same procedure as described in Example 28 using carboxylic acid corresponding to 4-carboxy-1,1-dioxidebenzo[b]thiophene and amine corresponding to (pyridin-3-ylmethyl)amine, the following compounds of the present invention were obtained.

EXAMPLE 36

5-Methylcarbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2149] 1959

[2150] TLC: Rf 0.38 (methanol:ethyl acetate=5:95);

[2151] NMR(DMSO-d6): δ 8.40 (d, J=4.8 Hz, 1H), 7.75 (d, J=7.0 Hz, 1H), 7.65 (d, J=7.8 Hz, 1H), 7.59 (d, J=7.8 Hz, 1H), 7.44 (d, J=7.0 Hz, 1H), 3.89 (s, 3H), 2.78 (d, J=4.8 Hz, 3H).

EXAMPLE 36 (1)

4-Dimethylcarbamoyl-1,1-dioxidebenzo[b]thiophene

[2152] 1960

[2153] TLC: Rf 0.34 (methanol:ethyl acetate=5:95);

[2154] NMR(CDCl3): δ 7.76 (dd, J=7.0 Hz, 1.4 Hz, 1H), 7.58 (t, J=7.0 Hz, 1H), 7.51 (dd, J=7.0 Hz, 1.4 Hz, 1H), 7.33 (d, J=6.8 Hz, 1H), 6.78 (d, J=6.8 Hz, 1H), 3.17 (s, 3H), 3.00 (s, 3H).

EXAMPLE 36 (2)

4-Carbamoyl-1,1-dioxidebenzo[b]thiophene

[2155] 1961

[2156] TLC: Rf 0.50 (methanol:ethyl acetate=5:95);

[2157] NMR(DMSO-d6): δ 8.22 (brs, 1H), 7.96 (d, J=7.2 Hz, 1H), 7.88 (d, J=8.0 Hz, 1H), 7.78 (brs, 1H), 7.67 (t, J=8.0 Hz, 1H), 7.55 (d, J=8.0 Hz, 1H), 7.43 (d, J=7.2 Hz, 1H).

EXAMPLE 36 (3)

4-(Furan-2-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2158] 1962

[2159] TLC: Rf 0.36 (ethyl acetate:hexane 1;1); NMR (CDCl3+DMSO-d6): δ 7.96 (dd, J=7.2, 0.9 Hz, 1H), 7.81-7.76 (m, 2H), 7.56 (t, J=7.8 Hz, 1H), 7.51 (t, J=5.7 Hz, 1H), 7.40-7.38 (m, 1H), 6.78 (d, J=7.2 Hz, 1H), 6.37-6.30 (m, 2H), 4.62 (d, J=5.7 Hz, 2H).

EXAMPLES 37˜37 (6)

[2160] By the same procedure as described in Example 18 using an alcohol derivative corresponding to the compound prepared in Example 9 (12) and a halogenated compound corresponding to 4-nitrobenzylbromide, or by the same procedure as described in Example 29 using an alcohol derivative corresponding to 4-hydroxy-1,1-dioxidebenzo[b]thiophene and an alcohol derivative corresponding to 1-(3-hydroxypropyl)pyrrole, the following compounds of the present invention were obtained.

EXAMPLE 37

4-(2-(Pyridin-4-yl)ethyl) oxy-1,1-dioxidebenzo[b]thiophene

[2161] 1963

[2162] TLC: Rf 0.23 (hexane:ethyl acetate=1:3);

[2163] NMR (CDCl3): δ 8.56 (d, J=6.0 Hz, 2H), 7.46 (t, J=8.0 Hz, 1H), 7.31 (d, J=7.2 Hz, 1H), 7.29 (d, J=8.0 Hz, 1H), 7.21 (d, J=6.0 Hz, 2H), 7.04 (d, J=8.0 Hz, 1H), 6.60 (d, J=7.2 Hz, 1H), 4.33 (t, J=6.5 Hz, 2H), 3.14 (t, J=6.5 Hz, 2H).

EXAMPLE 37 (1)

4-(2-(Pyridin-3-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2164] 1964

[2165] TLC: Rf 0.38 (ethyl acetate);

[2166] NMR(CDCl3): δ 8.56 (d, J=1.8 Hz, 1H), 8.52 (dd, J=4.8, 1.8 Hz, 1H), 7.60 (d, J=8.2 Hz, 1H), 7.45 (t, J=7.6 Hz, 1H), 7.35 (d, J=7.6 Hz, 1H), 7.28 (dd, J=7.0 Hz, 1H), 7.26 (d, J=7.6 Hz, 1H), 7.03 (d, J=8.2 Hz, 1H), 6.60 (d, J=7.0 Hz, 1H), 4.30 (t, J=6.4 Hz, 2H), 3.15 (t, J=6.4 Hz, 2H).

EXAMPLE 37(2)

4-Ethoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene

[2167] 1965

[2168] TLC: Rf 0.38 (hexane:ethyl acetate=1:1);

[2169] NMR (CDCl3): δ 7.53 (d, J=7.2 Hz, 1H), 7.47 (t, J=8.0 Hz, 1H), 7.34 (d, J=8.0 Hz, 1H), 6.94 (d, J=8.0 Hz, 1H), 6.65 (d, J=7.2 Hz, 1H), 4.72 (s, 2H), 4.27 (q, J=7.0 Hz, 2H), 1.30 (t, J=7.0 Hz, 3H).

EXAMPLE 37 (3)

6-Ethoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene

[2170] 1966

[2171] TLC: Rf 0.30 (hexane:ethyl acetate=1:1);

[2172] NMR (CDCl3): “ 7.28 (d, J=8.4 Hz, 1H), 7.24 (d, J=2.6 Hz,1H), 7.17 (d, J=7.0 Hz, 1H), 7.05 (dd, J=8.4,2.6 Hz, 1H), 6.63 (d, J=7.0 Hz, 1H), 4.68 (s, 2H), 4.29 (q, J=7.0 Hz, 2H), 1.31 (t, J=7.0 Hz, 3H).

EXAMPLE 37 (4)

6-Cyanomethyloxy-1,1-dioxidebenzo[b]thiophene

[2173] 1967

[2174] TLC: Rf 0.30 (hexane:ethyl acetate=1:1);

[2175] NMR (CDCl3): δ 7.36 (d, J=8.4Hz,1H), 7.34 (dd, J=2.6,0.8Hz, 1H), 7.20 (dd, J=7.0, 0.8 Hz, 1H), 7.14 (dd, J=8.4, 2.6 Hz, 1H), 6.69 (d, J=7.0 Hz,1H), 4.84 (s, 2H).

EXAMPLE 37 (5)

5-Ethoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene

[2176] 1968

[2177] TLC: Rf 0.31 (ethyl acetate:hexane=1:1);

[2178] NMR (CDCl3): δ 7.64 (d, J=8.2 Hz, 1H), 7.15 (d, J=6.8 Hz, 1H), 6.98-6.86 (m,2H), 6.74 (d, J=6.8 Hz, 1H), 4.69 (s, 2H), 4.29 (q, J=7.2 Hz, 2H), 1.31 (t, J=7.2 Hz, 3H).

EXAMPLE 37 (6)

7-Ethoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene

[2179] 1969

[2180] TLC: Rf 0.28 (ethyl acetate:hexane=1:1);

[2181] NMR (CDCl3): δ 7.46 (dd, J=8.6 Hz, 7.0 Hz, 1H), 7.14 (d, J=7.0 Hz, 1H), 6.96 (d, J=7.0 Hz,1H), 6.89 (d, J=8.6 Hz,1H), 6.68 (d, J=7.0 Hz,1H), 4.84 (s, 2H), 4.28 (q, J=7.0 Hz, 2H), 1.29 (t, J=7.0 Hz, 3H).

EXAMPLES 38˜38 (3)

[2182] By the same procedure as described in Example 32 using a carboxylic acid derivative corresponding to 4-carboxy-1,1-dioxidebenzo[b]thiophene and a halogenated compound corresponding to bromoethane, the following compounds of the present invention having the following physical data were obtained.

EXAMPLE 38

5-Benzyloxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2183] 1970

[2184] TLC: Rf 0.28 (hexane:ethyl acetate=1:1);

[2185] NMR (CDCl3): δ 7.98 (d, J=8.0 Hz, 1H), 7.51-7.36 (m, 7H), 6.73 (d, J=7.0 Hz, 1H), 5.38 (s, 2H), 3.87 (s, 3H).

EXAMPLE 38 (1)

5-Ethoxycarbonyl-1,1-dioxidebenzo[b]thiophene

[2186] 1971

[2187] TLC: Rf 0.43 (hexane:ethyl acetate=1:1);

[2188] NMR (CDCl3): δ 8.22 (dd, J=8.0, 1.0 Hz, 1H), 8.03 (d, J=1.0 Hz, 1H),7.79 (d, J=8.0 Hz, 1H), 7.15 (d, J=7.0 Hz, 1H), 6.80 (d, J=7.0 Hz, 1H), 4.43 (q , J=7.0 Hz,1H), 1.42 (t, J=7.0 Hz,, 3H).

EXAMPLE 38 (2)

7-Methoxycarbonyl-1,1-dioxidebenzo[b]thiophene

[2189] 1972

[2190] TLC: Rf 0.15 (hexane:ethyl acetate=2:1);

[2191] NMR (CDCl3): δ 8.11 (d, J=8 Hz, 1H), 7.66 (t, J=8 Hz, 1H), 7.55 (d, J=8 Hz, 1H), 7.20 (d, J=7 Hz, 1H), 6.77 (d, J=7 Hz, 1H), 4.05 (s, 3H).

EXAMPLE 38 (3)

7-Ethoxycarbonyl-1,1-dioxidebenzo[b]thiophene

[2192] 1973

[2193] TLC: Rf 0.39 (ethyl acetate:hexane=1:1);

[2194] NMR (CDCl3): δ 8.13 (dd, J=7.6 Hz, 1.2 Hz, 1H), 7.65 (t, J=7.6 Hz, 1H), 7.52 (dd, J=7.6 Hz, 1.2 Hz, 1H), 7.18 (d, J=6.8 Hz, 1H), 6.76 (d, J=6.8 Hz, 1H), 4.53 (q, J=7.2 Hz, 2H), 1.48 (t, J=7.2 Hz, 1H).

EXAMPLE 39

5-t-Butoxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2195] 1974

[2196] A suspension of 5-carboxy-4-methoxy-1,1-dioxidebenzo[b]thiophene (934 mg) in benzene (15 ml) was refluxed. Thereto was added dimethylformamidedi-t-butylacetal (4.02 g) dropwise. The mixture was refluxed for 1 hour. To the reaction mixture water was added. The mixture was extracted by benzene. The extract was washed by a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride sucessively, dried over anhydrous sodium sulfate and concentrated. The residue was purified with column chromatography on silica gel (ethyl acetate:hexane=1:0) to give the compound of the present invention (942 mg) having the following physical data.

[2197] TLC: Rf 0.25 (ethyl acetate:hexane=1:4);

[2198] NMR (CDCl3): δ 7.87 (d, J=7.8 Hz, 1H), 7.47 (d, J=7.8 Hz, 1H), 7.45 (d, J=7.0 Hz, 1H), 6.73 (d, J=7.0 Hz, 1H), 3.95 (s, 3H), 1.62 (s, 9H).

EXAMPLE 40

5-((E)-2-(Ethoxycarbonyl)ethenyl)-4-methoxybenzo[b]thiophene

[2199] 1975

[2200] To a suspension of 62.5% sodium hydride (920 mg) in anhydrous tetrahydrofuran (40 ml), was added a solution of triethylphosphonoacetate (5.83 g) in anhydrous tetrahydrofuran (20 ml) dropwise. The mixture was stirred for 15 minutes. To the reaction mixture, was added a solution of 5-formyl-4-methoxybenzo[b]thiophene (3.84 g) in anhydrous tetrahydrofuran (20 ml) dropwise. The mixture was stirred at room temperature for 1 hour. To the reaction mixture, was added acetic acid (1.5 ml). The mixture was concentrated. The residue was purified with column chromatography on silica gel (hexane:ethyl acetate=9:1) to give the compound of the present invention (5.17 g) having the following physical data.

[2201] TLC: Rf 0.37 (hexane:ethyl acetate=5:1);

[2202] NMR (CDCl3): δ 8.13 (d, J=16.2 Hz, 1H), 7.62-7.41 (m, 4H), 6.53 (d, J=16.2 Hz, 1H), 4.29 (q, J=7.2 Hz, 2H), 4.00 (s, 3H), 1.36 (t, J=7.2 Hz, 3H).

EXAMPLE 41

5-(2-(Ethoxycarbonyl)ethyl)-4-methoxybenzo[b]thiophene

[2203] 1976

[2204] To a solution of the compound prepared in Example 40 (5.16 g) in ethanol (100 ml), 10% palladium carbon (200 mg) was added. Under an atmosphere of hydrogen the mixture was stirred at room temperature. The reaction mixture was filtrated through celite, and the filtrate was concentrated. The residue was purified with column chromatography on silica gel (hexane:ethyl acetate=9:1) to give the compound of the present invention (3.23 g) having the following physical data.

[2205] TLC: Rf 0.40 (hexane:ethyl acetate=5:1);

[2206] NMR (CDCl3): δ 6 7.56 (d, J=8.1 Hz, 1H), 7.41 (q, J=5.4 Hz, 2H), 7.20 (d, J=8.1 Hz, 1H), 4.14 (q, J=7.2 Hz, 2H), 3.97 (s, 3H), 3.07 (t, J=8.0 Hz, 2H), 2.66 (t, J=8.0 Hz, 2H), 1.24 (t, J=7.2 Hz, 3H).

EXAMPLE 42

5-(2-(Ethoxycarbonyl)ethyl)-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2207] 1977

[2208] By the same procedure as described in 3 using the compound prepared in Example 41 instead of the compound prepared in Example 1, the compound of the present invention having the following physical data was obtained (with the proviso that 3-chloroperbenzoic acid was used instead of OXONE® as an oxidizer).

[2209] TLC: Rf 0.25 (hexane:ethyl acetate=2:1);

[2210] NMR (CDCl3): δ 7.45-7.36 (m, 3H), 6.70 (d, J=6.8 Hz, 1H), 4.15 (q, J=7.4 Hz, 2H), 3.92 (s, 3H), 3.01 (t, J=7.6 Hz, 2H), 2.62 (t, J=7.6 Hz, 2H), 1.24 (t, J=7.4 Hz, 3H).

EXAMPLE 43

5-(4.4-Dimethyl-4,5-dihydroxazol-2-yl)-1,1-dioxidebenzo[b]thiophene

[2211] 1978

[2212] Using the compound which was obtained with using 5-carboxy-1,1-dioxidebenzo[b]thiophene and (2-hydroxy-1,1-dimethylethyl)amine instead of 4-carboxy-1,1-dioxidebenzo[b]thiophene and (pyridin-3-ylmethyl)amine respectively, by the same procedure as described in Example 28, by the same procedure as described in Example 34, the compound of the present invention having the following physical data was obtained.

[2213] TLC: Rf 0.39 (ethyl acetate:hexane=1:1);

[2214] NMR (CDCl3): δ 8.08 (dd, J=8.0 Hz, 1.2 Hz, 1H), 7.98 (d, J=1.2 Hz, 1H), 7.75 (d, J=8.0 Hz, 1H), 7.23 (d, J=7.0 Hz, 1H), 6.77 (d, J=7.0 Hz, 1H), 4.16 (s, 2H), 1.40 (s, 6H).

EXAMPLES 44˜44 (24)

[2215] By the same procedure as described in Example 1 using the compounds prepared in Examples 36˜36 (2), Examples 37˜37 (6), Examples 38˜38 (3), Example 39, Example 42, Example 36 (3), Example 43 instead of 1,1-dioxidebenzo[b]thiophene or a corresponding derivative and thiol derivatives corresponding to thiophenol, the following compounds of the present invention were obtained.

EXAMPLE 44

5-Methylcarbamoyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2216] 1979

[2217] TLC: Rf 0.58 (methanol:ethyl acetate 5:95);

[2218] NMR (CDCl3): δ 8.10 (d, J=5.6 Hz, 1H), 7.56 (d, J=5.6 Hz, 1H), 7.54-7.48 (m, 2H), 7.43-7.35 (m, 3H), 7.17 (brs, 1H), 5.07 (dd, J=4.6 Hz, 1.4 Hz, 1H), 4.04 (s, 3H), 3.72 (dd, J=9.4 Hz, 4.6 Hz, 1H), 3.63 (dd, J=9.4 Hz, 1.4 Hz, 1H), 3.07 (d, J=4.8 Hz, 3H).

EXAMPLE 44 (1)

4-Dimethylcarbamoyl-3-phenylthio-2,3-di hydro-1,1-dioxidebenzo[b]thiophene

[2219] 1980

[2220] TLC: Rf 0.52 (methanol:ethyl acetate=5:95);

[2221] NMR (CDCl3): δ 7.78 (dd, J=7.5 Hz, 1.8 Hz, 1H), 7.63-7.51 (m, 4H), 7.43-7.34 (m, 3H), 5.41 (dd, J=7.8 Hz, 1.8 Hz, 1H), 3.74 (dd, J=14.1 Hz, 7.8 Hz, 1H), 3.61 (dd, J=14.1 Hz, 1.8 Hz, 1H), 3.17 (s, 3H), 3.00 (s, 3H).

EXAMPLE 44 (2)

4-Carbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2222] 1981

[2223] TLC: Rf 0.49 (methanol:ethyl acetate=5:95);

[2224] NMR (DMSO-d6): δ 8.19 (brs, 1H), 7.96-7.64 (m, 4H), 7.52-7.30 (m, 5H), 5.87 (d, J=7.4 Hz, 1H), 4.10 (dd, J=14.6 Hz, 7.4 Hz, 1H), 3.61 (d, J=14.6 Hz, 1H).

EXAMPLE 44 (3)

4-(2-(Pyridin-4-yl)ethyl)oxy-3-phenylthio-2,3-dihydro-11-dioxidebenzo[b]thiophene

[2225] 1982

[2226] TLC: Rf 0.44 (ethyl acetate:methanol=10:1);

[2227] NMR (CDCl3): δ 8.50 (d, J=6 Hz, 2H), 7.60-7.13 (m, 9H), 7.07 (d, J=8 Hz, 1H), 4.93 (dd, J=2, 7 Hz, 1H), 4.50-4.15 (m, 2H), 3.80-3.50 (m, 2H), 3.15 (t, J=7 Hz, 2H).

EXAMPLE 44 (4)

4-(2-(Pyridin-3-yl)ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2228] 1983

[2229] TLC: Rf 0.38 (ethyl acetate);

[2230] NMR (CDCl3): δ 8.57 (d, J=1.8 Hz, 1H), 8.48 (dd, J=5.0 Hz, 1.8 Hz, 1H), 7.63 (m, 1H), 7.54-7.32 (m, 7H), 7.19 (dd, J=7.8 Hz, 4.0 Hz, 1H), 7.05 (d, J=8.0 Hz, 1H), 4.97 (dd, J=6.2 Hz, 1.8 Hz, 1H), 4.32 (m, 2H), 3.67 (dd, J=14.2 Hz, 6.2 Hz, 1H), 3.58 (dd, J=14.2 Hz, 1.8 Hz, 1H), 3.16 (t, J=7.2 Hz, 2H).

EXAMPLE 44 (5)

4-Ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2231] 1984

[2232] TLC: Rf 0.45 (hexane:ethyl acetate=1:1);

[2233] NMR (CDCl3): δ 7.57-7.53 (m, 2H), 7.49 (d, J=8.1 Hz, 1H), 7.38-7.33 (m, 4H), 6.96 (d, J=8.1 Hz, 1H), 5.16 (dd, J=7.0, 1.8 Hz, 1H), 4.71 (s, 2H), 4.28 (q, J=7.2 Hz, 2H), 3.72 (dd, J=14.0, 7.0 Hz, 1H), 3.62 (dd, J=14.0, 1.8 Hz, 1H), 1.30 (t, J=7.2 Hz, 3H).

EXAMPLE 44 (6)

6-Ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2234] 1985

[2235] TLC: Rf 0.54 (hexane:ethyl acetate=1:1);

[2236] NMR (CDCl3): δ 7.62 (d, J=8.7 Hz, 1H), 7.43-7.40 (m, 2H), 7.35-7.33 (m, 3H), 7.25 (dd, J=8.7, 2.4 Hz, 1H), 7.10 (d, J=2.4 Hz, 1H), 4.91 (t, J=6.8 Hz, 1H), 4.66 (s, 2K), 4.28 (q, J=7.2 Hz, 2H), 3.81 (dd, J=13.7, 6.8 Hz, 1H), 3.52 (dd, J=13.7, 6.8 Hz, 1H), 1.31 (t, J=7.2 Hz, 3H).

EXAMPLE 44 (7)

6-Cyanomethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2237] 1986

[2238] TLC: Rf 0.54 (hexane:ethyl acetate=2:1);

[2239] NMR (CDCl3): δ 7.69 (d, J=8.4 Hz, 1H), 7.44-7.41 (m, 2H), 7.38-7.34 (m, 3H), 7.28 (dd, J=8.4, 2.4 Hz, 1H), 7.24 (d, J=2.4 Hz, 1H), 4.93 (t, J=6.9 Hz, 1H), 4.83 (s, 2H), 3.83 (dd, J=13.7, 6.9 Hz 1H) 3.54 (dd, J=13.7, 6.9 Hz, 1H).

EXAMPLE 44 (8)

5-Ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2240] 1987

[2241] TLC: Rf 0.45 (ethyl acetate:hexane=1:1);

[2242] NMR (CDCl3): δ 7.64 (d, J=8.6 Hz, 1H), 7.48-7.30 (m, 5H), 7.15 (d, J=2.2 Hz, 1H), 7.06 (dd, J=8.6 Hz, 2.2 Hz, 1H), 4.90 (t, J=7.0Hz, 1H), 4.69 (s, 2H), 4.29 (q, J=7.4Hz, 2H), 3.79 (dd, J=13.6 Hz, 7.0 Hz, 1H), 3.50 (dd, J=13.6 Hz, 7.0 Hz, 1H), 1.32 (t, J=7.4 Hz, 3H).

EXAMPLE 44 (9)

7-Ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2243] 1988

[2244] TLC: Rf 0.43 (ethyl acetate:hexane=1:1);

[2245] NMR (CDCl3): δ 7.55 (t, J=8.4 Hz, 1H), 7.46-7.27 (m, 6H), 6.82 (d, J=8.4 Hz, 1H), 4.91 (dd, J=7.6 Hz, 6.6 Hz, 1H), 4.80 (s, 2H), 4.26 (q, J=7.2 Hz, 2H), 3.80 (dd, J=13.6 Hz, 7.6 Hz, 1H) 3.54 (dd, J=13.6 Hz, 6.6 Hz, 1H), 1.28 (t, J=7.2 Hz, 3H).

EXAMPLE 44 (10)

5-Benzyloxycarbonyl-4-methoxy-3-phenylethio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2246] 1989

[2247] TLC: Rf 0.55 (hexane:ethyl acetate=1:1);

[2248] NMR (CDCl3): δ 7.99 (d, J=8.0 Hz, 1H), 7.54-7.34 (m, 1H), 5.40 (s, 2H), 5.08 (dd, J=6.0, 2.5 Hz, 1H), 3.97 (s, 3H), 3.69 (dd, J=14.0, 6.0 Hz, 1H), 3.60 (dd, J=14.0, 2.5 Hz, 1H).

EXAMPLE 44 (1 1)

5-Ethoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2249] 1990

[2250] TLC: Rf 0.55 (hexane:ethyl acetate=1:1);

[2251] NMR (CDCl3): δ 8.36 (s, 1H), 8.20 (d, J=8.2 Hz, 1H), 7.78 (d, J=8.2 Hz, 1H), 7.47-7.33 (m, 5H), 4.97 (t, J=7.0 Hz, 1H), 4.44 (q, J=7.0 Hz, 2H), 3.84 (dd, J=13.7, 7.0 Hz, 1H), 3.54 (dd, J=13.7, 7.0 Hz, 1H), 1.43 (t, J=7.0 Hz, 3H).

EXAMPLE 44 (12)

7-Methoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2252] 1991

[2253] TLC: Rf 0.39 (ethyl acetate:hexane=1:1);

[2254] NMR (CDCl3): δ 8.12 (d, J=7.8 Hz, 1H), 7.93 (d, J=7.8 Hz, 1H), 7.72 (t, J=7.8 Hz, 1H), 7.48-7.33 (m, 5H), 4.92 (dd, J=7.6 Hz, 6.8 Hz, 1H), 4.01 (s, 3H), 3.86 (dd, J=13.6 Hz, 7.6 Hz, 1H), 3.56 (dd, J=1 3.6 Hz, 6.8 Hz, 1H).

EXAMPLE 44 (13)

7-Ethoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2255] 1992

[2256] TLC: Rf 0.60 (ethyl acetate:hexane=1:1);

[2257] NMR (CDCl3): δ 8.13 (d, J=7.8 Hz, 1H), 7.91 (d, J=7.8 Hz, 1H), 7.72 (t, J=7.8 Hz, 1H), 7.46-7.38 (m, 2H), 7.38-7.30 (m, 3H), 4.92 (dd, J=7.8 Hz, 6.9 Hz, 1H), 4.48 (q, J=7.2 Hz, 2H), 3.84 (dd, J=13.5 Hz, 7.8 Hz, 1H), 3.55 (dd, J=13.5 Hz, 6.9 Hz, 1H), 1.44 (t, J=7.2 Hz, 3H).

EXAMPLE 44 (14)

5-t-Butoxycarbonyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2258] 1993

[2259] TLC: Rf 0.22 (ethyl acetate:hexane 1:4);

[2260] NMR (CDCl3): δ 7.88 (d, J=8.0 Hz,1H), 7.58-7.49 (m, 2H), 7.46 (d, J=8.0 Hz,1H), 7.43-7.34 (m, 3H), 5.10 (dd, J=6.0 Hz, 2.8 Hz, 1H), 4.08 (s, 3H), 3.70 (dd, J=13.8 Hz, 6.0 Hz, 1H), 3.61 (dd, J=13.8 Hz, 2.8 Hz, 1H), 1.63 (s, 9H).

EXAMPLE 44 (15)

5-(2-(Ethoxycarbonyl)ethyl)4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2261] 1994

[2262] TLC: Rf 0.25 (hexane:ethyl acetate=2:1);

[2263] NMR (CDCl3): δ 7.55-7.50 (m, 2H), 7.44 (s, 2H), 7.43-7.30 (m, 3H), 5.08 (dd, J=6.9, 2.1 Hz, 1H), 4.15 (q, J=7.2 Hz, 2H), 4.05 (s, 3H), 3.68 (dd, J=15.2, 7.2 Hz, 1H), 3.60 (dd, J=15.2, 2.1 Hz, 1H), 3.18-3.00 (m, 2H), 2.66 (t, J=7.8 Hz, 2H), 1.25 (t, J=7.2 Hz, 3H).

EXAMPLE 44 (16)

4-(Furan-2-ylmethyl)carbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2264] 1995

[2265] TLC: Rf 0.37 (ethyl acetate:benzene=1:2);

[2266] NMR (DMSO-d6): δ 9.24 (t, J=5.6 Hz, 1H), 7.93-7.82 (m, 2H), 7.77-7.66 (m, 1H), 7.55-7.51 (m, 1H), 7.47-7.31 (m, 5H), 6.37-6.29 (m, 2H), 5.75 (d, J=7.6 Hz, 1H), 4.46 (d, J=5.6 Hz, 2H), 4.12 (dd, J=14.2 Hz, 7.6 Hz, 1H), 3.62 (d, J=14.2 Hz, 1H).

EXAMPLE 44 (17)

5-(4,4-Dimethyl-4,5-dihydroxazol-2-yl)-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2267] 1996

[2268] TLC: Rf 0.50 (ethyl acetate:hexane=1:1);

[2269] NMR (CDCl3): δ 8.32 (brs, 1H), 8.12 (d, J=8.2 Hz, 1H), 7.75 (d, J=8.2 Hz, 1H), 7.50-7.30 (m, 5H), 4.96 (dd, J=7.2 Hz, 6.6 Hz, 1H), 4.18 (s, 2H), 3.82 (dd, J=13.8 Hz, 7.2 Hz, 1H), 3.54 (dd, J=13.8 Hz, 6.6 Hz, 1H), 1.42 (s, 6H).

EXAMPLE 44 (18)

3-Benzylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2270] 1997

[2271] TLC: Rf 0.52 (hexane:ethyl acetate 1:1);

[2272] NMR (CDCl3): δ 3.42 (dd, J=13.8Hz, 6.3Hz, 1H), 3.69 (dd, J=13.8Hz, 7.8Hz, 1H), 3.78 (d, J=13.7Hz, 1H), 3.86 (d, J=13.7Hz, 1H), 4.53 (t-like, J=7.1Hz, 1H), 7.27-7.33 (m, 5H), 7.46-7.56 (m,1H), 7.59-7.62 (m, 2H), 7.71 (d, J=7.6Hz, 1H).

EXAMPLE 44 (19)

3-(3,4-Dichlorophenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2273] 1998

[2274] TLC: Rf 0.57 (hexane:ethyl acetate=1:1);

[2275] NMR (CDCl3): δ 3.48 (dd, J=13.6Hz, 5.8Hz, 1H), 3.83 (dd, J=13.6Hz, 7.6Hz, 1H), 4.97 (t-like, J=6.8Hz, 1H), 7.23 (dd, J=8.3Hz, 2.2Hz, 1H), 7.41 (d, J=8.3Hz, 1H), 7.51 (d, J=2.2Hz, 1H), 7.54-7.62 (m, 1H), 7.66-7.69 (m, 2H), 7.74 (d, J=76Hz, 1H).

EXAMPLE 44 (20)

3-(4-Nitrophenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2276] 1999

[2277] TLC: Rf 0.15 (methylene chloride); NMR (CDCl3): δ 3.55 (dd, J=13.8Hz, 6.0Hz, 1H), 3.97 (dd, J=13.8Hz, 7.5Hz, 1H), 5.20 (t-like, J=6.8Hz, 1H), 7.47 (d, J=8.7Hz, 2H), 7.55-7.64 (m, 1H), 7.68-7.70 (m, 2H), 7.79 (d, J=7.6Hz,1H), 8.19 (d, J=8.7Hz, 2H).

EXAMPLE 44 (21)

5-Hydroxymethyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2278] 2000

[2279] TLC: Rf 0.64 (ethyl acetate);

[2280] NMR (CDCl3): δ 7.68 (d, J=7.8 Hz, 1H), 7.55-7.47 (m, 3H), 7.39-7.35 (m, 3H), 5.08 (dd, J=6.6, 2.5 Hz, 1H), 4.84 (d, J=6.0 Hz, 2H), 4.06 (s, 3H), 3.69 (dd, J=13.9, 6.6 Hz, 1H), 3.58 (dd, J=13.9, 2.5 Hz, 1H), 2.15 (t, J=6.0 Hz, 1H).

EXAMPLE 44 (22)

4-Hydroxymethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2281] 2001

[2282] TLC: Rf 0.22 (chloroform:ethyl acetate=4:1);

[2283] NMR (CDCl3): δ 7.77-7.66 (m, 2H), 7.61 (d, J=7.4 Hz, 1H), 7.57-7.44 (m, 2H), 7.43-7.32 (m, 3H), 5.20 (dd, J=6.8, 2.0 Hz, 1H), 5.03 (s, 2H), 3.72 (dd, J=14.0, 6.8 Hz, 1H), 3.62 (dd, J=14.0, 2.0 Hz, 1H), 2.45-2.15 (br,1H).

EXAMPLE 44 (23)

6-Fluoro-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2284] 2002

[2285] TLC: Rf 0.62 (ethyl acetate:hexane=1:4);

[2286] NMR (CDCl3): δ 7.70 (ddd, J=7.6Hz, 4.4Hz, 0.4Hz,1H), 7.47-7.29 (m, 7H),4.93 (t, J=7.0 Hz, 1H), 3.84 (dd, J=13.8 Hz, 7.0 Hz, 1H), 3.55 (dd, J=13.8 Hz, 7.0 Hz, 1H).

EXAMPLE 44 (24)

4-Fluoro-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2287] 2003

[2288] TLC: Rf 0.55 (ethyl acetate:hexane=1:4);

[2289] NMR (CDCl3): δ 7.64-7.45 (m, 4H), 7.42-7.27 (m, 4H), 5.06 (dd, J=7.4 Hz, 2.8 Hz, 1H), 3.77 (dd, J=14.2 Hz, 7.4 Hz, 1H), 3.63 (dd, J=14.2 Hz, 2.8 Hz, 1H).

EXAMPLES 45˜45 (22)

[2290] Using the compounds prepared in Examples 44˜44 (15) and Examples 44 (18)˜44 (24) instead of the compound prepared in Example 1 by the same procedure as described in Example 3, or by the same reaction using 3-chloroperbenzoic acid instead of OXONE@ as an oxidizer, and if necessary, by converting into a corresponding salt by known methods, the following compounds of the present invention were obtained.

EXAMPLE 45

5-Methylcarbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2291] 2004

[2292] TLC: Rf 0.33 (methanol:ethyl acetate=5:95); NMR (DMSO-d6): δ 8.47 (q-like, J=3.4 Hz, 1H), 7.87-7.73 (m, 3H), 7.69-7.60 (m, 3H), 7.50 (d, J=5.4 Hz, 1H), 5.65 (d, J=6.0 Hz, 1H), 4.13 (d, J=10.2 Hz, 1H), 3.98 (dd, J=10.2 Hz, 6.0 Hz, 1H), 3.59 (s, 3H), 2.77 (d, J=3.4 Hz, 3H).

EXAMPLE 45 (1)

4-Dimethylcarbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2293] 2005

[2294] TLC: Rf 0.55 (methanol:ethyl acetate=5:95);

[2295] NMR (DMSO-d6): δ 7.93-7.73 (m, 6H), 7.70-7.62 (m, 2H), 5.86 (d, J=9.3 Hz, 1H), 4.12 (dd, J=15.3 Hz, 9.3 Hz, 1H), 3.91 (d, J=15.3 Hz, 1H), 3.07 (s, 3H), 3.03 (s, 3H).

EXAMPLE 45 (2)

4-Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2296] 2006

[2297] TLC: Rf 0.43 (methanol:ethyl acetate=5:95);

[2298] NMR (DMSO-d6): δ 8.30 (brs, 1H), 8.03 (d, J=7.8 Hz, 1H), 7.91 (d, J=7.8 Hz, 1H), 7.86-7.72 (m, 5H), 7.68 (brs, 1H), 7.63 (t, J=7.8 Hz, 1H), 6.37 (d, J=9.3 Hz, 1H), 4.08 (dd, J=15.3 Hz, 9.3 Hz, 1H), 3.95 (d, J=15.3 Hz, 1H).

EXAMPLE 45 (3)

4-(2-Pyridin-4-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2299] 2007

[2300] Free Compound:

[2301] TLC: Rf 0.25 (ethyl acetate:methanol=10:1);

[2302] NMR (CDCl3): δ 8.58 (d, J=6 Hz, 2H), 7.80-7.35 (m, 6H), 7.35-7.14 (m, 3H), 6.98 (d, J=8 Hz, 1H), 5.12 (d, J=9 Hz, 1H), 4.30-4.05 (m, 3H), 3.70 (dd, J=9, 15 Hz, 1H), 3.25-2.90 (m, 2H).

[2303] Hydrochloride:

[2304] TLC: Rf 0.25 (ethyl acetate:methanol=10:1);

[2305] NMR (DMSO-d6): δ 8.83 (d, J=6.6 Hz, 2H), 7.96 (d, J=6.6 Hz, 2H), 7.78-7.58 (m, 6H), 7.35-7.30 (m, 2H), 5.40 (d, J=8.5 Hz, 1H), 4.36-4.28 (m, 1H), 4.19-4.12 (m, 1H), 4.11 (d, J=15.0 Hz, 1H),3.98 (dd, J=15.0, 8.5 Hz, 1H), 3.24-3.15 (m, 1H), 3.11-3.01 (m, 1H).

[2306] Methanesulfonic Acid Salt:

[2307] TLC: Rf 0.25 (ethyl acetate:methanol=10:1);

[2308] NMR (DMSO-d6): δ 8.85 (d, J=6.6 Hz, 2H), 7.98 (d, J=6.6 Hz, 2H), 7.78-7.58 (m, 6H), 7.35-7.30 (m, 2H), 5.39 (d, J=8.5 Hz, 1H), 4.36-4.29 (m, 1H), 4.19-4.13 (m, 1H), 4.11 (d, J=15.0 Hz, 1H), 3.97 (dd, J=15.0, 8.5 Hz,1H), 3.25-3.17 (m, 1H), 3.11-3.02 (m, 1H).

EXAMPLE 45 (4)

4-(2-(Pyridin-3-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1,-dioxidebenzo[b]thiophene.

[2309] 2008

[2310] Free Compound:

[2311] TLC: Rf 013 (ethyl acetate);

[2312] NMR (DMSO-d6): δ 8.46 (d, J=1.8 Hz, 1H), 8.43 (dd, J=4.8 Hz, 1.8 Hz, 1H), 7.86-7.54 (m, 6H), 7.42-7.30 (m, 4H), 5.43 (d, J=7.4Hz, 1H), 4.26-3.82, (m, 4H), 2.75 (t, J=6.6 Hz, 2H).

[2313] Hydrochloride:

[2314] TLC: Rf 0.13 (ethyl acetate);

[2315] NMR (DMSO-d6): δ 8.88 (s, 1H), 8.80 (d, J=5.7 Hz, 1H), 8.49 (d, J=7.8 Hz, 1H), 8.04-7.92 (m, 1H), 7.78-7.54 (m, 6H), 7.30 (d, J=7.8 Hz, 1H), 7.29 (d, J=8.4 Hz, 1H), 5.47 (d, J=7.8 Hz, 1H), 4.34-4.20 (m, 1H), 4.16-3.91 (m, 3H), 3.19-2.94 (m, 2H).

EXAMPLE 45 (5)

4-Ethoxycarbonylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2316] 2009

[2317] TLC: Rf 0.17 (hexane:ethyl acetate=1:1);

[2318] NMR (CDCl3): δ 7.82-7.78 (m, 2H), 7.68-7.60 (m, 1H), 7.58-7.44 (m, 3H), 7.36 (d, J=8.0 Hz, 1H), 6.86 (d, J=8.0 Hz, 1H), 5.38 (d, J=8.5 Hz, 1H), 4.45 (d, J=16.2 Hz, 1H), 4.30 (d, J=16.2 Hz, 1H), 4.25 (q, J=7.0 Hz, 2H), 4.24 (d, J=15.0 Hz, 1H), 3.76 (dd, J=15.0, 8.5 Hz, 1H), 1.30 (t, J=7.0 Hz, 3H).

EXAMPLE 45 (6)

6-Ethoxycarbonylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2319] 2010

[2320] TLC: Rf 0.31 (hexane:ethyl acetate=1:1);

[2321] NMR (CDCl3): δ 7.90 (d, J=8.8 Hz, 1H), 7.71-7.62 (m, 3H), 7.55-7.46 (m, 2H), 7.30 (dd, J=8.8, 2.4 Hz, 1H), 7.02 (d, J=2.4 Hz, 1H), 5.00 (dd, J=7.8, 5.4 Hz, 1H), 4.67 (s, 2H), 4.28 (q, J=7.2 Hz, 2H), 3.80 (dd, J=15.0, 5.4 Hz, 1H), 3.72 (dd, J=15.0, 7.8 Hz, 1H), 1.30 (t, J=7.2 Hz, 3H).

EXAMPLE 45 (7)

6-Cyanomethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2322] 2011

[2323] TLC: Rf 0.32 (hexane:ethyl acetate=2:1);

[2324] NMR (DMSO-d6): δ 7.81-7.75 (m, 3H), 7.68-7.60 (m, 3H), 7.53 (d, J=2.5 Hz, 1H), 7.48 (dd, J=8.5, 2.5 Hz, 1H), 5.73 (dd, J=9.5, 3.0 Hz, 1H), 5.33 (s, 2H), 4.03 (dd, J=15.0, 9.5 Hz, 1H), 3.81 (dd, J=15.0, 3.0 Hz, 1H).

EXAMPLE 45 (8)

5-Ethoxycarbonylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2325] 2012

[2326] TLC: Rf 0.35 (ethyl acetate:hexane=1:1);

[2327] NMR (CDCl3): δ 7.73-7.61 (m, 3H), 7.58-7.45 (m,3H), 7.44 (d, J=2.2 Hz, 1H), 7.18 (dd, J=8.8 Hz, 2.2 Hz, 1H), 5.00 (t, J=7.0 Hz, 1H), 4.78 (s, 2H), 4.33 (q, J=7.2 Hz, 2H), 3.81-3.65 (m, 2H), 1.35 (t, J=7.2 Hz, 3H).

EXAMPLE 45 (9)

7-Ethoxycarbonylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2328] 2013

[2329] TLC: Rf 0.17 (ethyl acetate:hexane=1:1);

[2330] NMR (CDCl3): δ 7.72-7.47 (m, 7H), 6.91 (d, J=6.9 Hz, 1H), 5.03 (dd, J=8.7 Hz, 5.4 Hz, 1H), 4.76 (s, 2H), 4.24 (q, J=7.2 Hz, 2H), 3.79 (dd, J=14.7 Hz, 5.4 Hz, 1H), 3.73 (dd, J=14.7 Hz, 8 .7 Hz, 1H), 1.27 (t, J=7.2 Hz, 3H).

EXAMPLE 45 (10)

5-Benzyloxycarbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2331] 2014

[2332] TLC: Rf 0.30 (hexane:ethyl acetate=1:1);

[2333] NMR (CDCl3): δ 7.90 (d, J=8.0 Hz, 1H), 7.76-7.71 (m, 2H), 7.63-7.55 (m, 1H), 7.47-7.36 (m, 8H), 5.37 (s, 2H), 5.24 (dd, J=9.0, 1.0Hz, 1H), 4.16 (dd, J=15.0, 1.0 Hz, 1H), 3.74 (s, 3H), 3.73 (dd, J=15.0, 9.0 Hz, 1H).

EXAMPLE 45 (11)

5-Ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2334] 2015

[2335] TLC: Rf 0.34 (hexane:ethyl acetate=1:1);

[2336] NMR (DMSO-d6): δ 8.23 (d-like, J=8.0 Hz, 1H), 8.12 (s, 1H), 7.97 (d, J=8.0 Hz, 1H), 7.85-7.78 (m, 3H), 7.69-7.61 (m, 2H), 5.91 (dd, J=9.3, 3.2 Hz, 1H), 4.38 (q, J=7.0 Hz, 2H), 4.10 (dd, J=15.3, 9.3 Hz, 1H), 3.91 (dd, J=15.3, 3.2 Hz; 1H); 1.35 (t, J=7.0 Hz, 3H).

EXAMPLE 45 (12)

7-Methoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2337] 2016

[2338] TLC: Rf 0.16 (ethyl acetate:hexane=1:1);

[2339] NMR (CDCl3): δ 8.23 (d, J=8.1 Hz, 2H), 7.81 (t, J=8.1 Hz, 1H), 7.72-7.64 (m, 3H), 7.55-7.47 (m, 2H), 5.07 (dd, J=9.3 Hz, 4.8 Hz, 1H), 3.97 (s, 3H), 3.84 (dd, J=14.7 (t, 4.8 Hz, 1H), 3.75 (dd, J=14.7 Hz, 9.3 Hz, 1H).

EXAMPLE 45 (13)

7-Ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2340] 2017

[2341] TLC: Rf 0.22 (ethyl acetate:hexane=1:1);

[2342] NMR (CDCl3): δ 8.25 (d, J=7.8 Hz, 1H), 8.23 (d, J=7.8 Hz, 1H), 7.80 (t, J=7.8 Hz, 1H), 7.73-7.65 (m, 3H), 7.56-7.48 (m, 2H), 5.06 (dd, J=9.3 Hz, 4.8 Hz, 1H), 4.44 (q, J=7.2 Hz, 2H), 3.83 (dd, J=14.7 Hz, 4.8 Hz, 1H), 3.73 (dd, J=14.7 Hz, 9.3 Hz, 1H), 1.40 (t, J=7.2 Hz, 3H).

EXAMPLE 45 (14)

5-t-Butoxycarbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2343] 2018

[2344] TLC: Rf 0.37 (ethyl acetate:hexane 1:1);

[2345] NMR (CDCl3): δ 7.80 (d, J=8.1 Hz, 1H), 7.78 (d, J=7.8 Hz, 2H), 7.66 (t, J=7.8 Hz, 1H), 7.51 (t, J=7.8 Hz, 2H), 7.37 (d, J=8.1 Hz, 1H), 5.27 (dd, J=9.3 Hz, 1.2 Hz, 1H), 4.14 (dd, J=15.0 Hz, 1.2 Hz, 1H), 3.86 (s, 3H), 3.74 (dd, J=15.0 Hz, 9.3 Hz, 1H), 1.61 (s, 9H).

EXAMPLE 45 (15)

5-(2-Ethoxycarbonylethyl)-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2346] 2019

[2347] TLC: Rf 0.28 (ethyl acetate:hexane=1:1);

[2348] NMR (CDCl3): δ 7.77-7.70 (m, 2H), 7.61 (t, J=7.5 Hz, 1H), 7.50-7.35 (m, 4H), 5.19 (dd, J=9.3, 1.8 Hz, 1H), 4.23 (dd, J=15.0, 1.8 Hz, 1H), 4.16 (q, J=7.2 Hz, 2H), 3.81 (dd, J=15.0, 9.3 Hz, 1H), 3.80 (s, 3H), 3.00-2.87 (m, 2H), 2.65-2.40 (m, 2H), 1.27 (t, J=7.2 Hz, 3H).

EXAMPLE 45 (16)

3-Benzylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2349] 2020

[2350] TLC: Rf 0.39 (hexane:ethyl acetate=1:1);

[2351] NMR (CDCl3): δ 3.89 (dd, J=15.0 Hz, 9.3 Hz, 1H), 3.98 (d, J=14.0 Hz, 1H), 4.03 (dd, J=15.0 Hz, 3.6 Hz, 1H), 4.31 (d, J=14.0 Hz, 1H), 4.91 (dd, J=9.3, Hz, 3.6 Hz, 1H), 7.21-7.35 (m, 5H), 7.62-7.71 (m, 2H), 7.80-7.90 (m, 2H).

EXAMPLE 45 (17)

3-(3,4-Dichlorophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2352] 2021

[2353] TLC: Rf 0.43 (hexane:ethyl acetate=1:1);

[2354] NMR (DMSO-d6): δ 7.98 (d, J=2.1 Hz, 1H), 7.75-7.89 (m, 5H), 7.63 (dd, J=8.4, 2.1 Hz, 1H), 5.91 (dd, J=8.0, 4.4 Hz, 1H), 4.04 (dd, J=15.4, 8.0 Hz, 1H), 3.95 (dd, J=15.4, 4.4 Hz,1H).

EXAMPLE 45 (18)

3-(4-Nitrophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2355] 2022

[2356] TLC: Rf 0.33 (hexane:ethyl acetate=1:1);

[2357] NMR (DMSO-d6): δ 8.41 (d, J=8.8 Hz, 2H), 8.04 (d, J=8.8 Hz, 2H), 7.76-7.85 (m, 4H), 5.97 (dd, J=9.0, 3.2 Hz, 1H), 4.04 (dd, J=15.4, 9.0 Hz, 1H), 3.90 (dd, J=15.4, 3.2 Hz,1H).

EXAMPLE 45 (19)

5-Hydroxymethyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2358] 2023

[2359] TLC: Rf 0.51 (ethyl acetate);

[2360] NMR (DMSO-d6): δ 7.80-7.72 (m, 4H), 7.64-7.51 (m, 3H), 5.66 (dd, J=8.5, 1.5 Hz, 1H), 5.43 (t, J=5.5 Hz, 1H), 4.52 (d, J=5.5 Hz, 1H), 4.13 (dd, J=15.0,8.5Hz, 1H), 4.00 (dd, J=15.0, 1.5 Hz, 1H), 3.58 (s, 3H).

EXAMPLE 45 (20)

4-Hydroxymethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2361] 2024

[2362] TLC: Rf 0.54 (chloroform:methanol=9:1);

[2363] NMR (CDCl3): δ 7.84 (d, J=7.5 Hz, 1H), 7.72-7.63 (m, 2H), 7.62-7.53 (m, 3H), 7.51-7.44 (m, 2H), 5.53 (d, J=9.3 Hz, 1H), 5.08 (d, J=13.5 Hz, 1H), 5.01 (d, J=13.5 Hz, 1H), 3.87 (d, J=15.0 Hz, 1H), 3.75 (dd, J=15.0, 9.3 Hz, 1H), 3.00-1.80 (br, 1H).

EXAMPLE 45 (21)

6-Fluoro-3-phenylsuifonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2364] 2025

[2365] TLC: Rf 0.40 (ethyl acetate:hexane=1:1);

[2366] NMR (DMSO-d6): δ 7.85-7.58 (m, 8H), 5.77 (dd, J=9.6 Hz, 2.7 Hz,1H), 4.07 (dd, J=15.6 Hz, 9.6 Hz, 1H), 3.87 (dd, J=15.6 Hz, 2.7 Hz, 1H).

EXAMPLE 45 (22)

4-Fluoro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2367] 2026

[2368] TLC: Rf 0.29 (ethyl acetate:hexane=1:1);

[2369] NMR (DMSO-d6): δ 7.83-7.57 (m, 8H), 5.81 (dd, J=9.0 Hz, 1.5 Hz, 1H), 4.09 (dd, J=15.6 Hz, 1.5 Hz, 1H), 3.99 (dd, J=15.6 Hz, 9.0 Hz, 1H).

EXAMPLE 46

5-Methoxycarbonyl-4-ethoxybenzo[b]thiophene

[2370] 2027

[2371] By the same procedure as described in Example 18 using 5-methoxycarbonyl-4-hydroxybenzo[b]thiophene instead of the compound prepared in Example 9 (12) and ethyl iodide instead of 4-nitrobenzylbromide, the compound of the present invention having the following physical data was obtained.

[2372] TLC: Rf 0.44 (hexane:ethyl acetate=4:1); NMR (CDCl3): δ 7.82 (d, J=8 Hz, 1H), 7.63 (d, J=8 Hz, 1H), 7.54 (d, J=6 Hz, 1H), 7.43 (d, J=6 Hz, 1H), 4.21 (q, J=7 Hz, 2H), 3.95 (s, 3H), 1.49 (t, J=7 Hz, 3H).

EXAMPLE 47

5-Carboxy-4-ethoxybenzo[b]thiophene

[2373] 2028

[2374] To the compound prepared in Example 46 (1.11 g), were added methanol (10 ml) and a 2N aqueous solution of sodium hydroxide (5.0 ml). The mixture was refluxed for 30 minutes. The reaction mixture was concentrated. The residue was acidified by addition of 1 N hydrochloric acid. The mixture was extracted by ethyl acetate. The extract was washed by water and a saturated aqueous solution of sodium chloride successively, dried over anhydrous sodium sulfate and concentrated to give the compound of the present invention (1.02 g) having the following physical data.

[2375] TLC: Rf 0.06 (hexane:ethyl acetate 4:1);

[2376] NMR (CDCl3): δ 8.09 (d, J=8 Hz, 1H), 7.75 (d, J=8 Hz, 1H), 7.52 (d, J=6 Hz, 1H), 7.49 (d, J=6 Hz, 1H), 4.44 (q, J=7 Hz, 2H), 1.58 (t, J=7 Hz, 3H).

EXAMPLE 48

5-Benzyloxycarbonyl-4-ethoxybenzo[b]thiophene

[2377] 2029

[2378] By the same procedure as described in Example 32 using the compound prepared in Example 47 instead of 4-carboxy-1,1-dioxidebenzo[b]thiophene, and benzyl bromide, the compound having the following physical data was obtained.

[2379] TLC: Rf 0.46 (hexane:ethyl acetate=4:1);

[2380] NMR (CDCl3): δ 7.85 (d, J=8 Hz, 1H), 7.62 (d, J=8 Hz, 1H), 7.56-7.26 (m, 7H), 5.40 (s, 2H), 4.15 (q, J=7 Hz, 2H), 1.37 (t, J=7 Hz, 3H).

EXAMPLE 49

5-Benzyloxycarbonyl-4-ethoxy-1,1-dioxidebenzo[b]thiophene

[2381] 2030

[2382] By the same procedure as described in 3 using the compound prepared in Example 48 instead of the compound prepared in Example 1, the compound having the following physical data was obtained (with the proviso that 3-chloroperbenzoic acid was used instead of OXONE™ as an oxidizer).

[2383] TLC: Rf 0.10 (hexane:ethyl acetate=4:1);

[2384] NMR (CDCl3): δ 7.99 (d, J=8 Hz, 1H), 7.60-7.30 (m, 7H), 6.72 (d, J=7 Hz, 1H), 5.38 (s, 2H) 4.03 (q, J=7 Hz, 2H), 131 (t, J=7 Hz, 3H.

EXAMPLES 50˜50 (2)

[2385] By the same procedure as described in Example 46→Example 47→Example 48→Example 49 using a corresponding halide compound instead of ethyl iodide, the following compounds of the present invention were obtained.

EXAMPLE 50

5-Benzyloxycarbonyl-4-hexyloxy-1,1-dioxidebenzo[b]thiophene

[2386] 2031

[2387] TLC: Rf 0.22 (hexane:ethyl acetate=4:1); (s, 2H), 3.93 (t, J=7 Hz, 2H), 7.55-7.30 (m, 7H), 6.72 (d, J=7 Hz, 1H), 5.38 (s, 2H), 3.93 (t, J=7 Hz, 2H), 1.80-1.45 (m, 2H), 1.45-1.10 (m, 6H), 0.90 (t, J=7 Hz, 3H).

EXAMPLE 50 (1)

5-Benzyloxycarbonyl-4-butoxy-1,1-dioxidebenzo[b]thiophene

[2388] 2032

[2389] TLC: Rf 0.24 (hexane:ethyl acetate=4:1);

[2390] NMR (CDCl3): δ 7.98 (d, J=8 Hz, 1H), 7.58-7.38 (m, 7H), 6.72 (d, J=7 Hz, 1H), 5.33 (s, 2H), 3.94 (t, J=7 Hz, 2H), 1.78-1.50 (m, 2H), 1.50-1.20 (m, 2H), 0.92 (t, J=7 Hz, 3H).

EXAMPLE 50 (2)

5-Benzyloxycarbonyl-4-octyloxy-1,1-dioxidebenzo[b]thiophene

[2391] 2033

[2392] TLC: Rf 0.33 (hexane:ethyl acetate=4:1);

[2393] NMR (CDCl3): δ 7.97 (d, J=8 Hz, 1H), 7.60-7.25 (m, 7H), 6.72 (d, J=7 Hz, 1H), 5.38 (s, 2H), 3.92 (t, J=7 Hz, 2H), 1.82-1.45 (m, 2H), 1.45-1.05 (m, 10H), 0.89 (t, J=7 Hz, 3H).

EXAMPLES 51˜51 (3)

[2394] By the same procedure as described in Example 27 using the compounds prepared in Example 49 and Examples 50˜50 (2) instead of 5-methyl-1,1-dioxidebenzo[b]thiophene, the following compounds of the present invention were obtained.

EXAMPLE 51

5-Benzyloxycarbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2395] 2034

[2396] TLC: Rf 0.41 (chloroform hexane:methanol=5:5:1);

[2397] NMR (CDCl3): δ 7.90 (d, J=8 Hz, 1H), 7.78-7.66 (m, 2H), 7.64-7.30 (m, 9H), 5.34 (s, 2H), 5.17 (d, J=9 Hz, 1H), 4.30 (dd, J=1, 15 Hz, 1H), 4.10-3.60 (m, 3H), 1.13 (t, J=7 Hz, 3H).

EXAMPLE 51 (1)

5-benzyloxycarbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2398] 2035

[2399] TLC: Rf 0.45 (chloroform:hexane:methanol=5:5:1);

[2400] NMR (CDCl3): δ 7.88 (d, J=8 Hz, 1H), 7.78-7.64 (m, 2H), 7.60-7.28 (m, 9H), 5.34 (s, 2H), 5.15 (d, J=9 Hz, 1H), 4.32 (dd, J=1, 15 Hz, 1H), 4.00-3.46 (m, 3H), 1.75-1.05 (m, 8H), 0.91 (t, J=7 Hz, 3H).

EXAMPLE 51 (2)

5-Benzyloxycarbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2401] 2036

[2402] TLC: Rf 0.43 (chloroform:hexane:methanol=5:5:1);

[2403] NMR (CDCl3): δ 7.88 (d, J=8 Hz, 1H), 7.78-7.64 (m, 2H), 7.60-7.28 (m, 9H), 5.34 (s, 2H), 5.15 (d, J=9 Hz, 1H), 4.32 (dd, J=1, 15 Hz, 1H), 4.02-3.48 (m, 3H), 1.70-1.10 (m, 4H), 0.87 (t, J=7 Hz, 3H).

EXAMPLE 51 (3)

5-Benzyloxycarbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2404] 2037

[2405] TLC: Rf 0.47 (chloroform:hexane:methanol=5:5:1);

[2406] NMR (CDCl3): δ 7.88 (d, J=8 Hz, 1H), 7.76-7.64 (m, 2H), 7.60-7.26 (m, 9H), 5.34 (s, 2H), 5.15 (d, J=9 Hz, 1H), 4.32 (dd, J=1, 15 Hz, 1H), 4.00-3.46 (m, 3H), 1.75-1.05 (m, 12H), 0.90 (t, J=7 Hz, 3H).

EXAMPLE 52

5-Carboxy-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2407] 2038

[2408] To a solution of the compound prepared in Example 51 (670 mg) in ethyl acetate (50 ml). Thereto was added 10% palladium carbon (220 mg). Under an atmosphere of hydrogen the mixture was stirred at room temperature for 2 hours. The reaction mixture was filtered through celite. The filtrate was washed by ethyl acetate and concentrated. The residue was dissolved in ethyl acetate under heating and was recrystallized by addition of hexane (5 ml). The crystal was separated by filtration and dried to give the compound of the present invention (471 mg) having the following physical data.

[2409] TLC: Rf 0.21 (chloroform:acetic acid=10:1);

[2410] NMR (CDCl3+acetone-d6): δ 8.02 (d, J=8 Hz, 1H), 7.86-7.72 (m, 2H), 7.72-7.58 (m, 1H), 7.58-7.32 (m, 3H), 5.33 (d, J=9 Hz, 1H), 4.30 (d, J=15 Hz, 1H), 4.24-4.06 (m, 1H), 4.20 (bs, 1H), 4.02-3. 74 (m, 2H), 1.25 (t, J=7 Hz, 3H).

EXAMPLES 52 (1)˜52 (3)

[2411] By the same procedure as described in Example 52 using the compounds prepared in Examples 51 (1)˜51 (3) instead of Example 51, the following compounds were obtained.

EXAMPLE 52 (1)

5-Carboxy-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2412] 2039

[2413] TLC: Rf 0.38 (chloroform:acetic acid=10:1);

[2414] NMR (CDCl3+acetone-d6): δ 8.00 (d, J=8 Hz, 1H), 7.88-7.72 (m, 2H), 7.72-7.56 (m, 1H), 7.56-7.34 (m, 3H), 5.32 (d, J=9 Hz,1H), 4.31 (dd, J=1, 15 Hz, 1H), 4.20 (brs, H), 4.14 (dt, J=7, 9 Hz, 1H), 4.02-3.66 (m, 2H), 1.80-1.45 (m, 2H), 1.45-1.12 (m, 6H), 0.91 (t, J=7 Hz, 3H).

EXAMPLE 52 (2)

5-Carboxy-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2415] 2040

[2416] TLC: Rf 0.34 (chloroform:acetic acid=10:1);

[2417] NMR (CDCl3+acetone-d6): δ 8.00 (d, J=8 Hz, 1H), 7.86-7.72 (m, 2H), 7.72-7.56 (m, 1H), 7.56-7.34 (m, 3H), 5.32 (d, J=9 Hz,1H), 4.31 (dd, J=1, 15 Hz, 1H), 4.20 (brs, 1H), 4.15 (dt, J=7,9 Hz, 1H), 4.00-3.66 (m, 2H), 1.74-1.48 (m, 2H), 1.48-1.20 (m, 2H), 0.92 (t, J=7 Hz, 3H).

EXAMPLE 52 (3)

5-Carboxy-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2418] 2041

[2419] TLC: Rf 0.40 (chloroform:acetic acid 10:1);

[2420] NMR (CDCl3+acetone-d6): δ 8.00 (d, J=8 Hz, 1H), 7.84-7.72 (m, 2H), 7.72-7.57 (m, 1H), 7.57-7.34 (m, 3H), 5.33 (d, J=9 Hz, 1H), 4.31 (dd, J=1, 15 Hz, 1H), 4.13 (dt, J=7, 9 Hz, 1H), 4.10 (brs,1 H ), 4.00-3.66 (m, 2H), 1.74-1.43 (m, 2H), 1.43-1.05 (m, 10H), 0.90 (t, J=7 Hz, 3H).

EXAMPLES 53˜53 (3)

[2421] By the same procedure as described in Example 32 using the compounds prepared in Examples 52˜52 (3) instead of 4-hydroxy 1,1-dioxidebenzo[b]thiophene and corresponding alcohol derivatives instead of 1-(3-hydroxypropyl)pyrrole, the following compounds of the present invention were obtained.

EXAMPLE 53

5-Methoxycarbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2422] 2042

[2423] TLC: Rf 0.35 (chloroform:hexane:methanol=5:5:1);

[2424] NMR (CDCl3): δ 6 7.91 (d, J=8 Hz, 1H), 7.84-7.72 (m, 2H), 7.72-7.57 (m, 1H), 7.57-7.32 (m, 3H), 5.21 (d, J=9 Hz,1H), 4.28 (dd, J=1,15 Hz,1H), 4.20-4.00 (m, 1H), 3.93 (s, 3H), 3.95-3.68 (m, 2H), 1.26 (t, J=7 Hz, 3H).

EXAMPLE 53 (1)

5-Methoxycarbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2425] 2043

[2426] TLC: Rf 0.42 (chloroform:hexane:methanol=5:5:1);

[2427] NMR (CDCl3): δ 7.89 (d, J=8 Hz, 1H), 7.82-7.69 (m, 2H), 7.69-7.55 (m, 1H), 7.55-7.30 (m, 3H), 5.19 (d, J=9 Hz, 1H), 4.30 (d, J=15 Hz, 1H), 4.08 (dt, J=7, 9 Hz, 1H), 3.93 (s, 3H), 3.95-3.55 (m, 2H), 1.80-1.46 (m, 2H), 1.46-1.15 (m, 6H), 0.92 (t, J=7 Hz, 3H).

EXAMPLE 53 (2)

5-Methoxycarbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2428] 2044

[2429] TLC: Rf 0.37 (chloroform:hexane:methanol=5:5:1);

[2430] NMR (CDCl3): δ 7.89 (d, J=8 Hz, 1H), 7.82-7.68 (m, 2H), 7.68-7.55 (m, 1H), 7.55-7.34 (m, 3H), 5.19 (d, J=9 Hz, 1H), 4.31 (dd, J=1, 15 Hz, 1H), 4.05 (dt, J=7, 9 Hz, 1H), 3.93 (s, 3H), 3.88-3.60 (m, 2H), 1.80-1.50 (m, 2H), 1.50-1.18 (m, 2H), 0.94 (t, J=7 Hz, 3H).

EXAMPLE 53 (3)

5-Methoxycarbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2431] 2045

[2432] TLC: Rf 0.44 (chloroform:hexane:methanol=5:5:1);

[2433] NMR (CDCl3): δ 7.89 (d, J=8 Hz, 1H), 7.80-7.69 (m, 2H), 7.69-7.55 (m, 1H), 7.55-7.34 (m, 3H), 5.19 (d, J=9 Hz, 1H), 4.30 (dd, J=1,15 Hz, 1H), 4.06 (dt, J=7, 9 Hz, 1H), 3.93 (s, 3H), 3.90-3.58 (m, 2H), 1.80-1.45 (m, 2H), 1.45-1.10 (m, 10H), 0.90 (t, J=7 Hz, 3H).

EXAMPLES 54˜54 (19)

[2434] By the same procedure as described in Example 28 using the compounds prepared in Examples 52˜52 (3) instead of 4-carboxy-1,1-dioxidebenzo[b]thiophene and amine derivatives corresponding to (pyridin-3-ylmethyl)amine, the following compounds of the present invention were obtained.

EXAMPLE 54

5-(4-(2-(2-Trifluoromethylphenyl)ethyl)piperazin-1-yl) carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2435] 2046

[2436] TLC: Rf 0.73 (chloroform:methanol=5:1);

[2437] NMR (CDCl3): δ 7.90 (d, J=8 Hz, 1H), 7.78-7.15 (m, 10H), 5.33 and 5.19 (each d, J=9 Hz, total 1H), 4.40-3.50 (m, 6H), 3.40-2.25 (m, 10H), 1.30-1.10 (m, 3H).

EXAMPLE 54 (1)

5-(4-(2-Chlorophenyl)piperazin-1-yl)carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2438] 2047

[2439] TLC: Rf 0.75 (chloroform:methanol=5:1);

[2440] NMR (CDCl3): δ 7.90 (d, J=8 Hz, 1H), 7.80-6.85 (m, 10H), 5.33 and 5.21 (each d, J=9 Hz, total 1H), 4.45-3.55 (m, 6H), 3.50-2.80 (m, 6H), 1.25 (t, J=7 Hz, 3H).

EXAMPLE 54 (2)

5-(2-Dimethylaminoethyl)carbamoyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2441] 2048

[2442] TLC: Rf 0.34 (chloroform:methanol 5:1);

[2443] NMR (CDCl3): δ 8.24 and 8.11 (each d, J=8 Hz, total 1H), 8.00-7.15 (m, 7H), 5.15 (d, J=9 Hz, 1H), 4.50-3.30 (m, 6H), 2.54 (t, J=7 Hz, 2H), 2.32 (s, 6H), 1.45-1.20 (m, 3H).

EXAMPLE 54 (3)

5-(2,3,4,5,6,7-Hexahydro-1H-azepin-1-yl)carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2444] 2049

[2445] TLC: Rf 0.19 (ethyl acetate:hexane=2:1);

[2446] NMR (CDCl3): δ 7.87 (d, J=8 Hz, 1H), 7.80-7.20 (m, 6H), 5.32 and 5.20 (each d, J=9 Hz, total 1H), 4.40-2.90 (m, 8H), 2.10-1.00 (m, 11H).

EXAMPLE 54 (4)

5-(2,3-Dihydroindol-1-yl)carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2447] 2050

[2448] TLC: Rf 0.40 (ethyl acetate:hexane=2:1);

[2449] NMR (CDCl3): δ 8.29 (d, J=8 Hz, 1H), 8.05-6.90 (m, 10H), 5.38-5.10 (m, 1H), 4.50-3.40 (m, 6H), 3.16 (t, J=8 Hz, 2H), 1.40-1.00 (m, 3H).

EXAMPLE 54 (5)

5-(4-(2-(2-Trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2450] 2051

[2451] TLC: Rf 0.57 (chloroform:methanol=10:1);

[2452] NMR (CDCl3): δ 7.89 (d, J=8 Hz, 1H), 7.76-7.20 (m, 10H), 5.30 and 5.17 (each d, J=9 Hz, total 1H), 4.25 (d, J=15 Hz, 1H), 4.20-3.50 (m, 5H), 3.50-2.80 (m, 4H), 280-2.20 (m, 6H), 1.90-1.05 (m, 8H), 0.90 (t, J=7 Hz, 3H).

EXAMPLE 54 (6)

5-(4-(2-Chlorophenyl)piperazin-1-yl)carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-di oxidebenzo[b]thiophene

[2453] 2052

[2454] TLC: Rf 0.66 (chloroform:methanol 10:1);

[2455] NMR (DMSO-d6): δ 8.31 (s, 1H), 8.00-6.95 (m, 10H), 5.66 (d, J=9 Hz, 1H), 4.32 (d, J=15 Hz, 1H), 4.22-2.70 (m, 11H), 1.60-1.02 (m, 8H), 0.87 (t, J=7 Hz, 3H).

EXAMPLE 54 (7)

5-(2-Dimethylaminoethyl)carbamoyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2456] 2053

[2457] TLC: Rf 0.23 (chloroform:methanol=10:1);

[2458] NMR (CDCl3): δ 8.21 and 8.07 (each d, J=8 Hz, total 1H), 7.90-7.10 (m, 7H), 5.13 (d, J=9 Hz,1H), 4.32 (d, J=15 Hz, 1H), 4.25-3.35 (m, 5H), 2.56 and 2.57 (each t, J=6 Hz, total 2H), 2.33 (s, 6H), 2.05-1.10 (m, 8H), 0.92 (t, J=7 Hz, 3H).

EXAMPLE 54 (8)

5-(2,3,4,5,6,7-Hexahydro-1H-azepin-1-yl)carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2459] 2054

[2460] TLC: Rf 0.23 (hexane:ethyl acetate 1:1);

[2461] NMR (CDCl3): δ 7.86 (d, J=8 Hz, 1lH), 7.78-7.20 (m, 6H), 5.30 and 5.18 (each d, J=9 Hz, total 1H), 4.25 (d, J=15 Hz, 1H), 4.35-3.00 (m, 7H), 2.10-1.10 (m, 16H), 0.91 (t, J=7 Hz, 3H).

EXAMPLE 54 (9)

5-(2,3-Dihydroindol-1-yl)carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2462] 2055

[2463] TLC: Rf 0.39 (hexane:ethyl acetate=1:1);

[2464] NMR (CDCl3) δ 8.29 (d, J=8 Hz, 1H), 8.10-6.80 (m, lIOH), 5.40-5.05 (m, 1H), 4.50-3.35 (m, 6H), 3.16 (t, J=8 Hz, 2H), 1.90-0.95 (m, 8H), 0.95-0.75 (m, 3H).

EXAMPLE 54 (10)

5-(4-(2-(2-Trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2465] 2056

[2466] TLC: Rf 0.56 (chloroform:methanol=10:1);

[2467] NMR (CDCl3): δ7.88 (d, J=8 Hz, 1H), 7.80-7.00 (m, 10H), 5.30 and 5.18 (each d, J=9 Hz, total 1H), 4.40-3.45 (m, 6H), 3.45-2.80 (m, 4H), 2.80-2.15 (m, 6H), 2.00-1.10 (m, 4H), 0.97 and 0.91 (each t, J=7 Hz, total 3H).

EXAMPLE 54 (11)

5-(4-(2-Chlorophenyl)piperazin-1-yl)carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2468] 2057

[2469] TLC: Rf 0.65 (chloroform:methanol=10:1);

[2470] NMR (CDCl3): δ 7.89 (d, J=8 Hz, 1H), 7.80-7.17 (m, 8H), 7.17-6.85 (m, 2H), 5.31 and 5.19 (each d, J=9 Hz, total 1H), 4.40-3.55 (m, 6H), 3.55-2.70 (m, 6H), 2.00-1.15 (m, 4H), 0.99 and 0.94 (each t, J=7 Hz, total 3H).

EXAMPLE 54 (12)

5-(2-Dimethylamino ethyl)carbamoyl-4-butoxy-3-phenyl sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2471] 2058

[2472] TLC: Rf 0.21 (chloroform:methanol=10:1);

[2473] NMR (CDCl3): δ 8.08 (d, J=8 Hz, 1H), 7.85-7.35 (m, 6H), 7.25 (broad peak, 1H), 5.13 (d, J=9 Hz, 1H), 4.32 (d, J=15 Hz, 1H), 4.05-3.66 (m, 3H), 3.66-3.35 (m, 2H), 2.52 (t, J=7 Hz, 2H), 2.3 1 (s, 6H), 1.90-1.15 (m, 4H), 0.96 (t, J=7 Hz, 3H).

EXAMPLE 54 (13)

5-(2,3,4,5,6,7-Hexahydro-1H-azepin-1-yl)carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2474] 2059

[2475] TLC: Rf 0.19 (ethyl acetate:hexane=1:1);

[2476] NMR (CDCl3). δ 7.85 (d, J=8 Hz, 1H), 7.76-7.20 (m, 6H), 5.29 and 5.18 (each d, J=9 Hz, total 1H), 4.25 (d, J=15 Hz, 1H), 4.25-3.60 (m, 4H), 3.60-3.00 (m, 3H), 2.10-1.10 (m, 12H), 0.96 and 0.92 (each t, J=7 Hz, total 3H).

EXAMPLE 54 (14)

5-(2,3-Dihydroindol-1-yl)carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2477] 2060

[2478] TLC: Rf 0.31 (ethyl acetate:hexane=1:1);

[2479] NMR (CDCl3): δ 8.29 (d, J=8 Hz, 1H), 8.05-7.42 (m, 6H), 7.42-6.95 (m, 4H), 5.36-5.06 (m, 1H), 4.50-3.40 (m, 6H), 3.16 (t, J=7 Hz), 1.90-1.05 (m, 4H), 0.81 (t, J=7 Hz, 3H).

EXAMPLE 54 (15)

5-(4-(2-(2-Trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2480] 2061

[2481] TLC: Rf 0.66 (chloroform:methanol=10:1);

[2482] NMR (CDCl3): δ 7.89 (d, J=8 Hz, 1H), 7.80-7.20 (m, 10H), 5.30 and 5.17 (each d, J=9 Hz, total 1H), 4.25 (d, J=15 Hz, 1H), 4.30-3.55 (m, 5H), 3.55-2.80 (m, 4H), 2.80-2.25 (m, 6H), 1.90-1.05 (m, 12H), 0.88 (t, J=7 Hz, 3H).

EXAMPLE 54 (16)

[2483] 5-(4-(2-Chlorophenyl)piperazin-1-yl)carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene 2062

[2484] TLC: Rf 0.74 (chloroform:methanol 10:1);

[2485] NMR (CDCl3): δ 7.89 (d, J=8 Hz, 1H), 7.82-6.85 (m, 10H), 5.31 and 5.19 (each d, J=9 Hz, total 1H), 4.38-2.70 (m, 12H), 1.90-1.05 (m, 12H), 0.89 (t, J=7 Hz, 3H).

EXAMPLE 54 (17)

5-(2-Dimethylaminoethyl)carbamoyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2486] 2063

[2487] TLC: Rf 0.34 (chloroform:methanol=10:1);

[2488] NMR (CDCl3): δ 7.99 (d, J=8 Hz, 1H), 7.92-7.10 (m, 7H), 5.30-5.00 (m, 1H), 4.40-3.45 (m, 6H), 2.70 (t, J=6 Hz, 2H), 2.46 (s, 6H), 1.95-1.05 (m, 12H), 0.90 (t, J=7 Hz, 3H).

EXAMPLE 54 (18)

5-(2,3,4,5,6,7-Hexahydro-1H-azepin-1-yl)carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2489] 2064

[2490] TLC: Rf 0.26 (hexane:ethyl acetate 1:1);

[2491] NMR (CDCl3): δ 7.85 (d, J=8 Hz, 1H), 7.88-7.15 (m, 6H), 5.29 and 5.18 (each d, J=9 Hz, total 1H), 4.40-3.00 (m, 8H), 2.10-1.05 (m, 20H), 0.90 (t, J=7 Hz, 3H).

EXAMPLE 54 (19)

5-(2,3-Dihydroindol-1-yl)carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2492] 2065

[2493] TLC: Rf 0.43 (hexane:ethyl acetate=1:1);

[2494] NMR (CDCl3): δ 8.29 (d, J=8 Hz, 1H), 8.10-6.80 (m, 10H), 5.40-5.05 (m, 1H), 4.60-3.40 (m, 6H), 3.16 (t, J=8 Hz, 2H), 1.90-1.00 (m, 12H), 0.85 (t, J=7 Hz, 3H).

EXAMPLE 55

5-Hydroxy-4-formylbenzo[b]thiophene

[2495] 2066

[2496] To a solution of 5-hydroxybenzo[b]thiophene (3.0 g) in methylene chloride (60 ml), were added at 0° C. dichloromethyl methyl ether (4.52 ml) and titanium tetrachloride (5.48 ml) dropwise. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured onto ice-water. The mixture was extracted by ethyl acetate. The extract was washed by a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue was purified with column chromatography on silica gel (methylene chloride) to give the compound of the present invention (1.50 g) having the following physical data.

[2497] TLC: Rf 0.69 (hexane:ethyl acetate=2:1);

[2498] NMR (CDCl3): δ 11.97 (s, 1H), 10.55 (s, 1H), 7.96 (d, J=8.8 Hz, 1H), 7.77 (d, J=5.6 Hz, 1H), 7.72 (d, J=5.6 Hz, 1H), 7.02 (d, J=8.8 Hz, 1H).

EXAMPLE 56

5-Benzyloxy-4-formylbenzo[b]thiophene

[2499] 2067

[2500] By the same procedure as described in Example 18 using the compound prepared in Example 55 instead of the compound prepared in Example 9 (12) and benzylbromide instead of 4-nitrobenzylbromide, the compound of the present invention having the following physical data was obtained.

[2501] TLC: Rf 0.65 (hexane:ethyl acetate=2:1);

[2502] NMR (CDCl3): δ 10.81 (s, 1H), 8.43 (d, J=5.6 Hz, 1H), 8.00 (d, J=8.8 Hz, 1H), 7.68 (d, J=5.6 Hz, 1H), 7.55-7.30 (m, 5H), 7.15 (d, J=8.8 Hz, 1H), 5.28 (s, 2H).

EXAMPLE 57

5-Benzyloxy-4-hydroxymethylbenzo[b]thiophene

[2503] 2068

[2504] To a solution of the compound prepared in Example 56 (1.24 g) in methylene chloride (9.0 ml), were added sodium borohydride (246 mg) and methanol, (3.0 ml). The mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured onto 1 N hydrochloric acid and was extracted by ethyl acetate. The extract was washed by a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue was purified with chromatography on silica gel (hexane:ethyl acetate=4:1) to give the compound of the present invention (1.25 g) having the following physical data.

[2505] TLC: Rf 0.40 (hexane:ethyl acetate=2:1);

[2506] NMR (CDCl3): δ 7.76 (d, J=8.8 Hz, 1H), 7.54-7.28 (m, 7H), 7.12 (d, J=8.8 Hz, 1H), 5.20 (s, 2H), 5.04 (br-s, 2H), 2.30-2.12 (br, 1H).

EXAMPLE 58

5-Benzyloxy-4-hydroxymethyl-1,1-dioxidebenzo[b]thiophene

[2507] 2069

[2508] By the same procedure as described in Example 3 using the compound prepared in Example 57 instead of the compound prepared in Example 1, the compound having the following physical data was obtained (with the proviso that 3-chloroperbenzoic acid was used instead of OXONE@ as an oxidizer.).

[2509] TLC: Rf 0.43 (hexane:ethyl acetate=1:1);

[2510] NMR (CDCl3): δ 7.61 (d, J=7.0 Hz,1H), 7.56 (d, J=7.0 Hz, 1H), 7.48-7.34 (m, 5H), 7.02 (d, J=8.4 Hz, 1H), 6.75 (d, J=7.0 Hz, 1H), 5.18 (s, 2H), 4.84 (brs, 2H), 2.26-2.10 (br, 1H).

EXAMPLE 59

5-Benzyloxy-4-hydroxymethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2511] 2070

[2512] By the same procedure as described in Example 1 using the compound prepared in Example 58 instead of 1,1-dioxidebenzo[b]thiophene, and thiophenol, the compound of the present invention having the following physical data was obtained.

[2513] TLC: Rf 0.60 (chloroform:ethyl acetate=19:1);

[2514] NMR (CDCl3): δ 7.67 (d, J=8.4 Hz, 1H), 7.57-7.48 (m, 2H), 7.46-7.32 (m, 8H), 7.15, (d, J=8.4 Hz, 1H), 5.24 (s, 2H), 5.19 (dd, J=6.6, 1.8 Hz, 1H), 4.99 (d, J=6.0 Hz, 2H), 3.71 (dd, J=14.0, 6.6 Hz, 1H), 3.59 (dd, J=14.0, 1.8 Hz, 1H), 2.59 (t, J=6.0 Hz,1H).

EXAMPLE 60

5-Benzyloxy-4-bromomethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenz[b]thiophene

[2515] 2071

[2516] To a solution of the compound prepared in Example 59 (1.45 g) in methylene chloride (15 ml), was added triphenylphosphine (1.38 g) and carbon tetrabromide (1.74 g). The mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated. The residue was purified with column chromatography on silica gel (hexane:ethyl acetate=2:1) to give the compound of the present invention having the following physical data.

[2517] TLC: Rf 0.76 (hexane:ethyl acetate=1:1); NMR (CDCl3): δ 7.66 (d, J=8.8 Hz, 1H), 7.60-7.51 (m, 2H), 7.50-7.30 (m, 8H), 7.12 (d, J=8.8 Hz, 1H), 5.27 (s, 2H), 5.15 (dd, J=6.8, 1.6 Hz, 1H), 5.02 (d, J=10 Hz, 1H), 4.94 (d, J=10 Hz, 1H), 3.74 (dd, J=13.8, 6.8 Hz, 1H), 3.60 (dd, J=13.8,1.6 Hz, 1H).

EXAMPLE 61

5-Benzyloxy-4-aminomethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2518] 2072

[2519] To a solution of 28% aqueous ammonia solution (6.75 ml) in tetrahydrofuran (30 ml), were added a solution of the compound prepared in Example 60 (1.60 g) in tetrahydrofuran (30 ml) and potassium carbonate (700 mg) successively. The mixture was stirred at room temperature for 1.5 hours. The reaction mixture was concentrated. The residue was purified with column chromatography on silica gel (chloroform:methanol=20:1) to give the compound of the present invention (747 mg) having the following physical data.

[2520] TLC: Rf 0.05 (hexane:ethyl acetate=1:1);

[2521] NMR (CDCl3): δ 7.63 (d, J=8.5 Hz, 1H), 7.58-7.48 (m, 2H), 7.46-7.28 (m, 8H), 7.14 (d, J=8.5 Hz, 1H), 5.23 (s, 2H), 5.13 (dd, J=6.4, 1.6 Hz, 1H), 4.12 (d, J=13.6 Hz, 1H), 4.02 (d, J=13.6 Hz, 1H), 3.70 (dd, J=14.0, 6.0 Hz, 1H), 3.59 (dd, J=14.0, 1.6 Hz, 1H).

EXAMPLE 62

5-Benzyloxy-4-t-butoxycarbonylaminomethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2522] 2073

[2523] To the solution of the compound prepared in Example 61 (735 mg) in tetrahydrofuran (12 ml) and water (3.0 ml), were added sodium bicarbonate (165 mg) and di-t-butyldicarbonate (430 mg) at 0° C. The mixture was stirred at room temperature for 1 hour. The reaction mixture was poured onto water and was extracted by ethyl acetate. The extract was washed by a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue was purified with column chromatography on silica gel (hexane:ethyl acetate=2:1) to give the compound of the present invention (867 mg) having the following physical data.

[2524] TLC: Rf 0.73 (hexane:ethyl acetate=1:1);

[2525] NMR (CDCl3): δ 7.70-7.56 (m, 3H), 7.48-7.30 (m, 8H), 7.12 (d, J=8.8 Hz, 1H), 5.66 (br-d, J=5.8 Hz, 1H), 5.22 (s, 2H), 5.20-4.88 (m, 2H), 4.25-4.10 (m, 1H), 3.71 (dd, J=14.0, 6.8 Hz, 1H), 3.56 (d, J=14.0 Hz, 1H), 1.41 (s, 9H).

EXAMPLE 63

5-Benzyloxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2526] 2074

[2527] By the same procedure as described in Example 3 using the compound prepared in Example 62 instead of the compound prepared in Example 1, the compound of the present invention having the following physical data (with the proviso that 3-chloroperbenzoic acid was used instead of OXONE@ as an oxidizer.).

[2528] TLC: Rf 0.31 (hexane:ethyl acetate=2:1);

[2529] NMR (CDCl3): δ 7.83-7.76 (m, 2H), 7.71-7.64 (m, 1H), 7.60 (d, J=8.7 Hz, 1H), 7.56-7.38 (m, 7H), 7.19 (d, J=8.7 Hz, 1H), 6.05 (brd, J=6.9 Hz, 1H), 5.27-5.15 (m, 1H), 5.25 (s, 2H), 5.10-4.95 (m, 1H), 4.27-4.16 (m, 1H), 3.81 (dd, J=15.3, 2.1 Hz, 1H), 3.74 (dd, J=15.3, 8.1, 1H), 1.37 (s, 9H).

EXAMPLE 64

5-Benzyloxy-4-aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene hydrochloride

[2530] 2075

[2531] By the same procedure as described in Example 7 using the compound prepared in Example 63 instead of the compound prepared in Example 6 (8), the compound of the present invention having the following physical data was obtained.

[2532] TLC: Rf 0.43 (chloroform:methanol=9:1);

[2533] NMR (DMSO-d6): δ 8.18 (brs, 3H), 7.86 (d, J=9.0 Hz, 1H), 7.83-7.75 (m, 3H), 7.67-7.48 (m, 5H), 7.47-7.33 (m, 3H), 6.37 (dd, J=6.0, 3.9 Hz, 1H), 5.41 (d, J=12.3 Hz, 1H), 5.33 (d, J=12.3 Hz, 1H), 4.44 (d, J=13.8 Hz, 1H), 4.24 (d, J=13.8 Hz, 1H), 3.90-3.76 (m, 2H).

EXAMPLE 65

5- Hydroxy-4-t-butoxycarbonylaminoethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2534] 2076

[2535] By the same procedure as described in Example 52 using the compound prepared in Example 63 instead of the compound prepared in Example 51, the compound of the present invention having the following physical data was obtained.

[2536] TLC: Rf 0.22 (hexane:ethyl acetate=1:1);

[2537] NMR (CDCl3): δ 10.75 (s, 1H), 7.75-7.58 (m, 3H), 7.56-7.41 (m, 3H), 7.18 (d, J=8.6 Hz, 1H), 6.35-6.50 (m, 1H), 5.24-5.15 (m, 1H), 4.76-4.60 (m, 1H), 4.34 (dd, J=16.0, 5.4 Hz,1H), 3.86-3.66 (m, 2H), 1.37 (s, 9H).

EXAMPLES 66˜66 (1)

[2538] By the same procedure as described in Example 29 using the compound prepared in Example 65 instead of 4-hydroxy-1,1-dioxidebenzo[b)thiophene and alcohol derivatives corresponding to 1-(3-hydroxypropyl)pyrrole, the following compounds of the present invention were obtained.

EXAMPLE 66

5-Methoxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2539] 2077

[2540] TLC: Rf 0.28 (hexane:ethyl acetate=1:1);

[2541] NMR (CDCl3): δ 7.86-7.75 (m, 2H), 7.74-7.47 (m, 4H), 7.14 (d, J=8.8 Hz, 1H), 6.10-6.00 (m, 1H), 5.32-5.18 (m, 1H), 5.10-4.92 (m, 1H), 4.25-4.10 (m, 1H), 4.00 (s, 3H), 3.85-3.65 (m, 2H), 1.38 (s, 9H).

EXAMPLE 66 (1)

5-(3-Phenylpropyl) oxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2542] 2078

[2543] TLC: Rf 0.51 (hexane:ethyl acetate=1:1);

[2544] NMR (CDCl3): δ 7.87-7.73 (m, 2H), 7.73-7.40 (m, 6H), 7.40-7.16 (m, 3H), 7.07 (d, J=8.8 Hz, 1H), 6.55-6.30 (br, 1H), 6.07-5.95 (m, 1H), 5.26-5.12 (m, 1H), 5.10-4.90 (m, 1H), 4.20-4.05 (m, 2H), 3.86-3.64 (m, 2H), 2.86 (t, J=7.0 Hz, 2H), 2.33-2.15 (m, 2H), 1.38 (s, 9H).

EXAMPLES 67˜67(1)

[2545] By the same procedure as described in Example 7 using the compounds prepared in Examples 66˜66 (1) instead of the compound prepared in Example 6 (8), the following compounds of the present invention were obtained.

EXAMPLE 67

5-Methoxy-4-aminomethyl-3-phenyisulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2546] 2079

[2547] TLC: Rf 0.19 (chloroform:methanol=4:1);

[2548] NMR (DMSO-d6): δ 8.19 (brs, 3H), 7.89-7.76 (m, 4H), 7.68-7.60 (m, 2H), 7.47 (d, J=8.7 Hz, 1H), 6.39 (t, J=5.4 Hz, 1H), 4.47-4.28 (br, 1H), 4.25-4.08 (br, 1H), 3.98 (s, 3H), 3.82 (d, J=5.4 Hz, 2H).

EXAMPLE 67 (1)

5-(3-Phenylpropyl)oxy-4-aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thibphene.hydrochloride

[2549] 2080

[2550] TLC: Rf 0.43 (chloroform:methanol=9:1);

[2551] NMR (DMSO-d6): δ 8.14 (brs, 3H), 7.86-7.76 (m, 4H), 7.68-7.61 (m, 2H), 7.45 (d, J=8.7 Hz, 1H), 7.34-7.27 (m, 4H), 7.25-7.15 (m, 1H), 6.45-6.34 (m, 1H), 4.47-4.13 (m, 4H), 3.89-3.75 (m, 2H), 2.86-2.73 (m, 2H), 2.22-2.08 (m, 2H).

EXAMPLE 68

5-Benzyloxy-4-hydroxymethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2552] 2081

[2553] By the same procedure as described in Example 3 using the compound prepared in Example 59 instead of the compound prepared in Example 1 the compound of the present invention having the following physical data was obtained (with the proviso that 3-chloroperbenzoic acid was used instead of OXONE@ as an oxidizer).

[2554] TLC: Rf 0.25 (hexane:ethyl acetate=1:1); NMR (CDCl3): δ 7.72-7.58 (m, 3H), 7.56-7.30 (m, 8H), 7.20 (d, J=8.8 Hz, 1H), 5.53 (dd, J=8.4,1.8Hz, 1H), 5.33 (d, J=11.8 Hz, 1H), 5.25 (d, J=11.8 Hz, 1H), 5.10-5.01 (m, 2H), 3.87 (dd, J=15.4,1.8 Hz, 1H), 3.75 (dd, J=15.4,1.8 Hz, 1H), 3.40-3.28 (m, 1H).

EXAMPLE 69

5-Benzyoxy-4-carboxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2555] 2082

[2556] To a solution of the compound prepared in Example 68 (444 mg) in methylene chloride (10 ml) were added pyridinium dichromate (564 mg) and magnesium sulfate (500 mg). The mixture was stirred at room temperature for 6 hours. The undissolved ingredients were filtered off. The filtrate was poured onto 1 N hydrochloric acid and was extracted by methylene chloride. The extract was washed by a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue was washed by methanol and was dried. The obtained solid was dissolved in dimethylformamide (16 ml) and water (4.0 ml). Thereto, were added 2-methyl-2-butene (0.48 ml), sodium phosphate bishydrate (120 mg) and sodium hypochloric acid (358 mg). The mixture was stirred at room temperature for 1 hour. The reaction mixture was poured onto 0.5 N hydrochloric acid and was extracted by ethyl acetate. The extract was concentrated. The residue was washed by ether to give the compound of the present invention (305 mg) having the following physical data.

[2557] TLC: Rf 0.17 (chloroform:methanol=9:1);

[2558] NMR (DMSO-d6): δ 13.52 (s, 1H), 7.92-7.68 (m, 4H), 7.67-7.30 (m, 8H), 5.88 (d, J 9.0 Hz, 1H), 5.37 (s, 2H), 4.09 (dd, J=15.0, 9.0 Hz, 1H), 3.88 (d, J=15.0 Hz, 1H).

EXAMPLE 70

5-Benzyloxy-4-(pyridin-3-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2559] 2083

[2560] By the same procedure as described in Example 28 using the compound prepared in Example 69 instead of 4-carboxy-1,1-dioxidebenzo[b]thiophene, and (pyridin-3-ylmethyl)amine, the compound of the present invention having the following physical data was obtained.

[2561] TLC: Rf 0.53 (chloroform:methanol=9:1);

[2562] NMR (DMSO-d6): δ 9.05 (t, J=6.0 Hz, 1H), 8.59 (d, J=1.5 Hz, 1H), 8.41 (dd, J=4.8, 1.5 Hz,1H), 7.85 (d, J=8.7 Hz, 1H), 7.80-7.72 (m, 3H), 7.65-7.55 (m, 4H), 7.48-7.41 (m, 2H), 7.38-7.30 (m, 3H), 7.15 (dd, J=8.1, 4.8 Hz, 1H), 5.96 (d, J=9.0 Hz, 1H), 5.29 (s, 2H), 4.63 (dd, J=15.0, 6.0 Hz,1H), 4.35 (dd, J=15.0, 6.0 Hz, 1H), 4.06 (dd, J=15.0,9.0 Hz, 1H), 3.87 (d, J=15.0 Hz, 1H).

EXAMPLE 71

5-Hydroxy-4-(pyridin-3-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2563] 2084

[2564] By the same procedure as described in Example 52 using the compound prepared in Example 70 instead of the compound prepared in Example 51, the compound of the present invention having the following physical data was obtained.

[2565] TLC: Rf 0.29 (chloroform:methanol=9:1);

[2566] NMR (DMSO-d6): δ 11.70 (br, 1H), 9.10-8.90 (br, 1H), 8.66 (d, 1H), 8.44 (dd, 1H), 7.88-7.81 (m, 1H), 7.78-7.68 (m, 3H), 7.67-7.54 (m, 3H), 7.34 (dd, J=7.5, 4.8 Hz, 1H), 7.23 (d, J=8.7 Hz,1H), 6.14 (d, J=9.0 Hz, 1H), 4.67 (dd, J=15.3, 6.3 Hz, 1H), 4.39 (dd, J=15.3, 5.4 Hz, 1H), 4.02 (dd, J=15.0, 9.0 Hz, 1H), 3.84 (d, J=15.0 Hz, 1H).

EXAMPLES 72˜72 (31)

[2567] By the same procedure as described in Example 28 using carboxylic acids corresponding to 4-carboxy-1,1-dioxidebenzo[b]thiophene and amine derivatives corresponding to (pyridin-3-ylmethyl)amine, and if necessary, by converting into the corresponding salts by known methods, the following compounds of the present invention were obtained.

EXAMPLE 72

4-(1,1-Dimethyl-2-hydroxyethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2568] 2085

[2569] TLC: Rf 0.64 (ethyl acetate);

[2570] NMR (DMSO-d6): δ 8.05 (brs, 1H), 7.91 (d, J=7.4 Hz, 1H), 7.76 (d, J=7.0 Hz, 1H), 7.75 (d, J=7.4 Hz, 1H), 7.63 (t, J=7.4 Hz, 1H), 7.43 (d, J=7.0 Hz, 1H), 4.87 (t, J=5.8 Hz, 1H), 3.54 (d, J=5.8 Hz, 2H), 1.29 (s, 6H).

EXAMPLE 72 (1)

4-(2-Hydroxyethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2571] 2086

[2572] TLC: Rf 0.30 (ethyl acetate);

[2573] NMR (DMSO-d6): δ 8.72 (t, J=5.6 Hz, 1H), 7.95 (d, J=7.4 Hz, 1H), 7.88-7.80 (m, 2H), 7.66 (t, J=7.4 Hz, 1H), 7.45 (d, J=7.0 Hz, 1H), 4.77 (t, J=5.6 Hz, 1H), 3.53 (q, J=5.6 Hz, 2H), 3.33 (q, J=5.6 Hz, 2H).

EXAMPLE 72 (2)

4-(4-(2-Hydroxyethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene

[2574] 2087

[2575] TLC: Rf 0.45 (ethyl acetate:methanol=9:1);

[2576] NMR (CDCl3): δ 7.76 (d, J=7.5 Hz, 1H), 7.57 (t, J=7.5 Hz, 1H), 7.47 (dd, J=7.5, 1.2 Hz, 1H), 7.32 (dd, J=7.2, 1.2 Hz, 1H), 6.79 (d, J=7.2 Hz, 1H), 4.26-4.19 (m, 1H), 4.03-3.96 (m,1H), 3.88-3.78 (m, 2H), 3.35 (br, 2H), 2.72-2.67 (m, 2H), 2.67-2.60 (m, 2H), 2.50-2.42 (m, 2H).

EXAMPLE 72 (3)

4-(N-Methyl-N-methoxycarbamoyl)-1,1-dioxidebenzo[b]thiophene

[2577] 2088

[2578] TLC: Rf 0.22 (hexane:ethyl acetate=1:1);

[2579] NMR (CDCl3) δ 7.78 (dt, J=7.8, 1.0 Hz, 1H), 7.72 (dd, J=7.8, 1.0 Hz, 1H), 7.57 (t, J=7.8 Hz, 1H), 7.41 (dd, J=7.0, 1.0 Hz, 1H), 6.76 (d, J=7.0 Hz, 1H), 3.49 (s, 3H), 3.40 (s, 3H).

EXAMPLE 72 (4)

4-(4-(Thiazol-2-ylsulfamoyl)phenyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2580] 2089

[2581] TLC: Rf 0.20 (chloroform:methanol 9:1);

[2582] NMR (CDCl3+DMSO-d6): δ 10.71 (s, 1H), 7.98 (d, J=7.5 Hz, 1H), 7.90-7.67 (m, 6H), 7.67 (t, J=7.8 Hz, 1H), 6.97 (d, J=7.5 Hz, 1H), 6.94 (d, J=5 Hz, 1H), 6.52 (d, J=5 Hz, 1H), 5.30 (broad peak, 1H).

EXAMPLE 72 (5)

4-((1 R)-1-t-Butoxycarbonyl-2-methylpropyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2583] 2090

[2584] TLC: Rf 0.48 (hexane:ethyl acetate=1:1);

[2585] NMR (CDCl3): δ 7.95 (dd, J=7.2, 1.0 Hz, 1H), 7.81 (d, J=7.8 Hz, 1H), 7.76 (dd, J=7.8, 1.0 Hz, 1H), 7.59 (t, J=7.8 Hz, 1H), 6.78 (d, J=7.2 Hz, 1H), 6.55 (d, J=8.4 Hz, 1H), 4.64 (dd, J=8.4, 4.5 Hz, 1H), 2.36-2.25 (m, 1H), 1.51 (s, 9H), 1.02 (d, J=6.9 Hz, 3H), 0.98 (d, J=6.9 Hz, 3H).

EXAMPLE 72 (6)

6-(1-Benzylpiperidin-4-yl)carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2586] 2091

[2587] TLC: Rf 0.44 (ethyl acetate:methanol 4:1);

[2588] NMR (CDCl3): δ 7.66 (s, 1H), 7.54 (s, 1H), 7.45 (d, J=7.0 Hz, 1H), 7.40-7.20 (m, 5H), 6.73 (d, J=7.0 Hz, 1H), 6.40-6.20 (m, 1H), 4.10-3.90 (m, 1H), 3.97 (s, 3H), 3.53 (s, 2H), 3.00-2.80 (m, 2H), 2.30-2.10 (m, 2H), 2.10-1.90 (m, 2H), 1.70-1.50 (m, 2H).

EXAMPLE 72 (7)

6-(2-Diethylaminoethyl)carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2589] 2092

[2590] TLC: Rf 0.33 (ethyl acetate:methanol:triethylamine=14:4:1);

[2591] NMR (CDCl3): δ 7.71 (s, 1H), 7.57 (s, 1H), 7.46 (d, J=6.9 Hz, 1H), 7.10-7.00 (m,1H), 6.71 (d, J=6.9 Hz, 1H), 3.98 (s, 3H), 3.52 (q, J=5.5 Hz, 2H), 2.53 (t, J=5.5 Hz, 2H), 2.28 (s, 6H).

EXAMPLE 72 (8)

6-(Pyridin-3-ylmethyl)carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2592] 2093

[2593] TLC: Rf 0.49 (ethyl acetate:methanol=4:1);

[2594] NMR (DMSO-d6): δ 9.36 (t, J=6.0 Hz, 1H), 8.58 (s, 1H), 8.48 (d, J=4.5 Hz, 1H), 7.88 (s, 1H), 7.81 (s, 1H), 7.75 (d, J=7.8Hz, 1H), 7.64 (d, J=7.0Hz, 1H), 7.42 (d, J=7.0 Hz, 1H), 7.36 (dd, J=7.8, 4.5 Hz, 1H), 4.53 (d, J=6.0 Hz, 2H), 3.99 (s, 3H).

EXAMPLE 72 (9)

5-(6-Dimethylaminohexyl)oxycarbonyl-1,1-dioxidebenzo[b]thiophene -hydrochloride

[2595] 2094

[2596] TLC: Rf 0.16 (chloroform:methanol=9:1);

[2597] NMR (CDCl3): δ 12.60-12.30 (br, 1H), 7.96 (d, J=7.4 Hz, 1H), 7.54-7.43 (m, 2H), 6.76 (d, J=7.2 Hz, 1H), 4.35 (t, J=6.6 Hz, 2H), 3.97 (s, 3H), 3.06-2.90 (m, 2H), 2.81 (s, 3H), 2.79 (s, 3H), 2.03-1.73 (m, 4H ), 1.57-1.35 (m, 4H).

EXAMPLE 72 (11)

4-(4-t-Butoxycarbonylpiperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene

[2598] 2095

[2599] TLC: Rf 0.65 (methylene chloride:methanol 10:1);

[2600] NMR (CDCl3): δ 7.78 (dd, J=7.2, 1.2 Hz, 1H), 7.59 (t, J=7.2 Hz, 1H), 7.48 (dd, J=7.2, 1.2 Hz, 1H), 7.32 (d, J=6.9 Hz, 1H), 6.80 (d, J=6.9 Hz, 1H), 3.85-3.70 (m, 2H), 3.65-3.45 (m, 2H), 3.45-3.24 (m, 4H), 1.47 (s, 9H).

EXAMPLE 72 (11)

4-(Piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene hydrochloride

[2601] 2096

[2602] TLC: Rf 0.13 (methylene chloride:methanol=10:1);

[2603] NMR (DMSO-d6): δ 9.35 (bs, 2H), 7.96 (d, J=6.9 Hz, 1H), 7.80-7.73 (m, 2H), 7.60 (d, J=7.2 Hz, 1H), 7.51 (d, J=7.2 Hz, 1H), 4.00-3.80 (m, 2H), 3.60-3.40 (m, 2H), 3.30-3.15 (m, 2H), 3.15-3.00 (m, 2H).

EXAMPLE 72 (12)

4-(4-(4-Methoxyphenylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2604] 2097

[2605] TLC: Rf 0.50 (methylene chloride:methanol=10:1);

[2606] NMR (DMSO-d6): δ 7.97 (t, J=4.2 Hz, 1H), 7.71 (d, J=4.2 Hz, 2H), 7.58-7.43 (m, 2H), 7.54 (d, J=4.2 Hz, 2H), 7.01 (d, J=8.4 Hz, 2H), 4.65-4.50 (m, 1H), 4.30-4.20 (m, 2H), 3.78 (s, 3H), 3.70-3.00 (m, 8H).

EXAMPLE 72 (13)

4-(4-(4-Phenylphenylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2607] 2098

[2608] TLC: Rf 0.33 (ethyl acetate);

[2609] NMR (DMSO-d6): δ 8.00-7.92 (m, 1H), 7.80-7.64 (m, 8H), 7.60-7.35 (m, 5H), 4.65-4.50 (m, 1H), 4.48-4.30 (m, 2H), 3.70-3.00 (m, 8H).

EXAMPLE 72 (14)

4-(4-(Naphthalen-1-ylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2610] 2099

[2611] TLC: Rf 0.70 (ethyl acetate);

[2612] NMR (DMSO-d6): δ 8.42-7.30 (m, 1H), 8.13-7.77 (m, 4H), 7.76-7.40 (m, 7H), 4.93-4.76 (m, 2H), 4.66-4.53 (m, 1H), 3.64-3.00 (m, 8H).

EXAMPLE 72 (15)

4-(4-(4-Ethylphenylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2613] 2100

[2614] TLC: Rf 0.40 (ethyl acetate);

[2615] NMR (DMSO-d6): δ 7.98 (t, J=4.2 Hz, 1H), 7.71 (d, J=4.2 Hz, 2H), 7.56 (d, J=7.2 Hz, 1H), 7.52 (d, J=7.2 Hz, 1H), 7.47 (d, J=7.8 Hz, 2H), 7.31 (d, J=7.8 Hz, 2H), 4.66-4.45 (m, 1H), 4.33-4.20 (m, 2H), 3.66-3.00 (m, 8H), 2.63 (q, J=7.5 Hz, 2H), 1.19 (t, J=7.5 Hz, 3H).

EXAMPLE 72 (16)

4-(4-(Naphthalen-2-ylcarbonylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene hydrochloride

[2616] 2101

[2617] TLC: Rf 0.40 (ethyl acetate);

[2618] NMR (DMSO-d6): δ 8.72 (s, 1H), 8.20-7.93 (m, 5H), 7.80-7.64 (m, 4H), 7.60 (d, J=7.2 Hz, 1H), 7.55 (d, J=7.2 Hz, 1H), 5.30-5.10 (m, 2H), 4.60-4.40 (m, 1H), 3.80-3.10 (m, 8H).

EXAMPLE 72 (17)

[2619] 4-(4-(Pyridin-2-ylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.2hydrochloride 2102

[2620] TLC: Rf 0.46 (methylene chloride:methanol=10:1);

[2621] NMR (DMSO-d6): δ 8.69 (d, J=5.1 Hz, 1H), 8.00-7.90 (m, 2H), 7.75-7.64 (m, 3H), 7.60-7.46 (m, 3H), 4.50 (s, 2H), 4.09-3.90 (m, 2H),3.67-3.59 (m, 2H), 3.48-3.35 (m, 2H), 3.33-3.20 (m, 2H).

EXAMPLE 72 (18)

4-(4-(Pyridin-3-ylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[2622] 2103

[2623] TLC: Rf 0.46 (methylene chloride:methanol=10:1);

[2624] NMR (DMSO-d6): δ 8.90 (s, 1H), 8.80-8.73 (m, 1H), 8.36-8.30 (m, 1H), 7.98-7.92 (m, 1H), 7.80-7.66 (m, 3H), 7.57 (d, J=7.2 Hz, 1H), 7.52 (d, J=7.2 Hz, 1H), 4.50-3.00 (m, 10H).

EXAMPLE 72 (19)

4-(4-benzoylpiperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene

[2625] 2104

[2626] TLC: Rf 0.52 (methylene chloride:methanol=10:1);

[2627] NMR (CDCl3): δ 7.79 (d, J=7.5 Hz, 1H), 7.59 (t, J=7.5 Hz, 1H), 7.53-7.36 (m, 6H), 7.34 (d, J=6.0 Hz, 1H), 6.81 (d, J=7.5 Hz, 1H), 4.00-3.25 (m, 8H).

EXAMPLE 72 (20)

4-(4-(Furan-2-ylcarbonyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene

[2628] 2105

[2629] TLC: Rf 0.46 (methylene chloride:methanol=10:1);

[2630] NMR (CDCl3): δ 7.80 (d, J=6.9 Hz, 1H), 7.61 (t, J=7.8 Hz, 1H), 7.51 (d, J=7.8 Hz, 2H), 7.35 (d, J=6.9 Hz, 1H), 7.11 (d, J=3.6 Hz, 1H), 6.81 (d, J=6.9 Hz, 1H), 6.52 (d, J=3.6 Hz, 1H), 4.06-3.36 (m, 8H).

EXAMPLE 72 (21)

4-(4-Benzylcarbonylpiperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene

[2631] 2106

[2632] TLC: Rf 0.47 (methylene chloride:methanol=10:1);

[2633] NMR (CDCl3): δ 7.77 (d, J=7.5 Hz, 1H), 7.57 (t, J=7.5 Hz, 1H), 7.48-7.14 (m, 6H), 7.28 (d, J=7.2 Hz, 1H), 6.78 (d, J=7.2 Hz, 1H), 3.86-3.00 (m, 10H).

EXAMPLE 72 (22)

4-(2-(pyrrolidin-1-yl)ethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2634] 2107

[2635] TLC: Rf 0.26 (ethyl acetate:acetic acid:water=3:1:1);

[2636] NMR (CDCl3): δ 8.00 (dd, J=7.5 Hz and 1 Hz, 1H), 7.79 (dt, J=7.5 Hz and 1 Hz, 1H), 7.72 (dd, J=7.5 Hz and 1 Hz, 1H), 7.57 (t, J=7.5 Hz, 1H), 6.90 (broad s, 1H), 6.76 (d, J=7.5 Hz, 1H), 3.55 (m, 2H ), 2.73 (t, J=6 Hz, 2H), 2.57 (m, 4H), 1.80 (m, 4H).

EXAMPLE 72 (23)

4-(3-(Pyrrolidin-1-yl)propyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2637] 2108

[2638] TLC: Rf 0.19 (ethyl acetate acetic acid:water 3:1:1);

[2639] NMR (CDCl3): δ 9.30 (broad s, 1H), 8.17 (d, J=7.5 Hz, 1H), 7.78 (d, J=7.5 Hz, 1H), 7.64 (d, J=7.5 Hz, 1H), 7.52 (t, J=7.5 Hz, 1H), 6.76 (d, J=7.5 Hz, 1H), 3.58 (m, 2H), 2.76 (t, J=6 Hz, 2H), 2.5 9 (m, 4H), 2.00-1.70 (m, 6H).

EXAMPLE 72 (24)

4-(4-(2-Methylphenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2640] 2109

[2641] TLC: Rf 0.64 (ethyl acetate:hexane=2:1);

[2642] NMR (DMSO-d6): δ 7.97-7.90 (m, 1H), 7.74-7.65 (m, 2H), 7.57 (d, J=7.2 Hz, 1H), 7.51 (d, J=7.2 Hz, 1H), 7.20-7.10 (m, 2H), 7.06-6.93 (m, 2H), 3.90-3.78 (m, 2H), 3.45-3.34 (m, 2H), 3.00-2.90 (m, 2H), 2.85-2.74 (m, 2H), 2.27 (s, 3H).

EXAMPLE 72 (25)

4-(4-(3-Methylphenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2643] 2110

[2644] TLC: Rf 0.48 (ethyl acetate:hexane=2:1);

[2645] NMR (DMSO-d6): δ 8.00-7.92 (m, 1H), 7.74-7.66 (m, 2H), 7.56 (d, J=7.2 Hz, 1H), 7.49 (d, J=7.2 Hz, 1H), 7.14 (t, J=7.8 Hz, 1H), 6.90-6.80 (m, 2H), 6.71 (d, J=7.8 Hz, 1H), 3.90-3.80(m, 2H), 3. 46-3.36 (m, 2H), 3.36-3.24 (m, 2H), 3.18-3.08 (m, 2H), 2.56 (s, 3H).

EXAMPLE 72 (26)

4-(4-(2-Fluorophenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2646] 2111

[2647] TLC: Rf 0.59 (ethyl acetate:hexane=2:1);

[2648] NMR (DMSO-d6): δ 8.00-7.90 (m, 1H), 7.74-7.66 (m, 2H), 7.56 (d, J=7.2 Hz, 1H), 7.50 (d, J=7.2 Hz, 1H), 7.20-6.96 (m, 4H), 3.90-3.80 (m, 2H), 3.46-3.36 (m, 2H), 3.18-3.06 (m, 2H), 3.02-2.90 (m, 2H).

EXAMPLE 72 (27)

4-(4-(4-Fluorophenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2649] 2112

[2650] TLC: Rf 0.40 (ethyl acetate:hexane=2:1);

[2651] NMR (DMSO-d6): δ 8.00-7.90 (m, 1H), 7.74-7.65 (m, 2H), 7.54 (d, J=6.9 Hz, 1H), 7.49 (d, J=6.9 Hz, 1H), 7.14-6.97 (m, 4H), 3.89-3.78 (m, 2H), 3.45-3.34 (m, 2H), 3.30-3.19 (m, 2H), 3.13-3.00 (m, 2H).

EXAMPLE 72 (28)

4-(4-(4-Methoxyphenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2652] 2113

[2653] TLC: Rf 0.22 (ethyl acetate:hexane=2:1);

[2654] NMR (DMSO-d6): δ 8.00-7.92 (m, 1H), 7.77-7.66 (m, 2H), 7.58 (d, J=6.9 Hz, 1H), 7.50 (d, J=6.9 Hz, 1H), 7.13-7.08 (m, 2H), 6.96-6.86 (m, 2H), 4.10-3.70 (m, 2H), 3.72 (s, 3H), 3.54-3.40 (m, 2H), 3.38-3.22 (m, 2H), 3.20-3.06 (m, 2H).

EXAMPLE 72 (29)

4-(4-(3-Trifluoromethylphenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2655] 2114

[2656] TLC: Rf 0.47 (ethyl acetate:hexane=2:1);

[2657] NMR (DMSO-d6): δ 7.98-7.93 (m, 1H), 7.74-7.67 (m, 2H), 7.56 (d, J=6.9 Hz, 1H), 7.49 (d, J=6.9 Hz, 1H), 7.48-7.40 (m, 1H), 7.27-7.16 (m, 2H), 7.14-7.07 (m, 1H), 3.88-3.67 (m, 2H), 3.46-3.34 (m, 4H), 3.27-3.18 (m, 2H).

EXAMPLE 72 (30)

4-((3R)-1-Benzylpyrrolidin-3-yl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2658] 2115

[2659] TLC: Rf 0.45 (chloroform:methanol=9:1);

[2660] NMR (CDCl3): δ 7.92 (dd, J=1.0 Hz and 7.0 Hz, 1H), 7.77 (d, J=7.5 Hz, 1H), 7.68 (dd, J=1.0 Hz and 7.5 Hz, 1H), 7.54 (t, J=7.5 Hz, 1H), 7.40-7.20 (m, 5H), 6.75 (d, J=7.0 Hz, 1H), 6.70 (m, 1H), 4.65 (m, 1H), 3.66 (s, 2H), 3.05-2.95 (m, 1H), 2.78 (dd, J=1.0 Hz and 10 Hz, 1H), 2.60 (dd, J=6.0 Hz and 10 Hz, 1H), 2.50-2.20 (m, 2H), 1.85-1.70 (m, 1H).

EXAMPLE 72 (31)

4-((3S)-1-Benzylpyrrolidin-3-yl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2661] 2116

[2662] TLC: Rf 0.45 (chloroform:methanol=9:1);

[2663] NMR (CDCl3): δ 7.92 (dd, J=1.0 Hz and 7.0 Hz, 1H), 7.77 (d, J=7.5 Hz, 1H), 7.68 (dd, J=1.0 Hz and 7.5 Hz, 1H), 7.54 (t, J=7.5 Hz, 1H), 7.40-7.20 (m, 5H), 6.75 (d, J=7.0 Hz, 1H), 6.70 (m, 1H), 4.65 (m, 1H), 3.66 (s, 2H), 3.05-2.95 (m, 1H), 2.78 (dd, J=1.0 Hz and 10 Hz, 1H), 2.60 (dd, J=6.0 Hz and 10 Hz, 1H), 2.50-2.20 (m, 2H), 1.85-1.70 (m, 1H).

EXAMPLES 73˜73 (29)

[2664] By the same procedure as described in Example 18 using an alcohol derivative corresponding to the compound prepared in Example 9 (12) and a halogenated compound corresponding to 4-nitrobenzylbromide, or by the same procedure as described in Example 29 using an alcohol derivative corresponding to 4-hydroxy-1,1-dioxidebenzo[b]thiophene and an alcohol derivative corresponding to 1-(3-hydroxypropyl)pyrrole, the following compounds of the present invention were obtained, with the proviso that when the compounds of the following Examples 73 (26)˜73 (29) were prepared by the same procedure as described in Example 18, an aqueous solution of sodium hydroxide was used instead of potassium carbonate.

EXAMPLE 73

5-Acetylmethyloxy-1,1-dioxidebenzo[b]thiophene

[2665] 2117

[2666] TLC: Rf 0.25 (ethyl acetate:hexane:methylene chloride=1:1:1);

[2667] NMR (CDCl3): δ 7.65 (d, J=8.2Hz, 1H), 7.15 (d, J=6.8Hz, 1H),6.92 (dd, J=8.2Hz, 2.2 Hz, 1H), 6.87 (d, J=2.2 Hz, 1H), 6.75 (d, J=6.8 Hz, 1H), 4.64 (s, 2H), 2.30 (s, 3H).

EXAMPLE 73 (1)

5-Cyanomethyloxy-1,1-dioxidebenzo[b]thiophene

[2668] 2118

[2669] TLC: Rf 0.36 (hexane:ethyl acetate=1:1);

[2670] NMR (CDCl3): δ 7.72 (d, J=8.4 Hz, 1H), 7.18 (d, J=7.2 Hz, 1H), 7.07 (dd, J=8.4, 2.4 Hz, 1H), 6.98 (d, J=2.4 Hz, 1H), 6.79 (d, J=7.2 Hz, 1H), 4.86 (s, 2H).

EXAMPLE 73 (2)

5-t-Butoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene

[2671] 2119

[2672] TLC: Rf 0.54 (hexane:ethyl acetate=1:1);

[2673] NMR (CDCl3): δ 7.63, (d, J=8.4 Hz, 1H), 7.13 (d, J=6.9 Hz, 1H), 6.91 (dd, J=8.4, 2.4 Hz, 1H), 6.88 (d, J=2.4 Hz, 1H), 6.73 (d, J=6.9 Hz, 1H), 4.58 (s, 2H), 1.49 (s, 9H).

EXAMPLE 73 (3)

5-(3-(Ethoxycarbonyl)propyloxy-1,1-dioxidebenzo[b]thiophene

[2674] 2120

[2675] TLC: Rf 0.50 (hexane:ethyl acetate=1:1);

[2676] NMR (CDCl3): δ 7.61 (d, J=8.7 Hz, 1H), 7.12 (d, J=6.9 Hz, 1H), 6.94 (dd, J=8.7, 2. 0 Hz, 1H), 6.84 (d, J=2.0 Hz, 1H), 6.71 (d, J=6.9 Hz, 1H), 4.15 (q, J=7.2 Hz, 2H), 4.08 (t, J=6.6 Hz, 1H), 2.51 (t, J=6.6 Hz, 1H), 2.13 (quint, J=6.6 Hz, 1H), 1.26 (t, J 7.2 Hz, 3H).

EXAMPLE 73 (4)

5-(4-(Ethoxycarbonyl)butyl)oxy-1,1-dioxidebenzo[b]thiophene

[2677] 2121

[2678] TLC: Rf 0.48 (hexane:ethyl acetate=1:1);

[2679] NMR (CDCl3): δ 7.61 (dd, J=8.4, 0.9 Hz, 1H), 7.12 (dd, J=6.9, 0.9 Hz, 1H), 6.93 (dd, J=8.4,2.4Hz, 1H), 6.84 (d, J=2.4Hz, 1H), 6.71 (d, J=6.9Hz, 1H), 4.13 (q, J=7.0Hz, 2H), 4.03 (t, J=6.0 Hz, 2H), 2.39 (t, J=7.0 Hz, 2H), 1.88-1.80 (m, 4H), 1.26 (t, J=7.0 Hz, 3H).

EXAMPLE 73 (5)

4-(Pyridin-3-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2680] 2122

[2681] TLC: Rf 0.42 (ethyl acetate:methanol=9:1);

[2682] NMR (CDCl3): δ 5.19 (s, 2H), 6.63 (d, J=7.0 Hz, 1H), 7.13 (d, J=8.0 Hz, 1H), 7.33 (d, J=8.0 Hz, 1H), 7.37 (dd, J=8.0 Hz, 5.0 Hz, 1H), 7.45 (dd, J=7.0 Hz, 1.0 Hz, 1H), 7.49 (t, J=8.0 Hz, 1H), 7.75 (dt, J=8.0 Hz, 2.0 Hz, 1H), 8.64 (dd, J=5.0 Hz, 2.0 Hz, 1H), 8.70 (d, J=2.0 Hz, 1H).

EXAMPLE 73 (6)

4-(Pyridin-4-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2683] 2123

[2684] TLC: Rf 0.16 (methylene chloride:ethyl acetate=1:1);

[2685] NMR (CDCl3): δ 8.66 (d, J=6.0 Hz, 2H), 7.51 (dd, J=7.0, 1.0 Hz, 1H), 7.47 (t, J=8.0 Hz, 1H), 7.36-7.31 (m, 3H), 7.03 (d, J=8.0 Hz, 1H), 6.67 (d, J=7.0 Hz, 1H), 5.21 (s, 2H).

EXAMPLE 73 (7)

4-(4-Trifluoromethylphenylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2686] 2124

[2687] TLC: Rf 0.67 (hexane:ethyl acetate=1:2);

[2688] NMR (CDCl3): δ 7.70 (d, J=7.5 Hz, 2H), 7.60-7.30 (m, 5H), 7.10 (d, J=10 Hz, 1H), 6.65 (d, J=7.5 Hz, 1H), 5.25 (s, 2H).

EXAMPLE 73 (8)

4-(3,5-Dimethylisoxazol-4-ylmethyl) oxy-1,1-dioxidebenzo[b]thiophene

[2689] 2125

[2690] TLC: Rf 0.53 (hexane:ethyl acetate=1:2);

[2691] NMR (CDCl3): δ 7.60-7.40 (m, 1H), 7.40-7.30 (m, 2H), 7.10 (d, J=7.5 Hz, 1H), 6.60 (d, J=7.5 Hz,1H), 4.90 (s, 2H), 2.40 (s, 3H), 2.30 (s, 3H).

EXAMPLE 73 (9)

4-(4-Methoxycarbonylphenylmethyl)oxy-1, -dioxidebenzo[b]thiophene

[2692] 2126

[2693] TLC: Rf 0.58 (hexane:ethyl acetate=1:2);

[2694] NMR (CDCl3): δ 8.10 (d, J=7.5 Hz, 2H), 7.55-7.30 (m, 5H), 7.10 (d, J=10 Hz, 1H), 6.65 (d, J=7.5 Hz,1H), 5.25 (s, 2H), 3.95 (s, 3H).

EXAMPLE 73 (10)

4-(Benzotriazol-1-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2695] 2127

[2696] TLC: Rf 0.62 (hexane:ethyl acetate 1:2);

[2697] NMR (CDCl3): δ 8.20-8.10 (m, 1H), 7.70-7.30 (m, 7H), 6.65 (s, 2H), 6.60 (d, J=7.5 Hz, 1H).

EXAMPLE 73 (11)

4-(2,6-Dimethylphenyl)carbamoylmethyloxy-1,1-dioxidebenzo[b]thiophene

[2698] 2128

[2699] TLC: Rf 0.50 (hexane:ethyl acetate=1:2);

[2700] NMR (CDCl3): δ 7.65-7.40 (m, 4H), 7.20-7.00 (m, 4H), 6.75 (d, J=7.5 Hz, 1H), 4.80 (s, 2H), 2.20 (s, 6H).

EXAMPLE 73 (12)

4-Trimethylsilylmethyloxy-1,1-dioxi debenzo[b]thiophene

[2701] 2129

[2702] TLC: Rf 0.60 (hexane:ethyl acetate=1:1);

[2703] NMR (CDCl3): δ 7.50-7.35 (m, 2H), 7.30-7.10 (m, 2H), 6.60 (d, J=7.5 Hz, 1H), 3.70 (s, 2H), 0.20 (s, 9H).

EXAMPLE 73 (13)

4-(Pyridin-2-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2704] 2130

[2705] TLC: Rf 0.31 (hexane:ethyl acetate=1:2);

[2706] NMR (CDCl3): δ 8.70-8.55 (m, 1H), 7.85-7.70 (m, 1H), 7.60-7.20 (m, 5H), 7.10 (d, J=7.5 Hz, 1H), 6.65 (d, J=7.5 Hz, 1H), 5.35 (s, 2H).

EXAMPLE 73 (14)

4-(2-(Pyridin-3-ylcarbonyl)aminoethyl) oxy-1,1-dioxidebenzo[b]thiophene

[2707] 2131

[2708] TLC: Rf 0.33 (ethyl acetate:methanol=9:1);

[2709] NMR (CDCl3): δ 8.98 (dd, J=1.8, 0.9 Hz, 1H), 8.72 (dd, J=4.5, 1.8 Hz, 1H), 8.12 (d, J=8.0, 1.8 Hz, 1H), 7.49-7.42 (m, 2H), 7.28 (d, J=7.0 Hz, 1H), 7.08 (d, J=8.0 Hz, 1H), 6.83 (br, 1H), 6.58 (d, J=7.0 Hz, 1H), 4.30 (t, J=5.4 Hz, 2H), 3.93 (q, J=5.4 Hz, 2H).

EXAMPLE 73 (15) 4-(3-(Pyridin-3-yl)propyl)oxy-1,1-dioxidebenzo[b]thiophene

[2710] 2132

[2711] TLC: Rf 0.32 (ethyl acetate:methanol 10:1);

[2712] NMR (CDCl3+CD3OD): δ 8.52-8.25 (m, 2H), 7.80-7.18 (m, 5H), 7.07 (d, J=8 Hz, 1H), 6.68 (d, J=7 Hz, 1H), 4.14 (t, J=7 Hz, 2H), 2.87 (t, J=7 Hz, 2H), 2.35-2.10 (m, 2H).

EXAMPLE 73 (16)

4-(2-(Pyridin-2-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2713] 2133

[2714] TLC: Rf 0.39 (ethyl acetate:methanol=10:1);

[2715] NMR (CDCl3): δ 8.57 (d, J=5 Hz, 1H), 7.64 (dt, J=2, 7 Hz, 1H), 7.45 (t, J=8 Hz, 1H), 7.35-6.98 (m, 5H), 6.56 (d, J=7 Hz. 1H), 4.50 (t, J=7 Hz, 2H), 3.29 (t, J=7 Hz, 2H).

EXAMPLE 73 (17)

4-(1-t-Butoxycarbonylpiperidin-4-yl)oxy-1,1-dioxidebenzo[b]thiophene

[2716] 2134

[2717] TLC: Rf 0.63 (ethyl acetate hexane=1:1);

[2718] NMR (CDCl3): δ 7.55-7.38 (m, 2H), 7.30 (d, J=8 Hz, 1H), 7.07 (d, J=8 Hz, 1H), 6.23 (d, J=7 Hz, 1H), 4.70-4.50 (m, 1H), 3.85-3.58 (m, 2H), 3.50-3.28 (m, 2H), 2.15-1.88 (m, 2H), 1.88-1.66 (m, 2H), 1.47 (s, 9H).

EXAMPLE 73 (18)

4-(5-Methyl-1-tritylimidazol-4-ylmethyl) oxy-1,1-dioxidebenzo[b]thiophene

[2719] 2135

[2720] TLC: Rf 0.11 (hexane:ethyl acetate=1:1);

[2721] NMR (CDCl3): δ 7.55-7.23 (m, 14H), 7.23-7.00 (m, 6H), 6.56 (d, J=7 Hz, 1H), 5.13 (s, 2H), 1.45 (s, 3H).

EXAMPLE 73(19)

4-(1,2,4-oxadiazol-3-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2722] 2136

[2723] TLC: Rf 0.45 (hexane:ethyl acetate=1:2);

[2724] NMR (DMSO-d6): δ 9.70 (s, 1H), 7.62 (t, J=8.0 Hz, 1H), 7.57 (d, J=6.9 Hz, 1H), 7.50 (d, J=8.0 Hz, 1H), 7.46 (d, J=8.0 Hz, 1H), 7.31 (d, J=6.9 Hz, 1H), 5.58 (s, 2H).

EXAMPLE 73 (20)

6-(Pyridin-3-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2725] 2137

[2726] TLC: Rf 0.40 (ethyl acetate);

[2727] NMR (CDCl3): δ 8.69 (d, J=1.7 Hz, 1H), 8.62 (dd, J=5.0, 1.7 Hz, 1H), 7.77 (d, J=7.8 Hz, 1i H), 7.39-7.27 (m, 3H), 7.18 (d, J=7.0 Hz, 1H), 7.09 (dd, J=8.2, 2.2 Hz, 1H), 6.58 (d, J=7.0 Hz, 1H), 5.14 (s, 2H).

EXAMPLE 73 (21)

6-(3-Nitrophenylmethyl)oxy-1,1-dioxidebenzo[b]thiophene

[2728] 2138

[2729] MS (APCI, Pos.): m/z 318 (M+H)+.

EXAMPLE 73 (22)

6-(3-(t-Butoxycarbonylamino)propyl)oxy-1,1-dioxidebenzo[b]thiophene

[2730] 2139

[2731] TLC: Rf 0.14 (hexane:ethyl acetate=2:1);

[2732] NMR (CDCl3): δ 7.27-7.23 (m, 2H), 7.16 (d, J=6.9 Hz, 1H), 7.01 (dd, J=8.3,-2.3 Hz, 1H), 6.60 (d, J=6.9 Hz, 1H), 4.69 (br, 1H), 4.08 (t, J=6.6 Hz, 2H), 3.32 (q, J=6.6 Hz, 2H), 2.01 (quint, J=6.6 Hz, 2H), 1.44 (s, 9H).

EXAMPLE 73 (23)

7-t-Butoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene

[2733] 2140

[2734] TLC: Rf 0.41 (hexane:ethyl acetate=1:1);

[2735] NMR (CDCl3): δ 7.45 (dd, J=8.5, 7.5 Hz, 1H), 7.12 (d, J=6.9 Hz, 1H), 6.94 (d, J=7.5 Hz, 1H), 6.86 (d, J=8.5 Hz, 1H), 6.66 (d, J=6.9 Hz, 1H); 4.72 (s, 2H), 1.46 (s, 9H).

EXAMPLE 73 (24)

6-(Pyridin-3-yloxy)methyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2736] 2141

[2737] TLC: Rf 0.36 (ethyl acetate);

[2738] NMR (CD3OD): δ 8.35 (d, J=3.0 Hz, 1H), 8.17 (d, J=4.0 Hz, 1H), 7.60-7.50 (m, 1H), 7.53 (d, J=7.2 Hz, 1H), 7.45-7.35 (m, 3H), 6.87 (d, J=7.2 Hz, 1H), 5.27 (s, 2H), 3.98 (s, 3H).

EXAMPLE 73 (25)

4,7-Bis(3-hydroxypropyl)-1,1-dioxidebenzo[b]thiophene

[2739] 2142

[2740] TLC: Rf 0.44 (ethyl acetate:methanol=9:1);

[2741] NMR (CDCl3): δ 7.34 (d, J=7.0 Hz, 1H), 7.04 (d, J=9.2 Hz,1H), 6.97 (d, J=9.2 Hz, 1H), 6.54 (d, J=7.0 Hz, 1H), 4.24 (t, J=5.8 Hz, 2H), 4.14 (t, J=5.8 Hz, 2H), 3.89 (t, J=5.8 Hz, 2H), 3.83 (t, J=5.8 Hz, 2H), 2.00-2.08 (m, 4H).

EXAMPLE 73 (26)

5-Carboxy-4-ethoxy-1,1-dioxidebenzo[b]thiophene

[2742] 2143

[2743] TLC: Rf 0.38 (chloroform:methanol=10:1);

[2744] NMR (CD3OD): δ 8.00 (d, J=7 Hz, 1H), 7.61 (dd, J=1, 7 Hz, 1H), 7.52 (dd, J=1, 7 Hz, 1H), 7.03 (d, J=7 Hz, 1H), 4.16 (q, J=7 Hz, 2H), 1.42 (t, J=7 Hz, 3H).

EXAMPLE 73 (27)

5-Carboxy-4-butoxy-1,1-dioxidebenzo[b]thiophene

[2745] 2144

[2746] TLC: Rf 0.48 (chloroform:methanol=10:1);

[2747] NMR (CD3OD): δ 7.98 (d, J=7 Hz, 1H), 7.58 (dd, J=1, 7 Hz,1H), 7.51 (dd, J=1, 7 Hz, 1H), 7.03 (d, J=7 Hz, 1H), 4.01 (t, J=7 Hz, 2H), 1.95-1.66 (m, 2H), 1.66-1.36 (m, 2H), 0.99 (t, J=7 Hz, 3H).

EXAMPLE 73 (28)

5-Carboxy-4-hexyioxy-1,1-dioxidebenzo[b]thiophene

[2748] 2145

[2749] TLC: Rf 0.50 (chloroform:methanol=10:1);

[2750] NMR (CD3OD): δ 7.98 (d, J=7 Hz, 1H), 7.58 (dd, J=1, 7 Hz, 1H), 7.51 (dd, J=1, 7 Hz, 1H), 7.03 (d, J=7 Hz, 1H), 4.10 (t, J=7 Hz, 2H), 1.95-1.65 (m, 2H), 1.65-1.05 (m, 6H), 0.92 (t, J=7 Hz, 3H).

EXAMPLE 73 (29)

5-Carboxy-4-octyloxy-1-dioxidebenzo[b]thiophene

[2751] 2146

[2752] TLC: Rf 0.50 (chloroform:methanol=10:1);

[2753] NMR (CD3OD): δ 7.98 (d, J=7 Hz, 1H), 7.57 (dd, J=1, 7 Hz, 1H), 7.51 (dd, J=1, 7 Hz, 1H), 7.03 (d, J=7 Hz, 1H), 4.10 (t, J=7 Hz, 2H), 1.95-1.65 (m, 2H), 1.65-1.05 (m, 10H), 0.90 (t, J=7 Hz, 3H).

EXAMPLES 74˜74 (5)

[2754] By the same procedure as described in Example 32 using carboxylic acid derivative corresponding to 4-carboxy-1,1-dioxidebenzo[b]thiophene and a halogenated compound corresponding to bromoethane, the compounds of the present invention having the following physical data were obtained, with the proviso that in the preparation of the compound of Example 74, 1 mol equivalent of bromoethane was used.

EXAMPLE 74

5-Ethoxycarbonyl-4-hydroxy-1,1-dioxidebenzo[b]thiophene

[2755] 2147

[2756] TLC: Rf 0.32 (hexane:ethyl acetate=2:1);

[2757] NMR (CDCl3): δπ11.37 (s, 1H), 8.07 (d, J=8.0 Hz, 1H), 7.52 (dd, J=7.0, 0.8 Hz, 1H), 7.24 (dd, J=8.0, 0.8 Hz, 1H), 6.66 (d, J=7.0 Hz, 1H), 4.47 (q, J=7.0 Hz, 2H), 1.45 (t, J=7.0 Hz, 3H).

EXAMPLE 74 (1)

5-Ethoxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2758] 2148

[2759] TLC: Rf 0.31 (hexane:ethyl acetate=2:1);

[2760] NMR (CDCl3): δ 7.98 (d, J=7.4 Hz, 1H), 7.49 (t, J=7.4 Hz, 2H), 6.75 (d, J=7.4 Hz, 1H), 4.43 (q, J=7.0 Hz, 2H), 3.97 (s, 3H), 1.43 (t, J=7.0 Hz, 3H).

EXAMPLE 74 (2)

5-lsopropyloxycarbonyl-4-methoxy-1,1-dinxidebenzo[b]thiophene

[2761] 2149

[2762] TLC: Rf 0.36 (hexane:ethyl acetate=2:1);

[2763] NMR (CDCl3): δ 7.94 (d, J=7.8 Hz, 1H), 7.52-7.42 (m, 2H), 6.74 (d, J=7.2 Hz, 1H), 5.38-5.19 (m, 1H), 3.96 (s, 3H), 1.40 (d, J=6.2 Hz, 6H).

EXAMPLE 74 (3)

5-(2-Methylpropyl)oxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2764] 2150

[2765] TLC: Rf 0.42 (hexane:ethyl acetate=2:1);

[2766] NMR (CDCl3): δ 7.97 (d, J=7.8 Hz, 1H), 7.53-7.43 (m, 2H), 6.75 (d, J=7.2 Hz, 1H), 4.15 (d, J=6.8 Hz, 2H), 3.97 (s, 3H), 2.20-1.98 (m, 1H), 1.03 (d, J=6.6 Hz, 6H).

EXAMPLE 74(4)

6-Methoxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2767] 2151

[2768] TLC: Rf 0.41 (hexane:ethyl acetate=1:1);

[2769] NMR (CDCl3): δ 7.95 (t, J=1.0 Hz, 1H), 7.75 (d, J=1.0 Hz, 1H), 7.46 (dd, J=7.0, 1.0 Hz, 1H), 6.74 (d, J=7.0 Hz, 1H), 3.98 (s, 3H), 3.96 (s, 3H).

EXAMPLE 74 (5)

6-Methoxymethoxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene

[2770] 2152

[2771] TLC: Rf 0.38 (hexane:ethyl acetate=1:1);

[2772] NMR (CDCl3): δ 7.99 (s, 1H), 7.79 (s, 1H), 7.47 (d, J=7.0 Hz, 1H), 6.76 (d, J=7.0 Hz, 1H), 5.52 (s, 2H), 4.00 (s, 3H), 3.58 (s, 3H).

EXAMPLES 75˜75(2)

[2773] By the same procedure as described in Example 31 using 4-bromomethyl-1,1-dioxidebenzo[b]thiophene and amine derivative corresponding to 2,4-dimethoxybenzylamine hydrochloride, the following compounds of the present invention were obtained.

[2774] With the proviso that in the preparation of the compounds of Example 75 and Example 75 (2), more than 2 mol equivalent of 4-bromomethyl-1,1-dioxidebenzo[b]thiophene versus amine derivative.

EXAMPLE 75

4-(N-(Pyridin-2-ylmethyl)-N-(1,1-dioxidebenzo[b]thiophen-4-ylmethyl)amino)methyl-1,1-dioxidebenzo[b]thiophene

[2775] 2153

[2776] TLC: Rf 0.48 (methanol:methylene chloride=1:10);

[2777] NMR (CDCl3): δ 8.59 (d, J=4.6 Hz, 1H), 7.72-7.55 (m, 3H), 7.55-7.38 (m, 4H), 7.35-7.16 (m, 3H), 7.10 (d, J=7.8 Hz, 1H), 6.68 (d, J=7.0 Hz, 2H), 3.76 (s, 4H), 3.73 (s, 2H).

EXAMPLE 75 (1)

4-(Pyridin-2-ylmethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene

[2778] 2154

[2779] TLC: Rf 0.31 (methylene chloride:methanol=10:1);

[2780] NMR (CD3OD+CDCl3): δ 8.75-8.52 (m, 1H), 7.96-7.72 (m, 4H), 7.64 (t, J=8 Hz, 1H), 7.55-7.25 (m, 2H), 6.93 (d, J=7 Hz, 1H), 4.43 (s, 2H), 4.38 (s, 2H).

EXAMPLE 75 (2)

4-(N-(2,4-Dimethoxyphenylmethyl)-N-(1,1-dioxidebenzo[b]thiophene-4-ylmethyl) amino) methyl-1,1-dioxidebenzo[b]thiophene

[2781] 2155

[2782] TLC: Rf 0.57 (ethyl acetate:benzene=1:1);

[2783] NMR (CDCl3): δ 7.65-7.55 (m, 2H), 7.50-7.38 (m, 4H), 7.07-6.99 (m, 1H), 6.87 (d, J=7.0 Hz, 2H), 6.57 (d, J=7.0 Hz, 2H), 6.48-6.40 (m, 2H), 3.81 (s, 3H), 3.63 (s, 3H), 3.60 (s, 4H), 3.45 (s, 2H).

EXAMPLES 76˜76 (1)

[2784] By the same procedure as described in Example 1 using a derivative corresponding to 1,1-dioxidebenzo[b]thiophene and thiophenol, the following compounds of the present invention were obtained.

EXAMPLE 76

4,7-Dimethoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2785] 2156

[2786] TLC: Rf 0.27 (hexane:methylene chloride 1:10);

[2787] NMR (CDCl3): δ 7.52-7.47 (m, 2H), 7.35-7.32 (m, 3H), 7.02 (d, J=8.9 Hz, 1H), 6.91 (d, J=8.9 Hz,1H), 5.00 (dd, J=7.0,1.6 Hz, 1H), 3.92 (s, 3H), 3.85 (s, 3H), 3.73 (dd, J=13.9, 7.0 Hz, 1H), 3.59 (dd, J=13.9,1.6 Hz, 1H).

EXAMPLE 76 (1)

6-Bromo-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2788] 2157

[2789] TLC: Rf 0.45 (hexane:ethyl acetate=2:1);

[2790] NMR (CDCl3): δ 7.83 (d, J=1.8 Hz, 1H), 7.75 (dd, J=8.3, 1.8 Hz, 1H), 7.58 (d, J=8.3 Hz, 1H), 7.43-7.40 (m, 2H), 7.37-7.34 (m, 3H), 4.88 (t, J=6.9 Hz, 1H), 3.80 (dd, J=13.8, 6.9 Hz, 1H), 3.50 (dd, J=13.8, 6.9 Hz, 1H).

EXAMPLE 77

5-Acetyloxy-4-nitro-1,1-dioxidebenzo[b]thiophene

[2791] 2158

[2792] By the same procedure as described in Example 12 using 5-hydroxy-4-nitro-1,1-dioxidebenzo[b]thiophene instead of the compound prepared in Example 11, the compound of the present invention having the following physical data was obtained.

[2793] TLC: Rf 0.49 (hexane:ethyl acetate=1:1);

[2794] NMR (DMSO-d6): δ 8.32 (dd, J=8.0,1.0 Hz,1H),7.78 (d, J=7.0 Hz, 1H), 7.76 (d, J=8.0 Hz, 1H), 7.69 (dd, J=7.0, 1.0 Hz, 1H), 2.35 (s, 3H).

EXAMPLES 78˜78 (1)

[2795] By the same procedure as described in Example 7 using the compounds prepared in Example 35 (39) and Example 35 (47) instead of the compound prepared in example 6 (8), the following compounds of the present invention were obtained.

EXAMPLE 78

4-(Piperidin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2796] 2159

[2797] TLC: Rf 0.41 and 0.50 (ethyl acetate:acetic acid:water=3:1:1);

[2798] NMR (CD3OD): δ 7.85-7.42 (m, 6H), 7.35-7.18 (m 2H), 5.68-5.50 (m, 1H), 4.15-3.90 (m, 3H), 3.90-3.50 (m, 2H), 3.50-3.30 (m, 1H), 3.20-2.90 (m, 2H), 2.45-2.15 (m, 1H), 2.15-1.40 (m, 4H).

EXAMPLE 78 (1)

5-(2-Aminoethyl)oxy-4-nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2799] 2160

[2800] TLC: Rf 0.17 (ethyl acetate:methanol=2:1);

[2801] NMR (DMSO-d6): δ 8.25 (br, 3H), 8.16 (d, J=8.7 Hz, 1H), 7.86-7.65 (m, 6H), 5.99 (d, J=7.2 Hz, 1H), 4.63-4.50 (m, 2H), 4.15-4.00 (m, 2H), 3.30-3.26 (m, 2H).

EXAMPLE 79

4-(2-(2-Hydroxyethoxy)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2802] 2161

[2803] To a solution of the compound prepared in Example 35 (42) (258 mg) in ethanol, was added 47% aqueous solution of hydrobromic acid (1.0 ml). The mixture was refluxed for 1 hour. The reaction mixture was concentrated. The residue was dissolved in ethyl acetate. The mixture was washed by a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride successively, dried over anhydrous sodium sulfate and concentrated. The residue was recrystallized from ethyl acetate to give the compound of the present invention (174 mg) having the following physical data.

[2804] TLC: Rf 0.22 (ethyl acetate);

[2805] NMR (CDCl3): δ 7.85-7.72 (m, 2H), 7.66-7.34 (m, 4H), 7.25 (d, J=8 Hz, 1H), 6.99 (d, J=8 Hz, 1H), 5.34 (d, J=9 Hz, 1H), 4.19 (d, J=15 Hz, 1H), 4.25-3.95 (m, 3H), 3.95-3.55 (m, 7H), 2.50 (brs, 1H).

EXAMPLE 80

4-(4,5-Dihydroxazol-2-yl)-1,1-dioxidebenzo[b]thiophene

[2806] 2162

[2807] The compound prepared in Example 72 (1) (369 mg) was dissolved in diisopropylethylamine (0.55 ml) and methylene chloride (40 ml). The mixture was cooled to −78° C. Thereto was added trifluoromethanesulfonate anhydride (0.30 ml). The mixture was stirred at O° C. for 2.5 hours and thereto was added trifluoromethanesulfonate anhydride (0.15 ml). The mixture was stirred at room temperature for 1 hour. To the reaction mixture, were added ethyl acetate and 1N hydrochloric acid. The mixture was extracted by ethyl acetate. The extract was washed by 1N sodium hydroxide and a saturated aqueous solution of sodium chloride successively, dried over anhydrous sodium sulfate and concentrated. The residue was purified with column chromatography on silica gel (ethyl acetate:hexane=1:1) to give the compound of the present invention (97 mg) having the following physical data.

[2808] TLC: Rf 0.53 (ethyl acetate);

[2809] NMR (CDCl3): δ 8.42 (d, J=7.0 Hz, 1H), 8.10 (d, J=7.8 Hz, 1H), 7.80 (d, J=7.8 Hz, 1H), 7.57 (t, J=7.8 Hz, 1H), 6.77 (d, J=7.0 Hz, 1H), 4.46 (t, J=9.4 Hz, 2H), 4.13 (t, J=9.4 Hz, 2H).

EXAMPLE 80 (1)

5-(4,5-Dihydroxazol-2-yl)-1,1-dioxidebenzo[b]thiophene

[2810] 2163

[2811] By the same procedure as described in Example 80 using the compound prepared in Example 28 (25) instead of the compound prepared in Example 72 (1), the compound of the present invention having the following physical data was obtained.

[2812] TLC: Rf 0.39 (ethyl acetate);

[2813] NMR (CDCl3): δ 8.10 (dd, J=7.8 Hz, 1.2 Hz, 1H), 7.97 (d, J=1.2 Hz, 1H), 7.76 (d, J=7.8 Hz, 1H), 7.25 (d, J=6.8 Hz, 1H), 6.78 (d, J=6.8 Hz, 1H), 4.50 (t, J=9.6 Hz, 2H), 4.11 (t, J=9.6 Hz, 2H).

EXAMPLES 81˜81 (1)

[2814] By the same procedure as described in Example 52 using the compounds prepared in Example 45 (10) and Example 35 (63) instead of the compound prepared in example 51, the following compounds of the present invention were obtained.

EXAMPLE 81

5-Carboxy-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2815] 2164

[2816] TLC: Rf 0.22 (ethyl acetate:methanol=2:1);

[2817] NMR (DMSO-d6): δ 7.91 (d, J=8.0 Hz, 1H), 7.86-7.74 (m, 3H), 7.68-7.61 (m, 2H), 7.56 (d, J=8.0 Hz, 1H), 5.68 (d, J=8.5 Hz, 1H), 4.19 (d, J=15.5 Hz, 1H), 4.01 (dd, J=15.5, 8.5 Hz, 1H), 3.66 (s, 3H). 3.35 (br, 1H).

EXAMPLE 81 (1)

[2818] 4-Carboxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene 2165

[2819] Free Compound:

[2820] TLC: Rf 0.11 (chloroform:methanol 9:1);

[2821] NMR (DMSO-d6): δ 13.78 (s, 1H), 8.24 (d, J=7.5 Hz, 1H), 8.05 (d, J=7.8 Hz, 1H), 7.91-7.84 (m, 1H), 7.82-7.74 (m, 3H), 7.69-7.61 (m, 2H), 6.27 (dd, J=7.8, 2.1 Hz, 1H), 4.20-3.95 (m, 2H).

[2822] Sodium Salt:

[2823] TLC: Rf 0.11 (chloroform:methanol=9:1);

[2824] NMR (DMSO-d6): δ 8.22 (dd, J=7.4 Hz and 1.4 Hz, 1H), 7.95-7.85 (m, 3H), 7.85-7.70 (m, 2H), 7.70-7.55 (m, 2H), 6.62 (dd, J=8.0 Hz and 2.0 Hz, 1H), 4.10 (dd, J=15 Hz and 8.0 Hz, 1H), 3.95 (dd, J=15 Hz and 2.0 Hz, 1H).

EXAMPLE 82

4-Formyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2825] 2166

[2826] To a solution of the compound prepared in Example 45 (20) (1.46 g) in methylene chloride (40 ml), were added pyridinium dichromate (2.44 g) and magnesium sulfate (1.0 g). The mixture was stirred at room temperature for 6 hours. The undissolved ingredients were filtered off. The filtrate was poured onto 1N hydrochloric acid. The mixture was extracted by ethyl acetate. The extract was washed by a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated. The residue was washed by methanol to give the compound of the present invention (1.03 g) having the following physical data.

[2827] TLC: Rf 0.65 (chloroform:methanol=9:1);

[2828] NMR (DMSO-d6): δ 10.29 (s, 1H), 8.29 (dd, J=7.4, 1.2 Hz, 1H), 8.16 (dd, J=7.6,1.2 Hz, 1H), 8.03-7.92 (m, 1H), 7.86-7.72 (m, 3H), 7.71-7.57 (m, 2H), 6.41 (dd, J=8.0, 2.2 Hz, 1H), 4.08 (dd, J=15.2, 8.0 Hz, 1H), 3.97 (dd, J=15.2, 2.2 Hz, 1H).

EXAMPLES 83˜83 (3)

[2829] By the same procedure as described in Example 21 using the compounds prepared in Example 73 (2), Example 73 (23), Example 28 (12) and Example 72 (5) instead of the compound prepared in Example 20 (27), the following compounds of the present invention were obtained.

EXAMPLE 83

5-Carboxymethyloxy-1,1-dioxidebenzo[b]thiophene

[2830] 2167

[2831] TLC: Rf 0.18 (ethyl acetate:methanol=5:1);

[2832] NMR (DMSO-d6): δ 7.75 (dd, J=8.3, 0.9 Hz, 1H), 7.53 (dd, J=6.9, 0.9 Hz, 1H), 7.34 (d, J=6.9 Hz, 1H), 7.16 (d, J=2.7 Hz, 1H), 7.07 (dd, J=8.3, 2.7 Hz, 1H), 4.83 (s, 2H).

EXAMPLE 83 (1)

7-Carboxymethyloxy-1,1-dioxidebenzo[b]thiophene

[2833] 2168

[2834] TLC: Rf 0.21 (ethyl acetate:methanol=4:1);

[2835] NMR (DMSO-d6): δ 7.57 (t, J=7.8 Hz, 1H), 7.51 (d, J=6.9 Hz, 1H), 7.25 (d, J=6.9 Hz, 1H), 7.11 (d, J=7.8 Hz, 2H), 4.92 (s, 2H).

EXAMPLE 83 (2)

4-((1S)-1-Carboxy-2-methylpropyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2836] 2169

[2837] TLC: Rf 0.16 (ethyl acetate:methanol=4:1);

[2838] NMR (DMSO-d6): δ 8.89 (d, J=7.8 Hz, 1H), 7.97 (d, J=7.3 Hz, 1H), 7.81 (d, J=7.3 Hz, 1H), 7.77 (d, J=7.3 Hz, 1H), 7.69 (t, J=7.3 Hz, 1H), 7.48 (d, J=7.3 Hz, 1H), 4.33 (dd, J=7.8, 6.0 Hz, 1H), 2.23-2.12 (m, 1H), 0.97 (d, J=6.6 Hz, 3H), 0.96 (d, J=6.6 Hz, 3H).

EXAMPLE 83 (3)

4-((1R)-1-Carboxy-2-methylpropyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2839] 2170

[2840] TLC: Rf 0.16 (ethyl acetate:methanol=4:1);

[2841] NMR (DMSO-d6): δ 8.89 (d, J=7.8 Hz, 1H), 7.97 (d, J=7.3 Hz, 1H), 7.81 (d, J=7.3 Hz, 1H), 7.77 (d, J=7.3 Hz, 1H), 7.69 (t, J=7.3 Hz, 1H), 7.47 (d, J=7.3 Hz, 1H), 4.33 (dd, J=7.8, 6.0 Hz, 1H), 2.25-2.13 (m, 1H), 0.97 (d, J=6.6 Hz, 3H), 0.96 (d, J=6.6 Hz, 3H).

EXAMPLE 84

5-(3-Carboxypropyl) oxy-1,1-dioxidebenzo[b]thiophene

[2842] 2171

[2843] To a solution of the compound prepared in Example 73 (3) (98 mg) in dimethylsulfoxide (5.0 ml) were added phosphate buffer (pH 7.4, 25 ml) and porcine liver esterase (100 μl). The mixture was stirred at room temperature for 18 hours. The reaction mixture was poured onto 1 N hydrochloric acid. The mixture was extracted by ethyl acetate. The extract was washed by a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated to give the compound of the present invention (90 mg) having the following physical data.

[2844] TLC: Rf 0.26 (chloroform:methanol=9:1);

[2845] NMR (CDCl3): δ 7.62 (d, J=8.4 Hz, 1H), 7.13 (d, J=6.8 Hz, 1H), 6.95 (dd, J=8.4, 2.2 Hz, 1H), 6.85 (d, J=2.2 Hz, 1H), 6.73 (d, J=6.8 Hz, 1H), 4.10 (t, J=6.2 Hz, 2H), 2.58 (t, J=7.0 Hz, 2H), 2.24-2.07 (m, 2H).

EXAMPLE 84 (1)

5-((2E)-3-Carboxy-2-propenyl) oxy-1,1-dioxidebenzo[b]thiophene

[2846] 2172

[2847] By the same procedure as described in Example 84 using the compound prepared in Example 30 (13) instead of the compound prepared in Example 73 (3), the compound of the present invention having the following physical data was obtained.

[2848] TLC: Rf 0.14 (chloroform:methanol=9:1);

[2849] NMR (CD3OD): δ 7.64 (d, J=8.8 Hz, 1H), 7.38 (d, J=7.0 Hz, 1H), 7.16-7.00 (m, 3H), 6.95 (d, J=7.0 Hz, 1H), 6.13 (dt, J=15.8, 2.0 Hz, 1H), 4.89-4.80 (m, 2H).

EXAMPLE 85

5-(4-Phenylbutyl)aminomethyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2850] 2173

[2851] To a solution of 4-Phenylbutylamine (164 mg) and the compound prepared in example 15 (366 mg) in methylene chloride (3.0 ml), was added sodium sulfate (1.0 g) at room temperature. The mixture was stirred for 1 hour. To the reaction mixture were added sodium borocyanohydride (63 mg), methanol (3.0 ml) and 4N solution of hydrogen chloride in dioxane (0.3 ml). The mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated. To the residue was added chloroform. The undissolved ingredients were filtered off. The filtrate was concentrated. The residue was purified with column chromatography on silica gel (chloroform:methanol=100:5) to give the compound of the present invention (340 mg) having the following physical data, and then converted into hydrochloride by a known method to give the compound of the present invention having the following physical data.

[2852] Free Compound:

[2853] TLC: Rf 0.42 (chloroform:methanol=10:1);

[2854] NMR (CDCl3): δ 7.80-7.50 (m, 6H), 7.33-7.12 (m, 6H), 5.34 (d, J=4.8 Hz, 1H), 4.15-3.90 (m, 4H), 3.75 (s, 3H), 2.98 (t, J=7.8 Hz, 2H), 2.63 (t, J=7.8 Hz, 2H), 1.88-1.60 (m, 4H).

[2855] Hydrochloride:

[2856] TLC: Rf 0.42 (chloroform:methanol=10:1);

[2857] NMR (CDCl3): δ 9.49 (bs, 2H), 7.93 (d, J=8.1 Hz, 1H), 7.77-7.70 (m, 2H), 7.65 (t, J=8.1 Hz, 1H), 7.50 (t, J=8.1 Hz, 2H), 7.35-7.12 (m, 6H), 5.27 (d, J=8.1 Hz, 1H), 4.18-4.02 (m, 2H), 3.98 (d, J=15.0 Hz, 1H), 3.88 (s, 3H), 3.85 (dd, J=15.0, 8.1 Hz, 1H), 3.00-2.85 (m, 2H), 2.63 (t, J=7.5 Hz, 2H), 2.00-1.60 (m, 4H).

EXAMPLE 85 (1)

5-(Pyridin-3-ylmethyl)aminomethyl-4-methoxy-3-phenysulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2858] 2174

[2859] By the same procedure as described in Example 85 using the compound prepared in Example 15, and (pyridin-3-ylmethyl)amine instead of 4-phenylbutylamine, the compound of the present invention having the following physical data was obtained. And then, by converting into hydrochloride using the obtained compound by a known method, the compound of the present invention having the following physical data was obtained.

[2860] Free Compound:

[2861] TLC: Rf 0.35 (chloroform:methanol=10:1);

[2862] NMR (CDCl3): δ 8.59 (d, J=2.0 Hz, 1H), 8.55 (dd, J=4.8, 2.0 Hz, 1H), 7.80-7.65 (m, 4H), 7.58 (d, J=6.0 Hz, 1H), 7.43 (dd, J=7.6, 2.0 Hz, 3H), 7.30 (dd, J=7.6, 4.8 Hz, 1H), 5.20 (d, J=8 .2 Hz, 1H), 4.17 (d, J=13.4 Hz, 1H), 3.95-3.70 (m, 5H), 3.80 (s, 3H).

[2863] 2hydrochloride:

[2864] TLC: Rf 0.35 (chloroform:methanol=10:1);

[2865] NMR (DMSO-d6): δ 10.35 (brs, 1H), 10.15 (bs, 1H), 9.03 (s, 1H), 8.85 (d, J=5.2 Hz, 1H), 8.55 (d, J=8.4 Hz, 1H), 8.06 (d, J=8.4 Hz, 1H), 7.95-7.72 (m, 4H), 7.70-7.55 (m, 3H), 5.85-5.77 (m, 1H), 4.40-4.00 (m, 6H), 3.69 (s, 3H).

EXAMPLE 86

6-Dimethylamino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2866] 2175

[2867] By the same procedure as described in Example 8 using the compound prepared in Example 35 (68) instead of the compound prepared in Example 7, the compound of the present invention having the following physical data was obtained.

[2868] TLC: Rf 0.48 (hexane:ethyl acetate=1:2);

[2869] NMR (DMSO-d6): δ 7.81-7.74 (m, 3H), 7.66-7.58 (m, 2H), 7.40 (d, J=9.0 Hz, 1H), 7.09 (dd, J=9.0, 2.5 Hz, 1H), 6.80 (d, J=2.5 Hz, 1H), 5.56 (dd, J=9.5, 3.0 Hz,1H), 3.91 (dd, J=15.0, 9.5 Hz, 1H), 3.67 (dd, J=15.0, 3.0 Hz, 1H), 2.99 (s, 6H).

EXAMPLE 87

4-(2-Dimethylaminoethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2870] 2176

[2871] By the same procedure as described in Example 28 using the compound prepared in Example 81 (1) instead of 4-carboxy-1,1-dioxidebenzo[b]thiophene, and (2-dimethylaminoethyl)amine instead of (pyridin-3-ylmethyl)amine, and then by converting into hydrochloride by known methods, the following compound of the present invention was obtained.

[2872] TLC: Rf 0.62 (chloroform:methanol:triethylamine=8:2:1);

[2873] NMR (DMSO-d6): δ 10.40-10.20 (br, 1H), 9.19 (t, J=5.4Hz, 1H), 8.13 (d, J=6.9 Hz, 1H), 7.94 (d, J=7.5 Hz, 1H), 7.87 (d, J=7.8 Hz, 1H), 7.84-7.72 (m, 3H), 7.67-7.58 (m, 2H), 6.27 (d, J=9.0 Hz, 1H), 4.13 (dd, J=9.0,15.0 Hz, 1H), 3.96 (d, J=15.0 Hz, 1H), 3.77-3.55 (m, 2H), 3.40-3.22 (m, 2H), 2.87-2.74 (m, 6H).

EXAMPLES 88˜88 (2)

[2874] Using the compounds prepared in Example 18 (40), Example 20 (4) and Example 45 (3) instead of the compound prepared in Example 1 by the same procedure as described in Example 3 or by the same reaction using 3-chloroperbenzoic acid instead of OXONE@ as an oxidizer, the following compounds of the present invention were prepared.

EXAMPLE 88

4,7-Bis(pyridin-3-ylmethyloxy)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2875] 2177

[2876] TLC: Rf 0.36 (ethyl acetate:methanol=2:1);

[2877] NMR (CDCl3): δ 8.65-8.60 (m, 3H), 8.57 (dd, J=5.0,1.5 Hz, 1H), 7.90-7.80 (m, 2H), 7.68-7.65 (m, 2H), 7.60-7.55 (m, 1H), 7.41-7.31 (m, 4H), 7.01 (d, J=9.0 Hz,1H), 6.98 (d, J=9.0 Hz, 1H), 5.25 (d, J=13.0 Hz, 1H), 5.21 (dd, J=9.5, 1.0 Hz, 1H), 5.20 (d, J=13.0 Hz,1H), 4.96 (d, J=12.0 Hz, 1H), 4.87 (d, J=12.0 Hz, 1H), 4.12 (dd, J=15.0, 1.0 Hz, 1H), 3.75 (dd, J=15.0, 9.5 Hz, 1H).

EXAMPLE 88 (1)

4-(N-Oxidepyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2878] 2178

[2879] TLC: Rf 0.30 (ethyl acetate:methanol=2:1);

[2880] NMR (DMSO-d6): δ 8.29 (s, 1H), 8.20 (d, J=6.2 Hz, 1H), 7.73-7.57 (m, 4H), 7.51-7.31 (m, 6H), 5.77 (d, J=8.8 Hz, 1H), 5.10 (d, J=12.8 Hz, 1H), 4.90 (d, J=12.8 Hz, 1H), 4.18 (d, J=15.0 Hz, 1H), 3.95 (dd, J=15.0, 8.8 Hz, 1H).

EXAMPLE 88 (2)

4-(2-(N-Oxidepyridin-4-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2881] 2179

[2882] TLC: Rf 0.23 (ethyl acetate:methanol=9:1);

[2883] NMR (DMSO-d6): δ 8.11 (d, J=6.9 Hz, 2H), 7.79-7.72 (m, 3H), 7.65-7.60 (m, 3H), 7.34 (d, J=7.5 Hz, 1H), 7.28-7.25 (m, 3H), 5.41 (d, J=8.5 Hz, 1H), 4.16 (d, J=15.0 Hz, 1H), 4.15-3.90 (m, 2H), 4.02 (dd, J=15.0, 8.5 Hz, 1H), 2.88-2.66 (m, 2H).

EXAMPLE 89

4-methoxy-3-(4-hydroxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2884] 2180

[2885] By the same procedure as describe in 1 using the compound prepared in example 28 (27) instead of 1,1-dioxidebenzo[b]thiophene and 4-mercaptphenol instead of thiophenol, the compound of the present invention having the following physical data was obtained.

[2886] TLC: Rf 0.27 (hexane:ethyl acetate=1:1);

[2887] NMR (CDCl3): δ 7.60-7.00 (m, 3H), 7.35 (d, J=7.5 Hz, 2H), 6.80 (d, J=7.5 Hz, 2H), 6.00 (s, 1H), 4.90 (dd, J=5.0, 1.2 Hz, 1H), 3.90 (s, 3H), 3.75-3.50 (m, 2H)

EXAMPLE 90

4-Methoxy-3-(4-(pyridin-3-ylmethyloxy) phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2888] 2181

[2889] By the same procedure as described in Example 18 using the compound prepared in Example 89 instead of the compound prepared in Example 9 (12) and a halogenated compound corresponding to 4-nitrobenzylbromide, the compound of the present invention having the following physical data was obtained.

[2890] TLC: Rf 0.22 (ethyl acetate).

EXAMPLE 91

4-Methoxy-3-(4-(pyridin-3-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[2891] 2182

[2892] By the same procedure as described in Example 3 using the compound prepared in Example 90 instead of the compound prepared in Example 1, the compound of the present invention having the following physical data was obtained.

[2893] TLC: Rf 0.39 (ethyl acetate:triethylamine=95:5);

[2894] NMR (DMSO-d6): δ 9.05 (br.s, 1H), 8.90 (d, J=5.0 Hz, 1H), 8.55 (d, J=7.5 Hz, 1H), 8.00 (dd, J=7.5, 5.0 Hz, 1H), 7.80-8.60 (m, 3H), 7.50-7.15 (m, 4H), 5.60-5.40 (m, 3H), 4.20 (d, J=15 Hz, 1H), 4.00 (dd, J=15, 7.5 Hz, 1H), 3.45 (s, 3H).

Examples 92˜92 (1)

[2895] By the same procedure as described in Example 1 using the compounds prepared in Example 28 (27) and Example 28 (26) instead of 1,1-dioxidebenzo[b]thiophene, and thiophenol, the following compounds of the present invention were obtained.

EXAMPLE 92

5-(2-Dimethylaminoethyl)carbamoyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2896] 2183

[2897] TLC: Rf 0.40 (ethyl acetate:methanol:triethylamine=8:1:1);

[2898] NMR (CDCl3): δ 8.10 (d, J=8.0 Hz, 1H), 7.67 (br, 1H), 7.55-7.48 (m, 3H), 7.39-7.36 (m, 3H), 5.10 (dd, J=6.5, 2.0 Hz, 1H), 4.06 (s, 3H), 3.71 (dd, J=14.0, 6.5 Hz, 1H), 3.61 (dd, J=14.0, 2.0 Hz, 1H), 3.57 (q, J=6.0 Hz, 2H), 2.53 (t, J=6.0 Hz, 2H), 2.29 (s, 6H).

EXAMPLE 92 (1)

5-(Pyridin-3-ylmethyl)carbamoyl-4-methoxy-3-phenylthio-2,3-dihydro 1,1-dioxidebenzo[b]thiophene

[2899] 2184

[2900] TLC: Rf 0.46 (ethyl acetate:methanol=9:1);

[2901] NMR (CDCl3): δ 8.60-8.52 (m, 2H), 8.06 (d, J=8.0 Hz, 1H), 7.77-7.74 (m, 2H), 7.53-7.45 (m, 3H), 7.37-7.30 (m, 4H), 5.03 (dd, J=6.5, 2.0 Hz, 1H), 4.67 (d, J=6.0 Hz, 2H), 3.92 (s, 3H), 3.70 (dd, J=14.0, 6.5 Hz, 1H), 3.58 (dd, J=14.0, 2.0 Hz, 1H).

EXAMPLE 93

4-(2-(Piperidin-1-yl)ethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene

[2902] 2185

[2903] By the same procedure as described in Example 31 using 4-bromomethyl-1,1-dioxidebenzo[b]thiophene, and 1-(2-aminoethyl)piperidine instead of 2,4-dimethoxybenzylamine -hydrochloride, the compound of the present invention having the following physical data was obtained. And then, the obtained compound was converted into hydrochloride by a known method to give the compound of the present invention having the following physical data.

[2904] Free Compound:

[2905] TLC: Rf 0.16 (ethyl acetate:methanol:triethylamine=90:5:5);

[2906] NMR (CDCl3): δ 7.75-7.60 (m, 2H), 7.60-7.40 (m, 2H), 6.70 (d, J=7.5 Hz, 1H), 3.90 (s, 2H), 2.70 (t, J=7.5 Hz, 2H), 2.50-2.20 (m, 4H), 2.40 (t, J=7.5 Hz, 2H), 1.65-1.35 (m, 6H).

[2907] 2hydrochloride:

[2908] TLC: Rf 0.28 (ethyl acetate:methanol:triethylamine=8:1:0.5);

[2909] NMR (DMSO-d6+pyridine-d5): δ 8.15 (d, J=7.5 Hz, 1H), 8.00 (d, J=7.5 Hz, 1H), 7.90 (d, J=7.5 Hz, 1H), 7.70 (t, J=7.5 Hz, 1H), 7.50 (d, J=7.5 Hz, 1H), 4.40 (s, 2H), 3.55-3.30 (m, 4H), 3.30-3.10 (m, 4H), 1.90-1.70 (m, 4H), 1.65-1.50 (m, 2H).

EXAMPLE 94

4-(2-(Piperidin-1-yl)ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2910] 2186

[2911] By the same procedure as described in Example 27 using the compound prepared in Example 93 instead of 5-methyl-1,1-dioxidebenzo[b]thiophene, the compound of the present invention having the following physical data was obtained. And then, the obtained compound was converted into hydrochloride by a known method to give the compound of the present invention having the following physical data.

[2912] Free Compound:

[2913] TLC: Rf 0.18 (ethyl acetate:methanol:triethylamine=90:5:5);

[2914] NMR (CDCl3): δ 7.80-7.40 (m, 8H), 6.10 (d, J=10 Hz, 1H), 4.60 (d, J=15 Hz, 1H), 3.95 (d, J=15 Hz, 1H), 3.90 (d, J=15 Hz, 1H), 3.75 (dd, J=15, 10 Hz, 1H), 2.80-2.60 (m, 2H), 2.60-2.20 (m, 6H), 1.60-1.30 (m, 6H).

[2915] 2hydrochloride:

[2916] TLC: Rf 0.30 (ethyl acetate:methanol:triethylamine=8:1:0.5);

[2917] NMR (DMSO-d6+pyridine-d5): δ 8.35 (d, J=7.5 Hz, 1H), 8.00-7.75 (m, 5H), 7.65 (t, J=7.5 Hz, 2H), 6.70 (d, J=7.5 Hz, 1H), 4.80 (d, J=15 Hz, 1H), 4.50 (d, J=15 Hz, 1H), 4.20-3.95 (m, 2H), 3.65-3.35 (m, 4H), 3.30-3.00 (m, 4H), 2.00-1.70 (m, 4H), 1.70-1.40 (m, 2H).

EXAMPLE 95

4-t-Butoxycarbonylaminobenzo[b]thiophene

[2918] 2187

[2919] To a suspension of 4-carboxybenzo[b]thiophene (3.2 g) in t-butanol (170 ml), were added triethylamine (7.5 ml) and diphenylphosphorylamide (4.2 ml). The mixture was stirred at 95° C. for 2 hours. The precipitate was filtered off and the filtrate was concentrated. The residue was extracted with ethyl acetate. The extract was washed by water, dried over anhydrous magnesium sulfate and concentrated. The residue was purified with column chromatopgaphy on silica gel (hexane:ethyl acetate=5:1) to give the compound of the present invention (3.0 g) having the following physical data.

[2920] TLC: Rf 0.41 (hexane:ethyl acetate=3:1); NMR (CDCl3): δ 7.81-7.78 (m, 1H), 7.60 (d, J=8.0 Hz, 1H), 7.44-7.24 (m, 3H), 6.74 (br, 1H), 1.55 (s, 9H).

EXAMPLE 96

4-t-Butoxycarbonylamino-1,1-dioxidebenzo[b]thiophene

[2921] 2188

[2922] To a solution of the compound prepared in Example 95 (3.0 g) in chloroform (100 ml) was added m-chloroperbenzoic acid (8.2 g) at 0° C. The mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated. The residue was extracted with ethyl acetate. The extract was washed by an aqueous solution of sodium hydroxide, water and a saturated solution of sodium chloride successively, dried over anhydrous magnesium sulfate and concentrated. The residue was dissolved in methylene chloride and was allowed to stand overnight. The crystals that appeared were filtered. The filtrate was concentrated. The residue was purified with column chromatography on silica gel (methylene chloride), combined with the said crystals, to give the compound of the present invention (3.0 g) having the following physical data.

[2923] TLC: Rf 0.41 (hexane:ethyl acetate=1:1); NMR (CDCl3): δ 7.83-7.80 (m, 1H), 7.49 (t, J=7.5 Hz, 1H), 7.46-7.43 (m, 1H), 7.31 (dd, J=7.2, 1.0 Hz,1H), 6.70 (d, J=7.2 Hz,1H), 6.54 (br,1H), 1.53 (s, 9H).

EXAMPLE 97

4-Amino-1,1-dioxidebenzo[b]thiophene hydrochloride

[2924] 2189

[2925] To a solution of the compound prepared in Example 96 (2.5 g) in ethyl acetate (30 ml) was added 4N solution of hydrogen chloride in ethyl acetate (10 ml). The mixture was stirred at room temperature for 3 hours. After removing the solvent, the residue was washed by ethyl acetate to give the compound of the present invention (1.8 g) having the following physical data.

[2926] TLC: Rf 0.29 (hexane:ethyl acetate=1:2);

[2927] NMR (CD3OD): δ 7.63 (dd, J=7.0, 1.0 Hz, 1H), 7.61 (t, J=7.5 Hz, 1H), 7.54 (dt, J=7.5,1.0 Hz, 1H), 7.42 (dd, J=7.5, 1.0 Hz, 1H), 7.08 (d, J=7.0 Hz, 1H).

EXAMPLE 98

4-(4-Fluorobenzylcarbonylamino)-1,1-dioxidebenzo[b]thiophene

[2928] 2190

[2929] To a solution of the compound prepared in Example 97 (100 mg), 4-fluorophenylacetic acid (192 mg) and triethylamine (1 ml) in dimethylformamide (3 ml) was added propanephosphonic acid cyclic anhydride (50 % solution in dimethylformamide; 3 ml). The mixture was stirred at room temperature for 1.5 hours. To the reaction mixture was added ethyl acetate. The mixture was washed by water, a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, and concentrated. The residue was purified with column chromatography on silica gel (hexane:ethyl acetate=1:1), followed by recrystallization from ethyl acetate-hexane to give the compound of the present invention having the following physical data.

[2930] TLC: Rf 0.63 (ethyl acetate);

[2931] NMR (DMSO-d6): δ 10.27 (s, 1H), 7.88-7.82 (m, -1H), 7.64 (d, J=7.0 Hz, 1H), 7.61-7.55 (m, 2H), 7.41-7.34 (m, 3H), 7.16 (t, J=9.0 Hz, 2H), 3.75 (s, 2H).

EXAMPLES 98 (1)˜98 (5)

[2932] By the same procedure as described in Example 98 using the compound prepared in Example 97 and a carboxylic acid derivative corresponding to 4-fluorophenylacetic acid, the compounds of the present invention having the following physical data.

EXAMPLE 98 (1)

4-(Pyridin-3-ylcarbonyl)amino-1,1-dioxidebenz[b]thiophene

[2933] 2191

[2934] TLC: Rf 0.18 (ethyl acetate);

[2935] NMR (DMSO-d6): δ 10.69 (s, 1H), 9.17 (d, J=2.0 Hz, 1H), 8.80 (dd, J=5.0, 2.0 Hz,1H), 8.34 (dt, J=7.8, 2.0 Hz, 1H), 7.82 (dd, J=7.5, 1.5 Hz, 1H), 7.72-7.63 (m, 3H), 7.60 (dd, J=7.8, 5.0 Hz, 1H), 7.36 (d, J=7.2 Hz, 1H).

EXAMPLE 98 (2)

4-(3-Chlorobenzoyl) amino-1,1-dioxidebenzo[b]thiophene

[2936] 2192

[2937] TLC: Rf 0.25 (hexane:ethyl acetate=1:1);

[2938] NMR (DMSO-d6): δ 10.62 (s, 1H), 8.07 (t, J=1.5Hz, 1H), 7.96 (dt, J=7.7,1.5 Hz, 1H), 7.78 (dd, J=7.7, 1.5 Hz, 1H), 7.73-7.64 (m, 4H), 7.60 (t, J=7.7 Hz, 1H), 7.35 (d, J=6.6 Hz,1H).

EXAMPLE 98 (3)

4-Benzylcarbonylamino-1,1-dioxidebenzo[b]thiophene

[2939] 2193

[2940] TLC: Rf 0.45 (hexane:ethyl acetate=1:2);

[2941] NMR (CDCl3): δ 7.75-7.72 (m, 1H), 7.48-7.35 (m, 7H), 7.29 (br, 1H), 6.79 (d, J=7.2 Hz, 1H), 6.58 (d, J=7.2 Hz, 1H), 3.79 (s, 2H).

EXAMPLE 98 (4)

4-(Dimethylaminoacetyl)amino-1,1-dioxidebenzo[b]thiophene

[2942] 2194

[2943] TLC: Rf 0.31 (ethyl acetate:methanol=4:1);

[2944] NMR (CDCl3): δ 9.52 (br, 1H), 8.06 (m, 1H), 7.56-7.48 (m, 2H), 7.28-7.25 (m, 1H), 6.73 (d, J=7.0 Hz, 1H), 3.15 (s, 2H), 2.44 (s, 6H).

EXAMPLE 98 (5)

4-Acetylamino-1,1-dioxidebenzo[b]thiophene

[2945] 2195

[2946] TLC: Rf 0.25 (ethyl acetate);

[2947] NMR (DMSO-d6): δ 1 0.05 (s, 1H), 7.89-7.83 (m, 1H), 7.70 (d, J=7.0 Hz, 1H), 7.61-7.55 (m, 2H), 7.33 (d, J=7.0 Hz, 1H), 2.12 (s, 3H).

EXAMPLES 99˜99 (10)

[2948] By the same procedure as described in Example 28 using 4-carboxy-1,1-dioxidebenzo[b]thiophene (prepared in Example 107 hereinafter described) and a corresponding amine derivative instead of (pyridin-3-ylmethyl)amine, and if necessary, by converting into the corresponding salt by known methods by a known method, the compounds of the present invention having the following physical data were obtained.

EXAMPLE 99

4-(3-(2-Oxopyrrolidin-1-yl)propyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2949] 2196

[2950] TLC: Rf 0.36 (chloroform:methanol=9:1);

[2951] NMR (CDCl3): δ 8.19 (dd, J=7.0 Hz and 1.0 Hz, 1H), 8.05 (broad s, 1H), 7.95 (dd, J=8.0 Hz and 1.0 Hz, 1H), 7.79 (d, J=8.0 Hz, 1H), 7.60 (t, J=8.0 Hz, 1H), 6.75 (d, J=7.0 Hz, 1H), 3.50-3.35 (m, 6H), 2.46 (t, J=8.0 Hz, 2H), 2.20-2.00 (m, 2H), 1.90-1.70 (m, 2H).

EXAMPLE 99 (1)

4-(2-Dimethylaminoethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2952] 2197

[2953] TLC: Rf 0.20 (ethyl acetate:acetic acid:water=3:1:1);

[2954] NMR (CDCl3): δ 8.03 (dd, J=7.2 Hz and 1.0 Hz, 1H), 7.79 (dt, J=7.8 Hz and 1.0 Hz, 1H), 7.69 (dd, J=7.8 Hz and 1.0 Hz, 1H), 7.57 (t, J=7.8 Hz, 1H), 6.77 (d, J=7.2 Hz, 1H), 3.49 (m, 2H), 2.67 (t, J=6.0 Hz, 2H), 2.58 (q, J=7.2 Hz, 4H), 1.04 (t, J=7.2 Hz, 6H).

EXAMPLE 99 (2)

4-(2-(N-Ethyl-N-(3-methylphenyl)amino)ethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2955] 2198

[2956] TLC: Rf 0.61 (chloroform:methanol 9:1);

[2957] NMR (CDCl3): δ 7.91 (d, J=7.0 Hz, 1H), 7.74 (m, 1H), 7.55-7.40 (m, 2H), 7.13 (dd, J=9.0 Hz and 7.4 Hz, 1H), 6.73 (d, J=7.0 Hz, 1H), 6.70-6.55 (m, 3H), 6.35 (broad s, 1H), 3.75-3.50 (m, 4H), 3.19 (q, J=7.0 Hz, 2H), 2.29 (s, 3H), 1.16 (t, J=7.0 Hz, 3H).

EXAMPLE 99 (3)

4-(2,4,6-Trimethoxybenzyl) carbamoyl-1,1-dioxidebenzo[b]thiophene

[2958] 2199

[2959] TLC: Rf 0.63 (chloroform:methanol=9:1);

[2960] NMR (CDCl3+DMSO-d6): δ 7.89 (d, J=7.0 Hz, 1H), 7.80-7.65 (m, 3H), 7.55 (t, J=7.4 Hz, 1H), 6.88 (d, J=7.0 Hz, 1H), 6.17 (s, 2H), 4.56 (d, J=4.8 Hz, 2H), 3.84 (s, 6H), 3.82 (s, 3H).

EXAMPLE 99 (4)

4-(4-(2-Hydroxyethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thioiphene.hydrochloride

[2961] 2200

[2962] TLC: Rf 0.33 (methylene chloride:methanol=10:1);

[2963] NMR (DMSO-d6): δ 8.00-7.93 (m, 1H), 7.76-7.66 (m, 2H), 7.58 (d, J=6.9 Hz, 1H), 7.52 (d, J=6.9 Hz, 1H), 5.40 (bs, 1H), 4.64-4.46 (m, 1H), 6.85-3.73 (m, 2H), 3.70-3.00 (m, 10H).

EXAMPLE 99 (5)

4-(4-Benzyloxycarbonylpiperazin-1-yl) carbonyl-1,1-dioxidebenzo[b]thiophene

[2964] 2201

[2965] TLC: Rf 0.64 (methylene chloride:methanol=10:1);

[2966] NMR (CDCl3): δ 7.78 (d, J=7.5 Hz, 1H), 7.59 (t, J=7.5 Hz, 1H), 7.47 (d, J=7.5 Hz, 1H), 7.36 (s, 5H), 7.32 (d, J=6.9 Hz, 1H), 6.79 (d, J=6.9 Hz, 1H), 5.16 (s, 2H), 3.88-3.72 (m, 2H), 3.70-3.56 (m, 2H), 3.54-3.40 (m, 2H), 3.40-3.25 (m, 2H).

EXAMPLE 99 (6)

4-(N-Ethyl-N-2-(piperidin-1-yl) ethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2967] 2202

[2968] TLC: Rf 0.25 (chloroform:methanol=9:1); NMR (CDCl3): δ 7.80-7.20 (m, 4H), 6.75 (d, J=6.8 Hz, 1H), 3.80-3.50 (m, 2H), 3.35-3.10 (m, 2H), 2.70-2.10 (m, 6H), 1.70-1.20 (m, 6H), 1.26 and 1.06 (each t, J=7.0 Hz, total 3H).

EXAMPLE 99 (7)

4-(3-(Imidazol-1-yl)propyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2969] 2203

[2970] TLC: Rf 0.43 (chloroform:methanol=4:1);

[2971] NMR (CDCl3): δ 7.95 (d, J=7.0 Hz, 1H), 7.72 (d, J=7.6 Hz, 1H), 7.69 (d, J=7.6 Hz, 1H), 7.52 (t, J=7.6 Hz, 1H), 7.55 (broad s, 1H), 7.41 (s, 1H), 6.98 (s, 1H), 6.96 (s, 1H), 6.76 (d, J=7.0 Hz, 1H), 4.07 (t, J=6.6 Hz, 2H), 3.44 (q, J=6.6 Hz, 2H), 2.14 (m, 2H).

EXAMPLE 99 (8)

4-(N-2-(Piperidin-1-yl)ethyl-N-methyl)carbamoyl-1,1-dioxidebenzo[b]thiophene

[2972] 2204

[2973] TLC: Rf 0.30 (methylene chloride:methanol=9:1);

[2974] NMR (CDCl3): δ 7.85-7.30 (m, 4H), 6.76 (d, J=7.2 Hz, 1H), 3.74 and 3.30 (each t, J=6.0 Hz, total 2H), 3.14 and 2.88 (each s, total 3H), 2.70-2.10 (m, 6H), 1.70-1.30 (m, 6H).

EXAMPLE 99 (9)

4-(4-(1,3-Dioxaindan-5-ylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene

[2975] 2205

[2976] TLC: Rf 0.26 (ethyl acetate);

[2977] NMR (DMSO-d6): δ 8.00-7.92 (m, 1H), 7.74-7.65 (m, 2H), 7.56 (d, J=6.9 Hz, 1H), 7.52 (d, J=6.9 Hz, 1H), 7.21 (s, 1H), 7.03-6.95 (m, 2H), 6.07 (s, 2H), 4.64-4.50 (m, 1H), 4.28-4.15 (m, 2H), 3.70-2.96 (m, 8H).

EXAMPLE 99 (10)

4-(4-((2E)-3-Phenyl-2-propenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene hydrochloride

[2978] 2206

[2979] TLC: Rf 0.10 (ethyl acetate);

[2980] NMR (DMSO-d6): δ 8.00-7.92 (m, 1H), 7.76-7.65 (m, 2H),7.58 (d, J=6.9 Hz, 1H), 7.53-7.46 (m, 2H),7.51 (d, J=6.9 Hz, 1H), 7.45-7.28 (m, 3H), 6.84 (d, J=15.3 Hz, 1H), 6.47-6.33 (m, 1H), 4.60 (m,1H), 3.98-3.84 (m, 2H), 3.70-2.97 (m, 8H).

EXAMPLES 100˜100 (24)

[2981] By the same procedure as described in Example 28 using the compound prepared in Example 81 (1) instead of 4-carboxy-1,1-dioxidebenzo[b]thiophene, and an amine derivative instead of (pyridin-3-yl)ethylamine, and if necessary, by converting into the corresponding salt by a known method, the following compounds of the present invention having the following physical data were obtained.

EXAMPLE 100

4-(Furan-2-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2982] 2207

[2983] TLC: Rf 0.43 (hexane:ethyl acetate=1:2);

[2984] NMR (DMSO-d6): 8 9.29 (t, J=5.5 Hz, 1H), 7.99 (d, J=7.6 Hz, 1H), 7.95 (d, J=7.6 Hz, 1H), 7.83 (t, J=7.6 Hz, 1H), 7.79-7.76 (m, 3H), 7.67-7.60 (m, 3H), 6.48-6.35 (m, 2H), 6.25 (d, J=9.0 Hz, 1H), 4.55 (dd, J=15.5, 5.5 Hz, 1H), 4.40 (dd, J=15.5, 5.5 Hz, 1H), 4.10 (dd, J=15.3, 9.0 Hz, 1H), 4.00 (d, J=15.3 Hz, 1H).

EXAMPLE 100 (1)

4-(2,4,6-Trimethoxybenzyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2985] 2208

[2986] TLC: Rf 0.55 (ethyl acetate);

[2987] NMR (DMSO-d6): δ 8.40 (t, J=4.8 Hz, 1H), 7.89-7.86 (m, 2H), 7.86-7.69 (m, 4H), 7.67-7.58 (m, 2H), 6.25 (s, 2H), 6.18 (dd, J=8.1, 2.1 Hz, 1H), 4.46-4.30 (m, 2H), 4.11-3.94 (m, 2H), 3.77 (s, 9H).

EXAMPLE 100 (2)

4-(3-(2-Oxopyrrolidin-1-yl)propyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2988] 2209

[2989] TLC: Rf 0.44 (ethyl acetate:methanol=2:1);

[2990] NMR (CDCl3): δ 8.20-8.08 (m, 1H), 8.02 (d, J=7.5 Hz, 1H), 7.83-7.62 (m, 5H), 7.59-7.49 (m, 2H), 6.40 (dd, J=9.3, 1.2 Hz, 1H), 3.89-3.61 (m, 4H), 3.51-3.33 (m, 2H), 3.32-3.20 (m, 1H), 3.20-3.06 (m, 1H), 2.53-2.33 (m, 2H), 2.15-1.88 (m, 3H), 1.85-1.74 (m,1H).

EXAMPLE 100 (3)

4-((3S)-1-Benzylpyrrolidin-3-yl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2991] 2210

[2992] More Polar Compound:

[2993] TLC: Rf 0.27 (methanol:ethyl acetate:triethylamine=1:8:0.05);

[2994] NMR (CDCl3): δ 7.90-7.80 (m, 4H), 7.75-7.66 (m, 2H), 7.62-7.53 (m, 2H), 7.37-7.13 (m, 5H), 6.70 (d, J=8.7 Hz, 1H), 6.24-6.17 (m, 1H), 4.74-4.62 (m, 1H), 3.80 (dd, J=15.0,1.5 Hz, 1H), 3.68 (d, J=12.9 Hz, 1H), 3.63 (dd, J=15.0, 9.3 Hz, 1H), 3.57 (d, J=12.9 Hz, 1H), 3.00-2.86 (m, 2H), 2.72 (dd, J=9.9, 6.3 Hz, 1H), 2.51-2.31 (m, 2H), 1.89-1.77 (m, 1H).

[2995] Less Polar Compound:

[2996] TLC: Rf 0.35 (methanol:ethyl acetate:triethylamine=1:8:0.05);

[2997] NMR (CDCl3): δ 7.94-7.87 (m, 2H), 7.87-7.78 (m, 2H), 7.75-7.66 (m, 2H), 7.64-7.56 (m, 2H), 7.41-7.23 (m, 5H), 6.73 (d, J=8.1 Hz, 1H), 6.28-6.21 (m, 1H), 4.71-4.59 (m, 1H), 3.80 (dd, J=14.7, 1.2 Hz, 1H), 3.64 (s, 2H), 3.62 (dd, J=14.7, 9.3 Hz, 1H), 2.95-2.84 (m, 1H), 2.80-2.67 (m, 2H), 2.46-2.30 (m, 2H), 2.12-1.95 (m, 1H).

[2998] The determination of the absolute configuration of * is not performed, but the said more polar and less polar isomers are each single optically active compounds.

EXAMPLE 100 (4)

4-(2-(Pyrrolidin-1-yl)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[2999] 2211

[3000] Free Compound:

[3001] TLC: Rf 0.33 (ethyl acetate:methanol:triethylamine=4:2:0.5);

[3002] NMR (CDCl3): δ 7.93-7.78 (m, 4H), 7.75-7.66 (m, 2H), 7.63-7.53 (m, 2H), 7.10 (brs, 1H), 6.31-6.24 (m, 1H), 3.83 (dd, J=15.0, 1.5 Hz, 1H), 3.73-3.49 (m, 3H), 2.80 (t, J=5.7 Hz, 2H), 2.69-2.53 (m, 4H), 1.86-1.73 (m, 4H).

[3003] Hydrochloride:

[3004] TLC: Rf 0.37 (ethyl acetate:methanol:triethylamine=4:2:0.5);

[3005] NMR (DMSO-d6): δ 9.18 (t, J=5.4 Hz, 1H), 8.14 (d, J=7.5 Hz, 1H), 7.96-7.90 (m, 1H), 7.85 (t, J=7.5 Hz, 1H), 7.81-7.72 (m, 3H), 7.67-7.58 (m, 2H), 6.27 (d, J=9.3 Hz, 1H), 4.13 (dd, J=15.6, 9.3 Hz, 1H), 3.96 (d, J=15.6 Hz, 1H), 3.78-3.50 (m, 4H), 3.48-3.28 (m, 2H), 3.06-2.94 (m, 2H), 2.09-1.78 (m, 4H).

EXAMPLE 100 (5)

4-(2-Diethylaminoethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3006] 2212

[3007] Free Compound:

[3008] TLC: Rf 0.47 (ethyl acetate:methanol:triethylamine=4:2:0.5);

[3009] NMR (CDCl3): δ 7.92-7.80 (m, 4H), 7.76-7.66 (m, 2H), 7.62-7.56 (m, 2H), 7.03 (brs, 1H), 6.29 (dd, J=9.0, 1.5 Hz, 1H), 3.84 (dd, J=14.4, 1.5 Hz, 1H), 3.72-3.44 (m, 3H), 2.73 (t, J=6.0 Hz, 2H), 2.60 (q, J=7.2 Hz, 4H), 1.04 (t, J=7.2 Hz, 6H).

[3010] Hydrochloride:

[3011] TLC: Rf 0.49 (ethyl acetate:methanol:triethylamine=4:2:0.5);

[3012] NMR (DMSO-d6): δ 10.32 (brs, 1H), 9.30-9.20 (m, 1H), 8.08 (d, J=7.5 Hz, 1H), 7.94 (d, J=7.5 Hz, 1H), 7.86 (t, J=7.5 Hz, 1H), 7.82-7.72 (m, 3H), 7.68-7.58 (m, 2H), 6.29 (d, J=9.3 Hz, 1H), 4.12 (dd, J=15.6, 9.3 Hz, 1H), 3.96 (d, J=15.6 Hz, 1H), 3.80-3.57 (m, 2H), 3.40-3.08 (m, 6H), 1.24 (t, J=7.2 Hz, 6H).

EXAMPLE 100 (6)

4-(2-(N-Ethyl-N-(3-methylphenyl)amino)ethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3013] 2213

[3014] Free Compound:

[3015] TLC: Rf 0.49 (ethyl acetate:triethylamine=6:0.5);

[3016] NMR (CDCl3): δ 7.94-7.87 (m, 2H), 7.82 (d, J=6.9 Hz, 1H), 7.75-7.67 (m, 1H), 7.67-7.54 (m, 4H), 7.17-7.11 (m, 1H), 6.72-6.64 (m, 2H), 6.56 (d, J=7.8 Hz, 1H), 6.49 (brs, 1H), 6.26 (dd, J=9.0, 1.2 Hz, 1H), 3.81 (dd, J=14.7, 1.2 Hz, 1H), 3.77-3.47 (m, 5H), 3.43 (q, J=7.2 Hz, 2H), 2.30 (s, 3H), 1.15 (t, J=7.2 Hz, 3H).

[3017] Hydrochloride:

[3018] TLC: Rf 0.47 (ethyl acetate:triethylamine=6:0.5);

[3019] NMR (CD3OD): δ 7.98-7.60 (m, 6H), 7.59-7.26 (m, 6H), 6.36-6.15 (m, 1H), 4.09-3.89 (m, 4H), 3.88-3.40 (m, 4H), 2.44 (s, 3H), 1.17 (t, J=7.2 Hz, 3H).

EXAMPLE 100 (7)

4-(N-Ethyl-N-2-(piperidin-1-yl)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3020] 2214

[3021] Free Compound:

[3022] TLC: Rf 0.29 (methylene chloride:methanol=6:1);

[3023] NMR (CDCl3): δ 8.00-7.55 (m, 8H), 5.85 (d, J=8 Hz, 1H), 3.85-3.30 (m, 6H), 2.85-2.50 (m, 2H), 2.55 (m, 2H), 2.40 (m, 2H), 1.80-1.40 (m, 6H), 1.34 and 1.36 (each t, J=7 Hz, total 3H).

[3024] Hydrochloride:

[3025] TLC: Rf 0.29 (methylene chloride:methanol=6:1);

[3026] NMR (CDCl3+DMSO-d6): δ 11.30 (broad s, 1H), 7.95-7.60 (m, 8H), 5.89 (d, J=8 Hz, 1H), 4.20-3.80 (m, 3H), 3.80-3.20 (m, 7H), 3.00 (m, 2H), 2.11 (m, 2H), 2.00 (m, 3H), 1.50 (m, 1H), 1.41 (t, J=7 Hz, 3H).

EXAMPLE 100 (8)

4-(3-(Imidazol-1-yl)propyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3027] 2215

Free Compound:

[3028] TLC: Rf 0.50 (methylene chloride:methanol=4:1);

[3029] NMR (CDCl3): δ 7.90-7.50 (m, 9H), 7.56 (s, 1H), 6.98 (s, 1H), 6.93 (s, 1H), 6.27 (dd, J=2 Hz and 7 Hz, 1H), 4.20-3.95 (m, 2H), 3.80-3.55 (m, 3H), 3.30 (m, 1H), 2.13 (m, 2H).

[3030] Hydrochloride:

[3031] TLC: Rf 0.50 (methylene chloride:methanol=4:1);

[3032] NMR (CDCl3+DMSO-d6): δ 9.59 (s, 1H), 9.49 (t-like, 1H), 8.23 (t, J=4.4 Hz, 1H), 7.85-7.60 (m, 5H), 7.60-7.40 (m, 4H), 7.29 (s, 1H), 6.23 (dd, J=4.0 Hz and 6.8 Hz, 1H), 4.65-4.35 (m, 2H), 3.82 (m, 2H), 3.65 (m, 1H), 3.25 (m, 1H), 2.40 (m, 1H), 2.20 (m, 1H).

EXAMPLE 100 (9)

4-((3R)-1-Benzylpyrrolidin-3-yl)carbamoyl-3-phenylsuilfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3033] 2216

[3034] Less Polar Compound:

[3035] TLC: Rf 0.35 (methanol:ethyl acetate:triethylamine=1:8:0.05);

[3036] NMR (CDCl3) δ 7.94-7.87 (m, 2H), 7.87-7.78 (m, 2H), 7.75-7.67 (m, 2H), 7.64-7.56 (m, 2H), 7.38-7.26 (m, 5H), 6.68 (d, J=8.1 Hz, 1H), 6.28-6.20 (m, 1H), 4.73-4.59 (m, 1H), 3.80 (dd, J=14.7, 1.5 Hz, 1H), 3.66 (s, 2H), 3.63 (dd, J=14.7, 9.3 Hz, 1H), 2.96-2.87 (m, 1H), 2.82-2.66 (m, 2H), 2.47-2.30 (m, 2H), 2.12-1.86 (m, 1H).

[3037] More Polar Compound:

[3038] TLC: Rf 0.27 (methanol:ethyl acetate:triethylamine=1:8:0.05);

[3039] NMR (CDCl3): δ 7.90-7.78 (m, 4H), 7.74-7.65 (m, 2H), 7.62-7.52 (m, 2H), 7.36-7.13 (m, 5H), 6.79 (d, J=8.4 Hz, 1H), 6.25-6.18 (m, 1H), 4.72-4.60 (m, 1H), 3.80 (dd, J=15.0,1.5 Hz, 1H), 3.65 (d, J=12.9 Hz, 1H), 3.62 (dd, J=15.0, 9.0 Hz, 1H), 3.54 (d, J=12.9 Hz, 1H), 2.96-2.83 (m, 2H), 2.72 (dd, J=9.9, 6.3 Hz, 1H), 2.49-2.32 (m, 2H), 1.90-1.73 (m, 1H).

[3040] The determination of the absolute configuration of * is not performed, but the said more polar and less polar isomers are each single optically active compounds.

EXAMPLE 100 (10)

4-(3-(Pyrrolidin-1-yl)propyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3041] 2217

[3042] Free Compound:

[3043] TLC: Rf 0.25 (methanol:ethyl acetate:triethylamine=2:4:0.5);

[3044] NMR (CDCl3): δ 9.16-9.06 (m, 1H), 7.91-7.84 (m, 2H), 7.84-7.77 (m, 2H), 7.75-7.62 (m, 2H), 7.61-7.53 (m, 2H), 6.44-6.37 (m, 1H), 3.85 (dd, J=14.7, 1.2 Hz, 1H), 3.80-3.61 (m, 2H), 3.59-3.44 (m, 1H), 2.91-2.72 (m, 2H), 2.71-2.59 (m, 4H), 2.00-1.63 (m, 6H).

[3045] Hydrochloride:

[3046] TLC: Rf 0.26 (methanol:ethyl acetate:triethylamine=2:4:0.5);

[3047] NMR (DMSO-d6): δ 10.43 (brs, 1H), 9.00 (t, J=5.7 Hz, 1H), 8.02 (d, J=7.5 Hz, 1H), 7.94 (d, J=7.5 Hz, 1H), 7.90-7.74 (m, 4H), 7.71-7.61 (m, 2H), 6.30 (d, J=9.0 Hz, 1H), 4.11 (dd, J=15.0, 9.0 Hz, 1H), 3.94 (d, J=15.0 Hz, 1H), 3.60-3.10 (m, 6H), 3.10-2.78 (m, 2H), 2.11-1.73 (m, 6H).

EXAMPLE 100 (11)

4-(N-2-(Piperidin-1-yl)ethyl-N-methyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3048] 2218

[3049] Free Compound:

[3050] TLC: Rf 0.29 (methylene chloride:methanol=6:1);

[3051] NMR (CDCl3): δ 8.05-7.55 (m, 8H), 5.88 (dd, J=8.8 Hz and 2.0 Hz, 1H), 4.00-3.55 and 3.30 (each m, total 4H), 3.20 and 3.17 (each s, total 3H), 2.80-2.35 (m, 6H), 1.70-1.40 (m, 6H)

[3052] Hydrochloride:

[3053] TLC: Rf 0.29 (methylene chloride:methanol=6:1);

[3054] NMR (DMSO-d6): δ 10.49 (broad s, 1H), 8.15 (d, J=6.2 Hz, 1H), 8.00-7.60 (m, 7H), 5.87 (d, J=8.8 Hz, 1H), 4.25-3.70 (m, 4H), 3.70-2.80 (m, 6H), 3.33 and 3.16 (each s, total 3H), 2.00-1.60 (m, 5H), 1.44 (m, 1H).

EXAMPLE 100 (12)

4-(3,5-Dimethoxybenzyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3055] 2219

[3056] TLC: Rf 0.45 (methylene chloride:ethyl acetate=4:1);

[3057] NMR (DMSO-d6): δ 9.26 (t, J=5.8 Hz, 1H), 7.78 (d, J=7.6 Hz, 1H), 7.91 (dd, J=7.6, 1.0 Hz, 1H), 7.84 (dd, J=7.0, 1.0 Hz, 1H), 7.13 (t, J=7.6 Hz, 1H), 7.45 (d, J=7.0 Hz, 1H), 6.51 (d, J=2.2 Hz, 2H), 6.39 (t, J=2.2 Hz, 1H), 4.42 (d, J=5.8 Hz, 2H), 3.73 (s, 6H).

EXAMPLE 100 (13)

4-(3-(Piperidin-1-yl) propyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene hydrochloride

[3058] 2220

[3059] TLC: Rf 0.30 (ethyl acetate:methanol:triethylamine=8:1.5:0.5);

[3060] NMR (DMSO-d6): δ 10.40 (broad s, 1H), 9.08 (t, J=5.3 Hz, 1H), 8.10-7.60 (m, 8H), 6.33 (d, J=9.2 Hz, 1H), 4.13 (dd, J=15.0 Hz and 9.2 Hz, 1H), 3.94 (d, J=15.0 Hz, 1H), 3.60-3.00 (m, 6H), 2.80 (m, 2H),2.05 (t, J=6.5 Hz, 2H), 1.73 (m, 5H), 1.36 (m,1H).

EXAMPLE 100 (14)

4-(2-Diisopropylaminoethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[3061] 2221

[3062] TLC: Rf 0.46 (ethyl acetate:methanol:triethylamine=8:1.5:0.5);

[3063] NMR (DMSO-d6): δ 10.01 (s, 1H), 9.27 (t, J=5.7 Hz, 1H), 8.09 (d, J=7.0 Hz, 1H), 7.97 (d, J=7.0 Hz, 1H), 7.88 (t, J=7.0 Hz, 1H), 7.80-7.76 (m, 3H), 7.68-7.60 (m, 2H), 6.36 (d, J=9.0 Hz, 1H), 4.11 (dd, J=15.3 Hz and 9.0 Hz, 1H), 3.96 (d, J=15.3 Hz,1H), 3.90-3.60 (m, 4H), 3.33 (m, 1H), 3.18 (m, 1H), 1.42 (d, J=6.6 Hz, 3H), 1.38 (d, J=6.6 Hz, 3H), 1.34 (d, J=6.6 Hz, 3H), 1.32 (d, J=6.6 Hz, 3H).

EXAMPLE 100 (15)

4-(2-(Morpholin-4-yl)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzolb]thiophene.hydrochloride

[3064] 2222

[3065] TLC: Rf 0.33 (ethyl acetate:methanol:triethylamine=8:1.5:0.5);

[3066] NMR (DMSO-d6): δ 11.14 (broad s, 1H), 9.27 (broad t-like, 1H), 8.13 (d, J=7.5 Hz, 1H), 7.93 (d, J=7.5 Hz, 1H), 7.86 (t, J=7.5 Hz, 1H), 7.82-7.70 (m, 3H), 7.70-7.60 (m, 2H), 6.30 (d, J=8.4 Hz, 1H), 4.14 (dd, J=15.6 Hz and 8.4 Hz, 1H), 4.00-3.65 (m, 7H), 3.65-3.00 (m, 6H).

EXAMPLE 100 (16)

4-(N-2-(Piperidin-1-yl)ethyl-N-propyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene hydrochloride

[3067] 2223

[3068] TLC: Rf 0.47 (ethyl acetate:methanol:triethylamine=8:1.5:0.5);

[3069] NMR (DMSO-d6): δ 10.70 and 10.66 (each broad s, total 1H), 8.00-7.65 (m, 8H), 5.83 (d, J=8.7 Hz, 1H), 4.14 (dd, J=15.3 Hz and 8.7 Hz, 1H), 4.00-3.70 (m, 3H), 3.65-3.10 (m, 6H), 3.10-2.80 (m, 2H), 2.00-1.60 (m, 6H), 1.40 (m, 1H), 0.98 and 0.86 (each t, J=7.2 Hz, total 3H).

EXAMPLE 100 (17)

4-(N-2-(Piperidin-1-yl)ethyl-N-isopropyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[3070] 2224

[3071] TLC;Rf 0.55 (ethyl acetate:methanol:triethylamine=8:1.5:0.5);

[3072] NMR (DMSO-d6): δ 10.78 (broad s, 1H), 8.00-7.60 (m, 8H), 5.90 (d, J=9.2 Hz, 1H), 4.40-4.03 (m, 3H), 4.00-2.80 (m, 8H), 2.00-1.60 (m, 5H), 1.40 (m, 1H), 1.44 and 1.28 and 1.04 (each d, J=6.4 Hz, total 6H).

EXAMPLE 100 (18)

4-(4-Benzoylpiperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3073] 2225

[3074] TLC: Rf 0.48 (methylene chloride:methanol=10:1);

[3075] NMR (DMSO-d6): δ 7.95-7.80 (m, 3H), 7.80-7.56 (m, 5H), 7.42 (s, 5H), 5.92 (dd, J=9.0, 1.5 Hz, 1H), 4.40-4.00 (m, 2H), 3.90-3.40 (m, 6H), 3.72 (dd, J=15.0, 1.5 Hz, 1H), 3.65 (dd, J=15.0, 9.0 H z, 1H).

EXAMPLE 100 (19)

4-(4-(4-Ethylbenzyl)piperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[3076] 2226

[3077] TLC: Rf 0.55 (methylene chloride:methanol 10:1);

[3078] NMR (DMSO-d6): δ 7.88-7.73 (m, 6H), 7.67-7.63 (m, 2H), 7.47 (d, J=7.0 Hz, 2H), 7.21 (d, J=7.0 Hz, 2H), 5.87 (dd, J=10.0, 1.5 Hz, 1H), 4.16 (bs, 2H), 4.05 (dd, J=15.0, 10.0 HZ, 1H), 3.79 (dd, J=15.0, 1.5 Hz, 1H), 3.30-2.90 (m, 8H), 2.58 (q, J=8.0 Hz, 2H), 1.17 (t, J=8.0 Hz, 3H).

EXAMPLE 100 (20)

4-(4-(4-Phenylbenzyl)piperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1dioxidebenzo[b]thiophene.hydrochloride

[3079] 2227

[3080] TLC: Rf 0.55 (methylene chloride:methanol=10:1);

[3081] NMR (DMSO-d6): δ 7.88-7.78 (m, 3H), 7.78-7.72 (m, 3H), 7.67-7.58 (m, 7H), 7.48-7.41 (m, 3H), 7.38-7.34 (m, 1H), 5.88 (d, J=9.5 Hz, 1H), 4.21 (bs, 2H), 4.10-3.70 (m, 8H), 4.06 (dd, J=15.5, 9.5 Hz, 1H), 3.79 (d, 15.5 Hz, 1H), 3.19 (s, 2H).

EXAMPLE 100 (21)

4-(4-(1,3-Dioxaindan-5-ylmethyl)piperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[3082] 2228

[3083] TLC: Rf 0.54 (methylene chloride:methanol=10:1);

[3084] NMR (DMSO-d6): δ 7.86-7.76 (m, 4H), 7.74 (d, J=8.0 Hz, 2H), 7.64 (t, J=8.0 Hz, 2H), 7.08 (bs, 1H), 6.98-6.92 (m, 1H), 6.83 (d, J=8.0 Hz, 1H), 5.96-5.92 (m, 2H), 5.86 (d, J=8.5 Hz, 1H), 4.15-3.70 (m, 2H), 4.04 (dd, J=15.0, 8.5 Hz, 1H), 3.78 (d, J=15.0 Hz, 1H), 3.15-2.80 (m, 8H).

EXAMPLE 100 (22)

4-(4-Benzyloxycarbonylpiperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3085] 2229

[3086] TLC: Rf 0.80 (methylene chloride:methanol=10:1);

[3087] NMR (DMSO-d6): δ 7.96-7.80 (m, 4H), 7.76 (d, J=7.5 Hz, 2H), 7.66 (t, J=7.5 Hz, 2H), 7.45-7.36 (m, 5H), 5.89 (d, J=8.7 Hz, 1H), 5.11 (s, 2H), 4.13 (dd, J=14.7, 8.7 Hz, 1H), 3.93 (d, J=14.7 Hz, 1H), 3.80-3.40 (m, 8H).

EXAMPLE 100 (23)

4-(4-(2-Methylphenyl)piperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-diozidebenzo[b]thiophene hydrochloride

[3088] 2230

[3089] TLC: Rf 0.80 (methylene chloride:methanol=10:1);

[3090] NMR (DMSO-d6): δ 7.97-7.90 (m, 2H), 7.90-7.74 (m, 4H), 7.74-7.63 (m, 2H), 7.23-7.10 (m, 2H), 7.10-6.83 (m, 2H), 5.92 (d, J=9.6 Hz, 1H), 4.15 (dd, J=15.3, 9.6 Hz, 1H), 3.93 (d, J=15.3 Hz, 1H), 3.92-3.80 (m, 2H), 3.08-2.90 (m, 6H), 2.30 (s, 3H).

EXAMPLE 100 (24)

4-(4-(4-Methoxyphenyl) piperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene hydrochloride

[3091] 2231

[3092] TLC: Rf 0.75 (methylene chloride:methanol=10:1); NMR (DMSO-d6): δ 8.02-7.92 (m, 2H), 7.92-7.73 (m, 4H), 7.72-7.64 (m, 2H), 7.36-7.14 (m, 2H), 7.00-6.90 (m, 2H), 5.91 (d, J=9.6 Hz, 1H), 4.20-3.76 (m, 4H), 4.14 (dd, J=15.3, 9.6 Hz, 1H), 3.93 (d, J=15.3 Hz, 1H), 3.72 (s, 3H), 3.45-3.26 (m, 4H).

EXAMPLES 101˜101 (1)

[3093] By the same procedure as described in Example 1 using the compounds prepared in Examples 28 (11) and 73 (16) instead of 1,1-dioxidebenzo[b]thiophene, the following compounds of the present invention were obtained.

EXAMPLE 101

4-2-(Piperidin-1-yl)ethyl)carbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3094] 2232

[3095] TLC: Rf 0.40 (methanol:water:acetic acid=1:1:0.1);

[3096] NMR (CDCl3): δ 7.81 (dd, J=7.6, 1.1 Hz, 1H), 7.75 (dd, J=7.6, 1.1 Hz, 1H), 7.61 (t, J=7.6 Hz, 1H), 7.56-7.53 (m, 2H), 7.38-7.35 (m, 3H), 6.91 (br, 1H), 5.74 (dd, J=7.3, 1.3 Hz, 1H), 3.72 (dd, J=13.9, 7.3 Hz, 1H), 3.68-3.58 (m, 1H), 3.60 (dd, J=13.9, 1.3 Hz, 1H), 3.55-3.45 (m, 1H), 2.55 (t, J=5.8 Hz, 2H), 2.38 (br, 4H), 1.56-1.48 (m, 4H), 1.44-1.39 (m, 2H).

EXAMPLE 101 (1)

4-(2-(Pyridin-2-yl)ethyl)oxy-3-phenylthio-1,1-dioxidebenzo[b]thiophene

[3097] 2233

[3098] TLC: Rf 0.30 (hexane:ethyl acetate=1:1);

[3099] NMR (CDCl3): δ 8.54 (ddd, J=4.8, 1.7, 1.0 Hz, 1H), 7.54 (dt, J=7.7, 1.7 Hz, 1H), 7.49 (t, J=8.0 Hz, 1H), 7.43-7.40 (m, 2H), 7.34-7.22 (m, 5H), 7.15-7.10 (m, 2H), 4.91 (dd, J=6.9, 1.8 Hz, 1H), 4.52 (t, J=6.6 Hz, 2H), 3.66 (dd, J=13.8, 6.9 Hz, 1H), 3.57 (dd, J=13.8, 1.8 Hz, 1H), 3.31 (t, J=6.6 Hz, 2H).

EXAMPLE 102

4-(2-(Piperidin-1-yl)ethyl)carbamoyl-3-(4-nitrophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3100] 2234

[3101] By the same procedure as described in Example 27 using the compound prepared in Example 28 (11) instead of 5-methyl-1,1-dioxidebenzo[b]thiophene, and 4-nitrobenzenesulfonic acid sodium salt instead of benzenesulfonic acid sodium salt, and if necessary, by converting into hydrochloride by a known method, the compounds of the present invention having the following physical data were obtained.

[3102] Free Compound:

[3103] TLC: Rf 0.40(methanol:water:acetic acid=5:5:0.5);

[3104] NMR (CDCl3): δ 8.35 (d, J=8.7 Hz, 2H), 8.01 (d, J=8.7 Hz, 2H), 7.91 (dd, J=7.5,1.7 Hz, 1H), 7.81 (dd, J=7.5, 1.7 Hz, 1H), 7.76 (t, J=7.5 Hz, 1H), 7.59 (br, 1H), 6.42 (dd, J=9.2, 1.5 Hz, 1H), 3.88 (dd, J=15.0,1.5 Hz, 1H), 3.75 (dd, J=15.0, 9.2 Hz, 1H), 3.75-3.64 (m, 1H), 3.57-3.48 (m, 1H), 2.77-2.65 (m, 2H), 2.53 (br, 4H), 1.66-1.57 (m, 4H), 1.52-1.45 (m, 2H).

[3105] Hydrochloride:

[3106] TLC: Rf 0.40 (methanol:water:acetic acid=5:5:0.5);

[3107] NMR (DMSO-d6): δ 9.98 (br, 1H), 9.28 (br, 1H), 8.42 (d, J=8.7 Hz, 2H), 8.11 (d, J=7.5 Hz, 1H), 8.03 (d, J=8.7 Hz, 2H), 7.97 (d, J=7.5 Hz, 1H), 7.89 (t, J=7.5 Hz, 1H), 6.41 (dd, J=7.3, 3.2 Hz, 1H), 4.16 (dd, J=15.5, 7.3 Hz, 1H), 4.10 (dd, J=15.5, 3.2 Hz, 1H), 3.72-3.70 (m, 2H), 3.57-3.48 (m, 2H), 3.32-3.25 (m, 2H), 2.96 (br, 2H), 1.82-1.68 (m, 5H), 1.45-1.35 (m, 1H).

EXAMPLES 103˜103 (41)

[3108] By the same procedure as described in Example 31 using 4-methylsulfonyloxymethyl-3-phenyisulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene instead of 4-bromomethyl-1,1-dioxidebenzo[b]thiophene and an amine derivative corresponding to 2,4-dimethoxybenzylamine hydrochloride, and if necessary, by converting into the corresponding salt by a known method, the following compounds of the present invention were obtained.

EXAMPLE 103

4-(N-2-(Piperidin-1-yl)ethyl-N-methyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[3109] 2235

[3110] TLC: Rf 0.48 (methanol:ethyl acetate:triethylamine=2:8:0.5);

[3111] NMR (CD3OD+D2O (4 drops)): δ 8.16 (d, J=7.5 Hz, 1H), 7.90 (t, J=7.5 Hz, 1H), 7.85-7.73 (m, 4H), 7.64-7.55 (m, 2H), 6.18-6.10 (m, 1H), 4.93 (d, J=14.4 Hz, 1H), 4.60 (d, J=14.4 Hz, 1H), 4.03 (dd, J=15.6, 9.0 Hz, 1H), 3.84 (dd, J=15.6, 0.9 Hz, 1H), 3.72-3.00 (m, 8H), 2.74 (s, 3H), 2.00-1.55 (m, 6H).

EXAMPLE 103 (1)

4-(2-(N-Ethyl-N-3-methylphenyl)aminoethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene 2hydrochloride

[3112] 2236

[3113] TLC: Rf 0.45 (ethyl acetate:triethylamine=6:0.5);

[3114] NMR (DMSO-d6): δ 9.64 (brs, 2H), 8.21 (d, J=6.3 Hz, 1H), 7.89-7.74 (m, 5H), 7.67-7.58 (m, 2H), 7.18-7.04 (m, 1H), 6.96-6.50 (m, 3H), 6.46 (dd, J=6.9, 3.0 Hz, 1H), 4.73-4.59 (m, 1H), 4.49-4.35 (m, 1H), 3.97-3.80 (m, 2H), 3.80-3.58 (m, 2H), 3.50-3.33 (m, 2H), 3.29-3.10 (m, 2H), 2.25 (s, 3H), 1.06 (t, J=6.9 Hz, 3H).

EXAMPLE 103 (2)

4-(N-Benzyl-N-ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene hydrochloride

[3115] 2237

[3116] TLC: Rf 0.67 (ethyl acetate:triethylamine=6:0.5);

[3117] NMR (CD3OD+pyridine-d5) δ 7.92 (d, J=7.2 Hz, 1H), 7.71-7.58 (m, 4H), 7.57-7.45 (m, 3H), 7.32-7.15 (m, 5H), 5.84 (dd, J=8.4, 1.8 Hz, 1H), 4.33 (d, J=14.7Hz, 1H), 3.90-3.62 (m, 4H),3.60 (d, J=13.2 Hz, 1H), 2.65 .(q, J=7.2Hz, 2H), 1.14 (t, J=7.2 Hz, 3H).

EXAMPLE 103 (3)

4-(2-Diethylaminoethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene-2hydrochloride

[3118] 2238

[3119] TLC: Rf 0.35 (methanol ethyl acetate triethylamine=2:8:0.5);

[3120] NMR (DMSO-d6): δ 10.66 (brs, 1H), 9.96 (brs, 1H), 9.76 (brs, 1H), 8.26-8.26 (m, 1H), 7.91-7.74 (m, 5H), 7.67-7.57 (m, 2H), 6.54-6.45 (m, 1H), 4.83-4.65 (m, 1H), 4.60-4.42 (m, 1H), 3.96-3.82 (m, 2H), 3.70-3.37 (m, 4H), 3.28-3.10 (m, 4H), 1.26 (t, J=7.2 Hz, 6H).

EXAMPLE 103 (4)

4-(4-Methylbenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[3121] 2239

[3122] TLC: Rf 0.47 (ethyl acetate:triethylamine=6:0.5);

[3123] NMR (DMSO-d6): δ 9.83 (brs, 1H), 9.54 (brs, 1H), 8.16 (d, J=6.9 Hz, 1H), 7.89-7.75 (m, 3H), 7.75-7.68 (m, 2H), 7.68-7.59 (m, 2H), 7.50 (d, J=8.1 Hz, 2H), 7.25 (d, J=8.1 Hz, 2H), 6.29 (dd, J=4.8, 3.9 Hz, 1H), 4.72-4.58 (m, 1H), 4.44-4.32 (m, 1H), 4.25 (brs, 2H), 3.93-3.80 (m, 2H), 2.32 (s, 3H).

EXAMPLE 103 (5)

4-(N-Ethyl-N-2-(piperidin-1-yl)ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[3124] 2240

[3125] TLC: Rf 0.47 (methanol ethyl:acetate triethylamine=2:8:0.5);

[3126] NMR (CD3OD+D2O (1 drop)) δ 8.24 (d, J=7.5 Hz, 1H), 7.92-7.69 (m, 5H), 7.61-7.52 (m, 2H), 6.21-6.10 (m, 1H), 5.15 (d, J=14.4 Hz, 1H), 4.70 (d, J=14.4 Hz, 1H), 4.05 (dd, J=15.3, 9.0 Hz, 1H), 3.84 (dd, J=15.3, 0.9 Hz, 1H), 3.76-2.80 (m, 10H), 1 98-1.50 (m, 6H), 1.45 (t, J=7.2 Hz, 3H).

EXAMPLE 103 (6)

4-(2-Methoxybenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[3127] 2241

[3128] TLC: Rf 0.49 (ethyl acetate:triethylamine=6:0.5);

[3129] NMR (DMSO-d6): δ 9.51 (brs, 2H), 8.21-8.11 (m, 1H), 7.89-7.775 (m, 3H), 7.74-7.58 (m, 4H), 7.51 (d, J=7.5 Hz, 1H), 7.47-7.38 (m, 1H), 7.08 (d, J=8.1 Hz, 1H), 7.01 (t, J=7.5 Hz, 1H), 6.16-6.06 (m, 1H), 4.77-4.62 (m, 1H), 4.52-4.37 (m, 1H), 4.31-4.12 (m, 2H), 3.95-3.82 (m, 2H), 3.81 (s, 3H).

EXAMPLE 103 (7)

4-(3-Phenylpropyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[3130] 2242

[3131] TLC: Rt 0.37 (ethyl acetate:triethylamine=6:0.5);

[3132] NMR (DMSO-d6): δ 9.50 (brs, 1H), 8.16 (d, J=6.3 Hz, 1H), 7.90-7.73 (m, 5H), 7.68-7.58 (m, 2H), 7.35-7.16 (m, 5H), 6.44 (dd, J=6.9, 3.0 Hz, 1H), 4.69-4.54 (m, 1H), 4.45-4.31 (m , 1H), 3.95-3.79 (m, 2H), 3.14-2.95 (m, 2H), 2.68 (t, J=7.2 Hz, 2H), 2.09-1.91 (m, 2H).

EXAMPLE 103 (8)

4-(3,5-Dimethoxybenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[3133] 2243

[3134] TLC: Rf 0.43(ethyl acetate:triethylamine=6:0.5);

[3135] NMR (DMSO-d6): δ 9.94 (brs, 1H), 9.65 (brs, 1H), 8.17 (d, J=6.9 Hz, 1H), 7.90-7.75 (m, 3H), 7.75-7.67 (m, 2H), 7.67-7.58 (m, 2H), 6.87 (d, J=2.1 Hz, 2H), 6.55 (t, J=2.1 Hz, 1H), 6.30 (t, J=4.5 Hz, 1H), 4.72-4.57 (m, 1H), 4.43-4.28 (m, 1H), 4.23 (brs, 2H), 4.00-3.67 (m, 2H), 3.75 (s, 6H).

EXAMPLE 103 (9)

4-((3R)-1-Benzylpyrrolidin-3-yl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[3136] 2244

[3137] TLC: Rf 0.45(methanol:ethyl acetate:triethylamine=2:8:0.5);

[3138] NMR (CD3OD): δ 8.20 (d, J=6.9 Hz, 1H), 7.91-7.70 (m, 5H), 7.66-7.54 (m, 4H), 7.53-7.43 (m, 3H), 6.18-6.05 (m, 1H), 4.77 (d, J=14.1 Hz, 1H), 4.67-4.32 (m, 4H), 4.02-3.66 (m, 5H), 3.62-3.38 (m, 1H), 2.88-2.40 (m, 2H).

EXAMPLE 103 (10)

4-((3S)-1-Benzylpyrrolidin-3-yl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene 2hydrochloride

[3139] 2245

[3140] TLC: Rf 0.45(methanol:ethyl acetate:triethylamine=2:8:0.5);

[3141] NMR (CD3OD): δ 8.20 (d, J=6.9 Hz, 1H), 7.91-7.70 (m, 5H), 7.66-7.54 (m, 4H), 7.53-7.43 (m, 3H), 6.18-6.04 (m, 1H), 4.78 (d, J=12.9 Hz, 1H), 4.68-4.32 (m, 4H), 4.02-3.66 (m, 5H), 3.62-3.38 (m, 1H), 2.88-2.40 (m, 2H).

EXAMPLE 103 (11)

4-(2-Phenylethyl)aminomethyl-3-phenylsulfonyl-2,3-dohydro-1,1-dioxidebenzo[b]thiophene

[3142] 2246

[3143] Free Compound:

[3144] TLC: Rf 0.28 (ethyl acetate);

[3145] NMR (CDCl3): δ 7.65-7.40 (m, 8H), 7.30-7.15 (m, 5H), 5.90 (dd, J=9.3, 0.9 Hz, 1H), 4.66 (d, J=14.2 Hz, 1H), 3.92 (d, J=14.2 Hz, 1H), 3.73 (dd, J=15.0, 0.9 Hz, 1H), 3.42 (dd, J=15.0, 9.3 Hz, 1H), 3.01-2.74 (m, 4H).

[3146] Hydrochloride:

[3147] TLC: Rf 0.28 (ethyl acetate);

[3148] NMR (DMSO-d6): δ 9.55 (br, 1H), 9.35 (br, 1H), 8.18 (dd, J=6.2, 2.5 Hz, 1H), 7.94-7.87 (m, 2H), 7.82-7.78 (m, 3H), 7.67-7.62 (m, 2H), 7.38-7.33 (m, 2H), 7.29-7.25 (m, 3H), 6.41 (dd, J=7.5, 2.1 Hz, 1H), 4.69-4.6 5 (m, 1H), 4.45-4.41 (m, 1H), 3.92 (dd, J=15.3, 7.5 Hz, 1H), 3.84 (dd, J=15.3, 2.1 Hz, 1H), 3.32-3.25 (m, 2H), 3,08-2.98 (m, 2H).

EXAMPLE 103 (12)

4-(N-Benzyl-N-methyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3149] 2247

[3150] Free Compound:

[3151] TLC: Rf 0.42 (hexane:ethyl acetate=1:2);

[3152] NMR (CDCl3): δ 7.71 (dd, J=7.2,1.2 Hz, 1H), 7.64-7.49 (m, 5H), 7.44-7.39 (m, 2H), 7.34-7.20 (m, 5H), 6.08 (dd, J=9.3, 1.0 Hz, 1H), 4.66 (d, J=14.1 Hz, 1H), 3.88 (dd, J=15.0, 1.0 Hz, 1H), 3.69 (dd, J=15.0, 9.3 Hz, 1H), 3.61 (d, J=12.9 Hz, 1H), 3.53 (d, J=14.1 Hz, 1H), 3.47 (d, J=12.9 Hz, 1H), 2.16 (s, 3H).

[3153] Hydrochloride:

[3154] TLC: Rf 0.42 (hexane:ethyl acetate=1:2);

[3155] NMR (CD3OD+pyridine-d5): δ 7.92 (d, J=7.5 Hz, 1H), 7.73-7.63 (m, 5H), 7.56-7.50 (m, 2H), 7.37-7.31 (m, 5H), 5.99 (dd, J=7.0, 3.0 Hz, 1H), 4.52 (d, J=14.4 Hz, 1H), 3.94-3.85 (m, 3H), 3.83 (d, J=13.0 Hz, 1H), 3.76 (d, J=13.0 Hz, 1H), 2.32 (s, 3H).

EXAMPLE 103 (13)

4-(3-(2-Oxopyrrolidin-1-yl)propyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3156] 2248

[3157] Free Compound:

[3158] TLC: Rf 0.27 (ethyl acetate:methanol:triethylamine=8:1:1);

[3159] NMR (CDCl3): δ 7.72 (dd, J=7.5, 1.5 Hz, 1H), 7.65-7.54 (m, 4H), 7.51 (dd, J=7.5, 1.5 Hz, 1H), 7.47-7.42 (m, 2H), 5.98 (t-like, J=5.1 Hz, 1H), 4.56 (d, J=13.8 Hz, 1H), 3.91-3.87 (m, 3H), 3.40-3.30 (m, 4H), 2.67-2.53 (m, 2H), 2.41-2.38 (m, 2H), 2.05-1.95 (m, 2H), 1.78-1.69 (m, 2H).

[3160] Hydrochloride:

[3161] TLC: Rf 0.27 (ethyl acetate:methanol:tiethylamine=8:1:1);

[3162] NMR (DMSO-d6): δ 9.32 (m, 1H), 9.08 (m, 1H), 8.14 (dd, J=6.3, 2.1 Hz, 1H), 7.90-7.78 (m, 5H), 7.67-7.62 (m, 2H), 6.40 (dd, J=7.5, 2.0 Hz, 1H), 4.66-4.60 (m, 1H), 4.43-4.37 (m, 1H), 3.94-3.81 (m, 2H), 3.38-3.25 (m, 4H), 3.03-2.97 (m, 2H), 2.26 (t, J=8.0 Hz, 2H), 1.99-1.83 (m, 4H).

EXAMPLE 103 (14)

4-(4-Aminobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3163] 2249

[3164] Free Compound:

[3165] TLC: Rf 0.47 (ethyl acetate:methanol:triethylamine=8:1:1);

[3166] NMR (DMSO-d6): δ 7.90 (dd, J=7.0, 2.0 Hz, 1H), 7.80-7.61 (m, 7H), 6.97 (d, J 8.5 Hz, 2H), 6.52 (d, J=8.5 Hz, 2H), 5.81 (dd, J=8.0, 1.8 Hz, 1H), 4.93 (s, 2H), 4.01 (d, J=14.7 Hz, 1H), 3.91 (dd, J=15.0, 8.0 Hz, 1H), 3.84 (dd, J=15.0, 1.8 Hz, 1H), 3.77 (d, J=14.7 Hz, 1H), 3.48 (s, 2H).

[3167] Hydrochloride:

[3168] TLC: Rf 0.47 (ethyl acetate:methanol:triethylamine=8:1:1);

[3169] NMR (DMSO-d6): δ 9.90 (br, 1H), 9.59 (br, 1H), 8.18 (dd, J=7.0, 1.5 Hz, 1H), 7.88-7.60 (m, 9H), 7.21 (d, J=7.8 Hz, 2H), 6.37-6.34 (m, 1H), 4.70-4.64 (m, 1H), 4.42-4.32 (m, 1H), 4.28 (s, 2H), 3.93-3.82 (m, 2H).

EXAMPLE 103 (15)

4-(4-((2E)-3-Phenyl-2-propenyl)piperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3170] 2250

[3171] Free Compound:

[3172] TLC: Rf 0.48 (ethyl acetate:methanol=9:1);

[3173] NMR (CDCl3): δ 7.65-7.20 (m, 13H), 6.52 (d, J=15.9 Hz, 1H), 6.30 (dd, J=9.3, 1.2 Hz, 1H), 6.26 (dt, J=15.9, 6.8 Hz, 1H), 4.70 (d, J=14.3 Hz, 1H), 3.91 (dd, J=15.0, 1.2 Hz, 1H), 3.73 (dd, J=15.0, 9.3 Hz, 1H), 3.42 (d, J=14.3 Hz, 1H), 3.16 (d, J=6.8 Hz, 2H), 2.60-2.40 (m, 8H).

[3174] Hydrochloride:

[3175] TLC: Rf 0.48 (ethyl acetate:methanol=9:1);

[3176] NMR (CD3OD+D2O): 5 7.93 (d, J=7.0 Hz, 1H), 7.78-7.72 (m, 4H), 7.66 (d, J=7.0 Hz, 1H), 7.61-7.50 (m, 2H), 7.41-7.33 (m, 3H), 6.95 (d, J=15.6 Hz, 1H), 6.33 (dt, J=15.6, 7.7 Hz, 1H), 6.16 (d, J=9.0 Hz, 1H), 4.54 (d, J=14.5 Hz, 1H), 4.02 (dd, J=15.0,9.0Hz, 1H), 3.96 (d, J=7.7Hz, 2H), 3.89 (d, J=15.0Hz, 1H), 3.85 (d, J=14.5 Hz, 1H), 3.42 (br, 4H), 3.29 (br, 4H).

EXAMPLE 103 (16)

4-(2-Aminobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3177] 2251

[3178] Free Compound:

[3179] TLC: Rf 0.30 (ethyl acetate);

[3180] NMR (CDCl3): δ 7.74 (d, J=7.5 Hz, 1H), 7.65-7.55 (m, 2H), 7.51-7.39 (m, 5H), 7.09 (dt, J=7.5, 1.5 Hz, 1H), 6.97 (dd, J=7.5, 1.5 Hz, 1H), 6.67 (dt, J=7.5, 1.5 Hz, 1H), 6.63 (dd, J=7.5, 1.5 Hz, 1H), 5.43 (dd, J=9.5, 1.2 Hz, 1H), 4.29 (d, J=14.3 Hz, 1H), 4.02 (d, J=14.3 Hz, 1H), 3.88 (d, J=12.6 Hz, 1H), 3.82 (dd, J=15.0, 1.2 Hz, 1H), 3.81 (d, J=12.6 Hz, 1H), 3.66 (dd, J=15.0, 9.5 Hz, 1H).

[3181] Hydrochloride:

[3182] TLC: Rf 0.30 (ethyl acetate); NMR (DMSO-d6): δ 8.17 (dd, J=6.3, 2.4 Hz, 1H), 7.87-7.71 (m, 5H), 7.66-7.61 (m, 2H), 7.50 (br, 2H), 7.29 (dd, J=7.5, 1.2 Hz, 1H), 7.13 (dt, J=7.5, 1.2 Hz, 1H), 6.75 (d, J=7.5 Hz, 1H), 6.63 (t, J=7.5 Hz, 1H), 6.21 (t-like, J=5.0 Hz, 1H), 4.72 (d, J=13.8 Hz, 1H), 4.46 (d, J=13.8 Hz, 1H), 4.26-4.17 (m, 2H), 3.93-3.82 (m, 2H).

EXAMPLE 103 (17)

4-(4-Benzylpiperidin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3183] 2252

[3184] Free Compound:

[3185] TLC: Rf 0.50 (hexane:ethyl acetate=1:1);

[3186] NMR (CDCl3) δ 7.66-7.56 (m, 4H), 7.53-7.51 (m, 2H), 7.48-7.43 (m, 2H), 7.30-7.25 (m, 2H), 7.21-7.11 (m, 3H), 6.36 (d, J=9.3 Hz, 1H), 4.62 (d, J=14.4 Hz, 1H), 3.89 (d, J=15.0 Hz, 1H), 3.71 (dd, J=15.0, 9.3 Hz, 1H), 3.35 (d, J=14.4 Hz, 1H), 3.04-3.00 (m, 1H), 2.53 (d, J=6.9 Hz, 2H), 2.55-2.50 (m, 1H), 2.05 (dt, J=11.5, 2.5 Hz, 1H), 1.85 (dt, J=11.5, 2.5 Hz, 1H), 1.74-1.68 (m, 1H), 1.62-1.15 (m, 2H), 1.35 (dt, J=12.0, 3.5 Hz, 1H), 1.16-1.02 (m, 1H).

[3187] Hydrochloride:

[3188] TLC: Rf 0.50 (hexane:ethyl acetate=1:1);

[3189] NMR (DMSO-d6): δ 10.42 (br, 1H), 8.22 (d, J=7.0 Hz, 1H), 7.92-7.72 (m, 5H), 7.65-7.60 (m, 2H), 7.31-7.15 (m, 5H), 6.30 (d, J=9.0 Hz, 1H), 4.72 (dd, J=13.8, 5.3 Hz, 1H), 4.53 (dd, J=13.8,5.3 Hz, 1H), 4.02 (dd, J=15.3,9.0 Hz, 1H), 3.83 (d, J=15.3 Hz, 1H), 3.42-3.39 (m, 1H), 3.12-3.00 (m, 3H), 2.60-2.42 (m, 2H), 1.79-1.49 (m, 5H).

EXAMPLE 103 (18)

4-(4-Chlorobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3190] 2253

[3191] Free Compound:

[3192] TLC: Rf 0.43(ethyl acetate);

[3193] NMR (CDCl3): δ 7.75 (dd, J=7.0,1.2 Hz, 1H), 7.66-7.51 (m, 5H), 7.47-7.42 (m, 2H), 7.32 (d, J=8.4 Hz, 2H), 7.24 (d, J=8.4 Hz, 2H), 5.81 (dd, J=9.3,1.3 Hz, 1H), 4.48 (d, J=14.0 Hz, 1H), 3.99 (d, J=14.0 Hz, 1H), 3.86 (dd, J=15.0,1.3 Hz, 1H), 3.84 (d, J=13.3 Hz, 1H), 3.78 (d, J=13.3 Hz, 1H), 3.68 (dd, J=15.0, 9.3 Hz, 1H).

[3194] Hydrochloride:

[3195] TLC: Rf 0.43 (ethyl acetate);

[3196] NMR (DMSO-d6): δ 9.86 (br, 1H), 9.55 (br, 1H), 8.16 (dd, J=6.6, 1.8 Hz, 1H), 7.88-7.72 (m, 5H), 7.67-7.62 (m, 4H), 7.53 (d, J=8.4 Hz, 2H), 6.31 (dd, J=6.2, 3.5 Hz, 1H), 4.70-4.66 (m, 1H), 4.43-4.39 (m, 1H), 4.32 (s, 2H), 3.90 (dd, J=15.5, 6.2 Hz, 1H), 3.84 (dd, J=15.5, 3.5 Hz, 1H).

EXAMPLE 103 (19)

4-(3-Chlorobenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3197] 2254

[3198] Free Compound:

[3199] TLC: Rf 0.51 (ethyl acetate);

[3200] NMR (CDCl3): δ 7.76 (dd, J=7.0, 1.2 Hz, 1H), 7.67-7.40 (m, 7H), 7.30-7.14 (m, 4H), 5.80 (dd, J=9.2,1.4 Hz, 1H), 4.48 (d, J=14.0 Hz, 1H), 3.99 (d, J=14.0 Hz, 1H), 3.87 (dd, J=15.4, 1.4 Hz, 1H), 3.86 (d, J=13.6 Hz, 1H), 3.77 (d, J=13.6 Hz, 1H), 3.69 (dd, J=15.4, 9.2 Hz, 1H).

[3201] Hydrochloride:

[3202] TLC: Rf 0.51 (ethyl acetate);

[3203] NMR (DMSO-d6): δ 9.92 (br, 1H), 9.62 (br, 1H), 8.18 (dd, J=6.6, 1.8 Hz, 1H), 7.88-7.74 (m, 6H), 7.67-7.59 (m, 3H), 7.52-7.45 (m, 2H), 6.39 (dd, J=5.7, 4.2 Hz, 1H), 4.74-4.69 (m, 1H), 4.44-4.40 (m, 1H), 4.35 (s, 2H), 3.90 (dd, J=15.6, 5.7 Hz, 1H), 3.84 (dd, J=15.6, 4.2 Hz, 1H).

EXAMPLE 103 (20)

4-(3-Methoxybenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3204] 2255

[3205] Free Compound:

[3206] TLC: Rf 0.41 (ethyl acetate);

[3207] NMR (CDCl3): δ 7.75 (dd, J=7.2, 1.2 Hz, 1H), 7.65-7.50 (m, 5H), 7.46-7.40 (m, 2H), 7.26-7.21 (m, 1H), 6.86-6.79 (m, 3H), 5.81 (dd, J=9.3, 1.2 Hz, 1H), 4.48 (d, J=14.1 Hz, 1H), 3.98 (d, J=14.1 Hz, 1H), 3.84 (d, J=13.5 Hz, 1H), 3.84 (dd, J=15.0, 1.2 Hz, 1H), 3.80 (s, 3H), 3.74 (d, J=13.5 Hz, 1H), 3.66 (dd, J=15.0, 9.3 Hz, 1H).

[3208] Hydrochloride:

[3209] TLC: Rf 0.41 (ethyl acetate);

[3210] NMR (DMSO-d6): δ 9.83 (br, 1H), 9.55 (br, 1H), 8.16 (dd, J=6.6, 1.8 Hz, 1H), 7.89-7.78 (m, 3H), 7.73-7.61 (m, 4H), 7.36 (t, J=7.9 Hz, 1H), 7.30 (d, J=2.5 Hz, 1H), 7.15 (d, J=7.9Hz, 1H), 7.00 (dd, J=7.9,2.5Hz, 1H), 6.27 (dd, J=6.0,3.9Hz, 1H), 4.70-4.65 (m, 1H), 4.42-4.37 (m,1H), 4.29 (br, 2H), 3.89 (dd, J=15.5, 6.0 Hz, 1H), 3.84 (dd, J=15.5, 3.9 Hz, 1H), 3.78 (s, 3H).

EXAMPLE 103 (21)

4-(3,4-Dichlorobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3211] 2256

[3212] Free Compound:

[3213] TLC: Rf 0.42(ethyl acetate);

[3214] NMR (CDCl3): δ 7.77 (dd, J=7.2, 1.2 Hz, 1H), 7.67-7.52 (m, 5H), 7.47-7.39 (m, 4H), 7.15 (dd, J=8.3, 2.0 Hz, 1H), 5.76 (dd, J=9.5, 1.2 Hz, 1H), 4.45 (d, J=13.8 Hz, 1H), 4.00 (d, J=13.8 Hz, 1H), 3.86 (dd, J=15.0, 1.2 Hz, 1H), 3.84 (d, J=13.8 Hz, 1H), 3.78 (d, J=13.8 Hz, 1H), 3.70 (dd, J=15.0, 9.5 Hz, 1H).

[3215] Hydrochloride:

[3216] TLC: Rf 0.42 (ethyl acetate);

[3217] NMR (DMSO-d6): δ 9.94 (br, 1H), 9.62 (br, 1H), 8.17 (dd, J=6.6, 2.1 Hz, 1H), 7.96 (d, J=1.8 Hz,1H), 7.89-7.73 (m, 6H), 7.67-7.60 (m, 3H), 6.40 (dd, J=5.5, 4.2 Hz, 1H), 4.75-4.68 (m, 1H), 4.45-4.40 (m, 1H), 4.35 (s, 2H), 3.95 (dd, J=15.5, 5.5 Hz, 1H), 3.85 (dd, J=15.5, 4.2 Hz, 1H).

EXAMPLE 103 (22)

4-(1,3-Dioxaindan-5-ylmethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3218] 2257

[3219] Free Compound:

[3220] TLC: Rf 0.43(ethyl acetate);

[3221] NMR (CDCl3): δ 7.73 (dd, J=7.5, 1.2 Hz, 1H), 7.65-7.49 (m, 5H), 7.46-7.41 (m, 2H), 6.77 (d, J=1.5 Hz,1H), 6.74 (d, J=8.0 Hz, 1H), 6.69 (dd, J=8.0, 1.5 Hz, 1H), 5.95-5.94 (m, 2H), 5.88 (dd, J=9.5,1.0 Hz, 1H), 4.50 (d, J=14.0 Hz,1H), 3.96 (d, J=14.0 Hz, 1H), 3.86 (dd, J=15.0, 1.0 Hz, 1H), 3.77 (d, J=13.0 Hz, 1H), 3.68 (d, J=13.0 Hz, 1H), 3.68 (dd, J=15.0, 9.5 Hz, 1H).

[3222] Hydrochloride:

[3223] TLC: Rf 0.43 (ethyl acetate);

[3224] NMR (DMSO-d6): δ 9.78 (br, 1H), 9.47 (br, 1H), 8.15 (dd, J=6.6, 1.8 Hz, 1H), 7.88-7.72 (m, 5H), 7.66-7.61 (m, 2H), 7.25 (d, J=1.5 Hz, 1H), 7.08 (dd, J=7.8, 1.5 Hz, 1H), 6.99 (d, J=7.8 Hz, 1H), 6.30 (t-like, J=4.5 Hz, 1H), 6.05 (s, 2H), 4.67-4.61 (m, 1H), 4.38-4.33 (m, 1H), 4.23 (s, 2H), 3.93-3.83 (m, 2H).

EXAMPLE 103 (23)

4-(2,3-Dimethoxybenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3225] 2258

[3226] Free Compound:

[3227] TLC: Rf 0.36(ethyl acetate);

[3228] NMR (CDCl3): δ 7.71 (dd, J=7.0, 1.3 Hz, 1H), 7.63-7.48 (m, 5H), 7.45-7.39 (m, 2H), 7.00 (t, J=7.8 Hz, 1H), 6.84 (dd, J=7.8, 1.5 Hz, 1H), 6.78 (dd, J=7.8, 1.5 Hz, 1H), 6.06 (dd, J=9.3, 1.3 Hz, 1H), 4.52 (d, J=14.1 Hz, 1H), 3.92 (d, J=14.1 Hz, 1H), 3.86 (s, 3H), 3.85 (dd, J=15.0, 1.3 Hz, 1H), 3.80 (d, J=13.3 Hz, 1H), 3.76 (s, 3H), 3.73 (dd, J=15.0, 9.3 Hz, 1H), 3.69 (d, J=13.3 Hz, 1H).

[3229] Hydrochloride:

[3230] TLC: Rf 0.36 (ethyl acetate);

[3231] NMR (DMSO-d6): δ 9.70-9.60 (br, 2H), 8.17 (dd, J=6.6, 2.1 Hz, 1H), 7.89-7.73 (m, 5H), 7.67-7.62 (m, 2H), 7.25-7.21 (m, 1H), 7.15-7.13 (m, 2H), 6.12 (dd, J=6.8, 2.5 Hz, 1H), 4.71-4.67 (m, 1H), 4.45-4.41 (m, 1H), 4.32-4.20 (m, 2H), 3.93-3.83 (m, 2H), 3.83 (s, 3H), 3.80 (s, 3H).

EXAMPLE 103 (24)

4-(3,4,5-Trimethoxybenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3232] 2259

[3233] Free Compound:

[3234] TLC: Rf 0.20(ethyl acetate);

[3235] NMR (CDCl3): δ 7.79 (dd, J=7.2, 1.2 Hz, 1H), 7.66-7.52 (m, 5H), 7.47-7.42 (m, 2H), 6.54 (s, 2H), 5.72 (dd, J=9.3, 1.2 Hz, 1H), 4.45 (d, J=14.0 Hz, 1H), 4.03 (d, J=14.0 Hz, 1H), 3.86 (s, 6H), 3.84 (s, 3H), 3.84 (dd, J=15.0, 1.2 Hz, 1H), 3.82 (d, J=13.5 Hz, 1H), 3.74 (d, J=13.5 Hz, 1H), 3.66 (dd, J=15.0, 9.3 Hz, 1H).

[3236] Hydrochloride:

[3237] TLC: Rf 0.20 (ethyl acetate);

[3238] NMR (DMSO-d6): δ 9.98 (br, 1H), 9.63 (br, 1H), 8.18 (dd, J=6.6, 1.5 Hz, 1H), 7.89-7.78 (m, 3H), 7.72-7.60 (m, 4H), 7.06 (s, 2H), 6.30 (dd, J=6.0, 3.5 Hz, 1H), 4.69-4.66 (m, 1H), 4.39-4.37 (m, 1H), 4.24 (s, 2H), 3.92-3.84 (m, 2H), 3.80 (s, 6H), 3.67 (s, 3H).

EXAMPLE 103 (25)

4-(4-(t-Butyloxycarbonyl)piperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3239] 2260

[3240] Free Compound:

[3241] TLC: Rf 0.49 (hexane:ethyl acetate=1:2);

[3242] NMR (CDCl3): δ 7.66-7.52 (m, 6H), 7.48-7.43 (m, 2H), 6.18 (dd, J=9.0, 1.0 Hz, 1H), 4.69 (d, J=14.3 Hz, 1H), 3.89 (dd, J=15.0, 1.0 Hz, 1H), 3.72 (dd, J=15.0, 9.0 Hz, 1H), 3.49-3.35 (m, 4H), 3.45 (d, J=14.3 Hz, 1H), 2.52-2.45 (m, 2H), 2.36-2.29 (m, 2H), 1.46 (s, 9H).

[3243] Hydrochloride:

[3244] TLC: Rf 0.49 (hexane:ethyl acetate=1:2);

[3245] NMR (CD3OD): δ 8.11 (d, J=7.2 Hz, 1H), 7.92-7.83 (m, 2H), 7.77-7.73 (m, 3H), 7.60-7.55 (m, 2H), 6.03 (dd, J=8.7, 1.0 Hz, 1H), 5.01 (d, J=14.3 Hz, 1H), 4.71 (d, J=14.3 Hz, 1H), 4.22 (br, 2H), 3.99 (dd, J=15.3, 8.7 Hz, 1H), 3.84 (dd, J=15.3,1.0 Hz, 1H), 3.65-3.25 (br, 6H), 1.47 (s, 9H).

EXAMPLE 103 (26)

4-(2-Diisopropylaminoethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[3246] 2261

[3247] TLC: Rf 0.43(methanol:ethyl acetate:triethylamine=2:8:0.5);

[3248] NMR (CD3OD+D2O): δ 8.18 (d, J=7.5 Hz, 1H), 7.97-7.76 (m, 5H), 7.70-7.60 (m, 2H), 6.20-6.12 (m, 1H), 4.85 (d, J=13.8 Hz, 1H); 4.67 (d, J=13.8 Hz, 1H), 4.01-3.50 (m, 8H), 1.44(d, J=6.3 Hz, 12H).

EXAMPLE 103 (27)

4-(2-(Morpholin-4-yl)ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene 2hydrochloride

[3249] 2262

[3250] TLC: Rf 0.37(methanol:ethyl acetate:triethylamine=2:8:0.5);

[3251] NMR (CD3OD+D2O): δ 8.18 (d, J=7.5 Hz, 1H), 7.97-7.76 (m, 5H), 7.69-7.60 (m, 2H), 6.17-6.10 (m, 1H), 4.86 (d, J=13.8 Hz, 1H), 4.69 (d, J=13.8 Hz, 1H), 4.05-3.90 (m, 5H), 3.89-3.71 (m, 3H), 3.67-3.53 (m, 2H), 3.5 1-3.33 (m, 4H).

EXAMPLE 103 (28)

4-(N-2-(Piperidin-1-yl)ethyl-N-propyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3252] 2263

[3253] Free Compound:

[3254] TLC: Rf 0.51 (ethyl acetate:triethylamine 9:1);

[3255] NMR (CDCl3): δ 7.68 (d, J=7.2 Hz, 1H), 7.64-7.46 (m, 5H), 7.44-7.39 (m, 2H), 6.29 (dd, J=9.3, 1.2 Hz, 1H), 4.69 (d, J=14.4 Hz, 1H), 3.90 (dd, J=15.0, 1.2 Hz, 1H), 3.72 (dd, J=15.0, 9.3 Hz, 1H), 3.58 (d, J=14.4 Hz, 1H), 2.70-2.30 (m, 10H), 1.57-1.38 (m, 8H), 0.79 (t, J=7.2 Hz, 3H).

Hydrochloride:

[3256] TLC: Rf 0.51 (ethyl acetate:triethylamine=9:1);

[3257] NMR (CD3OD+pyridine-d5): δ 7.93 (d, J=7.2 Hz, 1H), 7.74-7.68 (m, 4H), 7.61-7.52 (m, 3H), 6.01 (dd, J=8.7,1.2 Hz, 1H), 4.38 (d, J=14.7 Hz, 1H), 3.99 (dd, J=15.3, 8.7 Hz, 1H), 3.89 (dd, J=15.3, 1.2 Hz, 1H), 3.85 (d, J=14.7 Hz, 1H), 3.27-3.22 (m, 2H), 3.14 (br, 4H), 2.97-2.81 (m, 2H), 2.61-2.45 (m, 2H), 1.85-1.77 (m, 4H), 1.65-1.53 (m, 4H), 0.89 (t, J=7.3 Hz, 3H).

EXAMPLE 103 (29)

4-(N-2-(Piperidin-1-yl)ethyl-N-isopropyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3258] 2264

[3259] Free Compound:

[3260] TLC: Rf 0.48 (ethyl acetate:triethylamine=9:1);

[3261] NMR (CDCl3): δ 7.77 (d, J=7.2 Hz, 1H), 7.65-7.47 (m, 5H), 7.45-7.40 (m, 2H), 6.09 (d, J=9.0, 1.0 Hz, 1H), 4.54 (d, J=15.0 Hz, 1H), 3.88 (dd, J=15.0, 1.0 Hz, 1H), 3.74 (d, J=15.0 Hz, 1H), 3.73 (dd, J=15.0, 9.0 Hz, 1H), 2.84 (sept, J=6.6 Hz, 1H), 2.57-2.51 (m, 2H), 2.38-2.17 (m, 6H), 1.55-1.48 (m, 4H), 1.42-1.35 (m, 2H), 1.06 (d, J=6.6 Hz, 3H), 1.03 (d, J=6.6 Hz, 3H).

[3262] Hydrochloride:

[3263] TLC: Rf 0.48 (ethyl acetate:triethylamine=9:1);

[3264] NMR (CD3OD+pyridine-d5): δ 7.99 (d, J=7.5 Hz, 1H), 7.75-7.70 (m, 4H), 7.61-7.54 (m, 3H), 5.93 (dd, J=8.7, 1.5 Hz, 1H), 4.27 (d, J=15.6 Hz, 1H), 3.99 (dd, J=15.3, 8.7 Hz, 1H), 3.96 (d, J=15.6 Hz, 1H), 3.88 (dd, J=15.3, 1.5 Hz, 1H), 3.20-2.80 (m, 9H), 1.82-1.75 (m, 4H), 1.63-1.58 (m, 2H), 1.17-1.14 (m, 6H).

EXAMPLE 103 (30)

4-(3,4-Dimethoxybenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3265] 2265

[3266] Free Compound:

[3267] TLC: Rf 0.19 (ethyl acetate);

[3268] NMR (CDCl3): δ 7.76 (dd, J=7.2, 1.0 Hz, 1H), 7.65-7.51 (m, 5H), 7.46-7.41 (m, 2H), 6.84-6.82 (m, 3H), 5.79 (d, J=9.3 Hz, 1H), 4.47 (d, J=14.0 Hz, 1H), 4.00 (d, J=14.0 Hz, 1H), 3.87 (s, 6H), 3.85 (d, J=15.0 Hz, 1H), 3.82 (d, J=13.2 Hz, 1H), 3.73 (d, J=13.2 Hz, 1H), 3.66 (dd, J=15.0, 9.3 Hz, 1H).

[3269] Hydrochloride:

[3270] TLC: Rf 0.19 (ethyl acetate);

[3271] NMR (DMSO-d6): δ 10.00-9.70 (br, 2H), 8.38-8.28 (m, 1H), 8.06-7.94 (m, 3H), 7.88-7.76 (m, 4H), 7.56 (d, J=1.4 Hz, 1H), 7.27 (dd, J=8.4, 1.4 Hz, 1H), 7.18 (d, J=8.4 Hz, 1H), 6.43-6.38 (m, 1H), 4.80 (d, J=12.8 Hz, 1H), 4.53 (d, J=12.8 Hz, 1H), 4.40 (s, 2H), 4.13-4.00 (m, 2H), 3.94 (s, 6H).

EXAMPLE 103 (31)

4-(3-(2-Methylpiperidin-1-yl)propyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[3272] 2266

[3273] TLC: Rf 0.33 (ethyl acetate:methanol:triethylamine=8:2:0.5);

[3274] NMR (CD3OD): δ 8.18 (d, J=7.2 Hz, 1H), 7.92-7.73 (m, 5H), 7.67-7.57 (m, 2H), 6.22-6.23 (m, 1H), 4.80 (d, J=13.5 Hz, 1H), 4.62 (d, J=13.5 Hz, 1H), 3.98-3.91 (m, 1H), 3.83-3.74 (m, 1H), 3.64-2.98 (m, 7H), 2.37-2.17 (m, 2H), 2.07-1.52 (m, 6H), 1.41 (d, J=6.3 Hz, 3H).

EXAMPLE 103 (32)

4-(4-(Piperidin-1-yl)piperidin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[3275] 2267

[3276] TLC: Rf 0.41 (ethyl acetate methanol:triethylamine=8:2:0.5);

[3277] NMR (D2O): δ 8.17-8.08 (m, 1H), 8.03-7.94 (m, 2H), 7.91-7.82 (m, 1H), 7.79-7.73 (m, 2H), 7.72-7.62 (m, 2H), 4.71 (d, J=14.4 Hz, 1H), 4.65 (d, J=14.4 Hz, 1H), 4.21-4.05 (m, 2H), 3.87-3.75 (m, 1H), 3.69-3.48 (m, 4H), 3.38-2.98 (m, 4H), 2.52-2.32 (m, 2H), 2.19-1.93 (m, 4H), 1.91-1.65 (m, 3H), 1.59-1.40 (m, 1H).

EXAMPLE 103 (33)

4-(3-(Piperidin-1-yl)propyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[3278] 2268

[3279] TLC: Rf 0.25 (methanol:ethyl acetate:triethylamine=2:8:0.5);

[3280] NMR (CD3OD+D2O) δ 8.16 (d, J=7.2 Hz, 1H), 7.95-7.74 (m, 5H), 7.69-7.59 (m, 2H), 6.17-6.08 (m, 1H), 4.78 (d, J=14.1 Hz, 1H), 4.62 (d, J=14.1 Hz, 1H), 4.02-3.88 (m, 1H), 3.85-3.73 (m, 1H), 3.73-2.76 (m, 8H), 2.3 8-2.21 (m, 2H), 2.14-1.44 (m, 6H).

EXAMPLE 103 (34)

4-(3-Bromobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.hydrochloride

[3281] 2269

[3282] TLC: Rf 0.50 (ethyl acetate:triethylamine 6:0.5);

[3283] NMR (DMSO-d6): δ 9.83 (brs, 1H), 9.56 (brs, 1H), 8.16 (d, J=6.6 Hz, 1H), 7.90-7.70 (m, 6H), 7.68-7.58 (m, 4H), 7.41 (t, J=7.5 Hz, 1H), 6.41-6.28 (m, 1H), 4.80-4.60 (m, 1H), 4.52-4.22 (m, 3H), 3.96-3.80 (m, 2H).

EXAMPLE 103 (35)

4-(4-Nitrobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene hydrochloride

[3284] 2270

[3285] TLC: Rf 0.34 (ethyl acetate:triethylamine=6:0.5);

[3286] NMR (DMSO-d6): δ 10.05 (brs, 1H), 9.79 (brs, 1H), 8.29 (d, J=8.1 Hz, 2H), 8.18 (d, J=6.6 Hz, 1H), 7.94-7.70 (m, 7H), 7.67-7.57 (m, 2H), 6.48-6.33 (m, 1H), 4.83-4.64 (m, 1H), 4.59-4.35 (m, 3H), 3.95-3.81 (m, 2H).

EXAMPLE 103 (36)

4-(4-Aminosulfonylbenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3287] 2271

[3288] Free Compound:

[3289] TLC: Rf 0.40 (ethyl acetate:methanol=9:1);

[3290] NMR (DMSO-d6): δ 7.93 (dd, J=7.0, 1.5 Hz, 1H), 7.79-7.66 (m, 7H), 7.63-7.58 (m, 2H), 7.53 (d, J=8.0 Hz, 2H), 7.31 (s, 2H), 5.93 (dd, J=8.3, 1.5 Hz, 1H), 4.07 (d, J=14.1 Hz,1H), 3.95 (dd, J=15.0, 8.3 Hz, 1H), 3.87 (dd, J=15.0, 1.5 Hz, 1H), 3.82 (d, J=14.1 Hz, 1H), 3.75 (s, 2H), 2.86 (br, 1H).

[3291] Hydrochloride:

[3292] TLC: Rf 0.40 (ethyl acetate:methanol=9:1);

[3293] NMR (DMSO-d6): δ 9.80 (br, 1H), 9.52 (br, 1H), 8.15 (d, J=7.0 Hz, 1H), 7.89-7.74 (m, 9H), 7.67-7.62 (m, 2H), 7.44 (s, 2H), 6.37-6.32 (m, 1H), 4.78-4.70 (m, 1H), 4.47-4.41 (m, 1H), 4.41 (s, 2H), 3.96-3.84 (m, 2H).

EXAMPLE 103 (37)

4-(Piperazin-1-yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[3294] 2272

[3295] TLC: Rf 0.10 (ethyl acetate:methanol triethylamine=8:2:1);

[3296] NMR (CD3OD+D2O): δ 7.96 (d, J=7.8 Hz, 1H), 7.80-7.67 (m, SH), 7.61-7.56 (m, 2H), 6.16 (dd, J=9.0, 1.3 Hz, 1H), 4.60 (d, J=14.5 Hz, 1H), 4.01 (dd, J=15.4, 9.0 Hz, 1H), 3.95 (d, J=14.5 Hz, 1H), 3.89 (dd, J=15.4, 1.3 Hz, 1H), 3.37-3.33 (m, 4H), 2.98-2.90 (m, 4H).

EXAMPLE 103 (38)

4-(2,4,6-Trimethoxybenzyl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3297] 2273

[3298] Free Compound:

[3299] TLC: Rf 0.38 (ethyl acetate:methanol=9:1);

[3300] NMR (CDCl3): δ 7.69 (dd, J=7.0,1.5Hz, 1H), 7.64-7.49 (m, 5H), 7.45-7.40 (m, 2H), 6.19 (dd, J=9.0,1.0 Hz, 1H), 6.12 (s, 2H), 4.50 (d, J=14.3 Hz, 1H), 3.88 (d, J=14.3 Hz, 1H), 3.85 (dd, J=15.0,1.0 Hz, 1H), 3.81 (s, 3H), 3.75 (s, 6H), 3.73 (d, J=12.6 Hz, 1H), 3.65 (d, J=12.6 Hz, 1H), 3.64 (dd, J=15.0, 9.0 Hz, 1H).

[3301] Hydrochloride:

[3302] TLC: Rf 0.38 (ethyl acetate:methanol=9:1);

[3303] NMR (DMSO-d6): δ 9.11 (br, 1H), 8.94 (br, 1H), 8.16-8.13 (m, 1H), 7.88-7.87 (m, 2H), 7.84-7.79 (m, 1H), 7.71-7.61 (m, 4H), 6.31 (s, 2H), 5.92 (dd, J=8.0,1.8 Hz, 1H), 4.66-4.62 (m, 1H), 4.39-4.34 (m, 1H), 4.18-4 .13 (m, 1H), 3.97-3.91 (m, 1H), 3.92 (dd, J=15.3, 8.0 Hz, 1H), 3.83 (dd, J=15.3, 1.8 Hz, 1H), 3.82 (s, 3H), 3.79 (s, 6H).

EXAMPLE 103 (39)

4-(Piperidin-1-yl)carbonylmethylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3304] 2274

Free Compound:

[3305] TLC: Rf 0.42 (ethyl acetate:methanol:triethylamine=8:1:1);

[3306] NMR (CDCl3): δ 7.75.(dd, J=6.9, 2.1 Hz, 1H), 7.66-7.60 (m, 3H), 7.58-7.53 (m, 2H), 7.48-7.43 (m, 2H), 6.13 (dd, J=9.0, 1.2 Hz, 1H), 4.61 (d, J=13.8 Hz, 1H), 3.97 (d, J=13.8Hz, 1H), 3.87 (dd, J=15.0,1.2Hz, 1H), 3.75 (dd, J=15.0,9.0Hz, 1H), 3.58 (t, J=5.2 Hz, 2H), 3.50 (d, J=16.0 Hz, 1H), 3.41 (d, J=16.0 Hz, 1H), 3.30 (t, J=5.2 Hz, 2H), 1.69-1.55 (m, 6H).

[3307] Hydrochloride:

[3308] TLC: Rf 0.42 (ethyl acetate:methanol: triethylamine=8:1:1);

[3309] NMR (DMSO-d6): δ 9.63 (br, 1H), 9.18 (br, 1H), 8.11 (d, J=7.2 Hz, 1H), 7.93-7.80 (m, 5H), 7.70-7.64 (m, 2H), 6.28 (dd, J=6.0, 4.0 Hz, 1H), 4.83 (d, J=13.2 Hz, 1H), 4.32 (d, J=13.2 Hz, 1H), 4.28-4.16 (m, 2H), 3.85 (dd, J=15.3, 6.0 Hz, 1H), 3.80 (dd, J=15.3, 4.0 Hz, 1H), 3.54-3.50 (m, 2H), 3.37-3.32 (m, 2H), 1.64-1.49 (m, 6H).

EXAMPLE 103 (40)

4-(Pyrrolidin-1-yl)ethylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene 2hydrochloride

[3310] 2275

[3311] TLC: Rf 0.22(methanol:ethyl acetate:triethylamine=2:8:0.5);

[3312] NMR (CD3OD+D2O): 8.16 (d, J=7.5 Hz, 1H), 7.94-7.75 (m, 5H), 7.68-7.58 (m, 2H), 6.15-6.08 (m, 1H), 4.81 (d, J=13.8 Hz, 1H), 4.63 (d, J=13.8 Hz, 1H), 4.01-3.88 (m, 1H), 3.86-3.76 (m, 1H), 3.75-3.62 (m, 4H), 3.6 2-3.38 (m, 4H), 2.20-2.06 (m, 4H).

EXAMPLE 103 (41)

4-(4-(1,3-Dioxaindan-5-ylmethyl)piperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene-2hydrochloride

[3313] 2276

[3314] TLC: Rf 0.51 (ethyl acetate:triethylamine=6:0.5);

[3315] NMR (CD3OD+D2O): δ 7.90 (d, J=7.5 Hz, 1H), 7.79-7.52 (m, 7H), 7.04-6.96 (m, 2H), 6.95-6.87 (m, 1H), 6.15-6.07 (m, 1H), 6.01 (s, 2H), 4.45 (d, J=14.4 Hz, 1H), 4.25 (s, 2H), 4.01 (dd, J=15.6, 8.7 Hz,1H), 3.90 (dd, J=15.6, 1.2 Hz, 1H), 3.77 (d, J=14.4 Hz, 1H), 3.50-3.10 (br, 4H), 2.98-2.63 (br, 4H).

EXAMPLE 104

4-Cyano-6,7-dihydrobenzo[b]thiophene

[3316] 2277

[3317] To a suspension of zinc iodide (6.2 g) in acetonitrile (200 ml) were added 4-keto-4,5,6,7-tetrahydrothianaphthene (20 g) and trimethylsilylcyanide (18 ml) successively. The mixture was stirred at room temperature for 5 hours. The reaction mixture was concentrated. The residue was dissolved in pyridine (65 ml), followed by adding phosphryl chloride (15 ml) dropwise at room temperature. The mixture was refluxed for 30 minutes. The reaction mixture was cooled with ice and thereto was added dropwise isopropanol. The reaction mixture was poured onto ice water and extracted with ethyl acetate. The extract was washed by hydrochloric acid, water and a saturated aqueous solution of sodium chloride successively, dried over anhydrous magnesium sulfate and concentrated to give the title compound (17 g) having the following physical data.

[3318] TLC: Rf 0.45 (hexane:ethyl acetate=3:1);

[3319] NMR (CDCl3): δ 7.12 (d, J=5.4 Hz, 1H), 7.07 (d, J=5.4 Hz, 1H), 6.62 (t, J=4.8 Hz, 1H), 2.93 (t, J=9.0 Hz, 2H), 2.60 (t, J=9.0, 4.8 Hz, 2H).

EXAMPLE 105

4-Cyanobenzo[b]thiophene

[3320] 2278

[3321] To a solution of the compound prepared in Example 104 (17 g) in benzene (200 ml), was added 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (30 g). The mixture was refluxed for 1.5 hours. The mixture was filtered. The filtrate was concentrated. The residue was extracted with a mixed solvent (hexane:ethyl acetate=1:1). The extract was washed by an aqueous solution of sodium hydroxide, water and a saturated aqueous solution of sodium chloride successively, dried over anhydrous magnesium sulfate and concentrated. The residue was purified with column chromatopgaphy on silica gel (hexane:ethyl acetate=100:1) to give the title compound (14.5 g) having the following physical data.

[3322] TLC: Rf 0.40 (hexane:ethyl acetate=4:1);

[3323] NMR (CDCl3): δ 7.45 (t, J=7.5Hz, 1H), 7.60 (d, J=5.0 Hz, 1H), 7.70 (d, J=5.0 Hz, 1H), 7.75 (d, J=7.5Hz, 1H), 8.10 (d, J=7.5Hz, 1H).

EXAMPLE 106

4-Carboxybenzo[b]thiophene

[3324] 2279

[3325] 1) To a suspension of the compound prepared in Example 105 (14.5 g) in ethyleneglycol (50 ml) was added 85% potassium hydroxide (19 g). The mixture was stirred at 1 80“C for 2 hours. The reaction mixture was poured into hydrochloric acid, and the acidic mixture was extracted with ethyl acetate. The extract was washed by water and a saturated aqueous solution of sodium chloride sucessively, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from a mixed solvent of ethyl acetate and hexane to give the title compound (12.2 g) having the following physical data.

[3326] The above title compound may be prepared by the following method. 2) A mixture of the compound prepared in Example 104 (1.61 g), nitrobenzene (2.46 g), ethyleneglycol (10 ml) and 10% palladium carbon (161 mg) was stirred at 200° C. for 3 hours and at 1 80“C for 17 hours. To the reaction mixture, sodium hydroxide was added at 150° C. The mixture was stirred at 180° C. for 1 hour. The reaction mixture was cooled to room temperature. Thereto were added water (10 ml) and activated charcoal. The mixture was filtrated. The filtrate was washed by ethyl acetate (20 ml). To aqueous layer was added concentrated hydrochloric acid (2.5 ml). The mixture was extracted with ethyl acetate, washed by water and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue was recrystallized from acetonitrile (25 ml) to give the title compound (1.46 g).

[3327] TLC: Rf 0.10 (hexane:ethyl acetate=4:1);

[3328] NMR (CDCl3): δ 8.32 (dd, J=5.6, 1.0 Hz, 1H), 8.27 (dd, J=7.6, —1.0 Hz, 1H), 8.18-8.11 (m, 1H), 7.68 (d, J=5.6 Hz, 1H), 7.51-7.41 (m, 1H).

EXAMPLE 107

4-Carboxy-1,1-dioxidebenzo[b]thiophene

[3329] 2280

[3330] To a suspension of the compound prepared in Example 106 (35 g) in methanol (720 ml), was added a suspension of OXONE@ (362 g) in pure water (720 ml) at room temperature. The mixture was stirred at 40° C. for 2 hours. The reaction mixture was filtered. The filtrate was concentrated. The residue was extracted with ethyl acetate. The organic layer was washed by a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was crystallized from hexane, followed by drying to give the compound of the present invention (30 g) having the following physical data.

[3331] TLC: Rf 0.18 (ethyl acetate);

[3332] NMR (CDCl3): δ 8.28 (d, J=7.5 Hz, 1H), 8.26 (d, J=7.5 Hz, 1H), 7.94 (d, J=7.5 Hz, 1H), 7.66 (t, J=7.5 Hz, 1H), 6.87 (d, J=7.5 Hz, 1H).

[3333] Examples relates to different method for preparation of the compounds of the present invention

[3334] The compounds prepared in Examples 35 (49)˜(61), Example 70, Example 94, Examples 103˜103 (29) may be prepared by the same procedure as described hereinafter in Example 108 or Example 109.

[3335] 1) For example, the compound described in Example 35 (50) may be prepared by the following procedure.

EXAMPLE 108

4-(Pyridin-3-ylmethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene.2hydrochloride

[3336] 2281

[3337] Under an atmosphere of argon, to a solution of the compound prepared in Example 82 in dimethylformamide (5 ml) was added a solution of 3-(aminomethyl)pyridine (73 μl) in dimethylformamide (1 ml), followed by adding 5% palladium-carbon (50 mg). Then, an atmosphere was replaced by hydrogen. The mixture was stirred at room temperature for 1.5 hours. The reaction mixture was filtered. The filtrate was concentrated. The obtained residue was purified with column chromatography on silica gel (chloroform methanol 25:1) followed by converting into hydrochloride by addition of 4N hydrochloride/ethyl acetate and recrystallization using ethanol to give the compound of the present invention (231 mg).

[3338] A free compound of the compound described in Example 35 (52) may be prepared by the following procedure.

EXAMPLE 109

4-(N,N-Bis(2-hydroxyethyl)amino)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene

[3339] 2282

[3340] To a suspension of the compound prepared in Example 82 (168 mg) in methylene chloride (2 ml) were added diethanolamine (53 μl), sodium borocyanohydride (63 mg), concentrated hydrochloric acid (2 drops) and methanol (0.5 ml). The mixture was stirred at room temperature for 6 hours. The reaction mixture was poured into water, and extracted with a mixed solvent (methylene chloride and methanol). The organic layer was washed by a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue was purified with column chromatography on silica gel to give the compound of the present invention (50 mg).

[3341] 2) The compound prepared in Example 81 (1) may be prepared by the same procedure as described in Example 27 using the compound prepared in Example 107 instead of 5-methyl-1,1-dioxidebenzo[b]thiophene, and if necesary, by converting into a corresponding free compound by a known method.

[3342] 3) The compounds prepared in Examples 35˜35 (32), Examples 45 (1)˜45 (2), Example 70, Example 71 and Example 87 may be prepared by the same procedure as described in Example 100.

[3343] For example, the compound prepared in Example 35 (11) may be prepared by the same procedure as described in Example 100 using the compound (free compound or sodium salt) prepared in Example 81 (1), and 2-(piperidin-1-yl)ethylamine instead of furan-2-ylmethylamine.

FORMULATION EXAMPLE

Formulation Example 1

[3344] The following components were admixed in a conventional method and punched out to obtain 100 tablets each containing 50 mg of active ingredient.

4-(Pyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1- 5.0 g
dioxidebenzo[b]thiophene
Carboxymethylcellulose calcium (disintegrating agent) 0.2 g
Magnesium stearate (lubricating agent) 0.1 g
Microcrystalline cellulose       4.7 g

Formulation Example 2

[3345] The following components were admixed in a conventional method, and the solution was sterilized in a conventional method, placed 5 ml portions into ampoules and freeze-dried in a conventional method to obtain 100 ampoules each containing 20 mg of active ingredient.

4-(Pyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1- 2.0 g
dioxidebenzo[b]thiophene
Mannitol                         20 g
DIstilled water                  500 ml

Claims

1. An inhibitor of producing interleukin-6 and/or interieukin-12 comprising, as an active ingredient, a fused thiophene derivative of the formula (I)

2. An agent for the prevention and/or treatment of various inflammatory diseases, sepsis, multiple myeloma, plasma cell leukemia, osteoporosis, cachexia, psoriasis, nephritis, renal cell carcinoma, Kaposi's sarcoma, rheumatoid arthritis, gammopathy, Castleman's disease, atrial myxoma, diabetes mellitus, autoimmune diseases, hepatitis, multiple sclerosis, colitis, graft versus host immune diseases, infectious diseases containing a fused thiophene derivative of the formula (I) depicted in claim 1, an N-oxide derivative thereof or a non-toxic salt thereof as an active ingredient.

3. An inhibitor of producing interleukin-6 and/or interleukin-12 according to claim 1, comprising a compound which is (1) 3-(thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (2) 6-nitro-3-(thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (3) 3-(thiophen-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (4) 4,5-dimethyl-1,1-dioxidebenzo[b]thiophene, (5) 4,6-dimethyl-1,1-dioxidebenzo[b]thiophene, (6) 4,7-dimethyl-1,1-dioxidebenzo[b]thiophene, (7) 5,6-dimethyl-1,1-dioxidebenzo[b]thiophene, (8) 5,7-dimethyl-1,1-dioxidebenzo[b]thiophene, (9) 6,7-dimethyl-1,1-dioxidebenzo[b]thiophene, (10) 4-carboxymethyl-1,1-dioxidebenzo[b]thiophene, (11) 6-(2,2-bis(ethoxycarbonyl)ethenyl)amino-1,1-dioxidebenzo[b]thiophene, (12) 4-methylaminocarbonyloxy-1,1-dioxidebenzo[b]thiophene, (13) 5-(2-(N-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-N-methylamino) ethyl)-1-dioxidebenzo[b]thiophene, (14) 5-(2-hydroxyethyl)-1,1-dioxidebenzo[b]thiopherie, (15) 5-bromo-7-methyl-1,1-dioxidebenzo[b]thiophene, (16) 7-bromo-5-methyl -methyl-1,1-dioxidebenzo[b]thiophene, (17) 5-bromo-6-methyl-1,1-dioxidebenzo[b]thiophene, (18) 5-bromo-4-methyl-1,1-dioxidebenzo[b]thiophene, (19) 6-bromo-5-methyl-1,1-dioxidebenzo[b]thiophene, (20) 4-bromo-5-methyl- -methyl-1,1-dioxidebenzo[b]thiophene, (21) 6-amino-1,1-dioxidebenzo[b]thiophene, (22) 6-acetylamino-1,1-dioxidebenzo[b]thiophene, (23) 6-(4-diethylaminophenyl)-1,1-dioxidebenzo[b]thiophene, (24) 1,1-dioxidethieno[2,3-b]pyridine, (25) 1,1-dioxidethieno[3,2-b]pyridine, (26) 1,1-dioxidethieno[2,3-c]pyridine, (27) 5-amino-1,1-dioxidebenzo[b]thiophene, (28) 5-(3-methyl-5-oxo-4,5-dihydropyrazol-1-yl)-1,1-dioxidebenzo[b]thiophene, (29) 4-(2-(1,1-dioxidebenzo[b]thiophen-3-yl)ethyl)-1,1-dioxidebenzo[b]thiophene, (30) 7-methyl-1,1-dioxidethieno[2,3-c]pyridine, (31) 1,1-dioxidebenzo[b]thiophene, (32) 4-(4-methoxyphenyl)-1,1-dioxidethieno[3,2-c]pyridine, (33) 5-((E)-2-(ethoxycarbonyl)ethenyl)-4-methoxybenzo[b]thiophene, (34) 5-(2-(ethoxycarbonyl)ethyl-4-methoxybenzo[b]thiophene, (35) 5-methoxycarbonyl-4-ethoxybenzo[b]thiophene, (36) 5-carboxy-4-ethoxybenzo[b]thiophene, (37) 5-benzyloxycarbonyl-4-ethoxybenzo[b]thiophene, (38) 5-hydroxy-4-formylbenzo[b]thiophene, (39) 5-benzyloxy-4-formylbenzo[b]thiophene, (40) 5-benzyloxy-4-hydroxymethylbenzo[b]thiophene or (41) 4-t-butoxycarbonylaminobenzo[b]thiophene, or an N-oxide derivative thereof, or a non-toxic salt thereof as active ingredient.

4. A fused thiophene derivative of formula (IA)

5. A fused thiophene derivative of the formula (IA) depicted in claim 4, wherein is a double bond, an N-oxide derivative thereof, or a non-toxic salt thereof.

6. A fused thiophene derivative of the formula (IA) depicted in claim 4, wherein is a single bond, an N-oxide derivative thereof or a non-toxic salt thereof.

7. A fused thiophene derivative of the formula (IA) depicted in claim 4, wherein

8. A fused thiophene derivative of the formula (IA) depicted in claim 4, wherein

9. A fused thiophene derivative of the formula (IA) depicted in claim 4, wherein

10. A fused thiophene derivative of the formula (IA) depicted in claim 4, wherein

11. A fused thiophene derivative of the formula (IA) depicted in claim 4, wherein

12. A fused thiophene derivative of the formula (IA) depicted in claim 4, wherein

13. A compound according to claim 4, which is (1) 3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (2) 3-(thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (3) 3-(4-methylphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (4) 3-(4-methoxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (5) 3-(4-chlorophenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (6) 3-(4-fluorophenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (7) 3-(4-hydroxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (8) 3-(3-hydroxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (9) 3-(2-hydroxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (10) 3-(pyridin-4-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (11) 3-(pyrimidin-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (12) 3-(thiazol-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (13) 3-(3-methylfuran-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (14) 3-(3-methoxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (15) 3-(2-methoxycarbonylphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (16) 3-cyclohexylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (17) 3-(naphthalen-1-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (18) 3-(2-methoxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (19) 3-(1-methylimidazol-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (20) 3-phenylsulfinyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (21) 3-(thiophen-2-yl)sulfinyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (22) 3-(2-methoxycarbonylphenyl)sulfinyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (23) 3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (24) 3-(thiophen-2-yl) sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (25) 3-(4-methylphenyl) sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (26) 3-(4-methoxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (27) 3-(4-chlorophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (28) 3-(4-fluorophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (29) 3-(4-hydroxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (30) 3-(3-hydroxyphenyl)sulfonyl-2,3-dihydro-1,1-dloxidebenZo[b]thiophene, (31) 3-(2-hydroxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (32) 3-(pyridin-4-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (33) 3-(pyrimidin-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (34) 3-(thiazol-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (35) 3-(3-methylfuran-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (36) 3-(3-methoxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (37) 3-(2-methoxycarbonylphenyl) sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (38) 3-cyclohexylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene (39) 3-(naphthalen-1-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (40) 3-(2-methoxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (41) 3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (42) 3-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (43) 3-(4-(2-(morpholin-4-yl)ethoxy) phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (44) 3-(3-benzyloxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (45) 3-(2-benzyloxyphenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (46) 3-(4-(pyridin-2-ylmethyloxy) phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (47) 3-(4-(pyridin-3-ylmethyloxy) phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (48) 3-(4-pyridin-4-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (49) 3-(4-(3-hydroxypropyloxy) phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (50) 3-(3-(pyridin-3-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (51) 3-(3-(3-hydroxypropyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (52) 3-(2-(pyridin-3-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (53) 3-(2-(3-hydroxypropyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (54) 3-(4-(2-(t-butoxycarbonylamino)ethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (55) 3-(3-(2-(t-butoxycarbonylamino)ethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (56) 3-(4-(pyridin-2-ylmethyloxy) phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (57) 3-(4-(pyridin-3-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (58) 3-(4-(pyridin-4-ylmethyloxy) phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (59) 3-(4-(3-hydroxypropyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (60) 3-(3-(pyridin-3-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (61) 3-(3-(3-hydroxypropyloxy) phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (62) 3-(2-(pyridin-3-ylmethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (63) 3-(2-(3-hydroxypropyloxy) phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (64) 3-(4-(2-(t-butoxycarbonylamino)ethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (65) 3-(3-(2-(t-butoxycarbonylamino)ethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (66) 3-(4-(2-aminoethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (67) 3-(3-(2-aminoethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[bjthiophene, (68) 3-(4-(2-(N,N-dimethylamino)ethyloxyphenyl)sulfonyl-2,3dihydro-1,1-dioxidebenzo[b]thiophene, (69) 3-(3-(2-(N,N-dimethylamino)ethyloxy)phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (70) 5-nitro-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (71) 6-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (72) 4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (73) 5-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (74) 7-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (75) 4-chloro-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (76) 5-(t-butoxycarbonylamino) methyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (77) 4,7-dimethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (78) 4,6-dimethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (79) 4-ethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (80) 4-methoxy-5-ethoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (81) 4-bromo-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (82) 4-hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (83) 5-hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (84) 6-hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (85) 7-hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (86) 3-phenylthio-2,3-dihydro-1,1-dioxidethieno[2,3-b]pyridine, (87) 4,7-dihydroxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (88) 5-nitro-3-phenyisulfonyl-2,3-dihydro-1,1-di oxidebenzo[b]thiophene, (89) 6-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (90) 4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (91) 5-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (92) 7-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (93) 4-chloro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (94) 4-(t-butoxycarbonylamino) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (95) 4,7-dimethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (96) 4,6-dimethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (97) 4-ethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (98) 4-methoxy-5-ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (99) 4-bromo-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (100) 4-hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (101) 5-hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene (102) 6-hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (103) 7-hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (104) 3-phenylsulfonyl-2,3-dihydro-1,1-dioxidethieno[2,3-b]pyridine, (105) 5-amino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (106) 5-acetylamino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (107) 4-aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (108) 4-(N,N-dimethylamino) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (109) 4-methoxy-5-formyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (110) 4-methoxy-3-(thiophen-2-yl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (111 ) 4-methoxy-3-(thiophen-2-yl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (112) 4-(4-nitrophenylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (113) 4-(3-phenyloxypropyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (114) 4-benzyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (115) 4-(3-benzyloxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (116) 4-(pyridin-3-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (117) 4-(quinolin-2-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (118) 4-(pyridin-2-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (119) 4-(pyridin-4-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (120) 4-(3-(pyridin-3-yl)propyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (121) 4-(3-hydroxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (122) 5-pentoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (123) 5-(2-phenyloxyethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (124) 5-(3-hydroxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (125) 5-(pyridin-3-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (126) 5-(3-(pyridin-3-yl) propyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (127) 6-(3-phenyloxypropyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (128) 6-benzyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (129) 6-pentoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (130) 6-(2-(morpholin-4-yl) ethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (131) 6-(3-hydroxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (132) 6-(pyridin-3-ylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (133) 6-(3-nitrophenylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (134) 6-(3-bromopropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (135) 7-pentoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (136) 7-(2-phenyloxyethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (137) 7-(3-hydroxypropyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (138) 7-(pyridin-3-ylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (139) 4-(t-butoxycarbonylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (140) 5-(t-butoxycarbonylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (141) 6-(t-butoxycarbonylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (142) 7-(t-butoxycarbonylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (143) 4-(2-(t-butoxycarbonylamino)ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (144) 4-(3-(t-butoxycarbonylamino)propyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (145) 5-(2-(t-butoxycarbonylamino) ethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[bjthiophene, (146) 6-(3-(t-butoxycarbonylamino)propyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (147) 6-(2-(t-butoxycarbonylamino)ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (148) 7-(2-(t-butoxycarbonylamino) ethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (149) 4-(N-(t-butoxycarbonyl) piperidin-4-yl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (150) 4,7-bis[(2-(t-butoxycarbonylamino)ethyl)oxy]-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (151) 4-(3-nitrophenylmethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (152) 4,7-bis(pyridin-3-ylmethyloxy)-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (153) 4-(3-hydroxypropyl)oxy-3-phenylsulfinyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (154) 4-(4-nitrophenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (155) 4-(3-phenyloxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (156) 4-benzyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (157) 4-(3-benzyloxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (158) 4-(pyridin-3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (159) 4-(N-oxidequinolin-2-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (160) 4-(pyridin-2-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (161) 4-(N-oxidepyridin-2-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (162) 4-(pyridin-4-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (163) 4-(3-(pyridin-3-yl) propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (164) 4-(3-hydroxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (165) 5-pentoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (166) 5-(2-phenyloxyethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (167) 5-(3-hydroxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (168) 5-(pyridin-3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (169) 5-(3-(pyridin-3-yl)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (170) 6-(3-phenyloxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (171) 6-benzyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (172) 6-pentoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (173) 6-(2-(morpholin-4-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (174) 6-(3-hydroxypropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (175) 6-(pyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (176) 6-(3-nitrophenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (177) 6-(3-bromopropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (178) 7-pentoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (179) 7-(2-phenyloxyethyl)oxy-3-phenylsuffonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (180) 7-(3-hydroxypropyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (181) 7-(pyridin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (182) 7-(N-oxidepyridin-3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (183) 4-(t-butoxycarbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (184) 5-(t-butoxycarbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (185) 6-(t-butoxycarbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (186) 7-(t-butoxycarbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (187) 4-(2-(t-butoxycarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (188) 4-(3-(t-butoxycarbonylamino) propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (189) 5-(2-(t-butoxycarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (190) 6-(3-(t-butoxycarbonylamino) propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (191) 6-(2-(t-butoxycarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (192) 7-(2-(t-butoxycarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (193) 4-(N-(t-butoxycarbonyl) piperidin-4-yl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (194) 4,7-bis[(2-(t-butoxycarbonylamino)ethyl)oxy]-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (195) 4-(3-nitrophenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (196) 4-carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (197) 5-carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (198) 6-carboxymethoxy-3-phenylsutfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (199) 7-carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (200) 4-(N-(pyridin-3-ylmethyl) carbamoylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo [b]thiophene, (201) 4-((2-(N,N-dimethylamino)ethylamino)carbonylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (202) 4-(N-benzyl-2-(N′,N′-dimethylamino)ethylamino)carbonymethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (203) 4-(2-aminoethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (204) 4-(3-aminopropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (205) 5-(2-aminoethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (206) 6-(3-aminopropyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (207) 6-(2-aminoethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (208) 7-(2-aminoethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (209) 4-(piperidin-4-yl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (210) 4,7-bis[(2-aminoethyl)oxy] -3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (211) 4-(2-(N,N-dimethylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (212) 4-(3-(N,N-dimethylamino)propyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (213) 4-(3-(N-cyanomethyl-N-methylamino)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (214) 5-(2-(N,N-dimethylamino)ethyl)oxy-3-phenyisulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (215) 6-(3-(N,N-dimethylamino)propyl)oxy-3-phenyisulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (216) 6-(3-(N-cyanomethyl-N-methylamino)propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (217) 6-(2-(N,N-dimethylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (218) 7-(2-(N,N-dimethylaminoethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (219) 4-(3-aminophenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (220) 4-(3-(pyridin-3-ylcarbonylamino)phenylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (221) 4-(2-(pyridin-3-ylcarbonylamino)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (222) 5-methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (223) 5-(4-chlorophenylcarbonyl)amino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (224) 4-cyano-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (225) 6-nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (226) 4,7-dimethoxy-3-phenylsulfonyl-2;3-dihydro-1,1-dioxidebenzo[b]thiophene, (227) 4,7-bis(3-hydroxypropyl)oxy-3-phenyIsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (228) 4-(pyridin-3-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (229) 4-(4-benzylpiperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (230) 4-(N-(2-(pyridin-3-yl) ethyl)-N-methylcarbamoyl)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (231) 4-(2-(2-hydroxyethoxy)ethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (232) 4-(2,4-dimethoxyphenylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (233) 4-(1-benzylpiperidin-4-yl) carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (234) 4-(pyridin-4-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (235) 4-(2-t-butoxycarbonylethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (236) 4-(thiophen-2-ylmethyl)carbamoyl-3-phenylsufonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (237) 4-benzylcarbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (238) 4-(pyridin-2-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (239) 4-(2-(piperidin-1-yl)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (240) 4-((1S)-1-t-butoxycarbonyl-2-methylpropyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (241) 4-(2-fluorophenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (242) 4-(3-fluorophenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (243) 4-(3-methylphenylmethyl)carbamoyl-3-phenyisulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (244) 4-(2-methoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (245) 4-(2,3-dimethoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (246) 4-(3,4-dimethoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (247) 4-(2,5-difluorophenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (248) 4-(3,4,5-trimethoxyphenylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (249) 4-(benzimidazol-2-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (250) 4-(3,5-difluorophenylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (251) 4-(N-benzyl-N-methylcarbamoyl)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (252) 4-(4-nitrophenymethyl)carbamoyl-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (253) 5-(2-hydroxyethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (254) 5-(pyridin-3-ylmethyl)carbamoyl-4-methoxy-3-phenylsufonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (255) 5-(2-dimethylaminoethyl)carbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (256) 5-dimethylcarbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (257) 5-(2,3,4,5,6,7-hexahydro-1H-azepin-1-yl)carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (258) 5-(2,3-dihydroindol-1-yl)carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (259) 5-(4-(2-chlorophenyl)piperazin-1-yl)carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (260) 5-(4-(2-(2-trifluoromethylphenyl)ethyl)piperazin-1-yl) carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (261) 4-(pyridin-3-ylcarbonyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (262) 4-(3-(pyrrol-1-yl) propyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (263) 4-(quinolin-2-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (264) 4-(2-(pyrrol-1-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (265) 4-(2-(4-methylthiazol-5-yl)ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (266) 4-(3-(pyridin-4-yl) propyl)oxy-3-phenylsuffonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (267) 4-(1-t-butoxycarbonylpiperidin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (268) 4-(2-(pyrrolidin-1-yl)ethyl)oxy-3-phenyisulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (269) 4-(2-(piperidin-1-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (270) 4-(2-(2-acetyloxyethoxy)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (271) 4-(2-(4-benzylpiperazin-1-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (272) 4-diethylcarbamoylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (273) 4-cyanomethyloxy-3-phenyl sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (274) 5-(pyridin-3-yloxy)methyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (275) 5-(2-(t-butoxycarbonylamino)ethyl)oxy-4-nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (276) 5-((2E)-3-ethoxycarbonyl-2-propenyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (277) 4-(2,4-dimethoxyphenylmethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo [b]thiophene, (278) 4-(pyridin-3-ylmethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (279) 4-(2-dimethylaminoethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (280) 4-(N,N-bis(2-hydroxyethyl)amino)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (281) 4-(2-(2-hydroxyethoky)ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (282) 4-(4-benzylpiperazin-1-yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (283) 4-(4-(pyridin-2-yl)piperazi n-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (284) 4-(4-ethoxycarbonylpiperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (285) 4-(4-(2-hydroxyethyl)piperazin-1-yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (286) 4-(4-(pyridin-4-yl)piperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (287) 4-benzylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (288) 4-(1-benzylpiperidin-4-yl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (289) 4-(morpholin-4-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (290) 4-ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (291) 4-benzyloxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (292) 4-(pyridin-3-yl)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (293) 6-(pyridin-3-yl)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (294) 4-(4,4-dimethyl-4,5-dihydroxazol-2-yl)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (295) 6-bromo-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (296) 6-amino-3-phenylsufonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (297) 5-methyicarbamoyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (298) 4-dimethylxarbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (299) 4-carbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (300) 4-(2-(pyridin-4-yl)ethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (301) 4-(2-(pyridin-3-yl)ethyl)oxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (302) 4-ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (303) 6-ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (304) 6-cyanomethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (305) 5-ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (306) 7-ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (307) 5-benzyloxycarbonyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (308) 5-ethoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (309) 7-methoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (310) 7-ethoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (311) 5-t-butoxycarbonyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (312) 5-(2-(ethoxycarbonyl)ethyl)-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (313) 4-(furan-2-ylmethyl)carbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (314) 5-(4,4-dimethyl-4,5-dihydroxazol-2-yl) -3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (315) 3-benzylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (316) 3-(3,4-dichlorophenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (317) 3-(4-nitrophenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (318) 5-hydroxymethyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (319) 4-hydroxymethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (320) 6-fl uoro-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (321) 4-fluoro-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (322) 5-methylcarbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (323) 4-dimethylcarbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (324) 4-carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (325) 4-(2-(pyridin-4-yl)ethyl)oxy-3-phenylsufonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (326) 4-(2-(pyridin-3-yl)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (327) 4-ethoxycarbonylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (328) 6-ethoxycarbonylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (329) 6-cyanomethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (330) 5-ethoxycarbonylmethyloxy-3-phenylsufonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (331) 7-ethoxycarbonylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (332) 5-benzyloxycarbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (333) 5-ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (334) 7-methoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (335) 7-ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (336) 5-t-butoxycarbonyl-4-methoxy-3-phenyisulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (337) 5-(2-ethoxycarbonylethyl)-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (338) 3-benzylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (339) 3-(3,4-dichlorophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (340) 3-(4-nitrophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (341) 5-hydroxymethyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (342) 4-hydroxymethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (343) 6-fluoro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (344) 4-fluoro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (345) 5-benzylozycarbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (346) 5-benzyloxycarbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (347) 5-benzyloxycarbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (348) 5-benzyloxycarbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (349) 5-carboxy-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (350) 5-carboxy-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (351) 5-carboxy-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (352) 5-carboxy-4-octyloxy-3-phenylsuldonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (353) 5-methoxycarbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (354) 5-methoxycarbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (355) 5-methoxycarbonyl-4butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (356) 5-methoxycarbonyl-4-octyloxy-3-phenylsufonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (357) 5-(4-(2-(2-trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (358) 5-(4-(2-chlorophenyl)piperazin-1-yl)carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (359) 5-(dimethylaminoethylcarbamoyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo [b]thiophene, (360) 5-(2,3,4,5,6,7-hexahydro-1H-azepin-1-yl)carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (361) 5-(2,3-dihydroindol-1-yl)carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (362) 5-(4-(2-(2-trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (363) 5-(4-(2-chlorophenyl)piperazin-1-yl)carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo [b]thiophene, (364) 5-(2-dimethylaminoethyl)carbamoyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo [b]thiophene, (365) 5-(2,3,4,5,6,7-hexahydro-1H-azepin-1-yl)carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (366) 5-(2,3-dihydroindol-1-yl)carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo [b]thiophene, (367) 5-(4-(2-(2-trifluoromethylphenyl)ethyl)piperazin-1-yl) carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (368) 5-(4-(2-chlorophenyl) piperazin-1-yl)carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (369) 5-(2-dimethylaminoethyl)carbamoyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (370) 5-(2,3,4,5,6,7-hexahydro-1H-azepin-1-yl)carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (371) 5-(2,3-dihydroindol-1-yl) carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (372) 5-(4-(2-(2-trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (373) 5-(4-(2-chlorophenyl) piperazin-1-yl)carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (374) 5-(2-dimethylaminoethyl)carbamoyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (375) 5-(2,3,4,5,6,7-hexahydro-1H-azepin-1-yl)carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (376) 5-(2,3-dihydroindol-1-yl)carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-di oxidebenzo[b]thiophene, (377) 5-benzyloxy-4-hydroxymethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (378) 5-benzyloxy-4-bromomethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (379) 5-benzyloxy-4-aminomethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (380) 5-benzyloxy-4-t-butoxycarbonylaminomethyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (381) 5-benzyloxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (382) 5-benzyloxy-4-aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (383) 5-hydroxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (384) 5-methoxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (385) 5-(3-phenylpropyl) oxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (386) 5-methoxy-4-aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (387) 5-(3-phenylpropyl)oxy-4-aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (388) 5-benzyloxy-4-hydroxymethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (389) 5-benzyloxy-4-carboxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (390) 5-benzyloxy-4-(pyridin-3-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (391) 5-hydroxy-4-(pyridin-3-ylmethyl)carbamoyl-3-phenylsuifonyi-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (392) 4,7-dimethoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (393) 6-bromo-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (394) 4-(piperidin-3-ylmethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (395) 5-(2-aminoethyl)oxy-4-nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (396) 4-(2-(2-hydroxyethoxy)ethyl)oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (397) 5-carboxy-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (398) 4-carboxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (399) 4-formyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (400) 5-(4-phenylbutyl)aminomethyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (401) 5-(pyridin-3-ylmethyl)aminomethyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (402) 6-dimethylamino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (403) 4-(2-dimethylaminoethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (404) 4,7-bis(pyridin-3-ylmethyloxy)-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (405) 4-(N-oxidepyridin-3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (406) 4-(2-(N-oxidepyridin-4-yl)ethyl)oxy-3-phenylsulfonyl-2,3-di hydro-1,1-dioxidebenzo[b]thiophene, (407) 4-methoxy-3-(4-hydroxyphenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (408) 4-methoxy-3-(4-(pyridin-3-ylmethyloxy)phenyl)thio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (409) 4-methoxy-3-(4-(pyridin-3-ylmethyloxy) phenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (410) 5-(2-dimethylaminoethyl)carbamoyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (411) 5-(pyridin-3-ylmethyl)carbamoyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (412) 4-(2-(piperidin-1-yl)ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (413) 4-(furan-2-ylmethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (414) 4-(2,4,6-trimethoxybenzyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (415) 4-(3-(2-oxopyrrolidin-1-yl)propyl)carbamoyl-3-phenylsuIfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (416) 4-((3S)-1-benzylpyrrolidin-3-yl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (417) 4-(2-(pyrrolidin-1-yl)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (418) 4-(2-diethylaminoethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (419) 4-(2-(N-ethyl-N-(3-methylphenyl)amino)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (420) 4-(N-ethyl-N-2-(piperidin-1-yl)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (421) 4-(3-(imidazol-1-yl) propyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (422) 4-((3R)-1-benzylpyrrolidin-3-yl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (423) 4-(3-(pyrrolidin-1-yl)propyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (424) 4-(N-2-(piperidin-1-yl)ethyl-N-methyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (425) 4-(3,5-dimethoxybenzyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (426) 4-(3-(piperidin-1-yl)propyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (427) 4-(2-diisopropylamino)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (428) 4-(2-(morpholin-4-yl)ethyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (429) 4-(N-2-(piperidin-1-yl)ethyl-N-propyl)carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (430) 4-(N-2-(piperidin-1-yl)ethyl-N-isopropyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (431) 4-(4-benzoylpiperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (432) 4-(4-(4-ethylbenzyl)piperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (433) 4-(4-(4-phenylbenzyl)piperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (434) 4-(4-(1,3-dioxaindan-5-ylmethyl)piperazin-1-yl) carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (435) 4-(4-benzyloxycarbonylpiperazin-1-yl) carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (436) 4-(4-(2-methylphenyl) piperazin-1-yl)carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (437) 4-(4-(4-methoxyphenyl) piperazin-1-yl) carbonyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (438) 4-(2-(pyridin-2-yl)ethyl) oxy-3-phenylthio-1,1-dioxidebenzo[b]thiophene, (439) 4-(2-(piperidin-1-yl)ethyl)carbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (440) 4-(2-(piperidin-1-yl)ethyl)carbamoyl-3-(4-nitrophenyl)sulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (441) 4-(N-2-(piperidin-1-yl)ethyl-N-methyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (442) 4-(2-(N-ethyl-N-3-methylphenyl)aminoethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (443) 4-(N-benzyl-N-ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (444) 4-(2-diethylaminoethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (445) 4-(4-methylbenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (446) 4-(N-ethyl-N-2-(piperidin-1-yl)ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (447) 4-(2-methoxybenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (448) 4-(3-phenylpropyi)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (449) 4-(3,5-dimethoxybenzyl)aminomethyl-3-phenyisulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (450) 4-((3R)-1-benzylpyrrolidin-3-yl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (451) 4-((3S)-1-benzylpyrrolidin-3-yl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (452) 4-(2-phenylethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (453) 4-(N-benzyl-N-methyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (454) 4-(3-(2-oxopyrrolidin-1-yl)propyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (455) 4-(4-aminobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (456) 4-(4-((2E)-3-phenyl-2-propenyl) piperazin-1-yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (457) 4-(2-aminobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (458) 4-(4-benzylpiperidin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (459) 4-(4-chlorobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (460) 4-(3-chlorobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (461) 4-(3-methoxybenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (462) 4-(3,4-dichlorobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (463) 4-(1,3-dioxaindan-5-ylmethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (464) 4-(2,3-dimethoxybenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (465) 4-(3,4,5-trimethoxybenzyl)aminomethyl3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (466) 4-(4-(t-butyloxycarbonyl) piperazin-1-yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (467) 4-(2-diisopropylamino) ethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (468) 4-(2-(morpholin-4-yl) ethyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (469) 4-(N-2-(piperidin-1-yl) ethyl-N-propyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (470) 4-(N-2-(piperidin-1-yl)ethyl-N-isopropyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (471) 4-(3,4-dimethoxybenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (472) 4-(3-(2-methylpiperidin-1-yl)propyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (473) 4-(4-(piperidin-1-yl)piperidin-1-yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (474) 4-(3-(piperidin-1-yl)propyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (475) 4-(3-bromobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (476) 4-(4-nitrobenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (477) 4-(4-aminosulfonylbenzyl)aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (478) 4-(piperazin-1-yl)methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (479) 4-(2,4,6-trimethoxybenzyl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (480) 4-(piperidin-1-yl)carbonylmethylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (481) 4-(pyrrolidin-1-yl)ethylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxidebenzo[b]thiophene, (482) 4-(4-(1,3-dioxaindan-5-ylmethyl)piperazin-1-yl) methyl-1,1-dioxidebenzo[b]thiophene, or an N-oxide derivative thereof or a non-toxic salt thereof.

14. A compound ccording to claim 4, which is (1) 4-(pyridin-3-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (2) 4-(4-benzyl piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (3) 4-(N-(2-(pyridi n-3-yl)ethyl)-N-methylcarbamoyl) -1,1-dioxidebenzo[b]th iophene, (4) 4-(2-(2-hydroxyethoxy)ethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (5) 4-(2,4-dimethoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (6) 4-(1-benzylpiperidin-4-yl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (7) 4-(pyridin-4-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (8) 4-(2-t-butoxycarbonylethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (9) 4-(thiophen-2-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (10) 4-benzylcarbamoyl-1,1-dioxidebenzo[b]thiophene, (11) 4-(pyridin-2-ylmethyl) carbamoyl-1,1-dioxidebenzo[b]thiophene, (12) 4-(2-t(piperidin-1-yl)ethyl)carbamoyl-1,1-dioxidebenzo[b]thlophene, (13) 4-((1 S)-1-t-butoxycarbonyl-2-methylpropyl) carbamoyl-1,1-dioxidebenzo[b]thiophene, (14) 4-(2-fluorophenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (15) 4-(3-fluorophenylmethyl)carbamoyl-1,1-di oxidebenzo[b]thiophene, (16) 4-(3-methylphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (17) 4-(2-methoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (18) 4-(2,3-dimethoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (19) 4-(3,4-dimethoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (20) 4-(2,5-difluorophenylmethyl)carbamoyl-1,1-dioxidebenzo[bjthiophene, (21) 4-(3,4,5-trimethoxyphenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (22) 4-(benzimidazol-2-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (23) 4-(3,5-difluorophenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (24) 4-(N-benzyl-N-methylcarbamoyl)-1,1-dioxidebenzo[b]thiophene, (25) 4-(4-nitrophenylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (26) 5-(2-hydroxyethyl)carbamoyl-1,1-di oxidebenzo[b]thiophene, (27) 5-(pyridin-3-ylmethyl) carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (28) 5-(2-dimethylaminoethyl) carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (29) 5-dimethylcarbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (30) 5-(2,3,4,5,6,7-hexahydro-1H-azepin-1-yl)carbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (31) 5-(2,3-dihydroindol-1-yl) carbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (32) 5-(4-(2-chlorophenyl)piperazin-1-yl) carbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (33) 5-(4-(2-(2-trifluoromethylphenyl)ethyl)piperazin-1-yl)carbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (34) 4-(pyridin-3-ylcarbonyl) aminomethyl-1,1-dioxidebenzo[b]thiophene, (35) 4-(3-(pyrrol-1-yl)propyl)oxy-1,1-dioxidebenzo[b]thiophene, (36) 4-(quinolin-2-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene, (37) 4-(2-(pyrrol-1-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene, (38) 4-(2-(4-methylthiazol-5-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene, (39) 4-(3-(pyridin-4-yl) propyl)oxy-1,1-dioxidebenzo[b]thiophene, (40) 4-(1-t-butoxycarbonylpiperidin-3-ylmethyl)ox-1,1-dioxidebenzo[b]thiophene, (41) 4-(2-(pyrrolidin-1-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene, (42) 4-(2-(piperidin-1-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene, (43) 4-(2-(2-acetyloxyethoxy)ethyl)oxy-1,1-dioxidebenzo[b]thiophene, (44) 4-(2-(4-ebnzylpiperazin-1-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene, (45) 4-diethylcarbamoylmethyloxy-1,1-dioxidebenzo[b]thiophene, (46) 4-cyanomethyloxy-1,1-dioxidebenzo[b]thiophene, (47) 5-(pyridin-3-yloxy)methyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (48) 5-(2-t-butoxycarbonylaminoethyl)oxy-4-nitro-1,1-dioxidebenzo[b]thiophene, (49) 5-((2E)-3-ethoxycarbonyl-2-propenyl)oxy-1,1-dioxidebenzo[b]thiophene, (50) 4-(2,4-dimethoxyphenylmethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene, (51) 4-(pyridin-3-ylmethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene, (52) 4-(2-(dimethylamino)ethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene, (53) 4-(N,N-bis(2-hydroxyethyl) amino)methyl-1,1-dioxidebenzo[b]thiophene, (54) 4-(2-(2-hydroxyethoxy)ethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene, (55) 4-(4-benzylpiperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene, (56) 4-(4-(pyridin-2-yl)piperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene, (57) 4-(4-ethoxycarbonylpiperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene, (58) 4-(4-(2-hydroxyethyl)piperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene, (59) 4-(4-(pyridin-4-yl)piperazin-1-yl)methyl-1,1-dioxidebenzo[b]thiophene, (60) 4-benzylaminomethyl-1,1-dioxidebenzo[b]thiophene, (61) 4-(1-benzylpiperidin-4-yl)aminomethyl-1,1-dioxidebenzo[b]thiophene, (62) 4-(morpholin-4-yl)methyl-1,1-dioxidebenzo[b]thiophene, (63) 4-ethoxycarbonyl-1,1-dioxidebenzo[b]thiophene, (64) 4-benzyloxycarbonyl-1,1-dioxidebenzo[b]thiophene, (65) 4-(pyridin-3-yl)-1,1-dioxidebenzo[b]thiophene, (66) 6-(pyridin-3-yl)-1,1-dioxidebenzo[b]thiophene, (67) 4-(4,4-dimethyl-4,5-dihydroxazol-2-yl)-1,1-dioxidebenzo[b]thiophene, (68) 5-methylcarbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (69) 4-dimethylcarbamoyl-1,1-dioxidebenzo[b]thiophene, (70) 4-carbamoyl-1,1-dioxidebenzo[b]thiophene, (71) 4-(furan-2-ylmethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (72) 4-(2-(pyridin-4-yl)ethyl) oxy-1,1-dioxidebenzo[b]thiophene, (73) 4-(2-(pyridin-3-yl)ethyl)oxy-1,1-dioxidebenzo[b]thiophene, (74) 4-ethoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene, (75) 6-ethoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene, (76) 6-cyanomethyloxy-1,1-dioxidebenzo[b]thiophene, (77) 5-ethoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene, (78) 7-ethoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene, (79) 5-benzyloxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (80) 5-ethoxycarbonyl-1,1-dioxidebenzo[b]thiophene, (81) 7-methoxycarbonyl-1,1-dioxidebenzo[b]thiophene, (82) 7-ethoxycarbonyl-1,1-dioxidebenzo[b]thiophene, (83) 5-t-butoxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thi ophene, (84) 5-(2-(ethoxycarbonyl)ethyl)-4-methoxy-1,1-di oxidebenzo[b]thiophene, (85) 5-(4,4-dimethyl-4,5-dihydroxazol-2-yl)-1,1-dioxidebenzo[b]thiophene, (86) 5-benzyloxycarbonyl-4-ethoxy-1,1-dioxidebenzo[b]thiophene, (87) 5-benzyloxycarbonyl-4-hexyloxy-1,1-dioxidebenzo[b]thiophene, (88) 5-benzyloxycarbonyl-4-butoxy-11-dioxidebenzo[b]thiophene, (89) 5-benzyloxycarbonyl-4-octyloxy-1,1-di oxidebenzo[b]thiophene, (90) 5-benzyloxy-4-hydroxymethyl-1,1-dioxidebenzo[b]thiophene, (91) 4-(1,1-dimethyl-2-hydroxyethyl) carbamoyl-1,1-dioxidebenzo[b]thiophene, (92) 4-(2-hydroxyethyl) carbamoyl-1,1-dioxidebenzo[b]thiophene, (93) 4-(4-(2-hydroxyethyl)piperazin-1-yl) carbonyl-1,1-dioxidebenzo[b]thiophene, (94) 4-(N-methyl-N-methoxycarbamoyl)-1,1-dioxidebenzo[b]thiophene, (95) 4-(4-(thiazol-2-ylsulfamoyl)phenyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (96) 4-((1R) -1-t-butoxycarbonyl-2-methylpropyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (97) 6-(1-benzylpiperidin-4-yl)carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (98) 6-(2-diethylaminoethyl) carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (99) 6-(pyridin-3-ylmethyl) carbamoyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (100) 5-(6-dimethylaminohexyl)oxycarbonyl-1,1-dioxidebenzo[b]thiophene, (101) 4-(4-t-butoxycarbonylpiperazin-1-yl)carbonyl-11-dioxidebenzo[b]thiophene, (102) 4-(piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (103) 4-(4-(4-methoxyphenylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (104) 4-(4-(4-phenylphenylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (105) 4-(4-(naphthalen-1-ylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (106) 4-(4-(4-ethylphenylmethyl) piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (107) 4-(4-(naphthalen-2-ylcarbonylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (108) 4-(4-(pyridin-2-ylmethyl) piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (109) 4-(4-(pyridin-3-ylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (110) 4-(4-benzoylpiperazin-1-yl) carbonyl-1,1-dioxidebenzo[b]thiophene, (111) 4-(4-(furan-2-ylcarbonyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (112) 4-(4-benzylcarbonylpiperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (113) 4-(2-(pyrrolidin-1-yl) ethyl) carbamoyl-1,1-dioxidebenzo[b]thiophene, (114) 4-(3-(pyrrolidin-1-yl) propyl) carbamoyl-1,1-dioxidebenzo[b]thiophene, (115) 4-(4-(2-methylphenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (116) 4-(4-(3-methylphenyl) piperazin-1-yl) carbonyl-1,1-dioxidebenzo[b]thiophene, (117) 4-(4-(2-fluorophenyl) piperazin-1-yl) carbonyl-1,1-dioxidebenzo[b]thiophene, (118) 4-(4-(4-fluorophenyl)piperazin-1-yl) carbonyl-1,1-dioxidebenzo[b]thiophene, (119) 4-(4-(4-methoxyphenyl) piperazin-1-yl) carbonyl-1,1-dioxidebenzo[b]thiophene, (120) 4-(4-(3-trifluoromethylphenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (121) 4-((3R)-1-benzylpyrrolidin-3-yl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (122) 4-((3S)-1-benzylpyrrolidin-3-yl) carbamoyl-1,1-dioxidebenzo[b]thiophene, (123) 5-acetylmethyloxy-1,1-dioxidebenzo[b]thiophene, (124) 5-cyanomethyloxy-1,1-dioxidebenzo[b]thiophene, (125) 5-t-butoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene, (126) 5-(3-(ethoxycarbonyl)propyl)oxy-1,1-dioxidebenzo[b]thiophene, (127) 5-(4-(ethoxycarbonyl)butyl) oxy-1,1-dioxidebenzo[b]thiophene, (128) 4-(pyridin-3-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene, (129) 4-(pyridin-4-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene, (130) 4-(4-trifluoromethylphenylmethyl)oxy-3-phenylthio-1,1-dioxidebenzo[b]thiophene, (131) 4-(3,5-dimethylisoxazol-4-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene, (132) 4-(4-methoxycarbonylphenylmethyl)oxy-1,1-dioxidebenzo[b]thiophene, (133) 4-(benzotriazol-1-ylmethyl)oxy-11-dioxidebenzo[b]thiophene, (134) 4-(2,6-dimethylphenyl) carbamoylmethyloxy-1,1-dioxidebenzo[b]thiophene, (135) 4-trimethylsilylmethyloxy-1,1-dioxidebenzo[b]thiophene, (136) 4-(pyridin-2-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene, (137) 4-(2-(pyridin-3-ylcarbonyl)aminoethyl)oxy-1,1-dioxidebenzo[b]thiophene, (138) 4-(3-(pyridin-3-yl)propyl)oxy-1,1-dioxidebenzo[b]thiophene, (139) 4-(2-(pyridin-2-yl) ethyl) oxy-1,1-dioxidebenzo[b]thiophene, (140) 4-(1-t-butoxycarbonylpiperidin-4-yl)oxy-1,1-dioxidebenzo[b]thiophene, (141) 4-(5-methyl-1-tritylimidazol-4-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene, (142) 4-(1,2,4-oxadiazol-3-yl methyl)oxy-1,1-dioxidebenzo[b]thiophene, (143) 6-(pyridin-3-ylmethyl)oxy-1,1-dioxidebenzo[b]thiophene, (144) 6-(3-nitrophenylmethyl)oxy-1,1-dioxidebenzo[b]thiophene, (145) 6-(3-(t-butoxycarbonylamino) propyl)oxy-1,1-dioxidebenzo[b]thiophene, (146) 7-t-butoxycarbonylmethyloxy-1,1-dioxidebenzo[b]thiophene, (147) 6-(pyridin-3-yloxy) methyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (148) 4,7-bis(3-hydroxypropyl)-1,1-dioxidebenzo[b]thiophene, (149) 5-carboxy-4-ethoxy-1,1-dioxidebenzo[b]thiophene, (150) 5-carboxy-4-butoxy-1,1-dioxidebenzo[b]thiophene, (151) 5-carboxy-4-hexyloxy-1,1-dioxidebenzo[b]thiophene, (152) 5-carboxy-4-octyloxy-1,1-dioxidebenzo[b]thiophene, (153) 5-ethoxycarbonyl-4-hydroxy-1,1-dioxidebenzo[b]thiophene, (154) 5-ethoxycarbony-4-metoxy-1,1-dioxidebenzo[b]thiophene, (155) 5-isopropyloxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (156) 5-(2-methylpropyl)oxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (157) 6-meth oxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (158) 6-methoxymethoxycarbonyl-4-methoxy-1,1-dioxidebenzo[b]thiophene, (159) 4-(N-(pyridin-2-ylmethyl)-N-(1,1-dioxidebenzo[b]thiophen-4-ylmethyl)amino)methyl-1,1-dioxidebenzo[b]thiophene, (160) 4-(pyridin-2-ylmethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene, (161) 4-(N-(2,4-dimethoxyphenylmethyl)-N-(1,1-dioxidebenzo[b]thiophen-4-ylmethyl)amino)methyl-1,1-dioxidebenzo[b]thiophene, (162) 5-acetyloxy-4-nitro-1,1-dioxidebenzo[b]thiophene, (163) 4-(4,5-dihydroxazol-2-yl) -1,1-dioxidebenzo[b]thiophene, (164) 5-(4,5-dihydroxazol-2-yl) -1,1-dioxidebenzo[b]thiophene, (165) 5-carboxymethyloxy-1,1-dioxidebenzo[b]thiophene, (166) 7-carboxymethyloxy-1,1-dioxidebenzo[b]thiophene, (167) 4-((1S)-1-carboxy-2-methylpropyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (168) 4-((1R)-1-carboxy-2-methylpropyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (169) 5-(3-carboxypropyl)oxy-1,1-dioxidebenzo[b]thiophene, (170) 5-((2E)-3-carboxy-2-propenyl)oxy-1,1-dioxidebenzo[b]thiophene, (171) 4-2-(piperidin-1-yl) ethyl)aminomethyl-1,1-dioxidebenzo[b]thiophene, (172) 4-t-butoxycarbonylamino-1,1-dioxidebenzo[b]thiophene, (173) 4-amino-1,1-dioxidebenzo[b]thiophene, (174) 4-(4-fluorobenzylamino)-1,1-dioxidebenzo[b]thiophene, (175) 4-(pyridin-3-ylcarbonyl)amino-1,1-dioxidebenzo[b]thiophene, (176) 4-(3-chlorobenzoyl)amino-1,1-dioxidebenzo[b]thiophene, (177) 4-benzylcarbonylamino-1,1-dioxidebenzo[b]thiophene, (178) 4-(dimethylaminoacetyl)amino-1,1-dioxidebenzo[b]thiophene, (179) 4-acetylamino-1,1-dioxidebenzo[b]thiophene, (180) 4-(3-(2-oxopyrrolidin-1-yl)propyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (181) 4-(2-diethylaminoethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (182) 4-(2-(N-ethyl-N-(3-methylphenyl)amino)ethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (183) 4-(2,4,6-trimethoxybenzyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (184) 4-(4-(2-hydroxyethyl)piperazin-1-yl) carbonyl-1,1-dioxidebenzo[b]thiophene, (185) 4-(4-benzyloxycarbonylpiperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (186) 4-(N-ethyl-N-2-(piperidin-1-yl)ethyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (187) 4-(3-(imidazol-1-yl)propyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (188) 4-(N-2-(piperidin-1-yl)ethyl-N-methyl)carbamoyl-1,1-dioxidebenzo[b]thiophene, (189) 4-(4-(1,3-dioxaindan-5-ylmethyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, (190) 4-(4-((2E)-3-phenyl-2-propenyl)piperazin-1-yl)carbonyl-1,1-dioxidebenzo[b]thiophene, or an N-oxide derivative thereof or a non-toxic salt thereof.

15. A pharmaceutical composition comprising a fused thiophene derivative of the formula (IA) depicted in claim 4, an N-oxide derivative thereof or a non-toxic salt thereof as an active ingredient.

16. A method for preparation of a compound of the formula (XI)