Fused-ring compounds and use thereof as drugs

Information

  • Patent Application
  • 20040097438
  • Publication Number
    20040097438
  • Date Filed
    July 08, 2003
    21 years ago
  • Date Published
    May 20, 2004
    20 years ago
Abstract
The present invention provides a fused ring compound of the following formula [I] 1
Description


TECHNICAL FIELD

[0002] The present invention relates to a novel fused ring compound and a pharmaceutically acceptable salt thereof useful as a therapeutic agent for hepatitis C, and to an intermediate compound for the synthesis thereof. The present invention also relates to a novel use of a certain fused ring compound or a pharmaceutically acceptable salt thereof as a therapeutic agent for hepatitis C. More particularly, the present invention relates to a therapeutic agent for hepatitis C, which contains a novel fused ring compound or a Pharmaceutically acceptable salt thereof, which is effective for the prophylaxis or treatment of hepatitis C and which shows anti-hepatitis C virus (HCV) activity, particularly anti-HCV activity based on an RNA-dependent RNA polymerase inhibitory activity.



BACKGROUND ART

[0003] In 1989, a main causative virus of non-A non-B posttransfusion hepatitis was found and named hepatitis C virus (HCV). Since then, several types of hepatitis viruses have been found besides type A, type B and type C, wherein hepatitis caused by HCV is called hepatitis C.


[0004] The patients infected with HCV are considered to involve several percent of the world population, and the infection with HCV characteristically becomes chronic.


[0005] HCV is an envelope RNA virus, wherein the genome is a single strand plus-strand RNA, and belongs to the genus Hepacivirus of Flavivirus (from The International Committee on Taxonomy of Viruses, International Union of Microbiological Societies). Of the same hepatitis viruses, for example, hepatitis B virus (HBV), which is a DNA virus, is eliminated by the immune system and the infection with this virus ends in an acute infection except for neonates and infants having yet immature immunological competence. In contrast, HCV somehow avoids the immune system of the host due to an unknown mechanism. Once infected with this virus, even an adult having a mature immune system frequently develops persistent infection.


[0006] When chronic hepatitis is associated with the persistent infection with HCV, it advances to cirrhosis or hepatic cancer in a high rate. Enucleation of tumor by operation does not help much, because the patient often develops recurrent hepatic cancer due to the sequela inflammation in non-cancerous parts.


[0007] Thus, an effective therapeutic method of hepatitis C is desired. Apart from the symptomatic therapy to suppress inflammation with an anti-inflammatory agent, the development of a therapeutic agent that reduces HCV to a low level free from inflammation and that eradicates HCV has been strongly demanded.


[0008] At present, a treatment with interferon is the only effective method known for the eradication of HCV. However, interferon can eradicate the virus only in about one-third of the patient population. For the rest of the patients, it has no effect or provides only a temporary effect. Therefore, an anti-HCV drug to be used in the place of or concurrently with interferon is awaited in great expectation.


[0009] In recent years, Ribavirin (1-β-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide) has become commercially available as a therapeutic agent for hepatitis C, which is to be used concurrently with interferon. It enhances the efficacy of interferon but only to a low efficacy rate, and a different novel therapeutic agent for hepatitis C is desired.


[0010] Also, an attempt has been made to potentiate the immunocompetence of the patient with an interferon agonist, an interleukin-12 agonist and the like, thereby to eradicate the virus, but an effective pharmaceutical agent has not been found yet.


[0011] In addition, the inhibition of HCV growth, wherein HCV-specific protein is targeted, has been drawing attention these days.


[0012] The gene of HCV encodes a protein such as serine protease, RNA helicase, RNA-dependent RNA polymerase and the like. These proteins function as a specific protein essential for the growth of HCV.


[0013] One of the specific proteins, RNA-dependent RNA polymerase (hereinafter to be also briefly referred to as an HCV polymerase), is an enzyme essential for the growth of the virus. The gene replication of HCV having a plus-strand RNA gene is considered to involve synthesis of a complementary minus-strand RNA by the use of the plus-strand RNA as a template, and, using the obtained minus-strand RNA as a template, amplifying the plus-strand RNA. The portion called NS5B of a protein precursor, that HCV codes for, has been found to show an RNA-dependent RNA polymerase activity (EMBO J., 15, 12-22, 1996), and is considered to play a central role in the HCV gene replication.


[0014] Therefore, an HCV polymerase inhibitor can be a target in the development of an anti-HCV drug, and the development thereof is eagerly awaited. However, an effective HCV polymerase inhibitor has not been developed yet, like in other attempts to develop an anti-HCV drug based on other action mechanisms. As the situation stands, no pharmaceutical agent can treat hepatitis C satisfactorily.


[0015] The following discloses known compounds relatively similar to the compound of the present invention.


[0016] A known therapeutic agent for hepatitis C having a benzimidazole skeleton is disclosed in WO97/36866, Japanese Patent Application under PCT laid-open under kohyo No. 2000-511899 (EP906097) and WO99/51619.


[0017] WO97/36866 discloses the following compound D and the like, and HCV helicase inhibitory activity of the compounds.


[0018] Japanese Patent Application under PCT laid-open under kohyo No. 2000-511899 (EP906097) discloses the following compound E and the like, and WO99/51619 discloses the following compound F and the like, in both of which a possibility of these compounds being effective as an HCV inhibitor is mentioned.


[0019] However, these publications do not include the compound disclosed in the present specification, or a disclosure suggestive thereof.
2


[0020] A known anti-hepatitis virus agent having a benzimidazole skeleton is disclosed in Japanese Patent Application under PCT laid-open under kohyo No. 2000-503017 (WO97/25316) and Japanese Patent Application under PCT laid-open under kohyo No. 10-505092 (WO96/7646).


[0021] WO97/25316 discloses the following compound A and the like, wherein the use thereof is for a treatment of viral infection. The target virus is a DNA virus such as hepatitis B virus and the like. However, this publication does not include the compound disclosed in the present specification or a description regarding or suggestive of HCV.


[0022] Japanese Patent Application under PCT laid-open under kohyo No. 10-505092 discloses the following compound B and the like, wherein the use thereof is for a treatment of viral infection. The target virus is a DNA virus such as herpesvirus and hepatitis B virus. However, this publication does not include the compound disclosed in the present specification or a description regarding or suggestive of HCV.
3


[0023] The benzimidazole derivatives having an antiviral activity have been disclosed in JP-A-3-31264, U.S. Pat. Nos. 3,644,382 and 3,778,504. In addition, WO98/37072 discloses, as a production inhibitor of tumor necrosis factor (TNF) and cyclic AMP, a benzimidazole derivative for the use as an anti-human immunodeficiency virus (HIV) agent and an anti-inflammation agent. WO98/05327 discloses, as a reverse transcriptase inhibitor, a benzimidazole derivative for the use as an anti-HIV agent. J. Med. Chem. (13(4), 697-704, 1970) discloses, as a neuraminidase inhibitor, a benzimidazole derivative for the use as an anti-influenza virus agent.


[0024] However, none of these publications includes the compound of the present invention or a description regarding or suggestive of an anti-HCV effect.


[0025] Known benzimidazole derivatives having a pharmaceutical use other than as an antiviral agent are disclosed in JP-A-8-501318 (U.S. Pat. No. 5,814,651) and JP-A-8-134073 (U.S. Pat. No. 5,563,143). These publications disclose the following compound C and the like as a catechol diether compound, and the use thereof as an anti-inflammation agent. However, neither of the publications includes the compound of the present invention, and as the action mechanism, the former discloses phosphodiesterase IV and the latter discloses TNF. These publications do not include a description regarding or suggestive of an anti-HCV effect.


[0026] Japanese Patent Application under PCT laid-open under kohyo No. 2000-159749 (EP882718) discloses the following compound G and the like, and the use thereof for the treatment of bronchitis, glomerulonephritis and the like. However, this publication does not include the compound of the present invention, but discloses only a phosphodiesterase IV inhibitory and hypoglycemic action. This publication does not include a description regarding or suggestive of an anti-HCV effect.


[0027] U.S. Pat. No. 6,211,177 discloses the following compound H and the like with their use as antitumor agents. However, this publication does not encompass the compound of the present invention, and does not disclose or suggest an anti-HCV effect.
4


[0028] WO98/50029, WO98/50030 and WO98/50031 disclose benzimidazole derivatives as an antitumor agent having a protein isoprenyl transferase action. While this publication discloses a wide scope of the claims, at least it does not include a compound analogous to the compound of the present invention or a description regarding or suggestive of an anti-HCV effect.


[0029] JP-A-8-109169 (EP694535) discloses the application of a tachykinin receptor antagonist to treat an inflammatory disease, and WO96/35713 discloses the application thereof as a growth hormone release promoter to treat a growth hormone-related disease such as osteoporosis and the like. However, none of these publications includes a description regarding or suggestive of an anti-HCV effect.


[0030] WO2001/21634 discloses the following compound I in a chemical library. However, this publication does not encompass the compound of the present invention. While it discloses an antimicrobial activity of certain compounds, this publication does not teach or suggest an anti-HCV effect.
5


[0031] JP-A-53-14735 discloses a benzimidazole derivative as a brightener besides its pharmaceutical use, but this publication does not include the compound of the present invention.



SUMMARY OF THE INVENTION

[0032] Based on the findings from the preceding studies, it has been elucidated that a pharmaceutical agent having an anti-HCV activity is effective for the prophylaxis and treatment of hepatitis C, and particularly an anti-HCV agent having an inhibitory activity on RNA-dependent RNA polymerase of HCV can be a prophylactic and therapeutic agent effective against hepatitis C and a prophylactic and therapeutic agent for the disease caused by hepatitis C.


[0033] Accordingly, the present invention provides a pharmaceutical agent having an anti-HCV activity, particularly a pharmaceutical agent having an RNA-dependent RNA polymerase inhibitory activity.


[0034] The present inventors have made an in-depth study of compounds having an anti-HCV activity, particularly RNA-dependent RNA polymerase inhibitory activity, and completed the present invention.


[0035] Thus, the present invention provides the following (1) to (117).


[0036] (1) A therapeutic agent for hepatitis C, which comprises a fused ring compound of the following formula [I] or a pharmaceutically acceptable salt thereof as an active ingredient:
6


[0037] wherein


[0038] a broken line is a single bond or a double bond,


[0039] G1 is C(—R1) or a nitrogen atom,


[0040] G2 is C(—R2) or a nitrogen atom,


[0041] G3 is C(—R3) or a nitrogen atom,


[0042] G4 is C(—R4) or a nitrogen atom,


[0043] G5, G6, G8 and G9 are each independently a carbon atom or a nitrogen atom,


[0044] G7 is C(—R7), an oxygen atom, a sulfur atom, or a nitrogen atom optionally substituted by R8,


[0045] wherein R1, R2, R3 and R4 are each independently,


[0046] (1) hydrogen atom,


[0047] (2) C1-6 alkanoyl,


[0048] (3) carboxyl,


[0049] (4) cyano,


[0050] (5) nitro,


[0051] (6) C1-6 alkyl optionally substituted by 1 to 3 substituent(s) selected from the following group A,


[0052] group A; halogen atom, hydroxyl group, carboxyl, amino, C1-6 alkoxy, C1-6 alkoxy C1-6 alkoxy, C1-6 alkoxycarbonyl and C1-6 alkylamino,


[0053] (7) —COORa1


[0054] wherein Ra1 is optionally substituted C1-6 alkyl (as defined above), C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group B or glucuronic acid residue,


[0055] group B; halogen atom, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2, —(CH2)r—NRb1Rb2, —(CH2)r—NRb1—CORb2, —(CH2)r—NHSO2Rb1, —(CH2)r—ORb1, —(CH2)r—SRb1, —(CH2)r—SO2Rb1 and —(CH2)r—SO2NRb1Rb2 wherein Rb1 and Rb2 are each independently hydrogen atom or C1-6 alkyl and r is 0 or an integer of 1 to 6,


[0056] (8) —CONRa2Ra3


[0057] wherein Ra2 and Ra3 are each independently hydrogen atom, C1-6 alkoxy or optionally substituted C1-6 alkyl (as defined above),


[0058] (9) —C(═NRa4)NH2


[0059] wherein Ra4 is hydrogen atom or hydroxyl group,


[0060] (10) —NHRa5


[0061] wherein Ra5 is hydrogen atom, C1-6 alkanoyl or C1-6 alkylsulfonyl,


[0062] (11) —ORa6


[0063] wherein Ra6 is hydrogen atom or optionally substituted C1-6 alkyl(as defined above),


[0064] (12) —SO2Ra7


[0065] wherein Ra7 is hydroxyl group, amino, C1-6 alkyl or C1-6 alkylamino,


[0066] (13) —P(═O)(ORa31)2


[0067] wherein Ra31 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or


[0068] (14) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, and


[0069] R7 and R8 are each hydrogen atom or optionally substituted C1-6 alkyl (as defined above),


[0070] ring Cy is


[0071] (1) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group C, group C; hydroxyl group, halogen atom, C1-6 alkyl and C1-6 alkoxy,


[0072] (2) C3-8 cycloalkenyl optionally substituted by 1 to 5 substituent(s) selected from the above group C, or


[0073] (3)
7


[0074] wherein u and v are each independently an integer of 1 to 3,


[0075] ring A is


[0076] (1) C6-14 aryl,


[0077] (2) C3-8 cycloalkyl,


[0078] (3) C3-8 cycloalkenyl or


[0079] (4) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,


[0080] R5 and R6 are each independently


[0081] (1) hydrogen atom,


[0082] (2) halogen atom,


[0083] (3) optionally substituted C1-6 alkyl (as defined above) or


[0084] (4) —ORa8


[0085] wherein Ra8 is hydrogen atom, C1-6 alkyl or C6-14 aryl C1-6 alkyl, and


[0086] X is


[0087] (1) hydrogen atom,


[0088] (2) halogen atom,


[0089] (3) cyano,


[0090] (4) nitro,


[0091] (5) amino, C1-6 alkanoylamino,


[0092] (6) C1-6 alkylsulfonyl,


[0093] (7) optionally substituted C1-6 alkyl (as defined above),


[0094] (8) C2-6 alkenyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,


[0095] (9) —COORa9


[0096] wherein Ra9 is hydrogen atom or C1-6 alkyl,


[0097] (10) —CONH—(CH2)1—Ra10


[0098] wherein Ra10 is optionally substituted C1-6 alkyl (as defined above), C1-6 alkoxycarbonyl or C1-6 alkanoylamino and 1 is 0 or an integer of 1 to 6,


[0099] (11) —ORa11


[0100] wherein Ra11 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above) or


[0101] (12)
8


[0102]  wherein


[0103] ring B is


[0104] (1′) C6-14 aryl,


[0105] (2′) C3-8 cycloalkyl or


[0106] (3′) heterocyclic group (as defined above),


[0107] each Z is independently


[0108] (1′) a group selected from the following group D,


[0109] (2′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the following group D,


[0110] (3′) C3-8 cycloalkyl optionally substituted by 1 to substituent(s) selected from the following group D,


[0111] (4′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,


[0112] (5′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the following group D,


[0113] wherein the heterocyclic group has 1 to 4 hetero atom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or


[0114] (6′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,


[0115] wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, as defined above,


[0116] group D:


[0117] (a) hydrogen atom,


[0118] (b) halogen atom,


[0119] (c) cyano,


[0120] (d) nitro,


[0121] (e) optionally substituted C1-6 alkyl (as defined above),


[0122] (f) —(CH2)t—CORa18, (hereinafter each t means independently 0 or an integer of 1 to 6),


[0123] wherein Ra18 is


[0124] (1″) optionally substituted C1-6 alkyl (as defined above),


[0125] (2″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or


[0126] (3″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,


[0127] (g) —(CH2)t—COORa19


[0128] wherein Ra19 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0129] (h) —(CH2)t—CONRa27Ra28


[0130] wherein Ra27 and Ra28 are each independently,


[0131] (1″) hydrogen atom,


[0132] (2″) optionally substituted C1-6 alkyl (as defined above),


[0133] (3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0134] (4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0135] (5″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0136] (6″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0137] wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, as defined above,


[0138] (7″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0139] (8″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0140] (9″) hydroxyl group or


[0141] (10″) C1-6 alkoxy,


[0142] (i) —(CH2)t—C(═NRa33)NH2


[0143] wherein Ra33 is hydrogen atom, C1-6 alkyl, hydroxyl group or C1-6 alkoxy,


[0144] (j) —(CH2)t—ORa20


[0145] wherein Ra20 is


[0146] (1″) hydrogen atom,


[0147] (2″) optionally substituted C1-6 alkyl (as defined above),


[0148] (3″) optionally substituted C2-6 alkenyl (as defined above),


[0149] (4″) C2-6 alkynyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,


[0150] (5″) C6-14 aryl optionally substituted by 1 to substituent(s) selected from the above group B,


[0151] (6″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0152] (7″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0153] (8″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0154] (9″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or


[0155] (10″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0156] (k) —(CH2)t—O—(CH2)p—CORa21


[0157] wherein Ra21 is amino, C1-6 alkylamino or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, and p is 0 or an integer of 1 to 6,


[0158] (1) —(CH2)t—NRa22Ra23


[0159] wherein Ra22 and Ra23 are each independently


[0160] (1″) hydrogen atom,


[0161] (2″) optionally substituted C1-6 alkyl (as defined above),


[0162] (3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0163] (4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0164] (5″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or


[0165] (6″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0166] (m) —(CH2)t—NRa29CO—Ra24


[0167] wherein Ra29 is hydrogen atom, C1-6 alkyl or C1-6 alkanoyl, and


[0168] Ra24 is


[0169] (1″) amino,


[0170] (2″) C1-6 alkylamino,


[0171] (3″) optionally substituted C1-6 alkyl (as defined above),


[0172] (4″) C6-14 aryl optionally substituted by 1 to substituent(s) selected from the above group B,


[0173] (5″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B or


[0174] (6″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0175] (n) —(CH2)t—NRa29SO2—Ra25


[0176] wherein Ra29 is as defined above, and Ra25 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0177] (o) —(CH2)t—S(O)q—Ra25


[0178] wherein Ra25 is as defined above, and q is 0, 1 or 2,


[0179] (p) —(CH2)t—SO2—NHRa26


[0180] wherein Ra26 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, and


[0181] (q) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, and


[0182] w is an integer of 1 to 3, and


[0183] Y is


[0184] (1′) a single bond,


[0185] (2′) C1-6 alkylene,


[0186] (3′) C2-6 alkenylene,


[0187] (4′) —(CH2)m—O—(CH2)n—,


[0188] (hereinafter m and n are each independently 0 or an integer of 1 to 6),


[0189] (5′) —CO—,


[0190] (6′) —CO2—(CH2)n—,


[0191] (7′) —CONH—(CH2)n—NH—,


[0192] (8′) —NHCO2—,


[0193] (9′) —NHCONH—,


[0194] (10′) —O—(CH2)n—CO—,


[0195] (11′) —O—(CH2)n—O—,


[0196] (12′) —SO2—,


[0197] (13′) —(CH2)m—NRa12—(CH2)n


[0198] wherein Ra12 is


[0199] (1″) hydrogen atom,


[0200] (2″) optionally substituted C1-6 alkyl (as defined above),


[0201] (3″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0202] (4″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0203] (5″) —CORb5


[0204] wherein Rb5 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0205] (6″) —COORb5 (Rb5 is as defined above) or


[0206] (7″) —SO2Rb5 (Rb5 is as defined above),


[0207] (14′) —NRa12CO— (Ra12 is as defined above),


[0208] (15′) —CONRa13—(CH2)n


[0209] wherein Ra13 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0210] (16′) —CONH—CHRa14


[0211] wherein Ra14 is C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0212] (17′) —O—(CH2)m—CRa15Ra16—(CH2)n


[0213] wherein Ra15 and Ra16 are each independently


[0214] (1″) hydrogen atom,


[0215] (2″) carboxyl,


[0216] (3″) C1-6 alkyl,


[0217] (4″) —ORb6


[0218] wherein Rb6 is C1-6 alkyl or C6-14 aryl C1-6 alkyl, or


[0219] (5″) —NHRb7


[0220] wherein Rb7 is hydrogen atom, C1-6 alkyl, C1-6 alkanoyl or C6-14 aryl C1-6 alkyloxycarbonyl, or Ra15 is optionally


[0221] (6″)
9


[0222] wherein n′, ring B′, Z′ and w′ are the same as the above-mentioned n, ring B, Z and w, respectively, and may be the same as or different from the respective counterparts,


[0223] (18′) —(CH2)n—NRa12—CHRa15— (Ra12 and Ra15 are each as defined above),


[0224] (19′) —NRa17SO2


[0225] wherein Ra17 is hydrogen atom or C1-6 alkyl,


[0226] (20′) —S(O)e—(CH2)m—CRa15Ra16—(CH2)n— (e is 0, 1 or 2,


[0227] Ra15 and Ra16 are each as defined above), or


[0228] (21′) —(CH2)m—CRa15Ra16—(CH2)n— (Ra15 and Ra16 are each as defined above).


[0229] (2) The therapeutic agent of (1) above, wherein 1 to 4 of the G1, G2, G3, G4, G5, G6, G7, G8 and G9 is (are) a nitrogen atom.


[0230] (3) The therapeutic agent of (2) above, wherein G2 is C(—R2) and G6 is a carbon atom.


[0231] (4) The therapeutic agent of (2) or (3) above, wherein G5 is a nitrogen atom.


[0232] (5) The therapeutic agent of (1) above, wherein, in formula [I], the moiety
10


[0233] is a fused ring selected from
1112


[0234] (6) The therapeutic agent of (5) above, wherein, in formula [I], the moiety
13


[0235] is a fused ring selected from
14


[0236] (7) The therapeutic agent of (6) above, which comprises a fused ring compound of the following formula [I-1]
15


[0237] wherein each symbol is as defined in (1),


[0238] or a pharmaceutically acceptable salt thereof as an active ingredient.


[0239] (8) The therapeutic agent of (6) above, which comprises a fused ring compound of the following formula [I-2]
16


[0240] wherein each symbol is as defined in (1),


[0241] or a pharmaceutically acceptable salt thereof as an active ingredient.


[0242] (9) The therapeutic agent of (6) above, which comprises a fused ring compound of the following formula [I-3]
17


[0243] wherein each symbol is as defined in (1),


[0244] or a pharmaceutically acceptable salt thereof as an active ingredient.


[0245] (10) The therapeutic agent of (6) above, which comprises a fused ring compound of the following formula [I-4]
18


[0246] wherein each symbol is as defined in (1),


[0247] or a pharmaceutically acceptable salt thereof as an active ingredient.


[0248] (11) The therapeutic agent of any of (1) to (10) above, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1, —CONRa2Ra3, —SO2Ra7 (wherein Ra1, Ra2, Ra3 and Ra7 are as defined in (1)),
19


[0249] (12) The therapeutic agent of (11) above, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1, —CONRa2Ra3 or —SO2Ra7 wherein Ra1, Ra2, Ra3 and Ra7 are as defined in (1).


[0250] (13) The therapeutic agent of any of (1) to (10) above, wherein at least one of R1, R2, R3 and R4 is —COORa1 wherein Ra1 is glucuronic acid residue.


[0251] (14) The therapeutic agent of any of (1) to (10) above, wherein at least one of R1, R2, R3 and R4 is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom.


[0252] (15) The therapeutic agent of any of (1) to (14) above, wherein the ring Cy is cyclopentyl, cyclohexyl, cycloheptyl, tetrahydrothiopyranyl or piperidino.


[0253] (16) The therapeutic agent of any of (1) to (14) above, wherein the ring Cy is
20


[0254] wherein each symbol is as defined in (1).


[0255] (17) The therapeutic agent of any of (1) to (16) above, wherein the ring A is C6-14 aryl.


[0256] (18) The therapeutic agent of any of (1) to (17) above, wherein at least one substituent optionally substituted by group A is a substituent substituted by C1-6 alkoxy C1-6 alkoxy.


[0257] (19) The therapeutic agent of any of (1) to (17) above, wherein the Y is —(CH2)m—CRa15Ra16—(CH2)n— wherein each symbol is as defined in (1).


[0258] (20) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by Z is heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the group D.


[0259] (21) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by Z is a heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, wherein said heterocyclic group is selected from the following groups:
21


[0260] wherein E1 is an oxygen atom, a sulfur atom or N(—Ra35), E2 is an oxygen atom, CH2 or N(—Ra35), E3 is an oxygen atom or a sulfur atom, wherein each Ra35 is independently hydrogen atom or C1-6 alkyl, f is an integer of 1 to 3, and h and h′ are the same or different and each is an integer of 1 to 3.


[0261] (22) The therapeutic agent of (21) above, wherein at least one group represented by Z is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D wherein said heterocyclic group is selected from the following groups:
22


[0262] wherein each symbol is as defined in (21).


[0263] (23) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by group D is —(CH2)t—CONRa27Ra28 wherein each symbol is as defined in (1), and at least one of Ra27 and Ra28 is C1-6 alkoxy.


[0264] (24) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by group D is —(CH2)t—C(═NRa33)NH2 wherein each symbol is as defined in (1), and Ra33 is hydroxyl group or C1-6 alkoxy.


[0265] (25) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by group D is —(CH2)t—O—(CH2)p—CORa21 wherein each symbol is as defined in (1), and Ra21 is amino.


[0266] (26) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by group D is —(CH2)t—NRa29CO—Ra24 wherein each symbol is as defined in (1), and Ra24 is amino or C1-6 alkylamino.


[0267] (27) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by group D is —(CH2)t—NRa22Ra23 wherein each symbol is as defined in (1), and at lease one of Ra22 and Ra23 is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group B.


[0268] (28) The therapeutic agent of any of (1) to (19) above, wherein at least one group represented by group D is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom.


[0269] (29) The therapeutic agent of (1) above, which comprises a fused ring compound of the following formula [I] or a pharmaceutically acceptable salt thereof as an active ingredient:
23


[0270] wherein


[0271] a broken line is a single bond or a double bond,


[0272] G1 is C(—R1) or a nitrogen atom,


[0273] G2 is C(—R2) or a nitrogen atom,


[0274] G3 is C(—R3) or a nitrogen atom,


[0275] G4 is C(—R4) or a nitrogen atom,


[0276] G5, G6, G8 and G9 are each independently a carbon atom or a nitrogen atom,


[0277] G7 is C(—R7), an oxygen atom, a sulfur atom, or a nitrogen atom optionally substituted by R8,


[0278] wherein R1, R2, R3 and R4 are each independently,


[0279] (1) hydrogen atom,


[0280] (2) C1-6 alkanoyl,


[0281] (3) carboxyl,


[0282] (4) cyano,


[0283] (5) nitro,


[0284] (6) C1-6 alkyl optionally substituted by 1 to 3 substituent(s)selected from the following group A,


[0285] group A; halogen atom, hydroxyl group, carboxyl, amino, C1-6 alkoxy, C1-6 alkoxycarbonyl and C1-6 alkylamino,


[0286] (7) —COORa1


[0287] wherein Ra1 is optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group B,


[0288] group B; halogen atom, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2, —(CH2)r—NRb1Rb2, —(CH2)r—NRb1—CORb2, —(CH2)r—NHSO2Rb1, —(CH2)r—ORb1, —(CH2)r—SRb1, —(CH2)r—SO2Rb1 and —(CH2)r—SO2NRb1Rb2 wherein Rb1 and Rb2 are each independently hydrogen atom or C1-6 alkyl and r is 0 or an integer of 1 to 6,


[0289] (8) —CONRa2Ra3


[0290] wherein Ra2 and Ra3 are each independently hydrogen atom, C1-6 alkoxy or optionally substituted C1-6 alkyl (as defined above),


[0291] (9) —C(═NRa4)NH2


[0292] wherein Ra4 is hydrogen atom or hydroxyl group,


[0293] (10) —NHRa5


[0294] wherein Ra5 is hydrogen atom, C1-6 alkanoyl or C1-6 alkylsulfonyl,


[0295] (11) —ORa6


[0296] wherein Ra6 is hydrogen atom or optionally substituted C1-6 alkyl(as defined above),


[0297] (12) —SO2Ra7


[0298] wherein Ra7 is hydroxyl group, amino, C1-6 alkyl or C1-6 alkylamino or


[0299] (13) —P(═O)(ORa31)2


[0300] wherein Ra31 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, and


[0301] R7 and R8 are each hydrogen atom or optionally substituted C1-6 alkyl(as defined above),


[0302] ring Cy is


[0303] (1) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group C, group C; hydroxyl group, halogen atom, C1-6 alkyl and C1-6 alkoxy,


[0304] (2) C3-8 cycloalkenyl optionally substituted by 1 to 5 substituent(s) selected from the above group C, or


[0305] (3)
24


[0306]  wherein u and v are each independently an integer of 1 to 3,


[0307] ring A is


[0308] (1) C6-14 aryl,


[0309] (2) C3-8 cycloalkyl,


[0310] (3) C3-8 cycloalkenyl or


[0311] (4) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,


[0312] R5 and R6 are each independently


[0313] (1) hydrogen atom,


[0314] (2) halogen atom,


[0315] (3) optionally substituted C1-6 alkyl (as defined above) or


[0316] (4) —ORa8


[0317] wherein Ra8 is hydrogen atom, C1-6 alkyl or C6-14 aryl C1-6 alkyl, and


[0318] X is


[0319] (1) hydrogen atom,


[0320] (2) halogen atom,


[0321] (3) cyano,


[0322] (4) nitro,


[0323] (5) amino, C1-6 alkanoylamino,


[0324] (6) C1-6 alkylsulfonyl,


[0325] (7) optionally substituted C1-6 alkyl (as defined above),


[0326] (8) C2-6 alkenyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,


[0327] (9) —COORa9


[0328] wherein Ra9 is hydrogen atom or C1-6 alkyl,


[0329] (10) —CONH—(CH2)1—Ra10


[0330] wherein Ra10 is optionally substituted C1-6 alkyl (as defined above), C1-6 alkoxycarbonyl or C1-6 alkanoylamino and 1 is 0 or an integer of 1 to 6,


[0331] (11) —ORa11


[0332] wherein Ra11 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above) or


[0333] (12)
25


[0334]  wherein


[0335] ring B is


[0336] (1′) C6-14 aryl,


[0337] (2′) C3-8 cycloalkyl or


[0338] (3′) heterocyclic group (as defined above),


[0339] each Z is independently


[0340] (1′) a group selected from the following group D,


[0341] (2′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the following group D,


[0342] (3′) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,


[0343] (4′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D or


[0344] (5′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the following group D


[0345] wherein the heterocyclic group has 1 to 4 hetero-atom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,


[0346] group D:


[0347] (a) hydrogen atom,


[0348] (b) halogen atom,


[0349] (c) cyano,


[0350] (d) nitro,


[0351] (e) optionally substituted C1-6 alkyl (as defined above),


[0352] (f) —(CH2)t—CORa18,


[0353] (hereinafter each t means independently 0 or an integer of 1 to 6),


[0354] wherein Ra18 is


[0355] (1″) optionally substituted C1-6 alkyl (as defined above),


[0356] (2″) C6-14 aryl optionally substituted by 1 to substituent(s) selected from the above group B or


[0357] (3″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,


[0358] (g) —(CH2)t—COORa19


[0359] wherein Ra19 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0360] (h) —(CH2)t—CONRa27Ra28


[0361] wherein Ra27 and Ra28 are each independently,


[0362] (1″) hydrogen atom,


[0363] (2″) optionally substituted C1-6 alkyl (as defined above),


[0364] (3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0365] (4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0366] (5″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0367] (6″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, wherein the heterocycle C1-6 alkyl is C1-6


[0368] alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, as defined above,


[0369] (7″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or


[0370] (8″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0371] (i) —(CH2)t—C(═NRa33)NH2


[0372] wherein Ra33 is hydrogen atom or C1-6 alkyl,


[0373] (j) —(CH2)t—ORa20


[0374] wherein Ra20 is


[0375] (1″) hydrogen atom,


[0376] (2″) optionally substituted C1-6 alkyl (as defined above),


[0377] (3″) optionally substituted C2-6 alkenyl (as defined above),


[0378] (4″) C2-6 alkynyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,


[0379] (5″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0380] (6″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0381] (7″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0382] (8″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0383] (9″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or


[0384] (10″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0385] (k) —(CH2)t—O—(CH2)p—CORa21


[0386] wherein Ra21 is C1-6 alkylamino or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, and p is 0 or an integer of 1 to 6,


[0387] (l) —(CH2)t—NRa22Ra23


[0388] wherein Ra22 and Ra23 are each independently


[0389] (1″) hydrogen atom,


[0390] (2″) optionally substituted C1-6 alkyl (as defined above),


[0391] (3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0392] (4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or


[0393] (5″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0394] (m) —(CH2)t—NRa29CO—Ra24


[0395] wherein Ra29 is hydrogen atom, C1-6 alkyl or C1-6 alkanoyl, Ra24 is optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0396] (n) —(CH2)t—NHSO2—Ra25


[0397] wherein Ra25 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0398] (o) —(CH2)t—S(O)q—Ra25


[0399] wherein Ra25 is as defined above, and q is 0, 1 or 2, and


[0400] (p) —(CH2)t—SO2—NHRa26


[0401] wherein Ra26 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0402] w is an integer of 1 to 3, and


[0403] Y is


[0404] (1′) a single bond,


[0405] (2′) C1-6 alkylene,


[0406] (3′) C2-6 alkenylene,


[0407] (4′) —(CH2)m—O—(CH2)n—,


[0408] (hereinafter m and n are each independently 0 or an integer of 1 to 6),


[0409] (5′) —CO—,


[0410] (6′) —CO2—(CH2)n—,


[0411] (7′) —CONH—(CH2)n—NH—,


[0412] (8′) —NHCO2—,


[0413] (9′) —NHCONH—,


[0414] (10′) —O—(CH2)n—CO—,


[0415] (11′) —O—(CH2)n—O—,


[0416] (12′) —SO2—,


[0417] (13′) —(CH2)m—NRa12—(CH2)n


[0418] wherein Ra12 is


[0419] (1″) hydrogen atom,


[0420] (2″) optionally substituted C1-6 alkyl (as defined above),


[0421] (3″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0422] (4″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0423] (5″) —CORb5


[0424] wherein Rb5 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0425] (6″) —COORb5 (Rb5 is as defined above) or


[0426] (7″) —SO2Rb5 (Rb5 is as defined above),


[0427] (14″) NRa12CO— (Ra12 is as defined above),


[0428] (15′) —CONRa13—(CH2)n


[0429] wherein Ra13 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0430] (16′) —CONH—CHRa14


[0431] wherein Ra14 is C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0432] (17′) —O—(CH2)m—CRa15Ra16—(CH2)n


[0433] wherein Ra15 and Ra16 are each independently


[0434] (1″) hydrogen atom,


[0435] (2″) carboxyl,


[0436] (3″) C1-6 alkyl,


[0437] (4″) —ORb6


[0438] wherein Rb6 is C1-6 alkyl or C6-14 aryl C1-6 alkyl, or


[0439] (5″) —NHRb7


[0440] wherein Rb7 is hydrogen atom, C1-6 alkyl, C1-6 alkanoyl or C6-14 aryl C1-6 alkyloxycarbonyl, or Ra15 is optionally


[0441] (6″)
26


[0442]  wherein n′, ring B′, Z′ and w′ are the same as the above-mentioned n, ring B, Z and w, respectively, and may be the same as or different from the respective counterparts,


[0443] (18′) —(CH2)n—NRa12—CHRa15—(Ra12 and Ra15 are each as defined above),


[0444] (19′) —NRa17SO2


[0445] wherein Ra17 is hydrogen atom or C1-6 alkyl or


[0446] (20′) —S(O)e—(CH2)mCRa15Ra16—(CH2)n— (e is 0, 1 or 2, Ra15 and Ra16 are each as defined above).


[0447] (30) The therapeutic agent of (29) above, wherein 1 to 4 of the G1, G2, G3, G4, G5, G6, G7, G8 and G9 is (are) a nitrogen atom.


[0448] (31) The therapeutic agent of (30) above, wherein G2 is C(—R2) and G6 is a carbon atom.


[0449] (32) The therapeutic agent of (30) or (31) above, wherein G5 is a nitrogen atom.


[0450] (33). The therapeutic agent of (29) above, wherein, in formula [I], the moiety
27


[0451] is a fused ring selected from
2829


[0452] (34) The therapeutic agent of (33) above, wherein, in formula [I], the moiety
30


[0453] is a fused ring selected from
31


[0454] (35) The therapeutic agent of (34) above, which comprises a fused ring compound of the following formula [I-1]
32


[0455] wherein each symbol is as defined in (29), or a pharmaceutically acceptable salt thereof as an active ingredient.


[0456] (36) The therapeutic agent of (34) above, which comprises a fused ring compound of the following formula [I-2]
33


[0457] wherein each symbol is as defined in (29), or a pharmaceutically acceptable salt thereof as an active ingredient.


[0458] (37) The therapeutic agent of (34) above, which comprises a fused ring compound of the following formula [I-3]
34


[0459] wherein each symbol is as defined in (29), or a pharmaceutically acceptable salt thereof as an active ingredient.


[0460] (38) The therapeutic agent of (34) above, which comprises a fused ring compound of the following formula [I-4]
35


[0461] wherein each symbol is as defined in (29), or a pharmaceutically acceptable salt thereof as an active ingredient.


[0462] (39) The therapeutic agent of any of (29) to (38) above, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1, —CONRa2Ra3 or —SO2Ra7 wherein Ra1, Ra2, Ra3 and Ra7 are as defined in (29).


[0463] (40) The therapeutic agent of any of (29) to (39) above, wherein the ring Cy is cyclopentyl, cyclohexyl, cycloheptyl or tetrahydrothiopyranyl.


[0464] (41) The therapeutic agent of any of (29) to (40) above, wherein the ring A is C6-14 aryl.


[0465] (42) A fused ring compound of the following formula [II]
36


[0466] wherein


[0467] the moiety
37


[0468]  is a fused ring selected from
38


[0469]  wherein R1, R2, R3 and R4 are each independently,


[0470] (1) hydrogen atom,


[0471] (2) C1-6 alkanoyl,


[0472] (3) carboxyl,


[0473] (4) cyano,


[0474] (5) nitro,


[0475] (6) C1-6 alkyl optionally substituted by 1 to 3 substituent(s) selected from the following group A,


[0476] group A; halogen atom, hydroxyl group, carboxyl, amino, C1-6 alkoxy, C1-6 alkoxy C1-6 alkoxy, C1-6 alkoxycarbonyl and C1-6 alkylamino,


[0477] (7) —COORa1


[0478] wherein Ra1 is optionally substituted C1-6 alkyl (as defined above), C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group B or glucuronic acid residue,


[0479] group B; halogen atom, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2, —(CH2)r—NRb1Rb2, —(CH2)r—NRb1—CORb2, —(CH2)r—NHSO2Rb1, —(CH2)r—ORb1, —(CH2)r—SRb1, —(CH2)r—SO2Rb1 and —(CH2)r—SO2NRb1Rb2 wherein Rb1 and Rb2 are each independently hydrogen atom or C1-6 alkyl and r is 0 or an integer of 1 to 6,


[0480] (8) —CONRa2Ra3


[0481] wherein Ra2 and Ra3 are each independently hydrogen atom, C1-6 alkoxy or optionally substituted C1-6 alkyl (as defined above),


[0482] (9) —C(═NRa4)NH2


[0483] wherein Ra4 is hydrogen atom or hydroxyl group,


[0484] (10) —NHRa5


[0485] wherein Ra5 is hydrogen atom, C1-6 alkanoyl or C1-6 alkylsulfonyl,


[0486] (11) —ORa6


[0487] wherein Ra6 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above)


[0488] (12) —SO2Ra7


[0489] wherein Ra7 is hydroxyl group, amino, C1-6 alkyl or C1-6 alkylamino,


[0490] (13) —P(═O)(ORa31)2


[0491] wherein Ra31 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or


[0492] (14) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, and


[0493] R7 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above),


[0494] ring Cy′ is


[0495] (1) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group C, group C; hydroxyl group, halogen atom, C1-6 alkyl and C1-6 alkoxy, or


[0496] (2)
39


[0497]  wherein u and v are each independently an integer of 1 to 3,


[0498] ring A′ is a group selected from a group consisting of phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, cyclohexyl, cyclohexenyl, furyl and thienyl,


[0499] R5′ and R6′ are each independently


[0500] (1) hydrogen atom,


[0501] (2) halogen atom,


[0502] (3) optionally substituted C1-6 alkyl (as defined above) or


[0503] (4) hydroxyl group


[0504] ring B is


[0505] (1) C6-14 aryl,


[0506] (2) C3-8 cycloalkyl or


[0507] (3) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,


[0508] each Z is independently


[0509] (1) a group selected from the following group D,


[0510] (2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the following group D,


[0511] (3) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,


[0512] (4) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,


[0513] (5) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the following group D wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or


[0514] (6) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, as defined above,


[0515] group D:


[0516] (a) hydrogen atom,


[0517] (b) halogen atom,


[0518] (c) cyano,


[0519] (d) nitro,


[0520] (e) optionally substituted C1-6 alkyl (as defined above),


[0521] (f) —(CH2)t—CORa18, (hereinafter each t means independently 0 or an integer of 1 to 6),


[0522] wherein Ra18 is


[0523] (1′) optionally substituted C1-6 alkyl (as defined above),


[0524] (2′) C6-14 aryl optionally substituted by 1 to substituent(s) selected from the above group B or


[0525] (3′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,


[0526] (g) —(CH2)t—COORa19


[0527] wherein Ra19 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0528] (h) —(CH2)t—CONRa27Ra28


[0529] wherein Ra27 and Ra28 are each independently,


[0530] (1″) hydrogen atom,


[0531] (2″) optionally substituted C1-6 alkyl (as defined above),


[0532] (3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0533] (4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0534] (5″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0535] (6″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0536] wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, as defined above,


[0537] (7″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B.


[0538] (8″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0539] (9″) hydroxyl group or (10″) C1-6 alkoxy,


[0540] (i) —(CH2)t—C(═NRa33)NH2


[0541] wherein Ra33 is hydrogen atom, C1-6 alkyl, hydroxyl group or C1-6 alkoxy,


[0542] (j) —(CH2)t—ORa20


[0543] wherein Ra20 is


[0544] (1′) hydrogen atom,


[0545] (2′) optionally substituted C1-6 alkyl (as defined above),


[0546] (3′) optionally substituted C2-6 alkenyl (as defined above),


[0547] (4′) C2-6 alkynyl optionally substituted by 1 to 3 substituent(s) selected from the, above group A,


[0548] (5′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0549] (6′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0550] (7′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0551] (8′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0552] (9′) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or


[0553] (10′) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s). selected from the above group B,


[0554] (k) —(CH2)t—O—(CH2)p—CORa21


[0555] wherein Ra21 is amino, C1-6 alkylamino or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, and p is 0 or an integer of 1 to 6,


[0556] (1) —(CH2)t—NRa22Ra23


[0557] wherein Ra22 and Ra23 are each independently


[0558] (1′) hydrogen atom,


[0559] (2′) optionally substituted C1-6 alkyl (as defined above),


[0560] (3′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0561] (4′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected-from the above group B,


[0562] (5′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or


[0563] (6′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0564] (m) —(CH2)t—NRa29CO—Ra24


[0565] wherein Ra29 is hydrogen atom, C1-6 alkyl or C1-6 alkanoyl, and


[0566] Ra24 is


[0567] (1′) amino,


[0568] (2′) C1-6 alkylamino,


[0569] (3′) optionally substituted C1-6 alkyl (as defined above),


[0570] (4′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0571] (5′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, or


[0572] (6′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0573] (n) —(CH2)t—NRa29SO2—Ra25


[0574] wherein Ra29 is as defined above, and Ra25 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0575] (o) —(CH2)t—S(O)q—Ra25


[0576] wherein Ra25 is as defined above, and q is 0, 1 or 2,


[0577] (p) —(CH2)t—SO2—NHRa26


[0578] wherein Ra26 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, and


[0579] (q) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,


[0580] w is an integer of 1 to 3, and


[0581] Y is


[0582] (1) a single bond,


[0583] (2) C1-6 alkylene,


[0584] (3) C2-6 alkenylene,


[0585] (4) —(CH2)m—O—(CH2)n—, (hereinafter m and n are each independently 0 or an integer of 1 to 6),


[0586] (5) —CO—,


[0587] (6) —CO2—(CH2)n—,


[0588] (7) —CONH—(CH2)n—NH—,


[0589] (8) —NHCO2—,


[0590] (9) —NHCONH—,


[0591] (10) —O—(CH2)n—CO—,


[0592] (11) —O—(CH2)n—O—,


[0593] (12) —SO2—,


[0594] (13) —(CH2)m—NRa12—(CH2)n


[0595] wherein Ra12 is


[0596] (1′) hydrogen atom,


[0597] (2′) optionally substituted C1-6 alkyl (as defined above),


[0598] (3′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0599] (4′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0600] (5′) —CORb5


[0601] wherein Rb5 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0602] (6′) —COORb5 (Rb5 is as defined above) or


[0603] (7′) —SO2Rb5 (Rb5 is as defined above),


[0604] (14) —NRa12CO— (Ra12 is as defined above),


[0605] (15) —CONRa13—(CH2)n


[0606] wherein Ra13 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0607] (16) —CONH—CHRa14


[0608] wherein Ra14 is C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0609] (17) —O—(CH2)m—CRa15Ra16—(CH2)n


[0610] wherein Ra15 and Ra16 are each independently


[0611] (1′) hydrogen atom,


[0612] (2′) carboxyl,


[0613] (3′) C1-6 alkyl,


[0614] (4′) —ORb6


[0615] wherein Rb6 is C1-6 alkyl or C6-14 aryl C1-6 alkyl, or


[0616] (5′) —NHRb7


[0617] wherein Rb7 is hydrogen atom, C1-6 alkyl, C1-6 alkanoyl or C6-14 aryl C1-6 alkyloxycarbonyl, or


[0618] Ra15 is optionally


[0619] (6′)
40


[0620]  wherein n′, ring B′, Z′ and w′ are the same as the above-mentioned n, ring B, Z and w, respectively, and may be the same as or different from the respective counterparts,


[0621] (18) —(CH2)n—NRa12—CHRa15—(Ra12 and Ra15 are each as defined above),


[0622] (19) —NRa17SO2


[0623] wherein Ra17 is hydrogen atom or C1-6 alkyl,


[0624] (20) —S(O)e—(CH2)m—CRa15Ra16—(CH2)n— (e is 0, 1 or 2, Ra15 and Ra16 are each as defined above), or


[0625] (21) —(CH2)m—CRa15Ra16—(CH2)n— (Ra15 and Ra16 are each as defined above),


[0626] or a pharmaceutically acceptable salt thereof.


[0627] (43) The fused ring compound of (42) above, which is represented by the following formula [II-1]
41


[0628] wherein each symbol is as defined in (42),


[0629] or a pharmaceutically acceptable salt thereof.


[0630] (44) The fused ring compound of (42) above, which is represented by the following formula [II-2]
42


[0631] wherein each symbol is as defined in (42)


[0632] or a pharmaceutically acceptable salt thereof.


[0633] (45) The fused ring compound of (42) above, which is represented by the following formula [II-3]
43


[0634] wherein each symbol is as defined in. (42),


[0635] or a pharmaceutically acceptable salt thereof.


[0636] (46) The fused ring compound of (42) above, which is represented by the following formula [II-4]
44


[0637] wherein each symbol is as defined in (42),


[0638] or a pharmaceutically acceptable salt thereof.


[0639] (47) The fused ring compound of any of (42) to (46) above,


[0640] wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1, —CONRa2Ra3, —SO2Ra7 (wherein Ra1, Ra2, Ra3 and Ra7 are As defined in (42)),
45


[0641]  or a pharmaceutically acceptable salt thereof.


[0642] (48) The fused ring compound of (47) above, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1 or —SO2Ra7 wherein Ra1 and Ra7 are as defined in (42), or a pharmaceutically acceptable salt thereof.


[0643] (49) The fused ring compound of (48) above, wherein at least one of R1, R2, R3 and R4 is carboxyl or —COORa1 wherein Ra1 is as defined in (42), or a pharmaceutically acceptable salt thereof.


[0644] (50) The fused-ring compound of (49) above, wherein R2 is carboxyl and R1, R3 and R4 are hydrogen atoms, or a pharmaceutically acceptable salt thereof.


[0645] (51) The fused ring compound of any of (42) to (46) above, wherein at least one of R1, R2, R3 and R4 is carboxyl or —COORa1 wherein Ra1 is glucuronic acid residue, or a pharmaceutically acceptable salt thereof.


[0646] (52) The fused ring compound of any of (42) to (46) above, wherein at least one of R1, R2, R3 and R4 is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or a pharmaceutically acceptable salt thereof.


[0647] (53) The fused ring compound of any of (42) to (52) above, wherein the ring Cy′ is cyclopentyl, cyclohexyl, cycloheptyl or tetrahydrothiopyranyl, or a pharmaceutically acceptable salt thereof.


[0648] (54) The fused ring compound of (42) above, wherein the ring Cy′ is cyclopentyl, cyclohexyl or cycloheptyl, or a pharmaceutically acceptable salt thereof.


[0649] (55) The fused ring compound of any of (42) to (52) above, wherein the ring Cy′ is
46


[0650] wherein each symbol is as defined in (42), or a pharmaceutically acceptable salt thereof.


[0651] (56) The fused ring compound of any of (42) to (55) above, wherein the ring A′ is phenyl, pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl, or a pharmaceutically acceptable salt thereof.


[0652] (57) The fused ring compound of (56) above, wherein the ring A′ is phenyl or pyridyl, or a pharmaceutically acceptable salt thereof.


[0653] (58) The fused ring compound of (57) above, wherein the ring A′ is phenyl, or a pharmaceutically acceptable salt thereof.


[0654] (59) The fused ring compound of any of (42) to (58) above, wherein at least one substituent optionaly substituted by group A is a substituent substituted by C1-6 alkoxy C1-6 alkoxy, or a pharmaceutically acceptable salt thereof.


[0655] (60) The fused ring compound of any of (42) to (59) above, wherein the Y is —(CH2)m—O—(CH2)n—, —NHCO2—, —CONH—CHRa14—, —(CH2)m—NRa12—(CH2)n—, —CONRa13—(CH2)n—, —O—(CH2)m—CRa15Ra16—(CH2)n— or —(CH2)n—NRa12—CHRa15— (wherein each symbol is as defined in (42)), or a pharmaceutically acceptable salt thereof.


[0656] (61) The fused ring compound of (42) above, wherein the Y is —(CH2)m—O—(CH2)n— or —O—(CH2)m—CRa15Ra16—(CH2)n— (wherein each symbol is as defined in (42)), or a pharmaceutically acceptable salt thereof.


[0657] (62) The fused ring compound of (61) above, wherein the Y is —(CH2)m—O—(CH2)n— wherein each symbol is as defined in (42), or a pharmaceutically acceptable salt thereof.


[0658] (63) The fused ring compound of any of (42) to (59) above, wherein the Y is —(CH2)m—CRa15Ra16—(CH2)n— (wherein each symbol is as defined in (42)), or a pharmaceutically acceptable salt thereof.


[0659] (64) The fused ring compound of any of (42) to (63) above, wherein the R2 is carboxyl, R1, R3 and R4 are hydrogen atoms, the ring Cy′ is cyclopentyl, cyclohexyl or cycloheptyl, and the ring A′ is phenyl, or a pharmaceutically acceptable salt thereof.


[0660] (65) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by Z is heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the group D, or a pharmaceutically acceptable salt thereof.


[0661] (66) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by Z is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, wherein said heterocyclic group is selected from the following groups:
47


[0662] wherein E1 is an oxygen atom, a sulfur atom or N(—Ra35), E2 is an oxygen atom, CH2 or N(—Ra35), E3 is an oxygen atom or a sulfur atom, wherein each Ra35 is independently hydrogen atom or C1-6 alkyl, f is an integer of 1 to 3, and h and h′ are the same or different and each is an integer of 1 to 3, or a pharmaceutically acceptable salt thereof.


[0663] (67) The fused ring compound of (66) above, wherein at least one group represented by Z is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, wherein said heterocyclic group is selected from the following groups:
48


[0664] wherein each symbol is as defined in (66), or a pharmaceutically acceptable salt thereof.


[0665] (68) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by group D is —(CH2)t—CONRa27Ra28 wherein each symbol is as defined in (42), and at least one of Ra27 and Ra28 is C1-6 alkoxy, or a pharmaceutically acceptable salt thereof.


[0666] (69) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by group D is —(CH2)t—C(═NRa33)NH2 wherein each symbol is as defined in (42), and Ra33 is hydroxyl group or C1-6 alkoxy, or a pharmaceutically acceptable salt thereof.


[0667] (70) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by group D is —(CH2)t—O—(CH2)p—CORa21 wherein each symbol is as defined in (42), and Ra21 is amino, or a pharmaceutically acceptable salt thereof.


[0668] (71) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by group D is —(CH2)t—NRa29CO—Ra24 wherein each symbol is as defined in (42), and Ra24 is amino or C1-6 alkylamino, or a pharmaceutically acceptable salt thereof.


[0669] (72) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by group D is —(CH2)t—NRa22Ra23 wherein each symbol is as defined in (42), and at least one of Ra22 and Ra23 is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group B, or a pharmaceutically acceptable salt thereof.


[0670] (73) The fused ring compound of any of (42) to (64) above, wherein at least one group represented by group D is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or a pharmaceutically acceptable salt thereof.


[0671] (74) The fused ring compound of (42) above, which is represented by the following formula [II]
49


[0672] wherein


[0673] the moiety
50


[0674]  is a fused ring selected from
51


[0675]  wherein R1, R2, R3 and R4 are each independently,


[0676] (1) hydrogen atom,


[0677] (2) C1-6 alkanoyl,


[0678] (3) carboxyl,


[0679] (4) cyano,


[0680] (5) nitro,


[0681] (6) C1-6 alkyl optionally substituted by 1 to 3 substituent(s) selected from the following group A,


[0682] group A; halogen atom, hydroxyl group, carboxyl, amino, C1-6 alkoxy, C1-6 alkoxycarbonyl and C1-6 alkylamino,


[0683] (7) —COORa1


[0684] wherein Ra1 is optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group B,


[0685] group B; halogen atom, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2, —(CH2)r—NRb1Rb2, —(CH2)r—NRb1—CORb2, —(CH2)r—NHSO2Rb1, —(CH2)r—ORb1, —(CH2)r—SRb1, —(CH2)r—SO2Rb1 and —(CH2)r—SO2NRb1Rb2 wherein Rb1 and Rb2 are each independently hydrogen atom or C1-6 alkyl and r is 0 or an integer of 1 to 6,


[0686] (8) —CONRa2Ra3


[0687] wherein Ra2 and Ra3 are each independently hydrogen atom, C1-6 alkoxy or optionally substituted C1-6 alkyl (as defined above),


[0688] (9) —C(═NRa4)NH2


[0689] wherein Ra4 is hydrogen atom or hydroxyl group,


[0690] (10) —NHRa5


[0691] wherein Ra5 is hydrogen atom, C1-6 alkanoyl or C1-6 alkylsulfonyl,


[0692] (11) —ORa6


[0693] wherein Ra6 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above),


[0694] (12) —SO2Ra7


[0695] wherein Ra7 is hydroxyl group, amino, C1-6 alkyl or C1-6 alkylamino or


[0696] (13) —P(═O)(ORa31)2


[0697] wherein Ra31 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, and


[0698] R7 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above),


[0699] ring Cy′ is


[0700] (1) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group C,


[0701] group C; hydroxyl group, halogen atom, C1-6 alkyl and C1-6 alkoxy, or


[0702] (2)
52


[0703] wherein u and v are each independently an integer of 1 to 3,


[0704] ring A′ is a group selected from a group consisting of


[0705] phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, cyclohexyl, cyclohexenyl, furyl and thienyl,


[0706] R5′ and R6′ are each independently


[0707] (1) hydrogen atom,


[0708] (2) halogen atom,


[0709] (3) optionally substituted C1-6 alkyl (as defined above) or


[0710] (4) hydroxyl group


[0711] ring B is


[0712] (1) C6-14 aryl,


[0713] (2) C3-8 cycloalkyl or


[0714] (3) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,


[0715] each Z is independently


[0716] (1) a group selected from the following group D,


[0717] (2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the following group D,


[0718] (3) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,


[0719] (4) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D or


[0720] (5) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the following group D wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, group D:


[0721] (a) hydrogen atom,


[0722] (b) halogen atom,


[0723] (c) cyano,


[0724] (d) nitro,


[0725] (e) optionally substituted C1-6 alkyl (as defined above),


[0726] (f) —(CH2)t—CORa18,


[0727] (hereinafter each t means independently 0 or an integer of 1 to 6),


[0728] wherein Ra18 is


[0729] (1′) optionally substituted C1-6 alkyl (as defined above),


[0730] (2′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or


[0731] (3′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,


[0732] (g) —(CH2)t—COORa19


[0733] wherein Ra19 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0734] (h) —(CH2)t—CONRa27Ra28


[0735] wherein Ra27 and Ra28 are each independently,


[0736] (1″) hydrogen atom,


[0737] (2″) optionally substituted C1-6 alkyl (as defined above),


[0738] (3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0739] (4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0740] (5″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0741] (6″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0742] wherein the heterocycle C1-6 alkyl is C1-6 alkyl substituted by heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, as defined above,


[0743] (7″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or


[0744] (8″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0745] (i) —(CH2)t—C(═NRa33)NH2


[0746] wherein Ra33 is hydrogen atom or C1-6 alkyl,


[0747] (j) —(CH2)t—ORa20


[0748] wherein Ra20 is


[0749] (1′) hydrogen atom,


[0750] (2′) optionally substituted C1-6 alkyl (as defined above),


[0751] (3′) optionally substituted C2-6 alkenyl (as defined above),


[0752] (4′) C2-6 alkynyl optionally substituted by 1 to 3 substituent(s) selected from the above group A.


[0753] (5′) C6-14 aryl optionally substituted by 1 to substituent(s) selected from the above group B,


[0754] (6′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0755] (7′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0756] (8′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0757] (9′) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or


[0758] (10′) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0759] (k) —(CH2)t—O—(CH2)p—CORa21


[0760] wherein Ra21 is C1-6 alkylamino or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group. B,


[0761] and p is 0 or an integer of 1 to 6,


[0762] (l) —(CH2)t—NRa22Ra23


[0763] wherein Ra22 and Ra23 are each independently


[0764] (1′) hydrogen atom,


[0765] (2′) optionally substituted C1-6 alkyl (as defined above),


[0766] (3′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0767] (4′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or


[0768] (5′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0769] (m) —(CH2)t—NRa29CO—Ra24


[0770] wherein Ra29 is hydrogen atom, C1-6 alkyl or C1-6 alkanoyl, Ra24 is optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0771] (n) —(CH2)t—NHSO2—Ra25


[0772] wherein Ra25 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0773] (o) —(CH2)t—S(O)q—Ra25


[0774] wherein Ra24 is as defined above, and q is 0, 1 or 2, and


[0775] (p) —(CH2)t—SO2—NHRa26


[0776] wherein Ra26 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0777] w is an integer of 1 to 3, and


[0778] Y is


[0779] (1) a single bond,


[0780] (2) C1-6 alkylene,


[0781] (3) C2-6 alkenylene,


[0782] (4) —(CH2)m—O—(CH2)n—, (hereinafter m and n are each independently 0 or an integer of 1 to 6),


[0783] (5) —CO—,


[0784] (6) —CO2—(CH2)n—,


[0785] (7) —CONH—(CH2)n—NH—,


[0786] (8) —NHCO2—,


[0787] (9) —NHCONH—,


[0788] (10) —O—(CH2)n—CO—,


[0789] (11) —O—(CH2)n—O—,


[0790] (12) —SO2—,


[0791] (13) —(CH2)m—NRa12—(CH2)n


[0792] wherein Ra12 is


[0793] (1′) hydrogen atom,


[0794] (2′) optionally substituted C1-6 alkyl (as defined above),


[0795] (3′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0796] (4′) C6-14 aryl-optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0797] (5′) —CORb5


[0798] wherein Rb5 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above), C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0799] (6′) —COORb5 (Rb5 is as defined above) or


[0800] (7) —SO2Rb5 (Rb5 is as defined above),


[0801] (14) —NRa12CO— (Ra12 is as defined above),


[0802] (15) —CONRa13—(CH2)n


[0803] wherein Ra13 is hydrogen atom, optionally substituted C1-6 alkyl (as defined above) or C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0804] (16) —CONH—CHRa14


[0805] wherein Ra14 is C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,


[0806] (17) —O—(CH2)mCRa15Ra16—(CH2)n


[0807] wherein Ra15 and Ra16 are each independently


[0808] (1′) hydrogen atom,


[0809] (2′) carboxyl,


[0810] (3′) C1-6 alkyl,


[0811] (4′) —ORb6


[0812] wherein Rb6 is C1-6 alkyl or C6-14 aryl C1-6 alkyl, or


[0813] (5) —NHRb7


[0814] wherein Rb7 is hydrogen atom, C1-6 alkyl, C1-6 alkanoyl or C6-14 aryl C1-6 alkyloxycarbonyl, or Ra15 is optionally


[0815] (6′)
53


[0816] wherein n′, ring B′, Z′ and w′ are the same as the above-mentioned n, ring B, Z and w, respectively, and may be the same as or different from the respective counterparts,


[0817] (18) —(CH2)n—NRa12—CHRa15— (Ra12 and Ra15 are each as defined above),


[0818] (19) —NRa17SO2


[0819] wherein Ra17 is hydrogen atom or C1-6 alkyl or


[0820] (20) —S(O)e—(CH2)m—CRa15Ra16—(CH2)n— (e is 0, 1 or 2,


[0821] Ra15 and Ra16 are each as defined above),


[0822] or a pharmaceutically acceptable salt thereof.


[0823] (75) The fused ring compound of (74) above, which is represented by the following formula [II-1]
54


[0824] wherein each symbol is as defined in (74),


[0825] or a pharmaceutically acceptable salt thereof.


[0826] (76) The fused ring compound of (74) above, which is represented by the following formula [II-2]
55


[0827] wherein each symbol is as defined in (74),


[0828] or a pharmaceutically acceptable salt thereof.


[0829] (77) The fused ring compound of (74) above, which is represented by the following formula [II-3]
56


[0830] wherein each symbol is as defined in (74),


[0831] or a pharmaceutically acceptable salt thereof.


[0832] (78) The fused ring compound of (74) above, which is represented by the following formula [II-4]
57


[0833] wherein each symbol is as defined in (74),


[0834] or a pharmaceutically acceptable salt thereof.


[0835] (79) The fused ring compound of any of (74) to (78) above,


[0836] wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1 or —SO2Ra7 wherein Ra1 and Ra7 are as defined in (74), or a pharmaceutically acceptable salt thereof.


[0837] (80) The fused ring compound of (79) above, wherein at least one of R1, R2, R3 and R4 is carboxyl or —COORa1 wherein Ra1 is as defined in (74), or a pharmaceutically acceptable salt thereof.


[0838] (81) The fused ring compound of (80) above, wherein R2 is carboxyl and R1, R3 and R4 are hydrogen atoms, or a pharmaceutically acceptable salt thereof.


[0839] (82) The fused ring compound of any of (74) to (81) above, wherein the ring Cy′ is cyclopentyl, cyclohexyl, cycloheptyl or tetrahydrothiopyranyl, or a pharmaceutically acceptable salt thereof.


[0840] (83) The fused ring compound of (82) above, wherein the ring Cy′ is cyclopentyl, cyclohexyl or cycloheptyl, or a pharmaceutically acceptable salt thereof.


[0841] (84) The fused ring compound of any of (74) to (83) above, wherein the ring A′ is phenyl, pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl, or a pharmaceutically acceptable salt thereof.


[0842] (85) The fused ring compound of (84) above, wherein the ring A′ is phenyl or pyridyl, or a pharmaceutically acceptable salt thereof.


[0843] (86) The fused ring compound of (85) above, wherein the ring A′ is phenyl, or a pharmaceutically acceptable salt thereof.


[0844] (87) The fused ring compound of any of (74) to (86) above, wherein the Y is —(CH2)m—O—(CH2)n—, —NHCO2—, —CONH—CHRa14—, —(CH2)m—NRa12—(CH2)n—, —CONRa13—(CH2)n—, —O—(CH2)m—CRa15Ra16—(CH2)n— or —(CH2)n—NRa12—CHRa15— (wherein each symbol is as defined in (74)), or a pharmaceutically acceptable salt thereof.


[0845] (88) The fused ring compound of (87) above, wherein the Y is —(CH2)m—O—(CH2)n— or —O—(CH2)m—CRa15Ra16—(CH2)n— (wherein each symbol is as defined in (74)), or a pharmaceutically acceptable salt thereof.


[0846] (89) The fused ring compound of (88) above, wherein the Y is —(CH2)m—O—(CH2)n— wherein each symbol is as defined in (74), or a pharmaceutically acceptable salt thereof.


[0847] (90) The fused ring compound of any of (74) to (89) above, wherein the R2 is carboxyl, R1, R3 and R4 are hydrogen atoms, the ring Cy′ is cyclopentyl, cyclohexyl or cycloheptyl, and the ring A′ is phenyl, or a pharmaceutically acceptable salt thereof.


[0848] (91) The fused ring compound of the formula [I] or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of


[0849] ethyl 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 1),


[0850] 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 2),


[0851] ethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate (Example 3),


[0852] ethyl 2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 4),


[0853] ethyl 2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 5),


[0854] 2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 6),


[0855] ethyl 2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 7),


[0856] ethyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 8),


[0857] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 9),


[0858] ethyl 1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}benzimidazole-5-carboxylate (Example 10),


[0859] 1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}benzimidazole-5-carboxylic acid (Example 11),


[0860] 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 12),


[0861] 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide (Example 13),


[0862] 2-(4-benzyloxyphenyl)-5-cyano-1-cyclopentylbenzimidazole (Example 14),


[0863] 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide oxime (Example 15),


[0864] ethyl 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylate (Example 16),


[0865] 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 17),


[0866] ethyl 1-cyclohexyl-2-(2-fluoro-4-hydroxyphenyl)benzimidazole-5-carboxylate,(Example 18),


[0867] ethyl 2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 19),


[0868] 2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 20),


[0869] ethyl 1-cyclopentyl-2-(4-nitrophenyl)benzimidazole-5-carboxylate (Example 21),


[0870] ethyl 2-(4-aminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate (Example 22),


[0871] ethyl 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate (Example 23),


[0872] 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 24),


[0873] ethyl 2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 25),


[0874] 2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 26),


[0875] ethyl 2-[4-(3-acetoxyphenyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 27),


[0876] ethyl 1-cyclohexyl-2-[4-(3-hydroxyphenyloxy)phenyl]-benzimidazole-5-carboxylate (Example 28),


[0877] ethyl 1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]phenyl}-benzimidazole-5-carboxylate (Example 29),


[0878] 1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]phenyl}-benzimidazole-5-carboxylic acid (Example 30),


[0879] 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole (Example 31),


[0880] ethyl 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylate (Example 32),


[0881] 2-(4-benzyloxyphenyl)-1-cyclopentyl-N,N-dimethylbenzimidazole-5-carboxamide (Example 33),


[0882] 2-(4-benzyloxyphenyl)-1-cyclopentyl-N-methoxy-N-methylbenzimidazole-5-carboxamide (Example 34),


[0883] 2-(4-benzyloxyphenyl)-1-cyclopentyl-5-(1-hydroxy-1-methylethyl)benzimidazole (Example 35),


[0884] 5-acetyl-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole (Example 36),


[0885] 2-(4-benzyloxyphenyl)-1-cyclopentyl-N-(2-dimethylaminoethyl)-benzimidazole-5-carboxamide dihydrochloride (Example 37),


[0886] 2-(4-benzyloxyphenyl)-1-cyclopentyl-5-nitrobenzimidazole (Example 38),


[0887] 5-amino-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole hydrochloride (Example 39),


[0888] 5-acetylamino-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole (Example 40),


[0889] 2-(4-benzyloxyphenyl)-1-cyclopentyl-5-methanesulfonyl-aminobenzimidazole (Example 41),


[0890] 5-sulfamoyl-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole (Example 42),


[0891] 2-[4-(4-tert-butylbenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 43),


[0892] 2-[4-(4-carboxybenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 44),


[0893] 2-[4-(4-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 45),


[0894] 2-{4-[(2-chloro-5-thienyl)methoxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 46),


[0895] 1-cyclopentyl-2-[4-(4-trifluoromethylbenzyloxy)phenyl]-benzimidazole-5-carboxylic acid (Example 47),


[0896] 1-cyclopentyl-2-[4-(4-methoxybenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 48),


[0897] 1-cyclopentyl-2-[4-(4-pyridylmethoxy)phenyl]benzimidazole-5-carboxylic acid hydrochloride (Example 49),


[0898] 1-cyclopentyl-2-[4-(4-methylbenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 50),


[0899] 1-cyclopentyl-2-{4-[(3,5-dimethyl-4-isoxazolyl)methoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 51),


[0900] 1-cyclopentyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylic acid (Example 52),


[0901] [2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazol-5-yl]-carbonylaminoacetic acid (Example 53),


[0902] 2-[4-(2-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 54),


[0903] 2-[4-(3-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 55),


[0904] 2-(4-benzyloxyphenyl)-3-cyclopentylbenzimidazole-5-carboxylic acid (Example 56),


[0905] 2-[4-(benzenesulfonylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 57),


[0906] 1-cyclopentyl-2-[4-(3,5-dichlorophenylcarbonylamino)phenyl]-benzimidazole-5-carboxylic acid (Example 58),


[0907] 2-{4-[(4-chlorophenyl)carbonylamino]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 59),


[0908] 2-{4-[(4-tert-butylphenyl)carbonylamino]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 60),


[0909] 2-{4-[(4-benzyloxyphenyl)carbonylamino]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 61),


[0910] trans-4-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]cyclohexan-1-ol (Example 62),


[0911] trans-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-methoxycyclohexane (Example 63),


[0912] 2-(4-benzyloxyphenyl)-5-carboxymethyl-1-cyclopentylbenzimidazole (Example 64),


[0913] 2-[1-benzyloxycarbonyl-4-piperidyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 65),


[0914] 2-[(4-cyclohexylphenyl)carbonylamino]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 66),


[0915] 1-cyclopentyl-2-[4-(3,5-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 67),


[0916] 1-cyclopentyl-2-[4-(3,4-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 68),


[0917] 1-cyclopentyl-2-[4-(phenylcarbamoylamino)phenyl]benzimidazole-5-carboxylic acid (Example 69),


[0918] 1-cyclopentyl-2-[4-(diphenylmethoxy)phenyl]benzimidazole-5-carboxylic acid (Example 70),


[0919] 1-cyclopentyl-2-(4-phenethyloxyphenyl)benzimidazole-5-carboxylic acid (Example 71),


[0920] trans-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-tert-butylcyclohexane (Example 72),


[0921] 2-(4-benzyloxyphenyl)-5-carboxymethoxy-1-cyclopentylbenzimidazole (Example 73),


[0922] 2-(4-benzylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 74),


[0923] 2-[4-(N-benzenesulfonyl-N-methylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 75),


[0924] 2-[4-(N-benzyl-N-methylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 76),


[0925] 1-cyclohexyl-2-(4-phenethylphenyl)benzimidazole-5-carboxylic acid (Example 77),


[0926] 2-(1-benzyl-4-piperidyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 78),


[0927] 2-(1-benzoyl-4-piperidyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 79),


[0928] 1-cyclopentyl-2-[1-(p-toluenesulfonyl)-4-piperidyl]-benzimidazole-5-carboxylic acid (Example 80),


[0929] 1-cyclohexyl-2-[4-(3,5-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 81),


[0930] 1-cyclohexyl-2-[4-(diphenylmethoxy)phenyl]benzimidazole-5-carboxylic acid (Example 82),


[0931] 1-cyclohexyl-2-[4-(3,5-di-tert-butylbenzyloxy)phenyl]-benzimidazole-5-carboxylic acid (Example 83),


[0932] 2-(4-benzyloxyphenyl)-1-(4-methylcyclohexyl)benzimidazole-5-carboxylic acid (Example 84),


[0933] 1-cyclohexyl-2-{4-[2-(2-naphthyl)ethoxy]phenyl}benzimidazole-5-carboxylic acid (Example 85),


[0934] 1-cyclohexyl-2-[4-(1-naphthyl)methoxyphenyl]benzimidazole-5-carboxylic acid (Example 86),


[0935] 1-cyclohexyl-2-[4-(dibenzylamino)phenyl]benzimidazole-5-carboxylic acid (Example 87),


[0936] 2-[4-(2-biphenylylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 88),


[0937] 2-(4-benzyloxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 89),


[0938] 1-cyclohexyl-2-[4-(dibenzylmethoxy)phenyl]benzimidazole-5-carboxylic acid (Example 90),


[0939] 2-(4-benzoylmethoxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 91),


[0940] 2-(4-benzyl-1-piperazinyl)-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 92),


[0941] 1-cyclohexyl-2-[4-(3,3-diphenylpropyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 93),


[0942] 2-[4-(3-chloro-6-phenylbenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 94),


[0943] 2-(4-benzyloxypiperidino)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 95),


[0944] 1-cyclohexyl-2-{4-[2-(phenoxy)ethoxy]pheny}benzimidazole-5-carboxylic acid (Example 96),


[0945] 1-cyclohexyl-2-[4-(3-phenylpropyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 97),


[0946] 1-cyclohexyl-2-[4-(5-phenylpentyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 98),


[0947] 2-(3-benzyloxy-5-isoxazolyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 99),


[0948] 2-(2-benzyloxy-5-pyridyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 100),


[0949] 1-cyclohexyl-2-{4-[2-(3,4,5-trimethoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 101),


[0950] 2-(4-benzyloxyphenyl)-1-(4,4-dimethylcyclohexyl)benzimidazole-5-carboxylic acid (Example 102),


[0951] 1-cyclohexyl-2-{4-[2-(1-naphthyl)ethoxy]phenyl}benzimidazole-5-carboxylic acid (Example 103),


[0952] 2-[4-(2-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 104),


[0953] 2-[4-(3-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 105),


[0954] 1-cyclohexyl-2-[4-(2-hydroxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 106),


[0955] 1-cyclohexyl-2-[4-(3-hydroxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 107),


[0956] 1-cyclohexyl-2-[4-(2-methoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 108),


[0957] 1-cyclohexyl-2-[4-(3-methoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 109),


[0958] 1-cyclohexyl-2-[4-(2-propoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 110),


[0959] 1-cyclohexyl-2-[4-(3-propoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 111),


[0960] 1-cyclohexyl-2-{4-[2-(3-methyl-2-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 112),


[0961] 1-cyclohexyl-2-{4-[3-(3-methyl-2-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 113),


[0962] 1-cyclohexyl-2-[4-(2-isopentyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 114),


[0963] 1-cyclohexyl-2-[4-(3-isopentyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 115),


[0964] 1-cyclohexyl-2-{4-[2-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)ethoxy]phenyl}benzimidazole-5-carboxylic acid (Example 116),


[0965] 1-cyclohexyl-2-{4-[2-(4-trifluoromethylphenyl)benzyloxy]-phenyl}benzimidazole-5-carboxylic acid (Example 117),


[0966] 2-{4-[bis(4-chlorophenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 118),


[0967] 1-cyclohexyl-2-{4-[2-(4-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 119),


[0968] 1-cyclohexyl-2-{4-[2-(2-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 120),


[0969] 1-cyclohexyl-2-{4-[2-(3-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 121),


[0970] 2-(4-benzyloxyphenyl)-1-cycloheptylbenzimidazole-5-carboxylic acid (Example 122),


[0971] 1-cyclohexyl-2-[4-(2-phenethyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 123),


[0972] 1-cyclohexyl-2-[4-(3-phenethyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 124),


[0973] 1-cyclohexyl-2-[4-(2,2-diphenylethoxy)phenyl]benzimidazole-5-carboxylic acid (Example 125),


[0974] 2-(4-benzyloxyphenyl)-1-(3-cyclohexenyl)benzimidazole-5-carboxylic acid (Example 126),


[0975] cis-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-fluorocyclohexane (Example 127),


[0976] 1-cyclohexyl-2-[4-(2-phenoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 128),


[0977] 1-cyclohexyl-2-[4-(3-phenoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 129),


[0978] 2-{4-[(2R)-2-benzyloxycarbonylamino-2-phenylethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 130),


[0979] 1-cyclohexyl-2-{2-fluoro-4-[2-(4-trifluoromethylphenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid (Example 131),


[0980] 2-[4-(4-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 132),


[0981] 2-{4-[bis(4-methylphenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 133),


[0982] 2-{4-[bis(4-fluorophenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 134),


[0983] 1-cyclohexyl-6-methoxy-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic acid (Example 135),


[0984] 1-cyclohexyl-6-hydroxy-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic acid (Example 136),


[0985] 1-cyclohexyl-6-methyl-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic acid (Example 137),


[0986] 2-{4-[2-(2-benzyloxyphenyl)ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 138),


[0987] 2-{4-[2-(3-benzyloxyphenyl)ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 139),


[0988] 2-[4-(2-carboxymethyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 140),


[0989] 2-[4-(3-carboxymethyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 141),


[0990] 2-{4-[3-chloro-6-(4-methylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 142),


[0991] 2-{4-[3-chloro-6-(4-methoxyphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 143),


[0992] 1-cyclohexyl-2-{2-methyl-4-[2-(4-trifluoromethylphenyl)-benzyloxy]pheny}benzimidazole-5-carboxylic acid (Example 144),


[0993] 2-{4-[2-(4-tert-butylphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 145),


[0994] 2-{4-(3-chloro-6-phenylbenzyloxy)-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 146),


[0995] 2-{4-[3-chloro-6-(3,5-dichlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 147),


[0996] 2-{4-[bis(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 148),


[0997] 2-{4-(4-benzyloxyphenoxy)-2-chlorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 149),


[0998] 2-{4-(4-benzyloxyphenoxy)-2-trifluoromethylphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 150),


[0999] 2-{4-[3-chloro-6-(2-trifluoromethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 151),


[1000] 2-{4-[(2R)-2-amino-2-phenylethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 152),


[1001] 2-(4-(2-biphenylyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 153),


[1002] 2-[4-(3-biphenylyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 154),


[1003] 2-{4-[2-{(1-tert-butoxycarbonyl-4-piperidyl)methoxy}phenoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 155),


[1004] 2-{4-[3-{(1-tert-butoxycarbonyl-4-piperidyl)methoxy}phenoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 156),


[1005] 2-{4-[3-chloro-6-(3,4,5-trimethoxyphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 157),


[1006] 2-{4-[2-(2-biphenylyl)ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 158),


[1007] 2-[4-(2-biphenylylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 159),


[1008] 1-cyclohexyl-2-{4-[2-(4-piperidylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid hydrochloride (Example 160),


[1009] 1-cyclohexyl-2-{4-[3-(4-piperidylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid hydrochloride (Example 161),


[1010] 2-{4-[(2R)-2-acetylamino-2-phenylethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 162),


[1011] 1-cyclohexyl-2-{4-[3-(4-methyl-3-pentenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 163),


[1012] 1-cyclohexyl-2-{4-[3-(3-methyl-3-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 164),


[1013] 2-{4-[{(2S)-1-benzyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid hydrochloride (Example 165),


[1014] 2-{4-[3-chloro-6-(4-methylthiophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 166),


[1015] 2-{4-[3-chloro-6-(4-methanesulfonylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 167),


[1016] 2-{4-[3-chloro-6-(2-thienyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 168),


[1017] 2-{4-[3-chloro-6-(3-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 169),


[1018] 2-4-[3-chloro-6-(3-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 170),


[1019] 2-{4-[3-chloro-6-(4-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 171),


[1020] 2-[4-(4-benzyloxyphenoxy)-3-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 172),


[1021] 2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 173),


[1022] 2-{4-[3-chloro-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 174),


[1023] 2-{4-[2-{(1-acetyl-4-piperidyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 175),


[1024] 2-{4-[3-{(1-acetyl-4-piperidyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 176),


[1025] 1-cyclohexyl-2-{4-[3-(2-propynyloxy)phenoxy]phenyl}benzimidazole-5-carboxylic acid (Example 177),


[1026] 1-cyclohexyl-2-{4-[3-(3-pyridylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 178),


[1027] 2-(4-benzyloxy-2-methoxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 179),


[1028] 2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 180),


[1029] 2-[4-(carboxydiphenylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 181),


[1030] 2-{4-[2-(4-chlorophenyl)-5-nitrobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 182),


[1031] 2-{4-[3-acetylamino-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 183),


[1032] 2-{4-[2-(4-carboxyphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 184),


[1033] 2-{4-[{(2S)-1-benzyloxycarbonyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 185),


[1034] 2-{2-chloro-4-[2-(4-trifluoromethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 186),


[1035] 1-cyclohexyl-2-{4-[3-(2-pyridylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 187),


[1036] 2-{4-[2-(4-chlorophenyl)-5-fluorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 188),


[1037] 2-{4-[3-carboxy-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 189),


[1038] 2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 190),


[1039] 1-cyclohexyl-2-{4-[2-(dimethylcarbamoylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 191),


[1040] 1-cyclohexyl-2-{4-[2-(piperidinocarbonylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 192),


[1041] 2-{4-[{(2S)-1-benzenesulfonyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 193),


[1042] 2-{4-[{(2S)-1-benzoyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 194),


[1043] 2-{4-[2-(4-carbamoylphenyl)-5-chlorobenzyloxy]phenyl}1-cyclohexylbenzimidazole-5-carboxylic acid (Example 195),


[1044] 1-cyclohexyl-2-{4-[3-(dimethylcarbamoylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 196),


[1045] 1-cyclohexyl-2-{4-[3-(piperidinocarbonylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 197),


[1046] 1-cyclohexyl-2-{4-[3-{(1-methanesulfonyl-4-piperidyl)methoxy}-phenoxy]phenyl}benzimidazole-5-carboxylic acid (Example 198),


[1047] 1-cyclohexyl-2-{4-[{2-methyl-5-(4-chlorophenyl)-4-oxazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 199),


[1048] 2-{4-[3-(3-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 200),


[1049] 2-{4-[3-(4-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 201),


[1050] 1-cyclohexyl-2-{4-[3-(4-fluorobenzyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 202),


[1051] 1-cyclohexyl-2-{4-[{(2S)-1-(4-nitrophenyl)-2-pyrrolidinyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 203),


[1052] 1-cyclohexyl-2-{4-[{(2S)-1-phenyl-2-pyrrolidinyl}methoxy]-phenyl}benzimidazole-5-carboxylic acid hydrochloride (Example 204),


[1053] 2-{4-[{(2S)-1-(4-acetylaminophenyl)-2-pyrrolidinyl}methoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 205),


[1054] 2-{4-[{5-(4-chlorophenyl)-2-methyl-4-thiazolyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 206),


[1055] 2-{4-[bis(3-fluorophenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 207),


[1056] 1-cyclohexyl-2-{4-[2-(4-chlorophenyl)-3-nitrobenzyloxy]phenyl}-benzimidazole-5-carboxylic acid (Example 208),


[1057] 1-cyclohexyl-2-{4-[3-(4-tetrahydropyranyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 209),


[1058] 1-cyclohexyl-2-{4-[3-(4-trifluoromethylbenzyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 210),


[1059] 1-cyclohexyl-2-{4-[3-{(1-methyl-4-piperidyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 211),


[1060] 2-{4-[3-(4-tert-butylbenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 212),


[1061] 2-{4-[3-(2-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 213),


[1062] 1-cyclohexyl-2-{4-[3-(3-pyridyl)phenoxy]pheny}benzimidazole-5-carboxylic acid (Example 214),


[1063] 2-{4-[3-(4-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 215),


[1064] 1-cyclohexyl-2-{4-[3-(4-methoxyphenyl)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 216),


[1065] 1-cyclohexyl-2-{4-[{4-(4-methanesulfonylphenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 217),


[1066] 2-{4-[{4-(4-chlorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 218),


[1067] 2-{4-[1-(4-chlorobenzyl)-3-piperidyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 219),


[1068] 1-cyclohexyl-2-{4-[3-{(2-methyl-4-thiazolyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 220),


[1069] 1-cyclohexyl-2-{4-[3-{(2,4-dimethyl-5-thiazolyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 221),


[1070] 1-cyclohexyl-2-{4-[3-(3,5-dichlorophenyl)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 222),


[1071] 2-{4-[1-(4-chlorobenzyl)-4-piperidyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 223),


[1072] 2-{4-[3-(4-chlorobenzyloxy)piperidino]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 224),


[1073] 2-{4-[4-carbamoyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 225),


[1074] 2-{4-[4-(4-chlorobenzyloxy)piperidino]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 226),


[1075] 2-{4-[3-{(2-chloro-4-pyridyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 227),


[1076] 2-{4-[{(2S)-1-(4-dimethylcarbamoylphenyl)-2-pyrrolidinyl}-methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 228),


[1077] 2-{4-[2-(4-chlorophenyl)-5-ethoxycarbonylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 229),


[1078] 1-cyclohexyl-2-[4-(3-trifluoromethylphenoxy)phenyl]-benzimidazole-5-carboxylic acid (Example 230),


[1079] 1-cyclohexyl-2-{4-[{4-(4-dimethylcarbamoylphenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 231),


[1080] 2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 232),


[1081] 2-{4-[{4-(4-chlorophenyl)-2-methyl-5-pyrimidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 233),


[1082] 2-{4-[{2-(4-chlorophenyl)-3-pyridyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 234),


[1083] 2-{4-[{3-(4-chlorophenyl)-2-pyridyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 235),


[1084] 2-{4-[2-(3-chlorophenyl)-4-methylamino-1,3,5-triazin-6-yloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid trifluoroacetate (Example 236),


[1085] 2-{4-[2-(4-chlorophenyl)-4-(5-tetrazolyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 237),


[1086] 2-[4-(4-benzyloxy-6-pyrimidinyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 238),


[1087] 1-cyclohexyl-2-{4-[4-(4-pyridylmethoxy)-6-pyrimidinyloxy]phenyl}-benzimidazole-5-carboxylic acid (Example 239),


[1088] 2-{4-[4-(3-chlorophenyl)-6-pyrimidinyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 240),


[1089] methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 241),


[1090] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid hydrochloride (Example 242),


[1091] ethyl 2-{4-[3-(4-chlorophenyl)pyridin-2-ylmethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 243),


[1092] methyl 2-[4-(2-bromo-5-tert-butoxycarbonylbenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 244),


[1093] methyl 2-{4-[5-tert-butoxycarbonyl-2-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 245),


[1094] methyl 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride (Example 246),


[1095] methyl 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 247),


[1096] 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 248),


[1097] 2-{4-[3-(tert-butylsulfamoyl)-6-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 249),


[1098] 2-{4-[2-(4-chlorophenyl)-5-sulfamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid trifluoroacetate (Example 250),


[1099] 2-(4-benzyloxycyclohexyl)-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 251),


[1100] 2-[2-(2-biphenylyloxymethyl)-5-thienyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 252),


[1101] 2-[2-(2-biphenylyloxymethyl)-5-furyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 253),


[1102] 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-hydroxymethyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 254),


[1103] 1-cyclohexyl-2-{4-[{4-(4-carboxyphenyl)-2-methyl-5-thiazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid hydrochloride (Example 255),


[1104] 1-cyclohexyl-2-{2-fluoro-4-[4-fluoro-2-(3-fluorobenzoyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid (Example 256),


[1105] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-sulfonic acid (Example 257),


[1106] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-3-cyclohexylbenzimidazole-4-carboxylic acid (Example 258),


[1107] 1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-5-(4-pyridylmethoxy)-phenoxy]phenyl}benzimidazole-5-carboxylic acid dihydrochloride (Example 259),


[1108] 1-cyclohexyl-2-{4-[3-carboxy-5-(4-pyridylmethoxy)phenoxy]-phenylbenzimidazole-5-carboxylic acid dihydrochloride (Example 260),


[1109] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-4-carboxylic acid (Example 261),


[1110] 2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 262),


[1111] 2-{4-[{2-(4-carboxyphenyl)-3-pyridyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 263),


[1112] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-(4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 264),


[1113] 2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 265),


[1114] 1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-6-(4-trifluoromethylphenyl)benzyloxy]phenyl}benzimidazole-5-carboxylic acid hydrochloride (Example 266),


[1115] 1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-6-(4-methylthiophenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid hydrochloride (Example 267),


[1116] 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 268),


[1117] 2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 269),


[1118] 2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 270),


[1119] 2-{4-[3-dimethylcarbamoyl-6-(4-methanesulfonylphenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 271),


[1120] 2-{4-[3-dimethylcarbamoyl-6-(3-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 272),


[1121] 2-{4-[3-dimethylcarbamoyl-6-(4-dimethylcarbamoylphenyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 273),


[1122] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-(1-oxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 274),


[1123] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-(1,1-dioxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 275),


[1124] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]-2-fluorophenyl}-1-(4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 276),


[1125] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]-2-fluorophenyl}-1-(1-oxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 277),


[1126] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]-2-fluorophenyl}-1-(1,1-dioxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 278),


[1127] 2-{4-[2-(4-chlorophenyl)-5-dimethylsulfamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 279),


[1128] 2-{4-[2-(4-chlorophenyl)-5-methanesulfonylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 280),


[1129] methyl 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride (Example 281),


[1130] 2-{4-[2-(4-chlorophenyl)-5-dimethylaminobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 282),


[1131] 2-{4-[2-(4-chlorophenyl)-5-methanesulfonylaminobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 283),


[1132] 2-{4-[2-(4-chlorophenyl)-5-diethylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 284),


[1133] 2-{4-[2-(4-chlorophenyl)-5-isopropylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 285),


[1134] 2-{4-[2-(4-chlorophenyl)-5-piperidinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 286),


[1135] 2-{4-[2-(4-chlorophenyl)-5-(1-pyrrolidinyl)carbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 287),


[1136] 2-{4-[2-(4-chlorophenyl)--5-(2-hydroxyethyl)carbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 288),


[1137] 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidino)-carbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 289),


[1138] 2-{4-[2-(4-chlorophenyl)-5-morpholinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 290),


[1139] 2-{4-[2-(4-chlorophenyl)-5-thiomorpholinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 291),


[1140] 2-{4-[3-(carboxymethylcarbamoyl)-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 292),


[1141] 2-{4-[2-{4-(2-carboxyethyl)phenyl}-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 293),


[1142] 2-{4-[3-chloro-6-(4-hydroxymethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 294),


[1143] 2-{4-[3-chloro-6-(4-methoxymethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 295),


[1144] 2-{4-[2-(3-carboxyphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 296),


[1145] 2-{4-[2-(4-chlorophenyl)-5-methylthiobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 297),


[1146] 2-{4-[2-(4-chlorophenyl)-5-methylsulfinylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 298),


[1147] 2-{4-[2-(4-chlorophenyl)-5-cyanobenzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid hydrochloride (Example 299),


[1148] 2-{4-[bis(3-pyridyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 300),


[1149] 2-{4-[bis(4-dimethylcarbamoylphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 301),


[1150] sodium 2-{4-[2-thienyl-3-thienylmethoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 302),


[1151] methyl 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 303),


[1152] sodium 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 304),


[1153] 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 305),


[1154] 2-{4-[2-(4-carboxyphenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 306),


[1155] 2-{4-[2-(4-carbamoylphenyl)-5-(dimethylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 307),


[1156] 2-{4-[5-amino-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 308),


[1157] 2-{4-[5-(4-chlorophenyl)-2-methoxybenzylsulfinyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 309),


[1158] 2-{4-[5-(4-chlorophenyl)-2-methoxybenzylsulfonyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 310),


[1159] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzylthio]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 311),


[1160] 2-{4-[bis(4-carboxyphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 312),


[1161] 2-[4-(phenyl-3-pyridylmethoxy)-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 313),


[1162] methyl 2-{4-[2-(4-chlorophenyl)-5-(methylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 314),


[1163] 2-{4-[5-chloro-2-(4-pyridyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 315),


[1164] 2-{4-[2-(4-chlorophenyl)-5-(benzylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 316),


[1165] 2-{4-[2-(4-chlorophenyl)-5-(cyclohexylmethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 317),


[1166] 2-{4-[2-(4-chlorophenyl)-5-(4-pyridylmethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 318),


[1167] 2-{4-[2-(4-chlorophenyl)-5-(N-benzyl-N-methylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 319),


[1168] methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylate (Example 501),


[1169] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylic acid (Example 502),


[1170] 2-(4-benzyloxyphenyl)-1-cyclopentyl-1H-indole-5-carboxylic acid (Example 503),


[1171] ethyl 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylate (Example 601),


[1172] 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylic acid (Example 602), and


[1173] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-3-cyclohexyl-3H-imidazo[4,5-b]pyridine-6-carboxylic acid (Example 701).


[1174] (92) The fused ring compound of the formula [I] or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of


[1175] 2-{4-[5-dimethylaminocarbonyl-2-(4-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 320),


[1176] 2-{4-[2-(4-chlorophenyl)-5-(4-methylpiperazin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 321),


[1177] 2-{4-[2-(4-chlorophenyl)-5-{N-(3-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 322),


[1178] 2-{4-[2-(4-chlorophenyl)-5-{N-(2-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 323),


[1179] 2-{4-[2-(4-chlorophenyl)-5-(cyclohexylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 324),


[1180] 2-{4-[2-(4-chlorophenyl)-5-(2-pyridin-4-ylethylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 325),


[1181] 2-{4-[(4-fluorophenyl){4-(dimethylaminocarbonyl)phenyl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 326),


[1182] 2-{4-[(4-fluorophenyl)(4-carboxyphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 327),


[1183] 2-{4-[2-(4-chlorophenyl)-5-(4-oxopiperidinocarbonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 328),


[1184] 2-{4-[2-(4-chlorophenyl)-5-hydroxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 329),


[1185] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 330),


[1186] 2-{4-[2-(4-chlorophenyl)-5-(N-isopropyl-N-methylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 331),


[1187] 2-{4-[2-(4-chlorophenyl)-5-(phenylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 332),


[1188] 2-{4-[2-(4-chlorophenyl)-5-(4-methoxypiperidinocarbonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 333),


[1189] 2-{4-[2-(4-chlorophenyl)-5-(3-hydroxypropyloxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 334), and


[1190] 2-{4-[2-(4-chlorophenyl)-5-(2-hydroxyethoxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 335).


[1191] (93) The fused ring compound of the formula [I] or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of


[1192] methyl 2-[4-(2-bromo-5-nitrobenzyloxy)-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 336),


[1193] methyl 2-[4-{2-(4-chlorophenyl)-5-nitrobenzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 337),


[1194] methyl 2-[4-{5-amino-2-(4-chlorophenyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 338),


[1195] methyl 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 339),


[1196] 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 340),


[1197] 2-{4-[2-(4-chlorophenyl)-5-(4-methylpiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 341),


[1198] 2-{4-[5-acetyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 342),


[1199] 2-{4-[2-(4-chlorophenyl)-5-{(4-hydroxypiperidin-1-ylcarbonyl)-methoxy}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 343),


[1200] 2-{4-[2-(4-chlorophenyl)-5-(2-methoxyethoxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 344),


[1201] 2-{4-[2-(4-chlorophenyl)-5-{2-(2-methoxyethoxy)ethoxy}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 345),


[1202] 2-{4-[2-(4-chlorophenyl)-5-(isobutylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 346),


[1203] 2-{4-[2-(4-chlorophenyl)-5-(2-methylthiazol-4-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 347),


[1204] 2-{4-[2-(4-chlorophenyl)-5-(3,4-dihydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 348),


[1205] 2-{4-[2-(4-chlorophenyl)-5-(3-methyl-1,2,4-oxadiazol-5-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 349),


[1206] 2-{4-[2-(4-chlorophenyl)-4-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 350),


[1207] 2-{4-[2-(4-chlorophenyl)-4-(piperidinocarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 351),


[1208] 2-{4-[2-(4-chlorophenyl)-5-{(1-hydroxy-2-methylpropan-2-yl)carbamoyl}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 352),


[1209] 2-{4-[2-(4-chlorophenyl)-5-(4,4-dimethyl-2-oxazolin-2-yl)}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 353),


[1210] 2-{4-[2-(4-chlorophenyl)-4-(4-hydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 354),


[1211] 2-{4-[2-(4-chlorophenyl)-4-{(2-hydroxyethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 355),


[1212] 2-{4-[2-(4-chlorophenyl)-4-{(4-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 356),


[1213] 2-{4-[2-(4-chlorophenyl)-4-(dimethylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 357),


[1214] 2-{4-[5-(2-aminothiazol-4-yl)-2-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 358),


[1215] 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylsulfonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 359),


[1216] 2-{4-[5-(dimethylcarbamoyl)-2-(4-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 360),


[1217] 2-{4-[5-(dimethylcarbamoyl)-2-(3-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 361),


[1218] 2-{4-[2-(5-chlorothiophen-2-yl)-5-(dimethylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 362),


[1219] 2-{4-[2-bromo-5-(5-methyloxazol-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 363),


[1220] 2-{4-[2-bromo-5-(5-methylthiazol-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 364),


[1221] 2-{4-[2-(4-chlorophenyl)-5-(5-methyloxazol-2-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 365),


[1222] 2-{4-[2-(4-chlorophenyl)-5-(5-methylthiazol-2-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 366),


[1223] 2-{4-[2-(4-chlorophenyl)-5-tetrazol-5-ylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 367),


[1224] 2-{4-[5-chloro-2-(4-cyanophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 368),


[1225] 2-{4-[5-chloro-2-(4-tetrazol-5-ylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 369),


[1226] 2-{4-[2-(4-chlorophenyl)-5-{2-(4-hydroxypiperidin-1-yl)ethoxy}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 370),


[1227] 2-{4-[2-(4-chlorophenyl)-5-(2-oxopiperidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 371),


[1228] 2-{4-[3-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 372),


[1229] 2-{4-[2-(4-chlorophenyl)-5-(N-hydroxyamidino)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 373),


[1230] 2-{4-[2-(4-chlorophenyl)-5-(2,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 374),


[1231] 2-{4-[2-(4-chlorophenyl)-5-(2-oxo-3H-1,2,3,5-oxathiadiazol-4-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 375),


[1232] 2-{4-[2-(4-chlorophenyl)-5-(2,5-dihydro-5-oxo-4H-1,2,4-thiadiazol-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 376),


[1233] 2-{4-[2-(4-chlorophenyl)-5-(cyclopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 377),


[1234] 2-{4-[2-(4-chlorophenyl)-5-(cyclobutylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 378),


[1235] 2-{4-[2-(4-chlorophenyl)-5-(tert-butylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 379),


[1236] 2-{4-[2-(4-chlorophenyl)-5-(isobutylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 380),


[1237] 2-{4-[2-(4-chlorophenyl)-5-{(1-hydroxypropan-2-yl)carbamoyl}-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 381),


[1238] 2-{4-[2-(4-chlorophenyl)-5-(methoxycarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 382),


[1239] 2-{4-[2-(4-chlorophenyl)-5-{(2,3-dihydroxypropyl)carbamoyl}-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 383),


[1240] 2-{4-[2-(4-chlorophenyl)-5-(N-ethyl-N-methylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 384),


[1241] 2-{4-[2-(4-chlorophenyl)-5-(N-methyl-N-propylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 385),


[1242] 2-{4-[2-(4-chlorophenyl)-5-(N-isopropyl-N-methylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 386),


[1243] 2-{4-[2-(4-chlorophenyl)-5-(2,6-dimethylpiperidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 387),


[1244] 2-{4-[5-(butylcarbamoyl)-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 388),


[1245] 2-{4-[2-(4-chlorophenyl)-5-(propylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 389),


[1246] 2-{4-[2-(4-chlorophenyl)-5-(ethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 390),


[1247] 2-{4-[2-(4-chlorophenyl)-5-{(dimethylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 391),


[1248] 2-{4-[2-(4-chlorophenyl)-5-{(morpholinocarbonyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 392),


[1249] 2-{4-[2-(4-chlorophenyl)-5-ureidobenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 393),


[1250] 2-{4-[2-(4-chlorophenyl)-5-{(ethylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 394),


[1251] 2-{4-[2-(4-chlorophenyl)-5-{(isopropylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 395),


[1252] 2-{4-(2-(3,4-difluorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 396),


[1253] 2-{4-[2-(2,4-difluorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 397),


[1254] 2-{4-[2-(3,5-dichlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 398),


[1255] 2-{4-[2-(3-chloro-4-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 399),


[1256] 2-{4-[2-(3,4-dichlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 400),


[1257] 2-{4-[2-(4-chloro-2-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 401),


[1258] 2-{4-[2-(4-chloro-2-fluorophenyl)-5-(pyrrolidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 402),


[1259] 2-{4-[2-(4-chloro-3-fluorophenyl)-5-(pyrrolidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 403),


[1260] 2-{4-[2-(4-chloro-3-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 404),


[1261] 2-{4-[2-{4-(methylthio)phenyl}-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 405),


[1262] 2-{4-[2-{4-(methylthio) phenyl}-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 406),


[1263] 2-{4-[4-chloro-2-(4-chlorophenyl)-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 407),


[1264] 2-{4-[4-chloro-2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 408),


[1265] 2-{4-[2-(4-chlorophenyl)-5-(isopropylaminosulfonyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 409),


[1266] 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 410),


[1267] 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 411),


[1268] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 412),


[1269] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 413),


[1270] 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 414),


[1271] 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 415),


[1272] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 416),


[1273] 2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-phenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 417),


[1274] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 418),


[1275] 2-{4-[2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 419),


[1276] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-piperidinobenzimidazole-5-carboxylic acid hydrochloride (Example 420),


[1277] 2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-2-fluorophenyl}-1-piperidinobenzimidazole-5-carboxylic acid (Example 421),


[1278] 2-{4-[2-(4-chlorophenyl)-5-(2-imidazolin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 422),


[1279] 2-{4-[2-(4-chlorophenyl)-5-(2-oxooxazolidin-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 423),


[1280] 2-{4-[2-(4-chlorophenyl)-5-(2-oxoimidazolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 424),


[1281] 2-{4-[2-(4-chlorophenyl)-5-(2-oxazolin-2-ylamino)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 425),


[1282] 2-{4-[{2-[{(dimethylcarbamoyl)methoxy}methyl]-4-(4-fluorophenyl)thiazol-5-yl ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 426),


[1283] 2-{4-[{4-(4-fluorophenyl)-2-(4-hydroxypiperidin-1-ylmethyl)thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 427),


[1284] 2-{4-[{4-(4-fluorophenyl)-2-[(carbamoylmethoxy)methyl]thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 428),


[1285] 2-{4-[{4-(4-fluorophenyl)-2-(methylcarbamoyl)thiazol-5-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 429),


[1286] 2-{4-[{4-(4-fluorophenyl)-2-{(2-hydroxyethyl)carbamoyl}thiazol-5-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 430),


[1287] 2-{4-[2-(4-fluorophenyl)-5-(dimethylcarbamoyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 431),


[1288] 2-{4-[{2-(4-fluorophenyl)-5-(isopropylcarbamoyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 432),


[1289] 2-{4-[{2-(4-fluorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 433),


[1290] 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-tetrazol-5-ylbenzimidazole (Example 434),


[1291] 2-{4-[2-(4-carboxyphenyl)-5-chlorobenzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-tetrazol-5-ylbenzimidazole hydrochloride (Example 435),


[1292] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-(2,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl)benzimidazole hydrochloride (Example 436),


[1293] 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-5-cyano-1-cyclohexylbenzimidazole (Example 437),


[1294] 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-5-cyano-1-cyclohexylbenzimidazole (Example 438),


[1295] 2-{4-[{N-(4-dimethylcarbamoyl)-N-(4-fluorophenyl)amino}-methyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 439),


[1296] 2-{5-[bis(3-fluorophenyl)methyl]-2-fluoro-4-hydroxyphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 440),


[1297] 2-{3-[bis(3-fluorophenyl)methyl]-2-fluoro-4-hydroxyphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 441),


[1298] 2-{4-[(3-dimethylcarbamoylphenyl)(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 442),


[1299] 2-{4-[{3-(4-hydroxypiperidyl-1-ylcarbonyl)phenyl}(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 443),


[1300] 1-{[2-{4-([4-(4-fluorophenyl)-2-methylthiazol-5-yl]methoxy)phenyl}-1-cyclohexylbenzimidazol-5-yl]carbonyl}-β-D-glucuronic acid (Example 444),


[1301] {[2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl]-1-cyclohexylbenzimidazol-5-yl]carbonyl}-β-D-glucuronic acid (Example 445),


[1302] 2-{4-[2-(4-chlorophenyl)-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 446),


[1303] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-3-cyclohexyl-3H-dimidazo[4,5-b]pyridine-6-carboxylic acid hydrochloride (Example 702), and


[1304] 2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-phenyl}-3-cyclohexyl-3H-imidazo[4,5-b]pyridine-6-carboxylic acid hydrochloride (Example 703).


[1305] (94) A pharmaceutical composition comprising a fused ring compound of any of (42) to (93) above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.


[1306] (95) A hepatitis C virus polymerase inhibitor comprising a fused ring compound of any of (1) to (93) above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.


[1307] (96) An anti-hepatitis C virus agent comprising a fused ring compound of any of (1) to (93) above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.


[1308] (97) A therapeutic agent for hepatitis C comprising a fused ring compound of any of (42) to (93) above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.


[1309] (98) An anti-hepatitis C virus agent comprising (a) the anti-hepatitis C virus agent of (96) above and (b) at least one agent selected from the group consisting of a different antiviral agent, an antiinflammatory agent and an immunostimulant.


[1310] (99) An anti-hepatitis C virus agent comprising (a) the anti-hepatitis C virus agent of (96) above and (b) interferon.


[1311] (100) A therapeutic agent for hepatitis C comprising (a) the hepatitis C virus polymerase inhibitor of (95) above and (b) at least one agent selected from the group consisting of a different antiviral agent, an antiinflammatory agent and an immunostimulant.


[1312] (101) A therapeutic agent for hepatitis C comprising (a) the hepatitis C virus polymerase inhibitor of (95) above and (b) interferon.


[1313] (102) A benzimidazole compound of the folllowing formula [III]
58


[1314] wherein Ra36 is hydrogen atom or carboxyl-protecting group, Ra37 is cyclopentyl or cyclohexyl, and Ra38 is hydrogen atom or fluorine atom, or a salt thereof.


[1315] (103) A thiazole compound selected from the group consisting of 4-(4-fluorophenyl)-5-hydroxymethyl-2-methylthiazole and 4-(4-fluorophenyl)-5-chloromethyl-2-methylthiazole, or a pharmaceutically acceptable salt thereof.


[1316] (104) A pharmaceutical composition comprising (a) the fused compound of the formula [I] of (1) above or a pharmaceutically acceptable salt thereof and (b) at least one agent selected from the group consisting of an antiviral-agent other than the compound of (1) above, an antiinflammatory agent and an immunostimulant.


[1317] (105) A pharmaceutical composition comprising (a) the fused compound of the formula [I] of (1) above or a pharmaceutically acceptable salt thereof and (b) interferon.


[1318] (106) A method for treating hepatitis C, which comprises administering an effective amount of a fused ring compound of the formula [I] of (1) above, or a pharmaceutically acceptable salt thereof.


[1319] (107) The method of (106) above, further comprising administering an effective amount of at least one agent selected from the group consisting of an antiviral agent other than the compound of (1) above, an antiinflammatory agent and an immunostimulant.


[1320] (108) The method of (106) above, further comprising administering an effective amount of interferon.


[1321] (109) A method for inhibiting hepatitis C virus polymerase, which comprises administering an effective amount of a fused ring compound of the formula [I] of (1) above, or a pharmaceutically acceptable salt thereof.


[1322] (110) The method of (109) above, further comprising administering an effective amount of at least-one agent selected from the group consisting of an antiviral agent other than the compound of (1) above, an antiinflammatory agent and an immunostimulant.


[1323] (111) The method of (109) above, further comprising administering an effective amount of interferon.


[1324] (112) Use of a fused ring compound of the above-mentioned formula [I] or a pharmaceutically acceptable salt thereof for the production of a pharmaceutical agent for treating hepatitis C.


[1325] (113) Use of a fused ring compound of the above-mentioned formula [I] or a pharmaceutically acceptable salt thereof for the production of a hepatitis C virus polymerase inhibitor.


[1326] (114) A pharmaceutical composition for the treatment of hepatitis C, which comprises a fused ring compound of the above-mentioned formula [I] or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.


[1327] (115) A pharmaceutical composition for inhibiting hepatitis C virus polymerase, which comprises a fused ring compound of the above-mentioned formula [I] or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.


[1328] (116) A commercial package comprising a pharmaceutical composition of (114) above and a written matter associated therewith, the written matter stating that the pharmaceutical composition can or should be used for treating hepatitis C.


[1329] (117) A commercial package comprising a pharmaceutical composition of (115) above and a written matter associated therewith, the written matter stating that the pharmaceutical composition can or should be used for inhibiting hepatitis C virus polymerase.



DETAILED DESCRIPTION OF THE INVENTION

[1330] The definitions of respective substituents and moieties used in the present specification are as follows.


[1331] The halogen atom is a fluorine atom, chlorine atom, bromine atom or iodine atom, preferably fluorine atom, chlorine atom or bromine atom.


[1332] Particularly preferably, the halogen atom is fluorine atom at R5, R5′, R6, R6′, group A and group C, and fluorine atom or chlorine atom at X, Z, Z′, group B and group D.


[1333] The C1-6 alkyl is straight chain or branched chain alkyl having 1 to 6 carbon atoms, and is exemplified by methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, tert-pentyl, hexyl and the like.


[1334] Preferably, it is straight chain or branched chain alkyl having 1 to 4 carbon atoms, and is particularly preferably methyl at Ra7, Ra8, Ra9, Ra15, Ra16, Ra17, Ra29, Ra33, Ra35, Rb6 and Rb7 and methyl or tert-butyl at Rb1, Rb2, group B and group C.


[1335] The halogenated C1-6 alkyl is the above-defined C1-6 alkyl except that it is substituted by the above-defined halogen atom. Preferably, it is halogenated alkyl wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include fluoromethyl, difluoromethyl, trifluoromethyl, bromomethyl, chloromethyl, 1,2-dichloromethyl, 2,2-dichloromethyl, 2,2,2-trifluoroethyl and the like.


[1336] The halogenated C1-6 alkyl is particularly preferably trifluoromethyl at group B.


[1337] The C1-6 alkylene is straight chain alkylene having 1 to 6 carbon atoms, and is exemplified by methylene, ethylene, trimethylene, tetramethylene, pentamethylene or hexamethylene.


[1338] The C1-6 alkylene is preferably methylene or ethylene at Y.


[1339] The C2-6 alkenylene is straight chain alkenylene having 2 to 6 carbon atoms, and is exemplified by vinylene, propenylene, 1-butenylene, 1,3-butadienylene and the like.


[1340] The C2-6 alkenylene is preferably vinylene at Y.


[1341] The C1-6 alkoxy is alkyloxy wherein the alkyl moiety thereof is the above-defined C1-6 alkyl. Preferably, it is alkoxy wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include methoxy, ethoxy, propoxy, isopropyloxy, butoxy, isobutyloxy, tert-butyloxy, pentyloxy, hexyloxy and the like.


[1342] The C1-6 alkoxy is particularly preferably methoxy at Ra2, Ra3, Ra27, Ra28, Ra33, group A and group C.


[1343] The C1-6 alkoxy C1-6 alkoxy is that wherein C1-6 alkoxy in the above definition is substituted by C1-6 alkoxy defined above and is preferably that wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Specific examples include methoxymethyl, ethoxymethyl, methoxyethoxy, methoxypropoxy, isopropyloxyethoxy and the like.


[1344] The group A is particularly preferably methoxyethoxy.


[1345] The C1-6 alkanoyl is alkylcarbonyl wherein the alkyl moiety thereof is the above-defined C1-6 alkyl. Preferably, it is alkanoyl wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include acetyl, propionyl, butyryl, isobutyryl, pivaloyl and the like.


[1346] The C1-6 alkanoyl is particularly preferably acetyl at R1, R2, R3, R4, Ra5, Ra29, Rb7 and group B.


[1347] The C1-6 alkoxycarbonyl is alkyloxycarbonyl wherein the alkoxy moiety thereof is the above-defined C1-6 alkoxy. Preferably, it is alkoxycarbonyl wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropyloxycarbonyl, butoxycarbonyl, isobutyloxycarbonyl, tert-butyloxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl and the like.


[1348] The C1-6 alkoxycarbonyl is particularly preferably methoxycarbonyl or ethoxycarbonyl at Ra10 and group A.


[1349] The C1-6 alkylamino is alkylamino or dialkylamino wherein the alkyl moiety thereof is the above-defined C1-6 alkyl. Preferably, it is alkylamino or dialkylamino wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include methylamino, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, methylethylamino, N-isopropyl-N-isobutylamino and the like.


[1350] The C1-6 alkylamino is particularly preferably methylamino at Ra7, and particularly preferably dimethylamino at Ra21 and group A, and particularly preferably dimethylamino, ethylamino or isopropylamino at Ra24.


[1351] The C1-6 alkanoylamino is alkylcarbonylamino wherein the alkanoyl moiety thereof is the above-defined C1-6 alkanoyl. Preferably, it is alkylcarbonylamino wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include acetylamino, propionylamino, butyrylamino, isobutyrylamino, pivaloylamino and the like.


[1352] The C1-6 alkanoylamino is particularly preferably acetylamino at X and Ra10.


[1353] The C1-6 alkylsulfonyl is alkylsulfonyl wherein the alkyl moiety thereof is the above-defined C1-6 alkyl. Preferably, it is alkylsulfonyl wherein the alkyl moiety thereof is straight chain or branched chain alkyl having 1 to 4 carbon atoms. Examples thereof include methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, hexylsulfonyl and the like.


[1354] The C1-6 alkylsulfonyl is particularly preferably methylsulfonyl at X and Ra5.


[1355] The C6-14 aryl is aromatic hydrocarbon having 6 to 14 carbon atoms. Examples thereof include phenyl, naphthyl, anthryl, indenyl, azulenyl, fluorenyl, phenanthryl and the like.


[1356] The C6-14 aryl is preferably phenyl or naphthyl, particularly preferably phenyl at the ring A, ring A′, ring B and ring B′.


[1357] The C3-8 cycloalkyl is saturated cycloalkyl having 3 to 8, preferably 5 to 7, carbon atoms. Examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.


[1358] The C3-8 cycloalkyl is particularly preferably cyclohexyl at the ring A, ring A′, ring B and ring B′.


[1359] The C3-8 cycloalkenyl is cycloalkenyl having 3 to 8, preferably 5 to 7, carbon atoms and has at least 1, preferably 1 or 2, double bond(s). Examples thereof include cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, 2,4-cyclohexadien-1-yl, 2,5-cyclohexadien-1-yl, cycloheptenyl and cyclooctenyl and the like, but do not include aryl (e.g., phenyl) or completely saturated cycloalkyl.


[1360] The C3-8 cycloalkenyl is preferably cyclohexenyl at the ring A and ring A′.


[1361] The heterocyclic group has, as an atom constituting the ring, 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, besides a carbon atom, and includes saturated ring and unsaturated ring, monocyclic ring and fused ring having the number of ring atom constituting the ring of 3 to 14.


[1362] The heterocyclic group as a monocyclic ring includes, for example, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolinyl, pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl and the like.


[1363] The heterocyclic group includes the groups of the following formulas.
59


[1364] wherein E1 is an oxygen atom, a sulfur atom or N(—Ra35), E2 is an oxygen atom, CH2 or N(—Ra35), E3 is an oxygen atom or a sulfur atom, wherein Ra35 is independently hydrogen atom or C1-6 alkyl, f is an integer of 1 to 3, and h and h′ are the same or different and each is an integer of 1 to 3.


[1365] Specific examples of the heterocyclic group include
60


[1366] and the like.


[1367] Examples of the heterocyclic group as a fused ring include quinolyl, isoquinolyl, quinazolinyl, quinoxalyl, phthalazinyl, cinnolinyl, naphthyridinyl, 5,6,7,8-tetrahydroquinolyl, indolyl, benzimidazolyl, 2,3-dihydrobenzimidazolyl, 2,3-dihydro-2-oxobenzimidazolyl, indolinyl, benzofuranyl, benzothienyl, benzoxazolyl, benzothiazolyl and the like.


[1368] Preferably, it is a heterocyclic group which is a 5-membered or a 6-membered monocyclic group. Examples thereof include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolidinyl, piperidyl, piperazinyl
61


[1369] and the like.


[1370] At R1, R2, R3, R4, Z and group D, tetrazolyl and 5-oxo-Δ2-1,2,4-oxadiazolin-3-yl are particularly preferable.


[1371] The heterocyclic group is preferably pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl which is an aromatic group, and particularly preferably pyridyl at the ring A and ring A′.


[1372] The heterocyclic group is particularly preferably pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl or thiadiazolyl, which is an aromatic group, at the ring B and ring B′. More preferably it is pyridyl or thiazolyl, most preferably thiazolyl.


[1373] The C6-14 aryl C1-6 alkyl is arylalkyl wherein the alkyl moiety thereof is the above-defined C1-6 alkyl and the aryl moiety is the above-defined C6-14 aryl. Preferably, it is arylalkyl wherein the alkyl moiety thereof is straight chain alkyl having 1 to 4 carbon atoms and the aryl moiety is phenyl. Examples thereof include benzyl, phenethyl, 3-phenylpropyl, 2-phenylpropyl, 4-phenylbutyl and the like.


[1374] The C6-14 aryl C1-6 alkyl is particularly preferably benzyl at Ra8 and Rb6.


[1375] The glucuronic acid residue is glucuronic acid less any hydroxyl group, preferably β-D-glucuronic acid substituted at 1-position.


[1376] The C6-14 aryl C1-6 alkyloxycarbonyl is arylalkyloxycarbonyl wherein the C6-14 aryl C1-6 alkyl moiety thereof is the above-defined C6-14 aryl C1-6 alkyl. Preferably, it is arylalkyloxycarbonyl wherein the alkyl moiety thereof is straight chain alkyl having 1 to 4 carbon atoms and the aryl moiety is phenyl. Examples thereof include benzyloxycarbonyl, phenethyloxycarbonyl, 3-phenylpropyloxycarbonyl, 2-phenylpropyloxycarbonyl, 4-phenylbutyloxycarbonyl and the like.


[1377] The C6-14 aryl C1-6 alkyloxycarbonyl is particularly preferably benzyloxycarbonyl at Rb7.


[1378] The optionally substituted C1-6 alkyl is the above-defined C1-6 alkyl, preferably that wherein straight chain or branched chain alkyl having 1 to 4 carbon atoms is optionally substituted with 1 to 3 substituent(s), and includes unsubstituted alkyl. The substituent(s) is(are) selected from the above-defined halogen atom, hydroxyl group, carboxyl, amino, the above-defined C1-6 alkoxy, the above-defined C1-6 alkoxy C1-6 alkoxy, the above-defined C1-6 alkoxycarbonyl and the above-defined C1-6 alkylamino. Examples of optionally substituted C1-6 alkyl include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, tert-pentyl, neopentyl, 1-ethylpropyl, hexyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, 3-hydroxypropyl, 4-hydroxybutyl, 1-hydroxy-1-methylethyl, 1-hydroxypropan-2-yl, 1,3-dihydroxypropan-2-yl, 1-hydroxy-2-methylpropan-2-yl, carboxylmethyl, 2-carboxylethyl, methoxymethyl, methoxyethyl, methoxyethoxyethyl, ethoxycarbonylmethyl, 2-ethoxycarbonylethyl, 2-dimethylaminoethyl and the like.


[1379] Preferably, the optionally substituted C1-6 alkyl is methyl, 1-hydroxy-1-methylethyl, carboxylmethyl or 2-dimethylaminoethyl at R1, R2, R3 and R4, methyl or trifluoromethyl at R5, R5′, R6 and R6′, methyl at R7, R8, Ra25, Ra31 and Rb5, methyl, ethyl or isopropyl at Ra24, methyl or isopropyl at Ra18, methyl or ethyl at Ra1 and Ra19, methyl, carboxylmethyl or 2-dimethylaminoethyl at Ra2 and Ra3, methyl or carboxylmethyl at Ra6, methyl, ethyl, isopropyl, butyl or trifluoromethyl at X, methyl, ethyl, isopropyl, butyl, isobutyl, tert-butyl, isopentyl, neopentyl, 1-ethylpropyl or carboxylmethyl at Ra10, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, trifluoromethyl, 2-hydroxyethyl or carboxylmethyl at Ra11, methyl or 4-hydroxybutyl at Ra12, methyl, ethyl, isopropyl, butyl, 2-hydroxyethyl, 4-hydroxybutyl, ethoxycarbonylmethyl, 2-(ethoxycarbonyl)ethyl or 2-dimethylaminoethyl at Ra13, methyl, propyl, butyl, isopentyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, 3-hydroxypropyl, methoxyethyl, methoxyethoxyethyl or carboxymethyl at Ra20, methyl or ethyl at Ra22 and Ra32, methyl isopropyl or tert-butyl at Ra26, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, isobutyl, 2-hydroxyethyl 1-hydroxypropan-2-yl, 1-hydroxy-2-methylpropan-2-yl or carboxylmethyl at Ra27 and Ra28, and methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, 2-carboxylethyl, methoxymethyl or ethoxycarbonylmethyl at Z, Z′ and group D.


[1380] It is particularly preferably, trifluoromethyl at R5, R5′, R6 and R6′, methyl or tert-butyl at Ra26, methyl, tert-butyl, trifluoromethyl or hydroxymethyl at Z, Z′ and group D, and methyl at other substituents.


[1381] The optionally substituted C2-6 alkenyl is that wherein straight chain or branched chain alkenyl having 2 to 6 carbon atoms is optionally substituted by 1 to 3 substituent(s), and includes unsubstituted alkenyl. The substituent(s) is(are) selected from the above-defined halogen atom, hydroxyl group, carboxyl, amino the above-defined C1-6 alkoxy, the above-defined C1-6 alkoxy C1-6 alkoxy, the above-defined C1-6 alkoxycarbonyl and the above-defined C1-6 alkylamino. Examples of optionally substituted C2-6 alkenyl include vinyl, allyl, 1-propenyl, isopropenyl, 1-butenyl, 2-butenyl, 1,3-butadienyl, 2-isopentenyl, 3-isohexenyl, 4-methyl-3-pentenyl, 2-carboxylethenyl and the like.


[1382] The optionally substituted C2-6 alkenyl is preferably 2-carboxylethenyl at X, and preferably 2-isopentenyl, 3-isohexenyl or 4-methyl-3-pentenyl at Ra20.


[1383] The optionally substituted C2-6 alkynyl is that wherein straight chain or branched chain alkynyl having 2 to 6 carbon atoms is optionally substituted by 1 to 3 substituent(s), and includes unsubstituted alkynyl. The substituent(s) is (are) selected from the above-defined halogen atom, hydroxyl group, carboxyl, amino, the above-defined C1-6 alkoxy, the above-defined C1-6 alkoxycarbonyl and the above-defined C1-6 alkylamino. Examples thereof include ethynyl, 1-propynyl, 2-propynyl, 3-butynyl and the like.


[1384] The optionally substituted C2-6 alkynyl is preferably 2-propynyl at Ra20.


[1385] The C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group B is that wherein the above-defined C6-14 aryl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted aryl. The substituent(s) is(are) selected from the above-defined halogen atom, cyano, nitro, the above-defined C1-6 alkyl, the above-defined halogenated C1-6 alkyl, the above-defined C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2, —(CH2)r—NRb1Rb2, —(CH2)r—NRb1—CORb2, —(CH2)r—NHSO2Rb1, —(CH2)r—ORb1, —(CH2)r—SRb1, —(CH2)r—SO2Rb1 and —(CH2)r—SO2NRb1Rb2 (wherein Rb1 and Rb2 are each independently hydrogen atom or the above-defined C1-6 alkyl and r is 0 or an integer of 1 to 6).


[1386] Examples thereof include phenyl, naphthyl, anthryl, indenyl, azulenyl, fluorenyl, phenanthryl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 3,5-dichlorophenyl, pentafluorophenyl, 4-methylphenyl, 4-tert-butylphenyl, 2-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-nitrophenyl, 4-cyanophenyl, 4-acetylphenyl, 4-carboxylphenyl, 4-carbamoylphenyl, 4-aminophenyl, 4-dimethylaminophenyl, 4-acetylaminophenyl, 4-(methylsulfonylamino)phenyl, 4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 4-methylthiophenyl, 4-methylsulfonylphenyl, 4-aminosulfonylphenyl, 3-nitro-4-methoxyphenyl and 4-nitro-3-methoxyphenyl.


[1387] The aryl moiety is preferably phenyl, the group B here is preferably the above-defined halogen atom, nitro, the above-defined C1-6 alkyl, the above-defined halogenated C1-6 alkyl or —(CH2)r—ORb1. Examples of group B include fluorine atom, chlorine atom, nitro, methyl, tert-butyl, trifluoromethyl and methoxy. Particularly preferably, it is fluorine atom or chlorine atom.


[1388] With regard to “C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group B”, it is preferably phenyl, 4-tert-butylphenyl, 4-fluorophenyl, 3-chlorophenyl, chlorophenyl, 4-methoxyphenyl or 4-trifluoromethylphenyl at Ra12, Ra27 Ra28, phenyl at Ra14, Ra22, Ra23, Ra26 and Rb5, phenyl or 3-fluorophenyl at Ra18, phenyl or 2,4-dichlorophenyl at Ra20, phenyl, 4-chlorophenyl, 4-trifluoromethylphenyl, 3,5-dichlorophenyl, nitro-4-methoxyphenyl or 4-nitro-3-methoxyphenyl at Ra24, and phenyl or 4-methylphenyl at Ra25.


[1389] It is particularly preferably phenyl at other substituents.


[1390] The C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D is that wherein the above-defined C6-14 aryl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted aryl. The substituent(s) is(are) selected from the above-mentioned group D (substituents shown under (a) to (q)).


[1391] Examples of group D here include fluorine atom, chlorine atom, bromine atom, nitro, cyano, methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, methoxymethyl, 2-carboxylethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, acetyl, carboxyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl, methylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, (2-hydroxyethyl)aminocarbonyl, (carboxylmethyl)aminocarbonyl, hydroxyl group, methoxy, ethoxy, propyloxy, isopropyloxy, isopentyloxy, 2-isopentenyloxy, 3-isohexenyloxy, 4-methyl-3-pentenyloxy, 2-propynyloxy, hydroxymethyloxy, carboxylmethyloxy, (dimethylaminocarbonyl)methyloxy, amino, methylamino, dimethylamino, diethylamino, acetylamino, methylsulfonylamino, methylthio, methylsulfonyl, methylsulfinyl, aminosulfonyl, methylaminosulfonyl, dimethylaminosulfonyl and tetrazolyl.


[1392] Examples of C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D include phenyl, naphthyl, anthryl, indenyl, azulenyl, fluorenyl, phenanthryl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 4-bromophenyl, 4-nitrophenyl, pentafluorophenyl, 4-methylphenyl, 4-tert-butylphenyl, 2-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-(hydroxymethyl)phenyl, 4-(methoxymethyl)phenyl, 4-(2-carboxylethyl)phenyl, 3-carboxylphenyl, 4-carboxylphenyl, 4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 4-carbamoylphenyl, 4-methylthiophenyl, 4-(dimethylaminocarbonyl)phenyl, 4-methylsulfonylphenyl, 4-acetylaminophenyl, 4-cyanophenyl, 4-acetylphenyl, 4-aminophenyl, 4-dimethylaminophenyl, 4-(methylsulfonylamino)phenyl, 4-methylsulfinylphenyl, 4-aminosulfonylphenyl and 3-nitro-4-methoxyphenyl, 4-nitro-3-methoxyphenyl and 4-tetrazol-5-ylphenyl.


[1393] At Z and Z′, the aryl moiety is preferably phenyl, and group D here is preferably the above-defined halogen atom, nitro, the above-defined optionally substituted C1-6 alkyl, —(CH2)t—COORa19, —(CH2)t—CONRa27Ra28, —(CH2)t—ORa20, —(CH2)t—NRa29CO—Ra24, —(CH2)t—S(O)q—Ra25 or —(CH2)t—SO2—NHRa26,


[1394] Examples of C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D preferably include phenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,5-dichlorophenyl, 4-bromophenyl, 4-nitrophenyl, 4-methylphenyl, 4-tert-butylphenyl, 2-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-(hydroxymethyl)phenyl, 4-(methoxymethyl)phenyl, 4-(2-carboxylethyl)phenyl, 3-carboxylphenyl, 4-carboxylphenyl, 4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 4-carbamoylphenyl, 4-methylthiophenyl, 4-(dimethylaminocarbonyl)phenyl, 4-methylsulfonylphenyl, 4-acetylaminophenyl, 4-methylsulfinylphenyl, 4-aminosulfonylphenyl, 4-cyanophenyl and 4-tetrazolylphenyl.


[1395] Particularly preferably, it is the above-defined halogen atom, the above-defined optionally substituted C1-6 alkyl, —(CH2)t—COORa19, —(CH2)t—CONRa27Ra28, —(CH2)t—ORa20 or —(CH2)t—S(O)q—Ra25, which is specifically fluorine atom, chlorine atom, bromine atom, nitro, methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl or acetylamino. More preferably, it is fluorine atom, chlorine atom, methyl, tert-butyl, carboxyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl or acetylamino, most preferably fluorine atom or chlorine atom.


[1396] The heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group B is that wherein the above-defined heterocyclic group is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted heterocyclic group. The substituent(s) is(are) selected from the above-defined halogen atom, cyano, nitro, the above-defined C1-6 alkyl, the above-defined halogenated C1-6 alkyl, the above-defined C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2, —(CH2)r—NRb1Rb2, —(CH2)r—NRb1—CORb2, —(CH2)r—NHSO2Rb1, —(CH2)r—ORb1, —(CH2)r—SRb1, —(CH2)r—SO2Rb1 and —(CH2)r—SO2NRb1Rb2 wherein Rb1 and Rb2 are each independently hydrogen atom or the above-defined C1-6 alkyl and r is 0 or an integer of 1 to 6.


[1397] Examples thereof include 2-pyridyl, 3-pyridyl, 4-pyridyl, 3-fluoropyridin-4-yl, 3-chloropyridin-4-yl, 4-chloropyridin-3-yl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, 2-thienyl, 3-thienyl, furyl, oxazolyl, 2-methyloxazol-4-yl, isoxazolyl, thiazolyl, 2-methylthiazol-4-yl, 2,5-dimethylthiazol-4-yl, 2,4-dimethylthiazol-5-yl, isothiazolyl, thiadiazolyl, pyrrolinyl, pyrrolidinyl, 3-hydroxypyrrolidinyl, imidazolidinyl, azetidinyl, piperidyl, 3-hydroxypiperidino, 4-hydroxypiperidino, 3,4-dihydroxypiperidino, 4-methoxypiperidino, 4-carboxypiperidino, 4-(hydroxymethyl)piperidino, 2-oxopiperidino, 4-oxopiperidino, 2,2,6,6-tetramethylpiperidino, 2,2,6,6-tetramethyl-4-hydroxypiperidino, N-methylpiperidin-4-yl, N-(tert-butoxycarbonyl)piperidin-4-yl, N-acetylpiperidin-4-yl, N-methylsulfonylpiperidin-4-yl, piperazinyl, 4-methylpiperazinyl, 4-methylsulfonylpiperazinyl, morpholinyl, thiomorpholinyl, 1-oxothiomorpholin-4-yl, 1,1-dioxothiomorpholin-4-yl, tetrahydropyranyl, quinolyl, isoquinolyl, quinazolinyl, quinoxalyl, phthalazinyl, cinnolinyl, naphthyridinyl, 5,6,7,8-tetrahydroquinolyl, indolyl, benzimidazolyl, indolinyl, benzofuranyl, benzothienyl, benzoxazolyl, benzothiazolyl,
6263


[1398] and the like.


[1399] The heterocyclic moiety is preferably a heterocyclic group which is a 5-membered or a 6-membered monocyclic group. Examples thereof include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl and tetrahydropyranyl, and the group B here is preferably the above-defined halogen atom, the above-defined C1-6 alkyl, the above-defined halogenated C1-6 alkyl, the above-defined C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2 or —(CH2)r—ORb1.


[1400] Examples of heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group B preferably include piperidino, 4-methylpiperidino, 2,6-dimethylpiperidino, 4-hydroxypiperidino, 1-piperazinyl, 1-(methylsulfonyl)piperidin-4-yl, 1-pyrrolidinyl, morpholino, 4-thiomorpholinyl, tetrahydropyranyl, pyridyl, thiazolyl,
64


[1401] Particularly preferably, it is piperidino, 4-methylpiperidino, 2,6-dimethylpiperidino, 4-hydroxypiperidino, 1-piperazinyl, 1-pyrrolidinyl, morpholino or 4-thiomorpholinyl at Ra18, tetrahydropyranyl or 4-hydroxypiperidino at Ra20, piperidino, 4-hydroxypiperidino or 3,4-dihydroxypiperidino at Ra21, pyridyl or morpholino at Ra24, pyridyl or 4-hydroxypiperidino at Ra25, pyridyl or thiazolyl at Ra25 and at Ra26 and Ra28, it is 1-(methylsulfonyl)piperidin-4-yl, 3-hydroxypyrrolidinyl, 3-hydroxypiperidino, 4-hydroxypiperidino, 3,4-dihydroxypiperidino, 4-methoxypiperidino, 4-carboxypiperidino, 4-(hydroxymethyl)piperidino, 2-oxopiperidino, 4-oxopiperidino, 2,2,6,6-tetramethylpiperidino, 2,2,6,6-tetramethyl-4-hydroxypiperidino, 4-methylsulfonylpiperazinyl, 1-oxothiomorpholin-4-yl or 1,1-dioxothiomorpholin-4-yl, and 2-oxazolin-2-yl at Ra22 and Ra23.


[1402] The heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group D is that wherein the above-defined heterocyclic group is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted heterocyclic group. The substituent(s) is(are) selected from the substituent(s) of the above-mentioned group D (substituents shown under (a) to (q)).


[1403] Examples of the group D here include the substituent(s) exemplified for C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D.


[1404] Examples of heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group D include 2-pyridyl, 3-pyridyl, 4-pyridyl, 3-fluoropyridin-4-yl, 3-chloropyridin-4-yl, 4-chloropyridin-3-yl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, 2-thienyl, 3-thienyl, furyl, oxazolyl, 2-methyloxazol-4-yl, isoxazolyl, thiazolyl, 2-methylthiazol-4-yl, 2,5-dimethylthiazol-4-yl, 2,4-dimethylthiazol-5-yl, isothiazolyl, thiadiazolyl, pyrrolinyl, pyrrolidinyl, imidazolidinyl, piperidyl, N-methylpiperidin-4-yl, N-(tert-butoxycarbonyl)piperidin-4-yl, N-acetylpiperidin-4-yl, N-methylsulfonylpiperidin-4-yl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl, quinolyl, isoquinolyl, quinazolinyl, quinoxalyl, phthalazinyl, cinnolinyl, naphthyridinyl, 5,6,7,8-tetrahydroquinolyl, indolinyl, benzimidazolyl, indolinyl, benzofuranyl, benzothienyl, benzoxazolyl, benzothiazolyl
65


[1405] and the like.


[1406] In addition, the heterocyclic group may be substituted at the 3-, 4-, 5- or 6-position of 2-pyridyl, at the 2-, 4-, 5- or 6-position of 3-pyridyl, at the 2-, 3-, 5- or 6-position of 4-pyridinyl, at the 3-, 4- or 5-position of 2-thienyl, or at the 2-, 4- or 5-position of 3-thienyl, by fluorine atom, chlorine atom, bromine atom, nitro, methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl, amino or acetylamino.


[1407] At Z and Z′, the heterocyclic moiety is preferably a heterocyclic group which is a 5-membered or 6-membered monocyclic group. Examples thereof include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, 2-oxopyrrolidinyl, 2-oxopiperidyl, pyrazolyl, imidazolyl, 2-imidazolinyl, 2-oxoimidazolidinyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, 2-oxazolinyl, thiazolyl, isothiazolyl, 1,1-dioxoisothiazolidinyl, thiadiazolyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl, Δ2-1,2,4-oxadiazolyl, 5-oxo-Δ2-1,2,4-oxadiazolyl, 5-oxo-Δ2-1,2,4-thiadiazolinyl and 2-oxo-3H-1,2,3,5-oxathiadiazolinyl. The group D here is preferably the above-defined halogen atom, nitro, the above-defined optionally substituted C1-6 alkyl, —(CH2)t—COORa19, —(CH2)t—CONRa27Ra28, —(CH2)t—ORa20, —(CH2)t—NRa29CO—Ra24, —(CH2)t—S(O)q—Ra25 or —(CH2)t—SO2—NHRa26.


[1408] Examples of heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group D preferably include piperidino, 4-hydroxypiperidino, 2-oxopiperidin-1-yl, 1-piperazinyl, 1-pyrrolidinyl, 2-oxopyrrolidin-1-yl, morpholino, 4-thiomorpholinyl, 4-tetrahydropyranyl, 3-pyridyl, 2-pyrimidinyl, 2-imidazolin-2-yl, 2-oxoimidazolidin-1-yl, 2-oxooxazolidin-1-yl, 5-tetrazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-methylthiazol-4-yl, 5-methylthiazol-2-yl, 2-aminothiazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 1,1-dioxoisothiazolidin-2-yl, 4,4-dimethyl-Δ2-oxazolin-2-yl, 2-thienyl, 5-chlorothiophen-2-yl, 5-methyloxazol-2-yl, 5-oxo-Δ2-1,2,4-oxadiazolin-3-yl, 5-oxo-Δ2-1,2,4-thiadiazolin-3-yl and 2-oxo-3H-1,2,3,5-oxathiazolin-4-yl.


[1409] Particularly preferably, it is pyridyl, pyrimidinyl, tetrazolyl, thienyl, piperidyl, 2-oxopiperidin-1-yl, 2-oxopyrrolidin-1-yl, 2-imidazolin-2-yl, 2-oxoimidazolidin-1-yl, 2-oxooxazolidin-1-yl, 2-methylthiazol-4-yl, 5-methylthiazol-2-yl, 2-aminothiazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 1,1-dioxoisothiazolidin-2-yl, 4,4-dimethyl-Δ2-oxazolin-2-yl, 5-chlorothiophen-2-yl, 5-methyloxazol-2-yl, 5-oxo-Δ2-1,2,4-oxadiazolin-3-yl, 5-oxo-Δ2-1,2,4-thiadiazolin-3-yl or 2-oxo-3H-1,2,3,5-oxathiadiazolin-4-yl, more preferably 2-oxopyrrolidin-1-yl.


[1410] The C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from group C is that wherein the above-defined C3-8 cycloalkyl is optionally substituted by the 1 to 5 substituent(s) selected from hydroxyl group, the above-defined halogen atom, the above-defined C1-6 alkyl and the above-defined C1-6 alkoxy, which may be unsubstituted. Examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-fluorocyclohexyl, 2-methylcyclopentyl, 3-methylcyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl, 3,5-dimethylcyclohexyl, 4-tert-butylcyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl and 2,3,4,5,6-pentafluorocyclohexyl.


[1411] The cycloalkyl moiety is preferably cyclopentyl or cyclohexyl, particularly preferably cyclohexyl.


[1412] At the ring Cy and ring Cy′, the C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from group C is preferably cyclopentyl, cyclohexyl, 4-fluorocyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl, 4-tert-butylcyclohexyl, 4-hydroxycyclohexyl or 4-methoxycyclohexyl, more preferably cyclopentyl or cyclohexyl, particularly preferably cyclohexyl.


[1413] The C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B is that wherein the above-defined C3-8 cycloalkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted cycloalkyl. The substituents are selected from the above group B.


[1414] Specific examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-fluorocyclohexyl, 2-methylcyclopentyl, 3-methylcyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl, 3,5-dimethylcyclohexyl, 4-tert-butylcyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl and 2,3,4,5,6-pentafluorocyclohexyl.


[1415] Also exemplified are those wherein cyclopentyl or cyclohexyl is substituted by fluorine atom, chlorine atom, bromine atom, nitro, methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl or acetylamino.


[1416] At cycloalkyl moiety, it is preferably cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. As the C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, it is particularly preferably cyclopropyl, cyclobutyl, cyclohexyl or 4-hydroxycyclohexyl at Ra27 and Ra28.


[1417] The C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from group D is that wherein the above-defined C3-8 cycloalkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted cycloalkyl. The substituent(s) is(are) selected from the substituent(s) of the above-mentioned group D (substituents shown under (a) to (q)).


[1418] The group D here includes the substituents recited with regard to C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D.


[1419] Examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-fluorocyclohexyl, 2-methylcyclopentyl, 3-methylcyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl, 3,5-dimethylcyclohexyl, 4-tert-butylcyclohexyl, 4-hydroxycyclohexyl, 4-methoxycyclohexyl and 2,3,4,5,6-pentafluorocyclohexyl.


[1420] The group D may be, for example, cyclopentyl or cyclohexyl substituted by fluorine atom, chlorine atom, bromine atom, nitro, methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl or acetylamino.


[1421] The cycloalkyl moiety is preferably cyclopentyl or cyclohexyl, and at Z and Z′, it is particularly preferably cyclohexyl.


[1422] The optionally substituted C3-8 cycloalkenyl is that wherein the above-defined C3-8 cycloalkenyl is optionally substituted by substituent(s) selected from hydroxyl group, the above-defined halogen atom, the above-defined C1-6 alkyl and the above-defined C1-6 alkoxy, which may be unsubstituted. Examples thereof include cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, 4-fluoro-2-cyclohexenyl, 4-methyl-2-cyclohexenyl, 4-methyl-3-cyclohexenyl, 2,4-cyclohexadien-1-yl, 2,5-cyclohexadien-1-yl, cycloheptenyl and cyclooctenyl and the like, but do not include aryl (e.g., phenyl) or completely saturated cycloalkyl.


[1423] The optionally substituted C3-8 cycloalkenyl is particularly preferably cyclohexenyl at the ring Cy.


[1424] The C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group B is that wherein the above-defined C6-14 aryl C1-6 alkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted arylalkyl. The substituent(s) is(are) selected from the above-mentioned group B.


[1425] Examples thereof include benzyl, 1-naphthylmethyl, 2-naphthylmethyl, phenethyl, 3-phenylpropyl, 2-phenylpropyl, 3-fluorobenzyl, 4-fluorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2,4-dichlorobenzyl, 3,5-dichlorobenzyl, pentafluorobenzyl, 4-methylbenzyl, 4-tert-butylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 4-nitrobenzyl, 4-cyanobenzyl, 4-acetylbenzyl, 4-carboxylbenzyl, 4-carbamoylbenzyl, 4-aminobenzyl, 4-dimethylaminobenzyl, 4-acetylaminobenzyl, 4-(methylsulfonylamino)benzyl, 4-methoxybenzyl, 3,4,5-trimethoxybenzyl, 4-methylthiobenzyl, 4-methylsulfonylbenzyl, 4-aminosulfonylbenzyl, 3-nitro-4-methoxybenzyl and 4-nitro-3-methoxybenzyl.


[1426] The C6-14 aryl C1-6 alkyl moiety is preferably benzyl or phenethyl, particularly preferably benzyl. The group B is preferably the above-defined halogen atom, nitro, the above-defined C1-6 alkyl, the above-defined halogenated C1-6 alkyl or —(CH2)r—ORb1. Examples thereof include fluorine atom, chlorine atom, nitro, methyl, tert-butyl, trifluoromethyl, methoxy or trifluoromethyloxy, particularly preferably fluorine atom or chlorine atom.


[1427] The specific C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group B at Ra12 and Ra13 is preferably benzyl, phenethyl, 3-chlorobenzyl, 4-chlorobenzyl, 4-tert-butylbenzyl or 3-trifluoromethylbenzyl, it is preferably benzyl at Ra1, Ra19, Ra27, Ra28, Ra31 and Rb5, it is preferably benzyl, phenethyl, 4-fluorobenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 4-tert-butylbenzyl or 4-trifluoromethylbenzyl at Ra20, and 4-chlorobenzyl, 3,5-dichlorobenzyl or 4-trifluoromethylbenzyl at Ra22 and Ra23.


[1428] It is particularly preferably benzyl at other substituents.


[1429] The C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group D is that wherein the above-defined C6-14 aryl C1-6 alkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted aryl. The substituent(s) is(are) selected from the substituent(s) of the above-mentioned group D (substituents shown under (a) to (q)).


[1430] Examples of group D include fluorine atom, chlorine atom, bromine atom, nitro, cyano, methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, methoxymethyl, 2-carboxylethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, acetyl, carboxyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl, methylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, (2-hydroxyethyl)aminocarbonyl, (carboxylmethyl)aminocarbonyl, hydroxyl group, methoxy, ethoxy, isopropyloxy, hydroxymethyloxy, carboxylmethyloxy, (dimethylaminocarbonyl)methyloxy, amino, methylamino, dimethylamino, diethylamino, acetylamino, methylsulfonylamino, methylthio, methylsulfonyl, methylsulfinyl, aminosulfonyl, methylaminosulfonyl and dimethylaminosulfonyl.


[1431] Examples of C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group D include benzyl, 1-naphthylmethyl, 2-naphthylmethyl, phenethyl, 3-phenylpropyl, 2-phenylpropyl, 3-fluorobenzyl, 4-fluorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2,4-dichlorobenzyl, 3,5-dichlorobenzyl, 4-bromobenzyl, 4-nitrobenzyl, pentafluorobenzyl, 4-methylbenzyl, 4-tert-butylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 4-(hydroxymethyl)benzyl, 4-(methoxymethyl)benzyl, 4-(2-carboxylethyl)benzyl, 3-carboxylbenzyl, 4-carboxylbenzyl, 4-methoxybenzyl, 3,4,5-trimethoxybenzyl, 4-carbamoylbenzyl, 4-methylthiobenzyl, 4-(dimethylaminocarbonyl)benzyl, 4-methylsulfonylbenzyl, 4-(acetylamino) benzyl, 4-cyanobenzyl, 4-acetylbenzyl, 4-aminobenzyl, 4-dimethylaminobenzyl, 4-(methylsulfonylamino)benzyl, 4-methylsulfinylbenzyl, 4-aminosulfonylbenzyl, (3-nitro-4-methoxyphenyl)methyl and (4-nitro-3-methoxyphenyl)methyl.


[1432] At Z and Z′, the C6-14 aryl C1-6 alkyl moiety is preferably benzyl or phenethyl, and the group D here is preferably the above-defined halogen atom, nitro, the above-defined optionally substituted C1-6 alkyl, —(CH2)t—COORa19, —(CH2)t—CONRa27Ra28, —(CH2)t—ORa20, —(CH2)t—NRa29CO—Ra24, —(CH2)t—S(O)q—Ra25 or —(CH2)t—SO2—NHRa26.


[1433] The C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group D is preferably benzyl, 3-fluorobenzyl, 4-fluorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 3,5-dichlorobenzyl, 4-bromobenzyl, 4-nitrobenzyl, 4-methylbenzyl, 4-tert-butylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 4-(hydroxymethyl)benzyl, 4-(methoxymethyl)benzyl, 4-(2-carboxylethyl)benzyl, 3-carboxylbenzyl, 4-carboxylbenzyl, 4-methoxybenzyl, 3,4,5-trimethoxybenzyl, 4-carbamoylbenzyl, 4-methylthiobenzyl, 4-(dimethylaminocarbonyl)benzyl, 4-methylsulfonylbenzyl, 4-acetylaminobenzyl, 4-methylsulfinylbenzyl or 4-aminosulfonylbenzyl.


[1434] It is particularly preferably the above-defined halogen atom, the above-defined optionally substituted C1-6 alkyl, —(CH2)t—COORa19, —(CH2)t—CONRa27Ra28, —(CH2)t—ORa20 or —(CH2)t—S(O)q—Ra25. Examples thereof include fluorine atom, chlorine atom, bromine atom, nitro, methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl and acetylamino. It is more preferably fluorine atom, chlorine atom, methyl, tert-butyl, carboxyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl or methylsulfonyl, most preferably fluorine atom or chlorine atom.


[1435] The heterocycle C1-6 alkyl-optionally substituted by 1 to 5 substituent(s) selected from group B is that wherein the above-defined heterocycle C1-6 alkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted heterocycle C1-6 alkyl. The substituent(s) is(are) selected from the above-mentioned group B.


[1436] Examples thereof include 2-pyridylmethyl, 3-pyridylmethyl, 2-chloropyridin-4-ylmethyl, 4-pyridylmethyl, pyrrolylmethyl, imidazolylmethyl, 2-thienylmethyl, 3-thienylmethyl, 2-furylmethyl, 2-oxazolylmethyl, 5-isothiazolylmethyl, 2-methyloxazol-4-ylmethyl, 2-thiazolylmethyl, 4-thiazolylmethyl, 5-thiazolylmethyl, 2-methylthiazol-4-ylmethyl, 2-methylthiazol-5-ylmethyl, 2,5-dimethylthiazol-4-ylmethyl, 4-methylthiazol-2-ylmethyl, 2,4-dimethylthiazol-5-ylmethyl, 2-isothiazolylmethyl, 2-pyrrolinylmethyl, pyrrolidinylmethyl, piperidylmethyl, 4-piperidylmethyl, 1-methylpiperidin-4-ylmethyl, 4-hydroxypiperidinomethyl, 3-hydroxypyrrolidinylmethyl, 2-(4-hydroxypiperidino)ethyl, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyl, 1-acetylpiperidin-4-ylmethyl, 1-methylsulfonylpiperidin-4-ylmethyl, piperazinylmethyl, morpholinomethyl, thiomorpholinylmethyl, 1-tetrahydropyranylmethyl, 2-quinolylmethyl, 1-isoquinolylmethyl and the like.


[1437] The heterocyclic moiety is preferably a heterocyclic group which is a 5-membered or 6-membered monocyclic group. Examples thereof include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl and tetrahydropyranyl, and the alkyl moiety thereof is preferably straight chain alkyl having 1 to 4 carbon atoms. The group B here is preferably the above-defined halogen atom, the above-defined C1-6 alkyl, the above-defined halogenated C1-6 alkyl, the above-defined C1-6 alkanoyl, —(CH2)r—COORb1, —(CH2)r—CONRb1Rb2 or —(CH2)r—ORb1.


[1438] Examples of heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group B preferably include 2-pyridylmethyl, 3-pyridylmethyl, 2-chloropyridin-4-ylmethyl, 4-pyridylmethyl, piperidin-4-ylmethyl, 1-methylpiperidin-4-ylmethyl, 2-(4-hydroxypiperidino)ethyl, 1-acetylpiperidin-4-ylmethyl, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyl, 1-(methylsulfonyl)-piperidin-4-ylmethyl, 2-thiazolylmethyl, 4-thiazolylmethyl, 2-methylthiazolin-4-ylmethyl, 2,4-dimethylthiazolin-5-ylmethyl and 4-methylthiazol-2-ylmethyl. Particularly preferably, it is 2-pyridylmethyl, 3-pyridylmethyl, 2-chloropyridin-4-ylmethyl, 4-pyridylmethyl, piperidin-4-ylmethyl, 1-methylpiperidin-4-ylmethyl, 2-(4-hydroxypiperidino)ethyl, 1-acetylpiperidin-4-ylmethyl, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyl, 1-(methylsulfonyl)piperidin-4-ylmethyl, 2-methylthiazolin-4-ylmethyl, 2,4-dimethylthiazolin-5-ylmethyl or 4-methylthiazol-2-ylmethyl at Ra20, 2-pyridylmethyl at Ra22 and Ra23, and 4-pyridylmethyl or 4-methylthiazol-2-ylmethyl at Ra27 and Ra28.


[1439] The heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group D is that wherein the above-defined heterocycle C1-6 alkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted heterocycle C1-6 alkyl. The substituent(s) is(are) selected from the above-mentioned group D (substituents shown under (a) to (q)).


[1440] Examples of group D here include fluorine atom, chlorine atom, bromine atom, nitro, cyano, methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, methoxymethyl, 2-carboxylethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, acetyl, carboxyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl, methylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, (2-hydroxyethyl)aminocarbonyl, (carboxylmethyl)aminocarbonyl, hydroxyl group, methoxy, ethoxy, isopropyloxy, hydroxymethyloxy, carboxylmethyloxy, (dimethylaminocarbonyl)methyloxy, amino, methylamino, dimethylamino, diethylamino, acetylamino, methylsulfonylamino, methylthio, methylsulfonyl, methylsulfinyl, aminosulfonyl, methylaminosulfonyl and dimethylaminosulfonyl.


[1441] Examples of heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group D include 2-pyridylmethyl, 3-pyridylmethyl, 2-chloropyridin-4-ylmethyl, 4-pyridylmethyl, pyrrolylmethyl, imidazolylmethyl, 2-thienylmethyl, 3-thienylmethyl, 2-furylmethyl, 2-oxazolylmethyl, 5-isothiazolylmethyl, 2-methyloxazol-4-ylmethyl, 2-thiazolylmethyl, 4-thiazolylmethyl, 5-thiazolylmethyl, 2-methylthiazol-4-ylmethyl, 2-methylthiazol-5-ylmethyl, 2,5-dimethylthiazol-4-ylmethyl, 4-methylthiazol-2-ylmethyl, 2,4-dimethylthiazol-5-ylmethyl, 2-isothiazolylmethyl, 2-pyrrolinylmethyl, pyrrolidinylmethyl, piperidylmethyl, 4-piperidylmethyl, 1-methylpiperidin-4-ylmethyl, 4-hydroxypiperidinomethyl, 2-(4-hydroxypiperidino)ethyl, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyl, 1-acetylpiperidin-4-ylmethyl, 1-methylsulfonylpiperidin-4-ylmethyl, piperazinylmethyl, morpholinomethyl, thiomorpholinylmethyl, 1-tetrahydropyranylmethyl, 2-quinolylmethyl, 1-isoquinolylmethyl, and the like.


[1442] Preferable heterocyclic moiety at Z and Z′ is heterocylic group which is 5-membered or 6-membered monocyclic group. Examples of the heterocyclic moiety include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isooxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl and tetrahydropyranyl, and the alkyl moiety is preferably straight chain alkyl having 1 to 4 carbon atoms, particularly methyl (i.e., methylene).


[1443] Preferable group D is the above-defined halogen atom, nitro, the above-defined optionally substituted C1-6 alkyl, —(CH2)t—COORa19, —(CH2)t—CONRa27Ra28, —(CH2)t—ORa20, —(CH2)t—NRa29CO—Ra24, —(CH2)t—S(O)q—Ra25 or —(CH2)t—SO2—NHRa26.


[1444] Preferable examples of heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from group D include 2-pyridylmethyl, 3-pyridylmethyl, 2-chloropyridin-4-ylmethyl, 4-pyridylmethyl, piperidin-4-ylmethyl, 1-methylpiperidin-4-ylmethyl, 4-hydroxypiperidinomethyl, 2-(4-hydroxypiperidino)ethyl, 1-acetylpiperidin-4-ylmethyl, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyl, 1-(methylsulfonyl)piperidin-4-ylmethyl, 2-thiazolylmethyl, 4-thiazolylmethyl, 2-methylthiazolin-4-ylmethyl, 2,4-dimethylthiazolin-5-ylmethyl and 4-methylthiazol-2-ylmethyl.


[1445] Particularly preferred is 4-hydroxypiperidinomethyl.


[1446] The C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B is that wherein the above-defined C3-8 cycloalkyl C1-6 alkyl is optionally substituted by 1 to 5 substituent(s), and includes unsubstituted cycloalkylalkyl. The substituents are selected from the above group B.


[1447] Specific examples thereof include cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, 2-(cyclopentyl)ethyl, 2-(cyclohexyl)ethyl, cycloheptylmethyl, 4-fluorocyclohexylmethyl, 2-methylcyclopentylmethyl, 3-methylcyclohexylmethyl, 4-methylcyclohexylmethyl, 4,4-dimethylcyclohexylmethyl, 3,5-dimethylcyclohexylmethyl, 4-tert-butylcyclohexylmethyl, 4-hydroxycyclohexylmethyl, 4-methoxycyclohexylmethyl and 2,3,4,5,6-pentafluorocyclohexylmethyl.


[1448] Also exemplified are those wherein cyclopentylmethyl or cyclohexylmethyl is substituted by fluorine atom, chlorine atom, bromine atom, nito, methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl or acetylamino.


[1449] At cycloalkyl moiety, it is preferably cyclopentylmethyl or cyclohexylmethyl, and at Ra20, Ra27 and Ra28, it is particularly preferably cyclohexylmethyl.


[1450] The carboxyl-protecting group only needs to be suitable for reaction conditions, and is capable of protecting and deprotecting and may be, for example, methyl; substituted methyl group such as methoxymethyl, methylthiomethyl, 2-tetrahydropyranyl, methoxyethoxymethyl, benzyloxymethyl, phenacyl, diacylmethyl, phthalimidomethyl etc.; ethyl; substituted ethyl group such as 2,2,2-trichloroethyl, 2-chloroethyl, 2-(trimethylsilyl)ethyl, 2-methylthioethyl, 2-(p-toluenesulfonyl)ethyl, t-butyl etc.; benzyl; substituted benzyl group such as diphenylmethyl, triphenylmethyl, p-nitrobenzyl, 4-picolyl, p-methoxybenzyl, 2-(9,10-dioxo)anthrylmethyl etc.; silyl group such as trimethylsilyl, t-butyldimethylsilyl, phenyldimethylsilyl etc.; and the like.


[1451] Preferred are industrially effective protecting groups and specifically preferred as Ra36 are methyl and ethyl.


[1452] In formula [I], X is preferably
66


[1453] wherein each symbol is as defined above.


[1454] G1, G2, G3 and G4 are each preferably (C—R1), (C—R2), (C—R3) and (C—R4), G5 is preferably a nitrogen atom, and G6, G8 and G9 are preferably a carbon atom. G7 is preferably C(—R7) or unsubstituted nitrogen atom, wherein R7 is preferably hydrogen atom.


[1455] A preferable combination is G2 of (C—R2) and G6 of a carbon atom, particularly preferably G2 of (C—R2), G6 of a carbon atom and G5 of a nitrogen atom, most preferably G2 of (C—R2), G6 of a carbon atom, G5 of a nitrogen atom and G7 of unsubstituted nitrogen atom.


[1456] In formulas [I] and [II], 1 to 4 of G1 to G9 in the moiety
67


[1457] is(are) preferably a nitrogen atom, specifically preferably
6869


[1458] particularly preferably
70


[1459] more preferably
71


[1460] most preferably
72


[1461] It is also a preferable embodiment wherein the
73


[1462] moiety is aromatic ring.


[1463] R1 and R4 are preferably hydrogen atom. R2 is preferably carboxyl, —COORa1, —CONRa2Ra3, —SO2Ra7 (each symbol is as defined above) or heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, particularly preferably carboxyl, —COORa1 or —SO2Ra7, more preferably carboxyl or —COORa1, most preferably carboxyl. R3 is preferably hydrogen atom or —ORa6 (Ra6 is as defined above), particularly preferably hydrogen atom.


[1464] Ra1 is preferably optionally substituted C1-6 alkyl.


[1465] When R2 is carboxyl or —COORa1, at least one of R1, R3 and R4 is preferably hydroxyl group, halogen atom (particularly fluorine atom, chlorine atom) or —ORa6 (wherein Ra6 is preferably hydrogen atom or methyl).


[1466] The ring Cy and ring Cy′ are preferably cyclopentyl, cyclohexyl, cycloheptyl, tetrahydrothiopyranyl or piperidino, particularly preferably cyclopentyl, cyclohexyl or cycloheptyl, more preferably cyclohexyl.


[1467] The ring A and ring A′ are preferably phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, cyclohexyl, cyclohexenyl, furyl or thienyl, particularly preferably phenyl, pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl, more preferably phenyl or pyridyl, and most preferably phenyl.


[1468] The ring B and ring B′ are preferably C1-6 aryl or heterocyclic group, specifically preferably, phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl or thiadiazolyl, particularly preferably phenyl, pyridyl, pyrimidinyl, 1,3,5-triazinyl or thiazolyl, more preferably, phenyl, pyridyl or thiazolyl, and most preferably phenyl or thiazolyl.


[1469] With regard to R5 and R6, one of them is preferably hydrogen atom and the other is halogen atom, particularly fluorine atom. Alternatively, the both arepreferably hydrogen atoms. When ring A is phenyl, R5 and R6 preferably are present at an ortho position from G6. The same applies to R5′ and R6′.


[1470] Y is preferably —(CH2)m—O—(CH2)n—, —NHCO2—, —CONH—CHRa14—, —(CH2)m—NRa12—(CH2)n—, —CONRa13—(CH2)n—, —O—(CH2)m—CRa15Ra16—(CH2)n— or —(CH2)n—NRa12—CHRa15— (each symbol is as defined above), more preferably, —(CH2)m—O—(CH2)n— or —O—(CH2)m—CRa15Ra16—(CH2)n—, most preferably —O—(CH2)m—CRa15Ra16—(CH2)n—.


[1471] The l, m and n are preferably 0 or an integer of 1 to 4, particularly preferably 0, 1 or 2, at Y. In —(CH2)m—O—(CH2)n—, m=n=0 or m=0 and n=1 is more preferable, most preferably m=n=0. In —O—(CH2)m—CRa15Ra16—(CH2)n—, m=n=0, m=0 and n=1, m=1 and n=0 or m=1 and n=1 is more preferable, most preferably m=n=0.


[1472] When Y is —O—(CH2)m—CRa15Ra16—(CH2)n—, Ra16 is preferably hydrogen atom, Ra15 is preferably
74


[1473] wherein the
75


[1474] moiety is preferably symmetric. The preferable mode of n, ring B, Z and w and the preferable mode of n′, ring B′, Z′ and w′ are the same.


[1475] When ring A is phenyl, X or Y is preferably present at the para-position relative to G6. When ring B and ring B′ are phenyl, Z is preferably present at the ortho or meta-position relative to Y. It is preferable that the 3-position on phenyl have one substituent or the 2-position and the 5-position on phenyl each have one substituent.


[1476] When ring B is thiazolyl, Y is preferably)substituted at the 5-position, and Z is preferably substituted at the 2-position, the 4-position or the 2-position and the 4-position. Similarly, when ring B′ is thiazolyl, (CH2)n′ is also preferably substituted at the 5-position, and Z′ is preferably substituted at the 2-position, the 4-position or the 2-position and the 4-position.


[1477] Z and Z′ are preferably group D, “C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D” or “heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group D”, particularly preferably group D or “C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D”.


[1478] More preferably, they are the above-defined halogen atom, nitro, the above-defined optionally substituted C1-6 alkyl, —(CH2)t—COORa19, —(CH2)t—CONRa27Ra28, —(CH2)t—ORa20, —(CH2)t—NRa29CO—Ra24, —(CH2)t—S(O)q—Ra25 or —(CH2)t—SO2—NHRa26, or C6-14 aryl or heterocyclic group optionally substituted by these.


[1479] With regard to Z and Z′, the preferable mode of group D that directly substitutes each ring B and ring B′ and the preferable mode of group D that substitutes C6-14 aryl, C3-8 cycloalkyl, C6-14 aryl C1-6 alkyl or heterocyclic group are the same, wherein they may be the same with or different from each other.


[1480] Specific examples of the substituent preferably include fluorine atom, chlorine atom, bromine atom, nitro, cyano, methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, methoxymethyl, 2-carboxylethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, carbamoylmethoxymethyl, (dimethylaminocarbonyl)methoxymethyl, acetyl, isovaleryl, carboxyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl, methylaminocarbonyl, hydroxyaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, butylaminocarbonyl, isobutylaminocarbonyl, tert-butylaminocarbonyl, (4-hydroxybutyl)aminocarbonyl, (1-hydroxypropan-2-yl)aminocarbonyl, (2,3-dihydroxypropyl)-aminocarbonyl, (1,3-dihydroxypropan-2-yl)aminocarbonyl, methoxyaminocarbonyl, {2-[2-(methoxy)ethoxy]ethyl}aminocarbonyl, N-ethyl-N-methylaminocarbonyl, N-methyl-N-propylaminocarbonyl, N-isopropyl-N-methylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, (2-hydroxyethyl)aminocarbonyl, (2-hydroxy-2-methylpropan-2-yl)aminocarbonyl, (carboxylmethyl)aminocarbonyl, hydroxyl group, methoxy, ethoxy, propyloxy, isopropyloxy, butyloxy, isopentyloxy, 2-isopentenyloxy, 3-isohexenyloxy, 4-methyl-3-pentenyloxy, 2-propynyloxy, trifluoromethyloxy, hydroxymethyloxy, carboxylmethyloxy, (dimethylaminocarbonyl)-methyloxy, amino, methylamino, dimethylamino, diethylamino, acetylamino, N-acetyl-N-methylamino, ureido, isopropylcarbonylamino, isobutylcarbonylamino, tert-butylcarbonylamino, (ethylamino)carbonylamino, (isopropylamino)-carbonylamino, (dimethylamino)carbonylamino, (4-hydroxypiperidino)carbonylamino, [(4-hydroxypiperidino)methyl]-carbonylamino, [(3-hydroxypyrrolidinyl)methyl]carbonylamino, methylsulfonylamino, isopropylsulfonylamino, N-(isopropylsulfonyl)-N-methylamino, methylthio, methylsulfonyl, isopropylsulfonyl, isobutylsulfonyl, methylsulfinyl, isopropylsulfinyl, aminosulfonyl, methylaminosulfonyl, dimethylaminosulfonyl, isopropylaminosulfonyl, tert-butylamino-sulfonyl, hydroxyamidino, phenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,4-difluorophenyl, 3,4-difluorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 4-chloro-3-fluorophenyl, 4-chloro-2-fluorophenyl, 4-bromophenyl, 4-nitrophenyl, 4-cyanophenyl, 4-methylphenyl, 4-ethylphenyl, 4-propylphenyl, 4-isopropylphenyl, 4-tert-butylphenyl, 2-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-(hydroxymethyl)phenyl, 4-(2-hydroxyethyl)phenyl, 4-(methoxymethyl)phenyl, 4-(2-carboxylethyl)phenyl, 4-(methoxycarbonylmethyl)phenyl, 4-(ethoxycarbonylmethyl)phenyl, 4-acetylphenyl, 3-carboxylphenyl, 4-carboxylphenyl, 4-(methoxycarbonyl)phenyl, 4-(ethoxycarbonyl)phenyl, 4-carbamoylphenyl, 4-(methylaminocarbonyl)phenyl, 4-(isopropylaminocarbonyl)phenyl, 4-(dimethylaminocarbonyl)phenyl, 4-(diethylaminocarbonyl)phenyl, 4-[(2-hydroxyethyl)-aminocarbonyl]phenyl, 4-[(carboxylmethyl)aminocarbonyl]phenyl, 4-hydroxyphenyl, 4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 4-ethoxyphenyl, 4-propyloxyphenyl, 4-isopropyloxyphenyl, 4-butyloxyphenyl, 4-isopentyloxyphenyl, 4-(2-isopentenyloxy)phenyl, 4-(3-isohexenyloxy)phenyl, 4-(4-methyl-3-pentenyloxy)phenyl, 4-(2-propynyloxy)phenyl, 4-(trifluoromethyloxy)phenyl, 4-(hydroxymethyloxy)phenyl, 4-(carboxylmethyloxy)phenyl, 4-[(dimethylaminocarbonyl)methyloxy]phenyl, 4-aminophenyl, 4-(methylamino)phenyl, 4-(dimethylaminophenyl), 4-(diethylamino)-phenyl, 4-(acetylamino)phenyl, 4-(methylsulfonylamino)phenyl, 4-(methylthio)phenyl, 4-(methylsulfonyl)phenyl, 4-(methylsulfinyl)phenyl, 4-(aminosulfonyl)phenyl, 4-(methylaminosulfonyl)phenyl, 4-(dimethylaminosulfonyl)phenyl, 4-(tert-butylaminosulfonyl)phenyl, tetrazol-5-ylphenyl, cyclohexyl, benzyl, 4-chlorobenzyl, phenethyl, benzyloxy, 4-fluorobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 4-tert-butylbenzyloxy, 4-trifluoromethylbenzyloxy, phenethyloxy, 2-thienyl, 2-thiazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 6-fluoropyridin-3-yl, 5-fluoropyridin-2-yl, 6-chloropyridin-3-yl, 6-methylpyridin-3-yl, 2-pyrimidinyl, 5-tetrazolyl, piperidino, 2-oxopiperidin-1-yl, 2-oxopyrrolidin-1-yl, 2-imidazolin-2-yl, 2-oxoimidazolidin-1-yl, 2-oxooxazolidin-1-yl, 2-methylthiazol-4-yl, 5-methylthiazol-2-yl, 2-aminothiazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 1,1-dioxoisothiazolidin-2-yl, 4,4-dimethyl-Δ2-oxazolin-2-yl, 5-chlorothiophen-2-yl, 5-methyloxazol-2-yl, 5-oxo-Δ2-1,2,4-oxadiazolin-3-yl, 5-oxo-Δ2-1,2,4-thiadiazolin-3-yl, 2-oxo-3H-1,2,3,5-oxathiadiazolin-4-yl, 4-hydroxypiperidinomethyl, piperidinocarbonyl, 4-hydroxypiperidinocarbonyl, 3,4-dihydroxypiperidinocarbonyl, 1-piperazinylcarbonyl, 1-pyrrolidinylcarbonyl, morpholinocarbonyl, 4-thiomorpholinylcarbonyl, phenoxy, 2,4-dichlorophenoxy, tetrahydropyranyloxy, 2-pyridylmethyloxy, 3-pyridylmethyloxy, 2-chloropyridin-4-ylmethyloxy, 4-pyridylmethyloxy, 2-piperidylmethyloxy, 3-piperidylmethyloxy, 4-piperidylmethyloxy, 1-methylpiperidin-4-ylmethyloxy, 1-acetylpiperidin-4-ylmethyloxy, 1-(tert-butoxycarbonyl)piperidin-4-ylmethyloxy, 1-(methylsulfonyl)piperidin-4-ylmethyloxy, 2-methylthiazolin-4-yloxy, 2,4-dimethylthiazolin-5-yloxy, dimethylaminocarbonyl-methyloxy, piperidinocarbonylmethyloxy, 4-hydroxypiperidinocarbonylmethyloxy, 2-methylthiazol-4-yl, (2-methylthiazol-4-yl)methyloxy, (2,4-dimethylthiazol-5-yl)methyloxy, benzoyl, 3-fluorobenzoyl, 4-chlorobenzylamino, 3,5-dichlorobenzylamino, 4-trifluoromethylbenzylamino, 2-pyridylmethylamino, benzoylamino, 4-chlorobenzoylamino, 4-trifluoromethylbenzoylamino, 3,5-dichlorobenzoylamino, 3-nitro-4-methoxybenzoylamino, 4-nitro-3-methoxybenzoylamino, 3-pyridylcarbonylamino, morpholinocarbonyl-amino, 2-oxazolinylamino, 4-hydroxypiperidinosulfony, 4-methylphenylsulfonylamino, 2-thiazolylaminosulfonyl, 2-pyridylaminosulfonyl, benzylaminocarbonyl, N-benzyl-N-methylaminocarbonyl, (4-pyridylmethyl)aminocarbonyl or (cyclohexylmethyl)aminocarbonyl, 2-hydroxyethyloxy, 3-hydroxypropyloxy, 2-methoxyethoxy, 2-(2-methoxyethoxy)ethoxy, azetidinylcarbonyl, 3-hydroxypyrrolidinylcarbonyl, 3-hydroxypiperidinocarbonyl, 4-hydroxypiperidinocarbonyl, 3,4-dihydroxypiperidinocarbonyl, 4-methoxypiperidinocarbonyl, 4-carboxypiperidinocarbonyl, 4-(hydroxymethyl)piperidinocarbonyl, 2-oxopiperidinocarbonyl, 4-oxopiperidinocarbonyl, 2,6-dimethylpiperidinocarbonyl, 2,2,6,6-tetramethylpiperidinocarbonyl, 2,2,6,6-tetramethyl-4-hydroxypiperidinocarbonyl, 1-oxothiomorpholin-4-ylcarbonyl, 1,1-dioxothiomorpholin-4-ylcarbonyl, 1-(methylsulfonyl)piperidin-4-ylaminocarbonyl, 4-methylsulfonylpiperazinylcarbonyl, 4-methylpiperazinylcarbonyl, N,N-bis(2-hydroxyethyl)aminocarbonyl, phenylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclohexylaminocarbonyl, 4-hydroxycyclohexylaminocarbonyl, 4-methylthiazol-2-ylmethylaminocarbonyl, 2-(4-hydroxypiperidino)-ethyloxy, 2-pyridylmethylaminocarbonyl, 3-pyridylmethylamino-carbonyl, N-methyl-N-(4-pyridylmethyl)aminocarbonyl, cyclohexylmethyloxy, 4-hydroxypiperidinocarbonylmethyloxy and 4-methylthiazol-2-ylmethyloxy.


[1481] Particularly preferable examples of the substituent include fluorine atom, chlorine atom, bromine atom, nitro, cyano, methyl, hydroxymethyl, carboxyl, carbamoyl, methylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, diethylamino-carbonyl, (2-hydroxylethyl)aminocarbonyl, (carboxymethyl)-aminocarbonyl, methoxy, 2-isopentenyloxy, 2-propynyloxy, methylthio, methylamino, dimethylamino, acetylamino, methylsulfonylamino, methylsulfonyl, aminosulfonyl, dimethylaminosulfonyl, tert-butylaminosulfonyl, phenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,5-dichlorophenyl, 4-nitrophenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-trifluoromethylphenyl, 4-(methoxymethyl)phenyl, 4-(2-hydroxylethyl)phenyl, 3-carboxylphenyl, 4-carboxylphenyl, 4-methoxyphenyl, 4-carbamoylphenyl, 4-methylthiophenyl, 4-(dimethylaminocarbonyl)phenyl, 4-methylsulfonylphenyl, benzyl, phenethyl, benzyloxy, 4-fluorobenzyloxy, 4-chlorobenzyloxy, 2-thiazolyl, 3-pyridyl, 4-pyridyl, 4-pyridylmethyloxy, 2-piperidylmethyloxy, 3-piperidylmethyloxy, 4-piperidylmethyloxy, 1-methylpiperidin-4-ylmethyloxy, 1-acetylpiperidin-4-ylmethyloxy, 2-chloropiperidin-4-ylmethyloxy, 1-(methylsulfonyl)piperidin-4-ylmethyloxy, 2-methylthiazol-4-yl, (2-methylthiazol-4-yl)methyloxy, (2,4-dimethylthiazol-5-yl)methyloxy, 5-tetrazolyl, 3-fluorobenzoyl, piperidinocarbonyl, 4-hydroxylpiperidinocarbonyl, 1-pyrrolidinylcarbonyl, morpholinocarbonyl, 4-thiomorpholinylcarbonyl, benzylaminocarbonyl, N-benzyl-N-methylaminocarbonyl, (4-pyridylmethyl)aminocarbonyl and (cyclohexylmethyl)aminocarbonyl.


[1482] Most preferable substituents are fluorine atom, chlorine atom, methyl, hydroxymethyl, carboxyl, carbamoyl, methylaminocarbonyl, dimethylaminocarbonyl, methoxy, methylamino, acetylamino, aminosulfonyl, dimethylaminosulfonyl, tert-butylaminosulfonyl, phenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,5-dichlorophenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-trifluoromethylphenyl, 4-carboxylphenyl, 4-methoxyphenyl, 4-carbamoylphenyl, 4-methylthiophenyl, 4-(dimethylaminocarbonyl)phenyl, 4-methylsulfonylphenyl and 2-oxopyrrolidin-1-yl.


[1483] The w is preferably 1 or 2, r and t are preferably 0, 1 or 2, particularly preferably 0 or 1, more preferably 0, p is preferably 1, and q is preferably 0 or 2.


[1484] In formula [I], when X is
76


[1485] wherein each symbol is as defined above and w is 2 or above, one of Z is preferably C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group D, particularly preferably C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D.


[1486] The pharmaceutically acceptable salt may be any as long as it forms a non-toxic salt with a compound of the above-mentioned formula [I] or [II]. Such salt can be obtained by reacting the compound with an inorganic acid, such as hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid and the like, or an organic acid, such as oxalic acid, malonic acid, citric acid, fumaric acid, lactid acid, malic acid, succinic acid, tartaric acid, acetic acid, trifluoroacetic acid, gluconic acid, ascorbic acid, methylsulfonic acid, benzylsulfonic acid and the like, or an inorganic base, such as sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, ammonium hydroxide and the like, or an organic base, such as methylamine, diethylamine, triethylamine, triethanolamine, ethylenediamine, tris(hydroxymethyl)methylamine, guanidine, choline, cinchonine and the like, with an amino acid, such as lysine, arginine, alanine and the like. The present invention encompasses water-retaining product, hydrate and solvate of each compound.


[1487] The compounds of the above-mentioned formula [I] or [II] have various isomers. For example, E compound and Z compound are present as geometric isomers, and when the compound has an asymmetric carbon, an enantiomer and a diastereomer are present due to the asymmetric carbon. A tautomer may be also present. The present invention encompasses all of these isomers and mixtures thereof.


[1488] The present invention also encompasses prodrug and metabolite of each compound.


[1489] A prodrug means a derivative of the compound of the present invention, which is capable of chemical or metabolic decomposition, which shows inherent efficacy by reverting to the original compound after administration to a body, and which includes salts and complexes without a covalent bond.


[1490] When the inventive compound is used as a pharmaceutical preparation, the inventive compound is generally admixed with pharmaceutically acceptable carriers, excipients, diluents, binders, disintegrators, stabilizers, preservatives, buffers, emulsifiers, aromatics, coloring agents, sweeteners, thickeners, correctives, solubilizers, and other additives such as water, vegetable oil, alcohol such as ethanol, benzyl alcohol and the like, polyethylene glycol, glycerol triacetate, gelatin, lactose, carbohydrate such as starch and the like, magnesium stearate, talc, lanolin, petrolatum and the like, and prepared into a dosage form of tablets, pills, powders, granules, suppositories, infections, eye drops, liquids, capsules, troches, aerosols, elixirs, suspensions, emulsions, syrups and the like, which can be administered systemically or topically and orally or parenterally.


[1491] While the dose varies depending on the age, body weight, general condition, treatment effect, administration route and the like, it is from 0.1 mg to 1 g for an adult per dose, which is given one to several times a day.


[1492] The prophylaxis of hepatitis C means, for example, administration of a pharmaceutical agent to an individual found to carry an HCV by a test and the like but without a symptom of hepatitis C, or to an individual who shows an improved disease state of hepatitis after a treatment of hepatitis C, but who still carries an HCV and is associated with a risk of recurrence of hepatitis.


[1493] Inasmuch as HCV is known to be a virus associated with many genetic mutations, a compound effective for many genotypes is one of the preferable modes. If a compound ensures high blood concentration when administered as a pharmaceutical agent to an animal infected with HCV, it is also one of the preferable modes. From these aspects, a compound having high inhibitory activity on both HCV type 1a and type 1b and high blood concentration, such as 2-{4-[2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, is particularly preferable.


[1494] The fused ring compound of the formula [I] or [II] of the present invention can be administered to mammals inclusive of human for the purpose of prevention or treatment of hepatitis C or inhibition of hepatitis C virus polymerase. The fused ring compound of the present invention can be also administered to mammals inclusive of human along with at least one pharmaceutical agent (hereinafter combination drug) selected from an antiviral agent other than the compound of the formula [I], an antiinflammatory agent and an immunostimulant for the purpose of prevention or treatment of hepatitis C or inhibition of hepatitis C virus polymerase. In the case of combined administration, the compound of the present invention can be administered simultaneously with the combination drug or administered at certain time intervals. In the case of combined administration, a pharmaceutical composition containing the compound of the present invention and a combination drug can be administered. Alternatively, a pharmaceutical composition containing the compound of the present invention and a pharmaceutical composition containing a combination drug may be administered separately. The administration route may be the same or different.


[1495] In the case of a combined administration, the compound of the present invention can be administered once a day or several times a day in a single dose of 0.1 mg to 1 g, or may be administered in a smaller dose. The combination drug can be administered in a dose generally used for the prevention or treatment of hepatitis C or in a smaller dose.


[1496] Examples of other antiviral agent include interferons (interferon α, interferon β, interferon γ etc.), Ribavirin (1-β-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide) and the like.


[1497] Examples of the production method of the compound to be used for the practice of the present invention are given in the following. However, the production method of the compound of the present invention is not limited to these examples.


[1498] Even if no directly corresponding disclosure is found in the following Production Methods, the steps may be modified for efficient production of the compound, such as introduction of a protecting group into a functional group with deprotection in a subsequent step, and changing the order of Production Methods and steps.


[1499] The treatment after reaction in each step may be conventional ones, for which typical methods, such as isolation and purification, crystallization, recrystallization, silica gel chromatography, preparative HPLC and the like, can be appropriately selected and combined.



Production Method 1

[1500] In this Production Method, a benzimidazole compound is formed from a nitrobenzene compound.


[1501] Production Method 1-1
77


[1502] wherein Hal is halogen atom, such as chlorine atom, bromine atom and the like, Rc1 is halogen atom, such as chlorine atom, bromine atom and the like, or hydroxyl group, and other symbols are as defined above.


[1503] Step 1


[1504] A compound [1] obtained by a conventional method or a commercially available compound [1] is reacted with amine compound [2] in a solvent such as N,N-dimethylformamide (DMF), acetonitrile, tetrahydrofuran (THF), toluene and the like in the presence or absence of a base such as potassium carbonate, triethylamine, potassium t-butoxide and the like at room temperature or with heating to give compound [3].


[1505] Step 2


[1506] The compound [3] is hydrogenated in a solvent such as methanol, ethanol, THF, ethyl acetate, acetic acid, water and the like in the presence of a catalyst such as palladium carbon, palladium hydroxide, platinum oxide, Raney nickel and the like at room temperature or with heating to give compound [4]. In addition, compound [3] is reduced with a reducing agent such as zinc, iron, tin(II) chloride, sodium sulfite and the like, or reacted with hydrazine in the presence of iron(III) chloride to give compound [4].


[1507] Step 3


[1508] The compound [4] is condensed with carboxylic acid compound [5] in a solvent such as DMF, acetonitrile, THF, chloroform, ethyl acetate, methylene chloride, toluene and the like using a condensing agent such as dicyclohexylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, diphenylphosphoryl azide and the like and, where necessary, adding N-hydroxysuccinimide, 1-hydroxybenzotriazole and the like to give amide compound [6]. Alternatively, amide compound [6] can be obtained from compound [5] as follows. The carboxylic acid compound [5] is converted to an acid halide derived with thionyl chloride, oxalyl chloride and the like, or an active ester (e.g., mixed acid anhydride derived with ethyl chlorocarbonate and the like), which is then reacted in the presence of a base, such as triethylamine, potassium carbonate, pyridine and the like, or in an amine solvent, such as pyridine and the like, to give amide compound [6].


[1509] Step 4


[1510] The compound [6] is heated in a solvent such as ethanol, methanol, toluene, DMF, chloroform and the like or without a solvent in the presence of an acid such as acetic acid, formic acid, hydrochloric acid, dilute sulfuric acid, phosphoric acid, polyphosphoric acid, p-toluenesulfonic acid and the like, a halogenating agent such as zinc chloride, phosphorus oxychloride, thionyl chloride and the like or acid anhydride such as acetic anhydride and the like, to allow cyclization to give compound [I-2].


[1511] Production Method 1-2


[1512] This Production Method is an alternative method for producing compound [I-2].
78


[1513] wherein each symbol is as defined above.


[1514] Step 1


[1515] The compound [3] obtained in the same manner as in Step 1 of Production Method 1-1 is subjected to amide condensation with compound [5] in the same manner as in Step 3 of Production Method 1-1 to give compound [7].


[1516] Step 2


[1517] The compound [7] is reduced in the same manner as in Step 2 of Production Method 1-1 to give compound [8].


[1518] Step 3


[1519] The compound [8] is subjected to cyclization in the same manner as in Step 4 of Production Method 1-1 to give compound [I-2].


[1520] Production Method 1-3
79


[1521] wherein Rc2 is alkyl such as methyl, ethyl and the like, and other symbols are as defined above.


[1522] The compound [4] is reacted with imidate compound [9] in a solvent such as methanol, ethanol, acetic acid, DMF, THF, chloroform and the like at room temperature or with heating to give compound [I-2].


[1523] In addition, compound [4] may be reacted with aldehyde compound [10] in a solvent such as acetic acid, formic acid, acetonitrile, DMF, nitrobenzene, toluene and the like in the presence or absence of an oxidizing agent such as benzofuroxan, manganese dioxide, 2,3-dichloro-5,6-dicyano-p-benzoquinone, iodine, potassium ferricyanide and the like with heating to give compound [I-2].


[1524] Alternatively, compound [4] and carboxylic acid compound [11] may be heated to allow reaction in the presence of polyphosphoric acid, phosphoric acid, phosphorus oxychloride, hydrochloric acid and the like to give compound [I-2].



Production Method 2

[1525] In this Production Method, conversion of the substituents (R1, R2, R3, R4) on the benzene ring of benzimidazole is shown. While a method of converting R2 when R1, R3 and R4 are hydrogen atoms is shown, this Production Method is applicable irrespective of the position of substitution.


[1526] Production Method 2-1


[1527] Conversion of carboxylic acid ester moiety to amide
80


[1528] wherein E is a single bond, —(CH2)5—, —O—(CH2)5— or —NH—(CH2)5— (wherein s is an integer of 1 to 6), Rc3, Rc4 and Rc5 are C1-6 alkyl, and other symbols are as defined above.


[1529] Step 1


[1530] The compound [I-2-1] obtained in the same manner as in the above-mentioned Production Method is subjected to hydrolysis in a solvent such as methanol, ethanol, THF, dioxane and the like, or in a mixed solvent of these solvents and water under basic conditions with sodium hydroxide, potassium hydroxide, potassium carbonate, lithium hydroxide and the like or under acidic conditions with hydrochloric acid, sulfuric acid and the like to give compound [I-2-2].


[1531] Step 2


[1532] The compound [I-2-2] is reacted with compound [12] in the same manner as in Step 3 of Production Method 1-1 to give compound [I-2-3].


[1533] Production Method 2-2


[1534] Conversion of cyano group to substituted amidino group
81


[1535] wherein each symbol is as defined above.


[1536] The compound [I-2-4] obtained in the same manner as in the above-mentioned Production Method is reacted with hydroxylamine in a solvent such as water, methanol, ethanol, THF, DMF and the like to give compound [I-2-5]. When a salt of hydroxylamine such as hydrochloride and the like is used, the reaction is carried out in the presence of a base such as sodium hydrogencarbonate, sodium hydroxide, triethylamine and the like.


[1537] Production Method 2-3


[1538] Conversion of sulfonic acid ester moiety to sulfonic acid
82


[1539] wherein Rc6 is C1-6 alkyl, and other symbols are as defined above.


[1540] The compound [I-2-6] obtained in the same manner as in the lo above-mentioned Production Method is reacted with iodide salt such as sodium iodide, lithium iodide and the like, bromide salt :such as sodium bromide, trimethylammonium bromide and the like, amine such as pyridine, trimethylamine, triazole and the like, phosphine such as triphenylphosphine and the like in a solvent such as DMF, dimethyl sulfoxide (DMSO), acetonitrile, methanol, ethanol, water and the like with heating to give compound [I-2-7].



Production Method 3

[1541] This Production Method relates to convertion of the substituent(s) on phenyl group at the 2-position of benzimidazole. This Production Method can be used even when phenyl is a different ring.


[1542] Production Method 3-1


[1543] Conversion of hydroxyl group to ether
83


[1544] wherein Rc7 is optionally substituted alkyl corresponding to Ra11, G1 is a single bond, *—(CH2)n—, *—(CH2)n—O—, *—(CH2)n—CO— or *—(CH2)m—CRa15Ra16)—(CH2)n—, wherein * show the side to be bonded to Rc1, and other symbols are as defined above.


[1545] When Rc1 of compound [13] is halogen atom, compound [I-2-8] obtained in the same manner as in the above-mentioned Production Method is reacted with compound [13] in a solvent such as DMF, DMSO, acetonitrile, ethanol, THF and the like in the presence of a base such as sodium hydride, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium ethoxide, potassium t-butoxide and the like at room temperature or with heating to give compound [II-2-1].


[1546] When Rc1 of compound [13] is hydroxyl group, the hydroxyl group of compound [13] is converted to halogen atom with thionyl chloride, phosphorus tribromide, carbon tetrabromide-triphenylphosphine and the like and reacted with compound [I-2-8] by the aforementioned method to give compound [II-2-1]. In this case, compound [I-2-8] may be subjected to Mitsunobu reaction with compound [13] in a solvent such as DMF, acetonitrile, THF and the like using triphenylphosphine—diethyl azodicarboxylate and the like to give compound [II-2-1].


[1547] The compound [I-2-9] can be obtained in the same manner from compound [I-2-8] and compound [14].


[1548] Production Method 3-2


[1549] Conversion of nitro to substituted amino group
84


[1550] wherein Rc8 is C1-6 alkyl, G2 is *—(CH2)n— or *—CHRa15, G3 is —CO—, *—CO2—, *—CONH— or —SO2—, and other symbols are as defined above.


[1551] Step 1


[1552] The nitro compound [I-2-10] obtained in the same manner as in the above-mentioned Production Method is reacted in the same manner as in Step 2 of Production Method 1-1 to give compound [I-2-11].


[1553] Step 2


[1554] The compound [I-2-11] is alkylated with compound [15] in the same manner as in Production Method 3-1 to give compound [II-2-2].


[1555] Step 3


[1556] When G3 of compound [16] is —CO—, —CO2— or —CONH—, compound [I-2-11] is acylated with compound [16] in the same manner as in Step 3 of Production Method 1-1 to give compound [II-2-3].


[1557] When G3 of compound [16] is —SO2—, sulfonylation is conducted using sulfonyl halide instead of acid halide used in Step 3 of Production Method 1-1 to give compound [II-2-3].


[1558] The compound [I-2-11] is acylated with compound [17] in the same manner as above to give compound [I-2-12].


[1559] This Production Method is applied in the same manner as above to give disubstituted compounds (tertiary amine) of compound [II-2-2], compound [II-2-3] and compound [1-2-12].


[1560] Production Method 3-3


[1561] Conversion of carboxylic acid ester moiety to amide
85


[1562] wherein Rc9 is C1-6 alkyl, G4 is #—(CH2)n—, #—(CH2)n—NH— or #—CHRa14— wherein # shows the side that is bounded to amine and other symbols are as defined above.


[1563] Step 1


[1564] The compound [I-2-13] obtained in the same manner as in the above-mentioned Production Method is reacted in the same manner as in Step 1 of Production Method 2-1 to give compound [I-2-14].


[1565] Step 2


[1566] The compound [I-2-14] is reacted with compound [18] in the same manner as in Step 2 of Production Method 2-1 to give compound [II-2-4].


[1567] The compound [I-2-15] is obtained from compound [I-2-14] and compound [19] in the same manner as above.



Production Method 4

[1568] In this Production Method, additional substituent(s) is(are) introduced into ring B on phenyl group that substitutes the 2-position of benzimidazole. This Production Method is applicable even when phenyl is a different ring.


[1569] Production Method 4-1


[1570] Direct bonding of ring Z″ to ring B
86


[1571] wherein ring Z″—M is aryl metal compound, ring Z″ moiety is optionally substituted C6-14 aryl or optionally substituted heterocyclic group corresponding to substituent Z, and the metal moiety contains boron, zinc, tin, magnesium and the like, such as phenylboronic acid, w″ is 0, 1 or 2, and other symbols are as defined above.


[1572] The compound [II-2-5] obtained in the same manner as in the above-mentioned Production Method is reacted with aryl metal compound [20] in a solvent such as DMF, acetonitrile, 1,2-dimethoxyethane, THF, toluene, water and the like in the presence of a palladium catalyst such as tetrakis(triphenylphosphine)-palladium, bis(triphenylphosphine)palladium(II) dichloride, palladium acetate—triphenylphosphine and the like, a nickel catalyst such as nickel chloride, [1,3-bis(diphenylphosphino)-propane]nickel(II) chloride and the like, and a base such as potassium carbonate, potassium hydrogencarbonate, sodium hydrogen-carbonate, potassium phosphate, triethylamine and the like at room temperature or with heating, to give compound [II-2-6].


[1573] Production Method 4-2


[1574] Conversion of hydroxyl group to ether
87


[1575] wherein Rc10 is —Ra20 or —(CH2)p—CORa21 corresponding to substituent Z, and other symbols are as defined above.


[1576] The compound [II-2-7 ]obtained in the same manner as in the above-mentioned Production Method is reacted with compound [21] in the same manner as in Production Method 3-1 to give compound [II-2-8].


[1577] Production Method 4-3


[1578] Synthesis in advance of ring B part such as compound [13] in Production Method 3-1
88


[1579] wherein Rc11 is leaving group such as bromine atom, iodine atom, trifluoromethanesulfonyloxy and the like, Rc12 is formyl, carboxyl or carboxylic acid ester such as methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl and the like, and other symbols are as defined above.


[1580] Step 1


[1581] Commercially available compound [22] or compound [22] obtained by a conventional method is reacted with aryl metal compound [20] in the same manner as in Production Method 4-1 to give compound [23].


[1582] Step 2


[1583] The compound [23] obtained in the same manner as in the above-mentioned Production Method is reduced according to a conventional method to give compound [24].


[1584] For example, compound [23] is reacted with in a solvent such as methanol, ethanol, THF and the like in the presence of a reducing agent such as lithium aluminum hydride, sodium borohydride and the like under cooling to heating to give compound [24].


[1585] Step 3


[1586] The compound [24] obtained in the same manner as in the above-mentioned Production Method is reacted in a solvent such as 1,4-dioxane, diethyl ether, THF, dichloromethane, chloroform, toluene and the like with a halogenating agent, such as phosphorus pentachloride, phosphorus tribromide, thionyl chloride and the like, in the presence of a tertiary amine such as pyridine and the like to give compound [25].


[1587] Step 4


[1588] The compound [24] or [25] obtained in the same manner as in the above-mentioned Production Method is reacted with compound [I-2-8] in the same manner as in Production Method 3-1 to give compound [II-2-9].


[1589] Production Method 4-4
89


[1590] wherein M′ is a metal such as magnesium, lithium, zinc and the like, and other symbols are as defined above.


[1591] Step 1


[1592] Commercially available compound [41] or compound [41] obtained by a conventional method is converted to aryl metal reagent by a conventional method to give compound [42].


[1593] For example, when M′ is magnesium, magnesium is reacted with compound [41] in a solvent such as THF, diethyl ether, benzene, toluene and the like, preferably THF, from cooling to heating preferably at −100° C. to 100° C. to give compound [42].


[1594] Step 2


[1595] The compound [42] obtained in the same manner as in the above-mentioned Production Method is reacted with compound [43] to give compound [44].


[1596] The compound [42] is reacted in a solvent such as diethyl ether, benzene, toluene, THF and the like, preferably THF, from cooling to room temperature, preferably at −100° C. to 30° C. to give compound [44].


[1597] step 3


[1598] The compound [44] obtained in the same manner as in the above-mentioned Production Method is halogenated in the same manner as in Step 3 of Production Method 4-3 to give compound [45].


[1599] The compound [44] is reacted with thionyl chloride and pyridine preferably in toluene solvent to give compound [45].


[1600] When compound [45] is symmetric, namely, when the ring B—(Z)w moiety and the ring B′—(Z′)w′ moiety are the same, compound [42] is reacted with formate such as methyl formate, ethyl formate and the like, preferably ethyl formate, in a solvent such as diethyl ether, benzene, toluene, THF and the like, preferably THF, from cooling to room temperature, preferably at −100° C. to 30° C., to give compound [45].


[1601] Production Method 4-5


[1602] Method including steps to introduce a protecting group into a functional group
9091


[1603] wherein Rc13 is carboxylic acid protecting group such as tert-butyl and the like, Rc14 is carboxylic acid protecting group such as methyl and the like and other symbols are as defined above.


[1604] Step 1


[1605] Commercially available compound [26] or compound [26] obtained by a conventional method is protected by a conventional method to give compound [27].


[1606] For example, when Rc13 is tert-butyl, compound [26] is converted to acid halide with thionyl chloride, oxalyl chloride and the like in a solvent such as THF, chloroform, dichloromethane, toluene and the like, and reacted with potassium tert-butoxide to give compound [27].


[1607] As used herein, Rc13 may be a different protecting group as long as it is not removed during the Step 2 or Step 3 but removed in Step 4 without affecting —CO2Rc14.


[1608] Step 2


[1609] The methyl group of compound [27] obtained in the same manner as in the above-mentioned Production Method is converted to bromomethyl with N-bromosuccinimide and N,N′-azobisisobutyronitrile and reacted with compound [I-2-16] in the same manner as in Production Method 3-1 to give compound [II-2-10].


[1610] Step 3


[1611] The compound [II-2-10] obtained in the same manner as in the above-mentioned Production Method is reacted with aryl metal compound [20] in the same manner as in Production Method 4-1 to give compound [II-2-11].


[1612] Step 4


[1613] The Rc13 of the compound [II-2-11] obtained in the same manner as in the above-mentioned Production Method is removed by a conventional method to give compound [II-2-12].


[1614] The protecting group of carboxylic acid can be removed by a conventional deprotection method according to the protecting group. In this Step, the conditions free from reaction of Rc14 are preferable. For example, when Rc13 is tert-butyl, compound [II-2-11] is treated with trifluoroacetic acid in a solvent such as dichloromethane, chloroform and the like to give compound [II-2-12].


[1615] Step 5


[1616] The compound [II-2-12] obtained in the same manner as in the above-mentioned Production Method is subjected to amide condensation with compound [28] in the same manner as in Step 3 of Production Method 1-1 to give compound [II-2-13].


[1617] Step 6


[1618] The compound [II-2-13] obtained in the same manner as in the above-mentioned Production Method is deprotected in the same manner as in Step 1 of Production Method 2-1 to give compound [II-2-14].


[1619] As used herein, Rc14 is preferably a protecting group that does not react during the Step 1 through Step 5 but removed in this Step.


[1620] For example, when Rc14 is methyl, compound [II-2-13] is reacted in an alcohol solvent such as methanol, ethanol, n-propanol, isopropanol and the like or a mixed solvent of alcohol solvent and water in the presence of a base such as potassium carbonate, sodium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide and the like from cooling to heating for deprotection, followed by acidifying the reaction solution to give compound (II-2-14].


[1621] Production Method 4-6
92


[1622] wherein g is an integer of 1 to 5, and other sumbols are as defined above.


[1623] Step 1


[1624] The compound [I-2-16] obtained by the above-mentioned Production Method is reacted with toluene derivative [41] in the same manner as in Step 2 of Production Method 4-5 to give compound [II-2-17].


[1625] Step 2


[1626] The compound [II-2-17] obtained by the above-mentioned Production Method is reacted with aryl metal compound [20] in the same manner as in Production Method 4-1 to give compound [II-2-18].


[1627] Step 3


[1628] The compound [II-2-18] obtained by the above-mentioned Production Method is reduced in the same manner as in Step 2 of Production Method 1-1 to give compound [II-2-19].


[1629] Step 4


[1630] The compound [II-2-19] obtained by the above-mentioned Production Method is amide condensed with compound [42] in the same manner as in Step 3 of Production Method 1-1 and subjected to cyclization in the same manner as in Step 1 of Production Method 1-1 to give compound [II-2-20].


[1631] Step 5


[1632] The compound [II-2-20] obtained by the above-mentioned Production Method is hydrolyzed in the same manner as in Step 1 of Production Method 2-1 to give compound [II-2-21].



Production Method 5

[1633] Formation of indole ring
93


[1634] wherein Rc15 is protecting group such as trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl and the like, and other symbols are as defined above.


[1635] Step 1


[1636] The compound [29] obtained in the same manner as in the above-mentioned Production Method or conventional method is reacted with compound [30] in a solvent such as DMF, acetonitrile, 1,2-dimethoxyethane, THF, toluene, water and the like using a palladium catalyst such as tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium(II) dichloride, palladium acetate—triphenylphosphine and the like, a copper catalyst such as copper(I) iodide and the like or a mixture thereof, and in the presence of a base such as potassium carbonate, potassium hydrogencarbonate, sodium hydrogencarbonate, potassium phosphate, triethylamine and the like to give compound [31].


[1637] Step 2


[1638] The compound [31] obtained in the same manner as in the above-mentioned Production Method is reacted in an alcohol solvent such as methanol, ethanol and the like or a mixed solvent of an alcohol solvent and a solvent such as DMF, acetonitrile, THF, chloroform, dichloromethane, ethyl acetate, methylene chloride, toluene and the like in the presence of a base such as potassium carbonate, sodium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium hydride, sodium hydride, potassium hydride and the like at room temperature or with heating for deprotection, and reacted with compound [32] obtained in the same manner as in Step 1 of Production Method 1-1 in the same manner as in Step 1 of Production Method 5 to give compound [33].


[1639] Step 3


[1640] The compound [33] obtained in the same manner as in the above-mentioned Production Method was subjected to cyclization in a solvent such as DMF, acetonitrile, THF, chloroform, dichloromethane, ethyl acetate, methylene chloride, toluene and the like in the presence of a copper catalyst such as copper(I) iodide and the like or a palladium catalyst such as palladium(II) chloride and the like at room temperature or with heating to give compound [II-2-15].



Production Method 6

[1641] Formation of imidazo[1,2-a]pyridine ring
94


[1642] wherein Rc16 and Rc17 are each independently alkyl, such as methyl, ethyl and the like, and other symbols are as defined above.


[1643] Step 1


[1644] The compound [34] obtained by the above-mentioned Production Method or a conventional method is subjected to amide condensation with compound [35] in the same manner as in Step 3 of Production Method 1-1 to give compound [36].


[1645] Step 2


[1646] The compound [36] obtained by the above-mentioned Production Method is reacted with Grignard reagent [37] obtained by a conventional method to give compound [38].


[1647] Alternatively, an acid halide of compound [34] may be used instead of compound [36].


[1648] Step 3


[1649] The compound [38] obtained by the above-mentioned Production Method is subjected to halogenation by a conventional method to give compound [39].


[1650] For example, when Hal is a bromine atom, compound [38] is reacted with bromine under cooling or at room temperature in a solvent such as DMF, acetonitrile, THF, chloroform, dichloromethane, ethyl acetate, toluene and the like to give compound [39].


[1651] Alternatively, a halogenating agent such as hypohalite (e.g., hypochlorite and the like), N-bromosuccinimide and the like may be used instead of bromine for halogenation.


[1652] Step 4


[1653] The compound [39] obtained by the above-mentioned Production Method is subjected to cyclization with compound [40] obtained by a conventional or known method (JP-A-8-48651) in the presence of a base such as potassium carbonate, sodium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium hydride, sodium hydride, potassium hydride and the like in a solvent or without a solvent at room temperature or with heating to give compound [II-2-16].


[1654] In the compounds of the formulas [I] and [II], a desired heterocyclic group can be formed according to a method similar to the methods disclosed in known publications. Examples of such heterocyclic group and reference publications are recited in the following.


[1655] 5-oxo-Δ2-1,2,4-oxadiazolin-3-yl (or 2,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl), 5-oxo-Δ2-1,2,4-thiadiazolin-3-yl (or 2,5-dihydro-5-oxo-4H-1,2,4-thiadiazol-3-yl), 2-oxo-Δ3-1,2,3,5-oxathiadiazolin-4-yl (or 2-oxo-Δ3-1,2,4-oxathiadiazol-4-yl): Journal of Medicinal Chemistry, 39(26), 5228-35, 1996,


[1656] 5-oxo-Δ2-1,2,4-triazolin-3-yl: J Org Chem, 61(24), 8397-8401, 1996,


[1657] 1-oxo-Δ3-1,2,3,5-thiatriazolin-4-yl: Liebigs Ann Chem, 1376, 1980,


[1658] 3-oxo-Δ4-1,2,4-oxadiazolin-5-yl: EP145095,


[1659] 5-oxo-Δ2-1,3,4-oxadiazolin-2-yl: J Org Chem, 20, 412, 1955,


[1660] 5-oxo-Δ3-1,2,4-dioxazolin-3-yl: J Prakt Chem, 314, 145, 1972,


[1661] 3-oxo-Δ4-1,2,4-thiadiazolin-5-yl: JP-A-61-275271,


[1662] 5-oxo-Δ3-1,2,4-dithiazolin-3-yl: J Org Chem, 61(19), 6639-6645, 1996,


[1663] 2-oxo-Δ4-1,3,4-dioxazolin-5-yl: J Org Chem, 39, 2472, 1974,


[1664] 2-oxo-Δ4-1,3,4-oxathiazolin-5-yl: J Med Chem, 35(20), 3691-98, 1992,


[1665] 5-oxo-Δ2-1,3,4-thiadiazolin-2-yl: J Prakt Chem, 332(1), 55, 1990,


[1666] 5-oxo-Δ2-1,4,2-oxathiazolin-3-yl: J Org Chem, 31, 2417, 1966,


[1667] 2-oxo-Δ4-1,3,4-dithiazolin-5-yl: Tetrahedron Lett, 23, 5453, 1982,


[1668] 2-oxo-Δ4-1,3,2,4-dioxathiazolin-5-yl: Tetrahedron Lett, 319, 1968,


[1669] 3,5-dioxoisooxazolidin-4-yl: Helv Chim Acta, 1973, 48, 1965,


[1670] 2,5-dioxoimidazolidin-4-yl: Heterocycles, 43(1), 49-52, 1996,


[1671] 5-oxo-2-thioxoimidazolidin-4-yl: Heterocycles, 5, 391, 1983,


[1672] 2,4-dioxooxazolidin-5-yl: J Am Chem Soc, 73, 4752, 1951,


[1673] 4-oxo-2-thioxooxazolidin-5-yl: Chem Ber, 91, 300, 1958,


[1674] 2,4-dioxothiazolidin-5-yl: JP-A-57-123175,


[1675] 4-oxo-2-thioxothiazolidin-5-yl: Chem Pharm Bull, 30, 3563, 1982,


[1676] The Production Methods shown in the above-mentioned Production Methods 2 to 4 can be used for the synthesis of compounds other than benzimidazole of the formulas [I] and [II], such as compounds [II-2-15] and [II-2-16].


[1677] The compounds of the formulas [I], [II] and [III], 4-(4-fluorophenyl)-5-hydroxymethyl-2-methylthiazole and 4-(4-fluorophenyl)-5-chloromethyl-2-methylthiazole and production methods thereof of the present invention are explained in detail in the following by way of Examples. It is needless to say that the present invention is not limited by these Examples.







EXAMPLE 1


Production of Ethyl 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1678] Step 1: Production of Ethyl 4-chloro-3-nitrobenzoate


[1679] 4-Chloro-3-nitrobenzoic acid (300 g) was dissolved in ethyl alcohol (1500 ml) and concentrated sulfuric acid (100 ml) was added with ice-cooling. The mixture was refluxed under heating for 7 hr. The reaction mixture was poured into ice-cold water and the precipitated crystals were collected by filtration to give the title compound (332 g, yield 97%).


[1680]

1
H-NMR (300 MHz, CDCl3): 8.50(1H, d, J=2.1 Hz), 8.16(1H, dd, J=8.4, 2.1 Hz), 7.63(1H, d, J=8.4 Hz), 4.43(2H, q, J=7.5 Hz), 1.42(3H, t, J=7.5 Hz)


[1681] Step 2: Production of Ethyl 4-cyclohexylamino-3-nitrobenzoate


[1682] Ethyl 4-chloro-3-nitrobenzoate (330 g) obtained in the previous step was dissolved in acetonitrile (1500 ml), and cyclohexylamine (220 g) and triethylamine (195 g) were added. The mixture was refluxed under heating overnight. The reaction mixture was poured into ice-cold water and the precipitated crystals were collected by filtration to give the title compound (400 g, yield 94%).


[1683]

1
H-NMR (300 MHz, CDCl3): 8.87(1H, d, J=2.1 Hz), 8.35-8.46(1H, m), 8.02(1H, dd, J=9.1, 2.1 Hz), 6.87(1H, d, J=9.1 Hz), 4.35(2H, q, J=7.1 Hz), 3.65-3.50(1H, m), 2.14-1.29(10H, m), 1.38(3H, t, J=7.1 Hz)


[1684] Step 3: Production of Ethyl 3-amino-4-cyclohexylaminobenzoate


[1685] Ethyl 4-cyclohexylamino-3-nitrobenzoate (400 g) obtained in the previous step was dissolved in ethyl acetate (1500 ml) and ethyl alcohol (500 ml), and 7.5% palladium carbon (50% wet, 40 g) was added. The mixture was hydrogenated for 7 hr at atmospheric pressure. The catalyst was filtered off and the filtrate was concentrated under reduced pressure. Diisopropyl ether was added to the residue and the precipitated crystals were collected by filtration to give the title compound (289 g, yield 80%).


[1686]

1
H-NMR (300 MHz, CDCl3): 7.57(1H, dd, J=8.4, 1.9 Hz), 7.41(1H, d, J=1.9 Hz), 6.59(1H, d, J=8.4 Hz), 4.30(2H, q, J=7.1 Hz), 3.40-3.30(1H, m), 2.18-2.02(2H, m), 1.88-1.15(8H, m), 1.35(3H, t, J=7.1 Hz)


[1687] Step 4: Production of Ethyl 3-[4-(3-bromophenoxy)benzoyl]amino-4-cyclohexylaminobenzoate


[1688] 4-(3-Bromophenoxy)benzoic acid (74 g) was dissolved in chloroform (500 ml), and oxalyl chloride (33 ml) and dimethylformamide (catalytic amount) were added. The mixture was stirred for 4 hr at room temperature. The reaction mixture was concentrated under reduced pressure and dissolved in ,dichloromethane (150 ml). The resulting solution was added dropwise to a solution of ethyl 3-amino-4-cyclohexylaminobenzoate (66 g) obtained in the previous step in dichloromethane (500 ml) and triethylamine (71 ml), and the mixture was stirred for 1 hr at room temperature. The reaction mixture was poured into water and extracted with dichloromethane. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Diethyl ether was added to the residue for crystallization and the crystals were collected by filtration to give the title compound (129 g, yield 95%).


[1689]

1
H-NMR (300 MHz, CDCl3): 8.00-7.78(4H, m), 7.66(1H, brs), 7.37-7.18(3H, m), 7.13-6.59(3H, m), 6.72(1H, d, J=8.7 Hz), 4.50(1H, brs), 4.29(2H, q, J=7.2 Hz), 3.36(1H, m), 2.12-1.96(2H, m), 1, 83-1.56(3H, m), 1.47-1.12(5H, m), 1.37(3H, t, J=7.2 Hz)


[1690] Step 5: Production of Ethyl 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate


[1691] Ethyl 3-[4-(3-bromophenoxy)benzoyl]amino-4-cyclohexylaminobenzoate (129 g) obtained in the previous step was suspended in acetic acid (600 ml) and the resulting suspension was refluxed under heating for 3 hr. The reaction mixture was concentrated under reduced pressure. Water was added to the residue and the precipitated crystals were collected by filtration to give the title compound (124 g, yield 99%).


[1692]

1
H-NMR (300 MHz, CDCl3): 8.51(1H, d, J=1.5 Hz), 8.00(1H, dd, J=8.4, 1.5 Hz), 7.67(1H, d, J=8.4 Hz), 7.63(2H, d, J=8.7 Hz), 7.35-7.21(3H, m), 7.17(2H, d, J=8.7 Hz), 7.14(1H, m), 4.42(2H, q, J=7.2 Hz), 4.38(1H, m), 2.43-2.22(2H, m), 2.07-1.87(4H, m), 1.80(1H, m), 1.42(3H, t, J=7.2 Hz), 1.40-1.27(3H, m)



EXAMPLE 2


Production of 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid

[1693] Ethyl 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylate (1.0 g) obtained in Example 1 was dissolved in tetrahydrofuran (10 ml) and ethyl alcohol (10 ml), and 4N sodium hydroxide (10 ml) was added. The mixture was refluxed under heating for 1 hr. The reaction mixture was concentrated under reduced pressure and water was added to the residue. The mixture was acidified with 6N hydrochloric acid and the precipitated crystals were collected by filtration to give the title compound (0.9 g, yield 96%). melting point: 255-256° C. FAB-Ms: 491(MH+)


[1694]

1
H-NMR (300 MHz, DMSO-d6): (12.75(1H, brs), 8.24(1H, s), 7.96(1H, d, J=8.7 Hz), 7.86(1H, d, J=8.7 Hz), 7.71(2H, d, J=8.6 Hz), 7.47-7.34(3H, m), 7.24(2H, d, J=8.6 Hz), 7.20(1H, m), 4.31(1H, m), 2.38-2.18(2H, m), 2.02-1.79(4H, m), 1.65(1H, m), 1.44-1.20(3H, m)



EXAMPLE 3


Production of Ethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate

[1695] Ethyl 3-amino-4-cyclohexylaminobenzoate (130 g) obtained in Example 1, Step 3, and methyl 4-hydroxybenzimidate hydrochloride (139 g) were added to methyl alcohol (1500 ml), and the mixture was refluxed under heating for 4 hr. The reaction mixture was allowed to cool and the precipitated crystals were collected by filtration to give the title compound (131 g, yield 72%).


[1696]

1
H-NMR (300 MHz, CDCl3): 10.02(1H, brs), 8.21(1H, d, J=1.4 Hz), 7.93(1H, d, J=8.6 Hz), 7.83(1H, dd, J=8.6, 1.4 Hz), 7.48(2H, d, J=8.6 Hz), 6.95(2H, d, J=8.6 Hz), 4.39-4.25(1H, m), 4.33(1H, q, J=7.0 Hz), 2.35-2.18(2H, m), 1.98-1.79(4H, m), 1.70-1.60(1H, m), 1.46-1.19(3H, m), 1.35(3H, t, J=7.0 Hz)



EXAMPLE 4


Production of Ethyl 2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1697] 2-Bromo-5-chlorobenzyl bromide prepared from 2-bromo-5-chlorotoluene (50 g), N-bromosuccinimide and N,N′-azobisisobutyronitrile, and ethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate (50 g) obtained in Example 3 were suspended in dimethylformamide (300 ml). Potassium carbonate (38 g) was added and the mixture was stirred for 1 hr at 80° C. with heating. The reaction mixture was allowed to cool and then added to a mixed solvent of water-ethyl acetate. The precipitated crystals were collected by filtration to give the title compound (50 g, yield 64%).


[1698]

1
H-NMR (300 MHz, CDCl3): 8.50(1H, d, J=1.4 Hz), 7.97(1H, dd, J=8.6, 1.4 Hz), 7.70-7.57(5H, m), 7.20(1H, dd, J=8.4, 2.5 Hz), 7.14(2H, d, J=8.7 Hz), 5.17(2H, s), 4.46-4.30(1H, m), 4.41(2H, q, J=7.1 Hz), 2.40-2.20(2H, m), 2.02-1.21(8H, m), 1.42(3H, t, J=7.1 Hz)



EXAMPLE 5


Production of Ethyl 2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1699] Ethyl 2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (49 g) obtained in Example 4,4-chlorophenylboronic acid (18 g) and tetrakis-(triphenylphosphine)palladium (10 g) were suspended in 1,2-dimethoxyethane (600 ml). Saturated aqueous sodium hydrogencarbonate solution (300 ml) was added and the mixture was refluxed under-heating for 2 hr. Chloroform was added to the reaction mixture. The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (developing solvent, chloroform:ethyl acetate=97:3). Ethyl acetate and diisopropyl ether were added to the resulting oil for crystallization and the * resulting crystals were collected by filtration to give the title compound (44 g, yield 85%).


[1700]

1
H-NMR (300 MHz, CDCl3): 8.49(1H, d, J=1.4 Hz), 7.97(1H, dd, J=8.6, 1.6 Hz), 7.70-7.60(2H, m), 7.55(2H, d, J=8.7 Hz), 4.95(2H, s), 4.48-4.28(1H, m), 4.40(2H, m), 2.02-1.20(8H, m), 1.41(3H, t, J=7.1 Hz)



EXAMPLE 6


Production of 2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid

[1701] Ethyl 2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (43 g) obtained in Example 5 was treated in the same manner as in Example 2 to give the title compound (33 g, yield 76%).


[1702] melting point: 243-244° C. FAB-Ms: 571(MH+) 1H-NMR (300 MHz, DMSO-d6): 8.32(1H, s), 8.28(1H, d, J=8.9 Hz), 8.05(1H, d, J=8.8 Hz), 7.76-7.72(3H, m), 7.58-7.46(5H, m), 7.40(1H, d, J=8.3 Hz), 7.24(2H, d, J=8.9 Hz), 5.11(2H, s), 4.36(1H, m), 2.40-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m)



EXAMPLE 7


Production of Ethyl 2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1703] Ethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate obtained in Example 3 and 2-bromo-5-methoxybenzyl bromide were treated in the same manner as in Example 4 to give the title compound (59 g).



EXAMPLE 8


Production of Ethyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy[-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1704] Ethyl 2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate obtained in Example 7 was treated in the same manner as in Example 5 to give the title compound (48 g, yield 77%).


[1705]

1
H-NMR (300 MHz, CDCl3): 8.49(1H, d, J=1.4 Hz), 7.97(1H, dd, J=8.6, 1.4 Hz), 7.64(1H, d, J=8.6 Hz), 7.54(2H, d, J=8.7 Hz), 7.37(2H, d, J=8.6 Hz), 7.31(2H, d, J=8.6 Hz), 7.25(1H, d, J=8.4 Hz), 7.19(1H, d, J=2.7 Hz), 7.00(2H, d, J=8.7 Hz), 6.97(1H, dd, J=8.4, 2.7 Hz), 4.98(2H, s), 4.41(2H, q, J=7.1 Hz), 4.42-4.29(1H, m), 3.88(3H, s), 2.40-2.20(2H, m), 2.01-1.88(4H, m), 1.83-1.73(1H, m), 1.42(3H, t, J=7.1 Hz), 1.41-1.25(3H, m)



EXAMPLE 9


Production of 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid

[1706] Ethyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (52 g) obtained in Example 8 was treated in the same manner as in Example 2 to give the title compound (44 g, yield 89%).


[1707] melting point: 248-249° C. FAB-Ms: 568(MH+) 1H-NMR (300 MHz, DMSO-d6): 8.20(1H, s), 7.88(1H, d, J=8.7 Hz), 7.85(1H, d, J=8.7 Hz), 7.57(d, 2H, J=8.6 Hz), 7.46(2H, d, J=8.6 Hz), 7.44(2H, d, J=8.6 Hz), 7.29(1H, d, J=8.5 Hz), 7.24(1H, d, J=2.6 Hz), 7.11(2H, d, J=8.6 Hz), 7.06(1H, dd, J=8.5, 2.6 Hz), 5.04(2H, s), 4.26(1H, m), 3.83(3H, s), 2.38-2.29(2H, m)



EXAMPLE 10


Production of Ethyl 1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}-benzimidazole-5-carboxylate

[1708] Ethyl 3-amino-4-cyclohexylaminobenzoate (500 mg) obtained in Example 1, Step 3, was dissolved in methyl alcohol (6 ml) and trans-4-stilbenecarbaldehyde (397 mg) was added under ice-cooling. The mixture was stirred overnight at room temperature. The reaction mixture was ice-cooled and benzofuroxan (259 mg) dissolved in acetonitrile (2 ml) was. added. The mixture was stirred for 7 hr at 50° C., The reaction mixture was ice-cooled. After 1N sodium-hydroxide was added, ethyl acetate was added and the mixture was extracted. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (developing solvent, n-hexane:ethyl acetate=4:1) to give the title compound (540 mg, yield 63%).


[1709]

1
H-NMR (300 MHz, DMSO-d6): 8.28(1H d, J=1.4 Hz), 8.01(1H, d, J=8.7 Hz) 7.90-7.80(3H, m), 7.75-7.65(4H, m), 7.50-7.25(5H, m), 4.35(2H, q, J=7.0 Hz), 4.31(1H, m), 2.40-2.20(2H, m), 2.00-1.80(4H, m), 1.63(1H, m), 1.40-1.20(3H, m), 1.36(3H, t, J=7.0 Hz)



EXAMPLE 11


Production of 1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}-benzimidazole-5-carboxylic-acid

[1710] Ethyl 1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}-benzimidazole-5-carboxylate (127 mg) obtained in Example 10 was treated in the same manner as in Example 2 to give the title compound (116 mg, yield 97%).


[1711] melting point: not lower than 300° C. FAB-Ms: 423(MH+) 1H-NMR (300 MHz, DMSO-d6): 8.25(1H, s), 7.96-7.29(13H, m), 4.33(1H, brt), 2.41-2.23(2H, m), 2.03-1.78(4H, m), 1.71-1.59(1H, m), 1.49-1.20(3H, m)



EXAMPLE 12


Production of 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid

[1712] In the same manner as in Examples 1 and 2, the title compound (700 mg) was obtained.


[1713] FAB-Ms: 413(MH+) 1H-NMR (300 MHz, CDCl3): 8.60(1H, s), 8.04(1H, d, J=9.0 Hz), 7.63(2H, d, J=8.4 Hz), 7.51-7.32(6H, m), 7.14(2H, d, J=9.0 Hz), 5.16(2H, s), 5.03-4.89(1H, m), 2.41-1.63(8H, m)



EXAMPLE 13


Production of 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide

[1714] 2-(4-Benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (700 mg) obtained in Example 12 was dissolved in dimethylformamide (10 ml), and ammonium chloride (108 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (390 mg), 1-hydroxybenzotriazole (275 mg) and triethylamine (0.3 ml) were added. The mixture was stirred overnight at room temperature. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Ethyl acetate and diisopropyl ether were added to the residue for crystallization and the crystals were collected by filtration to give the title compound (571 mg, yield 81%).


[1715] melting point: 232-233° C. FAB-Ms: 412(MH+) 1H-NMR (300 MHz, CDCl3): 8.23(1H, d, J=1.5 Hz), 7.86(1H, dd, J=8.5, 1.5 Hz), 7.65-7.30(8H, m), 7.13(2H, d, J=8.8 Hz), 5.16(2H, s), 4.93(1H, quint, J=8.8 Hz), 2.40-1.60(8H, m)



EXAMPLE 14


Production of 2-(4-benzyloxyphenyl)-5-cyano-1-cyclopentylbenzimidazole

[1716] In the same manner as in Example 1, the title compound (400 mg) was obtained.


[1717] FAB-Ms: 394(MH+) 1H-NMR (300 MHz, CDCl3): 8.11(1H, s), 7.68-7.30(9H, m), 7.13(2H, s), 5.16(2H, s), 4.94(1H, quint, J=8.9 Hz), 2.35-1.60(8H, m)



EXAMPLE 15


Production of 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide oxime

[1718] 2-(4-Benzyloxyphenyl)-5-cyano-1-cyclopentylbenzimidazole (400 mg) obtained in Example 14 was suspended in ethyl alcohol (3 ml) and water (1.5 ml), and hydroxylamine hydrochloride (141 mg) and sodium hydrogencarbonate (170 mg) were added. The mixture was refluxed under heating overnight. The reaction mixture was allowed to cool and the precipitated crystals were collected by filtration to give the title compound (312 mg, yield 71%).


[1719] melting point: 225-226° C. FAB-Ms: 456(MH+) 1H-NMR (300 MHz, DMSO-d6): 8.20(1H, s), 7.50-7.31(9H, m), 7.12(2H, d, J=8.7 Hz), 5.15(2H, s), 4.94(1H, quint, J=8.7 Hz), 3.61(3H, s), 3.40(3H, s), 2.41-1.42(8H, m)



EXAMPLE 16


Production of Ethyl 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxyl]phenyl}benzimidazole-5-carboxylate

[1720] Step 1: Production of 4-(4-fluorophenyl)-5-hydroxymethyl-2-methylthiazole


[1721] Ethyl 4-(4-fluorophenyl)-2-methyl-5-thiazolecarboxylate (59 g) prepared by a known method (Chem. Pharm. Bull., 43(6), 947, 1995) was dissolved in tetrahydrofuran (700 ml). Lithium aluminum hydride (13 g) was added under ice-cooling and the mixture was stirred for 30 min. Water (13 ml), 15% sodium hydroxide (13 ml) and water (39 ml) were added successively to the reaction mixture, and the precipitated insoluble materials were filtered off. The filtrate was concentrated under reduced pressure to give the title compound (37 g, yield 71%).


[1722]

1
H-NMR (300 MHz, CDCl3): 7.60(2H, dd, J=8.7, 6.6 Hz), 7.11(2H, t, J=8.7 Hz), 4.80(2H, s), 2.70(3H, s)


[1723] Step 2: Production of 5-chloromethyl-4-(4-fluorophenyl)-2-methylthiazole,


[1724] 4-(4-Fluorophenyl)-5-hydroxymethyl-2-methylthiazole (37 g) obtained in the previous step was dissolved in chloroform (500 ml), and thionyl chloride (24 ml) and pyridine (2 ml) were added. The mixture was stirred for 3 hr at room temperature. The reaction mixture was poured into ice-cold water. The mixture was extracted with chloroform, and washed with water and saturated brine. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure to give the title compound (29 g, yield 76%).


[1725]

1
H-NMR (300 MHz, CDCl3): 7.67(2H, dd, J=8.8, 5.4 Hz), 7.16(2H, t, J=8.7 Hz), 4.79(2H, s), 2.73(3H, s)


[1726] Step 3: Production of Ethyl 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylate


[1727] 5-Chloromethyl-4-(4-fluorophenyl)-2-methylthiazole (28 g) obtained in the previous step and ethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate (36 g) obtained in Example 3 were treated in the same manner as in Example 4 to give the title compound (61 g, yield 100%).


[1728] APCI-Ms: 570(MH+) 1H-NMR (300 MHz, DMSO-d6): 8.25(1H, d, J=1.5 Hz), 7.97(1H, d, J=8.7 Hz), 7.86(1H, dd, J=8.6, 1.6 Hz), 7.74(2H, dd, J=8.8, 5.5 Hz), 7.62(2H, d, J=8.7 Hz), 7.33(2H, t, J=8.9 Hz), 7.22(2H, t, J=8.9 Hz), 5.41(2H, s), 4.34(2H, q, J=7.1 Hz), 4.31(1H, m), 2.71(3H, s), 2.40-2.15(2H, m), 2.05-1.75(4H, m), 1.55-1.15(3H, m), 1.36(3H, t, J=7.1 Hz)



EXAMPLE 17


Production of 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid

[1729] Ethyl 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylate (60 g) obtained in Example 16 was treated in the same manner as in Example 2 to give the title compound (39 g, yield 69%).


[1730] melting point: 196-198° C. FAB-Ms: 542(MH+) 1H-NMR (300 MHz, DMSO-d6): 13.1(1H, brs), 8.34(1H, s), 8.29(1H, d, J=8.8 Hz), 8.06(1H, d, J=8.7 Hz), 7.80-7.72(4H, m), 7.36-7.31(4H, m), 5.46(2H, s), 4.38(1H, m), 2.72(3H, s), 2.45-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.20(3H, m)



EXAMPLE 18


Production of Ethyl 1-cyclohexyl-2-(2-fluoro-4-hydroxyphenyl)-benzimidazole-5-carboxylate

[1731] In the same manner as in Example 3, the title compound (50 g) was obtained.



EXAMPLE 19


Production of Ethyl 2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1732] Step 1: Production of 3,3′-difluorobenzhydrol


[1733] To a stirred solution of magnesium strip (35.4 g) in THF (200 ml), iodine strip was added and the mixture was heated with stirring under nitrogen stream until most of color of iodine was disappeared. A solution of 3-fluoro-bromobenzene (250.0 g) in THF (1000 ml) was added dropwise over 2.5 hr while the temperature of the solution was maintained at 60° C., After the completion of the addition of the solution, the resulting mixture was refluxed for 1 hr with heating. The resulting Grignard solution was ice-cooled and a solution of ethyl formate (63.2 g) in THF (200 ml) was added dropwise over 1 hr. After a stirring of the reaction solution for an additional 30 min, saturated aqueous ammonium chloride solution (700 ml) was added dropwise with ice-cooling and water (300 ml) was added. The mixture was stirred for 10 min. The organic layer and water layer were separated. Water layer was extracted with ethyl acetate, and the combined organic layer was washed with 2N hydrochloric acid, saturated aqueous sodium hydrogencarbonate and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated off under reduced pressure to give the title compound (156.2 g, yield 99%).


[1734] 1H-NMR (300 MHz, CDCl3): 7.31(2H, td, J=7.9, 5.8 Hz), 7.15-7.80(4H, m), 6.97-6.94(2H, m), 5.82(1H, d, J=3.3 Hz), 2.30(1H, d, J=3.3 Hz)


[1735] Step 2: Production of 3,3′-difluorobenzhydryl chloride


[1736] To a solution of 3,3′-difluorobenzhydrol (150.0 g) obtained in the previous step in toluene (400 ml), pyridine (539 mg) was added at room temperature. To the solution, thionyl chloride (89.1 g) was added dropwise over 1 hr at room temperature and the resulting solution was stirred for an additional 2 hr. The solution was heated so that the temperature of the solution was at 40° C., and then stirred for an additional 1.5 hr. Thionyl chloride (8.1 g) was added again and the mixture was stirred for 30 min. To the reaction mixture, water was added. The organic layer was separated, and washed with water, saturated aqueous sodium hydrogencarbonate and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, the solvent was evaporated off under reduced pressure to give the title compound (158.2 g, yield 97%).


[1737]

1
H-NMR (300 MHz, CDCl3): 7.32(2H, td, J=8.0, 5.9 Hz), 7.18-7.10(4H, m), 7.01(2H, tdd, J=8.2, 2.5, 1.2 Hz), 6.05(1H, s)


[1738] Step 3: Production of Ethyl 2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate


[1739] Ethyl 1-cyclohexyl-2-(2-fluoro-4-hydroxyphenyl)-benzimidazole-5-carboxylate (50 g) obtained in Example 18 and 3,3′-difluorobenzhydryl chloride (34 g) obtained in the previous step were treated in the same manner as in Example 4 to give the title compound (76 g, yield 99%).


[1740] FAB-Ms: 585(MH+) 1H-NMR (300 MHz, DMSO-d6): 8.24(1H, d, J=1.4 Hz), 7.98(1H, d, J=8.7 Hz), 7.88(1H, d, J=8.7 Hz), 7.56(1H, t, J=8.6 Hz), 7.50-7.40(6H, m), 6.82(1H, s), 4.34(2H, q; J=7.1 Hz), 3.95(1H, m), 2.20-2.10(2H, m), 1.90-1.80(4H, m), 1.6(1H, m), 1.35(3H, t, J=7.2 Hz), 1.30-1.20(3H, mz)



EXAMPLE 20


Production of 2-{4-(bis[3-fluorophenyl]methoxy)-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid

[1741] Ethyl 2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (75 g) obtained in Example 19 was treated in the same manner as in Example 2 to give the title compound (48 g, yield 62%).


[1742] melting point: 242-243° C. FAB-Ms: 557(MH+) 1H-NMR (300 MHz, DMSO-d6): 8.29(1H, s), 8.16(1H, d, J=8.8 Hz), 7.99(1H, d, J=8.7 Hz), 7.66(1H, t, J=8.7 Hz), 7.51-7.40(6H, m), 7.30(1H, d, J=12.1 Hz), 7.20-7.14(3H, m), 6.88(1H, s), 4.07(1H, m), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.15(3H, m)



EXAMPLE 21


Production of Ethyl 1-cyclopentyl-2-(4-nitrophenyl)benzimidazole-5-carboxylate

[1743] In the same manner as in Example 1, the title compound (12 g) was obtained.



EXAMPLE 22


Production of Ethyl 2-(4-aminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate

[1744] Ethyl 1-cyclopentyl-2-(4-nitrophenyl)benzimidazole-5-carboxylate (12 g) obtained in Example 21 was dissolved in tetrahydrofuran (200 ml) and ethyl alcohol (50 ml), 7.5% palladium carbon (50% wet, 1 g) was added. The mixture was hydrogenated for 1 hr at atmospheric pressure. The catalyst was filtered off and the filtrate was concentrated under reduced pressure. Tetrahydrofuran was added to the residue to allow crystallization and the crystals were collected by filtration to give the title compound (11 g, yield 98%).


[1745]

1
H-NMR (300 MHz, CDCl3): 8.49(1H, d, J=1.3 Hz), 7.95(1H, dd, J=8.5, 1.3 Hz), 7.50-7.40(3H, m), 6.79(2H, d, J=4.6 Hz), 4.97(1H, quint, J=8.9 Hz), 4.40(2H, q; J=7.1 Hz), 3.74(2H, brs), 2.40-1.60(8H, m), 1.41(3H, t, J=7.1 Hz)



EXAMPLE 23


Production of Ethyl 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate

[1746] Ethyl 1-cyclopentyl-2-(4-aminophenyl)benzimidazole-5-carboxylate (300 mg) obtained in,Example 22 was dissolved in pyridine (3 ml) and chloroform (3 ml), and benzoyl chloride (127 mg) was added. The mixture was stirred for 30 min at room temperature. The reaction mixture was concentrated under reduced pressure and water was added to the residue to allow crystallization. The crystals were collected by filtration to give the title compound (403 mg; yield 100%).


[1747]

1
H-NMR (300 MHz, CDCl3): 8.58(1H, s), 8.00(1H, d, J=9.0 Hz), 7.84(2H, d, J=7.5 Hz), 7.60-7.40(6H, m), 7.14(2H, d, J=7.5 Hz), 4.84(1H, quint, J=8.7 Hz), 4.41(2H, q, J=7.5 Hz), 2.20-1.30(8H, m), 1.41(3H, t, J=7.5 Hz)



EXAMPLE 24


Production of 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid

[1748] Ethyl 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate (200 mg) obtained in Example 23 was treated in the same manner as in Example 2 to give the title compound (131 mg, yield 70%).


[1749] melting point: not lower than 300° C. FAB-Ms: 426(MH+) 1H-NMR (300 MHz, DMSO-d6): 10.75(1H, s), 8.35(1H, s), 8.15 and 7.85(4H, ABq, J=8.9 Hz), 8.10-7.98(4H, m), 7.70-7.55(3H, m), 5.02(1H, quint, J=8.7 Hz), 2.36-2.15(4H, m), 2.14-1.95(2H, m), 1.80-1.62(2H, m)



EXAMPLE 25


Production of Ethyl 2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1750] Ethyl 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (65 g) obtained in Example 1 and 3-chlorophenylboronic acid (23 g) were treated in the same manner as in Example 5 to give the title compound (59 g, yield 85%).


[1751]

1
H-NMR (300 MHz, CDCl3): 8.51(1H, d, J=1.8 Hz), 7.99(1H, dd, J=8.7, 1.8 Hz), 7.71-7.55(4H, m), 7.51-7.43(2H, m), 7.43-7.27(4H, m), 7.19(1H, d, J=8.4 Hz), 7.12(1H, m), 4.41(2H, q, J=7.2 Hz), 4.39(1H, m), 2.42-2.22(2H, m), 2.03-1.87(4H, m), 1.79(1H, m), 1.42(3H, t, J=7.2 Hz), 1.39-1.29(3H, m)



EXAMPLE 26


Production of 2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid

[1752] Ethyl 2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (59 g) obtained in Example 25 was treated in the same manner as in Example 2 to give the title compound (43 g, yield 76%).


[1753] melting point: 253-254° C. FAB-Ms: 523(MH+) 1H-NMR (300 MHz, DMSO-d6): 12.82(1H, brs), 8.24(1H, d, J=1.3 Hz), 7.98(1H, d, J=8.7 Hz), 7.89(1H, dd, J=8.7, 1.3 Hz), 7.78(1H, s), 7.72(2H, d, J=9.7 Hz), 7.70(1H, m), 7.64-7.42(5H, m), 7.25(2H, d, J=8.7 Hz), 7.20(1H, m), 4.33(1H, m), 2.39-2.17(2H, m), 2.00-1.76(4H, m), 1.65(1H, m), 1.50-1.22(3H, m)



EXAMPLE 27


Production of Ethyl 2-[4-(3-acetoxyphenyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1754] In the same manner as in Example 1, the title compound (87 g) was obtained.



EXAMPLE 28


Production of Ethyl 1-cyclohexyl-2-[4-(3-hydroxyphenyloxy)-phenyl]benzimidazole-5-carboxylate

[1755] Ethyl 2-[4-(3-acetoxyphenyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (87 g) obtained in Example 27 was dissolved in methyl alcohol (250 ml) and tetrahydrofuran (250 ml), and potassium carbonate (31 g) was added. The mixture was stirred for 30 min at room temperature. The insoluble materials were filtered off and the filtrate was concentrated under reduced pressure. Water was added to the residue and the mixture was neutralized with 2N hydrochloric acid. The precipitated crystals were collected by filtration to give the title compound (78 g, yield 97%).


[1756]

1
H-NMR (300 MHz, DMSO-d6): 9.71(1H, s), 7.98(1H, d, J=8.7 Hz), 7.87(1H, d, J=8.7 Hz), 7.68(2H, d, J=8.6 Hz), 7.24(1H, t, J=8.1 Hz), 7.18(2H, d, J=8.6 Hz), 6.63(1H, d, J=8.1 Hz), 6.57(1H, d, J=8.1 Hz), 6.51(1H, s), 4.38-4.23(1H; m), 4.35(2H, q, J=6.9 Hz), 2.36-2.18(2H, m), 1.99-1.78(4H, m), 1.71-1.59(1H, m), 1.45-1.20(3H, m), 1.36(3H, t, J=6.9 Hz)



EXAMPLE 29


Production of Ethyl 1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)-phenyloxy]phenyl}benzimidazole-5-carboxylate

[1757] Ethyl 1-cyclohexyl-2-[4-(3-hydroxyphenyloxy)phenyl]-benzimidazole-5-carboxylate (78 g) obtained in Example 28 was suspended in dimethylformamide (800 ml), and sodium hydride (60% oil, 14 g) was added under ice-cooling. The mixture was stirred for 1 hr at room temperature. After the reaction mixture was ice-cooled, 4-chloromethylpyridine hydrochloride (29 g) was added and the mixture was stirred for 30 min. The mixture was then stirred overnight at room temperature. Water was added to the reaction mixture and the precipitated crystals were collected by filtration. The resulting crystals were recrystallized from ethyl alcohol to give the title compound (77 g, yield 82%).


[1758]

1
H-NMR (300 MHz, CDCl3): 8.63(2H, d, J=6.0 Hz), 8.51 (1H, s), 7.99(1H, d, J=8.7 Hz), 7.66(2H, d, J=8.7 Hz), 7.62(2H, d, J=8.7 Hz), 7.36(2H, d, J=8.7 Hz), 7.31(1H, t, J=8.2 Hz), 7.26(1H, s), 7.16(2H, d, J=8.7 Hz), 6.79-6.70(3H, m), 5.09(2H, s), 4.47-4.31(1H, m), 4.42(2H, q, J=7.0 Hz), 2.42-2.22(2H, m), 2.04-1.71(5H, m), 1.45-1.25(3H, m), 1.42(3H, t, J=7.0 Hz)



EXAMPLE 30


Production of 1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]-phenyl}benzimidazole-5-carboxylic acid

[1759] Ethyl 1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]-phenyl}benzimidazole-5-carboxylate (60 g) obtained in Example 29 was treated in the same manner as in Example 2 to give the title compound (54 g, yield 75%).


[1760] melting point: 235-237° C. FAB-Ms: 520(MH+) 1H-NMR (300 MHz, DMSO-d6): 8.58(2H, d, J=6.0 Hz), 8.23(1H, s), 7.96 and 7.86(2H, ABq, J=8.7 Hz), 7.68 and 7.17(4H, A′B′q, J=8.7 Hz), 7.44(2H, d, J=8.7 Hz), 7.39(1H, t, J=8.3 Hz), 6.90(1H, d, J=8.1 Hz), 6.84(1H, s), 6.75(1H, d, J=8.1 Hz), 5.22(2H, s), 4.40-4.22(1H, m), 2.40-2.19(2H, m), 2.00-1.80(4H, m)



EXAMPLE 241


Production of Methyl 2-{44-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1761] Step 1: Production of 2-bromo-5-methoxybenzaldehyde


[1762] 3-Methoxybenzaldehyde (15 g) was dissolved in acetic acid (75 ml), and a solution of bromine (5.7 ml) dissolved in acetic acid (15 ml) was added dropwise. The mixture was stirred overnight at room temperature and water (150 ml) was added to the reaction mixture. The precipitated crystals were collected by filtration, washed with water and dried under reduced pressure to give the title compound (21 g, yield 88%).


[1763]

1
H-NMR (300 MHz, CDCl3): 10.31(1H, s), 7.52(1H, d, J=8.8 Hz), 7.41(1H, d, J=3.3 Hz), 7.03(1H, dd, J=8.8, 3.3 Hz), 3.48(3H, s)


[1764] Step 2: Production of 2-(4-chlorophenyl)-5-methoxybenzaldehyde


[1765] 2-Bromo-5-methoxybenzaldehyde (10 g) obtained in the previous step was treated in the same method as in Example 5 to give the title compound (11 g, yield 96%).


[1766]

1
H-NMR (300 MHz, CDCl3): 9.92(1H, s), 7.50(1H, d, J=2.6 Hz), 7.48-7.14(6H, m), 3.90(3H, s)


[1767] Step 3: Production of 2-(4-chlorophenyl)-5-methoxybenzyl alcohol


[1768] 2-(4-Chlorophenyl)-5-methoxybenzaldehyde (10 g) obtained in the previous step was dissolved in tetrahydrofuran (30 ml). The solution was added dropwise to a suspension of sodium borohydride (620 mg) in isopropyl alcohol (50 ml) and the mixture was stirred for 1 hr. The solvent was evaporated under reduced pressure and water was added to the residue. The precipitated crystals were collected by filtration and dried under reduced pressure. The resulting crystals were recrystallized from a mixture of methanol and water to give the title compound (9.2 g, yield 91%).


[1769]

1
H-NMR (300 MHz, CDCl3): 7.37(2H, d, J=8.6 Hz), 7.27(2H, d, J=8.6 Hz) 7.17(1H, d, J=8.6 Hz), 7.11(1H, d, J=2.6 Hz), 6.89(1H, dd, J=8.6, 2.6 Hz), 4.57(2H, s), 3.86(3H, s)


[1770] Step 4: Production of 2-(4-chlorophenyl)-5-methoxybenzyl chloride


[1771] 2-(4-Chlorophenyl)-5-methoxybenzyl alcohol (20 g) obtained in the previous step was dissolved in ethyl acetate (100 ml) and pyridine (0.5 ml), and thionyl chloride (11 ml) was added dropwise. The mixture was stirred for 1 hr. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water, saturated aqueous sodium hydrogencarbonate, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Isopropyl alcohol was added to the residue to allow crystallization. The resulting crystals were collected by filtration and dried under reduced pressure to give the title compound (16 g, yield 74%).


[1772]

1
H-NMR (300 MHz, CDCl3): 7.43-7.29(4H, m), 7.17(1H, d, J=8.6 Hz), 7.05(1H, d, J=2.6 Hz), 6.96-6.89(1H, m), 4.46(2H, s), 3.86(3H, s)


[1773] Step 5: Production of Methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate


[1774] 2-(4-Chlorophenyl)-5-methoxybenzyl chloride (4.0 g) obtained in the previous step and methyl 1-cyclohexyl-2-(4-hydroxyphenyl)-benzimidazole-5-carboxylate (5.0 g) obtained in the same manner as in Example 3 were treated in the same manner as in Example 4 to give the title compound (6.0 g, yield 72%).


[1775]

1
H-NMR (300 MHz, CDCl3): 8.48(1H, s), 8.00-7.93(1H, m), 7.68-7.62(1H, m), 7.54(2H, d, J=9.0 Hz), 7.41-7.16(6H, m), 7.04-6.93(3H, m), 4.97(2H, s), 4.36(1H, m), 3.94(3H, s), 3.87(3H, s), 2.39-2.21(2H, m), 2.02-1.88(4H, m), 1.85-1.45(4H, m)



EXAMPLE 242


Production of 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride

[1776] Methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (5.0 g) obtained in Example 241 was treated in the same manner as in Example 2 to give the title compound (5.1 g, yield 98%).


[1777] APCI-Ms: 568(MH+) 1H-NMR (300 MHz, DMSO-d6): 8.30(1H, d, J=1.4 Hz), 8.24(1H, d, J=8.7 Hz), 8.03(1H, d, J=8.7 Hz), 7.72(2H, d, J=8.7 Hz), 7.51-7.39(4H, m), 7.34-7.18(4H, m), 7.11-7.03(1H, m), 5.08(2H, s), 4.35(1H, m), 3.83(3H,m), 2.40-2.18(2H, m), 2.10-1.96(2H, m), 1.93-1.78(2Hm), 1.72-1.18(4H, m)



EXAMPLE 243


Production of Ethyl 2-{4-[3-(4-chlorophenyl)pyridin-2-ylmethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1778] Step 1: Production of Methyl 3-hydroxypicolinate


[1779] 3-Hydroxypicolinic acid (1.0 g) was suspended in methanol (10 ml) and concentrated sulfuric acid (1.0 ml) was added. The mixture was refluxed under heating for 5 hr. The reaction mixture was ice-cooled, neutralized with saturated aqueous sodium hydrogencarbonate, and extracted with chloroform. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (711 mg, yield 64%).


[1780]

1
H-NMR (300 MHz, CDCl3): 10.63(1H, s), 8.28(1H, dd, J=3.7, 1.8 Hz), 7.47-7.35(2H, m), 4.06(3H, s)


[1781] Step 2: Production of Methyl 3-(trifluoromethylsulfonyloxy)-pyridine-2-carboxylate


[1782] Methyl 3-hydroxypicolinate (710 mg) obtained in the previous step and triethylamine (0.77 ml) were dissolved in dichloromethane (7 ml), and trifluoromethanesulfonic anhydride (0.86 ml) was added under ice-cooling. The reaction mixture was allowed to warm to room temperature and the mixture was stirred for 2 hr. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (1.2 g, yield 90%).


[1783]

1
H-NMR (300 MHz, CDCl3): 8.80-8.73(1H, m), 7.75-7.70(1H, m), 7.63(1H, dd, J=8.2, 4.5 Hz), 4.05(3H, s)


[1784] Step 3: Production of Methyl 3-(4-chlorophenyl)pyridine-2-carboxylate


[1785] Methyl 3-(trifluoromethylsulfonyloxy)pyridine-2-carboxylate (1.2 g) obtained in the previous step was treated in the same manner as in Example 5 to give the title compound (728 mg, yield 69%).


[1786]

1
H-NMR (300 MHz, CDCl3): 8.73-8.66(1H, m), 7.77-7.68(1H, m), 7.49(1H, dd, J=7.8, 4.5 Hz), 7.46-7.37(2H, m), 7.32-7.23(2H, m), 3.80(3H, s)


[1787] Step 4: Production of [3-(4-chlorophenyl)pyridin-2-yl]methanol


[1788] Methyl 3-(4-chlorophenyl)pyridine-2-carboxylate (720 mg) obtained in the previous step was dissolved in tetrahydrofuran (10 ml) and the solution was ice-cooled. Lithium aluminum hydride (160 mg) was added to the solution and the mixture was stirred for 1 hr. To the reaction mixture were added successively water (1.6 ml), 15% sodium hydroxide (1.6 ml) and water (4.8 ml) The insoluble materials were filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (developing solvent, n-hexane:ethyl acetate=1:1) to give the title compound (208 mg, yield 32%).


[1789]

1
H-NMR (300 MHz, CDCl3): 8.60(1H, dd, J=4.8, 1.5 Hz), 7.60-7.55(1H, m), 7.40-7.48(2H, m), 7.29-7.36(1H, m), 7.27-7.20(3H, m), 4.63(2H, s)


[1790] Step 5: Production of Ethyl 2-{4-[3-(4-chlorophenyl)pyridin-2-ylmethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate


[1791] [3-(4-Chlorophenyl)pyridin-2-yl]methanol (200 mg) obtained in the previous step was dissolved in chloroform (3 ml), and thionyl chloride (0.13 ml) and pyridine (catalytic amount) were added. The mixture was stirred for 1 hr at room temperature and concentrated under reduced pressure. The residue was dissolved in dimethylformamide (3 ml), and ethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate (232 mg) obtained in the same manner as in Example 3 and potassium carbonate (250 mg) were added. The mixture was stirred for 3 hr with heating at 80° C., The reaction mixture was then allowed to cool. Water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (developing solvent, n-hexane:ethyl acetate=1:2) to give the title compound (246 mg, yield 68%).


[1792]

1
H-NMR (300 MHz, CDCl3): 8.71(1H, dd, J=4.7, 1.4 Hz), 8.49(1H, d, J=2.1 Hz), 7.96(1H, d, J=10.2 Hz), 7.71-7.62(2H, m), 7.53(2H, d, J=8.7 Hz), 7.45-7.34(5H, m), 7.04(2H, d, J=8.7 Hz), 5.14(2H, s), 4.48-4.29(3H, m), 2.38-2.19(2H, m), 2.02-1.22(1H, m)



EXAMPLE 244


Production of Methyl 2-[4-(2-bromo-5-tert-butoxycarbonyl-benzyloxy),phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1793] Step 1: Production of tert-butyl 4-bromo-3-methylbenzoate


[1794] 4-Bromo-3-methylbenzoic acid (25 g), was suspended in dichloromethane (200 ml), and oxalyl chloride (12 ml) and dimethylformamide (catalytic amount) were added. The mixture was stirred for 2 hr at room temperature and the solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (200 ml) and the solution was ice-cooled. To the solution was added dropwise a solution of potassium tert-butoxide dissolved in tetrahydrofuran (150 ml) and the mixture was stirred for 30 min. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (27 g, yield 85%).


[1795]

1
H-NMR (300 MHz, CDCl3): 7.83(1H, d, J=2.22 Hz), 7.67-7.53(2H, m), 2.43(3H, s), 1.58(9H, s)


[1796] Step 2: Production of Methyl 2-[4-(2-bromo-5-tert-butoxycarbonylbenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate tert-Butyl 4-bromo-3-methylbenzoate (7.0 g) obtained in the previous step and methyl 1-cyclohexyl-2-(4-hydroxyphenyl)-benzimidazole-5-carboxylate (6.3 g) obtained in the same manner as in Example 3 were treated in the same manner as in Example 4 to give the title compound (8.8 g, yield 77%).


[1797]

1
H-NMR (300 MHz, CDCl3): 8.49(1H, d, J=1.5 Hz), 8.21(1H, d, J=2.1 Hz), 7.97(1H, d, J=10.2 Hz), 7.82(1H, d, J=10.2 Hz), 7.71-7.58(4H, m), 7.16(2H, d, J=8.7 Hz), 5.23(2H, s), 4.38(1H, m), 3.95(3H, s), 2.40-2.23(2H, m), 2.04-1.90(4H, m), 1.84-1.73(1H, m), 1.59(9H, s), 1.44-1.27(3H, m)



EXAMPLE 245


Production of Methyl 2-{4-[5-tert-butoxycarbonyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1798] Methyl 2-[4-(2-bromo-5-tert-butoxycarbonylbenzyloxy)phenyl]-3-1-cyclohexylbenzimidazole-5-carboxylate (4.5 g) obtained in Example 244 was treated in the same manner as in Example 5 to give the title compound (3.6 g, yield 76%).


[1799]

1
H-NMR (300 MHz, CDCl3): 8.48(1H, s), 8.27(1H, d, J=1.8 Hz), 8.04(1H, dd, J=7.9, 1.5 Hz), 7.96(1H, dd, J=7.0, 1.5 Hz), 7.65(1H, d, J=8.6 Hz), 7.55(2H, d, J=8.6 Hz), 7.43-7.32(5H, m), 7.01(2H, d, J=8.6 Hz), 4.99(2H, s), 4.43-4.29(1H, m), 3.95(3H, s), 2.41-2.21(2H, m), 2.02-1.89(4H, m), 1.82-1.73(1H, m), 1.62(9H, s), 1.46-1.28(3H, m)



EXAMPLE 246


Production of Methyl 2-{4-[5-carboxy-2-(4-chlorophenyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride

[1800] Methyl 2-{4-[5-tert-butoxycarbonyl-2-(4-chlorophenyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (3.5 g) obtained in Example 245 was dissolved in dichloromethane (35 ml), and trifluoroacetic acid (35 ml) was added. The mixture was stirred for 1 hr at room temperature and the reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate, and 4N hydrochloric acid-ethyl acetate was added. The precipitated crystals were collected by filtration and dried under reduced pressure to give the title compound (3.3 g, yield 97%).


[1801]

1
H-NMR (300 MHz, DMSO-d6): 8.33(1H, d, J=1.5 Hz), 8.29(1H, s), 8.24(1H, d, J=1.8 Hz), 8.09-8.00(2H, m), 7.74(2H, d, J=8.6 Hz), 7.61-7.44(5H, m), 7.24(2H, d, J=8.6 Hz), 5.19(2H, s), 4.36(1H, m), 3.93(3H, s), 2.37-1.21(10H, m)



EXAMPLE 247


Production of Methyl 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoyl-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1802] Methyl 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride (400 mg) obtained in Example 246 was suspended in dichloromethane (5 ml), and oxalyl chloride (0.08 ml) and dimethylformamide (catalytic amount) were added. The mixture was stirred for 2 hr at room temperature. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in dichloromethane (5 ml). The resulting solution was added dropwise to a mixed solution of 40% aqueous methylamine solution (5 ml) and tetrahydrofuran (5 ml) under ice-cooling. The reaction mixture was stirred for 1 hr and concentrated under reduced pressure. Water was added to the residue and the mixture was extracted with ethyl acetate. The organic layer was washed with water, saturated aqueous sodium hydrogencarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was crystallized from ethyl acetate and diisopropyl ether. The crystals were collected by filtration and dried under reduced pressure to give the title compound (335 mg, yield 86%).


[1803]

1
H-NMR (300 MHz, CDCl3): 8.47(1H, s), 8.06(1H, d, J=1.8 Hz), 7.96(1H, dd, J=8.6, 1.5 Hz), 7.82(1H, dd, J=8.2, 2.2 Hz), 7.64(1H, d, J=8.6 Hz), 7.54(2H, d, J=9.0 Hz), 7.44-7.31(5H, m), 6.99(2H, d, J=9.0 Hz), 6.35-6.26(1H, m), 5.00(2H, s), 4.35(1H, m), 3.95(3H, s), 3.05(3H, d, J=4.8 Hz), 2.40-1.24(10H, m)



EXAMPLE 248


Production of 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride

[1804] Methyl 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (150 mg) obtained in Example 247 and tetrahydrofuran (2 ml) were treated in the same manner as in Example 2 to give the title compound (141 mg, yield 90%).


[1805] APCI-Ms: 594(MH+) 1H-NMR (300 MHz, DMSO-d6) 8.65-8.58(1H, m), 8.27(1H, d, J=1.5 Hz) 8.21(1H, d, J=8.2 Hz), 8.15(1H, d, J=1.5 Hz), 8.05-7.90(2H, m), 7.70(2H, d, J=8.6 Hz), 7.56-7.43(5H, m), 7.21(2H, d, J=8.6 Hz), 5.14(2H, s), 4.34(1H, m), 2.81(3H, d, J=4.5 Hz), 2.39-1.19(10H, m)



EXAMPLE 336


Production of Methyl 2-[4-(2-bromo-5-nitrobenzyloxy)-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1806] Commercially available 2-bromo-5-nitrotoluene was dissolved in carbon tetrachloride (30 ml), and N-bromosuccinimide (2.9 g) and N,N′-azobisisobutyronitrile (228 mg) were added, which was followed by refluxing under heating overnight. The reaction mixture was allowed to cool, water was added and the mixture was extracted with chloroform. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in dimethylformamide (30 ml) and methyl 2-(2-fluoro-4-hydroxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylate (3.8 g) obtained in the same manner as in Example 3 and potassium carbonate (3.8 g) were added, which was followed by stirring at 80° C. for 1 hr. The reaction mixture was allowed to cool, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (n-hexane:ethyl acetate=1:1) to give the title compound (3.7 g, yield 61%).


[1807]

1
H-NMR (300 MHz, CDCl3): 8.55-8.45(2H, m), 8.15-8.05(1H, m), 7.99(1H, dd, J=8.6 Hz, 1.5 Hz), 7.70-7.55(2H, m), 7.05-6.85(2H, m), 5.24(2H,s), 4.06(1H, m), 3.95(3H, s), 2.35-2.15(2H, m), 2.05-1.85(4H, m), 1.80-1.70(1H, m), 1.45-1.20(3H, m)



EXAMPLE 337


Production of Methyl 2-[4-2-(4-chlorophenyl)-5-nitrobenzyloxy-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1808] Methyl 2-[4-(2-bromo-5-nitrobenzyloxy)-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (2.0 g) obtained in Example 336, 4-chlorophenylboronic acid (590 mg) and tetrakis (triphenylphosphine) palladium (396 mg) were suspended in dimethoxyethane (40 ml), and saturated aqueous sodium hydrogencarbonate solution (20 ml) was added, which was followed by refluxing under heating for 1 hr. The reaction mixture was allowed to cool, water was added and the mixture was extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (n-hexane:ethyl acatate=2:1) to give the title compound (1.9 g, yield 90%).


[1809]

1
H-NMR (300 MHz, CDCl3): 8.55(1H, d, J=2.3 Hz), 8.49(1H, d, J=1.4 Hz), 8.29(1H, dd, J=8.4 Hz, 2.3 Hz), 7.98(1H, dd, J=8.6 Hz, 1.5 Hz), 7.60-7.30(6H, m), 6.85-6.70(2H, m), 5.03(2H, s), 4.02(1H, m), 3.95(3H, s), 2.35-2.10(2H, m), 2.05-1.70(5H, m), 1.40-1.20(3H, m)



EXAMPLE 338


Production of Methyl 2-[4-{5-amino-2-(4-chlorophenyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1810] Methyl 2-[4-{2-(4-chlorophenyl)-5-nitrobenzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (1.9 g) obtained in Example 337 was suspended in ethanol (40 ml), and tin(II) chloride dihydrate (3.5 g) was added, which was followed by refluxing under heating for 30 min. The reaction mixture was concentrated under reduced pressure, 4N sodium hydroxide was added and the mixture was extracted with chloroform. The organic layer was washed with 2N sodium hydroxide and water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Diisopropyl ether was added to the residue, and the precipitated crystals were collected by filtration to give the title compound (1.5 g, yield 82%).


[1811]

1
H-NMR (300 MHz, CDCl3): 8.49(1H, d, J=1.2 Hz), 7.98(1H, dd, J=9.0, 1.5 Hz), 7.66(1H, d, J=8.7 Hz), 7.49(1H, t, J=8.4 Hz), 7.40-7.20(3H, m), 7.13(1H, d, J=8.1 Hz), 6.92(1H, d, J=2.7 Hz), 6.85-6.65(4H, m) 4.92(2H, s), 4.03(1H, m), 3.95(3H, s), 3.82(2H, brs), 2.30-2.10(2H, m), 2.05-1.80(4H, m), 1.80-1.70(1H, m), 1.40-1.10(3H, m)



EXAMPLE 339


Production of Methyl 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1812] Methyl 2-[4-{5-amino-2-(4-chlorophenyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (500 mg) obtained in Example 338 and triethylamine (0.14 ml) were dissolved in chloroform (5 ml), and commercially available chlorobutyryl chloride (0.1 ml) was added under ice-cooling, which was followed by stirring at room temperature for 3 hr. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in dimethylformamide (6 ml) and potassium carbonate (244 mg) was added, which was followed by stirring at 80° C. for 1 hr. The reaction mixture was allowed to cool, water was added and the precipitated crystals were collected by filtration to give the title compound (502 mg, yield 89%).


[1813]

1
H-NMR (300 MHz, CDCl3): 4.89(1H, d, J=1.5 Hz), 7.98(1H, dd, J=8.6 Hz, 1.6 Hz), 7.72(1H, d, J=2.2 Hz), 7.75-7.65(2H, m), 7.49(1H, t, J=8.3 Hz), 7.45-7.20(5H, m), 6.85-7.65(2H, m), 4.99(2H, s), 4.10-3.85(6H, m), 2.66(2H, t, J=7.8 Hz), 2.30-2.15(4H, m), 2.00-1.85(4H, m), 1.80-1.70(1H, m), 1.45-1.20(3H, m)



EXAMPLE 340


Production of 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride

[1814] Methyl 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (200 mg) obtained in Example 339 was treated in the same manner as in Example 2 to give the title compound (182 mg, yield 87%).


[1815] Ms:638(M+1) 1H-NMR (300 MHz, CDCl3) 8.28(1H, d, J=1.3 Hz), 8.10(1H, d, J=8,7 Hz), 8.05-7.90(2H, m), 7.77(1H, dd, J=8.4 Hz, 2.2 Hz), 7.61(1H, t, J=8.5 Hz), 7.55-7.35(5H, m), 7.00-7.20(2H, m), 5.09(2H, s), 4.06(1H, m), 3.90(2H, t, J=6.9 Hz), 2.60-2.45(2H, m), 2.30-2.00(4H, m), 1.95-1.75(4H, m), 1.70-1.55(1H, m), 1.45-1.15(3H, m)


[1816] In the same manner as in Examples 1-30, 241-248 and 336-340 and optionally using other conventional methods, where necessary, the compounds of Examples 31-240, 249-335, 341-446, 701-703 and 1001-1559 were obtained. The chemical structures and properties are shown in Table 1 to 177, 185 to 212, 219 to 221 and 225 to 260.



EXAMPLE 501


Production of Methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylate

[1817] Step 1: Production of Methyl 3-bromo-4-cyclohexylaminobenzoate


[1818] 3-Bromo-4-fluorobenzoic acid (2.0 g) was dissolved in methanol (20 ml) and concentrated sulfuric acid (2 ml) was added. The mixture was refluxed for 3 hr. The reaction mixture was poured into ice-cold water and extracted with ethyl acetate (50 ml). The organic layer was washed with water (30 ml) and saturated brine (30 ml), and dried over sodium sulfate. After filtration, the solvent was evaporated under reduced pressure. The residue was dissolved in dimethyl sulfoxide (20 ml) and cyclohexylamine (10.3 ml) was added. The mixture was stirred overnight at 120° C., The reaction mixture was poured into 10% aqueous citric acid solution (100 ml) and extracted with ethyl acetate (100 ml). The organic layer was washed with water (50 ml) and saturated brine (50 ml), and dried over sodium sulfate. After filtration, the solvent was evaporated under reduced pressure and the residue was purified by silica gel flash chromatography (developing solvent, n-hexane:ethyl acetate=10:1) to give the title compound (2.6 g, yield 92%).


[1819]

1
H-NMR (300 MHz, CDCl3): 8.10(1H, d, J=1.9 Hz), 7.83(1H, dd, J=1.9 Hz, 8.6 Hz), 6.59(1H, d, J=8.7 Hz), 4.73(1H, brd, J=7.3 Hz), 3.85(3H, s), 3.38(1H, m), 2.10-2.00(2H, m), 1.90-1.20(8H, m)


[1820] Step 2: Production of 4′-chloro-2-(4-iodophenoxymethyl)-4-methoxybiphenyl


[1821] 4-Iodophenol (5.0 g) was dissolved in acetone (50 ml), and potassium carbonate (4.7 g) and 4′-chloro-2-chloromethyl-4-methoxybiphenyl (6.0 g) obtained in Example 241, Step 4 were added. The mixture was refluxed for 10 hr. The reaction mixture was concentrated and 4N aqueous sodium hydroxide solution (50 ml) was added. The precipitated crystals were collected by filtration, washed with water, and dried under reduced pressure to give the title compound (10.0 g, yield 98%).


[1822]

1
H-NMR (300 MHz, CDCl3): 7.52(2H, d, J=8.9 Hz), 7.35(2H, d, J=8.5 Hz), 7.27-7.20(3H, m), 7.12(1H, s), 6.95(1H, d, J=8.5 Hz), 6.62(2H, d, J=8.9 Hz), 4.84(2H, s), 3.85(3H, s)


[1823] Step 3: Production of [4-(4′-chloro-4-methoxybiphenyl-2-ylmethoxy)phenylethynyl]trimethylsilane


[1824] 4′-Chloro-2-(4-iodophenoxymethyl)-4-methoxybiphenyl (7.0 g) obtained in the previous step was dissolved in acetonitrile (50 ml), and trimethylsilylacetylene (2.3 g), tetrakis-(triphenylphosphine)palladium complex (1.8 g), copper(I) iodide (0.6 g) and triethylamine (50 ml) were added. The mixture was stirred overnight at room temperature and concentrated. Water (30 ml) was added and the mixture was extracted with ethyl acetate (50 ml). The organic layer was washed with water (30 ml) and saturated brine (30 ml) and dried over sodium sulfate. After filtration, the solvent was evaporated under reduced pressure and the residue was purified by silica gel flash chromatography. (developing solvent, n-hexane:ethyl acetate=10:1) to give the title compound (5.1 g, yield 79%).


[1825]

1
H-NMR (300 MHz, CDCl3): 7.37(2H, d, J=8.9 Hz), 7.34(2H, d, J=8.2 Hz), 7.28-7.21(3H, m), 7.13(1H, s), 6.94(1H, d, J=8.2 Hz), 6.75(2H, d, J=8.9 Hz), 4.87(2H, s), 3.85(3H, s); 0.23(9H, s)


[1826] Step 4: Production of Methyl 3-[4-(4′-chloro-4-methoxybiphenyl-2-ylmethoxy)phenylethynyl]-4-cyclohexylaminobenzoate


[1827] [4-(4′-Chloro-4-methoxybiphenyl-2-ylmethoxy)phenylethynyl]-trimethylsilane (5.1 g) obtained in the previous step was dissolved in methanol (50 ml) and chloroform (50 ml), and potassium carbonate (2.5 g) was added. The mixture was stirred for 3 hr at room temperature and concentrated. Water (30 ml) was added and the mixture was extracted with ethyl acetate (50 ml). The organic layer was washed with water (30 ml) and saturated brine (30 ml) and dried over sodium sulfate. After filtration, the solvent was evaporated under reduced pressure to give white crystals (3.8 g). The white crystals (2.3 g) were dissolved in acetonitrile (10 ml), and methyl 3-bromo-4-cyclohexylamino-benzoate (1.0 g) obtained in Step 1, tetrakis(triphenyl-phosphine)palladium complex (0.4 g), copper(I) iodide (0.1 g) and triethylamine (10 ml) were added. The mixture was stirred overnight at 100° C. and concentrated under reduced pressure. Water (30 ml) was added and the mixture was extracted with ethyl acetate (50 ml). The organic layer was washed with water (30 ml) and saturated brine (30 ml), and dried over sodium sulfate. After filtration, the solvent was evaporated under reduced pressure and the residue was purified by silica gel flash chromatography (developing solvent, n-hexane:ethyl acetate=8:1) to give the title compound (0.9 g, yield 49%).


[1828]

1
H-NMR (300 MHz, CDCl3): 8.03(1H, s), 7.84(1H, d, J=8.7 Hz), 7.42-7.22-(7H, m), 7.15(1H, s), 6.95(1H, d, J=8.2 Hz), 6.85(2H, d, J=8.8 Hz), 6.59(1H, d, J=8.8 Hz), 5.07(1H, brs), 4.91(2H, s), 3.86(3H, s), 3.85(3H, s), 3,42(1H, m), 2.15-2.00(2H, m), 1.80-1.20(8H, m)


[1829] Step 5: Production of Methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylate


[1830] Methyl 3-[4-(4′-chloro-4-methoxybiphenyl-2-ylmethoxy)phenyl-ethynyl]-4-cyclohexylaminobenzoate (0.5 g) obtained in the previous step was dissolved in N,N-dimethylformamide (5 ml), and copper(I) iodide (0.17 g) was added. The mixture was refluxed for 3 hr at 180° C., The insoluble materials were removed by filtration. Water (10 ml) was added and the mixture was extracted with ethyl acetate (30 ml). The organic layer was washed with water (10 ml) and saturated brine (10 ml), and dried over sodium sulfate. After filtration, the solvent was evaporated under reduced pressure and the residue was purified by silica gel flash chromatography (developing solvent, n-hexane:ethyl acetate=8:1) to give the title compound (0.27 g, yield 55%).


[1831]

1
H-NMR (300 MHz, CDCl3): 8.34(1H, s), 7.85(1H, d, J=8.8 Hz), 7.62(1H, d, J=8.8 Hz), 7.40-7.18(8H, m), 7.00-6.94(3H, m), 6.48(1H, s), 4.95(2H, m), 4.18(1H, m), 3.93(3H, s), 3.88(3H, s), 2.45-2.25(2H, m), 1.95-1.20(8H, m)



EXAMPLE 502


Production of 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylic acid

[1832] Methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylate (0.27 g) obtained in Example 501 was treated in the same manner as in Example 2 to give the title compound (0.19 g, yield 71%).


[1833] APCI-Ms: 566(MH+)


[1834]

1
H-NMR (300 MHz, DMSO-d6): 12.43(1H, brs), 8.20(1H, s), 7.79(1H, d, J=9.3 Hz), 7.72(1H, d, J=9.0 Hz), 7.50-7.20(8H, m), 7.07-7.03(3H, m), 6.53(1H, s), 5.01(2H, s), 4.13(1H, m), 3.83(3H, m), 2.35-2.25(2H, m), 1.85-1.10(8H, m)


[1835] In the same manner as in Examples 501 and 502, and optionally using other conventional methods where necessary, the compound of Example 503 was obtained. The chemical structure and properties are shown in Table 207.



EXAMPLE 601


Production of Ethyl 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo-[1,2-a]pyridine-7-carboxylate

[1836] Step 1: Production of 4-benzyloxy-N-methoxy-N-methylbenzamide 4-Benzyloxybenzoic acid (5.0 g) and N,O-dimethyl-hydroxylamine hydrochloride (2.5 g) were suspended in dimethylformamide (50 ml), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (5.0 g), 1-hydroxybenzotriazole (3.5 g) and triethylamine (3.6 ml) were added. The mixture was stirred overnight at room temperature. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water, saturated aqueous sodium hydrogencarbonate, water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (5.6 g, yield 94%).


[1837]

1
H-NMR (300 MHz, CDCl3): 7.22, 2H, d, J=8.8 Hz), 7.28-7.46(5H, m), 6.97(2H, d, J=8.8 Hz), 5.10(2H, s), 3.56(3H, s), 3.35(3H, s)


[1838] Step 2: Production of 1-(4-benzyloxyphenyl)-2-cyclohexylethanone


[1839] Magnesium (470 mg) was suspended in tetrahydrofuran (2 ml) and cyclohexylmethyl bromide (3.4 g) was added dropwise at room temperature. After the addition, the reaction mixture was stirred for 30 min at 60° C., The reaction mixture was allowed to cool and diluted with tetrahydrofuran (5 ml). Separately, 4-benzyloxy-N-methoxy-N-methylbenzamide (3.4 g) obtained in the previous step was dissolved in tetrahydrofuran (10 ml) and the solution was added dropwise to the reaction mixture at-room temperature. The mixture was stirred for 2 hr and saturated aqueous ammonium chloride solution was added to the reaction mixture. The mixture was extracted with diethyl ether. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel flash chromatography (developing solvent, n-hexane:ethyl acetate 9:1) to give the title compound (3.8 g, yield 66%).


[1840]

1
H-NMR (300 MHz, CDCl3): 7.93(2H, d, J=8.8 Hz), 7.28-7.46(5H, m), 7.00(2H, d, J=8.8 Hz), 5.13(2H, s), 2.76(2H, d, J=6.8 Hz), 1.95(1H, m), 0.78-1.82(10 H, m)


[1841] Step 3: Production of 1-(4-benzyloxyphenyl)-2-bromo-2-cyclohexylethanone


[1842] 1-(4-Benzyloxyphenyl)-2-cyclohexylethanone (1.0 g) obtained in the previous step was dissolved in 1,4-dioxane (10 ml) and bromine (0.17 ml) was added. The mixture was stirred for 10 min at room temperature. Saturated aqueous sodium hydrogencarbonate was added to the reaction mixture and the mixture was extracted with diethyl ether. The organic layer was washed with water and saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel flash chromatography (developing solvent, n-hexane:ethyl acetate=9:1) to give the title compound (696 mg, yield 55%),


[1843]

1
H-NMR (300 MHz, CDCl3): 7.98(2H, d, J=8.9 Hz), 7.28-7.48(5H, m), 7.02(2H, d, J=8.9 Hz), 5.14(2H, s), 4.89(1H, d, J=9.3 Hz), 0.86-3.30(1H, m)


[1844] Step 4: Production of Ethyl 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylate


[1845] Ethyl 2-aminopyridine-4-carboxylate (214 mg) prepared. according to JP-A-8-48651, 1-(4-benzyloxyphenyl)-2-bromo-2-cyclohexylethanone (500 mg) obtained in the previous step and potassium carbonate (356 mg) were stirred for 5 hr with heating at 140° C. The reaction mixture was allowed to cool and chloroform was added. The insoluble materials were filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (developing solvent, n-hexane:ethyl acetate=1:1) to give the title compound (95 mg, yield 16%).


[1846] APCI-MS: 455(MH+) 1H-NMR (300 MHz, CDCl3): 8.33(1H, s), 8.21(1H, d, J=7.5 Hz), 7.55(2H, d, J=8.7 Hz), 7.25-7.50(6H, m), 5.13(2H, s), 4.41(2H, q, J=7.1 Hz), 3.25(1H, m), 1.41(3H, t, J=7.1 Hz), 1.15-2.00(10H, m)



EXAMPLE 602


Production of 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylic acid

[1847] Ethyl 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylate (95 mg) obtained in the previous step was treated in the same manner as in Example 2 to give the title compound (33 mg, 37%).


[1848] APCI-MS: 427(MH+)


[1849]

1
H-NMR (300 MHz, DMSO-d6): 8.67(1H, d, J=7.3 Hz), 8.08(1H, s), 7.25-7.58(8H, m), 7.13(2H, d, J=8.7 Hz), 5.17(2H, s), 3.23(1H, m), 1.25-2.10(10 H, m)


[1850] The compounds shown in Tables 213 to 218 can be further obtained in the same manner as in Examples 1 to 701 or by other conventional method employed as necessary.


[1851] The evaluation of the HCV polymerase inhibitory activity of the compound of the present invention is explained in the following. This polymerase is an enzyme coded for by the non-structural protein region called NS5B on the RNA gene of HCV (EMBO J., 15:12-22, 1996).



EXPERIMENTAL EXAMPLE I


i) Preparation of Enzyme (HCV Polymerase)

[1852] Using, as a template, a cDNA clone corresponding to the full length RNA gene of HCV BK strain obtained from the blood of a patient with hepatitis C, a region encoding NS5B (591 amino acids; J Virol 1991 March, 65(3), 1105-13) was amplified by PCR. The objective gene was prepared-by adding a 6 His tag {base pair encoding 6 continuous histidine (His)} to the 5′ end thereof and transformed to Escherichia coli. The Escherichia coli capable of producing the objective protein was cultured. The obtained cells were suspended in a buffer solution containing a surfactant and crushed in a microfluidizer. The supernatant was obtained by centrifugation and applied to various column chromatographys {poly[U]-Sepharose, Sephacryl S-200, mono-S (Pharmacia)}, inclusive of metal chelate chromatography, to give a standard enzyme product.



ii) Synthesis of Substrate RNA

[1853] Using a synthetic primer designed based on the sequence of HCV genomic 3′ untranslated region, a DNA fragment (148 bp) containing polyU and 3′X sequence was entirely synthesized and cloned into plasmid pBluescript SK II(+) (Stratagene). The cDNA encoding full length NS5B, which was prepared in i) above, was digested with restriction enzyme KpnI to give a cDNA fragment containing the nucleotide sequence of from the restriction enzyme cleavage site to the termination codon. This cDNA fragment was inserted into the upstream of 3′ untranslated region of the DNA in pBluescript SK II(+) and ligated. The about 450 bp inserted DNA sequence was used as a template in the preparation of substrate RNA. This plasmid was cleaved immediately after the 3′X sequence, linearized and purified by phenol-chloroform treatment and ethanol precipitation to give DNA.


[1854] RNA was synthesized (37° C., 3 hr) by run-off method using this purified DNA as a template, a promoter of pBluescript SK II(+), MEGAscript RNA synthesis kit (Ambion) and T7 RNA polymerase. DNaseI was added and the mixture was incubated for 1 hr. The template DNA was removed by decomposition to give a crude RNA product. This product was treated with phenol-chloroform and purified by ethanol precipitation to give the objective substrate RNA.


[1855] This RNA was applied to formaldehyde denaturation agarose gel electrophoresis to confirm the quality thereof and preserved at −80° C.,



iii) Assay of Enzyme (HCV Polymerase) Inhibitory Activity

[1856] A test substance (compound of the present invention) and a reaction mixture (30 μl) having the following composition were reacted at 25° C. for 90 min.


[1857] 10% Trichloroacetic acid at 4° C. and 1% sodium pyrophosphate solution (150 μl) were added to this reaction mixture to stop the reaction. The reaction mixture was left standing in ice for 15 min to insolubilize RNA. This RNA was trapped on a glass filter (Whatman GF/C and the like) upon filtration by suction. This filter was washed with a solution containing 1% trichloroacetic acid and 0.1% sodium pyrophosphate, washed with 90% ethanol and dried. A liquid scintillation cocktail (Packard) was added and the radioactivity of RNA synthesized by the enzyme reaction was measured on a liquid scintillation counter.


[1858] The HCV polymerase inhibitory activity (IC50) of the compound of the present invention was calculated from the values of radioactivity of the enzyme reaction with and without the test substance.


[1859] The results are shown in Tables 178-184 and 222-224.


[1860] Reaction mixture HCV polymerase (5 μg/ml) obtained in i), substrate RNA (10 μg/ml) obtained in ii), ATP (50 μM), GTP (50 μM), CTP (50 μM), UTP (2 μM), [5,6-3H]UTP (46 Ci/mmol (Amersham), 1.5 μCi) 20 mM Tris-HCl (pH 7.5), EDTA (1 MM), MgCl2 (5 mM), NaCl (50 mM), DTT (1 mM), BSA (0.01%)
1TABLE 1Example No.311H NMR(δ) ppm95300 MHz, CDCl3 7.81 (2H, d, J=6.6 Hz), 7.60 (2H, d, J=8.8 Hz), 7.51-7.21 (8H, m), 7.11 (2H, d, J=8.8 Hz), 5.15 (2H, s), 4.93 (1H, quint, J=8.8 Hz), 2.36-2.32 (2H, m), 2.09-2.04 (3H, m), 1.75-1.68 (3H, m).Purity>90% (NMR)MS369 (M + 1)Example No.321H NMR(δ) ppm96300 MHz, CDCl3 8.51(1H, d, J=1.5 Hz), 7.98 (1H, d, J=8.4 Hz), 7.61 (2H, d, J=8.7 Hz), 7.56-7.10 (6H, m), 7.12 (2H, d, J=8.7 Hz), 5.15 (2H, s), 4.94 (1H, quint, J=9.3 Hz), 4.41 (2H, q, J=7.5 Hz), 2.40-1.50 (8H, m), 1.41 (3H, t, J=7.5 Hz)Purity>90% (NMR)MS441 (M + 1)Example No.331H NMR(δ) ppm97300 MHz, CDCl3 7.84(1H, s), 7.61(2H, d, J=9.0 Hz), 7.58-7.30(7H, m), 7.12(2H, d, J=9.0 Hz), 5.15(2H, s), 4.94(1H, quint, J=8.7 Hz), 3.10 (6H, brs), 2.40-1.50 (8H, m)Purity>90% (NMR)MS440 (M + 1)


[1861]

2







TABLE 2















Example No.
34
1H NMR (δ) ppm














98





300 MHz, CDCl3 8.20 (1H, s), 7.50-7.31 (9H, m), 7.12 (2H, d, J=8.7 Hz), 5.15 (2H, s), 4.94(1H, quint, J=8.7 Hz), 3.61 (3H, s), 3.40 (3H, s), 2.41-1.42 (8H, m)














Purity
>90% (NMR)


MS
456 (M + 1)










Example No.
35
1H NMR (δ) ppm














99





300 MHz, CDCl3 7.91(1H. s), 7.59 (2H, d, J=8.7 Hz), 7.49-7.30 (7H, m), 7.11 (2H, d, J=8.8 Hz), 5.15 (2H, s), 4.19 (1H, quint, J=8.8 Hz), 2.41-2.22 (2H, m), 2.13-1.49 (14H, m)














Purity
>90% (NMR)


MS
427 (M + 1)










Example No.
36
1H NMR (δ) ppm














100





300 MHz, CDCl3 8.40 (1H, d, J=1.4 Hz), 7.95 (1H, dd, J=8.6, 1.4 Hz), 7.61 (2H, d, J=8.7 Hz), 7.57-7.30 (6H, m), 7.13 (2H, d, J=8.7 Hz), 5.16 (2H, s), 4.95 (1H, quint, J=8.8 Hz), 2.64(3H, s), 2.40-1.54(8H, m)














Purity
>90% (NMR)


MS
411 (M + 1)










[1862]

3







TABLE 3















Example No.
37
1H NMR (δ) ppm














101





300 MHz, DMSO-d6 10.47(1H, brs,), 9.15(1H, brs), 8.40 (1H, s), 8.07 (1H, d, J=9.0 Hz), 7.93 (1H, d, J=8.7 Hz), 7.77 (2H, d, J=8.7 Hz), 7.55-7.29(7H, m), 5.26 (2H, s), 4.93 (1H, quint, J=9.0 Hz), 3.77-3.63 (2H, m), 3.39-3.23 (2H, m), 2.84 (6H, d, J=4.8 Hz), 2.32-1.60 (8H, m)














Purity
>90% (NMR)


MS
483 (M + 1)





Example No.
38
1H NMR (δ) ppm














102





300 MHz, CDCl3 8.69(1H, s), 8.19(1H, d, J=9.0 Hz), 7.62 (2H, d, J=8.7 Hz), 7.54(1H, d, J=9.0 Hz), 7.48-7.36 (5H, m), 7.15 (2H, d, J=8.7 Hz), 5.17 (2H, s), 4.98 (1H, quint, J=9.0 Hz), 2.27-2.07 (6H, m), 1.82-1.78 (2H, m).














Purity
>90% (NMR)


MS
414 (M + 1)





Example No.
39
1H NMR (δ) ppm














103





300 MHz, DMSO-d6 7.84 (1H, d, J=9.0 Hz), 7.79 (2H, d, J=8.7 Hz), 7.52-7.33 (8H, m), 7.26(1H, d, J=9.0 Hz), 5.27 (2H, s), 4.92 (1H, quint, J=9.3 Hz), 2.19-1.70 (8H, m).














Purity
>90% (NMR)


MS
384 (M + 1)










[1863]

4







TABLE 4















Example No.
40
1H NMR(δ) ppm














104





300 MHz, CDCl3 7.72 (1H, s), 7.60-7.35 (10H, m), 7.10 (2H, d, J=8.7 Hz), 5.14 (2H, s), 4.90 (1H, quint, J=8.8 Hz), 2.29-2.19 (2H, m), 2.19 (3H, s), 2.19-1.74 (6H, m).














Purity
>90% (NMR)


MS
426 (M + 1)





Example No.
41
1H NMR(δ) ppm














105





300 MHz, CDCl3 7.66 (1H, s), 7.61 (2H, d, J=8.8 Hz), 7.50-7.28 (7H, m), 7.12 (2H, d, J=8.8 Hz), 6.86 (1H, brs), 5.15 (2H, s), 4.94 (1H, quint, J=8.8 Hz), 2.97 (3H, s), 2.29-1.76 (8H, m).














Purity
>90% (NMR)


MS
462 (M + 1)





Example No.
42
1H NMR(δ) ppm














106





300 MHz, DMSO 8.11 (1H, s), 7.81 (1H, d, J=8.4 Hz), 7.72 (1H, d, J=8.4 Hz), 7.65(2H, d, J=8.4 Hz), 7.51 (2H, m), 7.43 (2H, m), 7.37 (1H, m), 7.29 (2H, s), 7.23 (2H, d, J=8.4 Hz), 5.22 (2H, s), 4.89 (1H, quintet, J=9.2 Hz), 2.2-2.0 (6H, m), 1.7 (2H, m).














Purity
>90%
(NMR)


MS
448 (M+)










[1864]

5







TABLE 5















Example No.
43
1H NMR(δ) ppm














107





300 MHz, DMSO-d6 8.33 (1H, s), 8.08 (1H, d, J=9.0 Hz), 7.99 (1H, d, J=9.0 Hz), 7.47-7.41 (4H, m), 7.33 (2H, d, J=8.4 Hz), 5.22 (2H, s), 4.96 (1H, quint, J=9.0 Hz), 2.25-1.60 (8H, m), 1.30 (9H, s).














Purity
>90% (NMR)


MS
469 (M + 1)










Example No.
44
1H NMR(δ) ppm














108





300 MHz, DMSO-d6 12.9 (2H, brs), 8.25 (1H, s), 8.00(2H, d, J=7.8 Hz), 7.90 (1H, d, J=8.4 Hz), 7.74(1H, d, J=8.7 Hz), 7.67 (2H, d, J=9.0 Hz), 7.62 (2H, d, J=8.1 Hz), 7.24(2H, d, J=8.4 Hz), 5.32 (2H, s), 4.88 (1H, quint, J=9.0 Hz, 2.25-1.60 (8H, m).














Purity
>90% (NMR)


MS
457 (M + 1)










Example No.
45
1H NMR(δ) ppm














109





300 MHz, DMSO-d6 13.4 (1H, brs), 8.32 (1H, s), 8.06 (1H, d, J=8.7 Hz), 7.97 (1H, d, J=8.7 Hz), 7.79 (2H, d, J=8.8 Hz), 7.56-7.48 (4H, m), 7.33(2H, d, J=8.8 Hz), 5.27 (2H, s), 4.95 (1H, quint, J=8.9 Hz), 2.30-1.60 (8H, m).














Purity
>90% (NMR)


MS
447 (M + 1)










[1865]

6







TABLE 6















Example No.
46
1H NMR(δ) ppm














110





300 MHz, DMSO-d6 8.33(1H, s), 8.07 (1H, d, J=8.7 Hz), 7.98 (1H, d, J=8.7 Hz), 7.80 (2H, d, J=8.4 Hz), 7.34 (2H, d, 8.4 Hz), 7.19 (1H, d, J=3.6 Hz), 7.09(1H, d, J=3.6 Hz), 5.41 (2H, s), 4.95 (1H, quint, J=8.7 Hz), 2.30-1.60 (8H, m).














Purity
>90% (NMR)


MS
453 (M + 1)





Example No.
47
1H NMR(δ) ppm














111





300 MHz, DMSO-d6 8.33 (1H, s), 8.07 (1H, d, J=8.4 Hz), 7.98 (1H, d, J=9.0 Hz), 7.82-7.72 (6H, m), 7.35 (2H, d, J=9.0 Hz), 5.40 (2H, s), 4.95 (1H, quint, J=8.7 Hz), 2.35-1.60 (8H, m).














Purity
>90% (NMR)


MS
481 (M + 1)





Example No.
48
1H NMR(δ) ppm














112





300 MHz, DMSO-d6 8.23 (1H, s), 7.88 (1H, d, J=8.4 Hz), 7.70 (1H, d, J=8.4 Hz), 7.64(2H, d, J=8.4 Hz), 7.43 (2H, d, J=8.4 Hz), 7.20 (2H, d, J=8.4 Hz), 6.98 (2H, d, J=8.4 Hz), 5.13 (2H, s), 4.88 (1H, quint, J=8.7 Hz), 3.77 (3H, s), 2.35-1.60 (8H, m).














Purity
>90% (NMR)


MS
443 (M + 1)










[1866]

7







TABLE 7















Example No.
49
1H NMR (δ) ppm














113





300 MHz, DMSO-d6 8.93 (2H, d, J=6.6 Hz), 8.35 (1H, s), 8.06-8.04 (3H, m), 7.97 (1H, d, J=8.7 Hz), 7.83 (2H, d, J=8.7 Hz), 7.38 (2H, d, J=8.7 Hz), 5.61 (2H, s), 4.94 (1H, quint, J=8.7 Hz), 2.40-1.60 (8H, m).














Purity
>90% (NMR)


MS
414 (M + 1)





Example No.
50
1H NMR (δ) ppm














114





300 MHz, DMSO-d6 8.33 (1H, s), 8.08 (1H, d, J=8.7 Hz), 7.99 (1H, d, J=9.0 Hz), 7.78 (2H, d, J=8.4 Hz), 7.39 (2H, d, J=8.1 Hz), 7.32 (2H, d, J=8.7 Hz), 7.23 (2H, d, J=7.8 Hz), 5.22 (2H, s), 4.96 (1H, quint, J=9.0 Hz), 2.32 (3H, s), 2.30-1.60 (8H, m).














Purity
>90% (NMR)


MS
427 (M + 1)


Example No.
51
1H NMR (δ) ppm














115





300 MHz, DMSO-d6 8.31 (1H, s), 8.03 (1H, d, J=9.0 Hz), 7.93 (1H, d, J=9.0 Hz), 7.77 (2H, d, J=8.4 Hz), 7.31 (2H, d, J=8.7 Hz), 5.07 (2H, s), 4.94 (1H, quint, J=8.7 Hz), 2.45 (3H, s), 2.26 (3H, s), 2.26-1.60 (8H, m).














Purity
>90% (NMR)


MS
432 (M + 1)










[1867]

8







TABLE 8















Example No.
52
1H NMR (δ) ppm














116





300 MHz, DMSO-d6 12.7 (1H, brs), 10.0 (1H, s), 8.22 (1H, s), 7.87 (1H, d, J=8.6 Hz), 7.69 (1H, d, J=8.6 Hz), 7.53 (2H, d, J=8.6 Hz), 6.96 (2H, d, J=8.6 Hz), 4.89(1H, quint, J=9.0 Hz), 2.30-1.60 (8H, m).














Purity
>90% (NMR)


MS
323 (M + 1)


Example No.
53
1H NMR (δ) ppm














117





300 MHz, DMSO-d6 9.18 (1H, t, J=5.6 Hz), 8.34 (1H, s), 8.04 (1H, d, J=9.6 Hz), 7.98 (1H, d, J=8.7 Hz), 7.80 (2H, d, J=8.7 Hz), 7.52-7.32 (7H, m), 5.27 (2H, s), 4.95 (1H, quint, J=9.0 Hz), 3.99 (2H, d, J=5.7 Hz), 2.40-1.60 (8H, m).














Purity
>90% (NMR)


MS
470 (M + 1)


Example No.
54
1H NMR (δ) ppm














118





300 MHz, DMSO-d6 8.32 (1H, s), 8.05 (1H, d, J=8.7 Hz), 7.95 (1H, d, J=8.7 Hz), 7.80 (2H, d, J=8.4 Hz), 7.67 (1H, t, J=4.5 Hz), 7.56 (1H, t, J=7.5 Hz), 7.45-7.42 (2H, m), 7.35 (2H, d, J=8.4 Hz), 5.31 (2H, s), 4.96 (1H, quint, J=9.0 Hz), 2.30-1.60 (8H, m).














Purity
>90% (NMR)


MS
447 (M + 1)










[1868]

9







TABLE 9















Example No.
55
1H NMR (δ) ppm














119





300 MHz, DMSO-d6 12.78(1H, brs), 8.24 (1H, s), 7.88 and 7.72 (2H, ABq, J=8.6 Hz), 7.66 and 7.23 (4H, A′ B′ q, J =8.6 Hz), 7.58 (1H, s), 7.48-7.42 (3H, m), 5.24 (1H, s), 4.88 (1H, quint, J=8.8 Hz), 2.30-1.91 (6H, m), 1.78-1.60 (2H, m)














Purity
90% (NMR)


MS
447 (M + 1)





Example No.
56
1H NMR (δ) ppm














120





300 MHz, DMSO 12.89 (1H, broad), 8.18 (1H, s), 7.87 (1H, d, J=8.4 Hz), 7.74 (1H, d, J=9.2 Hz), 7.67 (2H, d, J=8.8 Hz), 7.52 (2H, m), 7.45 (2H, m), 7.38 (1H, m), 7.23 (2H, d, J=8.8 Hz), 5.22 (2H, s), 4.94 (1H, quintet, J=8.9 Hz), 2.16 (4H, m), 1.98 (2H, m), 1.73 (2H, m).














Purity
>90% (NMR)


MS
413 (M+)


Example No.
57
1H NMR (δ) ppm














121





300 MHz, DMSO-d6 10.99 (1H, s), 8.26 (1H, s), 8.01-7.86 (4H, m), 7.69-7.59 (5H, m), 7.38 (2H, d, J=8.7 Hz), 4.86 (1H, quint, J=8.7 Hz), 2.12-1.90 (6H, m), 1.72-1.59 (2H, m)














Purity
>90% (NMR)


MS
462 (M + 1)










[1869]

10







TABLE 10















Example No.
58
1H NMR (δ) ppm














122





300 MHz, DMSO-d6 12.78 (1H. s), 10.69 (1H, s), 8.26-7.72 (9H, m), 4.92 (1H, quint, J=9.0 Hz), 2.34-1.70 (6H, m), 1.75-1.61 (2H, m)














Purity
>90% (NMR)


MS
494 (M + 1)


Example No.
59
1H NMR (δ) ppm














123





300 MHz, DMSO-d6 10.82 (1H, s), 8.34 (1H, s), 8.14 and 7.84 (4H, ABq, J =8.4 Hz), 8.06 and 7.66 (4H, A′ B′ q, J =8.6 Hz), 8.06-7.98 (4H, m), 5.01 (1H, quint, J=9.3 Hz), 2.35-2.15 (4H, m), 2.11-1.96 (2H, m), 1.80-1.62 (2H, m)














Purity
>90% (NMR)


MS
460 (M + 1)


Example No.
60
1H NMR (δ) ppm














124





300 MHz, DMSO-d6 10.61 (1H, s), 8.32 (1H, s), 8.12 and 7.81 (4H, ABq, J=8.9 Hz), 8.03 and 7.93 (2H, A′ B′ q, J=8.7 Hz), 7.95 and 7.59 (4H, A″B″ q, J=8.4 Hz), 4.99 (1H, quint, J=9.0 Hz), 2.33-2.12 (4H, m), 2.10-1.93 (2H, m), 1.80-1.63 (2H, m). 1.34 (9H, m)














Purity
>90% (NMR)


MS
482 (M + 1)










[1870]

11







TABLE 11















Example No.
61
1H NMR (δ) ppm














125





300 MHz, DMSO-d6 10.6 (1H, s), 8.34 (1H, s), 8.13 (2H, d, J=8.7 Hz), 8.09-7.98 (4H, m), 7.82 (2H, d, J=8.7 Hz), 7.50-7.35 (5H, m), 7.20-7.17 (2H, d, J=9.0 Hz), 5.24 (2H, s), 5.01 (1H, quint, J=9.3 Hz), 2.40-1.60 (8H, m).














Purity
>90% (NMR)


MS
532 (M + 1)





Example No.
62
1H NMR (δ) ppm














126





300 MHz, DMSO-d6 8.32 (1H, s), 8.26 (1H, d, J=8.7 Hz), 8.04 (1H, d, J=8.7 Hz), 7.77 (2H, d, J=8.4 Hz), 7.52 (2H, d, J=6.9 Hz), 7.46-7.39 (5H, m), 5.28 (2H, s), 4.38 (1H, m), 3.71 (1H, m), 2.60-2.15 (2H, m), 2.04-1.96 (4H, m), 1.30-1.20 (2H, m).














Purity
>90% (NMR)


MS
443 (m + 1)





Example No.
63
1H NMR (δ) ppm














127





300 MHz, DMSO-d6 8.27 (1H, s), 8.14 (1H, d, J=8.7 Hz), 7.96 (1H, d, J=8.4 Hz), 7.71 (2H, d, J=9.0 Hz), 7.51 (2H, d, J=6.9 Hz), 7.46-7.37 (3H, m), 7.30 (2H, d, J=8.4 Hz), 5.25 (3H, s), 4.39 (1H, m), 3.44 (1H, m), 3.27 (3H, s), 2.60-1.95 (6H, m), 1.25-1.05(2H, m).














Purity
>90% (NMR)


MS
457 (M + 1)










[1871]

12







TABLE 12















Example No.
64
1H NMR (δ) ppm














128





300 MHz, DMSO-d6 12.25 (1H, brs), 7.70-7.30 (9H, m), 7.20 (2H, d, J=8.7 Hz), 7.14 (1H, d, J=8.4 Hz), 5.20 (2H, s), 4.84 (1H, quint, J=6.0 Hz), 3.66 (2H, s), 2.30-1.51 (8H, m)














Purity
>90% (NMR)


MS
427 (M + 1)


Example No.
65
1H NMR (δ) ppm














129





300 MHz, DMSO-d6 12.64 (1H, brs), 8.13 (1H, s), 7.80 (1H, d, J=7.2 Hz), 7.59 (1H, d, J=8.7 Hz), 7.48-7.30 (5H, m), 5.11 (2H, s), 5.03 (1H, quint, J=8.7 Hz), 4.20-4.05 (2H, m), 3.45-3.90 (3H, m), 2.15-1.60 (12H, m)














Purity
>90% (NMR)


MS
448 (M + 1)


Example No.
66
1H NMR (δ) ppm














130





300 MHz, DMSO-d6 10.59 (1H, s), 8.31 (1H, s), 8.10 (2H, d, J=8.6 Hz), 8.03 (1H, d, J=8.7 Hz), 8.00-7.85 (3H, m), 7.80 (2H, d, J=8.6 Hz), 7.41 (2H, d, J=8.2 Hz), 4.98 (1H, quint, J=8.8 Hz), 2.71-1.10 (19H, m)














Purity
>90% (NMR)


MS
508 (M + 1)










[1872]

13







TABLE 13















Example No.
67
1H NMR (δ) ppm














131





300 MHz, DMSO-d6 12.81 (1H, brs), 8.42 (1H, s), 7.90 (1H, d, J=8.5 Hz), 7.80-7.52 (6H, m), 7.44 (2H, d, J=8.6 Hz), 5.25 (2H, s), 4.88 (1H, quint, J=8.8 Hz), 2.30-1.52 (8H, m)














Purity
>90% (NMR)


MS 481
(M + 1)





Example No.
68
1H NMR (δ) ppm














132





300 MHz, DMSO-d6 8.31 (1H, d, J=1.4 Hz), 8.05 (1H, d, J=8.6 Hz), 7.96 (1H, d, J=8.6 Hz), 8.86-8.61 (4H, m), 7.51 (1H, d, J=6.3 Hz), 7.33 (2H, d, J=8.8 Hz), 5.28 (2H, s), 4.94 (1H, quint, J=8.8 Hz), 2.31-1.60 (8H, m)














Purity
>90% (NMR)


MS
481 (M + 1)





Example No.
69
1H NMR (δ) ppm














133





300 MHz, DMSO-d6 9.88 (1H, s), 9.42 (1H, s), 8.32 (1H, s), 8.09 and 8.02 (2H, ABq, J=9.0 Hz), 7.81 and 7.78 (4H, A′ B′ q, J=9.2 Hz), 7.50 (2H, d, J=7.8 Hz), 7.31 (2H, t, J=7.8 Hz), 7.00 (1H, t, J=7.8 Hz), 5.03 (1H, quint, J=8.7 Hz), 2.34-2.17 (4H, m), 2.13-1.96 (2H, m), 1.83-1.64 (2H, m)














Purity
>90% (NMR)


MS
441 (M + 1)










[1873]

14







TABLE 14















Example No.
70
1H NMR (δ) ppm














134





300 MHz, DMSO-d6 8.27 (1H, d, J=1.2 Hz), 8.04 (1H, d, J=8.7 Hz), 7.94 (1H, d, J=8.7 Hz), 7.72 (2H, d, J=8.7 Hz), 7.60-7.20 (12H, m) 6.74 (1H, s), 4.92 (1H, quint, J=8.9 Hz), 2.30-1.58 (8H, m)














Purity
>90% (NMR)


MS
489 (M + 1)





Example No.
71
1H NMR (δ) ppm














135





300 MHz, DMSO-d6 8.31 (1H, s), 8.05 (1H, d, J=8.7 Hz), 7.97 (1H, d, J=8.7 Hz), 7.76 (2H, d, J=8.6 Hz), 7.44-7.19 (7H. m), 4.94 (1H, quint, J=8.8 Hz), 4.35 (2H, t, J=6.7 Hz), 3.10 (2H, t, J=6.7 Hz), 2.32-1.60 (8H, m)














Purity
>90% (NMR)


MS
427 (M + 1)


Example No.
72
1H NMR (δ) ppm














136





300 MHz, DMSO-d6 8.30 (1H, s), 8.25 (1H, d, J=8.7 Hz), 8.03 (1H, d, J=9.0 Hz), 7.75 (2H, d, J=8.7 Hz), 7.51 (2H, d, J=7.2 Hz), 7.46-7.33 (5H, m), 5.27 (2H, s), 4.36 (1H, m), 2.50-2.25 (2H, m), 2.15-2.00 (2H, m), 1.95-1.85 (2H, m), 1.35 (1H, m), 1.20-1.10 (2H, m), 0.87 (9H, s).














Purity
>90% (NMR)


MS
483 (M + 1)










[1874]

15







TABLE 15















Example No.
73
1H NMR (δ) ppm














137





300 MHz, DMSO-d6 7.59 (2H, d, J=8.4 Hz), 7.52-7.35 (6H, m), 7.20 (2H, d, J=8.7 Hz), 7.14 (1H, d, J=2.1 Hz), 6.90 (m, dd, J=9.0, 2.4 Hz), 5.21 (2H, s), 4.83 (1H, quint, J=8.7 Hz), 4.70 (2H, s), 2.30-1.90 (6H, m), 1.75-1.55 (2H, m).














Purity
>90% (NMR)


MS
443 (M + 1)





Example No.
74
1H NMR (δ) ppm














138





300 MHz, DMSO-d6 8.27 (1H, s), 8.06 and 7.97 (2H, ABq, J=8.7 Hz), 7.57 and 6.86 (4H, A′ B′ q, J=8.9 Hz), 7.42-7.26 (5H, m), 5.04(1H, quint, J=9.0 Hz), 4.42 (2H, s), 2.32-1.94 (6H, m), 1.80-1.62 (2H, m)














Purity
>90% (NMR)


MS
412 (M + 1)





Example No.
75
1H NMR (δ) ppm














139





300 MHz, DMSO-d6 12.80 (1H, s), 8.26 (1H, s), 7.90 (1H, d, J=9.2 Hz), 7.76-7.60 (8H, m), 7.35 (2H, d, J=8.4 Hz), 4.84 (1H, quint, J=8.8 Hz), 3.23 (3H, s), 2.32-1.90 (6H, m), 1.78-1.61 (2H, m)














Purity
>90% (NMR)


MS
475 (M + 1)










[1875]

16







TABLE 16















Example No.
76
1H NMR (δ) ppm














140





300 MHz, DMSO-d6 8.29 (1H, s), 8.07 and 7.49 (2H, ABq, J=8.7 Hz), 7.66 and 7.00 (4H, A′ B′ q, J=7.7 Hz), 7.39-7.24 (5H, m), 5.05 (1H, quint, J=8.8 Hz), 4.76 (2H, s), 3.21 (3H, s), 2.35-1.92 (6H, m), 1.81-1.62 (2H, m)














Purity
>90% (NMR)


MS
426 (M + 1)





Example No.
77
1H NMR (δ) ppm


















141





300 MHz, DMSO-d6 8.21 (1H, s), 7.87 (1H, s), 7.56 and 7.43 (4H, ABq, J=8.1 Hz), 7.34-7.16 (5H, m), 4.25 (1h, brt, J=12.5 Hz), 3.06-2.92 (4H, m), 2.41-2.17 (2H, m), 1.96-1.77 (4H, m), 1.72-1.58 (1H, m), 1.48-1.15 (3H, m)














Purity
>90% (NMR)


MS
425 (M + 1)





Example No.
78
1H NMR (δ) ppm














142





300 MHz, DMSO-d6 8.14 (1H, s), 7.79 (1H, d, J=9.0 Hz), 7.57 (1H, d, J=8.7 Hz), 7.40-7.20 (5H, m), 4.89 (1H, quint, J=8.7 Hz), 3.54 (2H, s), 3.19-2.90 (3H, m), 2.23-1.69 (14H, m)














Purity
>90% (NMR)


MS
404 (M + 1)










[1876]

17







TABLE 17















Example No.
79
1H NMR (δ) ppm














143





300 MHz, DMSO-d6 8.15 (1H, s), 7.81 (1H, d, J=8.4 Hz), 7.59 (1H, d, J=9.0 Hz), 7.50-7.38 (5H, m), 5.05 (1H, quint, J=9.0 Hz), 3.85-2.95 (3H, m), 2.20-1.65 (14H, m)














Purity
>90% (NMR)


MS
418 (M + 1)


Example No.
80
1H NMR (δ) ppm














144





300 MHz, DMSO-d6 8.17 (1H, m), 7.84 (1H, d, J=8.4 Hz), 7.78-7.62 (3H, m), 7.49 (2H, d, J=8.1 Hz), 5.05-4.91 (1H, m), 3.80-3.70 (2H, m), 3.30-3.12 (1H, m), 2.48-2.31 (5H, m), 2.15-1.60 (12H, m)














Purity
>90% (NMR)


MS
468 (M + 1)





Example No.
81
1H NMR (δ) ppm














145





300 MHz, DMSO-d6 12.75 (1H, brs), 8.21 (1H, d, J=1.4 Hz), 7.49 (1H, d, J=8.6 Hz), 7.85 (1H, dd, J=8.6, 1.4 Hz), 7.70-7.55 (5H, m), 7.23 (2H, d, J=8.7 Hz), 5.25 (2H, s), 4.36-4.15 (1H, m), 2.39-2.18 (2H, m), 2.00-1.78 (4H, m), 1.70-1.57 (1H, m), 1.48-1.15 (3H, m)














Purity
>90% (NMR)


MS
495 (M + 1)










[1877]

18







TABLE 18















Example No.
82
1H NMR (δ) ppm














146





300 MHz, DMSO-d6 8.27 (1H, s), 8.22 (1H, d, J=8.7 Hz), 8.02 (1H, d, J=8.7 Hz), 7.69 (2H, d, J=8.7 Hz), 7.60-7.50 (4H, m), 7.45-7.25 (8H, m), 6.75 (1H, s), 4.21-4.23 (1H, m), 2.39-2.18 (2H, m), 2.10-1.78 (4H, m), 1.70-1.15 (4H, m)














Purity
>90% (NMR)


MS
503 (M + 1)





Example No.
83
1H NMR (δ) ppm














147





300 MHz, DMSO-d6 13.2 (1H, brs), 8.30 (1H, s), 8.23 (1H, d, J=8.8 Hz), 8.02 (1H, d, J=8.7 Hz), 7.74 (2H, d, J=8.6 Hz), 7.40-7.33 (5H, m), 5.22 (2H, s), 4.36 (1H, m), 2.50-1.40 (10H, m), 1.31 (18H, s).














Purity
>90% (NMR)


MS
539 (M + 1)





Example No.
84
1H NMR (δ) ppm














148





mixture of isomers (cis:trans = 3:1) 300 MHz, DMSO-d6 8.30 (1H, s), 8.20-7.95 (2H, m), 7.72 (2H, d, J=8.4 Hz), 7.52-7.29 (7H, m), 5.25 (2H, s), 4.34, 3.40 (1H, m), 2.50-2.20 (2H, m), 2.05-1.50 (6H, m), 1.14, 0.90 (3H, d, J=6.9, 6.3 Hz), 1.09 (1H, m).














Purity
>90% (NMR)


MS
441 (M + 1)










[1878]

19







TABLE 19















Example No.
85
1H NMR (δ) ppm














149





300 MHz, DMSO-d6 8.25 (1H, s), 8.14-7.83 (6H, m), 7.77-7.44 (5H, m), 7.21 (2H, d, J=7.8 Hz), 4.44 (2H, brt), 4.31 (1H, brt), 3.56 (2H, brt), 2.20-2.16 (2H, m), 2.00-1.74 (4H, m), 1.70-1.55 (1H, m), 1.45-1.14 (3H, m)














Purity
>90% (NMR)


MS
491 (M + 1)





Example No.
86
1H NMR (δ) ppm














150





300 MHz, DMSO-d6 12.75 (1H, s), 8.23 (1H, s), 8.15 (1H, d, J=7.6 Hz), 8.02-7.53 (10H, m), 7.32 (2H, d, J=8.7 Hz), 5.68 (2H, s), 4.32 (1H, brt, J=12.2 Hz), 2.41-2.20 (2H, m), 2.01-1.78 (4H, m), 1.71-1.56 (1H, m), 1.50-1.16 (3H, m)














Purity
>90% (NMR)


MS
477 (M + 1)





Example No.
87
1H NMR (δ) ppm














151





300 MHz, DMSO-d6 12.75 (1H, brs), 8.16 (1H, s), 7.91 and 7.82 (2H, ABq, J=8.5 Hz), 7.44 and 6.86 (4H, A′ B′ q, J=8.6 Hz), 7.39-7.26 (10H, m), 4.82 (2H, s), 4.35 (1H, brt, J=12.2 Hz), 2.35-2.16 (2H, m), 1.97-1.75 (4H, m), 1.69-1.56 (1H, m), 1.45-1.16 (3H, m)














Purity
>90% (NMR)


MS
516 (M + 1)










[1879]

20







TABLE 20















Example No.
88
111 NMR(6) ppm














152





300 MHz, DMSO-d6 8.31 (1H, s), 8.26 and 8.06 (2H, ABq, J=8.9 Hz), 7.73 and 7.22 (4H, A′ B′ q, J=8.7 Hz), 7.50-7.36 (8H, m), 5.10 (2H, s), 4.37 (1H, brt, J=12.2 Hz), 2.38-2.28 (2H, m), 2.10-1.80 (4H, m), 1.70-1.56 (1H, m), 1.50-1.20 (3H, m)














Purity
>90% (NMR)


MS
503 (M + 1)





Example No.
89
1H NMR (δ) ppm












153



















Purity
91% (HPLC)


MS
427 (M + 1)





Example No.
90
1H NMR (δ) ppm














154





300 MHz, DMSO-d6 8.40-8.20 (2H, m), 8.04 (1H, d, J=8.4 Hz), 7.65 (2H, d, J=8.4 Hz), 7.50-7.10 (12H, m), 5.08 (1H, m), 4.33 (1H, m), 3.00 (4H, m), 2.50-1.10 (10H, m)














Purity
>90% (NMR)


MS
531 (M + 1)










[1880]

21







TABLE 21















Example No.
91
1H NMR (δ) ppm














155





300 MHz, DMSO-d6 8.31 (1H, s), 8.27 (1H, d, J=8.7 Hz), 8.08-8.03 (3H, m), 7.77-7.58 (5H, m), 7.31 (2H, d, J=8.7 Hz), 5.81 (2H, s), 4.40 (1H, m), 2.50-1.20 (10H, m).














Purity
about 90% (NMR)


MS
455 (M + 1)





Example No.
92
1H NMR (6) ppm














156





300 MHz, DMSO-d6 11.8 (1H, brs), 8.07 (1H, s), 7.89 (1H, d, J=8.7 Hz), 7.84 (1H, d, J=8.4 Hz), 7.69 (2H, m), 7.48 (3H, m), 4.42 (2H, s), 4.11 (1H, m), 3.73 (4H, m), 3.40 (4H, m), 2.40-1.40 (10H, m).














Purity
>90% (NMR)


MS
419 (M + 1)





Example No.
93
1H NMR (δ) ppm














157





300 MHz, DMSO-d6 8.32 (1H, s), 8.28(1H, d, J=8.9 Hz), 8.05 (1H, d, Jp32 8.7 Hz), 7.72 (2H, d, J=8.7 Hz), 7.38 (4H, d, J=7.2 Hz), 7.31 (4H, t, J=7.3 Hz), 7.21-7.17 (4H, m), 4.37 (1H, m), 4.26 (1H, t, J=7.9 Hz), 4.01 (2H, t, J=6.2 Hz), 2.57 (2H, m), 2.50-2.20 (2H, m), 2.10-2.00 (2H, m), 2.00-1.75 (2H, m), 1.75-1.55 (1H, m), 1.55-1.20 (3H, m).














Purity
>90% (NMR)


MS
531 (M + 1)










[1881]

22







TABLE 22















Example No.
94
1H NMR (δ) ppm














158





300 MHz, DMSO-d6 8.32 (1H, s), 8.27 (1H, d, J=9.0 Hz), 8.05 (1H, d, J=8.7 Hz), 7.75-7.70 (3H, m), 7.56 (1H, d, J=8.4 Hz), 7.55-7.35 (6H, m), 7.22 (2H, d, J=8.7 Hz), 5.11 (2H, s), 4.36 (1H, m), 2.40-2.15 (2H, m), 2.15-1.95 (2H, m), 1.95-1.75 (2H, m), 1.75-1.55 (1H, m), 1.55-1.20 (3H, m).














Purity
>90% (NMR)


MS
537 (M + 1)





Example No.
95
1H NMR (δ) ppm














159





300 Hz, DMSO-d6 12.9 (1H, brs), 8.02 (1H, s), 7.82 (2H, m), 7.40-7.25 (5H, m), 4.58 (2H, s), 4.09 (1H, m), 3.71 (1H, m), 3.49 (2H, m), 3.21 (2H, m), 2.35-1.30 (14H, m).














Purity
>90% (NMR)


MS
434 (M + 1)





Example No.
96
1H NMR (δ) ppm














160





300 MHz, DMSO-d6 8.31 (1H, d, J=1.3 Hz), 8.27 (1H, d, J=8.8 Hz), 8.05 (1H, d, J=8.8 Hz), 7.76 (2H, d, J=8.7 Hz), 7.40-7.25 (4H, m), 7.06-6.90 (3H, m), 4.53-4.26 (5H, m), 2.40-2.18 (2H, m), 2.12-1.56 (5H, m), 1.50-1.19 (3H, m)














Purity
>90% (NMR)


MS
457 (M + 1)










[1882]

23







TABLE 23















Example No.
97
1H NMR (δ) ppm














161





300 MHz, DMSO-d6 8.32 (1H, d, J=1.3 Hz), 8.29 (1H, d, J=8.8 Hz), 8.05 (1H, dd, J=8.8, 1.3 Hz), 8.42 (2H, d, J=8.8 Hz), 7.37-7.16 (7H, m), 4.48-4.30 (1H, m), 4.12 (2H, t, J=6.2 Hz), 2.83-2.70 (2H, m), 2.40-1.50 (9H, m), 1.59-1.19 (3H, m)














Purity
>90% (NMR)


MS
455 (M + 1)





Example No.
98
1H NMR (δ) ppm














162





300 MHz, DMSO-d6 8.28 (1H, d, J=1.3 Hz), 8.21 (1H, d, J=8.8 Hz), 8.01 (1H, d, J=10.1 Hz), 7.70 (2H, d, J=8.7 Hz), 7.33-7.12 (7H, m), 4.44-4.28 (1H, m), 4.10 (2H, t, J=6.3H z), 2.62 (2H, t, J=7.4 Hz), 2.39-2.15 (2H, m), 2.10-1.18 (14H, m)














Purity
>90% (NMR)


MS
483 (M + 1)





Example No.
99
1H NMR (δ) ppm














163





300 MHz, DMSO-d6 12.93 (1H, brs), 8.30 (1H, d, J=1.4 Hz), 8.04 (1H, d, J=8.7 Hz), 7.92 (1H, dd, J=8.7, 1.4 Hz), 7.59-7.34 (5H, m), 7.07 (1H, s), 5.38 (2H, s), 4.78-4.60 (1H, m), 2.32-2.14 (2H, m), 2.03-1.28 (8H, m)














Purity
>90% (NMR)


MS
418 (M + 1)










[1883]

24







TABLE 24















Example No.
100
1H NMR (δ) ppm














164





300 MHz, DMSO-d6 8.46 (1H, d, J=2.1 Hz), 8.16 (1H, s), 8.00 (1H, dd, J=8.5, 2.1 Hz), 7.87 (1H, d, J=8.5 Hz), 7.68 (1H, d, J=8.5 Hz), 7.55-7.30 (5H, m), 7.08 (1H, d, J=8.5 Hz), 5.45 (2H, s), 4.25-4.08 (1H, m), 2.39-2.18 (2H, m), 2.00-1.75 (4H, m), 1.70-1.55 (1H. m), 1.45-1.19 (3H, m)














Purity
>90% (NMR)


MS
427 (M + 1)





Example No.
101
1H NMR (δ) ppm














165





300 MHz, DMSO-d6 8.33 (1H, s), 8.31 (1H, d, J=6.9 Hz), 8.06 (1H, d, J=8.4 Hz), 7.76 and 7.29 (4H, ABq, J=8.9 Hz), 6.68 (2H, s), 4.37 (1H, m), 4.35 (2H, t, J=7.0 Hz), 3.79 (6H, s), 3.63 (3H, s), 3.04 (2H, t, J=6.9 Hz), 2.30 (2H, m), 2.04 (2H, m), 1.86 (2H, m), 1.65 (1H, m), 1.50-1.15 (3H, m)














Purity
>90% (NMR)


MS
531 (M + 1)





Example No.
102
1H NMR (δ) ppm














166





300 MHz, DMSO-d6 12.88 (1H, s), 8.34 (1H, s), 7.86 (1H, d, J=8.5 Hz), 7.73 (1H, d, J=8.5 Hz), 7.63 and 7.23 (4H, ABq, J=8.7 Hz), 7.52-7.35 (5H, m), 5.22 (2H, s), 4.31 (1H, m), 2.39 (2H, m), 1.79 (2H, m), 1.53 (2H, m), 1.31 (2H, m), 1.11 (3H, s), 0.95 (3H, s)














Purity
>90% (NMR)


MS
455 (M + 1)










[1884]

25







TABLE 25















Example No.
103
1H NMR (δ) ppm














167





300 MHz, DMSO-d6 12.79 (1H, brs), 8.22 (2H, s), 8.02-7.78 (4H, m), 7.63-7.42 (6H, m), 7.20-7.09 (2H, m), 4.43 (2H, s), 4.27 (1H, brt, J=12.2 Hz), 3.59 (2H, s), 2.39-2.15 (2H, m), 1.98-1.72 (4H, m), 1.68-1.59 (1H, m), 1.43-1.12 (3H, m)














Purity
>90% (NMR)


MS
491 (M + 1)





Example No.
104
1H NMR (δ) ppm














168





300 MHz, DMSO-d6 12.75 (1H, s), 8.23 (1H, s), 7.94 and 7.86 (2H, ABq, J=8.6 Hz), 7.64 and 7.05 (4H, A′ B′ q, J=8.7 Hz) 7.32-7.09 (9H, m), 5.13 (2H, s), 4.28 (1H, brt, J=12.2 Hz), 2.36-2.19 (2H, m), 1.95-1.77 (4H, m), 1.66-1.56 (1H, m), 1.46-1.10 (3H, m)














Purity
>90% (NMR)


MS
519 (M + 1)





Example No.
105
1H NMR (δ) ppm














169





300 MHz, DMSO-d6 8.23 (1H, s), 7.94 and 7.87 (2H, ABq, J=8.6 Hz), 7.68 and 7.17 (4H, A′ B′ q, J=8.7 Hz), 7.46-7.33 (6H, m), 6.93 and 6.75 (2H, A″B″q, J=8.2 Hz), 6.82 (1H, s), 5.13 (2H, s), 4.30 (1H, brt, J=12.2 Hz), 2.39-2.18 (2H, m), 1.98-1.77 (4H, m), 1.71-1.59 (1H, m), 1.48-1.20 (3H, m)














Purity
>90% (NMR)


MS
519 (M + 1)










[1885]

26







TABLE 26















Example No.
106
1H NMR (δ) ppm














170





300 MHz, DMSO-d6 12.89 (1H, brs), 9.73 (1H, s), 8.24 (1H, s), 8.03 and 7.91 (2H, ABq, J=8.7 Hz), 7.66 and 7.04 (4H, A′ B′ q, J=8.7 Hz), 7.16-7.03 (3H, m), 6.89 (2H, t, J=9.2 Hz), 4.33 (1H, brt, J=12.2 Hz), 2.40-2.18 (2H, m), 2.00-1.78 (4H, m), 1.70-1.58 (1H, m), 1.50-1.20 (3H, m)














Purity
>90% (NMR)


MS
429 (M + 1)





Example No.
107
1H NMR (δ) ppm














171





300 MHz, DMSO-d6 12.98 (1H, brs), 9.82 (1H, brs), 8.27 (1H, s), 8.09 and 7.94 (2H, ABq, J=8.7 Hz), 7.74 and 7.22 (4H, A′ B′ q, J=8.7 Hz), 7.28-7.22 (1H, m), 6.67-6.54 (3H, m), 4.35 (1H, brt, J=12.2 Hz), 2.40-2.20 (2H, m), 2.05-1.80 (4H, m), 1.72-1.59 (1H, m), 1.50-1.21 (3H, m)














Purity
>90% (NMR)


MS
429 (M + 1)





Example No.
108
1H NMR (δ) ppm














172





300 MHz, DMSO-d6 8.24 (1H, s), 8.01 and 7.90 (2H, ABq, J=8.7 Hz), 7.65 and 7.03 (4H, A′ B′ q, J=8.7 Hz), 7.32-7.20 (3H, m), 7.08-7.03 (1H, m), 4.32 (1H, brt, J=12.2 Hz), 3.77 (3H, s), 2.36-2.20 (2H, m), 2.00-1.78 (4H, m), 1.71-1.59 (1H, m), 1.44-1.11 (3H, m)














Purity
>90% (NMR)


MS
443 (M + 1)










[1886]

27







TABLE 27















Example No.
109
1H NMR (δ) ppm














173





300 MHz, DMSO-d6 12.75 (1H, s), 8.24 (1H, s), 7.96 and 7.87 (2H, ABq, J=9.0 Hz), 7.69 and 7.19 (4H, A′ B′ q, J=8.6 Hz), 7.37 (1H, t, J=7.1 Hz), 6.84-6.70 (3H, m), 4.31 (1H, brt, J=12.2 Hz), 3.78 (3H, s), 2.39-2.20 (2H, m), 1.98-1.78 (4H, m), 1.76-1.60 (1H, m), 1.48-1.13 (3H, m)














Purity
>90% (NMR)


MS
443 (M + 1)





Example No.
110
1H NMR (δ) ppm














174





300 MHz, DMSO-d6 8.31 (1H, s), 8.26 and 8.04 (2H, ABq, J=8.8 Hz), 7.75 and 7.71 (4H, A′ B′ q, J=8.8 Hz), 7.32-7.03 (4H, m), 4.34 (1H, brt, J=12.2 Hz), 3.94 (2H, t, J=6.3 Hz), 2.40-2.19 (2H, m), 2.11-1.81 (4H, m), 1.72-1.16 (6H, m), 0.71 (3H, t, J=7.3 Hz)














Purity
>90% (NMR)


MS
471 (M + 1)





Example No.
111
1H NMR (δ) ppm














175





300 MHz, DMSO-d6 8.22 (1H, s), 7.91 and 7.87 (2H, ABq, J=8.7 Hz), 7.68 and 7.18 (4H, A′ B′ q, J=8.7 Hz), 7.35 (1H, t, J=8.5 Hz), 6.80 (1H, d, J=9.0 Hz), 6.72-6.68 (2H, m), 4.30 (1H, brt, J=12.2 Hz), 3.94 (2H, t, J=6.5 Hz), 2.39-2.18 (2H, m), 1.97-1.58 (7H, m), 1.45-1.20 (3H, m), 0.97 (3H, t, J=7.4 Hz)














Purity
>90% (NMR)


MS
471 (M + 1)










[1887]

28







TABLE 28















Example No.
112
1H NMR (δ) ppm














176





300 MHz, DMSO-d6 12.73 (1H, s), 8.22 (1H, s), 7.94 and 7.85 (2H, ABq, J=9.3 Hz), 7.61 and 7.01 (4H, A′ B′ q, J=8.6 Hz), 7.25-7.00 (4H, m), 5.25 (2H, brs), 4.55 (2H, d, J=6.6 Hz), 4.29 (1H, brt, J=12.2 Hz), 2.38-2.18 (2H, m), 1.96-1.78 (4H, m), 1.70-1.56 (1H, m), 1.67 (3H, s), 1.60 (3H, s), 1.48-1.15 (3H, m)














Purity
>90% (NMR)


MS
497 (M + 1)





Example No.
113
1H NMR (δ) ppm














177





300 MHz, DMSO-d6 12.75 (1H, s), 8.23 (1H, s), 7.95 and 7.86 (2H, ABq, J=8.9 Hz), 7.69 and 7.18 (4H, A′ B′ q, J=8.9 Hz), 7.35 (1H, t, J=8.3 Hz), 6.81-6.69 (3H, m), 5.41 (2H, brs), 4.54 (2H, d, J=6.6 Hz), 4.31 (1H, brt, J=12.2 Hz), 2.41-2.18 (2H, m), 1.98-1.76 (4H, m), 1.73 (3H, s), 1.70-1.58 (1H, m), 1.68 (3H, s), 1.45-1.17 (3H, m)














Purity
>90% (NMR)


MS
497 (M + 1)





Example No.
114
1H NMR (δ) ppm














178





300 MHz, DMSO-d6 12.73 (1H, s), 8.22 (1H, s), 7.94 and 7.85 (2H, ABq, J=8.4 Hz), 7.60 and 6.99 (4H, A′ B′ q, J=8.6 Hz), 7.29-7.00 (4H, m), 4.29 (1H, brt, J=12.2 Hz), 3.99 (2H, t, J=6.3 Hz), 2.41-2.20 (2H, m), 1.95-1.76 (4H, m), 1.70-1.14 (7H, m), 0.76 (3H, d, J=6.6 Hz)














Purity
>90% (NMR)


MS
499 (M + 1)










[1888]

29







TABLE 29















Example No.
115
1H NMR (δ) ppm














179





300 MHz, DMSO-d6 8.23 (1H, s), 7.93 and 7.87 (2H, ABq, J=8.6 Hz), 7.69 and 7.19 (4H, A′ B′ q, J=8.6 Hz), 7.35 (1H, t, J=7.8 Hz), 6.82-6.69 (3H, m), 4.30 (1H, brt, J=12.2 Hz), 4.00 (2H, t, J=6.9 Hz), 2.38-2.20 (2H, m), 1.97-1.54 (8H, m), 1.47-1.20 (3H, m), 0.93 (6H, d, J=6.6 Hz)














Purity
>90% (NMR)


MS
499 (M + 1)





Example No.
116
1H NMR (δ) ppm














180





300 MHz, DMSO-d6 8.30 (1H, s), 8.25 (1H, d, J=8.9 Hz), 8.03 (1H, d, J=8.8 Hz), 7.68 (2H, d, J=8.8 Hz), 7.24 (2H, d, J=7.2 Hz), 7.19-7.10 (6H, m), 6.94 (2H, t, J=7.2 Hz), 4.34 (1H, m), 4.19 (4H, brs), 3.10 (4H, brs), 2.40-2.15 (2H, m), 2.10-1.95 (2H, m), 1.95-1.75 (2H, m), 1.75-1.55 (1H, m), 1.55-1.20 (3H, m).














Purity
>90% (NMR)


MS
557 (M + 1)





Example No.
117
1H NMR (δ) ppm














181





300 MHz, DMSO-d6 12.8 (1H, brs), 8.22 (1H, s), 7.98 (1H, d, J=8.7 Hz), 7.87 (1H, d, J=8.6 Hz), 7.80 (2H, d, J=8.2 Hz), 7.72-7.67 (3H, m), 7.59 (2H, d, J=8.7 Hz), 7.54-7.51 (2H, m), 7.42-7.41 (1H, m), 7.11 (2H, d, J=8.8 Hz), 5.09 (2H, s), 4.27 (1H, m), 2.40-2.15 (2H, m), 2.00-1.75 (4H, m), 1.75-1.55 (1H, m), 1.55-1.15 (3H, m).














Purity
>90% (NMR)


MS
571 (M + 1)










[1889]

30







TABLE 30















Example No.
118
1H NMR (δ) ppm














182





300 MHz, DMSO-d6 13.3 (1H, brs), 8.30 (1H, s), 8.25 (1H, d, J=8.9 Hz), 8.04 (1H, d, J=8.7 Hz), 7.72 (2H, d, J=8.8 Hz), 7.57 (4H, d, J=8.6 Hz), 7.33 (2H, d, J=8.9 Hz), 6.84 (1H, s), 4.33 (1H, m), 2.45-2.10 (2H, m), 2.10-1.95 (2H, m), 1.95-1.70 (2H, m), 1.70-1.55 (1H, m), 1.55-1.15 (3H, m).














Purity
>90% (NMR)


MS
571 (M + 1)





Example No.
119
1H NMR (δ) ppm














183





300 MHz, DMSO-d6 8.32-8.30 (2H, m), 8.07-8.03 (1H, m), 7.74 and 6.90 (4H, ABq, J=8.7 Hz), 4.37 (1H, m), 4.31 (2H, t, J—6.8 Hz), 3.74 (3H, s), 3.04 (2H, t, J=6.7 Hz), 2.30 (2H, m), 2.02 (2H, m), 1.86 (2H, m), 1.63 (1H, m), 1.55-1.15 (3H, m)














Purity
>90% (NMR)


MS
471 (M + 1)


Example No.
120
1H NMR (δ) ppm














184





300 MHz, DMSO-d6 8.23 (1H, s), 7.99 (1H, d, J=8.7 Hz), 7.88 (1H, d, J=8.4 Hz), 7.61 and 7.16 (4H, ABq, J=8.6 Hz), 7.30-7.22 (2H, m), 7.01 (2H, d, J=8.1 Hz), 6.92 (1H, t, J=7.5 Hz), 4.28 (1H, m), 4.25 (2H, t, J=7.2 Hz), 3.83 (3H, s), 3.07 (2H, t, J=7.1 Hz), 2.28 (2H, m) 2.00-1.75 (4H, m), 1.70-1.55 (1H, m), 1.50-1.15 (3H, m)














Purity
>90% (NMR)


MS
471 (M + 1)










[1890]

31







TABLE 31










Example No.
121
1H NMR(δ) ppm














185





300 MHz, DMSO-d6 12.85(1H, brs), 8.24(1H, s), 8.01(1H, d, J=8.7 Hz), 7.90 (1H, d, J=8.6 Hz), 7.62 and, 7.17(4H, ABq, J=8.7 Hz), 7.24 (1H, m), 6.94(2H, m), 6.82 (1H, m), 4.32(2H, t, J=6.7 Hz), 3.76(3H, s), 3.07(2H, t, J=6.7 Hz), 2.29 (2H, m), 2.00-1.75 (4H, m), 1.70-1.55 (1H, m), 1.50-1.15(3H, m)














Purity
>90% (NMR)


MS
471(M + 1)





Example No.
122
1H NMR(δ) ppm














186





300 MHz, DMSO-d6 12.8(1H, brs), 8.22(1H, s), 7.87(2H, m), 7.62(2H, d, J=8.1 Hz), 7.60-7.20 (7H, m), 5.23(2H, s), 4.46(1H, m), 2.50-2.30(2H, m), 1.70-1.40(10H, m).














Purity
>90% (NMR)


MS
441(M + 1)


Example No.
123
1H NMR(δ) ppm














187





300 MHz, DMSO-d6 8.24(1H, s), 7.97(1H, d, J=9.0 Hz), 7.87 (1H, d, J=8.4 Hz), 7.65(2H, d, J=8.7 Hz), 7.40-7.05(9H, m), 7.03(2H, d, J=8.4 Hz), 4.31(1H, m), 4.18(2H, t, J=6.6 Hz), 2.81 (2H, t, J=6.3 Hz), 2.40-2.20 (2H, m), 2.00-1.70(4H, m), 1.70-1.50(1H, m), 1.50-1.05(3H, m).














Purity
>90% (NMR)


MS
533(M + 1)










[1891]

32







TABLE 32















Example No.
124
1H NMR(δ) ppm














188





300 MHz, DMSO-d6 13.1(1H, brs), 8.29(1H, s), 8.17(1H, d, J=8.7 Hz), 7.99 (1H, d, J=8.7 Hz), 7.77 (2H, d, J=8.7 Hz), 7.40-7.20 (8H, m), 6.84(1H, d, J=9.3 Hz), 6.75-6.72(2H, m), 4.36(1H, m), 4.22(2H, t, J=6.8 Hz), 3.04 (2H, t, J=6.7 Hz), 2.40-2.15 (2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55 (1H, m), 1.55-1.15(3H, m).














Purity
>90% (NMR)


MS
533(M + 1)





Example No.
125
1H NMR(δ) ppm














189





300 MHz, DMSO-d6 8.32(1H, s), 8.28(1H, d, J=8.7 Hz), 8.05(1H, d, J=9.0 Hz), 7.73(2H, d, J=9.0 Hz), 7.43 (4H, d, J=7.2 Hz), 7.36-7.20 (8H, m), 4.74(2H, d, J=7.5 Hz), 4.57(1H, t, J=7.5 Hz), 4.38(1H, m), 2.40-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.85 (2H, m), 1.85-1.55(1H, m), 1.55-1.20(3H, m).














Purity
>90% (NMR)


MS
517(M + 1)





Example No.
126
1H NMR(δ) ppm














190





300 MHz, DMSO-d6 8.32 (1H, s), 8.14(1H, d, J=8.7 Hz), 8.03(1H, d, J=8.7 Hz), 7.77(2H, d, J=9.0 Hz), 7.52-7.31(7H, m), 5.74(2H, m), 5.26(2H, s), 4.61(1H, m), 2.96 (1H, m), 2.60-2.10(5H, m).










38



Purity
>90% (NMR)


MS
425(M + 1)










[1892]

33







TABLE 33















Example No.
127
1H NMR(δ) ppm














191





300 MHz, DMSO-d6 13.2(1H, brs), 8.33(1H, s), 8.12(1H, d, J=8.7 Hz), 7.96 (1H, d, J=8.8 Hz), 7.79(2H, d, J=8.7 Hz), 7.52-7.32(7H, m), 5.26(2H, s), 4.92(1H, d, J=49.4 Hz), 4.57(1H, m), 2.65-2.35(2H, m), 2.25-1.50 (6H, m).

















Purity
>90% (NMR)


MS
445(M + 1)





Example No.
128
1H NMR(δ) ppm














192





300 MHz, DMSO-d6 8.21(1H, s), 7.92 and 7.85 (2H, ABq, J=8.6 Hz), 7.61 and 7.06(4H, A′ B′ q, J=8.6 Hz), 7.36-6.91(9H, m), 4.24(1H, brt, J=12.2 Hz), 2.35-2.15(2H, m), 1.95-1.75(4H, m), 1.70-1.58(1H, m), 1.48-1.14(3H, m)














Purity
>90% (NMR)


MS
505(M + 1)





Example No.
129
1H NMR(δ) ppm














193





300 MHz, DMSO-d6 8.21(1H, s), 7.92 and 7.86 (2H, ABq, J=8.6 Hz), 7.69 and 7.22(4H, A′ B′ q, J=8.6 Hz), 7.52-7.39(1H, m), 7.47 and 7.41 (2H, A″B″q, J=8.1 Hz), 6.91 (1H, d, J=8.0 Hz), 6.89(1H, d, J=8.2 Hz), 6.75(1H, s,), 4.36-4.18(4H, m), 2.38-2.17(2H, m), 1.95-1.76(4H, m), 1.70-1.59(1H, m), 1.44-1.19(3H, m)














Purity
>90% (NMR)


MS
505(M + 1)










[1893]

34







TABLE 34















Example No.
130
1H NMR(δ) ppm














194





300 MHz, DMSO-d6 8.27(1H, s), 7.69(2H, d, J=8.6 Hz), 7.49-7.21(11H, m), 5.08 and 5.03(2H, ABq, J=12.6 Hz), 5.07-4.99(1H, m) 4.26 (2H, d, J=6.6 Hz), 2.40-2.18 (2H, m), 2.04-1.77(4H, m), 1.70-1.58(1H, m), 1.48-1.15 (3H, m)














purity
>90% (NMR)


MS
590(M + 1)





Example No.
131
1H NMR(δ) ppm














195





300 MHz, DMSO-d6 8.29(1H, s), 8.11(1H, d, J=9.0 Hz), 7.96(1H, d, J=8.4 Hz), 7.80(2H, d, J=8.1 Hz), 7.72-7.41(7H, m), 7.12(1H, d, J=12.6 Hz), 7.01(1H, d, J=8.4 Hz), 5.12(2H, s), 4.06(1H, m), 2.35-2.10(2H, m), 2.00-1.75(4H, m), 1.75-1.55(1H, m), 1.60-1.20(3H, m).














Purity
>90% (NMR)


MS
589(M + 1)





Example No.
132
1H NMR(δ) ppm














196





300 MHz, DMSO-d6 12.8(1H, brs), 8.23 (1H, s), 7.97(1H, d, J=8.7 Hz), 7.87 (1H, d, J=8.6 Hz), 7.66(2H, d, J=8.6 Hz), 7.49-7.33(5H, m), 7.17-7.05(6H, m), 5.12(2H, s), 4.31(1H, m), 2.40-2.15 (2H, m), 2.05-1.20(8H, m).














Purity
>90% (NMR)


MS
519(M + 1)










[1894]

35







TABLE 35















Example No.
133
1H NMR(δ) ppm














197





300 MHz, DMSO-d6 8.57(1H, s), 8.01(1H, d, J=8.7 Hz), 7.66(1H, d, J=8.7 Hz), 7.51(2H, d, J=8.7 Hz), 7.31 (4H, d, J=8.0 Hz), 7.16(4H, d, J=8.0 Hz), 7.09(2H, d, J=8.7 Hz), 6.26(1H, s), 4.37(1H, m), 2.41-2.28 (2H, m), 2.33 (6H, s), 2.03-1.84(4H, m), 1.77(1H, m), 1.45-1.20(3H, m).














Purity
>90% (NMR)


MS
531(M + 1)





Example No.
134
1H NMR(δ) ppm














198





8.59(1H, d, J=1.5 Hz), 8.02 (1H, dd, J=8.7, 1.5 Hz), 7.68 (1H, d, J=8.7 Hz), 7.54(2H, d, J=8.8 Hz), 7.39(4H, dd, J=8.7, 5.3 Hz), 7.08(4H, d, J=8.7 Hz), 7.05(2H, d, J=8.8 Hz), 6.29(1H, s), 4.36(1H, m), 2.43-2.19(2H, m), 2.04-1.85(4H, m), 1.78(1H, m), 1.45-1.23 (3H, m).














Purity
>90% (NMR)


MS
539(M + 1)





Example No.
135
1H NMR(δ) ppm














199





300 MHz, DMSO-d6 12.34(1H, brs), 7.93(1H, s), 7.55(1H, d, J=8.6 Hz), 7.33-7.15(6H, m), 7.11(2H, d, J=8.6 Hz), 4.30-4.20(1H, m), 4.07(2H, t, J=6.3 Hz), 3.93 (3H, s), 2.78(2H, t, J=7.4 Hz), 2.35-2.19(2H, m), 2.12-2.00(2H, m), 1.91-1.79(4H, m), 1.69-1.60(1H, m), 1.47-1.20(3H, m)














Purity
>90% (NMR)


MS
485(M + 1)










[1895]

36







TABLE 36















Example No.
136
1H NMR(δ) ppm














200





300 MHz, DMSO-d6 8.13(1H, s), 7.65(2H, d, J=8.7 Hz), 7.63(1H, s), 7.35-7.12(7H, m), 4.35-4.20(1H, m), 4.10(1H, t, J=6.3 Hz), 2.78 (2H, t, J=7.5 Hz), 2.33-1.78 (8H, m), 1.70-1.16(4H, m)














Purity
>90% (NMR)


MS
471(M + 1)





Example No.
137
1H NMR(δ) ppm














201





300 MHz, DMSO-d6 8.24(1H, s), 8.11(1H, s), 7.76(2H, d, J=9.0 Hz), 7.37-7.16(7H, m), 4.43-4.30(1H, m), 4.13(2H, t, J=6.3 Hz), 2.84-2.68(5H, m), 2.42-2.22 (2H, m), 2.18-1.80(6H, m), 1.70-1.20(4H, m)














Purity
>90% (NMR)


MS
469(M + 1)





Example No.
138
1H NMR(δ) ppm














202





300 MHz, DMSO-d6 12.73(1H, brs), 8.22(1H, s), 7.76(1H, d, J=8.7 Hz), 7.85 (1H, d, J=8.7 Hz), 7.54-7.49 (4H, m), 7.42-7.21 (5H, m), 7.11-7.09(3H, m), 6.93(1H, m), 5.17(2H, s), 4.29 (3H, m), 3.11(2H, m), 2.40-2.20(2H, m), 1.99-1.23(8H, m)














Purity
>90% (NMR)


MS
547(M + 1)










[1896]

37







TABLE 37















Example No.
139
1H NMR(δ) ppm














203





300 MHz, DMSO-d6 12.73(1H, brs), 8.22(1H, s), 7.93(1H, d, J=8.7 Hz), 7.73 (1H, m), 7.60-7.57(2H, m), 7.47-6.90(1H, m), 5.11(2H, s), 4.33-4.28(3H, m), 3.09-3.04(2H, t, J=6.7 Hz), 2.35-2.20(2H, m), 1.95-1.10(8H, m)














Purity
>90% (NMR)


MS
547(M + 1)





Example No.
140
1H NMR(δ) ppm














204





300 MHz, DMSO-d6 12.83(2H, brs), 8.22(1H, s), 7.94(1H, d, J=8.7 Hz), 7.85 (1H, d, J=8.4 Hz), 7.63-7.60 (2H, m), 7.26-7.03(6H, m), 4.73(2H, s), 4.30(1H, m), 2.40-2.15(2H, m), 2.00-1.20 (8H, m)














Purity
>90% (NMR)


MS
487(M + 1)





Example No.
141
1H NMR(δ) ppm














205





300 MHz, DMSO-d6 12.87(1H, brs), 8.24(1H, s), 7.97(1H, d, J=9.0 Hz), 7.87 (1H, d, J=8.7 Hz), 7.69 and 7.19(4H, ABq, J=8.7 Hz), 7.36 (1H, t, J=8.7 Hz), 6.80-6.72 (3H, m), 4.71(2H, s), 4.32(1H, m), 2.29(2H, m), 1.95-1.25 (8H, m)














Purity
>90% (NMR)


MS
487(M + 1)










[1897]

38







TABLE 38















Example No.
142
1H NMR(δ) ppm














206





300 MHz, DMSO-d6 8.32(1H, s), 8.27(1H, d, J=8.7 Hz), 8.05(1H, d, J=9.0 Hz), 7.76-7.72(3H, m), 7.54(1H, d, J=8.4 Hz), 7.39-7.22(7H, m), 5.11(1H, s), 4.36(1H, m), 2.35(3H, s), 2.35-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m).














Purity
>90% (NMR)


MS
551(M + 1)





Example No.
143
1H NMR(δ) ppm














207





300 MHz, DMSO-d6 13.1(1H, brs), 8.30 (1H, s), 8.24(1H, d, J=8.8 Hz), 8.03 (1H, d, J=8.7 Hz), 7.74-7.71 (3H, m), 7.52(1H, d, J=8.3 Hz), 7.40-7.36(3H, m), 7.23(2H, d, J=8.8 Hz), 7.01(2H, d, J=8.7 Hz), 5.11(2H, s), 4.35 (1H, m), 3.79(3H, s), 2.45-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15 (3H, m).














Purity
>90% (NMR)


MS
567(M + 1)





Example No.
144
1H NMR(δ) ppm














208





300 MHz, DMSO-d6 13.0 (1H, brs), 8.31 (1H, s), 8.23(1H, d, J=8.7 Hz), 8.04 (1H, d, J=8.7 Hz), 7.80(2H, d, J=8.3 Hz), 7.70-7.66(3H, m), 7.55-7.40(4H, m), 7.03-6.95(2H, m), 5.08(2H, s), 4.03 (1H, m), 2.40-2.15(2H, m), 2.18(3H, s), 2.05-1.70(4H, m), 1.70-1.50(2H, m), 1.50-1.10(3H, m).














Purity
>90% (NMR)


MS
585(M + 1)










[1898]

39







TABLE 39















Example No.
145
1H NMR(δ) ppm














209





300 MHz, DMSO-d6 8.31(1H, s), 8.23(1H, d, J=8.8 Hz), 8.02(1H, d, J=8.7 Hz), 7.73-7.71(3H, m), 7.54(1H, d, J=8.3 Hz), 7.48(2H, d, J=8.4 Hz), 7.41-7.37(3H, m), 7.22(2H, d, J=8.7 Hz), 5.13 (2H, s), 4.34(1H, m), 2.40-2.20 (2H, m), 2.15-1.95 (2H, m), 1.95-1.75(2H, m), 1.70-1.55 (1H, m), 1.50-1.15(3H, m), 1.31(9H, s).














Purity
>90% (NMR)


MS
593(M + 1)





Example No.
146
1H NMR(δ) ppm














210





300 MHz, DMSO-d6 8.29(1H, s), 8.13(1H, d, J=8.7 Hz), 7.97(1H, d, J=8.6 Hz), 7.76(1H, d, J=2.1 Hz), 7.63 (1H, t, J=8.5 Hz), 7.57(1H, dd, J=8.2, 2.2 Hz), 7.55-7.35 (6H, m), 7.15(1H, d, J=12.1 Hz), 7.02(1H, d, J=8.6 Hz), 5.10(2H, s), 4.07(1H, m), 2.35-2.10(2H, m), 2.00-1.70 (4H, m), 1.70-1.55 (1H, m), 1.50-1.15(3H, m).














Purity
>90% (NMR)


MS
555(M + 1)





Example No.
147
1H NMR(δ) ppm














211





300 MHz, CDCl3 8.61(1H, s), 8.04(1H, d, J=8.7 Hz), 7.69(1H, d, J=8.7 Hz), 7.66(1H, d, J=2.4 Hz), 7.59 (2H, d, J=8.7 Hz), 7.42(1H, d, J=8.0, 2.4 Hz), 7.38(1H, t, J=1.8 Hz), 7.28(2H, d, J=1.8 Hz), 7.26(1H, d, J=8.0 Hz), 7.03(2H, d, J=8.7 Hz), 4.94 (2H, s), 4.37(1H, m), 2.43-2.21(2H, m), 2.17-1.86(4H, m), 1.79(1H, m), 1.43-1.26(3H, m).














Purity
>90% (NMR)


MS
605(M + 1)










[1899]

40







TABLE 40















Example No.
148
1H NMR(δ) ppm














212





300 MHz, DMSO-d6 8.21(s, 1H), 7.89(1H, d, J=8.7 Hz), 7.87(1H, d, J=8.7 Hz), 7.63-7.46(5H, m), 7.30-7.12(5H, m), 7.08(1H, d, J=11.0 Hz), 6.81(1H, s), 3.92(1H, m), 2.15-2.06(2H, m), 1.89-172(4H, m), 1.61(1H, m), 1.42-1.09(3H, m).














Purity
>90% (NMR)


MS
557(M + 1)





Example No.
149
1H NMR(δ) ppm














213





300 MHz, DMSO-d6 8.24(1H, d, J=1.5 Hz), 7.96 (1H, d, J=9.0 Hz), 7.88(1H, dd, J=9.0, 1.5 Hz), 7.58(1H, d, J=8.7 Hz), 7.50-7.30(5H, m), 7.22-7.00(6H, m), 5.13(2H, s), 3.98-3.80(1H, s), 2.36-1.10(10H, m)














Purity
>90%(NMR)


MS
553(M + 1)





Example No.
150
1H NMR(δ) ppm














214





300 MHz, DMSO-d6 8.23(1H, s), 8.95(1H, d, J=8.4 Hz), 7.88(1H, d, J=8.7 Hz), 7.66(1H, d, J=8.4 Hz), 7.52-7.28(7H, m), 7.23(2H, d, J=9.3 Hz), 7.14(2H, d, J=8.7 Hz), 5.14(2H, s), 3.90-3.72(1H, m), 2.20-1.10(10H, m)














Purity
>90%(NMR)


MS
587(M + 1)










[1900]

41







TABLE 41















Example No.
151
1H NMR(δ) ppm














215





300 MHz, DMSO-d6 8.18(1H, s), 7.92-7.78 (3H, m), 7.78-7.58 (3H, m), 7.58-7.44(4H, m) 7.29(1H, d, J=8.2 Hz), 7.01(2H, d, J=8.7 Hz), 4.88(1H, d, J=11.8 Hz), 4.80(1H, d, J=11.8 Hz), 4.22 (1H, m), 2.37-2.16 (2H, m), 1.95-1.75(4H, m), 1.64(1H, m), 1.48-1.14(3H, m).














Purity
>90% (NMR)


MS
605(M + 1)





Example No.
152
1H NMR(δ) ppm














216





300 MHz, DMSO-d6 8.21(2H, m), 7.99-7.80 (2H, m), 7.63-7.08(9H, m), 4.20-3.98(4H, m), 2.20-2.15(2H, m), 1.95-1.74(4H, m), 1.70-1.54(1H, m), 1.44-1.14(3H, m)














Purity
>90% (NMR)


MS
456(M + 1)





Example No.
153
1H NMR(δ) ppm














217





300 MHz, DMSO-d6 8.20(1H, s), 8.93 and 7.83(2H, ABq, J=8.7 Hz), 7.86-7.21 (11H, m), 7.03(2H, d, J=8.7 Hz), 4.20(1H, brt, J=12.2 Hz), 2.32-2.13(2H, m), 1.92-1.74(4H, m), 1.69-1.58(1H, m), 1.45-1.15(3H, m)














Purity
>90% (NMR)


MS
489(M + 1)










[1901]

42







TABLE 42















Example No.
154
1H NMR(δ) ppm














218





300 MHz, DMSO-d6 8.23(1H, s), 7.94 and 7.86(2H, ABq, J=8.6 Hz), 7.72-7.16(13H, m), 5.25 (2H, brs), 4.55(2H, d, J=6.6 Hz), 4.31 (1H, brt, J=12.2 Hz), 2.37-2.18 (2H, m), 1.98-1.77(4H, m), 1.70-1.58(1H, m), 1.48-1.20(3H, m)














Purity
>90% (NMR)


MS
489 (M + 1)





Example No.
155
1H NMR(δ) ppm














219





300 MHz, DMSO-d6 8.21(1H, s), 7.85 and 7.61(2H, ABq, J=8.7 Hz), 7.6 1 and 6.99(4H, A′ B′ q, J=8.7 Hz), 7.28-7.18(1H, m), 7.25(2H, d, J=7.5 Hz), 7.07-6.99 (1Hm), 4.30(1H, brt, J=12.2 Hz), 3.83(2H, d, J=6.0 Hz), 3.82-3.72(1H, m), 2.68-2.49(2H, m), 2.39-2.21(2H, m), 1.95-1.80(4H, m), 1.79-1.60(2H, m), 1.46-1.22(5H, m), 1.30(9H, s), 1.00-0.82(2H, m)














Purity
>90% (NMR)


MS
626(M + 1)





Example No.
156
1H NMR(δ) ppm














220





300 MHz, DMSO-d6 8.22(1H, s), 7.92 and 7.86(2H, ABq, J=8.7 Hz), 7.68 and 7.18(4H, A′ B′ q, J=8.7 Hz), 7.35 (1H, t, J=8.5 Hz), 6.80 (1H, d, J=8.3 Hz), 6.72-6.70(2H, m) 4.30(1H, brt, J=12.2 Hz), 3.99(2H, brd, J=12.0 Hz), 3.85(2H, d, (2H, d, J=6.3 Hz), 2.82-2.62 (2H, m), 2.38-2.20(2H, m), 1.99-1.59 (8H, m), 1.42-1.03(5H, m), 1.39(9H, s)














Purity
>90% (NMR)


MS
626(M + 1)










[1902]

43







TABLE 43















Example No.
157
1H NMR(δ) ppm














221





300 MHz, DMSO-d6 12.78(1H, brs), 8.22 (1H, s), 7.96(1H, d, J=8.6 Hz), 7.86 (1H, d, J=8.6 Hz), 7.75(1H, d, J=2.2 Hz), 7.60(2H, d, J=8.4 Hz), 7.55(1H, dd, J=8.3, 2.2 Hz), 7.48(1H, d, J=8.3 Hz), 7.18(2H, d, J=8.4 Hz), 6.73 (2H, s), 5.08(2H, s), 4.23(1H, m), 3.68(9H, s), 2.37-2.17 (2H, m), 1.99-1.79(4H, m), 1.65(1H, s), 1.49-1.15 (3H, m).














Purity
>90% (NMR)


MS
627(M + 1)





Example No.
158
1H NMR(δ) ppm














222





300 MHz, DMSO-d6 12.75(1H, brs), 8.22 (1H, s), 7.93 (2H, d, J=8.7 Hz), 7.85 (2H, d, J=8.5 Hz), 7.53-7.21 (10H, m), 6.94(2H, d, J=8.7 Hz), 4.30-4.12(3H, m), 3.05 (2H, m), 2.35-2.15(2H, m), 1.95-1.75(4H, m), 1.75-1.55 (1H, m), 1.50-1.10(3H, m)














Purity
>90% (NMR)


MS
517(M + 1)





Example No.
159
1H NMR(δ) ppm














223





300 MHz, DMSO-d6 12.77(1H, brs), 8.22(1H, s), 7.95(1H, d, 8.6 Hz), 7.86(1H, d, 8.6 Hz), 7.80(1H, s), 7.70-7.35(10H, m), 7.27 (2H, d J=8.7 Hz), 5.30(2H, s), 4.28(1H, m), 2.35-2.15 (2H, m), 1.95-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.15(3H, m)














Purity
>90% (NMR)


MS
503(M + 1)










[1903]

44







TABLE 44















Example No.
160
1H NMR(δ) ppm














224





300 MHz, DMSO-d6 8.90(1H, brs), 8.59(1h, brs), 8.33(1H, s), 8.18 and 8.00 (2H, ABq, J=8.5 Hz), 7.73 and 7.10(4H, A′ B′ q, J=8.5 Hz), 7.32-7.05 (4H, m), 4.35(1H, brt, J=12.2 Hz), 3.86(2H, d, J=6.3 Hz), 3.25-3.08 (2H, m), 2.85-2.66(2H, m), 2.40-2.28(2H, m), 2.07-1.14(15H, m)














Purity
>90% (NMR)


MS
526(M + 1)





Example No.
161
1H NMR(δ) ppm














225





300 MHz, DMSO-d6 9.05(1H, brs), 8.76(1h, brs), 8.31(1H, s), 8.19 and 8.00 (2H, ABq, J=8.3 Hz), 7.79 and 7.25 (4H, A′ B′ q, J=8.3 Hz), 7.39(1H, brs), 6.86-6.74(4H, m), 4.37(1H, brt, J=12.2 Hz), 3.89(2H, d, J=5.0 Hz), 3.35-3.18(2H, m), 2.98-2.75(2H, m), 2.38-2.17(2H, m), 2.16-1.15(15H, m)














Purity
>90% (NMR)


MS
526(M + 1)





Example No.
162
1H NMR(δ) ppm














226





300 MHz, DMSO-d6 12.87(1H, brs), 8.58(1H, d, J=6.0 Hz), 8.23(1H, s), 7.99 and 7.80(2H, ABq, J=8.6 Hz), 7.61 and 7.18 (4H, A′ B′ q, J=8.0 Hz), 7.45-7.30(5H, m), 5.29 (1H, brs), 4.26(1H, brt, J=12.2 Hz), 2.37-2.11 (2H, m), 2.00-1.71 (4H, m), 1.92 (3H, s), 1.70-1.52(1H, m), 1.45-1.11(3H, m)














Purity
>90% (NMR)


MS
498(M + 1)










[1904]

45







TABLE 45















Example No.
163
1H NMR(δ) ppm














227





300 MHz, DMSO-d6 8.23 (1H, s), 7.95 and 7.86 (2H, ABq, J=8.6 Hz), 7.69 and 7.18 (4H, A′ B′ q, J=8.6 Hz), 7.35(1H, t, J=8.6 Hz), 6.80(1H, d, J=7.5 Hz), 6.72-6.69 (2H, m), 5.20(1H, t, J=1.7 Hz), 4.31(1H, brt, J=12.2 Hz), 3.95 2H, t, J=6.8 Hz), 2.49-2.19 (4H, m), 1.97-1.76 (4H, m), 1.68(3H, s), 1.67-1.54(1H, m), 1.61(3H, s), 1.45-1.20 (3H, m)














Purity
>90% (NMR)


MS
511(M + 1)





Example No.
164
1H NMR(δ) ppm














228





300 MHz, DMSO-d6 8.20(1H, s), 7.87(2H, s), 7.68 and 7.18(4H, ABq, 18.7 Hz), 7.35(1H, t, J=7.9 Hz), 6.81 (1H, d, J=9.4 Hz), 6.72(1Hs), 6.71(1H, d, J=6.8 Hz), 4.80 (2H, s), 4.29(1H, brt, J=12.2 Hz), 4.10 (1H, t, J=6.7 Hz), 2.43(1H, t, J=6.7 Hz), 2.39-2.19(2H, m), 1.97-1.78(4H, m), 1.76(3H, s), 1.70-1.56 (1H, m), 1.43-1.19(3H, m)














Purity
>90% (NMR)


MS
497(M + 1)





Example No.
165
1H NMR(δ) ppm














229





300 MHz, DMSO-d6 11.21(1H, brs), 8.33(1H, s), 8.25(1H, d, J=8.6 Hz), 8.04 (1H, d, J=8.6 Hz), 7.78(2H, d, J=8.7 Hz), 7.70-7.67(2H, m), 7.55-7.42(3H, m), 7.27(2H, d, J=8.7 Hz), 4.73-4.30(5H, m), 4.20-3.97(2H, m), 3.42-3.10(2H, m), 2.45-1.23(14H, m)














Purity
>90% (NMR)


MS










[1905]

46







TABLE 46










Example No.
166
1H NMR(δ) ppm














230





300MHz, DMSO-d6 8.27(1H, s), 8.13(1H, d, J=8.4Hz), 7.97(1H, d, J=9.0Hz), 7.73(1H, d, J=1.8Hz), 7.68(2H, d, J=8.4Hz), 7.54(1H, dd, J=8.4, 2.1Hz), 7.41-7.31(5H, m), 7.19(2H, d, J=8.4Hz), 5.10(2H, s), 4.32(1H, m), 2.50(3H, s), 2.40-2.15(2H, m), 2.10-1.75(4H, m), 1.75-1.55(1H, m), 1.55-1.10(3H, m).









Purity
>90% (NMR)



MS
583(M + 1)


Example No.
167
1H NMR(δ) ppm














231





300MHz, DMSO-d6



8.25(1H, s), 8.09(1H, d, J=8.4Hz), 8.00(2H, d, J=8.4Hz), 7.94(1H, d, J=8.7Hz), 7.80(1H, d, J=2.1Hz), 7.73(2H, d, J=8.1Hz), 7.65(2H, d, J=8.7Hz), 7.60(1H, dd, J=8.1, 2.1Hz), 7.44(1H, d, J=8.1Hz), 7.16(2H, d, J=8.7Hz), 5.13(2H, s), 4.30(1H, m), 3.26(3H, s), 2.40-1.15(2H, m), 2.05-1.75(4H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m).









Purity
>90% (NMR)



MS
615(M + 1)


Example No.
168
1H NMR(δ) ppm














232





300MHz, DMSO-d6 13.1(1H, brs), 8.32(1H, s), 8.28(1H, d, J=8.8Hz), 8.05(1H, d, J=8.7Hz), 7.80-7.75(3H, m), 7.69(1H, d, J=4.1Hz), 7.57(2H, m), 7.34-7.29(3H, m), 7.20-7.15(1H, m), 5.24(2H, s), 4.39(1H, m), 2.45-2.20(2H, m), 2.20-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m).









Purity
>90% (NMR)



MS
543(M + 1)










[1906]

47







TABLE 47










Example No.
169
1H NMR(δ) ppm














233





300MHz, DMSO-d6 8.31(1H, s), 8.26(1H, d, J=8.7Hz), 8.05(1H, d, J=8.7Hz), 7.78-7.71(3H, m), 7.59-7.41(6H, m), 7.23(2H, d, J=9.0Hz), 5.11(2H, s), 4.35(1H, m), 2.40-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m).









Purity
>90% (NMR)



MS
571(M + 1)


Example No.
170
1H NMR(δ) ppm














234





300MHz, DMSO-d6 12.7(1H, brs), 8.66(1H, s), 8.61(1H, m), 8.21(1H, s), 7.92-7.79(4H, m), 7.61-7.56(3H, m), 7.50-7.43(2H, m), 7.10(2H, d, J=8.7Hz), 5.09(2H, s), 4.26(1H, m), 2.40-2.15(2H, m), 2.00-1.75(4H, m), 1.75-1.55(1H, m), 1.50-1.15(3H, m).









Purity
>90% (NMR)



MS
538(M + 1)


Example No.
171
1H NMR(δ) ppm














235





300MHz, DMSO-d6 8.31(1H, s), 8.25(1H, d, J=8.7Hz), 8.04(1H, d, J=8.7Hz), 7.74-7.71(3H, m), 7.57-7.46(3H, m), 7.39(1H, d, J=8.1Hz), 7.31-7.21(4H, m), 5.11(2H, s), 4.35(1H, m), 2.40-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m).









Purity
>90% (NMR)



MS
555(M + 1)










[1907]

48







TABLE 48










Example No.
172
1H NMR(δ) ppm














236





300MHz, DMSO-d6 8.24(1H, s), 7.99(1H, d, J=8.7Hz), 7.88(1H, d, J=10.5Hz), 7.70(1H, dd, J=11.4, 1.8Hz), 7.48-7.32(6H, m), 7.17-7.09(5H, m), 5.12(2H, s), 4.30(1H, m), 2.40-2.15(2H, m), 2.05-1.75(4H, m), 1.75-1.55(1H, m), 1.55-1.20(3H, m).









Purity
>90% (NMR)



MS
537(M + 1)


Example No.
173
1H NMR(δ) ppm














237





300MHz, DMSO-d6 8.33(1H, s), 8.29(1H, d, J=8.7Hz), 8.06(1H, d, J=8.7Hz), 7.82-7.74(4H, m), 7.45(1H, dd, J=8.4, 3.0Hz), 7.39(2H, d, J=8.7Hz), 5.28(2H, s), 4.40(1H, m), 2.40-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m).









Purity
>90% (NMR)



MS
540(M + 1)


Example No.
174
1H NMR(δ) ppm














238





300MHz, DMSO-d6 12.80(1H, brs), 8.26(1H, s), 8.01(1H, d, J=8.7Hz), 7.85(1H, d, J=8.7Hz), 7.80-7.70(1H, m), 7.60-7.36(7H, m), 7.18-6.91(2H, m), 5.09(2H, s), 4.11-3.90(1H, m), 2.32-1.18(14H, m)









Purity
>90% (NMR)



MS
590(M + 1)










[1908]

49







TABLE 49










Example No.
175
1H NMR(δ) ppm














239





300MHz, DMSO-d6 12.75(1H, s), 8.21(1H, s), 7.94 and 7.85(2H, ABq, J=8.7Hz), 7.61 and 7.00(4H, A′ B′ q, J=8.5Hz), 7.31-6.91(2H, m), 7.25(2H, d, J=7.7Hz), 5.41(2H, brs), 4.54(2H, d, J=6.6Hz), 4.35-4.14(2H, m), 2.49-2.15(3H, m), 1.95-1.55(5H, m), 1.50-1.13(5H, m), 1.10-0.77(2H, m)









Purity
>90% (NMR)



MS
568(M + 1)


Example No.
176
1H NMR(δ) ppm














240





300MHz, DMSO-d6 8.24(1H, s), 7.97 and 7.87(2H, ABq, J=8.6Hz), 7.69 and 7.19(4H, A′ B′ q, J=8.6Hz), 7.35(1H, t, J=8.1Hz), 6.81(1H, d, J=9.2Hz), 6.72(1H, s), 6.71(1H, d, J=6.5Hz), 4.48-4.20(2H, m), 3.95-3.75(3H, m), 3.03(1H, t, J=12.3Hz), 2.60-2.40(1H, m), 2.39-2.15(2H, m), 2.07-1.58(6H, m), 1.99(3H, s), 1.50-1.00(5H, m)









Purity
>90% (NMR)



MS
568(M + 1)


Example No.
177
1H NMR(δ) ppm














241





300MHz, DMSO-d6 12.76(1H, s), 8.23(1H, s), 7.96 and 7.86(2H, ABq, J=8.6Hz), 7.69 and 7.20(4H, A′ B′ q, J=8.6Hz), 7.39(1H, t, J=8.2Hz), 6.86(1H, d, J=8.3Hz), 6.81(1H, s), 6.76(1h, d, J=8.0Hz), 4.83(2H, s), 4.31(1H, brt, J=12.2Hz), 2.39-2.19(2H, m), 1.99-1.79(4H, m), 1.70-1.58(1H, m), 1.48-1.20(3H, m)









Purity
>90% (NMR)



MS
467(M + 1)










[1909]

50







TABLE 50










Example No.
178
1H NMR(δ) ppm














242





300MHz, DMSO-d6 12.85(1H, s), 8.75(1H, s), 8.63(2H, d,


# J=3.8Hz), 8.25(1H, s), 8.04-8.01(2H, m), 8.02 and 7.90(2H, ABq, J=8.6Hz), 7.72 and 7.20(4H, A′ B′ q, J=8.6Hz), 7.57(2H, dd, J=7.8, 5.0Hz), 7.40(1H, t, J=8.2Hz), 6.93(1H, d, J=8.2Hz), 6.87(1H, s), 6.77(1H, d, J=8.2Hz), 5.23(2H, s), 4.33(1H, brt, J=12.2Hz), 2.40-2.18(2H, m), 2.00-1.55(5H, m), 1.50-1.15(3H, m)









Purity
>90% (NMR)



MS
520(M + 1)


Example No.
179
1H NMR(δ) ppm














243





300MHz, DMSO-d6 8.32(1H, s), 8.29(1H, d, J=9.0Hz), 8.06(1H, d, J=8.7Hz), 7.61(1H, d, J=8.4Hz), 7.58-7.32(5H, m), 6.98(1H, d, J=2.1Hz), 6.93(1H, dd, J=8.7, 2.1Hz), 5.27(2H, s), 4.16-4.00(1H, m), 3.87(3H, s), 2.20-2.12(2H, m), 2.02-1.98(4H, m), 1.70-1.60(1H, m), 1.52-1.10(3H, m)









Purity
>90% (NMR)



MS
457(M + 1)


Example No.
180
1H NMR(δ) ppm














244





300MHz, DMSO-d6 8.21(1H, s), 7.91(1H, d, J=8.6Hz), 7.85(1H, d, J=8.6Hz), 7.63(2H, d, J=8.4Hz), 7.60(1H, d, J=9.0Hz), 7.25(2H, d, J=8.4Hz), 7.23(1H, d, J=3.0Hz), 6.95(1H, dd, J=9.0, 3.0Hz), 5.19(2H, d), 4.30(1H, m), 3.78(3H, s), 2.40-2.19(2H, m), 2.00-1.87(4H, m), 1.66(1H, m), 1.49-1.18(3H, m).









Purity
>90% (NMR)



MS
536(M + 1)










[1910]

51







TABLE 51










Example No.
181
1H NMR(δ) ppm














245





300MHz, DMSO-d6 8.19(1H, s), 7.95(1H, d, J=8.7Hz), 7.86(1H, d, J=8.7Hz), 7.65(4H, d, J=7.4Hz), 7.47(2H, d, J=8.7Hz), 7.44-7.27(6H, m), 6.99(2H, d, J=8.7Hz), 4.20(1H, m), 2.34-2.12(2H, m), 1.98-1.75(4H, m), 1.64(1H, m), 1.46-1.13(3H, m).









Purity
>90% (NMR)



MS
547(M + 1)


Example No.
182
1H NMR(δ) ppm














246





300MHz, DMSO-d6 8.55(1H, d, J=2.1Hz), 8.32(1H, m), 8.21(1H, s), 7.95(1H, d, J=8.4Hz), 7.86(1H, d, J=7.8Hz), 7.68-7.56(7H, m), 7.14(2H, d, J=8.7Hz), 5.21(1H, s), 4.26(1H, m), 2.35-2.15(2H, m), 2.00-1.75(4H, m), 1.74-1.55(1H, m), 1.50-1.15(3H, m)









Purity
>90% (NMR)



MS
582(M+)


Example No.
183
1H NMR(δ) ppm














247





300MHz, DMSO-d6 10.16(1H, s), 8.25(1H, s), 8.07(1H, d, J=8.7Hz), 7.94-7.87(2H, m), 7.71-7.62(3H, m), 7.50-7.42(4H, m), 7.30(1H, d, J=8.4Hz), 7.14(2H, d, J=8.4Hz), 5.06(2H, s), 4.31(1H, m), 2.35-2.15(2H, m), 2.05-1.75(4H, m), 1.75-1.55(1H, m), 1.50-1.15(3H, m)









Purity
>90% (NMR)



MS
594(M+)










[1911]

52







TABLE 52










Example No.
184
1H NMR(δ) ppm














248





300MHz, DMSO-d6 13.2(2H, brs), 8.30(1H, s), 8.26(1H,


# d, J=8.8Hz), 8.04(1H, d, J=8.8Hz), 8.00(2H, d, J=8.2Hz), 7.79(1H, s), 7.73(2H, d, J=8.7Hz), 7.61-7.56(3H, m), 7.44(1H, d, J=8.3Hz), 7.23(2H, d, J=8.8Hz), 5.13(2H, s), 4.35(1H, m), 2.45-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(1H, m), 1.75-1.15(3H, m).









Purity
>90% (NMR)



MS
581(M + 1)


Example No.
185
1H NMR(δ) ppm














249





300MHz, DMSO-d6 8.30(1H, m), 8.24(1H, d, J=9.0Hz), 8.03(1H, d, J=9.0Hz), 7.79-7.10(9H, m), 5.20-5.07(2H, m), 4.43-4.04(4H, m), 3.50-3.36(2H, m), 2.40-1.19(14H, m)









Purity
>90% (NMR)



MS
554(M + 1)


Example No.
186
1H NMR(δ) ppm














250





(DMSO-d6) δ: 8.29(1H, brs), 8.10(1H, d, J=8.4Hz), 7.97(1H, d, J=8.4Hz), 7.79(2H, d, J=8.4Hz), 7.74-7.67(1H,


# m), 7.68(2H, d, J=8.4Hz), 7.61(1H, d, J=8.4Hz), 7.57-7.50(2H, m), 7.46-7.39(1H, m), 7.29(1H, d, J=2.4Hz), 7.11(1H, dd, J=2.4, 8.4Hz), 5.12(2H, s), 3.99-3.84(1H, m), 2.35-1.72(6H, m), 1.68-1.55(1H, m), 1.42-1.10(3H, m)









Purity
>90% (NMR)



MS
605(M + 1)










[1912]

53







TABLE 53










Example No.
187
1H NMR(δ) ppm














251





300MHz, DMSO-d6 12.76(1H, s), 8.57(1H, d, J=4.4Hz), 8.23(1H, s), 7.96 and 7.86(2H, ABq, J=8.2Hz), 7.87-7.82(1H, m), 7.68 and 7.12(4H,


# A′ B′ q, J=8.6Hz), 7.53(2H, d, J=7.8Hz), 7.37(1H, t, J=8.3Hz), 7.36-7.33(1H, m), 6.90(1H, d, J=8.3Hz), 6.83(1H, s), 6.74(1H, d, J=8.0Hz), 5.20(2H, s), 4.31(1H, brt, J=12.2Hz), 2.35-2.19(2H, m), 1.99-1.57(5H, m), 1.45-1.20(3H, m)









Purity
>90% (NMR)



MS
520(M + 1)


Example No.
188
1H NMR(δ) ppm














252





300MHz, DMSO-d6 12.77(1H, brs), 8.21(1H, d, J=1, 4Hz), 7.92(1H, d, J=8.7Hz), 7.88(1H, dd, J=8.7, 1.4Hz), 7.57(2H, d, J=8.7Hz), 7.57-7.27(7H, m), 7.11(2H, d, J=8.7Hz), 5.07(2H, s), 4.26(1H, m), 2.36-2.16(2H, m), 1.98-1.75(4H, m), 1.64(1H, m), 1.49-1.17(3H, m).









Purity
>90% (NMR)



MS
555(M + 1)


Example No.
189
1H NMR(δ) ppm














253





300MHz, DMSO-d6 8.32(1H, s), 8.30-8.20(2H, m), 8.10-7.98(2H, m), 7.74(2H, d, J=9.0Hz), 7.60-7.46(5H, m), 7.24(2H, d, J=9.0Hz), 5.19(2H, s), 4.44-4.30(1H, m), 2.40-2.20(2H, m), 2.12-1.78(4H, m), 1.72-1.58(4H, m)









Purity
>90% (NMR)



MS
581(M + 1)










[1913]

54







TABLE 54










Example No.
190
1H NMR(δ) ppm














254





300MHz, DMSO-d6 8.36-7.90(5H, m), 7.74(2H, d, J=8.6Hz), 7.60-7.40(5H, m), 7.25(2H, d, J=8.7Hz), 5.14(2H, s), 4.45-4.28(1H, m), 2.40-2.15(4H, m), 1.75-1.55(1H, m), 1.55-1.20(3H, m)









Purity
>90% (NMR)



MS
580(M + 1)


Example No.
191
1H NMR(δ) ppm














255





300MHz, DMSO-d6 8.22(1H, s), 7.94(1H, d, J=8.4Hz), 7.85(1H, d, J=8.7Hz), 7.61(2H, d, J=8.7Hz), 7.25-7.00(6H, m), 4.86(2H, s), 4.30(1H, m), 2.89(3H, s), 2.80(3H, s), 2.29(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.15(3H, m)









Purity
>90% (NMR)



MS
514(M + 1)


Example No.
192
1H NMR (δ) ppm














256





300MHz, DMSO-d6 8.22(1H, s), 7.94(1H, d, J=8.4Hz), 7.85(1H, d, J=8.7Hz), 7.61(2H, d, J=8.7Hz), 7.26-7.01(6H, m), 4.84(2H, s), 4.31(1H, m), 3.36(4H, m), 2.29(2H, m), 2.00-1.75(4H, m), 1.75-1.15(10H, m)









Purity
>90% (NMR)



MS
554(M + 1)










[1914]

55







TABLE 55










Example No.
193
1H NMR(δ) ppm














257





300MHz, DMSO-d6 13.00(1H, brs), 8.29(1H, d, J=1.4Hz), 8.15(1H, d, J=8.8Hz), 7.97(1H, dd, J=1.4Hz, 8.8Hz), 7.89(2H, d, J=8.8Hz), 7.80-7.60(5H, m) 7.25(2H, d, J=8.8Hz), 4.47-3.90(4H, m), 3.20-3.10(2H, m), 2.41-1.22(14H, m)









Purity
>90% (NMR)



MS
560(M + 1)


Example No.
194
1H NMR(δ) ppm














258





300MHz, DMSO-d6 12.80(1H, brs), 8.23(1H, s), 7.97(1H, d, J=8.5Hz), 7.87(1H, d, J=8.5Hz), 7.70-7.17(9H, m), 4.60-4.13(4H, m), 3.72-3.40(2H, m), 2.40-1.15(14H, m)









Purity
>90% (NMR)



MS
524(M + 1)


Example No.
195
1H NMR(δ) ppm














259





300MHz, DMSO-d6 8.25(1H, s), 8.09-7.92(5H, m), 7.77(1H, s), 7.65(2H, d, J=8.4Hz), 7.59-7.51(3H, m), 7.43(2H, d, J=8.4Hz), 7.17(2H, d, J=8.7Hz), 5.10(2H, s), 4.30(1H, m), 2.40-2.15(2H, m), 2.10-1.75(4H, m), 1.75-1.55(1H, m), 1.55-1.10(3H, m).









Purity
>90% (NMR)



MS
580(M + 1)










[1915]

56







TABLE 56










Example No.
196
1H NMR(δ) ppm














260





300MHz, DMSO-d6 8.22(1H, s), 7.95(1H, d, J=8.4Hz), 7.86(1H, d, J=8.4Hz), 7.69 and 7.18(4H, ABq, J=8.7Hz), 7.34(1H, t, J=8.0Hz), 6.80-6.69(3H, m), 4.83(2H, s), 4.31(1H, m), 2.98(3H, s), 2.84(3H, s), 2.29(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.15(3H, m)









Purity
>90% (NMR)



MS
514(M + 1)


Example No.
197
1H NMR(δ) ppm














261





300MHz, DMSO-d6 8.23(1H, s), 7.95(1H, d, J=8.4Hz), 7.86(1H, d, J=8.7Hz), 7.69 and 7.18(4H, ABq, J=8.7Hz), 7.35(1H, t, J=8.4Hz), 6.80-6.70(3H, m), 4.82(2H, s), 4.31(1H, m), 3.40(4H, m), 2.29(2H, m), 2.00-1.75(4H, m), 1.70-1.15(10H, m)









Purity
>90% (NMR)



MS
554(M + 1)


Example No.
198
1H NMR(δ) ppm














262





300MHz, DMSO-d6 12.75(1H, s), 8.23(1H, d, J=4.4Hz), 7.95 and 7.86(2H, ABq, J=8.6Hz), 7.69 and 7.19(4H, A′ B′ q, J=8.6Hz), 7.36(1H, t,


# J=7.8Hz), 6.82(1H, d, J=9.3Hz), 6.73(1H, s), 6.71(1H, d, J=7.2Hz), 4.30(1H, brt, J=12.2Hz), 3.89(2H, d, J=6.0Hz), 3.59(2H, d, J=11.7Hz), 2.85(3H, s), 2.73(2H, t, J=10.5Hz), 2.41-2.20(2H, m), 1.98-1.59(8H, m), 1.46-1.18(5H, m)









Purity
>90% (NMR)



MS
604(M + 1)










[1916]

57







TABLE 57










Example No.
199
1H NMR(δ) ppm














263





300MHz, DMSO-d6 8.33(1H, s), 8.30(1H, d, J=8.9Hz), 8.06(1H, d, J=8.7Hz), 7.79(2H, d, J=8.7Hz), 7.70(2H,


# d, J=8.7Hz), 7.61(2H, d, J=8.7Hz), 7.39(2H, d, J=8.8Hz), 5.28(2H, s), 4.39(1H, m), 2.50-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m).









Purity
>90% (NMR)



MS
542(M + 1)


Example No.
200
1H NMR(δ) ppm














264





(DMSO-d6) δ: 8.23(1H, s), 7.96(1H, d, J=8.6Hz), 7.86(1H, d, J=8.6Hz),


# 7.69(2H, d, J=8.4Hz), 7.52(1H, s), 7.50-7.30(4H, m), 7.18(2H, d, J=8.4Hz), 6.90(1H, d, J=8.3Hz), 6.84(1H, s), 6.74(1H, d, J=8.3Hz), 5.15(2H, s), 4.39-4.21(1H, m), 2.39-2.18(2H, m), 1.99-1.80(4H, m), 1.71-1.59(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
553(M + 1)


Example No.
201
1H NMR(δ) ppm














265





(DMSO-d6) δ: 8.26(1H, s), 8.06(1H, d, J=8.7Hz), 7.92(1H, d, J=8.7Hz), 7.72(2H, d, J=8.7Hz), 7.47(4H, s), 7.38(1H, t,


# J=8.2Hz), 7.20(2H, d, J=8.7Hz), 6.90(1H, d, J=8.2Hz), 6.83(1H, s), 6.74(1H, d, J=8.2Hz), 5.14(2H, s), 2.40-2.19(2H, m), 2.04-1.78(4H, m), 1.71-1.60(1H, m), 1.50-1.21(3H, m)









Purity
>90% (NMR)



MS
553(M + 1)










[1917]

58







TABLE 58










Example No.
202
1H NMR(δ) ppm














266





(DMSO-d6) δ: 12.81(1H, brs), 8.24(1H, s), 7.99(1H, d, J=8.7Hz), 7.87(1H, d, J=8.7Hz), 7.69(2H, d, J=8.6Hz), 7.53-7.47(2H, m), 7.38(1H, t, J=8.2Hz), 7.26-7.16(4H, m), 6.89(1H,


# d, J=8.2Hz), 6.82(1H, s), 6.73(1H, d, J=8.2Hz), 5.11(2H, s), 4.40-4.21(1H, m), 2.40-2.17(2H, m), 2.01-1.77(4H, m), 1.71-1.59(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
537(M + 1)


Example No.
203
1H NMR(δ) ppm














267





300MHz, DMSO-d6 12.74(1H, brs), 8.21(1H, s), 8.08(2H, d, J=9.0Hz), 7.93(1H, d, J=8.7Hz), 7.85(2h, d, J=8.7Hz), 7.58(2H, d, J=8.7Hz), 7.13(2H, d, J=8.7Hz), 6.83(2H, d, J=9.0Hz), 4.50-4.08(4H, m), 3.68-3.30(2H, m), 2.40-1.23(14H, m)









Purity
>90% (NMR)



MS
541(M + 1)


Example No.
204
1H NMR(δ) ppm














268





300MHz, DMSO-d6 8.39-8.28(2H, m), 8.08(1H, d, J=8.8Hz), 7.76(2H, d, J=8.7Hz), 7.29(2H, d, J=8.7Hz), 7.25-7.13(2H, m), 6.80-6.60(3H, m), 4.46-3.98(4H, m), 3.51-3.42(1H, m), 3.20-3.04(1H, m), 2.39-1.20(14H, m)









Purity
>90% (NMR)



MS










[1918]

59







TABLE 59










Example No.
205
1H NMR(δ) ppm














269





300MHz, DMSO-d6 9.59(1H, brs), 8.23(1H, s), 8.04(1H, d, J=8.4Hz), 7.90(1H, d, J=8.4Hz), 7.62(2H, d, J=8.7Hz), 7.39(2H, 2H,


# d, J=8.7Hz) 7.18(2H, d, J=8.7Hz), 6.63(2H, d, J=8.7Hz), 3.95-3.37(4H, m), 3.51-3.40(1H, m), 3.17-3.02(1H, m), 2.39-1.18(17H, m)









Purity
>90% (NMR)



MS
553(M + 1)


Example No.
206
1H NMR(δ) ppm














270





300MHz, DMSO-d6 13.1(1H, brs), 8.33(1H, s), 8.29(1H, d, J=8.8Hz),


# 8.06(1H, d, J=8.7Hz), 7.77(2H, d, J=8.7Hz), 7.59-7.52(4H, m), 7.35(2H, d, J=8.8Hz), 5.19(2H, s), 4.39(1H, m), 2.71(3H, s), 2.45-2.20(2H, m), 2.20-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m).









Purity
>90% (NMR)



MS
558(M + 1)


Example No.
207
1H NMR(δ) ppm














271





300MHz, DMSO-d6 8.29(1H, s), 8.26(1H, d, J=8.8Hz), 8.04(1H, d, J=8.7Hz), 7.73(2H, d, J=8.8Hz), 7.50-7.41(6H, m), 7.36(2H,


# d, J=8.8Hz), 7.18-7.13(2H, m), 6.84(1H, s), 4.33(1H, m), 2.40-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m).









Purity
>90% (NMR)



MS
539(M + 1)










[1919]

60







TABLE 60










Example No.
208
1H NMR(δ) ppm














272





300MHz, DMSO-d6 8.32(1H, s), 8.27(1H, d, J=9.0Hz), 8.07-8.00(3H, m), 7.79-7.70(3H, m), 7.51(2H, d,


# J=8.1Hz), 7.40(2H, d, J=8.4Hz), 7.18(2H, d, J=8.7Hz), 4.99(2H, s), 4.34(1H, m), 2.40-2.15(2H, m), 2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m).









Purity
>90% (NMR)



MS
582(M + 1)


Example No.
209
1H NMR(δ) ppm














273





300MHz, DMSO-d6 8.24(1H, d, J=4.4Hz), 7.98 and 7.88(2H, ABq, J=8.6Hz), 7.70 and 7.19(4H, A′ B′ q,


# J=8.4Hz), 7.35(1H, t, J=8.4Hz), 6.86(1H, d, J=8.1Hz), 6.79(1H, s), 6.71(1H, d, J=8.1Hz), 4.65-4.53(1H, m), 4.31(1H, brt, J=12.2Hz), 3.88-3.78(2H, m), 3.48(2H, t, J=9.0Hz), 2.39-2.19(2H, m), 1.02-1.71(6H, m), 1.70-1.50(3H, m), 1.46-1.19(3H, m)









Purity
>90% (NMR)



MS
513(M + 1)


Example No.
210
1H NMR(δ) ppm














274





300MHz, DMSO-d6 12.75(1H, s), 8.23(1H, s), 7.96 and 7.87(2H, ABq, J=8.7Hz), 7.84-7.66(6H, m), 7.38(1H, t,


# J=8.4Hz), 7.18(2H, d, J=8.4Hz), 6.91(1H, d, J=9.0Hz), 6.84(1H, s), 6.74(1H, d, J=8.1Hz), 5.26(2H, s), 4.31(1H, brt, J=12.2Hz), 2.40-2.20(2H, m), 1.99-1.76(4H, m), 1.69-1.58(1H, m), 1.45-1.20(3H, m)









Purity
>90% (NMR)



MS
587(M + 1)










[1920]

61







TABLE 61










Example No.
211
1H NMR (δ) ppm














275





300 MHz, DMSO-d6 8.29 (1H, s), 8.15 and 7.47 (2H, ABq, J=9.0 Hz), 7.77 and 7.24 (4H, ABq, J=8.9 Hz), 7.39 (1H, t, J=7.8 Hz), 6.84 (1H, d, J=9.3 Hz), 6.76 (1H, s), 6.75 (1H, d, J=9.5 Hz), 4.36 (1H, brt, J=12.2 Hz), 3.89 (2H, d, J=6.0 Hz), 3.42 (2H, d, J=10.8 Hz), 3.04-2.88 (2H, m), 2.78-2.60 (1H, m), 2.71 (2H, d, J=4.8 Hz), 2.38-2.20 (2H, m),









Purity
>90% (NMR)
2.07-1.80 (7H, m), 1.70-1.20


MS
540 (M + 1)
(5H, m)





Example No.
212
1H NMR (δ) ppm














276





300 MHz, DMSO-d6 8.22 (1H, s), 7.93 and 7.87 (2H, ABq, J=8.6 Hz), 7.68 and 7.17 (4H, A′ B′ q, J=8.7 Hz), 7.43-7.33 (5H, m), 6.87 (1H, d, J=8.1 Hz), 7.18 (2H, d, J=8.4 Hz), 6.91 (1H, d, J=9.0 Hz), 6.81 (1H, s), 6.72 (1H, d, J=8.0 Hz), 5.08 (2H, s), 4.36 (1H, brt, J=12.2 Hz), 2.37-2.20 (2H, m), 1.98-1.78 (4H, m), 1.69-1.60 (1H, m), 1.41-1.21 (3H, m), 1.28 (9H, s)









Purity
>90% (NMR)



MS
575 (M + 1)





Example No.
213
1H NMR (δ) ppm














277





300 MHz, DMSO-d6 8.23 (1H, s), 7.95 and 7.86 (2H, ABq, J=8.4 Hz), 7.69 and 7.19 (4H, A′ B′ q, J=8.7 Hz), 7.62-7.36 (5H, m), 6.90 (1H, d, J=8.1 Hz), 6.84 (1H, s), 6.76 (1H, d, J=8.1 Hz), 5.19 (2H, s), 4.31 (1H, brt, J=12.2 Hz), 2.40-2.19 (2H, m), 1.99-1.76 (4H, m), 1.68-1.55 (1H, m), 1.50-1.18 (3H, m)









Purity
>90% (NMR)



MS
553 (M + 1)










[1921]

62







TABLE 62










Example No.
214
1H NMR (δ) ppm














278





300 MHz, DMSO-d6 8.94 (1H, d, J=2.1 Hz), 8.60 (1H, dd, J=4.8, 1.5 Hz), 8.23 (1H, d, J=1.5 Hz), 8.12(1H, dt, J=8.1, 2.1 Hz), 7.93 (1H, d, J=8.7 Hz), 7.87 (1H, dd, J=8.7, 1.5 Hz), 7.70 (1H, d, J=8.7 Hz), 7.67-7.54 (3H, m), 7.50 (1H, dd, J=8.1, 4.8 Hz), 7.25 (2H, d, J=8.7 Hz), 7.21 (1H, m), 4.31 (1H, m), 2.38-2.19 (2H, m), 2.00-1.78 (4H, m), 1.65 (1H, m), 1.48-1.22 (3H, m).









Purity
>90% (NMR)



MS
490 (M + 1)





Example No.
215
1H NMR (δ) ppm














279





300 MHz, DMSO-d6 12.75 (1H, brs), 8.23 (1H, s), 7.95 (1H, d, J=8.7 Hz), 7.86 (1H, d, J=8.7 Hz), 7.73 (2H, d, J=8.4 Hz), 7.71 (2H, d, J=8.4 Hz), 7.63-7.39 (2H, m), 7.52 (2H, d, J=8.4 Hz), 7.24 (2H, d, J=8.4 Hz), 7.18 (1H, m), 4.31 (1H, m), 2.39-2.20 (2H, m), 2.00-1.76 (4H, m), 1.65 (1H, m), 1.49-1.18 (3H, m).









Purity
>90% (NMR)



MS
523 (M + 1)





Example No.
216
1H NMR (δ) ppm














280





300 MHz, DMSO-d6 12.77 (1H, s), 8.23 (1H, d, J=1.4 Hz), 7.95 (1H, d, J=8.6 Hz), 7.86 (1H, dd, J=8.6, 1.4 Hz), 7.70 (2H, d, J=8.7 Hz), 7.64 (2H, d, J=8.8 Hz), 7.56-7.48 (2H, m), 7.40 (1H, s), 7.23 (2H, d, J=8.7 Hz), 7.10 (1H, m), 7.03 (2H, d, J=8.8 Hz), 4.31 (1H, m), 3.80 (3H, s), 2.48-2.20 (2H, m), 2.00-1.88 (4H, m), 1.66 (1H, m), 1.50-1.21 (3H, m).









Purity
>90% (NMR)



MS
519 (M + 1)










[1922]

63







TABLE 63










Example No.
217
1H NMR (δ) ppm














281





(DMSO-d6) δ: 12.80 (1H, brs), 8.23 (1H, s), 8.04 (1H, d, J=8.6 Hz), 7.96 (3H, d, J=8.6 Hz), 7.86 (1H, d, J =8.7 Hz), 7.63 (2H, d, J=8.6 Hz), 7.25 (2H, d, J=8.6 Hz), 5.50 (2H, s), 4.36-4.21 (1H, m), 3.27 (3H, s), 2.74 (3H, s), 2.40-2.19 (2H, m), 1.99-1.79 (4H, m), 1.71-1.60 (1H, m), 1.49-1.19 (3H, m)









Purity
>90% (NMR)



MS
602 (M + 1)





Example No.
218
1H NMR (δ) ppm














282





300 MHz, DMSO-d6 12.9 (1H, brs), 8.25 (1H, s), 8.04 (1H, d, J=8.7 Hz), 7.91 (1H, d, J=8.6 Hz), 7.72 (2H, d, J=8.5 Hz), 7.67 (2H, d, J=8.7 Hz), 7.56 (2H, d, J=8.5 Hz), 7.26 (2H, d, J=8.7 Hz), 5.45 (2H, s), 4.31 (1H, m), 2.71 (3H, s), 2.40-2.15 (2H, m), 2.05-1.80 (4H, m), 1.75-1.55 (1H, m), 1.55-1.15 (3H, m).









Purity
>90% (NMR)



MS
558 (M + 1)





Example No.
219
1H NMR (δ) ppm














283





300 MHz, DMSO-d6 8.21 (1H, d, J=1.5 Hz), 7.93 (1H, d, J=9.0 Hz), 7.84 (1H, dd, J=9.0, 1.5 Hz), 7.56 (2H, d, J=8.7 Hz), 7.42-7.30 (4H, m), 7.12 (2H, d, J=8.7 Hz), 4.53 (1H, brs), 4.36-4.20 (1H, m), 3.55 (2H, brs), 3.00-2.90 (1H, m), 2.70-2.58 (1H, m), 2.40-1.10 (18H, m)









Purity
>90% (NMR)



MS
544 (M + 1)










[1923]

64







TABLE 64










Example No.
220
1H NMR (δ) ppm














284





300 MHz, DMSO-d6 12.76 (1H, s), 8.23 (1H, s), 7.96 and 7.87 (2H, ABq, J=8.9 Hz), 7.69 and 7.19 (4H, A′ B′ q, J=8.6 Hz), 7.55 (1H, s), 7.37 (1H, t, J=8.1 Hz), 6.91 (1H, d, J=7.8 Hz), 6.85 (1H, s), 6.74 (1H, d, J=7.5 Hz), 5.13 (2H, s), 4.31 (1H, brt, J=12.2 Hz), 2.65 (3H, s), 2.41-2.20 (2H, m), 2.00-1.74 (4H, m), 1.70-1.59 (1H, m), 1.58-1.20 (3H, m)









Purity
>90% (NMR)



MS
540 (M + 1)





Example No.
221
1H NMR (δ) ppm














285





300 MHz, DMSO-d6 8.23 (1H, s), 7.96 and 7.86 (2H, ABq, J=8.6 Hz), 7.69 and 7.18 (4H, A′ B′ q, J=8.7 Hz), 7.37 (1H, t, J=8.2 Hz), 6.87 (1H, d, J=8.2 Hz), 6.82 (1H, s), 6.75 (1H, d, J=8.0 Hz), 5.24 (2H, s), 4.32 (1H, brt, J=12.2 Hz), 2.58 (3H, s), 2.38-2.20 (2H, m), 2.30 (3H, s), 2.00-1.79 (4H, m), 1.70-1.59 (1H, m), 1.44-1.20 (3H, m)









Purity
>90% (NMR)



MS
554 (M + 1)





Example No.
222
1H NMR (δ) ppm














286





300 MHz, DMSO-d6 12.88 (1H, brs), 8.25 (s, 1H), 8.07-7.57 (11H, m), 7.26 (2H, d, J=8.7 Hz), 7.24 (1H, m), 4.34 (1H, m), 2.30-2.20 (2H, m), 2.03-1.78 (4H, m), 1.64 (1H, m), 1.49-1.19 (3H, m).









Purity
>90% (NMR)



MS
557 (M + 1)










[1924]

65







TABLE 65










Example No.
223
1H NMR (δ) ppm














287





300 MHz, DMSO-d6 10.96 (1H, brs), 8.21 (1H, d, J=1.4 Hz), 7.93 (1H, d, J=8.7 Hz), 7.84 (1H, dd, J=8.7, 1.4 Hz), 7.76-7.40 (7H, m), 7.18 (2H, d, J=8.0 Hz), 4.24-4.16 (2H, m), 2.40-1.12 (18H, m)









Purity
>90% (NMR)



MS
544 (M + 1)





Example No.
224
1H NMR (δ) ppm














288





(DMSO-d6) δ: 8.22 (1H, s), 8.07 (1H, d, J=8.4 Hz), 7.92 (1H, d, J=8.4 Hz), 7.54 (2H, d, J=8.7 Hz), 7.40 (2H, d, J=8.4 Hz), 7.30 (2H, d, J=8.4 Hz), 7.14 (2H, d, J=8.7 Hz), 4.61 (2H, s), 4.48-4.32 (1H, m), 3.82 (1H, brd, J=12.3 Hz), 3.65-3.47 (2H, m), 3.10 (brdd, J=8.4, 12.3 Hz), 2.40-2.20 (2H, m), 2.09-1.76 (6H, m), 1.71-1.16 (6H, m)









Purity
>90% (NMR)



MS
544 (M + 1)





Example No.
225
1H NMR (δ) ppm














289





(DMSO-d6) δ: 12.83 (1H, brs), 8.21(1H, s), 8.10 (1H, brs), 7.01-7.91 (2H, m), 7.89-7.82 (2H, m), 7.75 (1H, d, J=8.0 Hz), 7.59 (2H, d, J=8.7 Hz), 7.53 (4H, s), 7.46 (1H, brs), 7.12 (2H, d, J=8.7 Hz), 7.23 (2H, s), 4.35-4.17 (1H, m), 2.38-2.20 (2H, m), 1.99-1.79 (4H, m), 1.71-1.59 (1H, m), 1.48-1.18 (3H, m)









Purity
>90% (NMR)



MS
580 (M + 1)










[1925]

66







TABLE 66










Example No.
226
1H NMR (δ) ppm














290





300 MHz, DMSO-d6 8.33 and 8.08 (2H, ABq, J=8.7 Hz), 8.31 (1H, m), 7.66 and 7.26 (4H, A′ B′ q, J=9.2 Hz), 7.42 and 7.39 (4H, A″B″q, J=8.7 Hz), 4.57 (2H, s), 4.50 (1H, brt, J=12.2 Hz), 3.85-3.62 (3H, m), 3.28-3.16 (2H, m), 2.42-2.23 (2H, m), 2.14-1.81 (6H, m), 1.72-1.25 (6H, m)









Purity
>90% (NMR)



MS
544 (M + 1)





Example No.
227
1H NMR (δ) ppm














291





300 MHz, DMSO-d6 8.43 (1H, d, J=5.0 Hz), 8.23 (1H, s), 7.96 and 7.86 (2H, ABq, J=8.6 Hz), 7.69 and 7.18 (4H, A′ B′ q, J=8.6 Hz), 7.57 (1H, s), 7.47 (1H, d, J=5.0 Hz), 7.40 (2H, t, J=8.2 Hz), 6.91 (1H, d, J=8.3 Hz), 6.85 (1H, s), 6.77 (1H, d, J=7.9 Hz), 5.25 (2H, s), 4.31 (1H, brt, J=12.2 Hz), 2.40-2.19 (2H, m), 1.99-1.75 (4H, m), 1.73-1.57 (1H, m), 1.49-1.19 (3H, m)









Purity
>90% (NMR)



MS
554 (M + 1)





Example No.
228
1H NMR (δ) ppm














292





300 MHz, DMSO-d6 12.80 (1H, brs), 8.22 (1H, s), 7.94 (1H, d, J=8.6 Hz), 7.87 (1H, d, J=8.6 Hz), 7.60 (2H, d, J=8.7 Hz), 7.32 (2H, d, J=8.7 Hz), 7.17 (2H, d, J=8.7 Hz), 6.70 (2H, d, J=8.7 Hz), 4.35-3.97 (4H, m), 3.62-3.11 (2H, m), 2.96 (6H, s), 2.39-1.12 (14H, m)









Purity
>90% (NMR)



MS
567 (M + 1)










[1926]

67







TABLE 67










Example No.
229
1H NMR (δ) ppm














293





300 MHz, DMSO-d6 8.25 (1H, s), 8.20 (1H, s), 8.04 (1H, dd, J=8.1, 1.8 Hz), 7.92 (1H, d, J=8.1 Hz), 7.84 (1H, d, J=9.9 Hz), 7.62-7.50 (7H, m), 7.12 (2H, d, J=8.7 Hz), 5.14 (2H, s), 4.36 (2H, q, J=6.9 Hz), 4.30-4.20 (1H, m), 2.38-2.18 (2H, m), 1.98-1.18 (8H, m), 1.35 (3H, t, J=6.9 Hz)









Purity
>90% (NMR)



MS
608 (M + 1)





Example No.
230
1H NMR (δ) ppm














294





300 MHz, DMSO-d6 8.35 (1H, s), 8.27 (1H, d, J=8.7 Hz), 8.05 (1H, d, J=9.0 Hz), 7.87 (2H, d, J=8.7 Hz), 7.74 (1H, t, J=8.1 Hz), 7.64 (1H, d, J=7.8 Hz), 7.59-7.50 (2H, m), 7.36 (2H, d, J=8.7 Hz), 4.39 (1H, m), 2.40-2.15 (2H, m), 2.15-1.95 (2H, m), 1.95-1.75 (2H, m), 1.75-1.55 (1H, m), 1.55-1.20 (3H, m).









Purity
about 90% (NMR)



MS
481 (M + 1)





Example No.
231
1H NMR (δ) ppm














295





300 MHz DMSO-d6 12.78 (1H, brs), 8.23 (1H, d, J=1.5 Hz), 7.96 (1H, d, J=8.7 Hz), 7.87(1H, dd, J=8.7, 1.5 Hz), 7.75 (2H, d, J=8.4 Hz), 7.63 (2H, d, J=8.4 Hz), 7.52 (2H, d, J=8.4 Hz), 7.24 (2H, d, J=8.4 Hz), 5.47 (2H, s), 4.29 (1H, m), 2.97 (6H, brs), 2.72 (3H, s), 2.39-2.16 (2H, m), 2.00-1.78 (4H, m), 1.71-1.59 (1H, m), 1.49-1.17 (3H, m).









Purity
about 90% (NMR)



MS
595 (M + 1)










[1927]

68







TABLE 68










Example No.
232
1H NMR (δ) ppm














296





300 MHz, DMSO-d6 12.8 (1H, brs), 8.22 (1H, s), 7.96 (1H, d, J=8.7 Hz), 7.86 (1H, d, J=8.6 Hz), 7.70 (1H, s), 7.59 (2H, d, J=8.7 Hz), 7.53-7.50 (5H, m), 7.42 (1H, d, J=7.9 Hz), 7.12 (2H, d, J=8.7 Hz), 5.11 (2H, s), 4.27 (1H, m), 3.01 (3H, brs), 2.97 (3H, brs), 2.40-2.15 (2H, m), 2.00-1.75 (4H, m), 1.75-1.55 (1H, m), 1.50-1.15 (3H, m).









Purity
>90% (NMR)



MS
608 (M + 1)





Example No.
233
1H NMR (δ) ppm














297





DMSO-d6 13.20 (1H, brs), 8.99 (1H, s), 8.32 (1H, s), 8.25 (1H, d, J=8.8 Hz), 8.04 (1H, d, J=8.6 Hz), 7.79-7.74 (4H, m), 7.60 (2H, d, J=8.5 Hz), 7.30 (2H, d, J=8.7 Hz), 5.26 (2H, s), 4.36 (1H, m), 2.72 (3H, s), 2.50-2.15 (2H, m), 2.15-1.95 (2H, m), 1.95-1.75 (2H, m), 1.75-1.55 (1H, m), 1.55-1.15 (3H, m)









Purity
>90% (NMR)



MS
553 (M + 1 − HCl)





Example No.
234
1H NMR (δ) ppm














298





DMSO-d6 8.77 (1H, d, J=3.6 Hz), 8.36-8.26 (3H, m), 8.08 (1H, d, J=8.8 Hz), 7.79 (2H, d, J=8.7 Hz), 7.72-7.64 (3H, m), 7.58 (2H, d, J=8.4 Hz), 7.30 (2H, d, J=8.7 Hz), 5.26 (2H, s), 4.38 (1H, m), 2.50-2.15 (2H, m), 2.15-1.95 (2H, m), 1.95-1.75 (2H, m), 1.75-1.55 (1H, m), 1.55-1.15 (3H, m).









Purity
>90% (NMR)



MS
538 (M + 1 − 2HCl)










[1928]

69







TABLE 69










Example No.
235
1H NMR (δ) ppm














299





300 MHz, DMSO-d6 12.74 (1H, brs), 8.67 (1H, dd, J=3.1, 1.6 Hz), 8.21 (1H, d, J=1.6 Hz), 7.93 (1H, dJ=8.6 Hz), 7.90-7.80 (2H, m), 7.60-7.50 (7H, m), 7.09 (2H, d, J=8.7 Hz), 5.16 (2H, s), 4.26 (1H, m), 2.40-2.20 (2H, m), 2.00-1.60 (5H, m), 1.50-1.20 (3H, m)









Purity
>90% (NMR)



MS
APCI-Ms 538 (M + 1)





Example No.
236
1H NMR (δ) ppm














300





300 MHz, DMSO-d-6 8.40-7.40 (11H, m), 2.95, 2.81 (3H, each d, J=4.7 Hz), 2.40-2.20 (2H, m), 2.10-1.80 (4H, m), 1.70-1.60 (1H, m), 1.50-1.20 (3H, m)









Purity
>90% (NMR)



MS
APCI-Ms 555 (M + 1)





Example No.
237
1H NMR (δ) ppm














301





300 MHz, DMSO-d6 8.21 (1H, s), 8.15 (1H, d, J=9.5 Hz), 8.02 (1H, s), 8.00-7.80 (3H, m), 7.70-7.50 (6H, m), 7.12 (2H, d, J=8.7 Hz), 5.16 (2H, s), 4.28 (1H, m), 2.40-2.20 (2H, m), 2.00-1.80 (4H, m), 1.65 (1H, m), 1.50-1.20 (3H, m)









Purity
>90% (NMR)



MS
FAB-Ms 605 (M + 1)










[1929]

70







TABLE 70










Example No.
238
1H NMR (δ) ppm














302





300 MHz, DMSO-d6 12.80 (1H, brs), 8.54 (1H, s), 8.25 (1H, s), 7.98 and 7.88 (2H, Abq, J=8.6 Hz), 7.76 (2H, d, J=8.6 Hz), 7.53-7.31 (3H, m), 6.61 (1H, s), 5.46 (2H, s), 4.32 (1H, brt), 2.40-2.20 (2H, m), 2.02-1.79 (4H, m), 1.69-1.59 (1H, m), 1.48-1.19 (3H, m)









Purity
>90% (NMR)



MS
APCI-Ms 521 (M + 1)





Example No.
239
1H NMR (δ) ppm














303





300 MHz, DMSO-d6 12.79 (1H, brs), 8.60 (2H, d, J=1.5 Hz), 8.53 (1H, s), 8.25 (1H, s), 7.98 and 7.85 (2H, ABq, J=9.4 Hz), 7.76 (2H, d, J=9.0 Hz), 7.44 (4H, d, J=6.5 Hz), 6.69 (1H, s), 5.53 (2H, s), 4.32 (1H, brt), 2.40-2.19 (2H, m), 2.03-1.82 (4H, m), 1.72-1.61 (1H, m), 1.42-1.22 (3H, m)









Purity
>90% (NMR)



MS
APCI-Ms 522 (M + 1)





Example No.
240
1H NMR (δ) ppm














304





300 MHz, DMSO-d6 8.90 (1H, s), 8.32 (1H, s), 8.28 (1H, s), 8.25 (1H, d, J=8.3 Hz), 8.05 (1H, d, J=8.8 Hz), 7.96 (1H, s), 7.93 (1H, d, J=8.8 Hz), 7.83 (1H, d, J=8.4 Hz), 7.68-7.59 (2H, m), 7.54 (2H, d, J=8.8 Hz), 4.37 (1H, brt), 2.30 (2H, m), 2.00 (2H, m), 1.88 (2H, m), 1.67 (1H, m), 1.5-1.2 (3H, m)









Purity
>90% (NMR)



MS
APCI-Ms 525 (M + 1)










[1930]

71







TABLE 71













Ex. No.
Formula
MS






















1001


305





364 (M + H)





1002


306





454 (M + H)





1003


307





398 (M + H)





1004


308





357 (M + H)





1005


309





322 (M + H)





1006


310





385 (M + H)










[1931]

72







TABLE 72













Ex. No.
Formula
MS






















1007


311





357 (M + H)





1008


312





416 (M + H)





1009


313





310 (M + H)





1010


314





390 (M + H)





1011


315





395 (M + H)





1012


316





366 (M + H)










[1932]

73







TABLE 73













Ex. No.
Formula
MS






















1013


317





374 (M + H)





1014


318





382 (M + H)





1015


319





350 (M + H)





1016


320





402 (M + H)





1017


321





414 (M + H)





1018


322





340 (M + H)










[1933]

74







TABLE 74













Ex. No.
Formula
MS






















1019


323





350 (M + H)





1020


324





380 (M + H)





1021


325





366 (M + H)





1022


326





378 (M + H)





1023


327





402 (M + H)










[1934]

75







TABLE 75













Ex. No.
Formula
MS






















1024


328





518 (M + H)





1025


329





408 (M + H)





1026


330





336 (M + H)





1027


331





408 (M + H)





1028


332





366 (M + H)





1029


333





362 (M + H)










[1935]

76







TABLE 76








Ex. No.
Formula
MS












1030


334





473 (M + H)





1031


335





338 (M + H)





1032


336





307 (M + H)





1033


337





406 (M + H)





1034


338





466 (M + H)





1035


339





412 (M + H)










[1936]

77







TABLE 77








Ex. No.
Formula
MS












1036


340





412 (M + H)





1037


341





428 (M + H)





1038


342





466 (M + H)





1039


343





406 (M + H)





1040


344





417 (M + H)





1041


345





440 (M + H)










[1937]

78







TABLE 78








Ex. No.
Formula
MS












1042


346





417 (M + H)





1043


347





440 (M + H)





1044


348





312 (M + H)





1045


349





423 (M + H)





1046


350





352 (M + H)





1047


351





307 (M + H)










[1938]

79







TABLE 79








Ex. No.
Formula
MS












1048


352





374(M + H)





1049


353





398 (M + H)





1050


354





326 (M + H)





1051


355





442 (M + H)





1052


356





518 (M + H)










[1939]

80







TABLE 80








Ex. No.
Formula
MS












1053


357





442 (M + H)





1054


358





376 (M + H)





1055


359





442 (M + H)





1056


360





352 (M + H)





1057


361





367 (M + H)





1058


362





367 (M + H)










[1940]

81







TABLE 81








Ex. No.
Formula
MS












1059


363





364 (M + H)





1060


364





324 (M + H)





1061


365





352 (M + H)





1062


366





357 (M + H)





1063


367





360 (M + H)





1064


368





351 (M + H)










[1941]

82







TABLE 82








Ex. No.
Formula
MS












1065


369





351 (M + H)





1066


370





366 (M + H)





1067


371





367 (M + H)





1068


372





364 (M + H)





1069


373





350 (M + H)





1070


374





306 (M + H)










[1942]

83







TABLE 83








Ex. No.
Formula
MS












1071


375





365 (M + H)





1072


376





455 (M + H)





1073


377





399 (M + H)





1074


378





358 (M + H)





1075


379





337 (M + H)





1076


380





386 (M + H)










[1943]

84







TABLE 84








Ex. No.
Formula
MS












1077


381





358 (M + H)





1078


382





417 (M + H)





1079


383





311 (M + H)





1080


384





391 (M + H)





1081


385





396 (M + H)





1082


386





367 (M + H)










[1944]

85







TABLE 85








Ex. No.
Formula
MS












1083


387





375 (M + H)





1084


388





351 (M + H)





1085


389





383 (M + H)





1086


390





403 (M + H)





1087


391





415 (M + H)





1088


392





341 (M + H)










[1945]

86







TABLE 86








Ex. No.
Formula
MS












1089


393





351 (M + H)





1090


394





381 (M + H)





1091


395





367 (M + H)





1092


396





379 (M + H)





1093


397





403 (M + H)










[1946]

87







TABLE 87








Ex. No.
Formula
MS












1094


398





519 (M + H)





1095


399





409 (M + H)





1096


400





337 (M + H)





1097


401





409 (M + H)





1098


402





367 (M + H)





1099


403





363 (M + H)










[1947]

88







TABLE 88








Ex. No.
Formula
MS












1100


404





474 (M + H)





1101


405





339 (M + H)





1102


406





308 (M + H)





1103


407





467 (M + H)





1104


408





413 (M + H)





1105


409





413 (M + H)










[1948]

89







TABLE 89








Ex. No.
Formula
MS












1106


410





429 (M + H)





1107


411





467 (M + H)





1108


412










1109


413










1110


414





441 (M + H)





1111


415





418 (M + H)










[1949]

90







TABLE 90








Ex. No.
Formula
MS












1112


416





313 (M + H)





1113


417





308 (M + H)





1114


418





375 (M + H)





1115


419





399 (M + H)





1116


420





327 (M + H)





1117


421





443 (M + H)










[1950]

91







TABLE 91








Ex. No.
Formula
MS












1118


422





519 (M + H)





1119


423





443 (M + H)





1120


424





377 (M + H)





1121


425





443 (M + H)





1122


426





353 (M + H)










[1951]

92







TABLE 92








Ex. No.
Formula
MS












1123


427





368 (M + H)





1124


428





368 (M + H)





1125


429





365 (M + H)





1126


430





325 (M + H)





1127


431





353 (M + H)





1128


432





358 (M + H)










[1952]

93







TABLE 93








Ex. No.
Formula
MS












1129
361 (M + H)





1130
352 (M + H)





1131
352 (M + H)





1132
367 (M + H)





1133
368 (M + H)





1134
365 (M + H)










[1953]

94







TABLE 94








Ex. No.
Formula
MS












1135


433





351 (M + H)





1136


434





307 (M + H)





1137


435





385 (M + H)





1138


436





365 (M + H)





1139


437





467 (M + H)





1140


438





387 (M + H)










[1954]

95







TABLE 95








Ex. No.
Formula
MS












1141


439





322 (M + H)





1142


440





364 (M + H)





1143


441





323 (M + H)





1144


442





363 (M + H)





1145


443





484 (M + H)





1146


444





385 (M + H)










[1955]

96







TABLE 96








Ex. No.
Formula
MS












1147


445





427 (M + H)





1148


446





420 (M + H)





1149


447





508 (M + H)





1150


448





458 (M + H)





1151


449





458 (M + H)










[1956]

97







TABLE 97








Ex. No.
Formula
MS












1152


450





474 (M + H)





1153


451





458 (M + H)





1154


452





508 (M + H)





1155


453





454 (M + H)










[1957]

98







TABLE 98








Ex. No.
Formula
MS












1156


454





470 (M + H)





1157


455





496 (M + H)





1158


456





482 (M + H)





1159


457





448 (M + H)





1160


458





488 (M + H)










[1958]

99







TABLE 99








Ex. No.
Formula
MS












1161


459





468 (M + H)





1162


460





447 (M + H)





1163


461





466 (M + H)





1164


462





526 (M + H)





1165


463





420 (M + H)










[1959]

100







TABLE 100








Ex. No.
Formula
MS












1166


464





490 (M + H)





1167


465





435 (M + H)





1168


466





436 (M + H)





1169


467





436 (M + H)





1170


468





404 (M + H)





1171


469





406 (M + H)










[1960]

101







TABLE 101








Ex. No.
Formula
MS












1172


470





392 (M + H)





1173


471





420 (M + H)





1174


472





406 (M + H)





1175


473





420 (M + H)





1176


474





523 (M + H)





1177


475





406 (M + H)










[1961]

102







TABLE 102








Ex. No.
Formula
MS












1178


476





447 (M + H)





1179


477





433 (M + H)





1180


478





509 (M + H)





1181


479





513 (M + H)










[1962]

103







TABLE 103








Ex. No.
Formula
MS












1182


480





497 (M + H)





1183


481





496 (M + H)





1184


482





418 (M + H)





1185


483





508 (M + H)





1186


484





490 (M + H)










[1963]

104







TABLE 104








Ex. No.
Formula
MS












1187


485





441 (M + H)





1188


486





455 (M + H)





1189


487





455 (M + H)





1190


488





513 (M + H)





1191


489





504 (M + H)





1192


490





494 (M + H)










[1964]

105







TABLE 105








Ex. No.
Formula
MS












1193


491





512 (M + H)





1194


492





504 (M + H)





1195


493





516 (M + H)





1196


494





497 (M + H)





1197


495





456 (M + H)





1198


496





509 (M + H)










[1965]

106







TABLE 106








Ex. No.
Formula
MS






















1199


497





483(M + H)





1200


498





427(M + H)





1201


499





427(M + H)





1202


500





477(M + H)





1203


501





519(M + H)





1204


502





440(M + H)










[1966]

107







TABLE 107








Ex. No.
Formula
MS






















1205


503





454(M + H)





1206


504





325(M + H)





1207


505





341(M + H)





1208


506





385(M + H)





1209


507





363(M + H)





1210


508





332(M + H)










[1967]

108







TABLE 108








Ex. No.
Formula
MS






















1211


509





351(M + H)





1212


510





335(M + H)





1213


511





349(M + H)





1214


512





321(M + H)





1215


513





375(M + H)





1216


514





367(M + H)










[1968]

109







TABLE 109








Ex. No.
Formula
MS






















1217


515





433(M + H)





1218


516





391(M + H)





1219


517





337(M + H)





1220


518





385(M + H)





1221


519





341(M + H)





1222


520





332(M + H)










[1969]

110







TABLE 110








Ex. No.
Formula
MS






















1223


521





395(M + H)





1224


522





375(M + H)





1225


523





351(M + H)





1226


524





321(M + H)





1227


525





426(M + H)





1228


526





460(M + H)










[1970]

111







TABLE 111








Ex. No.
Formula
MS






















1229


527





442(M + H)





1230


528





468(M + H)





1231


529





456(M + H)





1232


530





494(M + H)





1233


531





451(M + H)





1234


532





468(M + H)










[1971]

112







TABLE 112








Ex. No.
Formula
MS






















1235


533





498(M + H)





1236


534





476(M + H)





1237


535





502(M + H)





1238


536





505(M + H)





1239


537





469(M + H)










[1972]

113







TABLE 113








Ex. No.
Formula
MS






















1240


538





483(M + H)





1241


539





408(M + H)





1242


540





460(M + H)





1243


541





468(M + H)





1244


542





494(M + H)





1245


543





454(M + H)










[1973]

114







TABLE 114








Ex. No.
Formula
MS






















1246


544





468(M + H)





1247


545





498(M + H)





1248


546





482(M + H)





1249


547





468(M + H)





1250


548





460(M + H)










[1974]

115







TABLE 115








Ex. No.
Formula
MS






















1251


549





442(M + H)





1252


550





468(M + H)





1253


551





456(M + H)





1254


552





494(M + H)










[1975]

116







TABLE 116








Ex. No.
Formula
MS






















1255


553





451(M + H)





1256


554





468(M + H)





1257


555





498(M + H)





1258


556





470(M + H)










[1976]

117







TABLE 117








Ex. No.
Formula
MS






















1259


557





476(M + H)





1260


558





502(M + H)





1261


559





505(M + H)





1262


560





469(M + H)










[1977]

118







TABLE 118








Ex. No.
Formula
MS






















1263


561





483(M + H)





1264


562





408(M + H)





1265


563





460(M + H)





1266


564





468(M + H)










[1978]

119







TABLE 119








Ex. No.
Formula
MS






















1267


565





494(M + H)





1268


566





454(M + H)





1269


567





468(M + H)





1270


568





498(M + H)










[1979]

120







TABLE 120








Ex. No.
Formula
MS






















1271


569





482(M + H)





1272


570





468(M + H)





1273


571





494(M + H)





1274


572





484(M + H)










[1980]

121







TABLE 121








Ex. No.
Formula
MS












1275


573





519 (M + H)





1276


574





427 (M + H)





1277


575





456 (M + H)





1278


576





516 (M + H)










[1981]

122







TABLE 122








Ex. No.
Formula
MS












1279


577





436 (M + H)





1280


578





426 (M + H)





1281


579





440 (M + H)





1282


580





454 (M + H)





1283


581





468 (M + H)










[1982]

123







TABLE 123








Ex. No.
Formula
MS












1284


582





482 (M + H)





1285


583





406 (M + H)





1286


584





420 (M + H)





1287


585





508 (M + H)





1288


586





508 (M + H)










[1983]

124







TABLE 124








Ex. No.
Formula
MS












1289


587





509 (M + H)





1290


588





455 (M + H)





1291


589





494 (M + H)





1292


590





418 (M + H)










[1984]

125







TABLE 125








Ex. No.
Formula
MS












1293


591





490 (M + H)





1294


592





496 (M + H)





1295


593





477 (M + H)





1296


594





508 (M + H)





1297


595





470 (M + H)










[1985]

126







TABLE 126








Ex. No.
Formula
MS












1298


596





435 (M + H)





1299


597





488 (M + H)





1300


598





454 (M + H)





1301


599





504 (M + H)










[1986]

127







TABLE 127








Ex. No.
Formula
MS












1302


600





513 (M + H)





1303


601





399 (M + H)





1304


602





530 (M + H)





1305


603





504 (M + H)





1306


604





440 (M + H)










[1987]

128







TABLE 128








Ex. No.
Formula
MS












1307


605





494 (M + H)





1308


606





508 (M + H)





1309


607





518 (M + H)





1310


608





532 (M + H)





1311


609





522 (M + H)










[1988]

129







TABLE 129








Ex. No.
Formula
MS












1312


610





546 (M + H)





1313


611





484 (M + H)





1314


612





517 (M + H)





1315


613





488 (M + H)





1316


614





481 (M + H)










[1989]

130







TABLE 130








Ex. No.
Formula
MS












1317


615





413 (M + H)





1318


616





423 (M + H)





1319


617





504 (M + H)





1320


618





510 (M + H)





1321


619





522 (M + H)





1322


620





522 (M + H)










[1990]

131







TABLE 131








Ex. No.
Formula
MS












1323


621





484 (M + H)





1324


622





449 (M + H)





1325


623





502 (M + H)





1326


624





491 (M + H)





1327


625





496 (M + H)










[1991]

132







TABLE 132








Ex. No.
Formula
MS












1328


626





497 (M + H)





1329


627





470 (M + H)





1330


628





530 (M + H)





1331


629





502 (M + H)





1332


630





522 (M + H)










[1992]

133







TABLE 133








Ex. No.
Formula
MS












1333


631





491 (M + H)





1334


632





536 (M + H)





1335


633





547 (M + H)





1336


634





484 (M + H)





1337


635





484 (M + H)





1338


636





498 (M + H)










[1993]

134







TABLE 134








Ex. No.
Formula
MS












1339


637





528 (M + H)





1340


638





498 (M + H)





1341


639





514 (M + H)





1342


640





513 (M + H)





1343


641





488 (M + H)





1344


642





502 (M + H)










[1994]

135







TABLE 135








Ex. No.
Formula
MS












1345


643





488 (M + H)





1346


644





502 (M + H)





1347


645





499 (M + H)





1348


646





480 (M + H)





1349


647





522 (M + H)





1350


648





546 (M + H)










[1995]

136







TABLE 136








Ex. No.
Formula
MS












1351


649





482 (M + H)





1352


650





484 (M + H)





1353


651





609 (M + H)





1354


652





532 (M + H)





1355


653





480 (M + H)





1356


654





566 (M + H)










[1996]

137







TABLE 137








Ex. No.
Formula
MS












1357


655





602 (M + H)





1358


656





596 (M + H)





1359


657





491 (M + H)





1360


658





491 (M + H)





1361


659





491 (M + H)





1362


660





496 (M + H)










[1997]

138







TABLE 138








Ex. No.
Formula
MS












1363


661





512 (M + H)





1364


662





494 (M + H)





1365


663





488 (M + H)





1366


664





481 (M + H)





1367


665





524 (M + H)





1368


666





497 (M + H)










[1998]

139







TABLE 139








Ex. No.
Formula
MS












1369


667





472 (M + H)





1370


668





469 (M + H)





1371


669





470 (M + H)





1372


670





469 (M + H)





1373


671





494 (M + H)





1374


672





458 (M + H)










[1999]

140







TABLE 140








Ex. No.
Formula
MS












1375


673





612 (M + H)





1376


674





554 (M + H)





1377


675





542 (M + H)





1378


676





526 (M + H)





1379


677





496 (M + H)





1380


678





510 (M + H)










[2000]

141







TABLE 141








Ex. No.
Formula
MS












1381


679





540 (M + H)





1382


680





525 (M + H)





1383


681





558 (M + H)





1384


682





523 (M + H)





1385


683





539 (M+ H)










[2001]

142







TABLE 142








Ex. No.
Formula
MS












1386


684





533 (M + H)





1387


685





500 (M + H)





1388


686





485 (M + H)





1389


687





523 (M + H)





1390


688





512 (M + H)










[2002]

143







TABLE 143








Ex. No.
Formula
MS












1391


689





540 (M + H)





1392


690





527 (M + H)





1393


691





525 (M + H)





1394


692





507 (M + H)





1395


693





491 (M + H)





1396


694





506 (M + H)










[2003]

144







TABLE 144








Ex. No.
Formula
MS












1397


695





522 (M + H)





1398


696





538 (M + H)





1399


697





522 (M + H)





1400


698





530 (M + H)





1401


699





600 (M + H)





1402


700





504 (M + H)










[2004]

145







TABLE 145








Ex. No.
Formula
MS












1403


701





534 (M + H)





1404


702





475 (M +H)





1405


703





472 (M + H)





1406


704





455 (M + H)





1407


705





469 (M + H)





1408


706





547 (M + H)










[2005]

146







TABLE 146








Ex. No.
Formula
MS












1409


707





529 (M + H)





1410


708





435 (M + H)





1411


709





504 (M + H)





1412


710





469 (M + H)





1413


711





522 (M + H)





1414


712





488 (M + H)










[2006]

147







TABLE 147








Ex. No.
Formula
MS












1415


713





502 (M + H)





1416


714





488 (M + H)





1417


715





502 (M + H)





1418


716





455 (M + H)





1419


717





455 (M + H)





1420


718





522 (M + H)










[2007]

148







TABLE 148








Ex. No.
Formula
MS












1421


719





469 (M + H)





1422


720





536 (M + H)





1423


721





510 (M + H)





1424


722





494 (M + H)





1425


723





458 (M + H)










[2008]

149







TABLE 149








Ex. No.
Formula
MS












1426


724





612 (M + H)





1427


725





526 (M + H)





1428


726





480 (M + H)





1429


727





441 (M + H)





1430


728





511 (M + H)










[2009]

150







TABLE 150








Ex. No.
Formula
MS












1431


729





530 (M + H)





1432


730





497 (M + H)





1433


731





441 (M + H)





1434


732





491 (M + H)





1435


733





491 (M + H)





1436


734





491 (M + H)










[2010]

151







TABLE 151








Ex. No.
Formula
MS












1437


735





524 (M + H)





1438


736





508 (M + H)





1439


737





474 (M + H)





1440


738





490 (M + H)





1441


739





508 (M + H)





1442


740





474 (M + H)










[2011]

152







TABLE 152








Ex. No.
Formula
MS












1443


741





516 (M + H)





1444


742





600 (M + H)





1445


743





504 (M + H)





1446


744





534 (M + H)





1447


745





475 (M + H)










[2012]

153







TABLE 153








Ex. No.
Formula
MS












1448


746





530 (M + H)





1449


747





440 (M + H)





1450


748





490 (M + H)





1451


749





474 (M + H)





1452


750





441 (M + H)





1453


751





508 (M + H)










[2013]

154







TABLE 154








Ex. No.
Formula
MS












1454


752





455 (M + H)





1455


753





522 (M + H)





1456


754





496 (M + H)





1457


755





516 (M + H)





1458


756





426 (M + H)





1459


757





482 (M + H)










[2014]

155







TABLE 155








Ex. No.
Formula
MS












1460


758





486 (M + H)





1461


759





516 (M + H)





1462


760





427 (M + H)





1463


761





476 (M + H)





1464


762





460 (M + H)





1465


763





502 (M + H)










[2015]

156







TABLE 156








Ex. No.
Formula
MS












1466


764





586 (M + H)





1467


765





518 (M + H)





1468


766





530 (M + H)





1469


767





598 (M + H)





1470


768





512 (M + H)





1471


769





544 (M + H)










[2016]

157







TABLE 157








Ex. No.
Formula
MS












1472


770





440 (M + H)





1473


771





490 (M + H)





1474


772





474 (M + H)





1475


773





441 (M + H)





1476


774





508 (M + H)





1477


775





455 (M + H)










[2017]

158







TABLE 158








Ex. No.
Formula
MS












1478


776





522 (M + H)





1479


777





496 (M + H)





1480


778





516 (M + H)





1481


779





426 (M + H)





1482


780





482 (M + H)










[2018]

159







TABLE 159








Ex. No.
Formula
MS












1483


781





486 (M + H)





1484


782





516 (M + H)





1485


783





427 (M + H)





1486


784





476 (M + H)










[2019]

160







TABLE 160








Ex. No.
Formula
MS












1487


785





460 (M + H)





1488


786





502 (M + H)





1489


787





586 (M + H)





1490


788





518 (M + H)










[2020]

161







TABLE 161








Ex. No.
Formula
MS












1491


789





530 (M + H)





1492


790





598 (M + H)





1493


791





512 (M + H)





1494


792





544 (M + H)










[2021]

162







TABLE 162








Ex. No.
Formula
MS












1495


793





580 (M + H)





1496


794





550 (M + H)





1497


795





606 (M + H)





1498


796





580 (M + H)





1499


797





550 (M + H)










[2022]

163







TABLE 163








Ex. No.
Formula
MS












1500


798





606 (M + H)





1501


799





630 (M + H)





1502


800





600 (M + H)





1503


801





656 (M + H)










[2023]

164







TABLE 164








Ex. No.
Formula
MS












1504


802





630 (M + H)





1505


803





600 (M + H)





1506


804





656 (M + H)





1507


805





580 (M + H)










[2024]

165







TABLE 165








Ex. No.
Formula
MS












1508


806





550 (M + H)





1509


807





606 (M + H)





1510


808





580 (M + H)





1511


809





550 (M + H)





1512


810





546 (M + H)










[2025]

166







TABLE 166













Ex. No.
Formula
MS






















1513


811





516 (M + H)





1514


812





572 (M + H)





1515


813





546 (M + H)





1516


814





516 (M + H)





1517


815





572 (M + H)










[2026]

167







TABLE 167








Ex. No.
Formula
MS






















1518


816





602 (M + H)





1519


817





572 (M + H)





1520


818





628 (M + H)





1521


819





606 (M + H)










[2027]

168







TABLE 168








Ex. No.
Formula
MS






















1522


820





573 (M + H)





1523


821





606 (M + H)





1524


822





602 (M + H)





1525


823





572 (M + H)










[2028]

169







TABLE 169








Ex. No.
Formula
MS






















1526


824





628 (M + H)





1527


825





606 (M + H)





1528


826





606 (M + H)





1529


827





614 (M + H)










[2029]

170







TABLE 170








Ex. No.
Formula
MS






















1530


828





584 (M + H)





1531


829





640 (M + H)





1532


830





618 (M + H)





1533


831





614 (M + H)





1534


832





584 (M + H)










[2030]

171







TABLE 171








Ex. No.
Formula
MS






















1535


833





640 (M + H)





1536


834





627 (M + H)





1537


835





627 (M + H)










[2031]

172







TABLE 172








Ex. No.
Formula
MS






















1538


836





560 (M + H)





1539


837





634 (M + H)





1540


838





593 (M + H)





1541


839





627 (M + H)










[2032]

173







TABLE 173








Ex. No.
Formula
MS






















1542


840





627 (M + H)





1543


841





560 (M + H)





1544


842





634 (M + H)





1545


843





593 (M + H)










[2033]

174







TABLE 174








Ex. No.
Formula
MS






















1546


844





627 (M + H)





1547


845





627 (M + H)





1548


846





560 (M + H)





1549


847





634 (M + H)










[2034]

175







TABLE 175








Ex. No.
Formula
MS






















1550


848





627 (M + H)





1551


849





560 (M + H)





1552


850





532 (M + H)





1553


851





565 (M + H)










[2035]

176







TABLE 176








Ex. No.
Formula
MS






















1554


852





599 (M + H)





1555


853





599 (M + H)





1556


854





532 (M + H)





1557


855





532 (M + H)










[2036]

177







TABLE 177








Ex. No.
Formula
MS






















1558


856





584 (M + H)





1559


857





570 (M + H)










[2037]

178










TABLE 178












HCV polymerase

HCV polymerase



Ex.
inhibitory activity
Ex.
inhibitory activity



No.
IC50 [μM]
No.
IC50 [μM]





















2
0.079
67
0.26



6
0.034
68
0.28



9
0.019
70
0.19



11
0.53
71
0.62



12
0.60
77
0.51



17
0.047
81
0.18



20
0.042
82
0.097



26
0.033
83
0.52



30
0.052
85
0.17



43
0.58
86
0.13



44
0.95
87
0.80



45
0.40
88
0.092



46
0.47
89
0.34



47
0.54
90
0.20



48
0.44
91
0.53



49
0.94
93
0.16



50
0.54
94
0.084



51
1.0
96
0.25



54
0.56
97
0.16



55
0.36
98
0.30











[2038]

179










TABLE 179












HCV polymerase

HCV polymerase



Ex.
inhibitory activity
Ex.
inhibitory activity



No.
IC50 [μM]
No.
IC50 [μM]





















99
0.53
120
0.16



100
0.78
121
0.19



101
0.14
122
0.51



103
0.17
123
0.10



104
0.073
124
0.091



105
0.076
125
0.12



106
0.40
128
0.14



107
0.11
129
0.12



108
0.21
130
0.16



109
0.11
131
0.046



110
0.24
132
0.055



111
0.14
133
0.12



112
0.11
134
0.071



113
0.071
139
0.26



114
0.56
140
0.11



115
0.17
141
0.43



116
0.37
142
0.055



117
0.075
143
0.053



118
0.14
144
0.19



119
0.13
145
0.088











[2039]

180










TABLE 180












HCV polymerase

HCV polymerase



Ex.
inhibitory activity
Ex.
inhibitory activity



No.
IC50 [μM]
No.
IC50 [μM]





















146
0.043
167
0.033



147
0.31
168
0.078



148
0.038
169
0.15



149
0.15
170
0.048



150
0.24
171
0.050



151
0.20
172
0.10



153
0.19
173
0.14



154
0.076
174
0.030



155
0.53
175
0.29



156
0.23
176
0.053



157
0.16
177
0.077



158
0.11
178
0.052



159
0.13
179
0.63



160
0.24
180
0.11



161
0.062
181
0.71



162
0.43
182
0.021



163
0.15
183
0.017



164
0.16
184
0.018



165
0.58
185
0.11



166
0.055
186
0.37











[2040]

181










TABLE 181












HCV polymerase

HCV polymerase



Ex.
inhibitory activity
Ex.
inhibitory activity



No.
IC50 [μM]
No.
IC50 [μM]





















187
0.056
207
0.081



188
0.038
208
0.039



189
0.017
209
0.12



190
0.020
210
0.31



191
0.43
211
0.059



192
0.22
212
0.23



193
0.13
213
0.10



194
0.52
214
0.059



195
0.023
215
0.078



196
0.20
216
0.084



197
0.11
217
0.058



198
0.044
218
0.033



199
0.11
219
0.13



200
0.10
220
0.073



201
0.14
221
0.058



202
0.095
222
0.041



203
0.063
223
0.21



204
0.16
225
0.014



205
0.077
227
0.045



206
0.05
228
0.18











[2041]

182










TABLE 182












HCV polymerase

HCV polymerase



Ex.
inhibitory activity
Ex.
inhibitory activity



No.
IC50 [μM]
No.
IC50 [μM]





















229
0.022
257
0.074



230
0.17
259
0.10



231
0.073
260
0.27



232
0.015
262
0.013



233
0.028
263
0.035



234
0.022
264
<0.01



235
0.036
265
0.014



236
0.075
266
0.018



237
0.015
267
0.014



238
0.19
268
0.012



239
0.17
269
0.013



240
0.055
270
0.012



248
0.012
271
0.024



249
0.022
272
0.066



250
0.018
273
0.041



252
0.32
276
0.023



253
0.65
279
0.017



254
0.038
280
0.016



255
0.038
281
0.052



256
0.079
282
0.019











[2042]

183










TABLE 183












HCV polymerase

HCV polymerase



Ex.
inhibitory activity
Ex.
inhibitory activity



No.
IC50 [μM]
No.
IC50 [μM]





















283
0.014
300
0.045



284
0.014
301
0.017



285
0.012
303
0.10



286
0.014
304
0.017



287
0.012
305
0.01



288
0.013
306
0.013



289
<0.01
307
0.022



290
0.012
308
0.023



291
0.016
311
0.16



292
0.015
312
0.023



293
0.034
313
0.025



294
0.032
314
0.097



295
0.045
315
0.028



296
0.034
316
0.022



297
0.022
317
0.032



298
0.011
318
0.012



299
0.018
319
0.030











[2043]

184










TABLE 184












HCV polymerase

HCV polymerase



Ex.
inhibitory activity
Ex.
inhibitory activity



No.
IC50 [μM]
No.
IC50 [μM]









320
0.036
328
0.015



321
0.015
329
0.047



322
0.016
330
0.011



323
0.018
331
0.017



324
0.027
332
0.023



325
0.019
333
0.016



326
0.018
334
0.016



327
0.019
335
0.013











[2044]

185







TABLE 185















Example No.
249
1H NMR(δ) ppm














858





300 MHz, DMSO-d6 8.02(1W d,J=1.5 Hz),8.11 (1H, d, J=1.8 Hz), 7.96-7.81 (3H, m), 7.67 (1H, s), 7.61-7.49(6H, m), 7.08 (2H, d, J=8.6 Hz), 5.19 (2H, s), 4.25 (1H, m), 2.38-2.17(2H, m),1.96-1.78 (4H, m), 1.70-1.56 (1H, m), 1.46-1.16 (3H, m), 1.11(9H, s)














Purity
>90% (NMR)


MS
672 (M + 1)










Example No.
250
1H NMR(δ) ppm














859





300 MHz, DMSO-d6 8.25 (1H, d, J=1.5 Hz) 8.16-8.08 (2H, m), 7.99-7.88 (2H, m), 7.66(2H, d, J=8.6 Hz), 7.60-7.48(5H, m), 7.19 (2H, d, J=8.6 Hz), 5.17(2H, s), 4.31 (1H, m), 2.39-2.20 (2H, m), 2.04-1.79 (4H, m), 1.72-1.60 (1H, m), 1.50-1.18(3H, m)














Purity
>90% (NMR)


MS
616(M + 1)










Example No.
251
1H NMR(δ) ppm














860





300 MHz, DMSO-d6 cis and trans mixture 8.13 and 8.11 (total 1H, each s), 7.90-7.74(2H, m), 7.42-7.22(5H, m), 4.56 and 4.52(total 2H, each s), 4.42(1H, brs), 3.78-3.06(2H, m) 2.33-1.33(18H, m)














Purity
>90% (NMR)


MS
433 (M + 1)










[2045]

186







TABLE 186















Example No.
252
1H NMR(δ) ppm














861





300 MHz, DMSO-d6 8.20(1H, d, J=1.85 Hz), 7.96 (1H, d, J=8.86 Hz), 7.84(1H, dd, J=8.6, 1.85 Hz), 7.54(2H, d, J=6.9 Hz), 7.48-7.26 (8H, m), 7.09 (1H, t, J=7.3 Hz), 5.43 (2H, s), 4.06(1H, m), 2.40-2.20(2H, m), 2.01-1.80(4H, m), 1.75-1.64 (1H, m), 1.51-1.28(3H, m)














Purity
>90% (NMR)


MS
509 (M + 1)










Example No.
253
1H NMR(δ) ppm














862





300 MHz, DMSO-d6 8.21(1H, d, J=1.5 Hz), 7.93 (1H, d, J=8.7 Hz), 7.85 (1H, dd, J=8.4, 1.5Hz), 7.54-7.47(2H, m), 7.40-7.24(6H, m), 7.15(1H, d, J=3.6 Hz), 7.11-7.05(1H, m), 6.81(1H, d, J=3.6 Hz), 5.26(2H, s), 4.96(1H, m), 2.32-2.13(2H, m), 1.95-1.72(4H, m), 1.68-1.55(1H, m), 1.43-1.18(3H, m)














Purity
>90% (NMR)


MS
493 (M + 1)










Example No.
254
1H NMR(δ) ppm














863





300 MHz, DMSO-d6 8.25(1H, s), 8.02(1H, d, J=8.7 Hz), 7.90(1H, dd, J=8.4, 1.4 Hz), 7.80-7.71 (2H, m), 7.67(2H, d, J=8.7 Hz), 7.33(2H, t, J=8.7 Hz), 7.26(2H, d, J=8.7 Hz), 5.46(2H, s), 4.78 (2H, s), 4.31(1H, m), 2.39-2.19(2H, m), 2.03-1.79(4H, m), 1.71-1.59(1H, m), 1.50-1.17(3H, m)














Purity
>90% (NMR)


MS
558 (M + 1)










[2046]

187







TABLE 187















Example No.
255
1H NMR(δ) ppm














864





300 MHz, DMSO-d6 8.34 (1H, s) 8.32 (1H, d, J=8.8 Hz), 8.09-8.03(3H, m), 7.83(2H, d, J=8.3 Hz), 7.79(2H, d, J=8.8 Hz), 7.36(2H, d, J=8.8 Hz), 5.54(2H, s), 4.38(1H, M), 2.74(3H, s), 2.40-2.18(2H, m), 2.13-1.96(2H, m), 1.93-1.78(2H, m), 1.73-1.57(1H, m), 1.55-1.15(3H, m)














Purity
>90% (NMR)


MS
568(M + 1)










Example No.
256
1H NMR(δ) ppm














865





300 MHz, DMSO-d6 12.67(1H, brs), 8.23(1H, s), 7.94 and 7.87(2H, ABq, J=8.6 Hz), 7.79(1H, dd, J=8.7, 5.4 Hz), 7.62-7.41 (7H, m), 6.80(1H, dd, J=11.9, 2.3 Hz), 6.69(1H, dd, J=8.1, 2.1 Hz), 5.20(2H, s), 3.93(1H, brt, J=15.3Hz), 2.30-2.11(2H, brm) 1.88-1.74(4H, brm), 1.64-1.58(1H, brm), 1.41-1.14(3H, brm)














Purity
>90% (NMR)


MS
585(M + 1)










Example No.
257
1H NMR(δ) ppm














866





300 MHz, DMSO-d6 8.19(1H, d, J=8.7 Hz), 7.93(H, s), 7.83-7.71(3H, m), 7.50-7.39(4H, m), 7.34-7.10(4H, m), 7.06(1H, dd, J=8.4, 2.9 Hz), 5.09(2H, s), 4.34(1H, m), 3.82(3H, s), 2.39-2.19(2H, m), 2.11-1.98(2H, m), 1.94-1.79(2H, m), 1.74-1.58 (1H, m), 1.52-1.21(3H, m)














Purity
>90% (NMR)


MS
603(M + 1)










[2047]

188







TABLE 188















Example No.
258
1H NMR (δ) ppm














867





300 MHz, DMSO-d6 7.79(1H, d, J=6.7 Hz), 7.56 (1H, d, J=7.5 Hz), 7.49 (2H, d, J=8.6 Hz), 7.42 (4H, s), 7.32-7.23 (3H, m), 7.09-7.03 (3H, m), 5.02 (2H, s), 4.46 (1H, m, 3.82 (3H, s), 1.95-1.83 (2H, m), 1.75-1.44 (5H, m), 1.30-1.10 (2H, m), 0.89-0.71 (1H, m)

















Purity
>90% (NMR)


MS
567 (M + 1)





Example No.
259
1H NMR (δ) ppm














868





300 MHz, DMSO-d6 8.93 (2H, d, J=6.6 Hz), 8.36 (1H, s), 8.28 (1H, d, J=8.7 Hz), 8.10-8.03 (3H, m), 7.85 (2H, d, J=8.7 Hz), 7.33 (2H, d, J=8.7 Hz), 7.23 (1H, s), 7.23 (1H, s), 6.81 (1H, s), 5.56 (2H, s), 4.39 (1H, m), 2.97, 2.92 (6H, s), 2.40-2.18 (2H, m), 2.16-1.95 (2H, m), 1.90-1.75 (2H, m), 1.70-1.55 (1H, m), 1.50-1.15 (3H, m)














Purity
>90% (NMR)


MS
591 (M + 1)





Example No.
260
1H NMR (δ) ppm














869





300 MHz, DMSO-d6 8.93 (2H, d, J=6.3 Hz), 8.35 (1H, s), 8.26 (1H, d, J=8.7 Hz), 8.09-8.02 (3H, m), 7.86 (2H, d, J=8.7 Hz), 7.50 (1H, s), 7.35 (2H, d, J=8.4 Hz), 7.24 (2H, d, J=7.8 Hz), 5.60 (2H, s), 4.39 (1H, m), 2.50-2.18 (2H, m), 2.15-1.95 (2H, m), 1.90-1.75 (2H, m), 1.70-1.55 (1H, m) 1.50-1.10 (3H, m)














Purity
>90% (NMR)


MS
564 (M + 1)










[2048]

189







TABLE 189















Example No.
261
1H NMR (δ) ppm














870





300 MHz, DMSO-d6 8.22 (1H, d, J=7.8 Hz), 7.85 (1H, d, J=6.7 Hz), 7.63 (2H, d, J=9.0 H), 7.51-7.38 (5H, m), 7.29 (1H, d, J=8.3 Hz), 7.23 (1H, d, J=3.0 Hz), 7.06 (2H, d, J=9.0 Hz), 7.06 (1H, dd, J=8.6, 3.0 Hz), 5.05 (2H, s), 4.41-4.25 (1H, m), 3.83 (3H, s), 2.40-2.20 (2H, m), 2.03-1.78 (4H, m), 1.72-1.57 (1H, m), 1.50-1.18 (3H, m)














Purity
>90% (NMR)


MS
567 (M + 1)





Example No.
262
1H NMR (δ) ppm














871





300 MHz, DMSO-d6 8.29 (1H, d, J=1.5 Hz), 8.26 (1H, d, J=9.0 Hz), 8.19 (1H, d, J=1.8 Hz), 8.13 (1H, brs), 8.08-7.96 (2H, m), 7.73 (2H, d, J=9.0 Hz), 7.57-7.43 (6H, m), 7.24 (2H, d, J=9.0 Hz), 5.14 (2H, s), 4.36 (1H, m), 2.38-2.18 (2H, m), 2.12-1.97 (2H, m), 1.93-1.80 (2H, m), 1.73-1.58 (1H, m), 1.50-1.20 (3H, m)














Purity
>90% (NMR)


MS
580 (M + 1)





Example No.
263
1H NMR (δ) ppm














872





300 MHz, DMSO-d6 12.85 (1H, brs), 8.72 (1H, d, J=4.8 Hz), 8.22 (1H, s), 8.14 (1H, d, J=6.3 Hz), 8.03 and 7.76 (4H, ABq, J=8.6 Hz), 7.93 and 7.85 (2H, A′ B′ q, J=8.6 Hz), 7.60 and 7.15 (4H, ABq, J=8.7 Hz), 7.55 (1H, dd, J=6.3, 4.8 Hz), 5.19 (2H, s), 4.26 (1H, brt, J=12.6 Hz), 2.35-2.18 (2H, brm), 1.95-1.77 (4H, brm), 1.70-1.60 (1H, brm), 1.45-1.15 (3H, brm)














Purity
>90% (NMR)


MS
548 (M + 1)










[2049]

190







TABLE 190















Example No.
264
1H NMR (δ) ppm














873





300 MHz, DMSO-d6 8.23 (1H, d, J=1.0 Hz), 7.92 (1H, dd, J=8.7, 1.0 Hz), 7.87 (1H, d, J=8.7 Hz), 7.60 (2H, d, J=8.6 Hz), 7.47 (2H, d, J=8.7 Hz), 7.44 (2H, d, J=8.7 Hz), 7.30 (1H, d, J=8.3 Hz), 7.23 H, d, J=2.6 Hz), 7.11 (2H, d, J=8.7 Hz), 7.06 (1H, dd, J=8.7, 2.6 Hz), 5.04 (2H, s), 4.36 (1H, m), 3.83 (3H, s), 2.80-2.70 (4H, m), 2.60-2.40 (2H, m), 2.30-2.20 (2H, m)














Purity
>90% (NMR)


MS
586, 588 (M + 1)





Example No.
265
1H NMR (δ) ppm














874





300 MHz, DMSO-d6 8.30 (1H, d, J=1.5 Hz), 8.25 (1H, d, J=9.1 Hz), 8.03 (1H, dd, J=8.7, 1.5 Hz), 7.76-7.96 (3H, m), 7.55-7.49 (5H, m), 7.42 (1H, d, J=7.6 z), 7.23 (2H, d, J=8.7 Hz), 5.15 (2H, s), 4.35 (1H, m), 3.01 (3H, s), 2.97 (3H, s), 2.37-2.20 (2H, m), 2.09-1.97 (2H, m), 1.94-1.81 (2H, m), 1.72-1.60 (1H, m), 1.50-1.21 (3H, m)














Purity
>90% (NMR)


MS
608 (M + 1)





Example No.
266
1H NMR (δ) ppm














875





300 MHz, DMSO-d6 8.27 (1H, d, J=1.5 Hz), 8.20 (1H, d, J=9.0 Hz), 8.00 (1H, dd, J=8.6, 1.5 Hz), 7.82 (2H, d, J=8.2 Hz), 7.76-7.65 (5H, m), 7.56 (1H, dd, J=7.9, 1.8 Hz), 7.47 (1H, d, J=7.5 Hz), 7.20 (2H, d, J=8.6 Hz), 5.16 (2H, s), 4.32 (1H, m), 3.02 (3H, s), 2.98 (3H, s), 2.38-2.19 (2H, m), 2.07-1.95 (2H, m), 1.93-1.80 (2H, m), 1.72-1.58 (1H, m), 1.52-1.18 (3H, m)














Purity
>90% (NMR)


MS
642 (M + 1)










[2050]

191







TABLE 191















Example No.
267
1H NMR (δ) ppm














876





300 MHz, DMSO-d6 8.34 (2H, m), 8.03 (1H, d, J=8.3 Hz), 7.77-7.68 (3H, m), 7.54-7.40 (4H, m), 7.33 (2H, d, J=8.6 Hz), 7.24 (2H, d, J=9.0 Hz), 5.16 (2H, s), 4.36 (1H, m), 3.01 (3H, s), 2.97 (3H, s), 2.40-2.20 (2H, m), 2.11-1.97 (2H, m), 1.93-1.81 (2H, m), 1.71-1.60 (1H, m), 1.50-1.21 (3H, m)














Purity
>90% (NMR)


MS
620 (M + 1)





Example No.
268
1H NMR (δ) ppm














877





300 MHz, DMSO-d6 8.67-8.59 (1H, m), 8.30 (1H, s), 8.13-8.20 (2H, m), 8.02-7.92 (2H, m), 7.65 (1H, t, J=8.3 Hz), 7.56-7.45 (5H, m), 7.18 (1H, dd, J=12.0, 2.2 Hz), 7.05 (1H, dd, J=8.6, 2.2 Hz), 5.14 (2H, s), 4.09 (1H, m), 2.82 (3H, d, J=4.5 Hz), 2.34-2.12 (2H, m), 1.99-1.79 (4H, m), 1.71-1.59 (1H, m), 1.49-1.21 (3H, m)














Purity
>90% (NMR)


MS
612 (M + 1)





Example No.
269
1H NMR (δ) ppm














878





300 MHz, DMSO-d6 8.29 (1H, s), 8.13 (1H, d, J=9.0 Hz), 7.97 (1H, dd, J=8.6, 1.5 Hz), 7.71 (1H, d, J=1.8 Hz), 7.63 (1H, t, J=8.2 Hz), 7.56-7.41 (6H, m), 7.17 (1H, dd, J=12.0, 2.2 Hz), 7.03 (1H, dd, J=8.2, 1.8 Hz), 5.14 (2H, s), 4.15-4.00 (1H, m), 3.01 (3H, s), 2.98 (3H, s), 2.32-2.13 (2H, m) 1.95-1.79 (4H, m), 1.72-1.59 (1H, m), 1.45-1.21 (3H, m)














Purity
>90% (NMR)


MS
626 (M + 1)










[2051]

192







TABLE 192















Example No.
270
1H NMR (δ) ppm














879





300 MHz, DMSO-d6 8.24 (1H, d, J=1.4 Hz), 8.19 (1H, d, J=1.8 Hz), 8.11 (1H, brs), 8.02-7.85 (3H, m), 7.60-7.44 (7H, m), 7.10 (1H, dd, J=12.0, 2.1 Hz), 6.98 (1H, dd, J=8.4, 2.1 Hz), 5.11 (2H, s), 3.98 (1H, m), 2.30-2.12 (2H, m), 1.91-1.73 (4H, m), 1.71-1.58 (1H, m), 1.45-1.15 (3H, m)














Purity
>90% (NMR)


MS
598 (M + 1)





Example No.
271
1H NMR (δ) ppm














880





300 MHz, DMSO-d6 8.29 (1H, d, J=1.5 Hz), 8.24 (1H, d, J=8.7 Hz), 8.07-7.98 (3H, m), 7.80-7.68 (5H, m), 7.56 (1H, dd, J=8.0, 1.8 Hz), 7.47 (1H, d, J=8.0 Hz), 7.21 (2H, d, J=8.4 Hz), 5.18 (2H, s), 4.34 (1H, m), 3.27 (3H, s), 3.02 (3H, s), 2.98 (3H, s), 2.38-2.18 (2H, m), 2.10-1.95 (2H, m), 1.93-1.79 (2H, m), 1.72-1.59 (1H, m), 1.50-1.19 (3H, m)














Purity
>90% (NMR)


MS
652 (M + 1)





Example No.
272
1H NMR (δ) ppm














881





300 MHz, DMSO-d6 8.97 (1H, d, J=1.8 Hz), 8.85 (1H, d, J=4.7 Hz), 8.46 (1H, d, J=8.0 Hz), 8.39-8.26 (2H, m), 8.06 (1H, d, J=8.7 Hz), 7.99-7.64 (6H, m), 7.24 (2H, d, J=8.7 Hz), 5.25 (2H, s), 4.36 (1H, m), 3.03 (3H, s), 2.97 (3H, s), 2.39-2.19 (2H, m), 2.14-1.96 (2H, m), 1.94-1.78 (2H, m), 1.73-1.60 (1H, m), 1.21-1.55 (3H, m)














Purity
>90% (NMR)


MS
575 (M + 1)










[2052]

193







TABLE 193















Example No.
273
1H NMR (δ) ppm














882





300 MHz, DMSO-d6 8.30 (1H, s), 8.27(1H, d, J=8.7 Hz), 8.05 (1H, d, J=8.7 Hz), 7.77-7.67 (3H, m), 7.58-7.48 (6H, m), 7.22 (2H, d, J=8.4 Hz), 5.18 (2H, s), 4.35 (1H, brt, J=9.8 Hz), 3.06-2.88 (12H, brm), 2.38-2.20 (2H, brm), 2.08-1.96 (2H, brm), 1.90-1.80 (2H, brm), 1.70-1.60 (1H, brm), 1.49-1.22 (3H, brm)














Purity
>90% (NMR)


MS
645 (M + 1)





Example No.
274
1H NMR (δ) ppm














883





300 MHz, DMSO-d6 mixture of cis and trans 8.35, 8.34 (1H, s), 8.15-8.10 (2H, m), 7.79-7.70 (3H, m), 7.49 (2H, d, J=8.7 Hz), 7.44 (2H, d, J=8.7 Hz), 7.31 (1H, d, J=8.4 Hz), 7.25-7.19 (2H, m), 7.07 (1H, d, J=8.5 Hz), 5.08 (2H, s), 4.75 (1H, m), 3.83 (3H, s), 3.70-1.90 (8H, m)














Purity
about 80% (NMR)


MS
601 (M + 1)





Example No.
275
1H NMR (δ) ppm














884





300 MHz, DMSO-d6 8.33 (1H, s), 8.13 (1H, d, J=7.5 Hz), 7.93 (1H, d, J=8.8 Hz), 7.74 (2H, d, J=8.7 Hz), 7.49 (2H, d, J=8.6 Hz), 7.44 (2H, d, J=8.6 Hz), 7.31 (1H, d, J=8.5 Hz), 7.25-7.15 (3H, m), 7.07 (1H, d, J=8.5 Hz), 5.08 (2H, s), 4.98 (1H, m), 3.83 (3H, s), 3.65-3.45 (2H, m), 3.30-3.10 (2H, m), 3.00-2.75 (2H, m), 2.60-2.30 (2H, m)














Purity
>90% (NMR)


MS
617 (M + 1)










[2053]

194







TABLE 194















Example No.
276
1H NMR (δ) ppm














885





300 MHz, DMSO-d6 8.25 (1H, s), 7.93 and 7.87 (2H, ABq, J=9.1 Hz), 7.55 (1H, t, J=8.6 Hz), 7.48 and 7.42 (4H, A′ B′ q, J=8.6 Hz), 7.31 (1H, d, J=8.5 Hz), 7.24 (1H, d, J=2.6 Hz), 7.09-6.95 (3H, m), 5.05 (2H, s), 4.11 (1H, brt, J=14.0 Hz), 3.84 (3H, s), 2.83-2.67 (4H, brm), 2.50-2.32 (2H, brm), 2.21-2.10 (2H, brm)














Purity
>90% (NMR)


MS
603 (M + 1)





Example No.
277
1H NMR (δ) ppm














886





300 MHz, DMSO-d6 cis and trans mixture 8.28 and 8.24 (total 1H, each s), 7.94-7.87 (1H, m), 7.60-7.41 (5H, m), 7.31 (1H, d, J=8.5 Hz), 7.23-7.21 (1H, m), 7.12-7.05 (2H, m), 7.00-6.95 (1H, m), 5.06 and 5.05 (total 2H, each s), 4.47 and 4.34 (total 1H, each brs), 3.83 (3H, s), 3.12-1.76 (8H, m)














Purity
>90% (NMR)


MS
619 (M + 1)





Example No.
278
1H NMR (δ) ppm














887





300 MHz, DMSO-d6 12.9 (1H, brs), 8.27 (1H, s), 7.97 and 7.74 (2H, ABq, J=8.6 Hz), 7.58 (1H, t, J=8.6 Hz), 7.49 and 7.43 (4H, A′ B′ q, J=8.5 Hz), 7.31 (1H, d, J=8.5 Hz), 7.22 (1H, d, J=2.6 Hz), 7.13-6.92 (3H, m), 5.05 (2H, s), 4.67 (1H, brt, J=14.2 Hz), 3.57-3.40 (2H, brm), 3.20-3.05 (2H, brm), 2.91-2.70 (2H, brm), 2.28-2.11 (2H, brm)














Purity
>90% (NMR)


MS
635 (M + 1)










[2054]

195







TABLE 195















Example No.
279
1H NMR (δ) ppm














888





300 MHz, DMSO-d6 8.30 (1H, s), 8.23 (1H, d, J=8.7 Hz), 8.06-8.00 (2H, m), 7.83 (1H, dd, J=8.0, 1.8 Hz), 7.71 (2H, d, J=8.4 Hz), 7.64 (1H, d, J=8.0 Hz), 7.59-7.54 (4H, m), 7.22 (2H, d, J=8.4 Hz), 5.25 (2H, s), 4.33 (1H, m), 2.66 (3H, s), 2.66 (3H, s), 2.37-2.19 (2H, m), 1.93-1.80 (2H, m), 1.70-1.59 (1H, m), 1.47-1.21 (3H, m)














Purity
>90% (NMR)


MS
644 (M + 1)





Example No.
280
1H NMR (δ) ppm














889





300 MHz, DMSO-d6 8.32-8.23 (3H, m), 8.08-8.01 (2H, m), 7.73 (2H, d, J=8.6 Hz), 7.65 (1H, d, J=8.2 Hz), 7.59-7.51 (4H, m), 7.25 (2H, d, J=8.6 Hz), 5.21 (2H, s), 4.34 (1H, m), 3.32 (3H, s), 2.37-2.19 (2H, m), 2.10-1.98 (2H, m), 1.93-1.80 (2H, m), 1.71-1.60 (1H, m), 1.51-1.21 (3H, m)














Purity
>90% (NMR)


MS
615 (M + 1)





Example No.
281
1H NMR (δ) ppm














890





300 MHz, DMSO-d6 8.30 (1H, d, J=1.5 Hz), 8.24 (1H, s), 8.14 (1H, d, J=8.6 Hz), 8.07-7.95 (2H, m), 7.63 (1H, t, J=8.6 Hz), 7.57-7.47 (5H, m), 7.16 (1H, dd, J=12.0, 2.2 Hz), 7.03 (1H, dd, J=8.6, 2.2 Hz), 5.17 (2H, s), 4.06 (1H, m), 3.90 (3H, s), 2.31-2.11 (2H, m), 1.97-1.78 (4H, m), 1.71-1.59 (1H, m), 1.43-1.22 (3H, m)














Purity
>90% (NMR)


MS
315










[2055]

196







TABLE 196















Example No.
282
1H NMR (δ) ppm














891





300 MHz, DMSO-d6 8.36 (1H, s), 8.35 (1H, d, J=9.3 Hz), 8.09 (1H, d, J=9.3 Hz), 7.78 (2H, d, J=8.7 Hz), 7.48-7.25 (9H, m), 5.09 (2H, s), 4.39 (1H, m), 3.04 (6H, s), 2.40-2.15 (2H, m), 2.10-1.95 (2H, m), 1.90-1.75 (2H, m), 1.70-1.55 (1H, m), 1.50-1.20 (3H, m)














Purity
>90% (NMR)


MS
580 (M + 1)





Example No.
283
1H NMR (δ) ppm














892





300 MHz, DMSO-d6 10.03 (1H, s), 8.33 (1H, s), 8.29 (1H, d, J=8.7 Hz), 8.06 (1H, d, J=9.0 Hz), 7.74 (2H, d, J=9.0 Hz), 7.51-7.42 (5H, m), 7.37-7.30 (2H, m), 7.22 (2H, d, J=8.7 Hz), 5.10 (2H, s), 4.37 (1H, m), 3.06 (3H, s), 2.40-2.18 (2H, m), 2.15-1.95 (2H, m), 1.90-1.80 (2H, m), 1.75-1.55 (1H, m), 1.50-1.20 (3H, m)














Purity
>90% (NMR)


MS
630 (M + 1)





Example No.
284
1H NMR (δ) ppm














893





300 MHz, DMSO-d6 8.30 (1H, s), 8.14 (1H, d, J=8.7 Hz), 7.97 (1H, d, J=8.7 Hz), 7.96-7.41 (8H, m), 7.16 (1H, dd, J=12.4, 2.2 Hz), 7.03 (1H, dd, J=8.4, 2.2 Hz), 5.15 (2H, s), 4.15 (1H, m), 3.54-3.16 (4H, m), 2.33-2.13 (2H, m), 1.97-1.79 (4H, m), 1.70-1.02 (9H, m)














Purity
>90% (NMR)


MS
654 (M + 1)










[2056]

197







TABLE 197















Example No.
285
1H NMR (δ) ppm














894





300 MHz, DMSO-d6 8.37 (1H, d, J=7.3 Hz), 8.30 (1H, s), 8.19-8.12 (2H, m), 8.02-7.95 (2H, m), 7.65 (1H, t, J=8.4 Hz), 7.56-7.43 (5H, m), 7.18 (1H, dd, J=12.0, 1.8 Hz), 7.06 (1H, dd, J=8.4, 2.1 Hz), 5.13 (2H, s), 4.22-4.03 (2H, m), 2.34-2.13 (2H, m), 1.99-1.78 (4H, m), 1.72-1.57 (1H, m), 1.44-1.14 (3H, m), 1.20, 1.18 (6H, each s)














Purity
>90% (NMR)


MS
640 (M + 1)





Example No.
286
1H NMR (δ) ppm














895





300 MHz, DMSO-d6 8.29 (1H, s), 8.13 (1H, d, J=8.7 Hz), 7.97 (1H, dd, J=8.7, 1.4 Hz), 7.69-7.40 (8H, m), 7.16 (1H, dd, J=12.0, 2.2 Hz), 7.02 (1H, dd, J=8.4, 2.2 Hz), 5.15 (2H, s), 4.07 (1H, m), 3.71-3.23 (2H, m), 1.98-1.71 (4H, m), 1.71-1.18 (10H, m)














Purity
>90% (NMR)


MS
666 (M + 1)





Example No.
287
1H NMR (δ) ppm














896





300 MHz, DMSO-d6 8.29 (1H, s), 8.13 (1H, d, J=8.0 Hz), 7.97 (1H, d, J=8.4 Hz), 7.83 (1H, s), 7.68-7.41 (7H, m), 7.17 (1H, d, J=12.0 Hz), 7.03 (1H, d, J=8.4 Hz), 5.15 (2H, s), 4.07 (1H, m), 3.58-3.41 (4H, m), 2.34-2.13 (2H, m), 1.97-1.77 (8H, m), 1.71-1.58 (1H, m), 1.49-1.18 (3H, m)














Purity
>90% (NMR)


MS
652 (M + 1)










[2057]

198







TABLE 198















Example No.
288
1H NMR (δ) ppm














897





300 MHz, DMSO-d6 8.62(1N, m), 8.31 (1H, s), 8.22-8.14 (2H, m), 8.99 (2H, d, J=8.7 Hz), 7.66 (1H, t, J=7.7 Hz), 7.58-7.44 (5H, m), 7.19 (1H, dd, J=8.7, 2.2 Hz), 5.14 (2H, s), 4.11 (1H, m), 3.67-3.49 (2H, m), 3.45-3.30 (2H, m), 2.37-2.12 (2H, m), 2.00-1.76 (4H, m), 1.70-1.58 (1H, m), 1.48-1.17 (3H, m)














Purity
>90% (NMR)


MS
642 (M + 1)





Example No.
289
1H NMR (δ) ppm














898





400 MHz, DMSO-d6 8.28 (1H, s), 8.11 (1H, d, J=8.9 Hz), 7.96 (1H, d, J=8.9 Hz), 7.68 (1H, s), 7.62 (1H, t, J=8.2 Hz), 7.55-7.41 (6H, m), 7.15 (1H, d, J=11.7 Hz), 7.02 (1H, d, J=8.4 Hz), 5.14 (2H, s), 4.12-3.13 (6H, m), 2.30-1.19 (13H, m)














Purity
>90% (NMR)


MS
682 (M + 1)





Example No.
290
1H NMR (δ) ppm














899





400 MHz, DMSO-d6 8.29 (1H, s), 8.15 (1H, d, J=8.6 Hz), 7.98 (1H, d, J=8.8 Hz), 7.72 (1H, s), 7.64 (1H, t, J=8.8 Hz), 7.57-7.43 (6H, m), 7.18 (1H, dd, J=12.1, 2.1 Hz), 7.03 (1H, d, J=10.7 Hz), 5.12 (2H, s), 4.15-4.01 (1H, m), 3.75-3.33 (8H, m), 2.31-2.14 (2H, m), 1.96-1.78 (4H, m), 1.70-1.58 (1H, m), 1.47-1.21 (3H, m)














Purity
>90% (NMR)


MS
668 (M + 1)










[2058]

199







TABLE 199















Example No.
291
1H NMR (δ) ppm














900





400 MHz,DMSO-d6 8.29 (1H, s), 8.14 (1H, d, J=8.9 Hz), 7.97 (1H, d, J=8.6 Hz), 7.71 (1H, s), 7.63 (1H, t, J=8.2 Hz), 7.56-7.42 (6H, m), 7.17 (1H, d, J=12.3 Hz), 7.03 (1H, d, J=10.7 Hz), 5.14 (2H, s), 4.07 (1H, m), 3.96-3.52 (4H, m), 2.79-2.56 (4H, m), 2.32-2.14 (2H, m), 1.97-1.79 (4H, m), 1.71-1.58 (1H, m), 1.51-1.19 (3H, m)














Purity
>90% (NMR)


MS
684 (M + 1)





Example No.
292
1H NMR (δ) ppm














901





300 MHz, DMSO-d6 9.07-8.99 (1H, m), 8.30 (1H, s), 8.23-8.12 (2H, m), 8.04-7.95 (2H, m), 7.65 (1H, t, J=8.2 Hz), 7.60-7.45 (5H, m), 7.19 (1H, dd, J=12.0, 2.6 Hz), 7.06 (1H, dd, J=8.6, 2.2 Hz), 5.16 (2H, s), 4.18-4.02 (1H, m), 3.97 (2H, d, J=6.0 Hz), 2.33-2.14 (2H, m), 1.99-1.79 (4H, m), 1.72-1.59 (1H, m), 1.45-1.19 (3H, m)














Purity
>90% (NMR)


MS
656 (M + 1)





Example No.
293
1H NMR (δ) ppm














902





300 MHz, DMSO-d6: 8.21 (1H, s), 7.94 and 7.86 (2H, ABq, J=8.6 Hz), 7.72 (1H, d, J=2.4 Hz), 7.59 and 7.11 (4H, A′ B′ q, J=8.9 Hz), 7.53 (1H, dd, J=8.4, 2.4 Hz), 7.38 (1H, d, J=8.4 Hz), 7.36 and 7.32 (4H, A″B″q, J=8.1 Hz), 5.07 (2H, s), 4.27 (1H, brt, J=13.8 Hz), 2.87 (2H, t, J=7.8 Hz), 2.57 (2H, t, J=7.8 Hz), 2.35-2.20 (2H, brm), 1.96-1.79 (4H, brm),


# 1.68-1.59 (1H, brm), 1.47-1.18 (3H, brm)














Purity
>90% (NMR),


MS
637 (M + 1)










[2059]

200







TABLE 200















Example No.
294
1H NMR (δ) ppm














903





300 MHz, DMSO-d6 8.30 (1H, s), 8.25 and 8.03 (2H, ABq, J=8.9 Hz), 7.73 (1H, s), 7.73 (2H, d, J=8.6 Hz), 7.55 (1H, dd, J=8.0, 2.3 Hz), 7.40 (4H, s), 7.39 (1H, d, J=8.0 Hz), 7.23 (2H, d, J=8.6 Hz), 5.11 (2H, s), 4.55 (2H, s), 4.36 (1H, brt, J=14.8 Hz), 2.37-2.19 (2H, brm), 2.09-1.96 (2H, brm), 1.91-1.79 (2H, brm), 1.71-1.59 (1H, brm), 1.50-1.20 (3H, brm)














Purity
>90% (NMR)


MS
567 (M + 1)





Example No.
295
1H NMR (δ) ppm














904





300 MHz, DMSO-d6 8.30 (1H, s), 8.25 and 8.04 (2H, ABq, J=8.7 Hz), 7.74 (1H, s), 7.72 (2H, d, J=8.7 Hz), 7.56 (1H, d, J=8.7 Hz), 7.48-7.35 (5H, m), 7.22 (2H, d, J=8.7 Hz), 5.11 (2H, s), 4.46 (2H, s), 4.35 (1H, brt, J=14.8 Hz), 3.31 (3H, s), 2.37-2.17 (2H, brm), 2.07-1.95 (2H, brm), 1.92-1.79 (2H, brm), 1.73-1.56 (1H, brm), 1.52-1.20 (3H, brm)














Purity
>90% (NMR)


MS
581 (M + 1)





Example No.
296
1H NMR (δ) ppm














905





300 MHz, DMSO-d6 8.21 (1H, d, J=1.5 Hz), 7.98 (1H, d, J=1.2 Hz), 7.97-7.91 (2H, m), 7.84 (1H, dd, J=8.7, 1.5 Hz), 7.77 (1H, d, J=2.1 Hz), 7.70 (1H, d, J=7.5 Hz), 7.60-7.54 (4H, m), 7.43 (1H, d, J=8.4 Hz), 7.09 (2H, d, J=8.7 Hz), 5.05 (2H, s), 4.25 (1H, brt, J=14.8 Hz), 2.36-2.18 (2H, brm), 1.95-1.79 (4H, brm), 1.71-1.6 (1H, brm), 1.43-1.18 (3H, brm)














Purity
>90% (NMR)


MS
581 (M + 1)










[2060]

201







TABLE 201















Example No.
297
1H NMR (δ) ppm














906





300 MHz, DMSO-d6 12.7 (1H, brs), 8.21 (1H, s), 7.94 and 7.85 (2H, ABq, J=8.6 Hz), 7.60-7.55 (3H, m), 7.49 and 7.45 (4H, A′ B′ q, J=8.3 Hz), 7.12 (2H, d, J=8.7 Hz), 5.05 (2H, s), 4.26 (1H, brt, J=13.0 Hz), 2.54 (3H, s), 2.38-2.20 (2H, brm), 1.97-1.80 (4H, brm), 1.71-1.59 (1H, brm), 1.47-1.20 (3H, brm)














Purity
>90% (NMR)


MS
583 (M + 1)





Example No.
298
1H NMR (δ) ppm














907





300 MHz, DMSO-d6 8.22 (1H, s), 8.01 (1H, s), 7.95 and 7.86 (2H, ABq, J=8.6 Hz), 7.79 (1H, d, J=7.8 Hz), 7.58 (3H, t, J=7.5 Hz), 7.53 (4H, s), 7.13 (2H, d, 8.7 Hz), 5.15 (2H, s), 4.26 (1H, brt, J=13.8 Hz), 2.83 (3H, s), 2.37-2.18 (2H, brm), 1.95-1.78 (4H, brm), 1.70-1.59 (1H, brm), 1.47-1.17 (3H, brm)














Purity
>90% (NMR)


MS
599 (M + 1)





Example No.
299
1H NMR (δ) ppm














908





300 MHz, DMSO-d6 8.43-8.16 (3H, m), 8.07-7.94 (2H, m), 7.72 (2H, d, J=8.6 Hz), 7.62-7.49 (5H, m), 7.23 (2H, d, J=8.6 Hz), 5.16 (2H, s), 4.34 (1H, m), 2.39-2.20 (2H, m), 2.10-1.96 (2H, m), 1.93-1.80 (2H, m), 1.71-1.58 (1H, m), 1.49-1.19 (3H, m)

















Purity
>90% (NMR)


MS
562 (M + 1)










[2061]

202







TABLE 202















Example No.
300
1H NMR (δ) ppm














909





300 MHz, DMSO-d6: 2.77(1H, brs), 8.83 (2H, d, J=1.9 Hz), 8.56 (2H, dd, J=4.9, 1.9 Hz), 8.22 (1H, d, J=1.5 Hz), 7.97 (2H, dt, J=7.9, 1.9 Hz), 7.95 (1H, d, J=8.6 Hz), 7.87 (1H, dd, J=8.6, 1.5 Hz), 7.57 (1H, t, J=8.7 Hz), 7.46 (2H, dd, J=7.9, 4.9 Hz), 7.26 (1H, dd, J=12.0, 4.9 Hz), 7.14 (1H, dd, J=8.8, 2.3 Hz), 6.99 (2H, s), 3.94 (1H, brt), 2.26-2.09 (2H, m), 1.87-1.73 (4H, m), 1.67-1.57 (1H,


# m), 1.42-1.12 (3H, m)














Purity
>90% (NMR)


MS
523 (M + 1)





Example No.
301
1H NMR (δ) ppm














910





300 MHz, DMSO-d6 8.22 (1H, s), 7.95(1H, d, J=8.7 Hz), 7.87 (1H, dd, J=1.5 Hz, 9.0 Hz), 7.62 (4H, d, J=8.4 Hz), 7.55 (1H, t, J=9.0 Hz), 7.44 (4H, d, J=8.1 Hz), 7.20 (1H, dd, J=2.1 Hz, 12.0 Hz), 7.11 (1H, dd, J=2.1 Hz, 8.7 Hz), 6.86 (1H, s), 3.94 (1H, m), 2.96, 2.88 (12H, s), 2.35-2.00 (2H, m), 1.95-1.70 (4H, m), 1.65-1.50 (1H, m), 1.45-1.10 (3H, m)














Purity
>90% (NMR)


MS
663 (M + 1)





Example No.
302
1H NMR (δ) ppm














911





300 MHz, DMSO-d6 8.14 (1H, s), 7.88 (1H, d, J=8.4 Hz), 7.68 (1H, d, J=8.7 Hz), 7.64-7.55 (3H, m), 7.50 (1H, t, J=8.7 Hz), 7.22-7.17 (3H, m), 7.11 (1H, s), 7.08-7.00 (2H, m), 3.90 (1H, m), 2.15-2.00 (2H, m), 1.95-1.50 (5H, m), 1.45-1.00 (3H, m)














Purity
>90% (NMR)


MS
532 (M + 1)










[2062]

203






TABLE 203










Example No. 303
1HNMR(δ)ppm




912





300MHz, CDCl3 8.49(1H, s), 7.98(1H, dd, J=8.6, 1.5Hz), 7.71(1H, d, J=1 .8Hz), 7.66(1H, d, J=8.6Hz), 7.55-7.29 (7H, m), 6.80(1H, dd, J=8.2, 2.2Hz), 6.69(1H, dd, J=11.2, 2.211z), 4.99(2 H, s), 4.10-3.92(1H, m), 3.9 5(3H, s), 3.15(3H, s), 3.06 (3H, s), 2.31-2.14(2H, m), 2.04-1.86(4H, m), 1.81-1.71


# 1H, m), 1.41-1.21(3H, m)


Purity > 90% (NMR)


MS 640(M + 1)





Example No. 304
1HNMR(δ) ppm




913





300MHz, DMSO-d6 8.21(1H, s), 7.94(1H,d,J=8.7 7Hz), 7.84(1H, d, J=9.1Hz), 7.70(1H, s), 7.26-7.39(9H, m), 7.11(2H, d, J=8.4Hz), 5.11(2H, s), 4.26(1H, m), 3.01 (3H, s), 2.97(3H, s), 2.38-2.19(2H, m), 1.97-1.78(4H, m), 1.72-1.57(1H, m), 1.48-1.17(3H, m)


Purity > 90%(NMR)


MS 608(M + 1)





Example No. 305
1HNMR(δ) ppm




914





300MHz, DMSO-d6 8.24(2H. s), 8.03(1H, d, J=8.0Hz), 7.96(1H, d, J=8.8Hz), 7.87(1H, d, J=9.1Hz), 7.60-7.46(6H, m), 7.09(1H, dd, J=12.0, 1.8Hz), 6.97(1H, dd, J=8.4, 1.8Hz), 5.16(2H, s), 3.97(1H, m), 2.31-2.11(2H, m), 1.92-1.73(4H, m), 1.70-1.57(1H, m), 1.46-1.13(3H, m)


Purity > 90% (NMR)


MS 599 (M + 1)










[2063]

204






TABLE 204










Example No. 306
1HNMR(δ) ppm




915





3H300MHz, DMSO-d6 12.84(1H, brs), 8.21(1H, s), 7.98-7.84(5H, m), 7.58(2H, d, J=8.7Hz), 7.54(2H, d, J=7.8Hz), 7.34(1H, , d, J=8.7H z), 7.26(1H, d, J=2.4Hz), 7.13-7.06(3H, m), 5.06(2H, s), 4.26(1H, brt, J=12.7Hz), 3.84(3H, s), 2.36-2.17(2H, b rm), 1.99-1.80(4H, brm), 1.73-1.59(1H, brm), 1.47-


#1.17(3H, brm)


Purity >90% (NMR)


MS 577 (M+1)





Example No. 307
1HNMR(δ) ppm




916





3H300MHz, DMSO-d6 8.22(1H, s), 8.04(1H, s), 7.96(2H, d, J=8.1Hz), 7.87(2H, s), 7.72(1H, d, J=1.2Hz), 7.59-7.41(7H, m), 5.12(2H, s), 4.25(1H, brt, J=11.8Hz), 3.02(3H, brs), 2.98(3H, brs), 2.38-2.15(2H, brm), 1.93-1.76(4H, brm),1.71-1.59 (1H, brm), 1.46-1.16(3H, brm)


Purity >90% (NMR)


MS 617(M+1)





Example No. 308
1HNMR(δ) ppm




917





3H300MHz, DMSO-d6 8.27(1H, s), 8.08(1H, d, J=9.0 Hz), 7.93(1H, d, J=8.7Hz), 7.65(2H, d, J=8.7Hz), 7.46 (2H, d, J=8.1Hz), 7.42(2H, d, J=8.4Hz), 7.30-7.04(5H, m), 5.03(2H, s) 4.32(1H m), 2.40-2.10(2H, m), 2.05-1.10 (8H, m)


Purity >90% (NMR)


MS 552 (M+1)










[2064]

205






TABLE 205










Example No. 309
1HNMR(δ)ppm




918





300MHz, DMSO-d6 8.33(1H, s), 8.15 and 7.99 (2H, ABq, J=8.9Hz), 7.84 and 7.59(4H, A′ B′ q, J=8.3Hz), 7.46 (2H, d, J=8.4Hz), 7.22-7.16 (3H, m), 7.01-6.98(2H, m), 4.27 and 4.23(2H, A″B″q, J=1 2.9Hz), 3.78(3H, s), 2.39-2.21(2H, brm), 2.07-1.95(2H, brm), 1.91-1.80(2H, brm),


# 1.72-1.59(1H, brm), 1.49-1.17(3H, brm)


Purity >90% (NMR)


MS





Example No. 310
1HNMR(δ)ppm




919





300MHz, DMSO-d6 8.33(1H, s), 8.09 and 7.95 (2H, ABq, J=8.7Hz), 7.87 and 7.71(4H, A′ B′ q, J=8.0Hz), 7.43(2H, d, J=7.8Hz), 7.15(1H, d, J=8.7Hz), 7.07-7.02(4H, m), 4.66(2H, s), 4.23(1H, br t, J=11.8Hz), 3.76(3H, s), 2.38-2.20(2H, brm), 2.04-1.93(2H, brm), 1.89-1.79(2H,


# brm), 1.70-1.59(1H, brm), 1.49-1.18(3H, brm)


Purity > 90% (NMR)


MS 615(M +1)





Example No. 311
1HNMR(δ) ppm




920





300MHz, DMSO-d6 8.30(1H, s), 8.21 and 8.01(2H, ABq, J=8.7Hz), 7.65(2H, d, J=8.4Hz), 7.52-7.41(6H, m), 7.20(1H, d, J=8.4Hz), 7.14 (1H, d, J=2.7Hz), 6.97(1H, dd, J=8.4, 2.4Hz), 4.31(1H, brt, J=9.8Hz), 4.28(2H, s), 3.78(3H, s), 2.37-2.20(2H, brm), 2.07-1.95(2H, brm), 1.92-1.80(2H, brm), 1.71-


# 1.60(1H, brm), 1.50-1.19(3H, brm)


MS 583(M +1)










[2065]

206






TABLE 206










Example No. 312
1HNMR(δ)ppm




921





J=8300MHz, DMSO-d6 8.22(1H, s), 8.12(1H, d, J=8.4Hz), 8.00-7.84(5H, m), 7.70(4H, d, J=8.4Hz), 7.56(1H, t, J=8.6Hz),7.23(1H, d, J=12.0Hz), 7.13(1H, d, J=8.6Hz), 6.97(1H, s), 3.92(1H, m), 2.35-2.00(2H, m), 1.95-1.70(4H, m), 1.65-1.55(1H, m), 1.50-1.05(3H, m)


Purity >90% (NMR)


MS 609(M+1)





Example No. 313
1HNMR(δ)ppm




922





J=8300MHz, DMSO-d6 8.89(1H, brs), 8.63(1H, brs), 8.24(1H, s), 8.11(1H, d, J=7.8Hz), 7.99(1H, d, J=8.8Hz), 7.89(1H, d, J=9.9Hz), 7.61-7.55(4H, m), 7.43(2H, t, J=7.7Hz), 7.34(1H, t, J=7.2 Hz), 7.24(1H, d, J=12.0Hz), 7.14(1H, d, J=8.6Hz), 6.95 (1H, s), 3.96(1H, m), 2.35-2.05(2H, m), 2.00-1.50(5H, m),


# 1.45-1.10(3H, m)


Purity >90% (NMR)


MS 522 (M+1)





Example No. 314
1HNMR(δ)ppm




923





J=8300MHz, CDCl3 8.48(1H, d, J=1.4Hz), 8.05 (1H, d, J=1.8Hz), 8.98(1H, d, J=8.6Hz), 7.82(1H, d, J=7.9 Hz), 7.66(1H, d, J=8.6Hz), 7.55-7.24(6H, m), 6.78(1H, dd, J=8.6, 2.6Hz), 6.69(1H, dd J=11.6Hz), 2.2Hz), 6.40-6.30(1H, m), 4.99(2H, s), 4.02(1H, m), 3.95(3H, s), 3.05 (3H, d, J=4.8Hz), 2.32-2.13


# (2H, m), 2.03-1.87(4H, m), 1.81-1.71(1H, m), 1.46-1.23 (3H, m)


Purity > 90% (NMR)


MS 626(M+1)










[2066]

207






TABLE 207










Example No. 503
1HNMR(δ)ppm




924





300MHz, DMSO-d6 8.23(1H, s), 7.76(1H, d, J=8.7 Hz), 7.58(1H, d, J=8.8Hz), 7.51-7.32(7H, m), 7.17(2H, d, J=8.7Hz), 6.55(1H, s), 5.18(2H, s), 4.75(1H, m), 2.35 2.12(2H, m), 2.10-1.85 (4H, m), 1.80-1.50(2H, m)


Purity >90% (NMR)


MS 412(M+1)





Example No. 701
1HNMR(δ)ppm




925





300MHz, DMSO-d6 8.96(1H, s), 8.50(1H, s), 7.77(2H, d, J=8.7Hz), 7.50-7.40(4H, m), 7.30(1H, d, J=8.4 Hz), 7.24(1H, d, J=2.4Hz), 7.16(2H, d, J=8.4Hz), 7.06(1H, dd, J=2.4Hz, 8.1Hz), 5.06 (2H, s), 4.31(1H, s), 3.83(3H, s), 2.80-2.55(2H, m), 2.00-1.80(4H, m), 1.70-1.55(1H, m), 1.40-1.15(3H, m)


Purity > 90% (NMR)


MS 568(M+1)










[2067]

208






TABLE 208










Example No. 315
1HNMR(δ) ppm




926





m)300MHz, DMSO-d6 8.84(2H, d, J=6.3Hz), 8.28(1H, s), 8.17 and 7.99(2H, ABq, J=8.7Hz), 7.87-7.85(3H, m), 7.70-7.50(3H, m), 7.52(1H, d, J=8.3 Hz), 7.18(2H, d, J=8.7Hz), 5.22(2H, s)4.31(1H, br t, J=12.5Hz), 2.36-2.18(2H, m), 2.03-1.78(4H, m), 1.70-1.58(1H, m), 1.50-1.23(3H, m)


Purity >90% (NMR)


MS 538 (M+1)





Example No. 316
1HNMR(δ) ppm




927





m)300MHz, DMSO-d6 9.23(1H, t, J=6.3Hz), 8.29(1H, s), 8.25-8.22(2H, m), 8.03(2H, d, J=7.9Hz), 7.55-7.48(5H, m) 7.34(4H, d, J=4.4Hz), 7.28-7.22 (3H, m), 5.15(2H, s), 4.52(2H, d, J=5.9Hz), 4.35(1H,br t, J=12.1Hz), 2.37-2.18(2H, m), 2.08-1.95(2H, m), 1.91-1.79 (2H, m), 1.72-1.59(1H, m), 1.47-1.19(3H,


# m)


Purity >90% (NMR)


MS 670(M+1)





Example No. 317
1HNMR(δ) ppm




928





m)300MHz, DMSO-d6 8.59(1H, t, J=5.5Hz), 8.28(1H, s), 8.21 and 8.01(2H, ABq, J=8.8 Hz), 8.16(1H, s), 7.97 and 7.46 (2H, A′B′q, J=8.0Hz), 7.71 and 7.23(4H, A″B″q, J=8.7Hz), 7.53 and 7.49(4H, A″′B″′q, J=9.2Hz), 5.14(2H, s), 4.34(1H,br Hz), 2.38-2.18(2H, m), 2.07-


# 1.78(4H, m), 1.78-1.47(7H, m), 1.47-1.07(6H, m), 1.03-0.83(2H, m)


Purity > 90% (NMR)


MS 676(M+1)










[2068]

209






TABLE 209










Example No. 318
1HNMR(δ) ppm




929





300MHz, DMSO-d6 9.63 (1H, t, J=4.8Hz), 8.86 and 7.97 (4H, ABq, J=6.6Hz), 8.30(1H, s), 8.27(1H, s), 8.23 and 8.03(2H, A′B′ q, J=8.8Hz), 8.09 and 7.54 (2H, A″B″q, J=8.1Hz), 7.73 and 7.24(4H, A″′B″′q, J=8.8Hz), 7.54 and 7. 52(4H, A″″B″″q, J=8.8Hz), 5.16(2H, s)4.78(2H, d, J=5.6Hz),


# 4.35(1H, br t, J=11.0Hz), 2.39-2.19(2H, m), 2.07-1.96(2H, m), 1.91-1.78 (2H, m), 1.70-1.57(1H, m)1.50-1.19(3H, m)


Purity > 90% (NMR)


MS 671(M+1)





Example No. 319
1HNMR(δ) ppm




930





300MHz, DMSO-d6 8.28(1H, s), 8.24 and 8.03(2H, A Bq, J=9.0Hz), 7.77(1H, s), 7.70 (2H, d, J=8.4Hz), 7.64-7.10 (13H, m), 5.16(2H, s), 4.74 and 4.57 (total 2H, each br s), 4.34(1H, br t, J=11.7Hz), 2.90(3H, s), 2.35-2.17(2H, m), 2.07-1.93(2H, m), 1.93-1.78(2H, m), 1.71-1.57 (1H, m), 1.51-1.19(3H, m)


Purity > 90% (NMR)


MS 684(M+1)





Example No. 320
1HNMR(δ) ppm




931





300MHz, DMSO-d6 8.94 and 8.06(4H, ABq, J=6.8Hz) 8.33(1H, s), 8.28 and 8.05(2H, A′B′q, J=8.7Hz), 7.80(1H, s), 7.73 and 7.22(4H, A″B″q, J=8.7Hz), 7.63 and 7.57(2H, A″′B″′q, J=7.9Hz), 5.30(2H, s), 4.34(1H, br t, J=12.1Hz), 3.04(3H, s), 2.97 (3H, s),2.38-2.18(2H, m), 2.10-1.96(2H, m). 1.93-1.80(2H. m),


# 1.72-1.58(1H, m), 1.52-1.08 (3H, m)


Purity > 90% (NMR)


MS 575(M+1)










[2069]

210






TABLE 210










Example No. 321
1HNMR(δ) ppm




932





H,300MHz, DMSO-d6 11.19(1H, br s), 8.31(1H, s), 8.23 and 8.02 (2H, ABq, J=9.0Hz), 7.77(1H, s), 7.72 and 7.23(4H, A′B′q, J=8.7Hz), 7.59 and 7.48(2H, A″B″q, J=7.9Hz), 7.53 and 7.51(4H, A″′B″′q, J=9.0Hz), 5.16(2H, s), 4.72-2.97(8H, br m), 4.34(1H, br t, J=12.1Hz), 2.79(3H, s), 2.38-


# 2.17(2H, m), 2.07-1.93(2H,m), 1.93-1.78(2H, m), 1.69-1.58 (1H, m), 1.50-1.10(3H, m)


Purity > 90% (NMR)


MS 663 (M+1)





Example No. 322
1 NMR(δ) ppm




933





H,300MHz, DMSO-d6 9.64(1H, t, J=5.7Hz), 8.91(1H, s), 8.81(1H, d, J=4.9Hz), 8.48(1H, d, J=7.9Hz), 8.32(1H, s), 8.27(1H, d, J=9.0Hz), 8.25(1H, s), 8.07-7.97(3H, m), 7.74 and 7.25 (4H, ABq, J=8.9Hz), 7.56-7.49 (5H, m) , 5.16(2H, s), 4.69(2H, d, J=5.6Hz), 4.36(1H, br t, J=12.4Hz), 2.37-2.20(2H, m), 2.09-1.97(2H, m), 1.91-1.78


# 2H, m) , 1.70-1.57(1H, m), 1.50-1.17(3H, m)


Purity >90% (NMR)


MS 671 (M+1)





Example No. 323
1HNMR(δ) ppm




934





H,300MHz, DMSO-d6 9.52(1H, t, J=6.0Hz), 8.72(1H, d, J=5.3Hz), 8.30-8.19(4H, m), 8. 08(1H, d, J7. 9Hz), 8. 02 (1H, d, J=7.6HZ), 7.77-7.64(4H, m), 7.57-7.49(5H, m), 7.24(2H, d, J=8.7Hz), 5.16(2H, s), 4.77(2H, d, J=5.6Hz), 4.34(1H, t, J=12.8 Hz), 2.36-2.19(2H, m), 2.07-1.95(2H, m), 1.91-1.78(2H, m),


#1.69-1.59(1H, m), 1.45-1.20(3H, m)


Purity >90% (NMR)


MS 671 (M+1)










[2070]

211






TABLE 211










Example No. 324
1HNMR(δ) ppm




935





300MHz, DMSO-d6 8.36(1H, d, J=7.9Hz), 8.30(1H, s), 8.28 and 8.05(2H, ABq, J=8.8Hz), 8.16(1H, s),7.79 and 7.46 (2H, A′B′q, J=8.3Hz), 7.74 and 7.25(4H, A″B″q, J=8.9Hz), 7.52 and 7.50(4H, A″′B″′q, J=8.7Hz), 5.14(2H, s), 4.36(1H, br t, J=12.1Hz), 3.80(1H, br s), 2.39-2.18(2H, m), 2.10-


#1.98(2H, m), 1.93-1.57(8H, m), 1.49-1.04(8H, m)


Purity >90% (NMR).


MS 662(M+1)





Example No. 325
1HNMR(δ) ppm




936





300MHz, DMSO-d6 8.86(1H, t, J=6.0Hz), 8.84 and 8.00(4H, ABq, J=6.6Hz), 8.33(1H, s), 8.27 and 8.04(2H, A′B′q, J=9.0Hz), 8.12(1H, s), 7.92 and 7.46 (2H, A″B″q, J=7.9Hz), 7.74 and 7.23(4H, A″′B″′q, J=9.0Hz), 7.53 and 7.49(4H, A″″B″″q, J=9.1 Hz), 5.13(2H, s), 4.36(1H, br t, J=12.8Hz), 3.70(2H, td, J=


#6.0Hz), 3.21(2H, t, J=6.8Hz), 2.38-2.20(2H, m), 2.09-1.95 (2H, m), 1.91-1.77(2H, m), 1.70-1.59(1H, m), 1.49-1.20(3H, m)


Purity >90% (NMR)


MS 685(M+1)





Example No. 326
1HNMR(δ) ppm




937





300MHz, DMSO-d6 12.80(1H, brs), 8.23(1H, s), 7.90(1H, d, J=8.7Hz), 7.83(1H, d, J=8.7Hz), 7.60-7.50(5H, m), 7.39(2H, d, J=7.8Hz), 7.23-7.10 (3H, m), 7.05(1H, d, J=7.8Hz), 6.85(1H, s), 3.94(1H, s), 2.97, 2.88(6H, s), 2.30-2.10(2H, m), 1.90-1.50(5H, m), 1.40-1.00(3H, m)


Purity >90% (NMR)


MS 610(M+1)










[2071]

212






TABLE 212










Example No. 327
1HNMR(δ) ppm




938





H,300MHz, DMSO-d6 13.20-12.60(2H, brs), 8.23(1H, s), 7.98(2H, d, J=6.6Hz), 7.95 (1H, d, J=8.7Hz), 7.87(1H, d, J=8.7Hz), 7.70-7.50(5H, m), 7.27-7.20(3H, m), 7.08(1H, d, J=7 8 Hz), 6.90(1H, s), 3.93(1H, s), 2.51-2.05(2H, m), 1.90-1.70(4H, m), 1.65-1.55(1H, m), 1.40-1.10(3H, m)


Purity >90% (NMR)


MS 583(M+1)










[2072]

213





TABLE 213















939

















Ex. No.
R
R′





2001
—H
4-(-Me)


2002
—H
3-(—CF3)


2003
5-(—F)
—H


2004
3-(—F)
2-(—F)


2005
3-(—F)
3-(—F)


2006
3-(—F)
4-(—F)


2007
4-(—F)
4-(—F)


2008
5-(—F)
4-(—F)


2009
6-(—F)
4-(—F)


2010
4-(—F)
4-(—Cl)


2011
5-(—F)
4-(—Me)


2012
5-(—F)
4-(—CF3)


2013
5-(—F)
4-(—CO2H)


2014
5-(—F)
4-(—CO2Me)





2015
5-(—F)


940










2016
5-(—F)
4-(—CONH2)


2017
5-(—F)
4-{—CON(Me)2}


2018
5-(—F)
4-(—OMe)


2019
5-(—F)
4-(—SMe)





2020
5-(—F)


941










2021
5-(—F)


942










2022
4-(—Cl)
—H


2023
4-(—Cl)
4-(—F)


2024
4-(—Cl)
4-(—Cl)


2025
4-(—Cl)
4-(—Me)


2026
5-(—Cl)
4-(—CF3)


2027
4-(—Cl)
4-(—CO2H)


2028
5-(—Cl)
4-(—CO2Me)





2029
5-(—Cl)


943










2030
4-(—Cl)
4-(—CONH2)


2031
5-(—Cl)
4-{—CON(Me)2}


2032
5-(—Cl)
3-(—OMe)


2033
4-(—Cl)
4-(—SMe)





2034
5-(—Cl)


944










2035
4-(Cl)


945










2036
5-(—CN)
4-(—F)


2037
4-(—CN)
4-(—Cl)


2038
5-(—NO2)
4-(—F)


2039
4-(—NO2)
4-(—Cl)


2040
5-(—Me)
4-(—CO2H)


2041
5-(—Me)
4-(—CO2Me)





2042
5-(—Me)


946










2043
5-(—CF3)
4-(—CO2H)


2044
5-(—CF3)
4-(—CO2Me)





2045
5-(—CF3)


947










2046
5-(—CO2H)
4-(—F)


2047
4-(—CO2H)
4-(—Cl)


2048
5-(—CO2Me)
4-(—F)


2049
5-(—CO2Me)
4-(—Cl)


2050
5-(—Ac)
4-(—F)


2051
5-(—Ac)
4-(—Cl)





2052


948





—H





2053


949





4-(—F)





2054


950





4-(—Cl)





2055


951





4-(—CN)





2056


952





4-(—NO2)





2057


953





4-(—Me)





2058


954





4-(—CF3)





2059


955





4-(—Ac)





2060


956





4-(—CO2H)





2061


957





4-(—CO2Me)





2063


958





4-(—CONH2)





2064


959





4-{—CON(Me)2}





2065


960





4-{—C(═NH)NH2}





2066


961





4-(—OMe)





2067


962







963










2068


964





4-(—NHMe)





2069


965





4-(—NHAc)





2070


966







967










2071


968





4-(—SMe)





2072


969







970










2073


971







972










2074


973







974










2075


975







976










2076
5-(—CONH2)
—H


2077
5-(—CONH2)
4-(—F)


2078
5-(—CONH2)
2,3,4,5,6-penta-(—F)


2079
5-(—CONH2)
2-(—Cl)


2080
5-(—CONH2)
3-(—Cl)


2081
3-(—CONH2)
2-(—Cl)


2082
3-(—CONH2)
3-(—Cl)


2083
3-(—CONH2)
4-(—Cl)


2084
4-(—CONH2)
2-(—CI)


2085
4-(—CONH2)
3-(—Cl)


2086
4-(—CONH2)
4-(—Cl)


2087
6-(—CONH2)
2-(—Cl)


2088
6-(—CONH2)
3-(—Cl)


2089
6-(—CONH2)
4-(—Cl)


2090
5-CONH2)
3,5-di-(—Cl)


2091
5-(—CONH2)
4-(—CN)


2092
5-(—CONH2)
4-(—NO2)


2093
5-(—CONH2)
4-(—Me)


2094
5-(—CONH2)
2,6-di-(—Me)


2095
5-(—CONH2)
4-(—CF3)


2096
5-(—CONH2)
4-(—Ac)


2097
5-(—CONH2)
4-(—CO2H)


2098
5-(—CONH2)
4-(—CO2Me)





2099
5-(—CONH2)


977










2100
5-(—CONH2)
4-(—CONH2)


2101
5-(—CONH2)
3,5-di-(—CONH2)


2102
5-(—CONH2)
4-{—CON(Me)2}


2103
5-(—CONH2)
4-{—C(═NH)NH2}


2104
5-(—CONH2)
4-(—OMe)


2105
5-(—CONH2)
3,4,5-tri-(—OMe)





2106
5-(—CONH2)


978










2107
5-(—CONH2)
4-(—NHMe)





2108
5-(—CONH2)
4-(—NHAc)





2109
5-(—CONH2)


979










2110
5-(—CONH2)
4-(—SMe)





2111
5-(—CONH2)


980










2112
5-(—CONH2)


981










2113
5-(—CONH2)


982










2114
5-(—CONH2)


983










2115
5-{—CON(Me)2}
—H


2116
5-{—CON(Me)2}
4-(—F)


2117
4-{—CON(Me)2}
4-(—Cl)


2118
5-{—CON(Me)2}
4-(—CN)


2119
5-{CON(Me)2}
4-(—NO2)


2120
5-{—CON(Me)2}
4-(—Me)


2121
4-{—CON(Me)2}
4-(—CF3)


2122
5-{—CON(Me)2}
4-(—Ac)


2123
5-{—CON(Me)2}
4-(—CO2H)


2124
5-{—CON(Me)hd 2}
4-(—CO2Me)





2125
5-{—CON(Me)2}


984










2126
5-{—CON(Me)2}
3-(—CONH2)


2127
4-({—CON(Me)2}
4-{—CON(Me)2}


2128
5-{—CON(Me)2}
4-{—C(═NH)NH2}


2129
5-{—CON(Me)2}
4-(—OMe)





2130
5-{—CON(Me)2{


985










2131
5-{—CON(Me)2}
4-(—NHMe)


2132
5-{CON(Me)2}
4-(—NHAc)





2133
5-{—CON(Me)2}


986










2134
4-{—CON(Me)2}
4-(—SMe)





2135
5-{—CON(Me)2}


987










2136
4-{—CON(Me)2}


988










2137
5-{-CON(Me)2}


989










2138
5-{-CON(Me)2}


990










2139
5-(—OMe)
—H


2140
5-(—OMe)
4-(—F)


2141
3-(—OMe)
4-(—Cl)


2142
4-(OMe)
4-(—Cl)


2143
5-(—OMe)
2-(—Cl)


2144
5-(—OMe)
3-(—Cl)


2145
6-(—OMe)
4-(—Cl)


2146
5-(—OMe)
4-(—CN)


2147
5-(—OMe)
4-(—NO2)


2148
5-(—OMe)
4-(—Me)


2149
5-(—OMe)
4-(—CF3)


2150
5-(—OMe)
4-(—Ac)


2151
4-(—OMe)
4-(—CO2H)


2152
4,5-di-(—OMe)
4-(—CO2H)


2153
5-(—OMe)
4-(—CO2Me)





2154
5-(—OMe)


991










2155
5-(—OMe)
4-(—CONH2)


2156
5-(—OMe)
4-{—CON(Me)2}


2157
5-(—OMe)
4-{—C(═NH)NH2}


2158
5-(—OMe)
4-(—OMe)





2159
5-(—OMe)


992










2160
5-(—OMe)
4-(—NHMe)


2161
5-(—OMe)
4-(—NHAc)





2162
5-(—OMe)


993










2163
5-(—OMe)
4-(—SMe)





2164
5-(—OMe)


994










2165
5-(—OMe)


995










2166
5-(—OMe)


996










2167
5-(—OMe)


997










2168
5-(—NHMe)
4-(—F)


2169
5-(—NHMe)
4-(—Cl)


2170
5-(—NHAc)
4-(—F)


2171
5-(—NHAc)
4-(—Cl)


2172
5-(—NHAc)
4-(—Ac)


2173
5-(—NHAc)
4-(—CONH2)


2174
5-(—NHAc)
4-{—CON(Me)2}





2175


998





4-(—F)





2176


999





4-(—Cl)





2177


1000





4-(—Me)





2178


1001





4-(—CF3)





2179


1002





4-(—CO2H)





2180


1003





4-(—CO2Me)





2181


1004







1005










2182


1006





4-(—SMe)





2183


1007







1008










2184


1009







1010










2185
5-(—SMe)
4-(—F)


2186
4-(—SMe)
4-(—Cl)


2187
5-(—SMe)
4-(—Me)


2188
5-(—SMe)
4-(—CF3)


2189
5-(—SMe)
4-(—Ac)


2190
5-(—SMe)
4-(—CONH2)


2191
5-(—SMe)
4-{—CON(Me)2}





2192


1011





4-(—F)





2193


1012





4-(—Cl)





2194


1013





4-(—Me)





2195


1014





4-(—CF3)





2196


1015





4-(—Ac)





2197


1016





4-(—CONH2)





2198


1017





4-{—CON(Me)2}





2199


1018





4-(—F)





2200


1019





4-(—Cl)





2201


1020





4-(—Me)





2202


1021





4-(—CF3)





2203


1022





4-(—Ac)





2204


1023





4-(—CONH2)





2205


1024





4-{—CON(Me)2}





2206


1025





4-(—F)





2207


1026





4-(—Cl)





2208


1027





2,4-di(—Cl)





2209


1028





4-(—Me)





2210


1029





3-(—CF3)





2211


1030





4-(—CF3)





2212


1031





4-(—CONH2)





2213


1032





4-{—CON(Me)2}





2214


1033





4-(—SMe)





2215


1034







1035










2216


1036







1037










2217


1038





4-(—F)





2218


1039





4-(—Cl)





2219


1040





4-(—Me)





2220


1041





4-(—CF3)





2221


1042





4-(—CONH2)





2222


1043





4-{—CON(Me)2}





2223


1044





4-(—SMe)





2224


1045







1046










2225


1047







1048










2226
5-{—O—(CH2)2—OH}
4-(—Cl)





2227
5-{—O—(CH2)3—OH}
4-(—Cl)





2229


1049





4-(—Cl)





2230


1050





4-(—Cl)





2231


1051





4-(—Cl)





2232


1052





4-(—Cl)





2233


1053





4-(—Cl)





2234


1054





4-(—Cl)





2235


1055





4-(—Cl)





2236


1056





4-(—Cl)





2237


1057





4-(—Cl)





2238


1058





4-(—Cl)





2239


1059





4-(—Cl)





2240


1060





4-(—Cl)





2241


1061





4-(—Cl)





2242


1062





4-(—Cl)





2243


1063





4-(—Cl)





2244


1064





4-(—Cl)





2245


1065





4-(—Cl)





2246


1066





4-(—Cl)





2247


1067





4-(—Cl)





2248


1068





4-(—Cl)





2249


1069





4-(—Cl)





2250


1070





4-(—Cl)





2251


1071





4-(—Cl)





2252


1072





4-(—Cl)





2253


1073





4-(—Cl)





2254


1074





4-(—Cl)










[2073]

214





TABLE 214















1075

















Ex. No.
R
R′





2255
—H
—H


2256
—H
4-(—Me)


2257
—H
3-(—CF3)


2258
5-(—F)
—H


2259
5-(—F)
4-(—F)


2260
5-(—F)
4-(—Cl)


2261
5-(—F)
4-(—Me)


2262
5-(—F)
4-(—CF3)


2263
5-(—F)
4-(—CO2H)


2264
5-(—F)
4-(—CO2Me)





2265
5-(—F)


1076










2266
5-(—F)
4-(—CONH2)


2267
5-(—F)
4-{—CON(Me)2}


2268
5-(—F)
4-(—OMe)


2269
5-(—F)
4-(—SMe)





2270
5-(—F)


1077










2271
5-(—F)


1078










2272
4-(—Cl)
—H


2273
5-(—Cl)
4-(—F)


2274
4-(—Cl)
4-(—Cl)


2275
5-(—Cl)
4-(—Me)


2276
5-(—Cl)
4-(—CF3)


2277
5-(—Cl)
4-(—CO2H)


2278
5-(—Cl)
4-(—CO2Me)





2279
5-(—Cl)


1079










2280
5-(—Cl)
4-(—CONH2)


2281
5-(—Cl)
4-{—CON(Me)2}


2282
5-(—Cl)
4-(—OMe)


2283
5-(—Cl)
4-(—SMe)





2284
5-(—Cl)


1080










2285
5-(—Cl)


1081










2286
5-(—Cl)
4-(—F)


2287
5-(—Cl)
4-(—Cl)


2288
5-(—NO2)
4-(—F)


2289
5-(—NO2)
4-(—Cl)


2290
5-(—Me)
4-(—CO2H)


2291
5-(—Me)
4-(—CO2Me)





2292
5-(—Me)


1082










2293
5-(—CF3)
4-(—CO2H)


2294
5-(CF3)
4-(—CO2Me)





2295
5-(—CF3)


1083










2296
5-(—CO2H)
4-(—F)


2297
4-(—CO2H)
4-(—Cl)


2298
5-(—CO2Me)
4-(—F)


2299
5-(—CO2Me)
4-(—Cl)


2300
5-(—Ac)
4-(—F)


2301
5-(—Ac)
4-(—Cl)





2302


1084





—H





2303


1085





4-(—F)





2304


1086





4-(—Cl)





2305


1087





4-(—CN)





2306


1088





4-(—NO2)





2307


1089





4-(—Me)





2308


1090





4-(—CF3)





2309


1091





4-(—Ac)





2310


1092





4-(—CO2H)





2311


1093





4-(—CO2Me)





2312


1094







1095










2313


1096





4-(—CONH2)





2314


1097





4-{{—CON(Me)256





2315


1098





4-{—C(═NH)NH2}





2316


1099





4-(—OMe)





2317


1100







1101










2318


1102





4-(—NHMe)





2319


1103





4-(—NHAc)





2320


1104







1105










2321


1106





4-(—SMe)





2322


1107







1108










2323


1109







1110










2324


1111







1112










2325


1113







1114










2326
5-(—CONH2)
—H





2327
5-(—CONH2)
4-(—F)


2328
5-(—CONH2)
4-(—Cl)


2329
5-(—CONH2)
4-(—CN)


2330
5-(—CONH2)
4-(—NO2)


2331
5-(—CONH2)
4-(—Me)


2332
5-(—CONH2)
4-(—CF3)


2333
5-(—CONH2)
4-(—Ac)


2334
5-(—CONH2)
4-(—CO2H)


2335
5-(—CONH2)
4-(—CO2Me)





2336
5-(—CONH2)


1115










2337
5-(—CONH2)
4-(—CONH2)


2338
5-(—CONH2)
4-{—CON(Me)2}


2339
5-(—CONH2)
4-{—C(═NH)NH2}


2340
5-(—CONH2)
4-(—OMe)





2341
5-(—CONH2)


1116










2342
5-(—CONH2)
4-(—NHMe)


2343
5-(—CONH2)
4-(—NHAc)





2344
5-(—CONH2)


1117










2345
5-(—CONH2)
4-(—SMe)





2346
5-(—CONH2)


1118










2347
5-(—CONH2)


1119










2348
5-(—CONH2)


1120










2349
5-(—CONH2)


1121










2350
5-{—CON(Me)2}
—H


2351
5-{—CON(Me)2}
4-(—F)


2352
4-{—CON(Me)2}
4-(Cl)


2353
5-{—CON(Me)2}
4-(—CN)


2354
5-{—CON(Me)2}
4-(—NO2)


2355
5-{—CON(Me)2}
4-(—Me)


2356
5-{—CON(Me)2}
4-(—CF3)


2357
5-{—CON(Me)2}
4-(—Ac)


2358
5-{—CON(Me)2}
4-(—CO2H)


2359
5-{—CON(Me)2}
4-(—CO2Me)





2360
5-(—CON(Me)2}


1122










2361
5-{—CON(Me)2}
4-(—CONH2)


2362
5-{—CON(Me)2}
4-{—CON(Me)2}


2363
5-{—CON(Me)2}
4-{—C(═NH)NH2}


2364
5-{—CON(Me)2}
4-(—OMe)





2365
5-{—CON(Me)2}


1123










2366
5-{—CON(Me)2}
4-(—NHMe)


2367
5-{—CON(Me)2}
4-(—NHAc)





2368
5-{—CON(Me)2}


1124










2369
5-{—CON(Me)2}
4-(—SMe)





2370
5-{—CON(Me)2}


1125










2371
5-{—CON(Me)2}


1126










2372
5-{—CON(Me)2}


1127










2373
5{CON(Me)2}


1128










2374
5-(—OMe)
—H


2375
5-(—OMe)
4-(—F)


2376
5-(—OMe)
4-(—Cl)


2377
5-(—OMe)
4-(—CN)


2378
5-(—OMe)
4-(—NO2)


2379
5-(—OMe)
4-(—Me)


2380
5-(—OMe)
4-(—CF3)


2381
5-(—OMe)
4-(—Ac)


2382
5-(—OMe)
4-(—CO2H)


2383
5-(—OMe)
4-(—CO2Me)





2384
5-(—OMe)


1129










2385
5-(—OMe)
4-(—CONH2)


2386
5-(—OMe)
4-{—CON(Me)2}


2387
5-(—OMe)
4-{—C(═NH)NH2}


2388
5-(—OMe)
4-(—OMe)





2389
5-(—OMe)


1130










2390
5-(—OMe)
4-(—NHMe)


2391
5-(—OMe)
4-(—NHAc)





2392
5-(—OMe)


1131










2393
5-(—OMe)
4-(—SMe)





2394
5-(—OMe)


1132










2395
5-(—OMe)


1133










2396
5-(—OMe)


1134










2397
5-(—OMe)


1135










2398
5-(—NHMe)
4-(—F)


2399
5-(—NHMe)
4-(—Cl)


2400
5-(—NHAc)
4-(—F)


2401
5-(—NHAc)
4-(—Cl)


2402
5-(—NHAc)
4-(—Ac)


2403
5-(—NHAc)
4-(—CONH2)


2404
5-(—NHAc)
4-{—CON(Me)2}





2405


1136





4-(—F)





2406


1137





4-(—Cl)





2407


1138





4-(—Me)





2408


1139





4-(—CF3)





2409


1140





4-(—CO2H)





2410


1141





4-(—CO2Me)





2411


1142







1143










2412


1144





4-(—SMe)





2413


1145







1146










2414


1147







1148










2415
5-(—SMe)
4-(—F)


2416
5-(—SMe)
4-(—Cl)


2417
5-(—SMe)
4-(—Me)


2418
5-(—SMe)
4-(—CF3)


2419
5-(—SMe)
4-(—Ac)


2420
5-(—SMe)
4-(—CONH2)


2421
5-(—SMe)
4-{—CON(Me)2}





2422


1149





4-(—F)





2423


1150





4-(—Cl)





2424


1151





4-(—Me)





2426


1152





4-(—Ac)





2427


1153





4-(—CONH2)





2428


1154





4-{—CON(Me)2}





2429


1155





4-(—F)





2430


1156





4-(—Cl)





2431


1157





4-(—Me)





2432


1158





4-(—CF3)





2433


1159





4-(—Ac)





2434


1160





4-(—CONH2)





2435


1161





4-{—CON(Me)2}





2436


1162





4-(—F)





2437


1163





4-(—Cl)





2438


1164





4-(—Me)





2439


1165





4-(—CF3)





2440


1166





4-(—CONH2)





2441


1167





4-{-CON(Me)2}





2442


1168





4-(—SMe)





2443


1169







1170










2444


1171







1172










2445


1173





4-(—F)





2446


1174





4-(—Cl)





2447


1175





4-(—Me)





2448


1176





4-(—CF3)





2449


1177





4-(—CONH2)





2450


1178





4-{—CON(Me)2}





2451


1179





4-(—SMe)





2452


1180







1181










2453


1182







1183















[2074]

215





TABLE 215















1184

















Ex. No.
R
R′





2454
2-(—F)
2-(—F)


2455
2-(—F)
3-(—F)


2456
2-(—F)
4-(—F)


2457
3-(—Cl)
3-(—Cl)


2458
3,5-di-(—Cl)
3,5-di-(—Cl)


2459
3-(—CN)
3-(—CN)


2460
3-(—NO2)
3-(—NO2)


2461
3-(—Me)
3-(—Me)


2462
3-(—CF3)
3-(—CF3)


2463
3-(—Ac)
3-(—Ac)


2464
3-(—CO2H)
3-(—CO2H)


2465
3-(—CO2Me)
3-(—CO2Me)





2466


1185







1186










2467
3-(—CONH2)
3-(—CONH2)


2468
3-(—CONH2)
3-(—F)


2469
3-(—CONH2)
3-(—Cl)


2470
3-(—CON(Me)2}
3-{-CON(Me)2}


2471
3-{—CON(Me)2}
3-(—F)


2472
3-(—CON(Me)2}
3-(—Cl)


2473
3-{—C(═NH)NH2}
3-{—C(═NH)NH2}


2474
3-(—OMe)
3-(—OMe)





2475


1187







1188










2476
3-(—NHMe)
3-(—NHMe)


2477
3-(—NHAc)
3-(—NHAc)





2478


1189







1190










2479
3-(—SMe)
3-(—SMe)





2480


1191







1192










2481


1193







1194










2482


1195







1196










2483


1197







1198










2484
3-(—F)
4-(—F)


2485
3-(—Cl)
4-(—Cl)


2486
4-(—CN)
4-(—CN)


2487
4-(—NO2)
4-(—NO2)


2488
3-(—Me)
4-(—Me)


2489
4-(—Me)
2,6-di-(—Me)


2490
4-(—CF3)
4-(—CF3)


2491
4-(—Ac)
4-(—Ac)


2492
4-(—CO2H)
4-(—CO2H)


2493
4-(—CO2Me)
4-(—CO2Me)





2494


1199







1200










2495
4-(—CONH2)
4-(—CONH2)


2496
4-(—CONH2)
4-(—F)


2497
4-(—CONH2)
2,3,4,5,6-penta-(—F)


2498
4-(—CONH2)
4-(—Cl)


2499
4-{—CON(Me)2}
4-{—CON(Me)2}


2500
4-{—CON(Me)2}
4-(—F)


2501
4-{—CON(Me)2}
4-(—Cl)


2502
4-{—CON(Me)2}
3,5-di-(—Cl)


2503
4-{—C(═NH)NH2}
4-{—C(═NH)NH2}


2504
4-(—OMe)
4-(—OMe)


2505
4-(—OMe)
3,4,5-tri-(—OMe)





2506


1201







1202










2507
4-(—NHMe)
4-(—NHMe)


2508
4-(—NHAc)
4-(—NHAc)





2509


1203







1204










2510
4-(—SMe)
4-(—SMe)





2511


1205







1206










2512


1207







1208










2513


1209







1210










2514


1211







1212















[2075]

216





TABLE 216















1213

















Ex. No.
R
R′





2515
—H
—H


2516
2-(—F)
3-(—F)


2517
3-(—Cl)
3-(—Cl)


2518
3-(—CN)
3-(—CN)


2519
3-(—NO2)
3-(—NO2)


2520
3-(—Me)
3-(—Me)


2521
3-(—CF3)
3-(—CF3)


2522
3-(—Ac)
3-(—Ac)


2523
3-(—CO2H)
3-(—CO2H)


2524
3-(—CO2Me)
3-(—CO2Me)





2525


1214







1215










2526
3-(—CONH2)
3-(—CONH2)


2527
3-(—CONH2)
3-(—F)


2528
3-(—CONH2)
3-(—Cl)


2529
3-{—CON(Me)2}
3-{—CON(Me)2}


2530
3-{—CON(Me)2}
3-(—F)


2531
3-{—CON(Me)2}
3-(—Cl)


2532
3-(—C(═NH)NH2}
3-{—C(═NH)NH2}


2533
3-(—OMe)
3-(—OMe)





2534


1216







1217










2535
3-(—NHMe)
3-(—NHMe)


2536
3-(—NHAc)
3-(—NHAc)





2537


1218







1219










2538
3-(—SMe)
3-(—SMe)





2539


1220







1221










2540


1222







1223










2541


1224







1225










2542


1226







1227










2543
3-(—F)
4-(—F)


2544
4-(—Cl)
4-(—Cl)


2545
4-(—CN)
4-(—CN)


2546
4-(—NO2)
4-(—NO2)


2547
4-(—Me)
4-(—Me)


2548
4-(—CF3)
4-(—CF3)


2549
4-(—Ac)
4-(—Ac)


2550
3-(—CO2H)
4-(—CO2H)


2551
4-(—CO2Me)
4-(—CO2Me)





2552


1228







1229










2553
4(—CONH2)
4-(—CONH2)


2554
4-(—CONH2)
4-(—F)


2555
4-(—CONH2)
4-(—Cl)


2556
3-{—CON(Me)2}
4-{—CON(Me)2}


2557
3-{—CON(Me)2}
4-(—F)


2558
4-{—CON(Me)2}
4-(—Cl)


2559
4-{—C(═NH)NH2}
4-{{C(═NH)NH2}


2560
4-{—OMe)
4-(—OMe)





2561


1230







1231










2562
4-(—NHMe)
4-(—NHMe)


2563
4-(—NHAc)
4-(—NHAc)





2564


1232







1233










2565
4-(—SMe)
4-(—SMe)





2566


1234







1235










2567


1236







1237










2568


1238







1239










2569


1240







1241















[2076]

217





TABLE 217















1242

















Ex. No.
Py
R′





2570
3-Py
—H


2571
3-Py
3-(—F)


2572
3-Py
3-(—Cl)


2573
3-Py
3-(—Me)


2574
3-Py
3-(—CF3)


2575
3-Py
3-(—Ac)


2576
3-Py
3-(—CO2H)


2577
3-Py
3-(—CO2Me)





2578
3-Py


1243










2579
3-Py
3-(—CONH2)


2580
3-Py
3-{—CON(Me)2}


2581
3-Py
4-(—F)


2582
3-Py
4-(—Cl)


2583
3-Py
4-(—Me)


2584
3-Py
4-(—CF3)


2585
3-Py
4-(—Ac)


2586
2-Py
4-(—CO2H)


2587
3-Py
4-(—CO2Me)





2588
3-Py


1244










2589
4-Py
4-(—CONH2)


2590
3-Py
4-{—CON(Me)2}










[2077]

218





TABLE 218















1245












Py: pyridyl group









Ex. No.
Py
R′










2591
3-Py
—H


2592
3-Py
3-(—F)


2593
3-Py
3-(—Cl)


2594
3-Py
3-(—Me)


2595
3-Py
3-(—CF3)


2596
3-Py
3-(—Ac)


2597
3-Py
3-(—CO2H)


2598
3-Py
3-(—CO2Me)





2599
3-Py


1246










2600
3-Py
3-(—CONH2)


2601
3-Py
3-{—CON(Me)2}


2602
3-Py
4-(—F)


2603
3-Py
4-(—Cl)


2604
3-Py
4-(—Me)


2605
3-Py
4-(—CF3)


2606
3-Py
4-(—Ac)


2607
3-Py
4-(—CO2H)


2608
3-Py
4-(—CO2Me)





2609
3-Py


1247










2610
3-Py
4-(—CONH2)


2611
3-Py
4-{—CON(Me)2}










[2078]

219







TABLE 219










Example No.
328
1H NMR(δ) ppm














1248





300MHz, DMSO-d6 8.29(1H, s), 8.23(1H, d, J=9.0Hz), 8.02(1H, d, J=8.4Hz), 7.80(1H, s), 7.71(2H, d, J=8.4Hz),


# 7.61(1H, d, J=9.3Hz), 7.55-7.45(3H, m), 7.46(2H, d, J=8.1Hz), 7.22(2H, d, J=8.7Hz), 5.16(2H, s,), 4.34(1H, m), 4.20-3.40(4H, m), 2.60-2.15(6H, m), 2.10-1.90(2H, m), 1.85-1.70(2H, m), 1.65-1.55(1H, m), 1.50-1.10(3H, m)









Purity
>90% (NMR)



MS
662(M + 1)


Example No.
329
1H NMR(δ) ppm














1249





400MHz, DMSO-d6 9.80(1H, brs), 8.32(1H, s), 8.30(1H, d, J=8.8Hz), 8.06(1H, d, J=8.8Hz), 7.74(2H, d,


# J=8.6Hz), 7.48-7.37(4H, m), 7.22(1H, d, J=8.6Hz), 7.17(1H, d, J=8.2Hz), 7.05(1H, d, J=2.3Hz), 6.88(1H, dd, J=8.3, 2.5Hz), 5.04(2H, s), 4.37(1H, m), 2.37-2.22(2H, m), 2.11-1.98(2H, m), 1.93-1.81(2H, m), 1.70-1.58(1H, m), 1.56-1.22(3H, m)









Purity
>90% (NMR)



MS
553(M + 1)


Example No.
330
1H NMR(δ) ppm














1250





300MHz, DMSO-d6 8.38(1H, d, J=7.5Hz), 8.32(1H, s), 8.29(1H, d, J=9.0Hz), 8.16(1H, s), 8.05(1H, d, J=9.0Hz), 7.96(1H, d, J=7.5Hz), 7.75(2H, d, J=8.4Hz), 7.53-7.43(5H,


# m), 7.25(2H, d, J=8.4Hz), 5.13(2H, s), 4.36(1H, m), 4.12(1H, sept, J=6.9Hz), 2.40-2.15(2H, m), 2.10-1.95(2H, m), 1.90-1.75(2H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m), 1.18(6H, d, J=6.6Hz)









Purity
>90% (NMR)



MS
622(M + 1)










[2079]

220







TABLE 220










Example No.
331
1H NMR(δ) ppm














1251





300MHz, DMSO-d6 8.31(1H, s), 8.27(1H, d, J=8.7Hz), 8.05(1H, d, J=8.7Hz), 7.75-7.41(9H, m), 7.23(2H, d, J=8.7Hz), 4.36(1H, m), 4.00-3.90(1H, m), 2.84(3H, brs), 2.40-2.15(2H, m), 2.10-2.00(2H, m), 1.95-1.75(2H, m), 1.70-1.55(1H, m), 1.50-1.00(7H, m)









Purity
>90% (NMR)



MS
636(M + 1)


Example No.
332
1H NMR(δ) ppm














1252





300MHz, DMSO-d6 10.42(1H, s), 8.29(1H, s), 8.27(1H, s), 8.10(1H, d, J=7.9Hz), 8.03(1H, d, J=8.6Hz), 7.82(2H, d, J=7.5Hz), 7.73(2H, d, J=8.7Hz), 7.56-7.52(5H,


# m), 7.38(2H, t, J=7.9Hz), 7.26(2H, d, J=8.7Hz), 7.13(1H, t, J=7.5Hz), 5.20(2H, s), 4.35(1H, brt, J=11.7Hz), 2.37-2.19(2H, m), 2.07-1.96(2H, m), 1.92-1.79(2H, m), 1.69-1.58(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
656(M + 1)


Example No.
333
1H NMR(δ) ppm














1253





300MHz, DMSO-d6 8.30(1H, s), 8.24 and 8.03(2H, ABq, J=8.8Hz), 7.71 and 7.22(4H, A′ B′ q, J-8.8Hz), 7.69(1H,


# s), 7.52(4H, s), 7.50 and 7.43(2H, A″ B″ q, J=7.7Hz), 5.15(2H, s) 4.35(1H, brt, J=12.1Hz), 4.05-3.15(5H, brm), 3.27(3H, s), 2.39-2.20(2H, m), 2.07-1.75(6H, m), 1.70-1.58(1H, m) 1.55-1.20(5H, m).









Purity
>90% (NMR)



MS
678(M + 1)










[2080]

221







TABLE 221










Example No.
334
1H NMR(δ) ppm














1254





300MHz, DMSO-d6 8.22(1H, d, J=1.5Hz), 8.01(1H, d, J=9.0Hz), 7.89(1H, dd, J=8.6, 1.5Hz), 7.61(2H, d, J=8.6Hz), 7.50-7.39(4H,


# m), 7.27(1H, d, J=8.6Hz), 7.22(1H, d, J=2.6Hz), 7.13(2H, d, J=8.6Hz), 7.04(1H, dd, J=8.2, 2.6Hz), 5.04(2H, s), 4.28(1H, m), 4.11(2H, t, J=6.3Hz), 3.57(2H, t, J=6.3Hz), 2.38-2.17(2H, m), 2.00-1.79(6H, m), 1.70-1.59(1H, m), 1.52-1.16(3H, m)









Purity
>90% (NMR)



MS
611(M + 1)


Example No.
335
1H NMR(δ) ppm














1255





300MHz, DMSO-d6 8.30(1H, d, J=1.5Hz), 8.27(1H, d, J=9.0Hz), 8.04(1H, dd, J=8.6, 1.5Hz), 7.72(2H, d, J=9.0Hz), 7.60-7.40(4H,


# m), 7.32-7.19(4H, m), 7.06(1H, dd, J=8.6, 3.0Hz), 5.08(2H, s), 4.36(1H, m), 4.06(2H, t, J=4.8Hz), 3.74(2H, t, J=4.8Hz), 2.38-2.19(2H, m), 2.13-1.97(2H, m), 1.94-1.78(2H, m), 1.72-1.59(1H, m), 1.52-1.20(3H, m)









Purity
>90% (NMR)



MS
597(M + 1)










[2081]

222










TABLE 222












HCV polymerase

HCV polymerase



Ex.
inhibitory activity
Ex.
inhibitory activity



No.
IC50 [μM]
No.
IC50 [μM]





















340
0.017
360
0.014



341
0.025
361
0.028



342
0.015
362
0.020



343
0.017
363
0.11



344
0.016
364
0.12



345
0.012
365
0.020



346
0.025
366
0.024



347
0.022
367
0.011



348
0.013
368
0.024



349
0.021
369
0.022



350
0.020
370
0.017



351
0.019
371
0.015



352
0.013
372
0.033



353
0.023
373
0.013



354
0.013
374
0.013



355
0.015
375
0.012



356
0.016
376
0.014



357
0.019
377
0.012



358
0.017
378
0.018



359
0.015
379
0.021











[2082]

223










TABLE 223












HCV polymerase

HCV polymerase



Ex.
inhibitory activity
Ex.
inhibitory activity



No.
IC50 [μM]
No.
IC50 [μM]









380
0.023
409
0.020



381
0.011
410
0.018



382
0.015
411
0.015



383
0.013
412
0.019



384
0.016
413
0.026



385
0.019
414
0.024



386
0.018
415
0.019



387
0.025
416
0.024



388
0.020
417
0.029



389
0.012
418
0.016



390
0.014
419
0.021



391
0.017
420
0.015



392
0.014
421
0.017



393
0.011
422
0.017



394
0.019
423
0.017



395
0.016
424
0.020



396
0.025
425
0.026



397
0.037
426
0.053



398
0.077
427
0.020



399
0.032
428
0.026











[2083]

224










TABLE 224












HCV polymerase

HCV polymerase



Ex.
inhibitory activity
Ex.
inhibitory activity



No.
IC50 [μM]
No.
IC50 [μM]





















429
0.017
442
0.024



430
0.017
443
0.030



431
0.015
445
0.33



432
0.022
446
0.016



433
0.014
502
0.024



434
0.011
503
0.196



435
0.012
601
0.32



436
0.026
701
0.052



440
0.070











[2084]

225







TABLE 225










Example No.
341
1H NMR(δ) ppm














1256





300MHz, DMSO-d6 8.29(1H, d, J=1.5Hz), 8.25(1H, d, J=8.7Hz), 8.03(1H, dd, J=8.7Hz), 7.72 and 7.22(4H, Abq, J=8.8Hz), 7.67(1H, d,


# J=1.5Hz), 7.52(4H, s), 7.49(1H, dd, J=7.9, 1.5Hz), 7.43(1H, d, J=7.9Hz), 4.46(1H, brs), 4.35(1H, brt, J=12.4Hz), 3.62(1H, brs), 3.06(1H, brs), 2.79(1H, brs), 2.38-2.20(2H, brm), 2.08-1.81(4H, brm), 1.77-1.52(4H, brm), 1.46-1.20(3H, brm), 1.19-1.00(2H, brm), 0.94 and 0.92(total 3H, each s)









Purity
>90% (NMR)



MS
662(M + 1)


Example No.
342
1H NMR(δ) ppm














1257





300Mz, DMSO-d6 8.28(1H, d, J=1.5Hz), 8.26(1H, d, J=1.8Hz), 8.19(1H, d, J=8.8Hz), 8.07(1H, dd, J=7.7, 1.8Hz), 8.00(1H, dd, J=8.8, 1.5Hz), 7.70


# and 7.22(4H, Abq, J=8.8Hz), 7.56-7.50(1H, m), 7.56(4H, s), 5.17(2H, s), 4.33(1H, brt, J=12.5Hz), 2.05(3H, s), 2.37-2.20(2H, brm), 2.06-1.80(4H, brm), 1.70-1.60(1H, brm), 1.50-1.20(3H, brm)









Purity
>90% (NMR)



MS
679(M + 1)


Example No.
343
1H NMR(δ) ppm














1258





300MHz, DMSO-d6 8.20(1H, d, J=1.5Hz), 7.93(1H, d, J=8.6Hz), 7.84(1H, dd, J=8.3Hz, 1.5Hz), 7.57(2H, d, J=8.6Hz), 7.50-7.40(4H, m), 7.27(1H,


# d, J=8.2Hz), 7.22(1H, d, J=2.6Hz), 7.10(2H, d, J=8.6Hz) 7.01(1H, dd, J=8.6Hz, 2.6Hz), 5.02(2H, s), 4.89(2H, s), 4.78(1H, d, J=4.1Hz), 4.38-4.18(1H, m), 3.96-3.81(1H, m), 3.78-3.62(2H, m), 3.27-2.99(2H, m), 2.35-1.15(14H, m)









Purity
>90% (NMR)



MS
694(M + 1)










[2085]

226







TABLE 226










Example No.
344
1H NMR(δ) ppm














1259





300MHz, DMSO-d6 8.30(1H, s), 8.23(1H, d, J=8.7Hz), 8.02(1H, d, J=8.4Hz), 7.71(2H, d, J=8.7Hz), 7.55-7.15(8H, m), 7.07(1H, dd, J=8.4Hz, 3.0Hz), 5.07(2H, s), 4.35(1H, m), 4.17(2H, t, J=4.5Hz), 3.69(2H, t, J=4.5Hz), 3.32(3H, s), 2.40-2.15(2H, m), 2.10-1.80(4H, m), 1.75-1.60(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
611(M + 1)


Example No.
345
1H NMR(δ) ppm














1260





300MHz, DMSO-d6 8.29(1H, d, J=1.5Hz), 8.22(1H, d, J=8.7Hz), 8.01(1H, d, J=8.7Hz), 7.70(1H, d, J=8.7Hz), 7.50-7.15(8H, m), 7.07(1H, dd,


# J=8.4Hz, 2.4Hz), 5.07(2H, s), 4.35(1H, m), 4.17(2H, t, J=4.2Hz), 3.76(2H, t, J=4.5Hz), 3.65-3.40(4H, m), 3.25(3H, s), 2.40-2.20(2H, m), 2.10-1.80(4H, m), 1.75-1.65(1H, m), 1.65-1.20(3H, m)









Purity
>90% (NMR)



MS
655(M + 1)


Example No.
346
1H NMR(δ) ppm














1261





300Mz, DMSO-d6 8.26(1H, d, J=1.9Hz), 8.23(1H, d, J=1.5Hz), 8.08-8.02(2H, m), 7.91(1H, dd, J=8.7, 1.5Hz), 7.63 and 7.16(4H, Abq,


# J=8.9Hz), 7.56-7.51(5H, m), 5.15(2H, s), 4.29(1H, brt, J=11.7Hz), 2.96(2H, d, J=6.9Hz), 2.37-2.12(3H, m), 2.00-1.79(4H, brm), 1.71-1.60(1H, brm) 1.49-1.19(3H, brm), 0.97 and 0.95 (total 6H, each s)









Purity
>90% (NMR)



MS
621(M + 1)










[2086]

227







TAB1E 227










Example No.
347
1H NMR(δ) ppm














1262





300Mz, DMSO-d6 8.26(1H, s), 8.22(1H, s), 8.06(1H, s), 8.05(1H, d, J=8.0Hz), 7.94 and 7.85(2H, ABq, J=8.8Hz), 7.59 and 7.15(4H, A′ B′ q, J=8.6Hz), 7.52(4H,


# s), 7.44(1H, d, J=8.0Hz), 5.12(2H, s), 4.27(1H, brt, J=11.4Hz), 2.38-2.18(2H, brm), 1.97-1.77(4H, brm), 1.70-1.59(1H, brm), 1.49-1.17(3H, brm)









Purity
>90% (NMR)



MS
634(M + 1)


Example No.
348
1H NMR(δ) ppm














1263





300MHz, DMSO-d6 8.32(1H, s), 8.29(1H, d, J=9.0Hz), 8.06(1H, d, J=8.7Hz), 7.74(2H, d, J=9.0Hz), 7.72(1H, brs), 7.60-7.45(5H, m), 7.42(1H, d, J=7.8Hz), 7.24(2H, d, J=8.7Hz), 5.15(2H, s), 4.37(1H, m), 4.00-3.10(6H, m), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.80(2H, m), 1.75-1.20(6H, m)









Purity
>90% (NMR)



MS
680(M + 1)


Example No.
349
1H NMR(δ) ppm














1264





300MHz, DMSO-d6 8.41(1H, d, J=1.5Hz), 8.33(1H, d, J=1.5Hz), 8.26(1H, d, J=8.7Hz), 8.18(1H, dd, J=2.0Hz, 8.0Hz), 8.04(1H, dd, J=1.5Hz, 9.0Hz), 7.75(2H,


# d, J=8.7Hz), 7.63(1H, d, J=8.1Hz), 7.62-7.45(4H, m), 7.26(2H, d, J=8.7Hz), 5.25(2H, s), 4.35(1H, m), 2.45(3H, s), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.80(2H, m), 1.75-1.55(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
619(M + 1)










[2087]

228







TABLE 228










Example No.
350
1H NMR(δ) ppm














1265





300MHz, DMSO-d6



8.36(1H, d, J=7.7Hz), 8.29(1H, s), 8.23(1H, d, J=8.8Hz),



8.02(1H, d, J=8.6Hz), 7.94(1H, d, J=7.9Hz), 7.84(1H, d,



J=1.6Hz), 7.80-7.65(3H, m), 7.53(4H, s), 5.15(2H, s),



4.34(1H, m), 4.12(1H, m), 2.35-2.20(2H, m),



2.10-1.60(5H, m), 1.50-1.20(3H, m), 1.17(6H, d, J=6.5Hz)









Purity
>90% (NMR)



MS
622(M + 1)


Example No.
351
1H NMR(δ) ppm














1266





300MHz, DMSO-d6



8.29(1H, s), 8.24(1H, d, J=8.8Hz), 8.02(1H, d, J=8.6Hz),



7.80-7.65(3H, m), 7.55-7.45(5H, m), 7.32(1H, d,



J=1.5Hz), 7.22(2H, d, J=8.8Hz), 5.13(2H, s), 4.35(1H, m),



3.60(2H, m), 3.33(2H, m), 2.40-2.15(2H, m),



2.10-1.15(14H, m)









Purity
>90% (NMR)



MS
648(M + 1)


Example No.
352
1H NMR(δ) ppm














1267





300MHZ, DMSO-d6



13.20(1H, brs), 8.30-8.24(2H, m), 8.13(1H, s), 8.04(1H, d,



J=8.7Hz), 7.94(1H, d, J=8.0Hz), 7.75-7.70(3H, m),



7.55-7.43(5H, m), 7.25(2H, d, J=8.7Hz), 5.13(2H, s),



4.36(1H, m), 3.53(2H, s), 2.40-2.18(2H, m),



2.15-1.95(2H, m), 1.90-1.80(2H, m), 1.75-1.55(1H, m),



1.50-1.20(9H, m)









Purity
>90% (NMR)



MS
652(M + 1)










[2088]

229







TABLE 229










Example No.
353
1H NMR(δ) ppm














1268





300MHz, DMSO-d6 8.41(1H, s), 8.33-8.29(2H, m), 8.16(1H, d, J=8.2Hz), 8.07(1H, d, J=8.6Hz), 7.77(2H, d, J=8.7Hz), 7.62(1H, d, J=8.0Hz), 7.59-7.51(4H, m), 7.28(2H, d, J=8.8Hz), 5.21(2H, s), 4.56(2H, s), 4.37(1H, m), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.80(2H, m), 1.75-1.55(1H, m), 1.50-1.20(9H, m)









Purity

90% (NMR)




MS
634(M + 1)


Example No.
354
1H NMR(δ) ppm














1269





300MHz, DMSO-d6 8.31(1H, s), 8.25(1H, d, J=9.0Hz), 8.03(1H, d, J=8.7Hz), 7.76-7.71(3H, m), 7.51-7.47(5H, m), 7.33(1H, s), 7.23(2H, d, J=9.0Hz), 5.14(2H, s), 4.36(1H, m), 4.02(1H, m), 3.75(1H, m), 3.56(1H, m), 3.22(2H, m), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.55(5H, m), 1.50-1.20(5H, m)









Purity
>90% (NMR)



MS
664(M + 1)


Example No.
355
1H NMR(δ) ppm














1270





300MHz, DMSO-d6 8.62(1H, t, J=5.7Hz), 8.32-8.30(2H, m), 8.25(1H, d, J=8.7Hz), 8.03(1H, d, J=8.7Hz), 7.96(1H, d, J=8.1Hz), 7.86(1H, s), 7.75(1H, d,


# J=9.0Hz), 7.72(2H, d, J=9.0Hz), 7.55-7.50(4H, m), 7.22(2H, d, J=9.0Hz), 5.17(2H, s), 4.35(1H, m), 3.52(2H, t, J=6.0Hz), 3.36(2H, t, J=6.0Hz), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.80(2H, m), 1.75-1.55(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
624(M + 1)










[2089]

230







TABLE 230










Example No.
356
1H NMR(δ) ppm














1271





300Mz, DMSO-d6 9.30(1H, t, J=5.9Hz), 8.54(2H, d, J=5.9Hz), 8.22(1H, s), 8.02-7.79(5H, m), 7.59 and 7.12(4H, ABq, J=8.6Hz), 7.55(4H, s), 7.37(2H, d, J=5.9Hz), 5.15(2H, s), 4.54(2H, d, J=5.7Hz), 4.26(1H, brt, J=12.8Hz), 2.36-2.18(2H, brm), 1.97-1.78(4H, brm), 1.70-1.60(1H, brm), 1.47-1.17(3H, brm)









Purity
>90% (NMR)



MS
671(M + 1)


Example No.
357
1H NMR(δ) ppm














1272





300Mz, DMSO-d6 8.31(1H, d, J=1.5Hz), 8.43(1H, d, J=8.4Hz), 8.03(1H, dd, J=8.4, 1 5Hz), 7.74(1H, d, J=8.1Hz), 7.73 and 7.23(4H, ABq, J=9.0Hz), 7.54-7.51(5H, m), 7.37(1H, d, J=1.8Hz), 5.14(2H, s), 4.36(1H, brt, J=12.1Hz), 2.98(6H, brs), 2.37-2.20(2H, brm), 2.08-1.81(4H, brm), 1.70-1.60(1H, brm), 1.50-1.21(3H, brm)









Purity
>90% (NMR)



MS
608(M + 1)


Example No.
358
1H NMR(δ) ppm














1273





300MHz, DMSO-d6 8.33(1H, s), 8.31(1H, d, J=8.7Hz), 8.14(1H, s), 8.07(1H, d, J=8.7Hz), 7.92(1H, d, J=8.0Hz), 7.76(2H, d, J=8.7Hz), 7.52-7.40(5H, m), 7.31-7.26(3H, m), 5.15(2H, s), 4.37(1H, m), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.80(2H, m), 1.75-1.55(1H, m), 1.50-1.20(3H, m)









Purity

90% (NMR)




MS
635(M + 1)










[2090]

231







TABLE 231










Example No.
359
1H NMR(δ) ppm














1274





300MHz, DMSO-d6 8.31(1H, s), 8.25(1H, d, J=8.7Hz), 8.10-7.90(2H, m), 7.82(1H, dd, J=7.8Hz, 1.8Hz), 7.72(2H, d, J=9.0Hz), 7.63(1H, d, J=8.1Hz), 7.23(2H, d, J=9.0Hz), 5.25(2H, s), 4.34(1H, m), 3.65-3.50(1H, m), 3.20-3.05(2H, m), 2.90-2.75(2H, m), 2.40-2.15(2H, m), 2.10-1.10(12H, m)









Purity
>90% (NMR)



MS
700(M + 1)


Example No.
360
1H NMR(δ) ppm














1275





300MHz, DMSO-d6 8.33(1H, s), 8.30(1H, d, J=8.5Hz), 8.06(1H, d, J=10.1Hz), 8.80-8.65(3H, m), 8.60-8.45(3H, m), 7.42(1H, d, J=7.8Hz), 7.35-7.15(4H, m), 5.15(2H, s), 4.36(1H, m), 3.01, 2.97(6H, s), 2.40-2.15(2H, m), 2.10-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
592(M + 1)


Example No.
361
1H NMR(δ) ppm














1276





300MHz, DMSO-d6 8.35-8.20(2H, m), 8.05(1H, d, J=8.7Hz), 8.80-8.65(3H, m), 7.60-7.40(3H, m), 7.40-7.30(5H, m), 5.17(2H, s), 4.35(1H, m), 3.01, 2.97(6H, s), 2.40-2.15(2H, m), 2.10-1.80(4H, m), 1.70-1.20(4H, m)









Purity
>90% (NMR)



MS
592(M + 1)










[2091]

232







TABLE 232










Example No.
362
1H NMR(δ) ppm














1277





300MHz, DMSO-d6 8.33(1H, s), 8.29(1H, d, J=8.7Hz), 8.06(1H, d, J=8.7Hz), 7.79(2H, d, J=9.0Hz), 7.76(1H, d, J=9.0Hz), 7.60(1H, d, J=8.1Hz), 7.53(1H, dd,



J=1.7Hz, 8.0Hz), 7.35(2H, d, J=8.7Hz), 6.85-6.80(2H, m), 5.29(2H, s), 4.38(1H, m), 3.01, 2.96(6H, s), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.80(2H, m), 1.75-1.55(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
614(M + 1)


Example No.
363
1H NMR(δ) ppm














1278





300MHz, DMSO-d6 8.28(1H, d, J=1.3Hz), 8.20-8.10(2H, m), 8.98(1H, d, J=8.6Hz), 7.90-7.80(2H, m), 7.75(2H, d, J=8.7Hz), 7.36(2H, d, J=8.7Hz), 7.04(1H, d, J=1.3Hz), 5.35(2H, s), 4.36(1H, m), 2.39(3H, s), 2.35-2.15(2H, m), 2.05-1.75(4H, m), 1.70-1.60(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
586(M + 1)


Example No.
364
1H NMR(δ) ppm














1279





300MHz, DMSO-d6 8.31(1H, s), 8.26(1H, d, J=8.7Hz), 8.13(1H, s), 8.04(1H, d, J=9.0Hz), 7.90-7.70(4H, m), 7.65(1H, s), 7.39(2H, d, J=9.0Hz), 5.37(2H, s), 4.38(1H, m), 2.40-2.20(2H, m), 2.15-2.00(2H, m), 1.95-1.80(2H, m), 1.75-1.60(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
604(M + 1)










[2092]

233







TABLE 233










Example No.
365
1H NMR(δ) ppm














1280





300MHz, DMSO-d6 8.28(1H, s), 8.23(1H, s), 8.17(1H, d, J=8.7Hz), 8.00(2H, t, J=6.9Hz), 7.69(2H, d, J=8.4Hz), 7.60-7.45(5H, m), 7.21(2H, d, J=8.4Hz), 7.05(1H, s) 5.19(2H, s), 4.33(1H, m), 2.41(3H, s), 2.40-2.20(2H, m), 2.10-1.80(4H, m), 1.70-1.60(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
618(M + 1)


Example No.
366
1H NMR(δ) ppm














1281





300MHz, DMSO-d6 8.26(1H, s), 8.17(1H, s), 8.11(1H, d, J=8.7Hz), 7.95(2H, d, J=9.6Hz), 7.70-7.40(8H, m), 7.19(2H, d, J=8.4Hz), 5.18(2H, s), 4.30(1H, m), 2.51(3H, s), 2.40-2.15(2H, m), 2.05-1.80(4H, m), 1.75-1.60(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
634(M + 1)


Example No.
367
1H NMR(δ) ppm














1282





300Mz, DMSO-d6 8.42(1H, d, J=1.9Hz), 8.30(1H, J=, 1.5Hz), 8.27(1H, d, J=8.7Hz), 8.18(1H, dd,


# J=7.9, 1.9Hz), 8.04(1H, dd, J=8.7, 1.5Hz), 7.75 and 7.29(4H, ABq, J=8.9Hz) 7.63(1H, d, J=7.9Hz), 5.23(2H, s), 4.36(1H, brt, J=12.3Hz) 2.37-2.20(2H, brm), 2.08-1.80(4H, brm), 1.71-1.60(1H, brm), 1.51-1.21(3H, brm)









Purity
>90% (NMR)



MS
605(M + 1)










[2093]

234







TABLE 234










Example No.
368
1H NMR(δ) ppm














1283





300Mz, DMSO-d6 8.30(1H, d, J=1.5Hz), 8.25(1H, d, J=8.6Hz), 8.04(1H, dd, J=8.6, 1.5Hz), 7.93 and 7.67(4H, ABq, J=8.1Hz), 7.80(1H,


# d, J=2.2Hz), 7.72 and 7.21(4H, A′ B′ q, J=8.6Hz), 7.60(1H, dd, J=8.1, 2.2Hz), 7.44(1H, d, J=8.1Hz), 5.13(2H, s), 4.34(1H, brt, J=11.7Hz), 2.37-2.19(2H, brm), 2.09-1.80(4H, brm), 1.72-1.60(1H, brm), 1.50-1.21(3H, brm)









Purity
>90% (NMR)



MS
562(M + 1)


Example No.
369
1H NMR(δ) ppm














1284





300Mz, DMSO-d6 8.30(1H, d, J=1.5Hz), 8.25(1H, d, J=8.6Hz), 8.16 and 7.72(4H, ABq, J=8.4Hz), 8.13(1H, dd, J=8.6, 1.5Hz), 7.80(1Hd, J=2.2Hz), 7.70 and 7.24(4H, A′ B′ q, J=8.8Hz),


# 7.61(1H, dd, J=8.1, 2.2Hz), 7.48(1H, d, J=8.1Hz), 5.17(2H, s), 4.33(1H, brt, J=12.1Hz), 2.36-2.18(2H, brm), 2.08-1.77(4H, brm), 1.69-1.57(1H, brm), 1.49-1.17(3H, brm)









Purity
>90% (NMR)



MS
605(M + 1)


Example No.
370
1H NMR(δ) ppm














1285





300MHz, DMSO-d6 10.94(1H, brs), 8.33(1H, s), 8.27(1H, d, J=8.7Hz), 8.04(1H, d, J=8.7Hz), 7.74(2H, d, J=8.4Hz), 7.56-7.29(6H, m), 7.23(2H, d, J=8.7Hz), 7.13(1H, d, J=8.7Hz), 5.08(2H, s), 4.51(2H, brs), 4.36(1H, m), 3.94(1H, brs), 3.75-3.00(6H, m), 3.20-1.20(14H, m)









Purity
>90% (NMR)



MS
680(M + 1)










[2094]

235







TABLE 235










Example No.
371
1H NMR(δ) ppm














1286





300MHz, DMSO-d6 8.31(1H, d, J=1.5Hz), 8.17(1H, d, J=9.0Hz), 7.99(1H, dd, J=8.7Hz, 1.4Hz), 7.70-7.55(2H, m), 7.50-7.30(6H, m), 7.19(1H, dd, J=12.0Hz,


# 2.2Hz), 7.06(1H, dd, J=8.6Hz, 2.2Hz), 5.08(2H, 4.10(1H, m), 3.68(2H, brt, J=5.2), 2.50(2H, brt, J=1.8Hz), 2.30-2.10(2H, m), 2.00-1.75(8H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
652(M + 1)


Example No.
372
1H NMR(δ) ppm














1287





300Mz, DMSO-d6 8.29(1H, d, J=1.5Hz), 8.11(1H, d, J=8.6Hz), 7.96(1H, dd, J=8.6, 1.5Hz), 7.89(1H, s), 7.78 and 7.56(4H, ABq, J=8.4Hz), 7.69(1H, s), 7.66(1H, t,


# J=8.8Hz), 7.31(1H, dd, J=12.1, 2.2Hz), 7.18(1H, dd, J=8.8, 2.2Hz), 5.37(2H, s), 4.08(1H, brt, J=11.0Hz), 3.02(3H, s), 2.96(3H, s), 2.31-2.14(2H, brm), 1.95-1.77(4H, brm,) 1.69-1.59(31H, brm), 1.46-1.18(3H, brm)









Purity
>90% (NMR)



MS
626(M + 1)


Example No.
373
1H NMR(δ) ppm














1288





300MHz, DMSO-d6 11.40(1H, brs), 9.25(2H, brs), 8.29(1H, d, J=1.3Hz), 8.12-8.09(2H, m), 7.96(1H, d, J=8.7Hz), 7.88(1H, dd, J=1.8Hz, 8.1Hz), 7.67-7.63(2H, m), 7.56(2H,


# d, J=8.7Hz), 7.51(2H, d, J=8.7Hz), 7.17(1H, d, J=12.0Hz), 7.05(1H, d, J=8.6Hz), 5.16(2H, s), 4.05(1H, m), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
613(M + 1)










[2095]

236







TABLE 236










Example No.
374
1H NMR(δ) ppm














1289





300MHz, DMSO-d6 13.21(1H, brs), 8.31(1H, d, J=1.4Hz), 8.18-8.15(2H, m), 7.99(1H, d, J=8.7Hz), 7.94(1H, dd, J=1.8Hz, 8.0Hz), 7.70-7.53(6H, m), 7.17(1H, d, J=12.0Hz), 7.05(1H, d, J=8.6Hz), 5.20(2H, s), 4.09(1H, m), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
639(M + 1)


Example No.
375
1H NMR(δ) ppm














1290





300MHz, DMSO-d6 8.32(1H, d, J=1.5Hz), 8.23(1H, z), J=1.5Hz), 8.19(1H, d, J=9.0Hz), 8.03-7.98(2H, m), 7.68(1H, t, J=8.4Hz), 7.60(1H, d, J=8.1Hz), 7.56(2H, d, J=9.3Hz), 7.53(2H, d, J=9.0Hz), 7.22(1H, dd, J=2.1Hz, 12.0Hz), 7.09(1H, dd, J=2.1Hz, 8.4Hz), 5.21(2H, s), 4.12(1H, m), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
658(M + 1)


Example No.
376
1H NMR(δ) ppm














1291





300MHz, DMSO-d6 13.61(1H, brs), 8.34-8.30(2H, m), 8.21(1H, d, J=8.7Hz), 8.07(1H, dd, J=1.8Hz, 8.1Hz), 8.02(1H, dd, J=1.5Hz, 8.7Hz), 7.69(1H, t, J=8.4Hz), 7,57-7.49(5H, m), 7.22(1H, dd, J=2.7Hz, 12.0Hz), 7.09(1H, dd, J=2.4Hz, 9.0Hz), 5.19(2H, s), 4.12(1H, m), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
655(M + 1)










[2096]

237







TABLE 237










Example No.
377
1H NMR(δ) ppm














1292





300Mz, DMSO-d6 8.60(1H, d, J=4.5Hz), 8.29(1H, d, J=1.5Hz), 8.14(1H, d, J=8.9Hz), 8.13(1H, d,


# J=1.5Hz), 7.98(1H, dd, J=8.9, 1.5Hz), 7.94(1H, dd, J=8.1, 1.5Hz), 7.64(1H, t, J=8.7Hz), 7.52 and 7.49(4H, ABq, J=9.0Hz), 7.46(1H, d, J=8.1Hz), 7.18(1H, dd, J=12.1, 2.3Hz), 7.05(1H, dd, J=8.7, 2.3Hz), 5.13(2H, s), 4.08(1H, brt, J=12.1H), 2.95-2.84(1H, ,), 2.31-2.14(2H, brm), 1.97-1.78(4H, brm), 1.72-1.59(1H, brm), 1.47-1.21(3H, brm), 0.76-0.58(4H, m)









Purity
>90% (NMR)



MS
638(M + 1)


Example No.
378
1H NMR(δ) ppm














1293





300Mz, DMSO-d6 8.77(1H, d, J=1.4Hz), 8.30(1H, d, J=1.4Hz), 8.16(1H, d,


# J=1.8Hz), 8.13(1H, d, J=8.4Hz), 7.98(2H, dd, J=8.4, 1.8Hz), 7.65(1H, t, J=8.4Hz), 7.53 and 7.49(4H, ABq, J=8.8Hz), 7.47(1H, d, J=7.7Hz), 7.18(1H, dd, J=12.1, 2.2Hz), 7.05(1H, dd, J=8.4, 2.2Hz), 5.13(2H, s), 4.53-4.40(1H, m), 4.09(1H, brt, J=12.8Hz), 2.31-2.02(6H, brm), 1.96-1.80(4H, brm), 1.78-1.60(3H, brm), 1.47-1.21(3H, brm)









Purity
>90% (NMR)



MS
652(M + 1)


Example No.
379
1H NMR(δ) ppm














1294





300Mz, DMSO-d6 8.29(1H, d, J=1.1Hz), 8.11(1H, d, J=1.5Hz), 8.11(1H, d, J=8.8Hz), 7.98-7.91(2H, m), 7.89(1H, s), 7.63(1H, t, J=8.8Hz), 7.52 and 7.48(4H, ABq, J=8.6Hz), 7.44(1H, d, J=8.1Hz), 7.17(1H, dd, J=12.1, 2.2Hz), 7.04(1H, dd, J=8.8, 2.2Hz), 5.12(2H, s), 4.07(1H, brt, J=12.4Hz), 2.33-2.14(2H, brm), 1.96-1.79(4H, brm), 1.70-1.60(1H,


# brm), 1.48-1.21(3H, brm), 1.41(9H, s)









Purity
>90% (NMR)



MS
654(M + 1)










[2097]

238







TABLE 238










Example No.
380
1H NMR(δ) ppm














1295





300Mz, DMSO-d6 8.62(1H, t, J=5.5Hz), 8.30(1H, d, J=1.5Hz), 8.17(1H, d, J=1.8Hz), 8.14(1H, d, J=8.8Hz), 7.98(1H,


# dd, J=8.1, 1.8Hz), 7.64(1H, t, J=8.8Hz), 7.52 and 7.50(4H, ABq, J=8.8Hz), 7.48(1H, d, J=8.1Hz), 7.18(1H, dd, J=12.1, 2.2Hz), 7.05(1H, dd, J=8.8, 2.2Hz), 5.14(2H, s), 4.08(1H, brt, J=12.1Hz), 3.13(1H, t, J=6.2Hz), 2.31-2.14(2H, brm), 1.97-1.78(5H, brm), 1.70-1.60(1H, brm), 1.47-1.21(3H, brm), 0.92(3H, s), 0.90(3H, s)









Purity
>90% (NMR)



MS
654(M + 1)


Example No.
381
1H NMR(δ) ppm














1296





300Mz, DMSO-d6 8.29(1H, d, J=1.5Hz), 8.27(1H, d, J=8.3Hz), 8.18(1H, d,


# J=1.9Hz), 8.13(1H, d, J=8.7Hz), 8.01-7.96(2H, m), 7.64(1H, t, J=8.7Hz), 7.52 and 7.49(1H, ABq, J=8.8Hz), 7.49(1H, d, J=7.9Hz), 7.18(1H, dd, J=12.1, 2.3Hz), 7.05(1H, dd, J=8.7, 2.3Hz), 5.13(2H, s), 4.12-4.00(2H, m), 3.52-3.34(2H, m), 2.31-2.14(2H, brm), 1.97-1.79(4H, brm), 1.71-1.60(1H, brm), 1.48-1.21(3H, m, 1.17 and 1.15(total 3H, each s)









Purity
>90% (NMR)



MS
656(M + 1)


Example No.
382
1H NMR(δ) ppm














1297





300Mz, DMSO-d6 8.30(1H, d, J=1.5Hz), 8.13(1H, d, J=8.8Hz), 8.09(1H, d, J=1.5Hz), 7.98(1H, dd, J=8.8, 1.5Hz), 7.86(1H, dd, J=8.1, 1.5Hz), 7.64(1H, J=8.8Hz), 7.55-7.47(5H, m), 7.17(1H, dd, J=12.1, 2.2Hz), 7.05(1H, dd, J=8.8, 2.2Hz), 5.14(2H, s), 4.08(1H, brt, J=12.8 Hz), 3.75(3H, s), 2.32-2.14(2H, brm), 1.96-1.78(4H,


# brm), 1.70-1.59(1H, brm), 1.47-1.21(3H, brm)









Purity
>90% (NMR)



MS
628(M + 1)










[2098]

239







TABLE 239










Example No.
383
1H NMR(δ) ppm














1298





300Mz, DMSO-d6 8.57(1H, t, J=5.5Hz), 8.29(1H, d, J=1.4Hz), 8.19(1H, d, J=1.5Hz), 8.12(1H,


# d, J=9.2Hz), 8.01-7.95(2H, m), 7.64(1H, t, J=8.8Hz), 7.53 and 7.50(4H, ABq, J=8.8Hz), 7.48(1H, d, J=7.7Hz), 7.17(1H, dd, J=12.1, 2.2Hz), 7.04(1H, dd, J=8.8, 2.2Hz), 5.14(2H, s), 4.08(1H, brt, J=13.9Hz), 3.70-3.66(1H, m), 3.48-3.36(3H, m), 3.28-3.20(1H, m), 2.32-2.13(2H, brm), 1.96-1.79(4H, brm), 1.71-1.60(1H, brm), 1.47-1.19(3H, brm)









Purity
>90% (NMR)



MS
672(M + 1)


Example No.
384
1H NMR(δ) ppm














1299





300Mz, DMSO-d6 8.30(1H, d, J=1.5Hz), 8.14(1H, d, J=8.4Hz), 7.98(1H, dd, J=8.4, 1.5Hz), 7.68(1H, brs), 7.63(1H,


# t, J=8.4Hz), 7.51(5H, s), 7.43(1H, d, J=8.1Hz), 7.17(1H, dd, J=12.5, 1.8Hz), 7.03(1H, dd, J=8.4, 1.8Hz), 4.08(1H, brt, J=11.4Hz), 3.50 and 3.30(total 2H, each brs), 2.97(3H, brs), 2.33-2.13(2H, brm), 1.96-1.79(4H, brm), 1.70-1.59(1H, brm), 1.47-1.03(6H, brm),









Purity
>90% (NMR)



MS
640(M + 1)


Example No.
385
1H NMR(δ) ppm














1300





300Mz, DMSO-d6 8.29(1H, d, J=1.5Hz), 8.12(1H, d, J=8.8Hz), 7.97(1H, dd, J=8.8, 1.5Hz), 7.72-7.60(2H, m), 7.55-7.42(6H, m), 7.16(1H, d, J=11.7Hz), 7.03(1H, d, J=8.4Hz), 5.15(2H, s), 4.07(1H, brt, J=12.5Hz), 3.44 and 3.22(total 2H, each s), 2.97(3H, brs), 2.32-2.13(2H, brm), 1.72-1.50(3H, brm), 1.47-1.23(3H, brm), 0.93 and 0.72(total 3H, each brs)









Purity
>90% (NMR)



MS
654(M + 1)










[2099]

240







TABLE 240










Example No.
386
1H NMR(δ) ppm














1301





300Mz, DMSO-d6 8.29(1H, d, J=1.5Hz), 8.12(1H, d, J=8.7Hz), 7.97(1H, dd, J=8.7, 1.5Hz)7.74-7.60(2H, m), 7.54-7.42(6H, m), 7.17(1H, dd, J=12.1, 2.2Hz), 7.02(1H, dd, J=8.3, 2.2Hz), 5.15(2H, s), 4.06(1H, brt, J=12.8Hz), 3.92(1H, brs), 2.85(3H, brs), 2.32-2.14(2H, brm), 1.96-1.79(4H, brm), 1.70-1.59(1H, brm), 1.46-1.07(3H, brm), 1.15(6H, brs)









Purity
>90% (NMR)



MS
654(M + 1)


Example No.
387
1H NMR(δ) ppm














1302





300Mz, DMSO-d6 8.29(1H, s), 8.14 and 7.97(2H, ABq, J=8.7Hz), 7.63(1H, s), 7.63(1H, t, J=8.7Hz), 7.51-7.41(6H, m), 7.16(1H, dd, J=12.1, 1.9Hz), 7.02(1H, dd, J=8.7, 1.9Hz), 5.16(2H, s), 4.26(2H, brs), 4.07(1H, brt, J=12.1Hz), 2.32-2.14(2H, brm), 1.97-1.78(5H, brm) 1.70-1.15(9H, brm), 1.24(3H, s), 1.21(3H, s)









Purity
>90% (NMR)



MS
694(M + 1)


Example No.
388
1H NMR(δ) ppm














1303





300MHz, DMSO-d6 628.58(1H, m), 8.29(1H, s), 8.20-8.10(2H, m), 8.05-7.90(2H, m), 7.64(1H < t, J=8.4Hz), 7.60-7.40(5H, m), 7.15(1H, d, J=12.3Hz), 7.04(1H, d, J=8.4Hz), 5.13(2H, s), 4.08(1H, m), 3.40-3.20(2H, m), 2.35-2.10(2H, m), 2.00-1.20(12H, m), 0.91(3H, t, J=6.9Hz)









Purity
>90% (NMR)



MS
654(M + 1)










[2100]

241







TABLE 241










Example No.
389
1H NMR(δ) ppm














1304





300MHz, DMSO-d6 8.60(1H, m), 8.29(1H, s), 8.20-7.90(4H, m), 7.64(1H, t, J=9.0Hz), 7.60-7.40(5H, m), 7.17(1H, d, J=12.0Hz), 7.04(1H, d, J=8.7Hz), 5.13(2H, s), 4.80(1H, m), 3.35-3.15(2H, m), 2.30-2.05(2H, m), 2.00-1.10(10H, m), 0.91(3H, t, J=7.5Hz)









Purity
>90% (NMR)



MS
640(M + 1)


Example No.
390
1H NMR(δ) ppm














1305





300MHz, DMSO-d6 8.62(1H, m), 8.30(1H, s), 8.20-8.10(2H, m), 8.05-7.90(2H, m), 7.65(1H, t, J=8.4Hz), 7.60-7.40(5H, m), 7.18(1H, d, J=12.0Hz), 7.05(1H, d, J=8.4Hz), 5.14(2H, s), 4.09(1H, m), 3.40-3.20(2H, m), 2.35-2.10(2H, m), 2.00-1.80(4H, m), 1.75-1.60(1H, m), 1.45-1.20(3H, m), 1.15(3H, t, J=7.2Hz)









Purity
>90% (NMR)



MS
626(M + 1)


Example No.
391
1H NMR(δ) ppm














1306





400NHz, DMSO-d6 8.54(1H, s), 8.31(1H, s), 8.19(1H, d, J=8.6Hz), 8.01(1H, d, J=8.6Hz), 7.81(1H, d, J=2.1Hz), 7.64(1H,


# t, J=8.4Hz), 7.61(1H, dd, J=2.3Hz, 8.4Hz), 7.47(2H, d, J=8.6Hz), 7.43(2H, d, J=8.8Hz), 7.25(1H, d, J=8.4Hz), 7.17(1H, dd, J=2.3Hz, 12.1Hz), 7.05(1H, dd, J=2.3Hz, 8.6Hz), 5.05(2H, s), 4.12(1H, m), 2.96(6H, s), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
641(M + 1)










[2101]

242







TABLE 242










Example No.
392
1H NMR(δ) ppm














1307





300Mz, DMSO-d6 8.79(1H, s), 8.29(1H, d, J=1.5Hz), 8.13(1H, d, J=8.8Hz), 7.98(1H, dd, J=8.8,


# 1.5Hz), 7.80(1H, d, J=2.2Hz), 7.63(1H, t, J=8.4Hz), 7.61(1H, dd, J=8.2, 2.2Hz), 7.47 and 7.43(4H, ABq, J=8.8Hz), 7.26(1H, d, J=8.2Hz), 7.14(1H, dd, J=12.1, 2.2Hz), 7.02(1H, dd, J=8.4, 2.2Hz), 5.05(2H, s), 4.08(1H, brt, J=12.1Hz), 3.64-3.61(2H, m), 3.48-3.45(2H, m), 2.32-2.13(2H, brm), 1.96-1.78(4H, brm), 1.70-1.66(1H, brm), 1.44-1.19(3H, brm)









Purity
>90% (NMR)



MS
683(M + 1)


Example No.
393
1H NMR(δ) ppm














1308





400MHz, DMSO-d6 8.94(1H, s), 8.31(1H, d, J=1.0Hz), 8.18(1H, d, J=8.6Hz), 8.00(1H, dd, J=1.4Hz, 8.8Hz), 7.71(1H,


# d, J=2.2Hz), 7.66(1H, t, J=8.6Hz), 7.52(1H, dd, J=2.4Hz, 8.6Hz), 7.46(2H, d, J=8.6Hz), 7.42(2H, d, J=8.2Hz), 7.24(1H, d, J=8.4Hz), 7.16(1H, d, J=12.1Hz), 7.04(1H, dd, J=2.4Hz, 8.8Hz), 5.05(2H, s), 4.13(1H, m), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
613(M + 1)


Example No.
394
1H NMR(δ) ppm














1309





300MHZ, DMSO-d6 8.93(1H, s), 8.31(1H, d, J=1.4Hz), 8.19(1H, d, J=8.8Hz), 8.01(1H, d, J=8.7Hz), 7.71(1H, d,


# J=2.2Hz), 7.66(1H, t, J=8.5Hz), 7.51(1H, dd, J=2.2Hz, 8.4Hz), 7.46(2H, d, J=8.6Hz), 7.41(2H, d, J=8.7Hz), 7.23(1H, d, J=8.4Hz), 7.16(1H, d, J=12.2Hz), 7.05(1H, d, J=8.7Hz), 5.05(2H, s), 4.13(1H, m), 3.12(2H, q, J=7.2Hz), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.60(1H, m), 1.55-1.20(3H, m), 1.06(3H, t, J=7.2Hz)









Purity
>90% (NMR)



MS
641(M + 1)










[2102]

243







TABLE 243










Example No.
395
1H NMR(δ) ppm














1310





300MHz, DMSO-d6 8.83(1H, s), 8.32(1H, d, J=1.4Hz), 8.21(1H, d, J=8.8Hz), 8.02(1H, dd, J=1.4Hz, 8.7Hz), 7.71(1H, d, J=2.1Hz), 7.68(1H, t,


# J=8.6Hz), 7.49(1H, dd, J=2.2Hz, 8.4Hz), 7.46(2H, d, J=8.4Hz), 7.41(2H, d, J=8.6Hz), 7.23(1H, d, J=8.4Hz), 7.17(1H, d, J=12.2Hz), 7.06(1H, d, J=8.7Hz), 6.30(1H, brs), 5.05(2H, s), 4.14(1H, m), 3.77(1H, sept, J=6.5Hz), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m), 1.11(6H, d, J=6.5Hz)









Purity
>90% (NMR)



MS
655(M + 1)


Example No.
396
1H NMR(δ) ppm














1311





300MHz, DMSO-d6 8.37(1H, d, J=7.3Hz), 8.25(1H, s), 8.15(1H, s), 7.97(2H, d, J=8.8Hz), 7.88(1H, d, J=8.8Hz), 7.58-7.47(4H, m), 7.31(1H, m), 7.11(1H, dd, J=8.4, 2.2Hz), 6.98(1H, dd, J=8.4, 2.2), 5.13(2H, s), 4.13(1H, q, J=6.6Hz), 3.98(1H, m), 2.19(2H, m), 1.86(4H, m) 1.62(1H, m) 1.31(3H, m), 1.20(6H, d, J=6.6Hz)









Purity
>90% (NMR)



MS
642(M + 1)


Example No.
397
1H NMR(δ) ppm














1312





300MHz, DMSO-d6 8.40(1H, d, J=7.9Hz), 8.28(1H, d, J=1.9Hz), 8.15(1H, d, J=1.9Hz), 8.11(1H, d, J=8.7Hz), 7.96(2H, m), 7.56(1H, t, J=8.7Hz), 7.45(3H, m), 7.18(1H, m), 7.08(1H, dd, J=12.1, 1.9Hz), 6.96(1H, dd, J=8.3, 2.3Hz), 5.09(2H, s), 4.14(1H, m), 4.04(1H, m), 2.23(2H, m), 1.86(3H, m), 1.62(1H, m), 1.33(3H, m), 1.20(6H, d, J=6.4Hz)









Purity
>90% (NMR)



MS
642(M + 1)










[2103]

244







TABLE 244










Example No.
398
1H NMR(δ) ppm














1313





8.41(1H, d, J=8.1Hz), 8.29(1H, d, J=1.5Hz), 8.17(1H, d, J=1.8Hz), 8.12(1H, d, J=8.4Hz), 8.01-7.95(2H, m), 7.67-7.62(2H, m), 7.55-7.51(3H, m), 7.19(1H, dd, J=12.1, 2.2Hz), 7.05(1H, dd, J=8.8, 2.2Hz), 5.13(2H, s), 4.10-4.00(2H, m), 2.32-2.13(4H, m), 1.71-1.60(1H, m), 1.49-1.14(3H, m), 1.21(3H, s), 1.19(3H, s)









Purity
>90% (NMR)



MS
674(M + 1)


Example No.
399
1H NMR(δ) ppm














1314





300Mz, DMSO-d6 8.39(1H, d, J=7.7Hz), 8.29(1H, d, J=1.5Hz), 8.16(1H, d, J=1.8Hz), 8.11(1H, d, J=8.8Hz), 8.00-7.95(2H, m), 7.69-7.61(2H, m), 7.54-7.46(3H, m), 7.18(1H, dd, J=12.1, 2.2Hz), 7.04(1H, dd, J=8.8, 2.2Hz), 5.13(2H, s), 4.20-4.02(2H, m), 2.33-2.13(2H, brm), 1.97-1.80(4H, m), 1.72-1.61(1H, m), 1.44-1.13(3H, m), 1.21(3H, s), 1.19(3H, s)









Purity
>90% (NMR)



MS
658(M + 1)


Example No.
400
1H NMR(δ) ppm














1315





300MHz, DMSO-d6



8.39(1H, d, J=7.7Hz), 8.29(1H, s), 8.17(1H, d, J=1.5Hz), 8.11(1H, d, J=8.8Hz), 7.98(2H, m), 7.73(2H, m), 7.64(1H, t, J=8.4Hz), 7.52(1H, d, J=8.0Hz), 7.46(1H, dd, J=8.4, 1.8Hz), 7.18(1H, dd, J=11.9, 2.0Hz), 7.05(1H, dd, J=8.6, 2.4Hz), 5.14(2H, s), 4.13(2H, m), 2.22(2H, m), 1.88(4H, m) 1.64(1H, m), 1.34(3H, m), 1.20(6H, d, J=6.6Hz)









Purity
>90% (NMR)



MS
642(M + 1)










[2104]

245







TABLE 245










Example No.
401
1H NMR(δ) ppm














1316





300MHz, DMSO-d6 8.38(1H, d, J=7.8Hz), 8.28(1H, s), 8.20-8.05(2H, m), 8.00-7.90(2H, m), 7.65-7.30(5H, m), 7.09(1H, d, J=12.3Hz), 6.97(1H, d, J=10.2Hz), 5.09(2H, s), 4.20-4.00(2H, m), 2.30-2.10(2H, m), 2.00-1.80(4H, m), 1.70-1.60(1H, m), 1.40-1.10(3H, m), 1.19(6H, d, J=6.6Hz)









Purity
>90% (NMR)



MS
658(M + 1)


Example No.
402
1H NMR(δ) ppm














1317





300MHz, DMSO-d6 8.25(1H, s), 8.03(1H, d, J=8.7Hz), 7.91(1H, d, J=8.7Hz), 7.83(1H, s), 7.70-7.35(6H, m), 7.04(1H, d, J=12.0Hz), 6.93(1H, d, J=8.4Hz), 5.09(2H, s), 4.00(1H, m), 3.60-3.40(4H, m), 2.30-2.10(2H, m), 1.45-1.15(3H, m)









Purity
>90% (NMR)



MS
670(M + 1)


Example No.
403
1H NMR(δ) ppm














1318





400MHz, DMSO-d6 8.25(1H, s), 8.08(1H, d, J=8.4Hz), 7.92(1H, d, J=9.2Hz), 7.79(1H, s), 7.66-7.49(4H, m), 7.42(1H, d, J=7.6Hz), 7.31-7.28(1H, m), 7.14(1H, d, J=11.3Hz), 6.99(1H, d, J=8.8Hz), 5.13(2H, s), 4.02(1H, m), 3.54-3.33(4H, m), 2.29-2.08(2H, m), 1.93-1.73(8H, m), 1.67-1.52(1H, m), 1.48-1.11(3H, m)









Purity
>90% (NMR)



MS
670(M + 1)










[2105]

246







TABLE 246










Example No.
404
1H NMR(δ) ppm














1319





400MHz, DMSO-d6 8.41(1H, d, J=7.6Hz), 8.32(1H, d, J=1.5Hz), 8.20(1H, d,


# J=8.6Hz), 8.17(1H, d, J=1.7Hz), 8.00(1H, dt, J=8.8Hz, 1.5Hz), 7.71-7.64(2H, m), 7.54(1H, dd, J=10.3Hz, 1.9Hz), 7.32(1H, dd, J=8.2Hz, 1.9Hz), 7.22(1H, dd, J=12.1Hz, 2.3Hz), 7.08(1H, dd, J=8.6Hz), 2.3Hz), 5.17(2H, s), 4.15(1H, m), 2.31-2.14(2H, m), 1.99-1.70(4H, m), 1.70-1.60(1H, m), 1.46-1.20(3H, m), 1.19(6H, d, J=6.6Hz)









Purity
>90% (NMR)



MS
658(M + 1)


Example No.
405
1H NMR(δ) ppm














1320





300MHz, DMSO-d6 8.32(1H, s), 8.19(1H, d, J=9.0Hz), 8.03-7.98(2H, m), 7.75(1H, dd, J=2.1Hz, 8.4Hz), 7.67(1H, t, J=8.6Hz), 7.40-7.36(3H,


# m), 7.32(2H, d, J=8.4Hz), 7.19(1H, dd, J=2.1Hz, 12.3Hz), 7.07(1H, dd, J=2.1Hz, 8.7Hz), 5.11(2H, s), 4.12(1H, m), 4.12(1H, m), 3.90(2H, t, J=6.9Hz), 2.54(2H, t, J=8.1Hz), 2.50(3H, s), 2.40-2.05(4H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
650(M + 1)


Example No.
406
1H NMR(δ) ppm














1321





300MHz, DMSO-d6 8.34(1H, d, J=7.7Hz), 8.29(1H, s), 8.15(1H, s), 8.11(1H, d, J=8.8Hz), 7.97(2H, d, J=9.2Hz), 7.63(1H, t, J=8.8Hz), 7.47-7.31(5H, m), 7.18(1H, dd, J=12.4, 2.2Hz), 7.06(1H, dd, J=12.4, 2.2Hz), 5.13(2H, s), 4.13(2H, m), 1.96(2H, m), 1.87(4H, m), 1.62(1H, m), 1.34(3H, m), 1.20(6H, d, J=6.2Hz)









Purity
>90% (NMR)



MS
652(M + 1)










[2106]

247







TABLE 247










Example No.
407
1H NMR(δ) ppm














1322





400MHz, DMSO-d6 8.32(1H, d, J=1.4Hz), 8.20(1H, d, J=8.8Hz), 8.01(1H, dd,


# J=1.6Hz, 8.8Hz), 7.90(1H, s), 7.67(1H, t,J=8.4Hz), 7.61(1H, s), 7.55-7.50(4H, m), 7.21(1H, dd, J=2.3Hz, 12.0Hz), 7.06(1H, dd, J=2.2Hz, 8.7Hz), 5.10(2H, s), 4.11(1H, m), 3.78(2H, t, J=6.7Hz), 3.47(2H, t, J=7.4Hz), 2.54-2.48(2H, m), 2.40-2.10(2H, m), 2.00-1.80(4H, m), 1.75-1.55(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
708(M + 1)


Example No.
408
1H NMR(δ) ppm














1323





400MHz, DMSO-d6 8.32(1H, d, J=1.6Hz), 8.21(1H, d, J=8.8Hz), 8.02(1H, dd, J=1.6Hz, 8.8Hz), 7.76(1H, s), 7.68(1H, t, J=8.5Hz), 7.59(1H, s),


# 7.54-7.51(4H, m), 7.21(1H, dd, J=2.4Hz, 12.1Hz), 7.07(1H, dd, J=2.4Hz, 8.8Hz), 5.08(2H, s), 4.11(1H, m), 3.77(2H, t, J=6.9Hz), 2.47(2H, t, J=8.0Hz), 2.40-2.10(4H, m), 2.00-1.80(4H, m), 1.70-1.60(1H, m), 1.45-1.20(3H, m)









Purity
>90% (NMR)



MS
672(M + 1)


Example No.
409
1H NMR(δ) ppm














1324





300MHz, DMSO-d68.28(1H, d, J=1.5Hz), 8.20-8.85(4H, m), 7.75(1H, d, J=6.9Hz), 7.70-7.45(6H, m), 7.13(1H, dd, J=12.0Hz, 2.1Hz), 7.00(1H, dd, J=8.7Hz), 2.1Hz), 5.22(2H, s), 4.05(1H, m), 3.40-3.20(1H, m), 2.30-2.10(2H, m), 2.00-1.55(5H, m), 1.45-1.10(3H, m), 1.00(6H, d, J=6.6Hz)









Purity
>90% (NMR)



MS
676(M + 1)










[2107]

248







TABLE 248










Example No.
410
1H NMR(δ) ppm














1325





300MHz, DMSO-d6 8.31(1H, s), 8.00(1H, d, J=8.7Hz), 7.88(1H, d, J=8.7Hz), 7.70(1H, s), 7.65(1H, t, J=8.4Hz), 7.53(2H, d, J=8.4Hz), 7.49(2H, d, J=8.7Hz), 7.45-7.41(2H, m), 7.16(1H, d, J=12.0Hz), 7.04(1H, d, J=8.7Hz), 5.14(2H, s), 4.68(1H, quint, J=8.4Hz), 3.02, 2.98(6H, s), 2.30-1.85(6H, m), 1.80-1.50(2H, m)









Purity
>90% (NMR)



MS
612(M + 1)


Example No.
411
1H NMR(δ) ppm














1326





300MHz, DMSO-d6 8.30(1H, s), 7.99(1H, d, J=9.0Hz), 7.87(1H, d, J=8.7Hz), 7.67(1H, s), 7.64(1H, t, J=8.7Hz), 7.53(2H, d, J=8.7Hz), 7.49(2H, d, J=7.5Hz), 7.45-7.41(2H, m), 7.15(1H, d, J=12.3Hz), 7.02(1H, d, J=8.4Hz), 5.15(2H, s), 4.67(1H, quint, J=8.7Hz), 4.02(1H, m), 3.76(1H, m), 3.55(1H, m), 3.22(2H, m), 2.40-1.20(12H, m)









Purity
>90% (NMR)



MS
668(M + 1)


Example No.
412
1H NMR(δ) ppm














1327





300MHz, DMSO-d6 8.38(1H, d, J=7.5Hz), 8.33(1H, s), 8.16(1H, s), 8.02(1H, d, J=8.7Hz), 7.98(1H, d, J=9.0Hz), 7.91(1H, d, J=8.4Hz), 7.67(1H, t,


# J=8.4Hz), 7.53(2H, d, J=8.7Hz), 7.48(2H, d, J=8.7Hz), 7.46(1H, d, J=8.1Hz), 7.18(1H, d, J=11.7Hz), 7.06(1H, d, J=8.7Hz), 5.13(2H, s), 4.70(1H, quint, J=8.4Hz), 4.13(1H, sept, J=6.6Hz), 2.30-1.85(6H, m), 1.80-1.50(2H, m), 1.16(6H, d, J=6.3Hz)









Purity
>90% (NMR)



MS
626(M + 1)










[2108]

249







TABLE 249










Example No.
413
1H NMR(δ) ppm














1328





300Mz, DMSO-d6 8.39(1H, d, J=7.5Hz), 8.31(1H, d, J=1.5Hz), 8.16(1H, d, J=1.9Hz), 8.06(1H, dd, J=8.8,


# 1.5Hz), 7.99-7.95(2H, m), 7.76 and 7.24(4H, ABq, J=8.9Hz), 7.53 and 7.50(4H, A′B′q, J=9.1Hz), 7.46(1H, d, J=8.3Hz), 5.14(2H, s), 4.94(1H, quint, J=9.0Hz), 4.19-4.08(1H, m), 2.32-2.11(4H, brm), 2.10-1.95(2H, brm), 1.78-1.62(2H, brm), 1.26(3H, s), 1.18(3H, s)









Purity
>90% (NMR)



MS
608(M + 1)


Example No.
414
1H NMR(δ) ppm














1329





300Mz, DMSO-d6 8.31(1H, d, J=1.5Hz), 8.06(1H, dd, J=8.7, 1.5Hz), 7.97(1H, d, J=8.7Hz), 7.75 and 7.22(4H, ABq, J=8.9Hz), 7.70(1H, d, J=1.9Hz), 7.53(1H, dd, J=7.9, 1.9Hz), 7.52(4H, s), 7.43(1H, d, J=7.9Hz), 5.15(2H, s), 4.93(1H, quint, J=8.9Hz), 3.01(3H, s), 2.97(3H, s), 2.32-2.11(4H, brm), 2.09-1.94(2H, brm), 1.77-1.62(2H, brm)









Purity
>90% (NMR)



MS
594(M + 1)


Example No.
415
1H NMR(δ) ppm














1330





300Mz, DMSO-d6 8.31(1H, d, J=1.5Hz), 8.06(1H, dd, J=8.7, 1.5Hz), 7.98(1H, d,


# J=8.7Hz), 7.75 and 7.22(4H, ABq, J=8.9Hz), 7.67(1H, d, J=1.5Hz), 7.52(4H, s), 7.49(1H, dd, J=7.9, 1.5Hz), 7.43(1H, d, J=8.9Hz), 5.16(2H, s), 4.93(1H, quint, J=8.9Hz), 3.76(1H, brs), 3.55(2H, brs), 3.22(2H, brs), 2.31-2.11(4H, brm), 2.16-1.95(2H, brm), 1.88-1.62(4H, brm), 1.48-1.28(2H, brm)









Purity
>90% (NMR)



MS
650(M + 1)










[2109]

250







TABLE 250










Example No.
416
1H NMR(δ) ppm














1331





300MHz, DMSO-d6 8.38(1H, d, J=7.7Hz), 8.30(1H, s), 8.20-7.90(4H, m), 7.72(2H, d, J=8.7Hz), 7.60-7.40(5H, m), 7.22(2H, d, J=8.7Hz), 5.13(2H, s), 4.47(1H, m), 4.15(1H, m), 2.90-2.70(4H, m), 2.60-2.30(4H, m), 1.19(6H, d, J=6.5Hz)









Purity
>90% (NMR)



MS
640(M + 1)


Example No.
417
1H NMR(δ) ppm














1332





400MHz, DMSO-d6 8.33(1H, s), 8.17(1H, d, J=8.6Hz), 8.10(1H, d, J=8.6Hz), 7.82(1H, d, J=1.4Hz), 7.74(2H, d, J=8.7Hz), 7.64(1H, dd, J=8.0Hz, 1.7Hz), 7.55-7.50(4H, m), 7.43(1H, d, J=7.8Hz), 7.24(1H, d, J=8.7Hz), 5.16(2H, s), 4.49(1H, m), 3.60-3.40(4H, m), 2.90-2.70(4H, m), 2.60-2.30(4H, m), 2.20-1.80(4H, m)









Purity
>90% (NMR)



MS
652(M + 1)


Example No.
418
1H NMR(δ) ppm














1333





400MHz, DMSO-d6 8.34(1H, d, J=7.6Hz), 8.25(1H, s), 8.11(1H, d, J=1.3Hz), 7.90-8.00(3H, m), 7.59(1H, t, J=8.6Hz), 7.40-7.55(5H, m), 7.12(1H, d, J=11.9Hz), 7.00(1H, d, J=8.6Hz), 5.08(2H, s), 4.30-4.10(2H, m), 2.80-2.65(4H, m), 2.45-2.30(2H, m), 1.15(6H, d, J=4.8Hz)









Purity
>90% (NMR)



MS
658(M + 1)










[2110]

251







TABLE 251










Example No.
419
1H NMR(δ) ppm














1334





400MHz, DMSO-d6 8.30(1H, s), 8.05-7.95(3H, m), 7.80-7.75(1H, m), 7.63(1H, t, J=8.6Hz), 7.55-7.35(5H, m), 7.15(1H, dd, J=12.1Hz, 2.1Hz), 7.03(1H, dd, J=8.7Hz, 2.3Hz), 5.10(2H, s), 4.23(1H, m), 3.90(2H, t, J=7.0Hz), 2.95-2.70(4H, m), 2.60-2.35(4H, m), 2.30-2.00(4H, m)









Purity
>90% (NMR)



MS
656(M + 1)


Example No.
420
1H NMR(δ) ppm














1335





300Mz, DMSO-d6 8.37(1H, d, J=7.5Hz), 8.28(1H, d, J=1.5Hz), 8.17(1H, d, J=1.5Hz), 8.13(1H, d, J=8.7Hz), 7.97(1H, dd, J=8.1, 1.5Hz), 7.94(1H, dd, J=8.7, 1.5Hz), 7.61(1H, t, J=8.7Hz), 7.51 and 7.49(4H, ABq, J=8.9Hz), 7.46(1H, d, J=8.1Hz), 7.08(1H, dd, J=12.4, 2.3Hz), 6.97(1H, dd, J=8.7, 2.3Hz), 5.10(2H, s),


# 4.20-4.08(1H, m), 3.62-3.56(2H, brm), 3.13-3.10(2H, brm), 1.79-1.60(3H, brm), 1.54-1.34(3H, brm), 1.21(3H,









Purity
>90% (NMR)



MS
641(M + 1)


Example No.
421
1H NMR(δ) ppm














1336





300Mz, DMSO-d6 8.24(1H, d, J=1.5Hz), 8.02(1H, d, J=8.7Hz), 7.88(1H, dd, J=8.7,


# 1.5Hz), 7.82(1H, d, J=1.9Hz), 7.63(1H, dd, J=7.9, 1.9Hz), 7.54(1H, t, J=8.7Hz), 7.50(4H, s), 7.42(1H, d, J=7.9Hz), 7.01(1H, dd, J=12.0, 2.3Hz), 6.91(1H, dd, J=8.7, 2.3Hz), 5.11(2H, s), 3.63-3.41(6H, m), 3.07-3.04(2H, brm), 1.95-1.79(4H, brm), 1.77-1.57(3H, brm), 1.50-1.32(3H, brm)









Purity
>90% (NMR)



MS
653(M + 1)










[2111]

252







TABLE 252










Example No.
422
1H NMR(δ) ppm














1337





300MHz, DMSO-d6 10.99(2H, s), 8.44(1H, s), 8.30(1H, s), 8.18(1H, d, J=8.7Hz), 8.14(1H,


# d, J=8.7Hz), 7.98(1H, d, J=9.0Hz), 7.70-7.66(2H, m), 7.57(2H, d, J=8.7Hz), 7.54(2H, d, J=8.7Hz), 7.21(1H, d, J=12.0Hz), 7.09(1H, d, J=8.4Hz), 5.19(2H, s), 4.05(4H, s), 2.40-2.18(2H, m), 2.15-1.80(4H, m), 1.75-1.55(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
623(M + 1)


Example No.
423
1H NMR(δ) ppm














1338





300MHz, DMSO-d6 8.27(1H, s), 8.05(1H, d, J=8.7Hz), 7.93(1H, d, J=8.7Hz), 7.90(1H, s), 7.70(1H, d, J=8.4Hz), 7.59(1H, t, J=8.4Hz), 7.50(2H, d,


# J=9.0Hz), 7.45(2H, d, J=8.7Hz), 7.41(1H, d, J=8.4Hz), 7.12(1H, d, J=12.0Hz), 7.00(1H, d, J=8.7Hz), 5.10(2H, s), 4.49(2H, t, J=7.8Hz), 4.14(2H, t, J=8.0Hz), 4.04(1H, m), 2.40-2.10(2H, m), 2.00-1.50(5H, m), 1.45-1.20(3H, m)









Purity
>90% (NMR)



MS
640(M + 1)


Example No.
424
1H NMR(δ) ppm














1339





300MHz, DMSO-d6 8.30(1H, s), 8.14(1H, d, J=8.4Hz), 7.98(1H, d, J=9.3Hz), 7.89(1H, s), 7.68(1H, d, J=8.4Hz), 7.62(1H,


# d, J=9.0Hz), 7.48(2H, d, J=8.4Hz), 7.43(2H, d, J=8.4Hz), 7.33(1H, d, J=8.4Hz), 7.16(1H, d, J=12.0Hz), 7.04(1H, d, J=9.0Hz), 5.07(2H, s), 4.10(1H, m), 3.92(2H, t, J=8.0Hz), 3.45(2H, t, J=8.0Hz), 2.40-2.10(2H, m), 2.00-1.50(5H, m), 1.45-1.20(3H, m)









Purity
>90% (NMR)



MS
639(M + 1)










[2112]

253







TABLE 253










Example No.
425
1H NMR(δ) ppm














1340





300MHz, DMSO-d6 9.05(1H, s), 8.30(1H, s), 8.16(1H, d, J=8.8Hz), 7.99(1H, d, J=8.6Hz), 7.72(1H, s), 7.64(1H, t,


# J=8.6Hz), 7.52(1H, d, J=8.4Hz), 7.47(2H, d, J=8.7Hz), 7.42(2H, d, J=8.6Hz), 7.25(1H, d, J=8.4Hz), 7.15(1H, d, J=12.2Hz), 7.04(1H, d, J=8.6Hz), 6.60(1H, brs), 5.05(2H, s), 4.10(1H, m), 3.68(2H, t, J=6.1Hz), 3.45(2H, t, J=6.1Hz), 2.40-2.10(2H, m), 2.00-1.55(5H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
639(M + 1)


Example No.
426
1H NMR(δ) ppm














1341





300MHz, DMSO-d6 8.32(1H, s), 8.24(1H, d, J=8.7Hz), 8.03(1H, d, J=8.7Hz), 7.78-7.73(4H, m), 7.38-7.32(4H, m), 5.52(2H, s), 4.88(2H, s), 4.40(2H, s), 4.37(1H, m), 2.92, 2.84(6H, s), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.80(2H, m), 1.75-1.55(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
643(M + 1)


Example No.
427
1H NMR(δ) ppm














1342





300MHz, DMSO-d6 11.26(1H, brs), 8.35(1H, s), 8.27(1H, d, J=9.0Hz), 8.05(1H, d, J=8.4Hz), 7.83-7.78(4H, m), 7.42-7.35(4H, m), 5.57(2H, s), 4.77, 4.73(2H, s), 4.37(1H, m), 3.95(1H, s), 3.70-3.00(4H, m), 2.40-1.00(14H, m)









Purity
>90% (NMR)



MS
641(M + 1)










[2113]

254







TABLE 254










Example No.
428
1H NMR(δ) ppm














1343





300MHz, DMSO-d6 8.31(1H, s), 8.26(1H, d, J=9.0Hz), 8.04(1H, d, J=8.7Hz), 7.79-7.73(4H, m), 7.38-7.31(6H, m), 5.53(2H, s), 4.90(2H, s), 4.37(1H, m), 4.05(2H, s), 2.40-2.18(2H, m), 2.15-1.95(2H, m), 1.90-1.80(2H, m), 1.75-1.55(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
615(M + 1)


Example No.
429
1H NMR(δ) ppm














1344





300MHz, DMSO-d6 8.88(1H, q, J=4.5Hz), 8.33(1H, d, J=1.5Hz), 8.18(1H, d,


# J=8.7Hz), 8.01(1H, dd, J=1.5Hz, 8.7Hz), 7.89-7.83(2H, m), 7.50-7.34(3H, m), 7.20(1H, dd, J=2.1Hz, 8.4Hz), 5.61(2H, s), 4.13(1H, m), 2.84(3H, d, J=4.8Hz), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
603(M + 1)


Example No.
430
1H NMR(δ) ppm














1345





400MHz, DMSO-d6 8.79(1H, t, J=5.9Hz), 8.31(1H, s), 8.15(1H, d, J=8.7Hz), 7.99(1H, d, J=8.8Hz), 7.87(1H, d, J=8.1Hz), 7.85(1H, d, J=8.7Hz), 7.70(1H, t, J=8.4Hz), 7.42-7.33(3H, m), 7.18(1H, d, J=8.8Hz), 5.60(2H, s), 4.11(1H, m), 3.62-3.54(4H, m), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
633(M + 1)










[2114]

255







TABLE 255










Example No.
431
1H NMR(δ) ppm














1346





300MHz, DMSO-d6 8.31(1H, s), 8.16(1H, d, J=8.8Hz), 7.99(1H, d, J=8.7Hz), 7.74-7.60(4H, m), 7.37(2H, t, J=8.8Hz), 7.28(1H, dd, J=2.2Hz, 12.2Hz), 7.14(1H, dd, J=2.2Hz, 8.6Hz), 5.17(2H, s), 4.10(1H, m), 3.15(6H, brs), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.15(3H, m)









Purity
>90% (NMR)



MS
616(M + 1)


Example No.
432
1H NMR(δ) ppm














1347





300MHz, DMSO-d6 8.45(1H, d, J=7.7Hz), 8.32(1H, s), 8.19(1H, d, J=8.8Hz), 8.02-7.99(2H, m), 7.70(1H, t, J=8.6Hz),


# 7.60(2H, dd, J=5.4Hz, 8.7Hz), 7.37(2H, t, J=8.8Hz), 7.27(1H, dd, J=2.3Hz, 12.2Hz), 7.14(1H, dd, J=2.2Hz), 8.7Hz), 5.16(2H, s), 4.20-4.00(2H, m), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m), 1.18(6H, d, J=6.6Hz)









Purity
>90% (NMR)



MS
630(M + 1)


Example No.
433
1H NMR(δ) ppm














1348





300MHz, DMSO-d6 8.31(1H, d, J=1.4Hz), 8.15(1H, d, J=8.8Hz), 7.98(1H, dd, J=1.4Hz, 8.7Hz), 7.68-7.60(4H, m), 7.36(2H,


# t, J=8.8Hz), 7.28(1H, dd, J=2.2Hz, 12.2Hz), 7.15(1H, dd, J=2.2Hz, 8.6Hz), 5.17(2H, s), 4.10(1H, m), 4.05-3.90(2H, m), 3.85-3.70(1H, m), 3.55-3.25(2H, m), 2.40-2.10(2H, m), 2.00-1.75(6H, m), 1.70-1.55(1H, m), 1.50-1.20(5H, m)









Purity
>90% (NMR)



MS
672(M + 1)










[2115]

256







TABLE 256










Example No.
434
1H NMR(δ) ppm














1349





300Mz, DMSO-d6 8.45(1H, d, J=1.5Hz), 8.26(1H, d, J=8.8Hz), 8.10(1H, dd, J=8.8,


# 1.5Hz), 7.72(1H, d, J=1.5Hz), 7.64(1H, t, J=8.6Hz), 7.56-7.48(5H, m), 7.44(1H, d, J=J=7.7Hz), 7.18(1H, dd, J=12.3, 2.4Hz), 7.04(1H, dd, J=8.6, 2.4Hz), 5.15(2H, s), 4.08(1H, brt, J=11.7Hz), 3.02(3H, s), 2.99(3H, s), 2.34-2.17(2H, brm), 1.97-1.81(4H, brm), 1.70-1.60(1H, brm), 1.49-1.21(3H, brm)









Purity
>90% (NMR)



MS
650(M + 1)


Example No.
435
1H NMR(δ) ppm














1350





300Mz, DMSO-d6 8.42(1H, d, J=1.5Hz), 8.24(1H, d, J=8.8Hz), 8.08(1H, dd, J=8.8, 1.5Hz), 8.00(2H, d, J=8.8Hz), 7.79(1H,


# d, J=7.8Hz), 7.62(1H, t, J=8.4Hz), 7.61-7.55(3H, m), 7.44(1H, d, J=8.1Hz), 7.16(1H, dd, J=12.1, 2.6Hz), 7.02(1H, dd, J=8.4, 2.6Hz), 5.12(2H, s), 4.07(1H, brt, J=12.5Hz), 2.33(2H, brm), 1.96-1.79(4H, brm), 1.71-1.61(1H, brm), 1.49-1.21(3H, brm)









Purity
>90% (NMR)



MS
623(M + 1)


Example No.
436
1H NMR(δ) ppm














1351





300MHz, DMSO-d6 8.41(1H, d, J=7.7Hz), 8.30-8.26(2H, m), 8.18(1H, d, J=1.4Hz), 7.99(1H,


# dd, J=1.7Hz, 8.0Hz), 7.89(1H, d, J=10.1Hz), 7.67(1H, t, J=8.8Hz), 7.55-7.45(5H, m), 7.20(1H, d, J=12.2Hz), 7.07(1H, dd, J=2.1Hz, 8.7Hz), 5.14(2H, s), 4.18-4.11(2H, m), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.20(3H, m), 1.20(6H, d, J=6.6Hz)









Purity
>90% (NMR)



MS
680(M + 1)










[2116]

257







TABLE 257










Example No.
437
1H NMR(δ) ppm














1352














Purity
>90% (NMR)



MS
580(M + 1)


Example No.
438
1H NMR(δ) ppm














1353














Purity
>90% (NMR)



MS
607(M + 1)


Example No.
439
1H NMR(δ) ppm














1354





300MHz, CDCl3 8.60(1H, d, J=1.5Hz), 8.05(1H, dd, J=1.6Hz, 8.7Hz), 7.70(1H, d, J=8.7Hz), 7.62(2H, d, J=8.2Hz), 7.49(2H, d, J=8.2Hz), 7.31(2H, d, J=8.8Hz), 7.27-7.23(2H, m), 7.06(2H, t, J=8.6Hz), 6.80(2H, d, J=8.8Hz), 5.05(2H, s), 4.38(1H, m), 3.06(6H, s), 2.45-2.20(2H, m), 2.10-1.70(5H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
591(M + 1)










[2117]

258







TABLE 258










Example No.
440
1H NMR(δ) ppm














1355





300MHz, DMSO-d6 8.20(1H, s), 7.86(2H, m), 7.39(1H, d, J=7.9Hz), 7.34(1H, d, J=7.9Hz), 7.07(2H, dt, J=2.3Hz, 8.6Hz), 6.98-6.88(5H, m), 6.83(1H, d, J=8.3Hz), 5.91(1H, s), 3.96(1H, m), 2.30-1.95(2H, m), 1.90-1.50(4H, m), 1.40-1.10(3H, m)









Purity
>90% (NMR)



MS
557(M + 1)


Example No.
441
1H NMR(δ) ppm














1356





300MHz, DMSO-d6 8.24(1H, d, J=1.4Hz), 8.01(1H, d, J=8.8Hz), 7.91(1H, dd, J=1.4Hz, 8.7Hz), 7.47(1H, t, J=8.4Hz), 7.43-7.35(2H, m), 7.15-7.01(5H, m), 6.92(2H, d, J=10.4Hz), 6.11(1H, s), 3.90(1H, m), 2.30-1.95(2H, m), 1.90-1.50(4H, m), 1.40-1.10(3H, m)









Purity
>90% (NMR)



MS
557(M + 1)


Example No.
442
1H NMR(δ) ppm














1357





300Mz, DMSO-d6 8.26(1H, d, J=1.5Hz), 8.11(1H, d, J=8.9Hz), 7.96(1H, dd, J=8.9, 1.5Hz), 7.65-7.57(5H, m), 7.47(1H, t, J=7.7Hz), 7.35(1H, d, J=7.6Hz), 7.30-7.22(3H, m), 7.16(1H, dd, J=8.7, 2.3Hz), 6.88(1H, s), 4.04(1H, brt, J=11.3Hz), 2.98(3H, s) 2.84(3H, s), 2.30-2.10(2H, brm), 1.94-1.75(4H, brm), 1.68-1.57(1H, brm), 1.45-1.14(3H, brm)









Purity
>90% (NMR)



MS
610(M + 1)










[2118]

259







TABLE 259










Example No.
443
1H NMR(δ) ppm














1358





300Mz, DMSO-d6 8.23(1H, s), 7.98 and 7.89(2H, ABq, J=8.8Hz), 7.62-7.06(11H, m), 6.86(1H, s), 4.12-3.77(2H, brm), 3.72(1H, brs), 3.69(1H, brs), 3.18(1H, brs), 3.05(1H, brs), 2.31-2.08(2H, brm), 1.90-1.54(7H, brm), 1.48-1.13(5H, brm)









Purity
>90% (NMR)



MS
666(M + 1)


Example No.
444
1H NMR(δ) ppm














1359





300MHz, DMSO-d6 8.36(1H, s), 8.00(1H, d, J=8.7Hz), 7.90(1H, d, J=9.3Hz), 7.80-7.70(2H, m), 7.63(2H, d, J=8.4H z), 7.32(2H, t, J=8.7Hz), 7.22(2H, d, J=8.4Hz), 5.62(1H, d, J=7.5Hz), 5.57(1H, brd, J=4.8Hz), 5.41(2H, s), 5.31(1H, m), 4.29(1H, m), 3.84(1H, d, J=9.0Hz), 3.50-3.20(3H, m), 2.71(3H, s), 2.40-2.20(2H, m), 1.75-1.60(1H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
718(M + 1)


Example No.
445
1H NMR(δ) ppm














1360





300MHz, DMSO-d6 8.36(1H, s), 8.00(1H, d, J=8.7Hz), 7.92(1H, d, J=9.3Hz), 7.57(1H, t, J=8.4Hz), 7.50-7.35(6H, m), 7.25-7.05(4H, m), 6.82(1H, s), 5.62(1H, d, J=7.2Hz), 5.56(1H, m), 5.28(1H, brs), 3.95(1H, m), 3.82(1H, d, J=8.7Hz), 3.50-3.20(3H, m), 2.30-2.05(2H, m), 1.90-1.55(5H, m), 1.40-1.10(3H, m)









Purity
>90% (NMR)



MS
733(M + 1)










[2119]

260







TABLE 260










Example No.
446
1H NMR(δ) ppm














1361





300MHz, DMSO-d6 8.29(1H, s), 8.13(1H, d, J=9.0Hz), 7.97(1H, d, J=9.0Hz), 7.63(1H, t, J=8.6Hz), 7.51-7.32(7H, m), 7.15(1H, d, J=12.0Hz), 7.03(1H, d, J=9.0Hz), 5.10(2H, s), 4.09(1H, m), 3.82(2H, t, J=6.3Hz), 3.56(2H, t, J=7.4Hz), 2.45(2H, m), 2.40-2.10(2H, m), 2.00-1.55(5H, m), 1.50-1.20(3H, m)









Purity
>90% (NMR)



MS
674(M + 1)


Example No.
702
1H NMR(δ) ppm














1362





300MHz, DMSO-d6 8.97(1H, d, J=1.8Hz), 8.52(1H, d, J=2.4Hz), 8.36(1H, d, J=7.8Hz), 8.16(1H, s), 7.96(!H, d, J=8.1Hz), 7.55-7.40(5H, m),7.14(1H, d, J=12.6Hz), 7.01(1H, dd, J=8.4Hz, 1.8Hz), 5.11(2H, s), 4.20-3.95(2H, m), 2.65-2.45(2H, m), 1.95-1.80(5H, m), 1.20-1.10(3H, m)









Purity
>90% (NMR)



MS
641(M + 1)


Example No.
703
1H NMR(δ) ppm














1363





300MHz, DMSO-d6 8.97(1H, d, J=1.8Hz), 8.52(1H, d, J=1.8Hz), 7.82(1H, s), 7.70-7.35(7H, m), 7.13(1H, d, J=12.3Hz), 7.00(1H, d, J=11.1Hz), 5.14(2H, s), 3.60-3.35(4H, m), 2.65-2.40(2H, m), 2.00-2.55(9H, m), 1.40-1.10(3H, m)









Purity
>90% (NMR)



MS
653(M + 1)










[2120] Formulation Example is given in the following. This example is merely for the purpose of exemplification and does not limit the invention.



FORMULATION EXAMPLE

[2121]

261


















(a) compound of Example 1
10 g



(b) lactose
50 g



(c) corn starch
15 g



(d) sodium carboxymethylcellulose
44 g



(e) magnesium stearate
 1 g











[2122] The entire amounts of (a), (b) and (c) and 30 g of (d) are kneaded with water, dried in vacuo and granulated. The obtained granules are mixed with 14 g of (d) and 1 g of (e) and processed into tablets with a tableting machine to give 1000 tablets each containing 10 mg of (a).



INDUSTRIAL APPLICABILITY

[2123] As is evident from the above-mentioned results, the compound of the present invention shows a high inhibitory activity against HCV polymerase.


[2124] Therefore, the compound of the present invention can provide a pharmaceutical agent effective for the prophylaxis or treatment of hepatitis C, based on the anti-HCV effect afforded by the HCV polymerase inhibitory activity. When used concurrently with a different anti-HCV agent, such as interferon, and/or an anti-inflammatory agent and the like, it can provide a pharmaceutical agent more effective for the prophylaxis or treatment of hepatitis C. Its high inhibitory activity specific to HCV polymerase suggests the possibility of the compound being a pharmaceutical agent with slight side effects, which can be used safely for humans.


[2125] This application is based on patent application Nos. 369008/1999, 391904/2000 and 193786/2001 filed in Japan, and international application No. PCT/JP00/09181, the contents of which are hereby incorporated by reference.


Claims
  • 1. A therapeutic agent for hepatitis C, which comprises a fused ring compound of the following formula [I] or a pharmaceutically acceptable salt thereof as an active ingredient:
  • 2. The therapeutic agent of claim 1, wherein 1 to 4 of the G1, G2, G3, G4, G5, G6, G7, G8 and G9 is(are) a nitrogen atom.
  • 3. The therapeutic agent of claim 2, wherein G2 is C(—R2) and G6 is a carbon atom.
  • 4. The therapeutic agent of claim 2, wherein G5 is a nitrogen atom.
  • 5. The therapeutic agent of claim 1, wherein, in formula [I], the moiety
  • 6. The therapeutic agent of claim 5, wherein, in formula [I], the moiety
  • 7. The therapeutic agent of claim 6, which comprises a fused ring compound of the following formula [I-1]
  • 8. The therapeutic agent of claim 6, which comprises a fused ring compound of the following formula [I-2]
  • 9. The therapeutic agent of claim 6, which comprises a fused ring compound of the following formula [I-3]
  • 10. The therapeutic agent of claim 6, which comprises a fused ring compound of the following formula [1-4]
  • 11. The therapeutic agent of claim 1, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1, —CONRa2Ra3, —SO2Ra7 (wherein Ra1, Ra2, Ra3 and Ra7 are as defined in claim 1),
  • 12. The therapeutic agent of claim 11, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1, —CONRa2Ra3 or —SO2Ra7 wherein Ra1, Ra2, Ra3 and Ra7 are as defined in claim 1.
  • 13. The therapeutic agent of claim 1, wherein at least one of R1, R2, R3 and R4 is —COORa1 wherein Ra1 is glucuronic acid residue.
  • 14. The therapeutic agent of claim 1, wherein at least one of R1, R2, R3 and R4 is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom.
  • 15. The therapeutic agent of claim 1, wherein the ring Cy is cyclopentyl, cyclohexyl, cycloheptyl, tetrahydrothiopyranyl or piperidino.
  • 16. The therapeutic agent of claim 1, wherein the ring Cy is
  • 17. The therapeutic agent of claim 1, wherein the ring A is C6-14 aryl.
  • 18. The therapeutic agent of claim 1, wherein at least one substituent optionally substituted by group A is a substituent substituted by C1-6 alkoxy C1-6 alkoxy.
  • 19. The therapeutic agent of claim 1, wherein the Y is —(CH2)m—CRa15Ra16—(CH2)n— wherein each symbol is as defined in claim 1.
  • 20. The therapeutic agent of claim 1, wherein at least one group represented by Z is heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the group D.
  • 21. The therapeutic agent of claim 1, wherein at least one group represented by Z is a heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, wherein said heterocyclic group is selected from the following groups:
  • 22. The therapeutic agent of claim 21, wherein at least one-group, represented by z is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D wherein said heterocyclic group is selected from the following groups:
  • 23. The therapeutic agent of claim 1, wherein at least one group represented by group D is —(CH2)t—CONRa27Ra28 wherein each symbol is as defined in claim 1, and at least one of Ra27 and Ra27 is C1-6 alkoxy.
  • 24. The therapeutic agent of claim 1, wherein at least one group represented by group D is —(CH2)t—C(═NRa33)NH2 wherein each symbol is as defined in claim 1, and Ra3 is hydroxyl group or C1-6 alkoxy.
  • 25. The therapeutic agent of claim 1, wherein at least one group represented by group D is —(CH2)t—O—(CH2)p—CORa21, wherein each symbol is as defined in claim 1, and Ra21 is amino.
  • 26. The therapeutic agent of claim 1, wherein at least one group represented by group D is —(CH2)t—NRa29CO—Ra24 wherein each symbol is as defined in claim 1, and Ra24 is amino or C1-6 alkylamino.
  • 27. The therapeutic agent of claim 1, wherein at least one group represented by group D is —(CH2)t—NRa22Ra23 wherein each symbol is as defined in claim 1, and at lease one of Ra22 and Ra23 is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group B.
  • 28. The therapeutic agent of claim 1, wherein at least one group represented by group D is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom.
  • 29. The therapeutic agent of claim 1, which comprises a fused ring compound of the following formula [I] or a pharmaceutically acceptable salt thereof as an active ingredient:
  • 30. The therapeutic agent of claim 29, wherein 1 to 4 of the G1, G2, G3, G4, G5, G6, G7, G8 and G9 is(are) a nitrogen atom.
  • 31. The therapeutic agent of claim 30, wherein G2 is C(—R2) and G6 is a carbon atom.
  • 32. The therapeutic agent of claim 30, wherein G5 is a nitrogen atom.
  • 33. The therapeutic agent of claim 29, wherein, in formula [I], the moiety
  • 34. The therapeutic agent of claim 33, wherein, in formula [I], the moiety
  • 35. The therapeutic agent of claim 34, which comprises a fused ring compound of the following formula [I-1]
  • 36. The therapeutic agent of claim 34, which comprises a fused ring compound of the following formula [I-2]
  • 37. The therapeutic agent of claim 34, which comprises a fused ring compound of the following formula [I-3]
  • 38. The therapeutic agent of claim 34, which comprises a fused ring compound of the following formula [I-4]
  • 39. The therapeutic agent of claim 29, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1, —CONRa2Ra3 or —SO2Ra7 wherein Ra1, Ra2, Ra3 and Ra7 are as defined in claim 29.
  • 40. The therapeutic agent of claim 29, wherein the ring Cy is cyclopentyl, cyclohexyl, cycloheptyl or tetrahydrothiopyranyl.
  • 41. The therapeutic agent of claim 29, wherein the ring A is C6-14 aryl.
  • 42. A fused ring compound of the following formula [II]
  • 43. The fused ring compound of claim 42, which is represented by the following formula [II-1]
  • 44. The fused ring compound of claim 42, which is represented by the following formula [II-2]
  • 45. The fused ring compound of claim 42, which is represented by the following formula [II-3]
  • 46. The fused ring compound of claim 42, which is represented by the following formula [II-4]
  • 47. The fused ring compound of claim 42, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1, —CONRa2Ra3, —SO2 Ra7 (wherein Ra1, Ra2, Ra3 and Ra7 are as defined in claim 42),
  • 48. The fused ring compound of claim 47, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1 or —SO2Ra7 wherein Ra1 and Ra7 are as defined in claim 42, or a pharmaceutically acceptable salt thereof.
  • 49. The fused ring compound of claim 48, wherein at least one of R1, R2, R3 and R4 is carboxyl or —COORa1 wherein Ra1 is as defined in claim 42, or a pharmaceutically acceptable salt thereof.
  • 50. The fused ring compound of claim 49, wherein R2 is carboxyl and R1, R3 and R4 are hydrogen atoms, or a pharmaceutically acceptable salt thereof.
  • 51. The fused ring compound of claim 42, wherein at least one of R1, R2, R3 and R4 is carboxyl or —COORa1 wherein Ra1 is glucuronic acid residue, or a pharmaceutically acceptable salt thereof.
  • 52. The fused ring compound of claim 42, wherein at least one of R1, R2, R3 and R4 is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or a pharmaceutically acceptable salt thereof.
  • 53. The fused ring compound of claim 42, wherein the ring Cy′ is cyclopentyl, cyclohexyl, cycloheptyl or tetrahydrothiopyranyl, or a pharmaceutically acceptable salt thereof.
  • 54. The fused ring compound of claim 42, wherein the ring Cy′ is cyclopentyl, cyclohexyl or cycloheptyl, or a pharmaceutically acceptable salt thereof.
  • 55. The fused ring compound of claim 42, wherein the ring Cy′ is
  • 56. The fused ring compound of claim 42, wherein the ring A′ is phenyl, pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl, or a pharmaceutically acceptable salt thereof.
  • 57. The fused ring compound of claim 56, wherein the ring A′ is phenyl or pyridyl, or a pharmaceutically acceptable salt thereof.
  • 58. The fused ring compound of claim 57, wherein the ring A′ is phenyl, or a pharmaceutically acceptable salt thereof.
  • 59. The fused ring compound of claim 42, wherein at least one substituent optionaly substituted by group A is a substituent substituted by C1-6 alkoxy C1-6 alkoxy, or a pharmaceutically acceptable salt thereof.
  • 60. The fused ring compound of claim 42, wherein the Y is —(CH2)m—O—(CH2)n—, —NHCO2—, —CONH—CHRa14—, —(CH2)m—NRa12—(CH2)n—, —CONRa13—(CH2)n—, —O—(CH2)m—CRa15Ra16—(CH2)n— or —(CH2)n—NRa12—CHRa15— (wherein each symbol is as defined in claim 42), or a pharmaceutically acceptable salt thereof.
  • 61. The fused ring compound of claim 42, wherein the Y is —(CH2)m—O—(CH2)n— or —O—(CH2)m—CRa15Ra16—(CH2)n— (wherein each symbol is as defined in claim 42), or a pharmaceutically acceptable salt thereof.
  • 62. The fused ring compound of claim 61, wherein the Y is —(CH2)m—O—(CH2)n— wherein each symbol is as defined in claim 42, or a pharmaceutically acceptable salt thereof.
  • 63. The fused ring compound of claim 42, wherein the Y is —(CH2)m—CRa15Ra16—(CH2)n— (wherein each symbol is as defined in claim 42), or a pharmaceutically acceptable salt thereof.
  • 64. The fused ring compound of claim 42, wherein the R2 is carboxyl, R1, R3 and R4 are hydrogen atoms, the ring Cy′ is cyclopentyl, cyclohexyl or cycloheptyl, and the ring A′ is phenyl, or a pharmaceutically acceptable salt thereof.
  • 65. The fused ring compound of claim 42, wherein at least one group represented by Z is heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the group D, or a pharmaceutically acceptable salt thereof.
  • 66. The fused ring compound of claim 42, wherein at least one group represented by Z is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, wherein said heterocyclic group is selected from the following groups:
  • 67. The fused ring compound of claim 66, wherein at least one group represented by Z is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group D, wherein said heterocyclic group is selected from the following groups:
  • 68. The fused ring compound of claim 42, wherein at least one group represented by group D is —(CH2)t—CONRa27Ra28 wherein each symbol is as defined in claim 42, and at least one of Ra27 and Ra28 is C1-6 alkoxy, or a pharmaceutically acceptable salt thereof.
  • 69. The fused ring compound of claim 42, wherein at least one group represented by group D is —(CH2)t—C(═NRa33)NH2 wherein each symbol is as defined in claim 42, and Ra33 is hydroxyl group or C1-6 alkoxy, or a pharmaceutically acceptable salt thereof.
  • 70. The fused ring compound of claim 42, wherein at least one group represented by group D is —(CH2)t—(CH2)p—CORa21 wherein each symbol is as defined in claim 42, and Ra21 is amino, or a pharmaceutically acceptable salt thereof.
  • 71. The fused ring compound of claim 42, wherein at least one group represented by group D is —(CH2)t—NRa29CO—Ra24 wherein each symbol is as defined in claim 42, and Ra24 is amino or C1-6 alkylamino, or a pharmaceutically acceptable salt thereof.
  • 72. The fused ring compound of claim 42, wherein at least one group represented by group D is —(CH2)t—NRa22Ra23 wherein each symbol is as defined in claim 42, and at least one of Ra22 and Ra23 is heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the group B, or a pharmaceutically acceptable salt thereof.
  • 73. The fused ring compound of claim 42, wherein at least one group represented by group D is heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or a pharmaceutically acceptable salt thereof.
  • 74. The fused ring compound of claim 42, which is represented by the following formula [II]
  • 75. The fused ring compound of claim 74, which is represented by the following formula [II-1]
  • 76. The fused ring compound of claim 74, which is represented by the following formula [II-2]
  • 77. The fused ring compound of claim 74, which is represented by the following formula [II-3]
  • 78. The fused ring compound of claim 74, which is represented by the following formula [II-4]
  • 79. The fused ring compound of claim 74, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1 or —SO2Ra7 wherein Ra1 and Ra7 are as defined in claim 74, or a pharmaceutically acceptable salt thereof.
  • 80. The fused ring compound of claim 79, wherein at least one of R1, R2, R3 and R4 is carboxyl or —COORa1 wherein Ra1 is as defined in claim 74, or a pharmaceutically acceptable salt thereof.
  • 81. The fused ring compound of claim 80, wherein R2 is carboxyl and R1, R3 and R4 are hydrogen atoms, or a pharmaceutically acceptable salt thereof.
  • 82. The fused ring compound of claim 74, wherein the ring Cy′ is cyclopentyl, cyclohexyl, cycloheptyl or tetrahydrothiopyranyl, or a pharmaceutically acceptable salt thereof.
  • 83. The fused ring compound of claim 82, wherein the ring Cy′ is cyclopentyl, cyclohexyl or cycloheptyl, or a pharmaceutically acceptable salt thereof.
  • 84. The fused ring compound of claim 74, wherein the ring A′ is phenyl, pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl, or a pharmaceutically acceptable salt thereof.
  • 85. The fused ring compound of claim 74, wherein the ring A′ is phenyl or pyridyl, or a pharmaceutically acceptable salt thereof.
  • 86. The fused ring compound of claim 85, wherein the ring A′ is phenyl, or a pharmaceutically acceptable salt thereof.
  • 87. The fused ring compound of claim 74, wherein the Y is —(CH2)m—O—(CH2)n—, —NHCO2—, —CONH—CHRa14—, —(CH2)m—NRa12—(CH2)n—, —CONRa13—(CH2)n—, —O—(CH2)m—CRa15Ra16—(CH2)n— or —(CH2)n—NRa12—CHRa15— (wherein each symbol is as defined in claim 74), or a pharmaceutically acceptable salt thereof.
  • 88. The fused ring compound of claim 87, wherein the Y is —(CH2)m—O—(CH2)n— or —O—(CH2)m—CRa15Ra16—(CH2)n— (wherein each symbol is as defined in claim 74), or a pharmaceutically acceptable salt thereof.
  • 89. The fused ring compound of claim 88, wherein the Y is —(CH2)m—O—(CH2)n— wherein each symbol is as defined in claim 74, or a pharmaceutically acceptable salt thereof.
  • 90. The fused ring compound of claim 74, wherein the R2 is carboxyl, R1, R3 and R4 are hydrogen atoms, the ring Cy′ is cyclopentyl, cyclohexyl or cycloheptyl, and the ring A′ is phenyl, or a pharmaceutically acceptable salt thereof.
  • 91. The fused ring compound of claim 42 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of ethyl 2-[4-(3—bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate, 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid, ethyl 2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate, ethyl 2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate, 2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, ethyl 2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate, ethyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate, 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, ethyl 1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}benzimidazole-5-carboxylate, 1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}benzimidazole-5-carboxylic acid, 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid, 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide, 2-(4-benzyloxyphenyl)-5-cyano-1-cyclopentylbenzimidazole, 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide oxime, ethyl 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylate, 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid, ethyl 2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate, 2-{4[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, ethyl 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate, 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid, ethyl 2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate, 2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, ethyl 2-[4-(3-acetoxyphenyloxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylate, ethyl 1-cyclohexyl-2-[4-(3-hydroxyphenyloxy)phenyl]-benzimidazole-5-carboxylate, ethyl 1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]phenyl}-benzimidazole-5-carboxylate, 1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]phenyl}-benzimidazole-5-carboxylic acid, 2-(benzyloxyphenyl)-1-cyclopentylbenzimidazole, ethyl 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylate, 2-(4-benzyloxyphenyl)-1-cyclopentyl-N,N-dimethylbenzimidazole-5-carboxamide, 2-(4-benzyloxyphenyl)-1-cyclopentyl-N-methoxy-N-methylbenzimidazole-5-carboxamide, 2-(4-benzyloxyphenyl)-1-cyclopentyl-5-(1-hydroxy-1-methylethyl)-benzimidazole, 5-acetyl-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole, 2-(4-benzyloxyphenyl)-1-cyclopentyl-N-(2-dimethylaminoethyl)-benzimidazole-5-carboxamide dihydrochloride, 2-(4-benzyloxyphenyl)-1-cyclopentyl-5-nitrobenzimidazole, 5-amino-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole hydrochloride, 5-acetylamino-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole, 2-(4-benzyloxyphenyl)-1-cyclopentyl-5-methanesulfonyl-aminobenzimidazole, 5-sulfamoyl-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole, 2-[4-(4-tert-butylbenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid, 2-[4-(4-carboxybenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid, 2-[4-(4-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid, 2-{4-[(2-chloro-5-thienyl)methoxy]phenyl}-1-cyclopentyl-benzimidazole-5-carboxylic acid, 1-cyclopentyl-2-[4-(4-trifluoromethylbenzyloxy)phenyl]-benzimidazole-5-carboxylic acid, 1-cyclopentyl-2-[4-(4-methoxybenzyloxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclopentyl-2-[4-(4-pyridylmethoxy)phenyl]benzimidazole-5-carboxylic acid hydrochloride, 1-cyclopentyl-2-[4-(4-methylbenzyloxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclopentyl-2-{4-[(3,5-dimethyl-4-isoxazolyl)methoxy]phenyl}-benzimidazole-5-carboxylic acid, [2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazol-5-yl]-carbonylaminoacetic acid, 2-[4-(2-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid, 2-[4-(3-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid, 2-(4-benzyloxyphenyl)-3-cyclopentylbenzimidazole-5-carboxylic acid, 2-[4-(benzenesulfonylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid, 1-cyclopentyl-2-[4-(3,5-dichlorophenylcarbonylamino)phenyl]-benzimidazole-5-carboxylic acid, 2-{4-[(4-chlorophenyl)carbonylamino]phenyl}-1-cyclopentyl-benzimidazole-5-carboxylic acid, 2-{4-[(4-tert-butylphenyl)carbonylamino]phenyl}-1-cyclopentyl-benzimidazole-5-carboxylic acid, 2-{4-[(4-benzyloxyphenyl)carbonylamino]phenyl}-1-cyclopentyl-benzimidazole-5-carboxylic acid, trans-4-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]cyclohexan-1-ol, trans-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-methoxycyclohexane, 2-(4-benzyloxyphenyl)-5-carboxymethyl-1-cyclopentylbenzimidazole, 2-[(4-cyclohexylphenyl)carbonylamino]-1-cyclopentylbenzimidazole-5-carboxylic acid, 1-cyclopentyl-2-[4-(3,5-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclopentyl-2-[4-(3,4-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclopentyl-2-[4-(phenylcarbamoylamino)phenyl]benzimidazole-5-carboxylic acid, 1-cyclopentyl-2-[4-(diphenylmethoxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclopentyl-2-(4-phenethyloxyphenyl)benzimidazole-5-carboxylic acid, trans-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-tert-butylcyclohexane, 2-(4-benzyloxyphenyl)-5-carboxymethoxy-1-cyclopentylbenzimidazole, 2-(4-benzylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid, 2-[4-(N-benzenesulfonyl-N-methylamino)phenyl]-1-cyclopentyl-benzimidazole-5-carboxylic acid, 2-[4-(N-benzyl-N-methylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid, 1-cyclohexyl-2-(4-phenethylphenyl)benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(3,5-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(diphenylmethoxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(3,5-di-tert-butylbenzyloxy)phenyl]-benzimidazole-5-carboxylic acid, 2-(4-benzyloxyphenyl)-1-(4-methylcyclohexyl)benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[2-(2-naphthyl)ethoxy]phenyl}benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(1-naphthyl)methoxyphenyl]benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(dibenzylamino)phenyl]benzimidazole-5-carboxylic acid, 2-[4-(2-biphenylylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-(4-benzyloxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(dibenzylmethoxy)phenyl]benzimidazole-5-carboxylic acid, 2-(4-benzoylmethoxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(3,3-diphenylpropyloxy)phenyl]benzimidazole-5-carboxylic acid, 2-[4-(3-chloro-6-phenylbenzyloxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[2-(phenoxy)ethoxy]phenyl}benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(3-phenylpropyloxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(5-phenylpentyloxy)phenyl]benzimidazole-5-carboxylic acid, 2-(2-benzyloxy-5-pyridyl)-1-cyclohexylbenzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[2-(3,4,5-trimethoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid, 2-(4-benzyloxyphenyl)-1-(4,4-dimethylcyclohexyl)benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[2-(1-naphthyl)ethoxy]phenyl}benzimidazole-5-carboxylic acid, 2-[4-(2-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-[4-(3-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(2-hydroxyphenoxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(3-hydroxyphenoxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(2-methoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(3-methoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(2-propoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(3-propoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[2-(3-methyl-2-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[3-(3-methyl-2-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(2-isopentyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(3-isopentyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[2-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)ethoxy]phenyl}benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[2-(4-trifluoromethylphenyl)benzyloxy]-phenyl}benzimidazole-5-carboxylic acid, 2-{4-[bis(4-chlorophenyl)methoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[2-(4-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[2-(2-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[2-(3-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid, 2-(4-benzyloxyphenyl)-1-cycloheptylbenzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(2-phenethyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(3-phenethyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(2,2-diphenylethoxy)phenyl]benzimidazole-5-carboxylic acid, cis-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-fluorocyclohexane, 1-cyclohexyl-2-[4-(2-phenoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(3-phenoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid, 2-{4-[(2R)-2-benzyloxycarbonylamino-2-phenylethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{2-fluoro-4-[2-(4-trifluoromethylphenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid, 2-[4-(4-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[bis(4-methylphenyl)methoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[bis(4-fluorophenyl)methoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 1-cyclohexyl-6-methoxy-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic acid, 1-cyclohexyl-6-hydroxy-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic acid, 1-cyclohexyl-6-methyl-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic acid, 2-{4-[2-(2-benzyloxyphenyl)ethoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[2-(3-benzyloxyphenyl)ethoxy]phenyl-}1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-[4-(2-carboxymethyloxyphenoxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-[4-(3-carboxymethyloxyphenoxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[3-chloro-6-(4-methylphenyl)benzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[3-chloro-6-(4-methoxyphenyl)benzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxlic acid, 1-cyclohexyl-2-{2-methyl-4-[2-(4-trifluoromethylphenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid, 2-{4-[2-(4-tert-butylphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-(3-chloro-6-phenylbenzyloxy)-2-fluorophenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[3-chloro-6-(3,5-dichlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[bis(4-fluorophenyl)methoxy]-2-fluorophenyl}1-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-(4-benzyloxyphenoxy)-2-chlorophenyl-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-(4-benzyloxyphenoxy)-2-trifluoromethylphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[3-chloro-6-(2-trifluoromethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[(2R)-2-amino-2-phenylethoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-[4-(2-biphenylyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-[4-(3-biphenylyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-{(1-tert-butoxycarbonyl-4-piperidyl)methoxy}phenoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[3-{(1-tert-butoxycarbonyl-4-piperidyl)methoxy}phenoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[3-chloro-6-(3,4,5-trimethoxyphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(2-biphenylyl)ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-[4-(2-biphenylylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[2-(4-piperidylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid hydrochloride, 1-cyclohexyl-2-{4-[3-(4-piperidylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid hydrochloride, 2-{4-[(2R)-2-acetylamino-2-phenylethoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[3-(4-methyl-3-pentenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[3-(3-methyl-3-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid, 2-{4-[{(2S)-1-benzyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[3-chloro-6-(4-methylthiophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[3-chloro-6-(4-methanesulfonylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[3-chloro-6-(2-thienyl)benzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[3-chloro-6-(3-chlorophenyl)benzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[3-chloro-6-(3-pyridyl)benzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[3-chloro-6-(4-fluorophenyl)benzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-[4-(4-benzyloxyphenoxy)-3-fluorophenyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[3-chloro-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-{(1-acetyl-4-piperidyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[3-{(1-acetyl-4-piperidyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[3-(2-propynyloxy)phenoxy]phenyl}benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[3-(3-pyridylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid, 2-(4-benzyloxy-2-methoxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-[4-(carboxydiphenylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-5-nitrobenzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[3-acetylamino-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(4-carboxyphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid 2-{4-[{(2S)-1-benzyloxycarbonyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{2-chloro-4-[2-(4-trifluoromethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[3-(2-pyridylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-5-fluorobenzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[3-carboxy-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]phenyl}1-cyclohexylbenzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[2-(dimethylcarbamoylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[2-(piperidinocarbonylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid, 2-{4-[{(2S)-1-benzenesulfonyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[{(2S)-1-benzoyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(4-carbamoylphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[3-(dimethylcarbamoylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[3-(piperidinocarbonylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[3-{(1-methanesulfonyl-4-piperidyl)methoxy}-phenoxy]phenyl}benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[{2-methyl-5-(4-chlorophenyl)-4-oxazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid, 2-{4-[3-(3-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[3-(4-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[3-(4-fluorobenzyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[{(2S)-1-(4-nitrophenyl)-2-pyrrolidinyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[{(2S)-1-phenyl-2-pyrrolidinyl}methoxy]phenyl}-benzimidazole-5-carboxylic acid hydrochloride, 2-{4-[{(2S)-1-(4-acetylaminophenyl)-2-pyrrolidinyl}methoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[{5-(4-chlorophenyl)-2-methyl-4-thiazolyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[bis(3-fluorophenyl)methoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[2-(4-chlorophenyl)-3-nitrobenzyloxy]phenyl}-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[3-(4-tetrahydropyranyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[3-(4-trifluoromethylbenzyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[3-(1-methyl-4-piperidyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic acid, 2-{4-[3-(4-tert-butylbenzyloxy)phenoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[3-(2-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[3-(3-pyridyl)phenoxy]phenyl}benzimidazole-5-carboxylic acid, 2-{4-[3-(4-chlorophenyl)phenoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[3-(4-methoxyphenyl)phenoxy]phenyl}-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[{4-(4-methanesulfonylphenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid, 2-{4-[{4-(4-chlorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[1-(4-chlorobenzyl)-3-piperidyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[3-{(2-methyl-4-thiazolyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[3-{(2,4-dimethyl-5-thiazolyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[3-(3,5-dichlorophenyl)phenoxy]phenyl}-benzimidazole-5-carboxylic acid, 2-{4-[1-(4-chlorobenzyl)-4-piperidyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[3-(4-chlorobenzyloxy)piperidino]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[4-carbamoyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[4-(4-chlorobenzyloxy)piperidino]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[3-{(2-chloro-4-pyridyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[{(2S)-1-(4-dimethylcarbamoylphenyl)-2-pyrrolidinyl}-methoxy]phenyl}1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-5-ethoxycarbonylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 1-cyclohexyl-2-[4-(3-trifluoromethylphenoxy)phenyl]-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[{4-(4-dimethylcarbamoylphenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboloxylic acid, 2-{4-[{4-(4-chlorophenyl)-2-methyl-5-pyrimidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[{2-(4-chlorophenyl)-3-pyridyl}methoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid dihydrochloride, 2-{4-[{3-(4-chlorophenyl)-2-pyridyl}methoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[2-(3-chlorophenyl)-4-methylamino-1,3,5-triazin-6-yloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid trifluoroacetate, 2-{4-[2-(4-chlorophenyl)-4-(5-tetrazolyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-[4-(4-benzyloxy-6-pyrimidinyloxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[4-(4-pyridylmethoxy)-6-pyrimidinyloxy]phenyl}-benzimidazole-5-carboxylic acid, 2-{4-[4-(3-chlorophenyl)-6-pyrimidinyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate, 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, ethyl 2-{4-[3-(4-chlorophenyl)pyridin-2-ylmethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate, methyl 2-[4-(2-bromo-5-tert-butoxycarbonylbenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate, methyl 2-{4-[5-tert-butoxycarbonyl-2-(4-chlorophenyl) benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate, methyl 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride, methyl 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate, 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[3-(tert-butylsulfamoyl)-6-(4-chlorophenyl) benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-5-sulfamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid trifluoroacetate, 2-(4-benzyloxycyclohexyl)-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-[2-(2-biphenylyloxymethyl)-5-thienyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-[2-(2-biphenylyloxymethyl)-5-furyl]1-cyclohexylbenzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-hydroxymethyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid, 1-cyclohexyl-2-{4-[{4-(4-carboxyphenyl)-2-methyl-5-thiazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid hydrochloride, 1-cyclohexyl-2-{2-fluoro-4-[4-fluoro-2-(3-fluorobenzoyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-sulfonic acid, 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-3-cyclohexyl-benzimidazole-4-carboxylic acid, 1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-5-(4-pyridylmethoxy)-phenoxy]phenyl}benzimidazole-5-carboxylic acid dihydrochloride, 1-cyclohexyl-2-{4-[3-carboxy-5-(4-pyridylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic acid dihydrochloride, 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-benzimidazole-4-carboxylic acid, 2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[{2-(4-carboxyphenyl)-3-pyridyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-(4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-6-(4-trifluoromethyl-phenyl) benzyloxy]phenyl}benzimidazole-5-carboxylic acid hydrochloride, 1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-6-(4-methylthiophenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]-2-fluorophenyl}1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]-2-fluorophenyl}1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[3-dimethylcarbamoyl-6-(4-methanesulfonylphenyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[3-dimethylcarbamoyl-6-(3-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride, 2-{4-[3-dimethylcarbamoyl-6-(4-dimethylcarbamoylphenyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]-2-fluorophenyl}-1-(4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-5-dimethylsulfamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-methanesulfonylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, methyl 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-dimethylaminobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride, 2-{4-[2-(4-chlorophenyl)-5-methanesulfonylaminobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-diethylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-isopropylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-piperidinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(1-pyrrolidinyl)carbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(2-hydroxyethyl)carbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidino)-carbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-morpholinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-thiomorpholinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[3-(carboxymethylcarbamoyl)-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-{4-(2-carboxyethyl)phenyl}-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[3-chloro-6-(4-hydroxymethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[3-chloro-6-(4-methoxymethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(3-carboxyphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-5-methylthiobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-5-methylsulfinylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-5-cyanobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[bis(3-pyridyl)methoxy]-2-fluorophenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[bis(4-dimethylcarbamoylphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, sodium 2-{4-[2-thienyl-3-thienylmethoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate, methyl 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate, sodium 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate, 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(4-carboxyphenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(4-carbamoylphenyl)-5-(dimethylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[5-amino-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid, 2-{4-[5-(4-chlorophenyl)-2-methoxybenzylsulfinyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[5-(4-chlorophenyl)-2-methoxybenzylsulfinyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-methoxybenzylthio]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[bis(4-carboxyphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-[4-(phenyl-3-pyridylmethoxy)-2-fluorophenyl]-1-cyclohexyl-benzimidazole-5-carboxylic acid, methyl 2-{4-[2-(4-chlorophenyl)-5-(methylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate, 2-{4-[5-chloro-2-(4-pyridyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(benzylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(cyclohexylmethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-4-[2-(4-chlorophenyl)-5-(4-pyridylmethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(N-benzyl-N-methylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylate, 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylic acid, 2-(4-benzyloxyphenyl)-1-cyclopentyl-1H-indole-5-carboxylic acid, ethyl 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylate, 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylic acid, and 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-3-cyclohexyl-3H-imidazo[4,5-b]pyridine-6-carboxylic acid.
  • 92. The fused ring compound of claim 42 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of 2-{4-[5-dimethylaminocarbonyl-2-(4-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(4-methylpiperazin-1-ylcarbonyl) benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride, 2-{4-[2-(4-chlorophenyl)-5-{N-(3-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride, 2-{4-[2-(4-chlorophenyl)-5-{N-(2-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(cyclohexylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(2-pyridin-4-ylethylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride, 2-{4-[(4-fluorophenyl){4-(dimethylaminocarbonyl)phenyl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[(4-fluorophenyl)(4-carboxyphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-5-(4-oxopiperidinocarbonyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-hydroxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(N-isopropyl-N-methylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(phenylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(4-methoxypiperidinocarbonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(3-hydroxypropyloxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, and 2-{4-[2-(4-chlorophenyl)-5-(2-hydroxyethoxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride.
  • 93. The fused ring compound of claim 42 or a pharmaceutically acceptable salt thereof, which is selected from the group, consisting of methyl 2-[4-(2-bromo-5-nitrobenzyloxy)-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate, methyl 2-[4-{2-(4-chlorophenyl)-5-nitrobenzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate, methyl 2-[4-{5-amino-2-(4-chlorophenyl)benzyloxy-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate, methyl 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate, 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(4-methylpiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[5-acetyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-{(4-hydroxypiperidin-1-ylcarbonyl)methoxy}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-5-(2-methoxyethoxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-{2-(2-methoxyethoxy)ethoxy}benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(isobutylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-5-(2-methylthiazol-4-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-5-(3,4-dihydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(3-methyl-1,2,4-oxadiazol-5-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-4-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-4-(piperidinocarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-{(1-hydroxy-2-methylpropan-2-yl)carbamoyl}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(4,4-dimethyl-2-oxazolin-2-yl)}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride, 2-{4-[2-(4-chlorophenyl)-4-(4-hydroxypiperidin-1-ylcarbonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-4-{(2-hydroxyethyl)carbamoyl}benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-4-{(4-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-4-(dimethylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[5-(2-aminothiazol 4-yl)-2-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylsulfonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[5-(dimethylcarbamoyl)-2-(4-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[5-(dimethylcarbamoyl)-2-(3-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(5-chlorothiophen-2-yl)-5-(dimethylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-bromo-5-(5-methyloxazol-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-bromo-5-(5-methylthiazol-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(5-methyloxazol-2-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(5-methylthiazol-2-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-tetrazol-5-ylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[5-chloro-2-(4-cyanophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[5-chloro-2-(4-tetrazol-5-ylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-{2-(4-hydroxypiperidin-1-yl)ethoxy}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(2-oxopiperidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[3-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(N-hydroxyamidino)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(2,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(2-oxo-3H-1,2,3,5-oxathiadiazol-4-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(2,5-dihydro-5-oxo-4H-1,2,4-thiadiazol-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(cyclopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(cyclobutylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(tert-butylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(isobutylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-{(1-hydroxypropan-2-yl)carbamoyl}-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(methoxycarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-{(2,3-dihydroxypropyl)carbamoyl}-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(N-ethyl-N-methylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(N-methyl-N-propylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(N-isopropyl-N-methylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(2,6-dimethylpiperidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[5-(butylcarbamoyl)-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(propylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(ethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-{(dimethylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-{(morpholinocarbonyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-ureidobenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-{(ethylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-{(isopropylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(3,4-difluorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[2-(2,4-difluorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(3,5-dichlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(3-chloro-4-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(3,4-dichlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chloro-2-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chloro-2-fluorophenyl)-5-(pyrrolidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chloro-3-fluorophenyl)-5-(pyrrolidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chloro-3-fluorophenyl)-5-(isopropylcarbamoyl-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-{4-(methylthio)phenyl}-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-{4-(methylthio)phenyl}-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[4-chloro-2-(4-chlorophenyl)-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[4-chloro-2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(isopropylaminosulfonyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl-benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)-benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-phenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-piperidinobenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-2-fluorophenyl}-1-piperidinobenzimidazole-5-carboxylic acid, 2-{4-[2-(4-chlorophenyl)-5-(2-imidazolin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride, 2-44-(2-(4-chlorophenyl)-5-(2-oxooxazolidin-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(2-oxoimidazolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(2-oxazolin-2-ylamino)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride, 2-{4-[{2-[{(dimethylcarbamoyl)methoxy}methyl]-4-(4-fluorophenyl)thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[{4-(4-fluorophenyl)-2-(4-hydroxypiperidin-1-ylmethyl)thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride, 2-{4-[{4-(4-fluorophenyl)-2-[(carbamoylmethoxy)methyl]thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[{4-(4-fluorophenyl)-2-(methylcarbamoyl)thiazol-5-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[{4-(4-fluorophenyl)-2-{(2-hydroxyethyl)carbamoyl}thiazol-5-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[{2-(4-fluorophenyl)-5-(dimethylcarbamoyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[{2-(4-fluorophenyl)-5-(isopropylcarbamoyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[{2-(4-fluorophenyl)-5-(4-hydroxypiperidin-1-yl carbonyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-tetrazol-5-ylbenzimidazole, 2-{4-[2-(4-carboxyphenyl)-5-chlorobenzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-tetrazol-5-ylbenzimidazole hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-(2,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl)benzimidazole hydrochloride, 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-5-cyano-1-cyclohexylbenzimidazole, 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-5-cyano-1-cyclohexylbenzimidazole, 2-{4-[{N-(4-dimethylcarbamoyl)-N-(4-fluorophenyl)amino}methyl]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{5-[bis(3-fluorophenyl)methyl]-2-fluoro-4-hydroxyphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{3-[bis(3-fluorophenyl)methyl]-2-fluoro-4-hydroxyphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid, 2-{4-[(3-dimethylcarbamoylphenyl)(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[{3-(4-hydroxypiperidyl-1-ylcarbonyl)phenyl}(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 1-{[2-{4-([4-(4-fluorophenyl)-2-methylthiazol-5-yl]methoxy)phenyl}-1-cyclohexylbenzimidazol-5-yl]carbonyl}-β-D-glucuronic acid, {[2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazol-5-yl]carbonyl}-β-D-glucuronic acid, 2-{4-[2-(4-chlorophenyl)-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride, 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-3-cyclohexyl-3H-imidazo[4,5-b]pyridine-6-carboxylic acid hydrochloride, and 2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-phenyl}-3-cyclohexyl-3H-imidazo[4,5-b]pyridine-6-carboxylic acid hydrochloride.
  • 94. A pharmaceutical composition comprising a fused ring compound of claim 42, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
  • 95. A hepatitis C virus polymerase inhibitor comprising a fused ring compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
  • 96. An anti-hepatitis C virus agent comprising a fused ring compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
  • 97. A therapeutic agent for hepatitis C comprising a fused ring compound of claim 42, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
  • 98. An anti-hepatitis C virus agent comprising (a) the anti-hepatitis C virus agent of claim 96 and (b) at least one agent selected from the group consisting of a different antiviral agent, an antiinflammatory agent and an immunostimulant.
  • 99. An anti-hepatitis C virus agent comprising (a) the anti-hepatitis C virus agent of claim 96 and (b) interferon.
  • 100. A therapeutic agent for hepatitis C comprising (a) the hepatitis C virus polymerase inhibitor of claim 95 and (b) at least one agent selected from the group consisting of a different antiviral agent, an antiinflammatory agent and an immunostimulant.
  • 101. A therapeutic agent for hepatitis C comprising (a) the hepatitis C virus polymerase inhibitor of claim 95 and (b) interferon.
  • 102. A thiazole compound selected from the group consisting of 4-(4-fluorophenyl)-5-hydroxymethyl-2-methylthiazole and 4-(4-fluorophenyl)-5-chloromethyl-2-methylthiazole, or a pharmaceutically acceptable salt thereof.
  • 103. A pharmaceutical composition comprising (a) the fused compound of the formula [I] of claim 1 or a pharmaceutically acceptable salt thereof and (b) at least one agent selected from the group consisting of an antiviral agent other than the compound of claim 1, an antiinflammatory agent and an immunostimulant.
  • 104. A pharmaceutical composition comprising (a) the fused compound of the formula [I] of claim 1 or a pharmaceutically acceptable salt thereof and (b) interferon.
  • 105. A method for treating hepatitis C, which comprises administering an effective amount of a fused ring compound of the formula [I] of claim 1 or a pharmaceutically acceptable salt thereof.
  • 106. The method of claim 105, further comprising administering an effective amount of at least one agent selected from the group consisting of an antiviral agent other than the compound of claim 1, an antiinflammatory agent and an immunostimulant.
  • 107. The method of claim 105, further comprising administering an effective amount of interferon.
  • 108. A method for inhibiting hepatitis C virus polymerase, which comprises administering an effective amount of a fused ring compound of the formula [I] of claim 1 or a pharmaceutically acceptable salt thereof.
  • 109. The method of claim 108, further comprising administering an effective amount of at least one agent selected from the group consisting of an antiviral agent other than the compound of claim 1, an antiinflammatory agent and an immunostimulant.
  • 110. The method of claim 108, further comprising administering an effective amount of interferon.
Priority Claims (3)
Number Date Country Kind
369008/1999 Dec 1999 JP
391904/2000 Dec 2000 JP
193786/2001 Jun 2001 JP
Parent Case Info

[0001] This application is a divisional of copending U.S. patent application Ser. No. 09/939,374, filed Aug. 24, 2001, which is a continuation-in-part of PCT/JP00/09181 filed on Dec. 22, 2000.

Divisions (1)
Number Date Country
Parent 09939374 Aug 2001 US
Child 10615329 Jul 2003 US
Continuation in Parts (1)
Number Date Country
Parent PCT/JP00/09181 Dec 2000 US
Child 09939374 Aug 2001 US