Fused cyclic compounds and medicinal use thereof

TECHNICAL FIELD

[0001] 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

[0002] 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.

[0003] The patients infected with HCV are considered to involve several percent of the world population, and the infection with HCV characteristically becomes chronic.

[0004] 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.

[0005] 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. In addition, there is a report on the involvement of HCV infection in dermatosis such as chronic urticaria, lichen planus, cryoglobulinemic purpura and the like (The Japanese Journal of Dermatology, 111(7), 1075-81, 2001).

[0006] 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.

[0007] 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.

[0008] 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.

[0009] 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.

[0010] In addition, the inhibition of HCV growth, wherein HCV-specific protein is targeted, has been drawing attention these days.

[0011] 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.

[0012] 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.

[0013] 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.

[0014] The following discloses known compounds relatively similar to the compound of the present invention.

[0015] The therapeutic agents for hepatitis C, which have a benzimidazole skeleton, are known from JP-A-2001-247550 (WO01/47883, EP1162196A1) and WO02/04425.

[0016] These publications disclose the following β-ketoamide compounds J etc. and K etc., respectively, as anti-HIV agents having an integrase inhibitory activity:

[0017] Note that the earliest publication dates of these publications are Jul. 5, 2001 (WO01/47883) and Jan. 17, 2002 (WO02/04425), and the priority date of the present application is Jun. 26, 2001, antedating these publication dates.

[0018] In addition, a known therapeutic agent for hepatitis C having a benzimidazole skeleton is also disclosed in WO97/36866, Japanese Patent Application under PCT laid-open under kohyo No. 2000-511899 (EP906097) and WO99/51619.

[0019] WO97/36866 discloses the following compound D and the like, and HCV helicase inhibitory activity of the compounds.

[0020] 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.

[0021] However, these publications do not include the compound disclosed in the present specification, or a disclosure suggestive thereof.

[0022] 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).

[0023] 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.

[0024] 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.

[0025] The benzimidazole derivatives having an antiviral activity have been disclosed in JP-A-3-31264, U.S. Pat. No. 3,644,382 and U.S. Pat. No. 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.

[0026] However, none of these publications includes the compound of the present invention or a description regarding or suggestive of an anti-HCV effect.

[0027] 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.

[0028] 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.

[0029] 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.

[0030] 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.

[0031] 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.

[0032] 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.

[0033] 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

[0034] 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.

[0035] 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.

[0036] 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.

[0037] Thus, the present invention provides the following (1) to (87).

[0038] (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:

[0039] wherein

[0040] a broken line is a single bond or a double bond,

[0041] G1 is C(—R1) or a nitrogen atom,

[0042] G2 is C(—R2) or a nitrogen atom,

[0043] G3 is C(—R3) or a nitrogen atom,

[0044] G4 is C(—R4) or a nitrogen atom,

[0045] G5, G6, G8 and G9 are each independently a carbon atom or a nitrogen atom,

[0046] G7 is C(—R7), an oxygen atom, a sulfur atom, or a nitrogen atom optionally substituted by R8,

[0047] wherein R1, R2, R3 and R4 are each independently,

[0048] (1) hydrogen atom,

[0049] (2) C1-6 alkanoyl,

[0050] (3) carboxyl,

[0051] (4) cyano,

[0052] (5) nitro,

[0053] (6) C1-6 alkyl optionally substituted by 1 to 3 substituent(s) selected from the following group A, group A; halogen atom, hydroxyl group, carboxyl, amino,

[0054] C1-6 alkoxy, C1-6 alkoxy C1-6 alkoxy, C1-6 alkoxycarbonyl and C1-6 alkylamino,

[0055] (7) —COORa1

[0056] 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, group B; halogen atom, cyano, nitro, C1-6 alkyl,

[0057] 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,

[0058] (8) —CONRa2Ra3

[0059] wherein Ra2 and Ra3 are each independently hydrogen atom, C1-6 alkoxy or optionally substituted C1-6 alkyl (as defined above),

[0060] (9) —C(═NRa4)NH2

[0061] wherein Ra4 is hydrogen atom or hydroxyl group,

[0062] (10) —NHRa5

[0063] wherein Ra5 is hydrogen atom, C1-6 alkanoyl or C1-6 alkylsulfonyl,

[0064] (11) —ORa6

[0065] wherein Ra6 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above),

[0066] (12) —SO2Ra7

[0067] wherein Ra7 is hydroxyl group, amino, C1-6 alkyl or C1-6 alkylamino,

[0068] (13) —P(═O) (ORa31)2

[0069] 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

[0070] or

[0071] (14) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, and

[0072] R7 and R8 are each hydrogen atom or optionally substituted

[0073] C1-6 alkyl (as defined above),

[0074] ring Cy is

[0075] (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,

[0076] (2) C3-8 cycloalkenyl optionally substituted by 1 to 5 substituent(s) selected from the above group C, or

[0077] (3)

[0078] wherein u and v are each independently an integer of 1 to 3,

[0079] ring A is

[0080] (1) C6-14 aryl,

[0081] (2) C3-8 cycloalkyl,

[0082] (3) C3-8 cycloalkenyl or

[0083] (4) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

[0084] R5 and R6 are each independently

[0085] (1) hydrogen atom,

[0086] (2) halogen atom,

[0087] (3) optionally substituted C1-6 alkyl (as defined above) or

[0088] (4) —ORa8

[0089] wherein Ra8 is hydrogen atom, C1-6 alkyl or C6-14 aryl C1-6 alkyl, and

[0090] x is

[0091] (1) hydrogen atom,

[0092] (2) halogen atom,

[0093] (3) cyano,

[0094] (4) nitro,

[0095] (5) amino, C1-6 alkanoylamino,

[0096] (6) C1-6 alkylsulfonyl,

[0097] (7) optionally substituted C1-6 alkyl (as defined above),

[0098] (8) C2-6 alkenyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,

[0099] (9) —COORa9

[0100] wherein Ra9 is hydrogen atom or C1-6 alkyl,

[0101] (10) —CONH—(CH2)1—Ra10

[0102] 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,

[0103] (11) —ORa11

[0104] wherein Ra11 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above)

[0105] or

[0106] (12)

[0107] wherein

[0108] ring B is

[0109] (1′) C6-14 aryl,

[0110] (2′) C3-8 cycloalkyl or

[0111] (3′) heterocyclic group (as defined above),

[0112] each Z is independently

[0113] (1′) a group selected from the following group D,

[0114] (2′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

[0115] (3′) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

[0116] (4′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

[0117] (5′) heterocyclic group optionally substituted by 1 to S substituent(s) selected from the following group D,

[0118] wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, or

[0119] (6′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

[0120] 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,

[0121] group D:

[0122] (a) hydrogen atom,

[0123] (b) halogen atom,

[0124] (c) cyano,

[0125] (d) nitro,

[0126] (e) optionally substituted C1-6 alkyl (as defined above),

[0127] (f) —(CH2)t—CORa18,

[0128] (hereinafter each t means independently 0 or an integer of 1 to 6),

[0129] wherein Ra18 is

[0130] (1″) optionally substituted C1-6 alkyl (as defined above),

[0131] (2″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

[0132] (3″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B

[0133] wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

[0134] (g) —(CH2)t—COORa19

[0135] 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,

[0136] (h) —(CH2)t—CONRa27Ra28

[0137] wherein Ra27 and Ra28 are each independently,

[0138] (1″) hydrogen atom,

[0139] (2″) optionally substituted C1-6 alkyl (as defined above),

[0140] (3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0141] (4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0142] (5″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0143] (6″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0144] 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,

[0145] (7″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0146] (8″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0147] (9″) hydroxyl group or

[0148] (10″) C1-6 alkoxy,

[0149] (i) —(CH2)t—C(═NRa33)NH2

[0150] wherein Ra33 is hydrogen atom, C1-6 alkyl, hydroxyl group or C1-6 alkoxy,

[0151] (j) —(CH2)t—ORa20

[0152] wherein Ra20 is

[0153] (1″) hydrogen atom,

[0154] (2″) optionally substituted C1-6 alkyl (as defined above),

[0155] (3″) optionally substituted C2-6 alkenyl (as defined above),

[0156] (4″) C2-6 alkynyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,

[0157] (5″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0158] (6″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0159] (7″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0160] (8″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0161] (9″) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

[0162] (10″) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0163] (k) —(CH2)t—O—(CH2)p—CORa21

[0164] 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,

[0165] (1) —(CH2)t—NRa22Ra23

[0166] wherein Ra22 and Ra23 are each independently

[0167] (1″) hydrogen atom,

[0168] (2″) optionally substituted C1-6 alkyl (as defined above),

[0169] (3″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0170] (4″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0171] (5″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

[0172] (6″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0173] (m) —(CH2)t—NRa29CO—Ra24

[0174] wherein Ra29 is hydrogen atom, C1-6 alkyl or C1-6 alkanoyl, and Ra24 is

[0175] (1″) amino,

[0176] (2″) C1-6 alkylamino,

[0177] (3″) optionally substituted C1-6 alkyl (as defined above),

[0178] (4″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0179] (5″) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B or

[0180] (6″) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0181] (n) —(CH2)t—NRa29SO2—Ra25

[0182] 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,

[0183] (o) —(CH2)t—S(O)qRa25

[0184] wherein Ra25 is as defined above, and q is 0, 1 or 2,

[0185] (p) —(CH2)t—SO2—NHRa26

[0186] 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,

[0187] and

[0188] (q) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, and

[0189] w is an integer of 1 to 3, and

[0190] Y is

[0191] (1′) a single bond,

[0192] (2′) C1-6 alkylene,

[0193] (3′) C2-6 alkenylene,

[0194] (4′) —(CH2)m—O—(CH2)n—, (hereinafter m and n are each independently 0 or an integer of 1 to 6),

[0195] (5′) —CO—,

[0196] (6′) —CO2—(CH2)n—,

[0197] (7′) —CONH—(CH2)n—NH—,

[0198] (8′) —NHCO2—,

[0199] (9′) —NHCONH—,

[0200] (10′) —O—(CH2)n—CO—,

[0201] (11′) —O—(CH2)n—O—,

[0202] (12′) —SO2—,

[0203] (13′) —(CH2)m—NRa12—(CH2)n—

[0204] wherein Ra12 is

[0205] (1″) hydrogen atom,

[0206] (2″) optionally substituted C1-6 alkyl (as defined above),

[0207] (3″) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0208] (4″) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0209] (5″) —CORb5

[0210] 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,

[0211] (6″) —COORb5 (Rb5 is as defined above) or

[0212] (7″) —SO2Rb5 (Rb5 is as defined above),

[0213] (14′) —NRa12CO— (Ra12 is as defined above),

[0214] (15′) —CONRa13—(CH2)n—

[0215] 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,

[0216] (16′) —CONH—CHRa14—

[0217] wherein Ra14 is C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0218] (17′) —O—(CH2)m—CRa15Ra16—(CH2)n—

[0219] wherein Ra15 and Ra16 are each independently

[0220] (1″) hydrogen atom,

[0221] (2″) carboxyl,

[0222] (3″) C1-6 alkyl,

[0223] (4″) —ORb6

[0224] wherein Rb6 is C1-6 alkyl or C6-14 aryl C1-6 alkyl, or

[0225] (5 ″) —NHRb7

[0226] wherein Rb7 is hydrogen atom, C1-6 alkyl, C1-6 alkanoyl or C6-14 aryl C1-6 alkyloxycarbonyl, or Ra15 is optionally

[0227] (6″)

[0228] 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,

[0229] (18′) —(CH2)n—NRa12—CHRa15—(Ra12 and Ra15 are each as defined above),

[0230] (19′) —NRa17SO2—

[0231] wherein Ra17 is hydrogen atom or C1-6 alkyl,

[0232] (20′) —S(O)e—(CH2)m—CRa15Ra16—(CH2)n—(e is 0, 1 or 2, Ra15 and Ra16 are each as defined above),

[0233] or

[0234] (21′) —(CH2)m—CRa15Ra16—(CH2)n— (Ra15 and Ra16 are each as defined above).

[0235] (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.

[0236] (3) The therapeutic agent of (2) above, wherein G2 is C(—R2) and G6 is a carbon atom.

[0237] (4) The therapeutic agent of (2) or (3) above, wherein G5 is a nitrogen atom.

[0238] (5) The therapeutic agent of (1) above, wherein, in formula [I], the moiety

[0239] is a fused ring selected from

[0240] (6) The therapeutic agent of (5) above, wherein, in formula [I], the moiety

[0241] is a fused ring selected from

[0242] (7) The therapeutic agent of (6) above, which comprises a fused ring compound of the following formula [I-1]

[0243] wherein each symbol is as defined in (1), or a pharmaceutically acceptable salt thereof as an active ingredient.

[0244] (8) The therapeutic agent of (6) above, which comprises a fused ring compound of the following formula [I-2]

[0245] wherein each symbol is as defined in (1), or a pharmaceutically acceptable salt thereof as an active ingredient.

[0246] (9) The therapeutic agent of (6) above, which comprises a fused ring compound of the following formula [I-3]

[0247] wherein each symbol is as defined in (1), or a pharmaceutically acceptable salt thereof as an active ingredient.

[0248] (10) The therapeutic agent of (6) above, which comprises a fused ring compound of the following formula [I-4]

[0249] wherein each symbol is as defined in (1), or a pharmaceutically acceptable salt thereof as an active ingredient.

[0250] (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)),

[0251] (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).

[0252] (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.

[0253] (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.

[0254] (15) The therapeutic agent of any of (1) to (14) above, wherein the ring Cy is cyclopentyl, cyclohexyl, cycloheptyl,. tetrahydrothiopyranyl or piperidino.

[0255] (16) The therapeutic agent of any of (1) to (14) above, wherein the ring Cy is

[0256] wherein each symbol is as defined in (1).

[0257] (17) The therapeutic agent of any of (1) to (16) above, wherein the ring A is C6-14 aryl.

[0258] (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.

[0259] (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).

[0260] (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.

[0261] (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:

[0262] 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.

[0263] (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:

[0264] wherein each symbol is as defined in (21).

[0265] (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.

[0266] (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.

[0267] (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.

[0268] (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.

[0269] (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 claim 1, and at least one of Ra22 and Ra23 is amino or C1-6 alkylamino.

[0270] (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.

[0271] (29) A fused ring compound of the following formula [II]

[0272] wherein the moiety

[0273] is a fused ring selected from

[0274] wherein R1, R2, R3 and R4 are each independently,

[0275] (1) hydrogen atom,

[0276] (2) C1-6 alkanoyl,

[0277] (3) carboxyl,

[0278] (4) cyano,

[0279] (5) nitro,

[0280] (6) C1-6 alkyl optionally substituted by 1 to 3 substituent(s) selected from the following group A, group A; halogen atom, hydroxyl group, carboxyl, amino,

[0281] C1-6 alkoxy, C1-6 alkoxy C1-6 alkoxy, C1-6 alkoxycarbonyl and C1-6 alkylamino,

[0282] (7) —COORa1

[0283] 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; group B; halogen atom, cyano, nitro, C1-6 alkyl,

[0284] 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,

[0285] (8) —CONRa2Ra3

[0286] wherein Ra2 and Ra3 are each independently hydrogen atom, C1-6 alkoxy or optionally substituted C1-6 alkyl (as defined above),

[0287] (9) —C(═NRa4 )NH2

[0288] wherein Ra4 is hydrogen atom or hydroxyl group,

[0289] (10) —NHRa5

[0290] wherein Ra5 is hydrogen atom, C1-6 alkanoyl or C1-6 alkylsulfonyl,

[0291] (11) —ORa6

[0292] wherein Ra6 is hydrogen atom or optionally substituted C1-6 alkyl (as defined above),

[0293] (12) —SO2Ra7

[0294] wherein Ra7 is hydroxyl group, amino, C1-6 alkyl or C1-6 alkylamino,

[0295] (13) —P(═O) (ORa31)2

[0296] 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,

[0297] or

[0298] (14) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom, and

[0299] R7 is hydrogen atom or optionally substitute C1-6 alkyl (as defined above),

[0300] ring Cy′ is

[0301] (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

[0302] (2)

[0303] wherein u and v are each independently an integer of 1 to 3,

[0304] ring A′ is a group selected from a group consisting of phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, cyclohexyl, cyclohexenyl, furyl and thienyl,

[0305] R5 and R6 are each independently

[0306] (1) hydrogen atom,

[0307] (2) halogen atom,

[0308] (3) optionally substituted C1-6 alkyl (as defined above) or (4) hydroxyl group

[0309] ring B is

[0310] (1) C6-14 aryl,

[0311] (2) C3-8 cycloalkyl or

[0312] (3) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

[0313] each Z is independently

[0314] (1) a group selected from the following group D,

[0315] (2) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

[0316] (3) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

[0317] (4) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the following group D,

[0318] (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

[0319] (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, group D:

[0320] (a) hydrogen atom,

[0321] (b) halogen atom,

[0322] (c) cyano,

[0323] (d) nitro,

[0324] (e) optionally substituted C1-6 alkyl (as defined above),

[0325] (f) —(CH2)t—CORa18, (hereinafter each t means independently 0 or an integer of 1 to 6),

[0326] wherein Ra18 is

[0327] (1′) optionally substituted C1-6 alkyl (as defined above),

[0328] (2′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

[0329] (3′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B

[0330] wherein the heterocyclic group has 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

[0331] (g) —(CH2)t—COORa19

[0332] 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,

[0333] (h) —(CH2)t—CONRa27Ra28

[0334] wherein Ra27 and Ra28 are each independently,

[0335] (1′) hydrogen atom,

[0336] (2′) optionally substituted C1-6 alkyl (as defined above),

[0337] (3′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0338] (4′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0339] (5′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0340] (6′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0341] 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,

[0342] (7′) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0343] (8′) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0344] (9′) hydroxyl group or

[0345] (10′) C1-6 alkoxy,

[0346] (i) —(CH2)t—C(═NRa33)NH2

[0347] wherein Ra33 is hydrogen atom, C1-6 alkyl, hydroxyl group or C1-6 alkoxy,

[0348] (j) —(CH2)t—ORa20

[0349] wherein Ra20 is

[0350] (1′) hydrogen atom,

[0351] (2′) optionally substituted C1-6 alkyl (as defined above),

[0352] (3′) optionally substituted C2-6 alkenyl (as defined above),

[0353] (4′) C2-6 alkynyl optionally substituted by 1 to 3 substituent(s) selected from the above group A,

[0354] (5′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0355] (6′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0356] (7′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0357] (8′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0358] (9′) C3-8 cycloalkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

[0359] (10′) C3-8 cycloalkyl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0360] (k) —(CH2)t—O—(CH2)p—CORa21

[0361] wherein Ra21 is amino, C1-6 alkylamino or heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0362] and p is 0 or an integer of 1 to 6,

[0363] (l) —(CH2)t—NRa22Ra23

[0364] wherein Ra22 and Ra23 are each independently

[0365] (1′) hydrogen atom,

[0366] (2′) optionally substituted C1-6 alkyl (as defined above),

[0367] (3′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0368] (4′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0369] (5′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B or

[0370] (6′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0371] (m) —(CH2)t—NRa29CO—Ra24

[0372] wherein Ra29 is hydrogen atom, C1-6 alkyl or C1-6 alkanoyl, and

[0373] Ra24 is

[0374] (1′) amino,

[0375] (2′) C1-6 alkylamino,

[0376] (31) optionally substituted C1-6 alkyl (as defined above),

[0377] (4′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0378] (5′) heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from the above group B, or

[0379] (6′) heterocycle C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0380] (n) —(CH2)t—NRa29SO2—Ra25

[0381] 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,

[0382] (o) —(CH2)t—S(O)q—Ra25

[0383] wherein Ra25 is as defined above, and q is 0, 1 or 2,

[0384] (p) —(CH2)t—SO2—NHRa26

[0385] 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,

[0386] and

[0387] (q) heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfur atom,

[0388] w is an integer of 1 to 3, and

[0389] Y is

[0390] (1) a single bond,

[0391] (2) C1-6 alkylene,

[0392] (3) C2-6 alkenylene,

[0393] (4) —(CH2)m—O—(CH2)n—,

[0394] (hereinafter m and n are each independently 0 or an integer of 1 to 6),

[0395] (5) —CO—,

[0396] (6) —CO2—(CH2)n—,

[0397] (7) —CONH—(CH2)n—NH—,

[0398] (8) —NHCO2—,

[0399] (9) —NHCONH—,

[0400] (10) —O—(CH2)n—CO—,

[0401] (11) —O—(CH2)n—O—,

[0402] (12) —SO2—,

[0403] (13) —(CH2)m—NRa12—(CH2)n—

[0404] wherein Ra12 is

[0405] (1′) hydrogen atom,

[0406] (2′) optionally substituted C1-6 alkyl (as defined above),

[0407] (3′) C6-14 aryl C1-6 alkyl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0408] (4′) C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0409] (5′) —CORb5

[0410] 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,

[0411] (6′) —COORb5 (Rb5 is as defined above) or

[0412] (7′) —SO2Rb5 (Rb5 is as defined above),

[0413] (14) —NRa12CO— (Ra12 is as defined above),

[0414] (15) —CONRa13—(CH2)n—,

[0415] 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,

[0416] (16) —CONH—CHRa14—

[0417] wherein Ra14 is C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from the above group B,

[0418] (17) —O—(CH2)m—CRa15Ra16—(CH2)n—

[0419] wherein Ra15 and Ra16 are each independently

[0420] (1′) hydrogen atom,

[0421] (2′) carboxyl,

[0422] (3′) C1-6 alkyl,

[0423] (4′) —ORb6

[0424] wherein Rb6 is C1-6 alkyl or C6-14 aryl C1-6 alkyl,

[0425] or

[0426] (5′) —NHRb7

[0427] wherein Rb7 is hydrogen atom, C1-6 alkyl, C1-6 alkanoyl or C6-14 aryl C1-6 alkyloxycarbonyl, or Ra15 is optionally

[0428] (6′)

[0429] 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,

[0430] (18) —(CH2)n—NRa12—CHRa15— (Ra12 and Ra15 are each as defined above),

[0431] (19) —NRa17SO2—

[0432] wherein Ra17 is hydrogen atom or C1-6 alkyl,

[0433] (20) —S(O)e—(CH2)m—CRa15Ra16—(CH2)n— (e is 0, 1 or 2, Ra15 and Ra16 are each as defined above),

[0434] or

[0435] (21) —(CH2)m—CRa15Ra16—(CH2)n— (Ra15 and Ra16 are each as defined above),

[0436] or a pharmaceutically acceptable salt thereof.

[0437] (30) The fused ring compound of (29) above, which is represented by the following formula [II-1]

[0438] wherein each symbol is as defined in (29), or a pharmaceutically acceptable salt thereof.

[0439] (31) The fused ring compound of (29) above, which is represented by the following formula [II-2]

[0440] wherein each symbol is as defined in (29), or a pharmaceutically acceptable salt thereof.

[0441] (32) The fused ring compound of (29) above, which is represented by the following formula [II-3]

[0442] wherein each symbol is as defined in (29), or a pharmaceutically acceptable salt thereof.

[0443] (33) The fused ring compound of (29) above, which is represented by the following formula [II-4]

[0444] wherein each symbol is as defined in (29), or a pharmaceutically acceptable salt thereof.

[0445] (34) The fused ring compound of any of (29) to (33) 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 (29)),

[0446] or a pharmaceutically acceptable salt thereof.

[0447] (35) The fused ring compound of (34) above, wherein at least one of R1, R2, R3 and R4 is carboxyl, —COORa1 or —SO2Ra7 wherein Ra1 and Ra7 are as defined in (29), or a pharmaceutically acceptable salt thereof.

[0448] (36) The fused ring compound of (35) above, wherein at least one of R1, R2, R3 and R4 is carboxyl or —COORa1 wherein Ra1 is as defined in (29), or a pharmaceutically acceptable salt thereof.

[0449] (37) The fused ring compound of (36) above, wherein R2 is carboxyl and R1, R3 and R4 are hydrogen atoms, or a pharmaceutically acceptable salt thereof.

[0450] (38) The fused ring compound of any of (29) to (33) above, wherein at least one of R1, R2, R3 and R4 is —COORa1 wherein Ra1 is glucuronic acid residue, or a pharmaceutically acceptable salt thereof.

[0451] (39) The fused ring compound of any of (29) to (33) 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.

[0452] (40) The fused ring compound of any of (29) to (39) above, wherein the ring Cy′ is cyclopentyl, cyclohexyl, cycloheptyl or tetrahydrothiopyranyl, or a pharmaceutically acceptable salt thereof.

[0453] (41) The fused ring compound of (40) above, wherein the ring Cy′ is cyclopentyl, cyclohexyl or cycloheptyl, or a pharmaceutically acceptable salt thereof.

[0454] (42) The fused ring compound of any of (29) to (39) above, wherein the ring Cy′ is

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

[0456] (43) The fused ring compound of any of (29) to (42) above, wherein the ring A′ is phenyl, pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl, or a pharmaceutically acceptable salt thereof.

[0457] (44) The fused ring compound of (43) above, wherein the ring A′ is phenyl or pyridyl, or a pharmaceutically acceptable salt thereof.

[0458] (45) The fused ring compound of (44) above, wherein the ring A′ is phenyl, or a pharmaceutically acceptable salt thereof.

[0459] (46) The fused ring compound of any of (29) to (45) 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.

[0460] (47) The fused ring compound of any of (29) to (46) 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 (29)), or a pharmaceutically acceptable salt thereof.

[0461] (48) The fused ring compound of (47) above, wherein the Y is —(CH2)m—O—(CH2)n— or —O—(CH2)m—CRa15Ra16—(CH2)n— (wherein each symbol is as defined in (29)), or a pharmaceutically acceptable salt thereof.

[0462] (49) The fused ring compound of (48) above, wherein the Y is —(CH2)m—O—(CH2)n— wherein each symbol is as defined in (29), or a pharmaceutically acceptable salt thereof.

[0463] (50) The fused ring compound of any of (29) to (46) above, wherein the Y is —(CH2)m—CRa15Ra16—(CH2)n— (wherein each symbol is as defined in (29)), or a pharmaceutically acceptable salt thereof.

[0464] (51) The fused ring compound of any of (29) to (50) 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.

[0465] (52) The fused ring compound of any of (29) to (51) 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.

[0466] (53) The fused ring compound of any of (29) to (51) 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:

[0467] 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.

[0468] (54) The fused ring compound of (53) 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:

[0469] wherein each symbol is as defined in (53), or a pharmaceutically acceptable salt thereof.

[0470] (55) The fused ring compound of any of (29) to (51) above, wherein at least one group represented by group D is —(CH2)t—CONRa27Ra28 wherein each symbol is as defined in (29), and at least one of Ra27 and Ra28 is C1-6 alkoxy, or a pharmaceutically acceptable salt thereof.

[0471] (56) The fused ring compound of any of (29) to (51) above, wherein at least one group represented by group D is —(CH2)t—C(═NRa33)NH2 wherein each symbol is as defined in (29), and Ra33 is hydroxyl group or C1-6 alkoxy, or a pharmaceutically acceptable salt thereof.

[0472] (57) The fused ring compound of any of (29) to (51) above, wherein at least one group represented by group D is —(CH2)t—O—(CH2)p—CORa21 wherein each symbol is as defined in (29), and Ra21 is amino, or a pharmaceutically acceptable salt thereof.

[0473] (58) The fused ring compound of any of (29) to (51) above, wherein at least one group represented by group D is —(CH2)t—NRa29CO—Ra24 wherein each symbol is as defined in (29), and Ra24 is amino or C1-6 alkylamino, or a pharmaceutically acceptable salt thereof.

[0474] (59) The fused ring compound of any of (29) to (51) above, wherein at least one group represented by group D is —(CH2)t—NRa22Ra23 wherein each symbol is as defined in (29), and at least one of Ra22 and Ra23 is amino or C1-6 alkylamino, or a pharmaceutically acceptable salt thereof.

[0475] (60) The fused ring compound of any of (29) to (51) 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.

[0476] (61) The fused ring compound of the formula. [I] or a pharmaceutically acceptable salt thereof, which is selected from. the group consisting of

[0477] ethyl 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 1),

[0478] 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 2),

[0479] ethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate (Example 3),

[0480] ethyl 2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 4),

[0481] ethyl 2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 5),

[0482] 2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 6),

[0483] ethyl 2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 7),

[0484] ethyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 8),

[0485] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 9),

[0486] ethyl 1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}benzimidazole-5-carboxylate (Example 10),

[0487] 1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}benzimidazole-5-carboxylic acid (Example 11),

[0488] 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 12),

[0489] 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide (Example 13),

[0490] 2-(4-benzyloxyphenyl)-5-cyano-1-cyclopentylbenzimidazole (Example 14),

[0491] 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide oxime (Example 15),

[0492] ethyl 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylate (Example 16),

[0493] 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 17),

[0494] ethyl 1-cyclohexyl-2-(2-fluoro-4-hydroxyphenyl)benzimidazole-5-carboxylate (Example 18),

[0495] ethyl 2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 19),

[0496] 2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 20),

[0497] ethyl 1-cyclopentyl-2-(4-nitrophenyl)benzimidazole-5-carboxylate (Example 21),

[0498] ethyl 2-(4-aminophenyl)-l-cyclopentylbenzimidazole-5-carboxylate (Example 22),

[0499] ethyl 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate (Example 23),

[0500] 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 24),

[0501] ethyl 2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 25),

[0502] 2-{4-[3-(3-chlorophenyl)phenoxy]phenyl-}1-cyclohexylbenzimidazole-5-carboxylic acid (Example 26),

[0503] ethyl 2-[4-(3-acetoxyphenyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 27),

[0504] ethyl 1-cyclohexyl-2-[4-(3-hydroxyphenyloxy)phenyl]-benzimidazole-5-carboxylate (Example 28),

[0505] ethyl 1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]phenyl}-benzimidazole-5-carboxylate (Example 29),

[0506] 1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]phenyl}-benzimidazole-5-carboxylic acid (Example 30),

[0507] 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole (Example 31),

[0508] ethyl 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylate (Example 32),

[0509] 2-(4-benzyloxyphenyl)-1-cyclopentyl-N,N-dimethylbenzimidazole-5-carboxamide (Example 33),

[0510] 2-(4-benzyloxyphenyl)-1-cyclopentyl-N-methoxy-N-methylbenzimidazole-5-carboxamide (Example 34),

[0511] 2-(4-benzyloxyphenyl)-1-cyclopentyl-5-(1-hydroxy-1-methylethyl)benzimidazole (Example 35),

[0512] 5-acetyl-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole (Example 36),

[0513] 2-(4-benzyloxyphenyl)-1-cyclopentyl-N-(2-dimethylaminoethyl)-benzimidazole-5-carboxamide dihydrochloride (Example 37),

[0514] 2-(4-benzyloxyphenyl)-1-cyclopentyl-5-nitrobenzimidazole (Example 38),

[0515] 5-amino-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole hydrochloride (Example 39),

[0516] 5-acetylamino-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole (Example 40),

[0517] 2-(4-benzyloxyphenyl)-1-cyclopentyl-5-methanesulfonyl-aminobenzimidazole (Example 41),

[0518] 5-sulfamoyl-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole (Example 42),

[0519] 2-[4-(4-tert-butylbenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 43),

[0520] 2-[4-(4-carboxybenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 44),

[0521] 2-[4-(4-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 45),

[0522] 2-{4-[(2-chloro-5-thienyl)methoxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 46),

[0523] 1-cyclopentyl-2-[4-(4-trifluoromethylbenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 47),

[0524] 1-cyclopentyl-2-[4-(4-methoxybenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 48),

[0525] 1-cyclopentyl-2-[4-(4-pyridylmethoxy)phenyl]benzimidazole-5-carboxylic acid hydrochloride (Example 49),

[0526] 1-cyclopentyl-2-[4-(4-methylbenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 50),

[0527] 1-cyclopentyl-2-{4-[(3,5-dimethyl-4-isoxazolyl)methoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 51),

[0528] 1-cyclopentyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylic acid (Example 52),

[0529] [2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazol-5-yl]-carbonylaminoacetic acid (Example 53),

[0530] 2-[4-(2-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 54),

[0531] 2-[4-(3-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 55),

[0532] 2-(4-benzyloxyphenyl)-3-cyclopentylbenzimidazole-5-carboxylic acid (Example 56),

[0533] 2-[4-(benzenesulfonylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 57),

[0534] 1-cyclopentyl-2-[4-(3,5-dichlorophenylcarbonylamino)phenyl]-benzimidazole-5-carboxylic acid (Example 58),

[0535] 2-{4-[(4-chlorophenyl)carbonylamino]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 59),

[0536] 2-{4-[(4-tert-butylphenyl)carbonylamino]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 60),

[0537] 2-{4-[(4-benzyloxyphenyl)carbonylamino]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 61),

[0538] trans-4-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]cyclohexan-1-ol (Example 62),

[0539] trans-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-methoxycyclohexane (Example 63),

[0540] 2-4-benzyloxyphenyl)-5-carboxymethyl-1-cyclopentylbenzimidazole (Example 64),

[0541] 2-[1-benzyloxycarbonyl-4-piperidyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 65),

[0542] 2-[(4-cyclohexylphenyl)carbonylamino]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 66),

[0543] 1-cyclopentyl-2-[4-(3,5-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 67),

[0544] 1-cyclopentyl-2-[4-(3,4-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 68),

[0545] 1-cyclopentyl-2-[4-(phenylcarbamoylamino)phenyl]benzimidazole-5-carboxylic acid (Example 69),

[0546] 1-cyclopentyl-2-[4-(diphenylmethoxy)phenyl]benzimidazole-5-carboxylic acid (Example 70),

[0547] 1-cyclopentyl-2-(4-phenethyloxyphenyl)benzimidazole-5-carboxylic acid (Example 71),

[0548] trans-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-tert-butylcyclohexane (Example 72),

[0549] 2-(4-benzyloxyphenyl)-5-carboxymethoxy-1-cyclopentylbenzimidazole (Example 73),

[0550] 2-(4-benzylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 74),

[0551] 2-[4-(N-benzenesulfonyl-N-methylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 75),

[0552] 2-[4-(N-benzyl-N-methylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 76),

[0553] 1-cyclohexyl-2-(4-phenethylphenyl)benzimidazole-5-carboxylic acid (Example 77),

[0554] 2-(1-benzyl-4-piperidyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 78),

[0555] 2-(1-benzoyl-4-piperidyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (Example 79),

[0556] 1-cyclopentyl-2-[1-(p-toluenesulfonyl)-4-piperidyl]-benzimidazole-5-carboxylic acid (Example 80),

[0557] 1-cyclohexyl-2-[4-(3,5-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 81),

[0558] 1-cyclohexyl-2-[4-(diphenylmethoxy)phenyl]benzimidazole-5-carboxylic acid (Example 82),

[0559] 1-cyclohexyl-2-[4-(3,5-di-tert-butylbenzyloxy)phenyl]-benzimidazole-5-carboxylic acid (Example 83),

[0560] 2-(4-benzyloxyphenyl)-1-(4-methylcyclohexyl)benzimidazole-5-carboxylic acid (Example 84),

[0561] 1-cyclohexyl-2-{4-[2-(2-naphthyl)ethoxy]phenyl}benzimidazole-5-carboxylic acid (Example 85),

[0562] 1-cyclohexyl-2-[4-(1-naphthyl)methoxyphenyl]benzimidazole-5-carboxylic acid (Example 86),

[0563] 1-cyclohexyl-2-[4-(dibenzylamino)phenyl]benzimidazole-5-carboxylic acid (Example 87),

[0564] 2-[4-(2-biphenylylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 88),

[0565] 2-(4-benzyloxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 89),

[0566] 1-cyclohexyl-2-[4-(dibenzylmethoxy)phenyl]benzimidazole-5-carboxylic acid (Example 90),

[0567] 2-(4-benzoylmethoxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 91),

[0568] 2-(4-benzyl-1-piperazinyl)-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 92),

[0569] 1-cyclohexyl-2-[4-(3,3-diphenylpropyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 93),

[0570] 2-[4-(3-chloro-6-phenylbenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 94),

[0571] 2-(4-benzyloxypiperidino)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 95),

[0572] 1-cyclohexyl-2-{4-[2-(phenoxy)ethoxy]phenyl}benzimidazole-5-carboxylic acid (Example 96),

[0573] 1-cyclohexyl-2-[4-(3-phenylpropyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 97),

[0574] 1-cyclohexyl-2-[4-(5-phenylpentyloxy)phenyl]benzimidazole-5-carboxylic acid (Example 98),

[0575] 2-(3-benzyloxy-5-isoxazolyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 99),

[0576] 2-(2-benzyloxy-5-pyridyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 100),

[0577] 1-cyclohexyl-2-{4-[2-(3,4,5-trimethoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 101),

[0578] 2-(4-benzyloxyphenyl)-1-(4,4-dimethylcyclohexyl)benzimidazole-5-carboxylic acid (Example 102),

[0579] 1-cyclohexyl-2-{4-[2-(1-naphthyl)ethoxy]phenyl}benzimidazole-5-carboxylic acid (Example 103),

[0580] 2-[4-(2-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 104),

[0581] 2-[4-(3-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 105),

[0582] 1-cyclohexyl-2-[4-(2-hydroxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 106),

[0583] 1-cyclohexyl-2-[4-(3-hydroxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 107),

[0584] 1-cyclohexyl-2-[4-(2-methoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 108),

[0585] 1-cyclohexyl-2-[4-(3-methoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 109),

[0586] 1-cyclohexyl-2-[4-(2-propoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 110),

[0587] 1-cyclohexyl-2-[4-(3-propoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 111),

[0588] 1-cyclohexyl-2-{4-[2-(3-methyl-2-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example. 112),

[0589] 1-cyclohexyl-2-{4-[3-(3-methyl-2-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 113),

[0590] 1-cyclohexyl-2-[4-(2-isopentyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 114),

[0591] 1-cyclohexyl-2-[4-(3-isopentyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 115),

[0592] 1-cyclohexyl-2-{4-[2-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)ethoxy]phenyl}benzimidazole-5-carboxylic acid (Example 116),

[0593] 1-cyclohexyl-2-{4-[2-(4-trifluoromethylphenyl)benzyloxy]-phenyl}benzimidazole-5-carboxylic acid (Example 117),

[0594] 2-{4-[bis(4-chlorophenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 118),

[0595] 1-cyclohexyl-2-{4-[2-(4-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 119),

[0596] 1-cyclohexyl-2-{4-[2-(2-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 120),

[0597] 1-cyclohexyl-2-{4-[2-(3-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 121),

[0598] 2-(4-benzyloxyphenyl)-1-cycloheptylbenzimidazole-5-carboxylic acid (Example 122),

[0599] 1-cyclohexyl-2-[4-(2-phenethyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 123),

[0600] 1-cyclohexyl-2-[4-(3-phenethyloxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 124),

[0601] 1-cyclohexyl-2-[4-(2,2-diphenylethoxy)phenyl]benzimidazole-5-carboxylic acid (Example 125),

[0602] 2-(4-benzyloxyphenyl)-1-(3-cyclohexenyl)benzimidazole-5-carboxylic acid (Example 126),

[0603] cis-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-fluorocyclohexane (Example 127),

[0604] 1-cyclohexyl-2-[4-(2-phenoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 128),

[0605] 1-cyclohexyl-2-[4-(3-phenoxyphenoxy)phenyl]benzimidazole-5-carboxylic acid (Example 129),

[0606] 2-{4-[(2R)-2-benzyloxycarbonylamino-2-phenylethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 130),

[0607] 1-cyclohexyl-2-{2-fluoro-4-[2-(4-trifluoromethylphenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid (Example 131),

[0608] 2-[4-(4-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 132),

[0609] 2-{4-[bis(4-methylphenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 133),

[0610] 2-{4-[bis(4-fluorophenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 134),

[0611] 1-cyclohexyl-6-methoxy-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic acid (Example 135),

[0612] 1-cyclohexyl-6-hydroxy-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic acid (Example 136),

[0613] 1-cyclohexyl-6-methyl-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic acid (Example 137),

[0614] 2-{4-[2-(2-benzyloxyphenyl)ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 138),

[0615] 2-{4-[2-(3-benzyloxyphenyl)ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 139),

[0616] 2-[4-(2-carboxymethyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 140),

[0617] 2-[4-(3-carboxymethyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 141),

[0618] 2-{4-[3-chloro-6-(4-methylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 142),

[0619] 2-{4-[3-chloro-6-(4-methoxyphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 143),

[0620] 1-cyclohexyl-2-{2-methyl-4-[2-(4-trifluoromethylphenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid (Example 144),

[0621] 2-{4-[2-(4-tert-butylphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 145),

[0622] 2-{4-(3-chloro-6-phenylbenzyloxy)-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 146),

[0623] 2-{4-[3-chloro-6-(3,5-dichlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 147),

[0624] 2-{4-[bis(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 148),

[0625] 2-{4-(4-benzyloxyphenoxy)-2-chlorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 149),

[0626] 2-{4-(4-benzyloxyphenoxy)-2-trifluoromethylphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 150),

[0627] 2-{4-[3-chloro-6-(2-trifluoromethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 151),

[0628] 2-{4-[(2R)-2-amino-2-phenylethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 152),

[0629] 2-[4-(2-biphenylyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 153),

[0630] 2-[4-(3-biphenylyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 154),

[0631] 2-{4-[2-{(1-tert-butoxycarbonyl-4-piperidyl)methoxy}phenoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 155),

[0632] 2-{4-[3-{(1-tert-butoxycarbonyl-4-piperidyl)methoxy}phenoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 156),

[0633] 2-{4-[3-chloro-6-(3,4,5-trimethoxyphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 157),

[0634] 2-{4-[2-(2-biphenylyl)ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 158),

[0635] 2-[4-(2-biphenylylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 159),

[0636] 1-cyclohexyl-2-{4-[2-(4-piperidylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid hydrochloride (Example 160),

[0637] 1-cyclohexyl-2-{4-[3-(4-piperidylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid hydrochloride (Example 161),

[0638] 2-{4-[(2R)-2-acetylamino-2-phenylethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 162),

[0639] 1-cyclohexyl-2-{4-[3-(4-methyl-3-pentenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 163),

[0640] 1-cyclohexyl-2-{4-[3-(3-methyl-3-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 164),

[0641] 2-{4-[{(2S)-1-benzyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid hydrochloride (Example 165),

[0642] 2-{4-[3-chloro-6-(4-methylthiophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 166),

[0643] 2-{4-[3-chloro-6-(4-methanesulfonylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 167),

[0644] 2-{4-[3-chloro-6-(2-thienyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 168),

[0645] 2-{4-[3-chloro-6-(3-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 169),

[0646] 2-{4-[3-chloro-6-(3-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 170),

[0647] 2-{4-[3-chloro-6-(4-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 171),

[0648] 2-[4-(4-benzyloxyphenoxy)-3-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 172),

[0649] 2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 173),

[0650] 2-{4-[3-chloro-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 174),

[0651] 2-{4-[2-{(1-acetyl-4-piperidyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 175),

[0652] 2-{4-[3-{(1-acetyl-4-piperidyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 176),

[0653] 1-cyclohexyl-2-{4-[3-(2-propynyloxy)phenoxy]phenyl}benzimidazole-5-carboxylic acid (Example 177),

[0654] 1-cyclohexyl-2-{4-[3-(3-pyridylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 178),

[0655] 2-(4-benzyloxy-2-methoxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 179),

[0656] 2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 180),

[0657] 2-[4-(carboxydiphenylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 181),

[0658] 2-{4-[2-(4-chlorophenyl)-5-nitrobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 182),

[0659] 2-{4-[3-acetylamino-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 183),

[0660] 2-{4-[2-(4-carboxyphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 184),

[0661] 2-{4-[{(2S)-1-benzyloxycarbonyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 185),

[0662] 2-{2-chloro-4-[2-(4-trifluoromethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 186),

[0663] 1-cyclohexyl-2-{4-[3-(2-pyridylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 187),

[0664] 2-{4-[2-(4-chlorophenyl)-5-fluorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 188),

[0665] 2-{4-[3-carboxy-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 189),

[0666] 2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 190),

[0667] 1-cyclohexyl-2-{4-[2-(dimethylcarbamoylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 191),

[0668] 1-cyclohexyl-2-{4-[2-(piperidinocarbonylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 192),

[0669] 2-{4-[{(2S)-1-benzenesulfonyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 193),

[0670] 2-{4-[{(2S)-1-benzoyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 194),

[0671] 2-{4-[2-(4-carbamoylphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 195),

[0672] 1-cyclohexyl-2-{4-[3-(dimethylcarbamoylmethoxy)phenoxy]phenyl}benzimidazole-5-carboxylic acid (Example 196),

[0673] 1-cyclohexyl-2-{4-[3-(piperidinocarbonylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 197),

[0674] 1-cyclohexyl-2-{4-[3-{(1-methanesulfonyl-4-piperidyl)methoxy}-phenoxy]phenyl}benzimidazole-5-carboxylic acid (Example 198),

[0675] 1-cyclohexyl-2-{4-[{2-methyl-5-(4-chlorophenyl)-4-oxazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 199),

[0676] 2-{4-[3-(3-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 200),

[0677] 2-{4-[3-(4-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 201),

[0678] 1-cyclohexyl-2-{4-[3-(4-fluorobenzyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 202),

[0679] 1-cyclohexyl-2-{4-[{(2S)-1-(4-nitrophenyl)-2-pyrrolidinyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 203),

[0680] 1-cyclohexyl-2-{4-[{(2S)-1-phenyl-2-pyrrolidinyl}methoxy]-phenyl}benzimidazole-5-carboxylic acid hydrochloride (Example 204),

[0681] 2-{4-[{(2S)-1-(4-acetylaminophenyl)-2-pyrrolidinyl}methoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 205),

[0682] 2-{4-[{5-(4-chlorophenyl)-2-methyl-4-thiazolyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 206),

[0683] 2-{4-[bis(3-fluorophenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 207),

[0684] 1-cyclohexyl-2-{4-[2-(4-chlorophenyl)-3-nitrobenzyloxy]phenyl}-benzimidazole-5-carboxylic acid (Example 208),

[0685] 1-cyclohexyl-2-{4-[3-(4-tetrahydropyranyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 209),

[0686] 1-cyclohexyl-2-{4-[3-(4-trifluoromethylbenzyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 210),

[0687] 1-cyclohexyl-2-{4-[3-{(1-methyl-4-piperidyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 211),

[0688] 2-{4-[3-(4-tert-butylbenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 212),

[0689] 2-{4-[3-(2-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 213),

[0690] 1-cyclohexyl-2-{4-[3-(3-pyridyl)phenoxy]phenyl}benzimidazole-5-carboxylic acid (Example 214),

[0691] 2-{4-[3-(4-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 215),

[0692] 1-cyclohexyl-2-{4-[3-(4-methoxyphenyl)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 216),

[0693] 1-cyclohexyl-2-{4-[{4-(4-methanesulfonylphenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 217),

[0694] 2-{4-[{4-(4-chlorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 218),

[0695] 2-{4-[1-(4-chlorobenzyl)-3-piperidyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 219),

[0696] 1-cyclohexyl-2-{4-[3-{(2-methyl-4-thiazolyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 220),

[0697] 1-cyclohexyl-2-{4-[3-{(2,4-dimethyl-5-thiazolyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic acid (Example 221),

[0698] 1-cyclohexyl-2-{4-[3-(3,5-dichlorophenyl)phenoxy]phenyl}-benzimidazole-5-carboxylic acid (Example 222),

[0699] 2-{4-[1-(4-chlorobenzyl)-4-piperidyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 223),

[0700] 2-{4-[3-(4-chlorobenzyloxy)piperidino]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 224),

[0701] 2-{4-[4-carbamoyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 225),

[0702] 2-{4-[4-(4-chlorobenzyloxy)piperidino]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 226),

[0703] 2-{4-[3-{(2-chloro-4-pyridyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 227),

[0704] 2-{4-[{(2S)-1-(4-dimethylcarbamoylphenyl)-2-pyrrolidinyl}-methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 228),

[0705] 2-{4-[2-(4-chlorophenyl)-5-ethoxycarbonylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 229),

[0706] 1-cyclohexyl-2-[4-(3-trifluoromethylphenoxy)phenyl]-benzimidazole-5-carboxylic acid (Example 230),

[0707] 1-cyclohexyl-2-{4-[{4-(4-dimethylcarbamoylphenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 231),

[0708] 2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 232),

[0709] 2-{4-[{4-(4-chlorophenyl)-2-methyl-5-pyrimidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 233),

[0710] 2-{4-[{2-(4-chlorophenyl)-3-pyridyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 234),

[0711] 2-{4-[{3-(4-chlorophenyl)-2-pyridyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 235),

[0712] 2-{4-[2-(3-chlorophenyl)-4-methylamino-1,3,5-triazin-6-yloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid trifluoroacetate (Example 236),

[0713] 2-{4-[2-(4-chlorophenyl)-4-(5-tetrazolyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 237),

[0714] 2-[4-(4-benzyloxy-6-pyrimidinyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 238),

[0715] 1-cyclohexyl-2-{4-[4-(4-pyridylmethoxy)-6-pyrimidinyloxy]phenyl}-benzimidazole-5-carboxylic acid (Example 239),

[0716] 2-{4-[4-(3-chlorophenyl)-6-pyrimidinyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 240),

[0717] methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 241),

[0718] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid hydrochloride (Example 242),

[0719] ethyl 2-{4-[3-(4-chlorophenyl)pyridin-2-ylmethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 243),

[0720] methyl 2-[4-(2-bromo-5-tert-butoxycarbonylbenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 244),

[0721] methyl 2-{4-[5-tert-butoxycarbonyl-2-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic (Example 245),

[0722] methyl 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride (Example 246),

[0723] methyl 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 247),

[0724] 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 248),

[0725] 2-{4-[3-(tert-butylsulfamoyl)-6-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 249),

[0726] 2-{4-[2-(4-chlorophenyl)-5-sulfamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid trifluoroacetate (Example 250),

[0727] 2-(4-benzyloxycyclohexyl)-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 251),

[0728] 2-[2-(2-biphenylyloxymethyl)-5-thienyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 252),

[0729] 2-[2-(2-biphenylyloxymethyl)-5-furyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 253),

[0730] 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-hydroxymethyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid (Example 254),

[0731] 1-cyclohexyl-2-{4-[{4-(4-carboxyphenyl)-2-methyl-5-thiazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic acid hydrochloride (Example 255),

[0732] 1-cyclohexyl-2-{2-fluoro-4-[4-fluoro-2-(3-fluorobenzoyl)benzyloxy]phenyl}benzimidazole-5-carboxylic acid (Example 256),

[0733] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-sulfonic acid (Example 257),

[0734] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-3-cyclohexylbenzimidazole-4-carboxylic acid (Example 258),

[0735] 1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-5-(4-pyridylmethoxy)-phenoxy]phenyl}benzimidazole-5-carboxylic acid dihydrochloride (Example 259),

[0736] 1-cyclohexyl-2-{4-[3-carboxy-5-(4-pyridylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic acid dihydrochloride (Example 260),

[0737] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-4-carboxylic acid (Example 261),

[0738] 2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 262),

[0739] 2-{4-[{2-(4-carboxyphenyl)-3-pyridyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 263),

[0740] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-(4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 264),

[0741] 2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 265),

[0742] 1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-6-(4-trifluoromethylphenyl)benzyloxy]phenyl}benzimidazole-5-carboxylic acid hydrochloride (Example 266),

[0743] 1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-6-(4-methylthiophenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic acid hydrochloride (Example 267),

[0744] 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 268),

[0745] 2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 269),

[0746] 2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 270),

[0747] 2-{4-[3-dimethylcarbamoyl-6-(4-methanesulfonylphenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 271),

[0748] 2-{4-[3-dimethylcarbamoyl-6-(3-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 272),

[0749] 2-{4-[3-dimethylcarbamoyl-6-(4-dimethylcarbamoylphenyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 273),

[0750] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-(1-oxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 274),

[0751] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-(1,1-dioxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example275),

[0752] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]-2-fluorophenyl}-1-(4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 276),

[0753] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]-2-fluorophenyl}-1-(1-oxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 277),

[0754] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]-2-fluorophenyl}-1-(1,1-dioxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic acid (Example 278),

[0755] 2-{4-[2-(4-chlorophenyl)-5-dimethylsulfamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 279),

[0756] 2-{4-[2-(4-chlorophenyl)-5-methanesulfonylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 280),

[0757] 2-{4-[2-(4-chlorophenyl)-5-methylsulfamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 281),

[0758] 2-{4-[2-(4-chlorophenyl)-5-dimethylaminobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 282),

[0759] 2-{4-[2-(4-chlorophenyl)-5-methanesulfonylaminobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 283),

[0760] 2-{4-[2-(4-chlorophenyl)-5-diethylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid. (Example 284),

[0761] 2-{4-[2-(4-chlorophenyl)-5-isopropylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 285),

[0762] 2-{4-[2-(4-chlorophenyl)-5-piperidinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 286),

[0763] 2-{4-[2-(4-chlorophenyl)-5-(1-pyrrolidinyl)carbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 287),

[0764] 2-{4-[2-(4-chlorophenyl)-5-(2-hydroxyethyl)carbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 288),

[0765] 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidino)-carbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 289),

[0766] 2-{4-[2-(4-chlorophenyl)-5-morpholinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 290),

[0767] 2-{4-[2-(4-chlorophenyl)-5-thiomorpholinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 291),

[0768] 2-{4-[3-(carboxymethylcarbamoyl)-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 292),

[0769] 2-{4-[2-{4-(2-carboxyethyl)phenyl}-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 293),

[0770] 2-{4-[3-chloro-6-(4-hydroxymethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 294),

[0771] 2-{4-[3-chloro-6-(4-methoxymethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 295),

[0772] 2-{4-[2-(3-carboxyphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 296),

[0773] 2-{4-[2-(4-chlorophenyl)-5-methylthiobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 297),

[0774] 2-{4-[2-(4-chlorophenyl)-5-methylsulfinylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 298),

[0775] 2-{4-[2-(4-chlorophenyl)-5-cyanobenzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic acid (Example 299),

[0776] 2-{4-[bis(2-pyridyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 300),

[0777] 2-{4-[bis(4-dimethylcarbamoylphenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 301),

[0778] 2-{4-[bis (2-thienyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 302),

[0779] methyl 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 303),

[0780] sodium 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 304),

[0781] 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 305),

[0782] 2-{4-[2-(4-carboxyphenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 306),

[0783] 2-{4-[2-(4-carbamoylphenyl)-5-(dimethylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 307),

[0784] 2-{4-[5-amino-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 308),

[0785] 2-{4-[5-(4-chlorophenyl)-2-methoxybenzylsulfinyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 309),

[0786] 2-{4-[5-(4-chlorophenyl)-2-methoxybenzylsulfonyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 310),

[0787] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzylthio]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 311),

[0788] 2-{4-[bis(4-carboxyphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 312),

[0789] 2-[4-(phenyl-3-pyridylmethoxy)-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 313),

[0790] methyl 2-{4-[2-(4-chlorophenyl)-5-(methylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate (Example 314),

[0791] 2-{4-[5-chloro-2-(4-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 315),

[0792] 2-{4-[2-(4-chlorophenyl)-5-(benzylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 316),

[0793] 2-{4-[2-(4-chlorophenyl)-5-(cyclohexylmethylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 317),

[0794] 2-{4-[2-(4-chlorophenyl)-5-(4-pyridylmethylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 318),

[0795] 2-{4-[2-(4-chlorophenyl)-5-(N-benzyl-N-methylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 319),

[0796] 2-{4-[5-dimethylaminocarbonyl-2-(4-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 320),

[0797] 2-{4-[2-(4-chlorophenyl)-5-(4-methylpiperazin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 321),

[0798] 2-{4-[2-(4-chlorophenyl)-5-{N-(3-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 322),

[0799] 2-{4-[2-(4-chlorophenyl)-5-{N-(2-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 323),

[0800] 2-{4-[2-(4-chlorophenyl)-5-(cyclohexylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 324),

[0801] 2-{4-[2-(4-chlorophenyl)-5-(2-pyridin-4-ylethylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 325),

[0802] 2-{4-[(4-fluorophenyl){4-(dimethylaminocarbonyl)phenyl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 326),

[0803] 2-{4-[(4-fluorophenyl)(4-carboxyphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 327),

[0804] 2-{4-[2-(4-chlorophenyl)-5-(4-oxopiperidinocarbonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 328),

[0805] 2-{4-[2-(4-chlorophenyl)-5-hydroxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 329),

[0806] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 330),

[0807] 2-{4-[2-(4-chlorophenyl)-5-(N-isopropyl-N-methylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 331),

[0808] 2-{4-[2-(4-chlorophenyl)-5-(phenylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 332),

[0809] 2-{4-[2-(4-chlorophenyl)-5-(4-methoxypiperidinocarbonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 333),

[0810] 2-{4-[2-(4-chlorophenyl)-5-(3-hydroxypropyloxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 334),

[0811] 2-{4-[2-(4-chlorophenyl)-5-(2-hydroxyethoxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 335),

[0812] methyl 2-[4-(2-bromo-5-nitrobenzyloxy)-2-fluorophenyl]-1cyclohexylbenzimidazole-5-carboxylate (Example 336),

[0813] methyl 2-[4-{2-(4-chlorophenyl)-5-nitrobenzyloxy}-2fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 337),

[0814] methyl 2-[4-{5-amino-2-(4-chlorophenyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 338),

[0815] methyl 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 339),

[0816] 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidole-5-carboxylic acid hydrochloride (Example 340),

[0817] 2-{4-[2-(4-chlorophenyl)-5-(4-methylpiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5carboxylic acid hydrochloride (Example 341),

[0818] 2-{4-[5-acetyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 342),

[0819] 2-{4-[2-(4-chlorophenyl)-5-{(4-hydroxypiperidin-1-ylcarbonyl)-methoxy}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 343),

[0820] 2-{4-[2-(4-chlorophenyl)-5-(2-methoxyethoxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 344),

[0821] 2-{4-[2-(4-chlorophenyl)-5-{2-(2-methoxyethoxy)ethoxy}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 345),

[0822] 2-{4-[2-(4-chlorophenyl)-5-(isobutylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 346),

[0823] 2-{4-[2-(4-chlorophenyl)-5-(2-methylthiazol-4-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 347),

[0824] 2-{4-[2-(4-chlorophenyl)-5-(3,4-dihydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidole-5-carboxylic acid hydrochloride (Example 348),

[0825] 2-{4-[2-(4-chlorophenyl)-5-(3-methyl-1,2,4-oxadiazol-5-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 349),

[0826] 2-{4-[2-(4-chlorophenyl)-4-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 350),

[0827] 2-{4-[2-(4-chlorophenyl)-4-(piperidinocarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 351),

[0828] 2-{4-[2-(4-chlorophenyl)-5-{(1-hydroxy-2-methylpropan-2-yl)carbamoyl}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 352),

[0829] 2-{4-[2-(4-chlorophenyl)-5-(4,4-dimethyl-2-oxazolin-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 353),

[0830] 2-{4-[2-(4-chlorophenyl)-4-(4-hydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 354),

[0831] 2-{4-[2-(4-chlorophenyl)-4-{(2-hydroxyethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 355),

[0832] 2-{4-[2-(4-chlorophenyl)-4-{(4-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 356),

[0833] 2-{4-[2-(4-chlorophenyl)-4-(dimethylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 357),

[0834] 2-{4-[5-(2-aminothiazol-4-yl)-2-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 358),

[0835] 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylsulfonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 359),

[0836] 2-{4-[5-(dimethylcarbamoyl)-2-(4-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 360),

[0837] 2-{4-[5-(dimethylcarbamoyl)-2-(3-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 361),

[0838] 2-{4-[2-(5-chlorothiophen-2-yl)-5-(dimethylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 362),

[0839] 2-{4-[2-bromo-5-(5-methyloxazol-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 363),

[0840] 2-{4-[2-bromo-5-(5-methylthiazol-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 364),

[0841] 2-{4-[2-(4-chlorophenyl)-5-(5-methyloxazol-2-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 365),

[0842] 2-{4-[2-(4-chlorophenyl)-5-(5-methylthiazol-2-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 366),

[0843] 2-{4-[2-(4-chlorophenyl)-5-tetrazol-5-ylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 367),

[0844] 2-{4-[5-chloro-2-(4-cyanophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 368),

[0845] 2-{4-[5-chloro-2-(4-tetrazol-5-ylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 369),

[0846] 2-{4-[2-(4-chlorophenyl)-5-{2-(4-hydroxypiperidin-1-yl)ethoxy}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 370),

[0847] 2-{4-[2-(4-chlorophenyl)-5-(2-oxopiperidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 371),

[0848] 2-{4-[3-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 372),

[0849] 2-{4-[2-(4-chlorophenyl)-5-(N-hydroxyamidino)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 373),

[0850] 2-{4-[2-(4-chlorophenyl)-5-(2,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl)benzyloxy]-2fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 374),

[0851] 2-{4-[2-(4-chlorophenyl)-5-(2-oxo-3H-1,2,3,5-oxathiadiazol-4-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexybenzimidazole-5-carboxylic acid hydrochloride (Example 375),

[0852] 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),

[0853] 2-{4-[2-(4-chlorophenyl)-5-(cyclopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 377),

[0854] 2-{4-[2-(4-chlorophenyl)-5-(cyclobutylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 378),

[0855] 2-{4-[2-(4-chlorophenyl)-5-(tert-butylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 379),

[0856] 2-{4-[2-(4-chlorophenyl)-5-(isobutylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 380),

[0857] 2-{4-[2-(4-chlorophenyl)-5-{(1-hydroxypropan-2-yl)carbamoyl}-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 381),

[0858] 2-{4-[2-(4-chlorophenyl)-5-(methoxycarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 382),

[0859] 2-{4-[2-(4-chlorophenyl)-5-{(2,3-dihydroxypropyl)carbamoyl}-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 383),

[0860] 2-{4-[2-(4-chlorophenyl)-5-(N-ethyl-N-methylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 384),

[0861] 2-{4-[2-(4-chlorophenyl)-5-(N-methyl-N-propylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 385),

[0862] 2-{4-[2-(4-chlorophenyl)-5-(N-isopropyl-N-methylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 386),

[0863] 2-{4-[2-(4-chlorophenyl)-5-(2,6-dimethylpiperidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 387),

[0864] 2-{4-[5-(butylcarbamoyl)-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 388),

[0865] 2-{4-[2-(4-chlorophenyl)-5-(propylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 389),

[0866] 2-{4-[2-(4-chlorophenyl)-5-(ethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 390),

[0867] 2-{4-[2-(4-chlorophenyl)-5-{(dimethylcarbamoyl)amino}benzyloxyl]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 391),

[0868] 2-{4-[2-(4-chlorophenyl)-5-{(morpholinocarbonyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 392),

[0869] 2-{4-[2-(4-chlorophenyl)-5-ureidobenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 393),

[0870] 2-{4-[2-(4-chlorophenyl)-5-{(ethylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 394),

[0871] 2-{4-[2-(4-chlorophenyl)-5-{(isopropylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 395),

[0872] 2-{4-[2-(3,4-difluorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 396),

[0873] 2-{4-[2-(2,4-difluorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 397),

[0874] 2-{4-[2-(3,5-dichlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 398),

[0875] 2-{4-[2-(3-chloro-4-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 399),

[0876] 2-{4-[2-(3,4-dichlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 400),

[0877] 2-{4-[2-(4-chloro-2-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 401),

[0878] 2-{4-[2-(4-chloro-2-fluorophenyl)-5-(pyrrolidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 402),

[0879] 2-{4-[2-(4-chloro-3-fluorophenyl)-5-(pyrrolidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 403),

[0880] 2-{4-[2-(4-chloro-3-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 404),

[0881] 2-{4-[2-{4-(methylthio)phenyl}-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 405),

[0882] 2-{4-[2-{4-(methylthio)phenyl}-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 406),

[0883] 2-{4-[4-chloro-2-(4-chlorophenyl)-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 407),

[0884] 2-{4-[4-chloro-2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 408),

[0885] 2-{4-[2-(4-chlorophenyl)-5-(isopropylaminosulfonyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 409),

[0886] 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 410),

[0887] 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 411),

[0888] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 412),

[0889] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 413),

[0890] 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 414),

[0891] 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 415),

[0892] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 416),

[0893] 2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-phenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 417),

[0894] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 418),

[0895] 2-{4-[2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-(tetrahydrothiopyran-4)benzimidazole-5-carboxylic acid hydrochloride (Example 419),

[0896] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy)-2-fluorophenyl}-1-piperidinobenzimidazole-5-carboxylic acid hydrochloride (Example 420),

[0897] 2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-2-fluorophenyl}-1-piperidinobenzimidazole-5-carboxylic acid (Example 421),

[0898] 2-{4-[2-(4-chlorophenyl)-5-(2-imidazolin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 422),

[0899] 2-{4-[2-(4-chlorophenyl)-5-(2-oxooxazolidin-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 423),

[0900] 2-{4-[2-(4-chlorophenyl)-5-(2-oxoimidazolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 424),

[0901] 2-{4-[2-(4-chlorophenyl)-5-(2-oxazolin-2-ylamino)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 425),

[0902] 2-{4-[{2-[{(dimethylcarbamoyl)methoxy}methyl]-4-(4-fluorophenyl)thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 426),

[0903] 2-{4-[{4-(4-fluorophenyl)-2-(4-hydroxypiperidin-1-ylmethyl)thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 427),

[0904] 2-{4-[{4-(4-fluorophenyl)-2-[(carbamoylmethoxy)methyl]thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 428),

[0905] 2-{4-[{4-(4-fluorophenyl)-2-(methylcarbamoyl)thiazol-5-ylmethoxyl-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 429),

[0906] 2-{4-[{4-(4-fluorophenyl)-2-{(2-hydroxyethyl)carbamoyl}thiazol-5-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 430),

[0907] 2-{4-[{2-(4-fluorophenyl)-5-(dimethylcarbamoyl)thiophen-3-yl}methoxyl-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 431),

[0908] 2-{4-[{2-(4-fluorophenyl)-5-(isopropylcarbamoyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 432),

[0909] 2-{4-[{2-(4-fluorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)thiophen-3-yl methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 433),

[0910] 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-tetrazol-5-ylbenzimidazole (Example 10 434),

[0911] 2-{4-[2-(4-carboxyphenyl)-5-chlorobenzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-tetrazol-5-ylbenzimidazole hydrochloride (Example 435),

[0912] 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),

[0913] 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-5-cyano-1-cyclohexylbenzimidazole (Example 437),

[0914] 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-5-cyano-l-cyclohexylbenzimidazole (Example 438),

[0915] 2-{4-[{N-(4-dimethylcarbamoyl)-N-(4-fluorophenyl)amino}-methyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 439),

[0916] 2-{5-[bis(3-fluorophenyl)methyl]-2-fluoro-4-hydroxyphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 440),

[0917] 2-{3-[bis(3-fluorophenyl)methyl]-2-fluoro-4-hydroxyphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 441),

[0918] 2-{4-[(3-dimethylcarbamoylphenyl)(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 442),

[0919] 2-{4-[{3-(4-hydroxypiperidyl-1-ylcarbonyl)phenyl}(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 443),

[0920] 1-{[2-{4-([4-(4-fluorophenyl)-2-methylthiazol-5-yl]methoxy)phenyl}-1-cyclohexylbenzimidazol-5-yl]carbonyl}-β-D-glucuronic acid (Example 444),

[0921] {[2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazol-5-yl]carbonyl}-β-D-glucuronic acid (Example 445),

[0922] 2-{4-[2-(4-chlorophenyl)-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 446),

[0923] 3-([4-(5-aminosulfonyl-1-cyclohexylbenzimidazol-2-yl)-3-fluorophenoxy]methyl}-4-(4-chlorophenyl)-N-isopropylbenzamide (Example 447),

[0924] 2-[4-{2-(4-chlorophenyl)-6-(isopropylaminocarbonyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 448),

[0925] 2-[4-{2-(4-chlorophenyl)-4-fluoro-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 449),

[0926] 2-[4-{2-(4-chlorophenyl)-5-(isopropylaminocarbonyl)benzyloxy}-2-fluorophenyl]-1-cyclohexyl-4-methoxybenzimidazole-5-carboxylic acid hydrochloride (Example 450),

[0927] 2-[4-{2-(4-chlorophenyl)-5-(N-isopropylcarbonyl-N-methylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 451),

[0928] 2-[4-{2-(4-chlorophenyl)-5-(isopropylcarbonylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 452),

[0929] 2-[3-{[4-(4-fluorophenyl)-2-methylthiazol-5-yl]methyl}-4-hydroxyphenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 453),

[0930] 2-[4-(2-(4-chlorophenyl)-4-fluoro-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 454),

[0931] 2-[4-{2-(4-chlorophenyl)-5-(methylsulfonylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 455),

[0932] 2-[4-{2-(4-chlorophenyl)-5-[N-methyl-N-(methylsulfonyl)amino]benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 456),

[0933] 2-[4-{[3-(4-chlorophenyl)-6-(2-oxopyrrolidin-1-yl)pyridin-2-yl]methyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 457),

[0934] 2-[4-{2-(4-chlorophenyl)-5-(acetylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 458),

[0935] 2-[4-{2-(4-chlorophenyl)-5-(N-acetyl-N-ethylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 459),

[0936] 2-[4-{2-(4-chlorophenyl)-5-(N-acetyl-N-propylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 460),

[0937] 2-[4-{2-(4-chlorophenyl)-5-[N-ethyl-N-(methylsulfonyl)amino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 461),

[0938] 2-[4-{2-(4-chlorophenyl)-5-[N-(methylsulfonyl)-N-propylamino]benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 462),

[0939] 2-[4-{2-(4-chlorophenyl)-5-(N-acetyl-N-methylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 463),

[0940] 2-[4-{2-(4-chlorophenyl)-5-[N-(ethylsulfonyl)-N-methylamino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 464),

[0941] 2-[4-{2-(4-chlorophenyl)-5-[N-ethyl-N-(ethylsulfonyl)amino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 465),

[0942] 2-[4-{2-(4-chlorophenyl)-5-[N-(ethylcarbonyl)-N-methylamino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 466),

[0943] 2-[4-{2-(4-chlorophenyl)-5-[N-ethyl-N-(ethylcarbonyl)amino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 467),

[0944] 2-[4-{2-(4-chlorophenyl)-5-methoxybenzyloxy}-2-fluorophenyl]-1cyclohexylbenzimidazole-5-acid (Example 468),

[0945] 2-[4-{2-(4-chlorophenyl)-5-(N-acetyl-N-isopropylamino)-benzyloxyl-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 469),

[0946] {([2-{4-[2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzoimidazol-5-yl]carbonyl}-β-D-glucuronic acid (Example 470),

[0947] methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylindole-5-carboxylate (Example 501),

[0948] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylic acid (Example 502),

[0949] 2-(4-benzyloxyphenyl)-1-cyclopentyl-1H-indole-5-carboxylic acid (Example 503),

[0950] ethyl 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylate (Example 601),

[0951] 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylic acid (Example 602),

[0952] 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-3-cyclohexyl-3H-imidazo[4,5-b]pyridine-6-carboxylic acid (Example 701),

[0953] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-3-cyclohexyl-3H-imidazo[4,5-b]pyridine-6-carboxylic acid hydrochloride (Example 702), and

[0954] 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).

[0955] (62) The fused ring compound of the formula [I] or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of

[0956] 2-{4-[2-(4-chlorophenyl)-5-(4-oxopiperidinocarbonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 328),

[0957] 2-{4-[2-(4-chlorophenyl)-5-hydroxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 329),

[0958] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 330),

[0959] 2-{4-[2-(4-chlorophenyl)-5-(N-isopropyl-N-methylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 331),

[0960] 2-{4-[2-(4-chlorophenyl)-5-(phenylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 332),

[0961] 2-{4-[2-(4-chlorophenyl)-5-(4-methoxypiperidinocarbonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 333),

[0962] 2-{4-[2-(4-chlorophenyl)-5-(3-hydroxypropyloxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 334),

[0963] 2-{4-[2-(4-chlorophenyl)-5-(2-hydroxyethoxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 335),

[0964] methyl 2-[4-(2-bromo-5-nitrobenzyloxy)-2-fluorophenyl)-1-cyclohexylbenzimidazole-5-carboxylate (Example 336),

[0965] methyl 2-[4-{2-(4-chlorophenyl)-5-nitrobenzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 337),

[0966] methyl 2-[4-{5-amino-2-(4-chlorophenyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 338),

[0967] methyl 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (Example 339),

[0968] 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5carboxylic acid hydrochloride (Example 340),

[0969] 2-{4-[2-(4-chlorophenyl)-5-(4-methylpiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 341),

[0970] 2-{4-[5-acetyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 342),

[0971] 2-{4-[2-(4-chlorophenyl)-5-{(4-hydroxypiperidin-1-ylcarbonyl)-methoxy{benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 343),

[0972] 2-{4-[2-(4-chlorophenyl)-5-(2-methoxyethoxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 344),

[0973] 2-{4-[2-(4-chlorophenyl)-5-{2-(2-methoxyethoxy)ethoxy}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 345),

[0974] 2-{4-[2-(4-chlorophenyl)-5-(isobutylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 346),

[0975] 2-{4-[2-(4-chlorophenyl)-5-(2-methylthiazol-4-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 347),

[0976] 2-{4-[2-(4-chlorophenyl)-5-(3,4-dihydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 348),

[0977] 2-{4-[2-(4-chlorophenyl)-5-(3-methyl-1,2,4-oxadiazol-5-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 349),

[0978] 2-{4-[2-(4-chlorophenyl)-4-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 350),

[0979] 2-{4-[2-(4-chlorophenyl)-4-(piperidinocarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 351),

[0980] 2-{4-[2-(4-chlorophenyl)-5-{(1-hydroxy-2-methylpropan-2-yl)carbamoyl}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 352),

[0981] 2-{4-[2-(4-chlorophenyl)-5-(4,4-dimethyl-2-oxazolin-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 353),

[0982] 2-{4-[2-(4-chlorophenyl)-4-(4-hydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 354),

[0983] 2-{4-[2-(4-chlorophenyl)-4-{(2-hydroxyethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 355),

[0984] 2-{4-[2-(4-chlorophenyl)-4-{(4-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 356),

[0985] 2-{4-[2-(4-chlorophenyl)-4-(dimethylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 357),

[0986] 2-{4-[5-(2-aminothiazol-4-yl)-2-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 358),

[0987] 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylsulfonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 359),

[0988] 2-{4-[5-(dimethylcarbamoyl)-2-(4-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 360),

[0989] 2-{4-[5-(dimethylcarbamoyl)-2-(3-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 361),

[0990] 2-{4-[2-(5-chlorothiophen-2-yl)-5-(dimethylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 362),

[0991] 2-{4-[2-bromo-5-(5-methyloxazol-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 363),

[0992] 2-{4-[2-bromo-5-(5-methylthiazol-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 364),

[0993] 2-{4-[2-(4-chlorophenyl)-5-(5-methyloxazol-2-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 365),

[0994] 2-{4-[2-(4-chlorophenyl)-5-(5-methylthiazol-2-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 366),

[0995] 2-{4-[2-(4-chlorophenyl)-5-tetrazol-5-ylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 367),

[0996] 2-{4-[5-chloro-2-(4-cyanophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 368),

[0997] 2-{4-[5-chloro-2-(4-tetrazol-5-ylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 369),

[0998] 2-{4-[2-(4-chlorophenyl)-5-{2-(4-hydroxypiperidin-1-yl)ethoxy}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 370),

[0999] 2-{4-[2-(4-chlorophenyl)-5-(2-oxopiperidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 371),

[1000] 2-{4-[3-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 372),

[1001] 2-{4-[2-(4-chlorophenyl)-5-(N-hydroxyamidino)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 373),

[1002] 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),

[1003] 2-{4-[2-(4-chlorophenyl)-5-(2-oxo-3H-1,2,3,5-oxathiadiazol-4-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5carboxylic acid hydrochloride (Example 375),

[1004] 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),

[1005] 2-{4-[2-(4-chlorophenyl)-5-(cyclopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 377),

[1006] 2-{4-[2-(4-chlorophenyl)-5-(cyclobutylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 378),

[1007] 2-{4-[2-(4-chlorophenyl)-5-(tert-butylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 379),

[1008] 2-{4-[2-(4-chlorophenyl)-5-(isobutylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 380),

[1009] 2-{4-[2-(4-chlorophenyl)-5-{(1-hydroxypropan-2-yl)carbamoyl}-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 381),

[1010] 2-{4-[2-(4-chlorophenyl)-5-(methoxycarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 382),

[1011] 2-{4-[2-(4-chlorophenyl)-5-{(2,3-dihydroxypropyl)carbamoyl}-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 383),

[1012] 2-{4-[2-(4-chlorophenyl)-5-(N-ethyl-N-methylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 384),

[1013] 2-{4-[2-(4-chlorophenyl)-5-(N-methyl-N-propylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 385),

[1014] 2-{4-[2-(4-chlorophenyl)-5-(N-isopropyl-N-methylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 386),

[1015] 2-{4-[2-(4-chlorophenyl)-5-(2,6-dimethylpiperidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 387),

[1016] 2-{4-[5-(butylcarbamoyl)-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 388),

[1017] 2-{4-[2-(4-chlorophenyl)-5-(propylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 389),

[1018] 2-{4-[2-(4-chlorophenyl)-5-(ethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 390),

[1019] 2-{4-[2-(4-chlorophenyl)-5-{(dimethylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 391),

[1020] 2-{4-[2-(4-chlorophenyl)-5-{(morpholinocarbonyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 392),

[1021] 2-{4-[2-(4-chlorophenyl)-5-ureidobenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 393),

[1022] 2-{4-[2-(4-chlorophenyl)-5-{ethylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 394),

[1023] 2-{4-[2-(4-chlorophenyl)-5-{isopropylcarbamoyl)amino}benzyloxy]2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 395),

[1024] 2-{4-[2-(3,4-difluorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 396),

[1025] 2-{4-[2-(2,4-difluorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid. hydrochloride (Example 397),

[1026] 2-{4-[2-(3,5-dichlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 398),

[1027] 2-{4-[2-(3-chloro-4-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 399),

[1028] 2-{4-[2-(3,4-dichlorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 400),

[1029] 2-{4-[2-(4-chloro-2-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 401),

[1030] 2-{4-[2-(4-chloro-2-fluorophenyl)-5-(pyrrolidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 402),

[1031] 2-{4-[2-(4-chloro-3-fluorophenyl)-5-(pyrrolidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 403),

[1032] 2-{4-[2-(4-chloro-3-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 404),

[1033] 2-{4-[2-{4-(methylthio)phenyl}-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 405),

[1034] 2-{4-[2-{4-(methylthio)phenyl}-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 406),

[1035] 2-{4-[4-chloro-2-(4-chlorophenyl)-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 407),

[1036] 2-{4-[4-chloro-2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 408),

[1037] 2-{4-[2-(4-chlorophenyl)-5-(isopropylaminosulfonyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 409),

[1038] 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 410),

[1039] 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 411),

[1040] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 412),

[1041] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 413),

[1042] 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 414),

[1043] 2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic acid hydrochloride (Example 415),

[1044] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 416),

[1045] 2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]phenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 417),

[1046] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 418),

[1047] 2-{4-[2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic acid hydrochloride (Example 419),

[1048] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-piperidinobenzimidazole-5-carboxylic acid hydrochloride (Example 420),

[1049] 2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-2-fluorophenyl}-1-piperidinobenzimidazole-5-carboxylic acid (Example 421),

[1050] 2-{4-[2-(4-chlorophenyl)-5-(2-imidazolin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 422),

[1051] 2-{4-[2-(4-chlorophenyl)-5-(2-oxooxazolidin-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 423),

[1052] 2-{4-[2-(4-chlorophenyl)-5-(2-oxoimidazolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 424),

[1053] 2-{4-[2-(4-chlorophenyl)-5-(2-oxazolin-2-ylamino)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 425),

[1054] 2-{4-[{2-[{(dimethylcarbamoyl)methoxy}methyl]-4-(4-fluorophenyl)thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 426),

[1055] 2-{4-[{4-(4-fluorophenyl)-2-(4-hydroxypiperidin-1-ylmethyl)thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid dihydrochloride (Example 427),

[1056] 2-{4-[{4-(4-fluorophenyl)-2-[(carbamoylmethoxy)methyl]thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 428),

[1057] 2-{4-[{4-(4-fluorophenyl)-2-(methylcarbamoyl)thiazol-5-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 429),

[1058] 2-{4-[{4-(4-fluorophenyl)-2-{(2-hydroxyethyl)carbamoyl}thiazol-5-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 430),

[1059] 2-{4-[{2-(4-fluorophenyl)-5-(dimethylcarbamoyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 431),

[1060] 2-{4-[{2-(4-fluorophenyl)-5-(isopropylcarbamoyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 432),

[1061] 2-{4-[{2-(4-fluorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 433),

[1062] 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-tetrazol-5-ylbenzimidazole (Example 434),

[1063] 2-{4-[2-(4-carboxyphenyl)-5-chlorobenzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-tetrazol-5-ylbenzimidazole hydrochloride (Example 435),

[1064] 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),

[1065] 2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-5-cyano-1-cyclohexylbenzimidazole (Example 437),

[1066] 2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-5-cyano-1-cyclohexylbenzimidazole (Example 438),

[1067] 2-{4-[{N-(4-dimethylcarbamoyl)-N-(4-fluorophenyl)amino}-methyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 439),

[1068] 2-{5-[bis(3-fluorophenyl)methyl]-2-fluoro-4-hydroxyphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 440),

[1069] 2-{3-[bis(3-fluorophenyl)methyl]-2-fluoro-4-hydroxyphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 441),

[1070] 2-{4-[(3-dimethylcarbamoylphenyl) (4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 442),

[1071] 2-{4-[{(3-(4-hydroxypiperidyl-1-ylcarbonyl)phenyl}(4-fluorophenyl)methoxy)-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 443),

[1072] 1-{[2-{4-([4-(4-fluorophenyl)-2-methylthiazol-5-yl]methoxy)phenyl}-1-cyclohexylbenzimidazol-5-yl]carbonyl}-β-D-glucuronic acid (Example 444),

[1073] {[2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazol-5-yl]carbonyl}-β-D-glucuronic acid (Example 445),

[1074] 2-{4-[2-(4-chlorophenyl)-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 446),

[1075] 3-{[4-(5-aminosulfonyl-1-cyclohexylbenzimidazol-2-yl)-3-fluorophenoxy]methyl}-4-(4-chlorophenyl)-N-isopropylbenzamide (Example 447),

[1076] 2-[4-{2-(4-chlorophenyl)-6-(isopropylaminocarbonyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 448),

[1077] 2-[4-{2-(4-chlorophenyl)-4-fluoro-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 449),

[1078] 2-[4-{2-(4-chlorophenyl)-5-(isopropylaminocarbonyl)benzyloxy}-2-fluorophenyl]-1-cyclohexyl-4-methoxybenzimidazole-5-carboxylic acid hydrochloride (Example 450),

[1079] 2-[4-{2-(4-chlorophenyl)-5-(N-isopropylcarbonyl-N-methylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 451),

[1080] 2-[4-{2-(4-chlorophenyl)-5-(isopropylcarbonylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 452),

[1081] 2-[3-{[4-(4-fluorophenyl)-2-methylthiazol-5-yl]methyl}-4-hydroxyphenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 453),

[1082] 2-[4-{2-(4-chlorophenyl)-4-fluoro-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 454),

[1083] 2-[4-{2-(4-chlorophenyl)-5-(methylsulfonylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 455),

[1084] 2-[4-{2-(4-chlorophenyl)-5-[N-methyl-N-(methylsulfonyl)amino]benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 456),

[1085] 2-[4-{[3-(4-chlorophenyl)-6-(2-oxopyrrolidin-1-yl)pyridin-2-yl]methyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 457),

[1086] 2-[4-{2-(4-chlorophenyl)-5-(acetylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 458),

[1087] 2-[4-{2-(4-chlorophenyl)-5-(N-acetyl-N-ethylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 459),

[1088] 2-[4-{2-(4-chlorophenyl)-5-(N-acetyl-N-propylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 460),

[1089] 2-[4-{2-(4-chlorophenyl)-5-[N-ethyl-N-(methylsulfonyl)amino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 461),

[1090] 2-[4-{2-(4-chlorophenyl)-5-[N-(methylsulfonyl)-N-propylamino]benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 462),

[1091] 2-[4-{2-(4-chlorophenyl)-5-(N-acetyl-N-methylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 463),

[1092] 2-[4-{2-(4-chlorophenyl)-5-[N-(ethylsulfonyl)-N-methylamino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 464),

[1093] 2-[4-{2-(4-chlorophenyl)-5-[N-ethyl-N-(ethylsulfonyl)amino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 465),

[1094] 2-[4-{2-(4-chlorophenyl)-5-[N-(ethylcarbonyl)-N-methylamino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 466),

[1095] 2-[4-{2-(4-chlorophenyl)-5-[N-ethyl-N-(ethylcarbonyl)amino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 467),

[1096] 2-[4-{2-(4-chlorophenyl)-5-methoxybenzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (Example 468),

[1097] 2-[4-{2-(4-chlorophenyl)-5-(N-acetyl-N-isopropylamino)-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride (Example 469),

[1098] {[2-{4-[2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzoimidazol-5-yl]carbonyl}-β-D-glucuronic acid (Example 470),

[1099] 2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-3-cyclohexyl-3H-imidazo[4,5-b]pyridine-6-carboxylic acid hydrochloride (Example 702), and

[1100] 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).

[1101] (63) A pharmaceutical composition comprising a fused ring compound of any of (29) to (62) above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[1102] (64) A hepatitis C virus polymerase inhibitor comprising a fused ring compound of any of (1) to (28) and (29) to (62) above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[1103] (65) An anti-hepatitis C virus agent comprising a fused ring compound of any of (1) to (28) and (29) to (62) above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[1104] (66) A therapeutic agent for hepatitis C comprising a fused ring compound of any of (29) to (62) above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[1105] (67) An anti-hepatitis C virus agent comprising (a) the anti-hepatitis C virus agent of (65) above and (b) at least one agent selected from the group consisting of a different antiviral agent, an antiinflammatory agent and an immunostimulant.

[1106] (68) An anti-hepatitis C virus agent comprising (a) the anti-hepatitis C virus agent of (65) above and (b) interferon.

[1107] (69) A therapeutic agent for hepatitis C comprising (a) the hepatitis C virus polymerase inhibitor of (64) above and (b) at least one agent selected from the group consisting of a different antiviral agent, an antiinflammatory agent and an immunostimulant.

[1108] (70) A therapeutic agent for hepatitis C comprising (a) the hepatitis C virus polymerase inhibitor of (64) above and (b) interferon.

[1109] (71) A benzimidazole compound of the folllowing formula [III]

[1110] 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.

[1111] (72) 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.

[1112] (73) A biphenyl compound selected from the group consisting of 1-(4′-chloro-2-hydroxymethyl-biphenyl-4-yl)-2-pyrrolidinone and 1-(4′-chloro-2-chloromethyl-biphenyl-4-yl)-2-pyrrolidinone, or a pharmaceutically acceptable salt thereof.

[1113] (74) A pharmaceutical composition comprising (a) a fused ring 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.

[1114] (75) A pharmaceutical composition comprising (a) a fused ring compound of the formula [I] of (1) above or a pharmaceutically acceptable salt thereof and (b) interferon.

[1115] (76) 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.

[1116] (77) The method of (76) 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.

[1117] (78) The method of (76) above, further comprising administering an effective amount of interferon.

[1118] (79) 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.

[1119] (80) The method of (79) 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.

[1120] (81) The method of (79) above, further comprising administering an effective amount of interferon.

[1121] (82) Use of a fused ring compound of the formula [I] of (1) above or a pharmaceutically acceptable salt thereof for the production of a pharmaceutical agent for treating hepatitis C.

[1122] (83) Use of a fused ring compound of the formula [I] of (1) above or a pharmaceutically acceptable salt thereof for the production of a hepatitis C virus polymerase inhibitor.

[1123] (84) A pharmaceutical composition for the treatment of hepatitis C, which comprises a fused ring compound of the formula [I] of (1) above or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[1124] (85) A pharmaceutical composition for inhibiting hepatitis C virus polymerase, which comprises a fused ring compound of the formula [I] of (1) above or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[1125] (86) A commercial package comprising a pharmaceutical composition of (84) above and a written matter associated therewith, the written matter stating that the pharmaceutical composition can or should be used for treating hepatitis C.

[1126] (87) A commercial package comprising a pharmaceutical composition of (85) 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.

[1127] The definitions of respective substituents and moieties used in the present specification are as follows.

[1128] The halogen atom is a fluorine atom, chlorine atom, bromine atom or iodine atom, preferably fluorine atom, chlorine atom or bromine atom.

[1129] 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.

[1130] 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.

[1131] 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, Ra33, Ra35, Rb6 and Rb7 and methyl or tert-butyl at Rb1, Rb2, group B and group C, and methyl, ethyl, propyl or isopropyl at Ra29.

[1132] 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.

[1133] The halogenated C1-6 alkyl is particularly preferably trifluoromethyl at group B.

[1134] 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.

[1135] The C1-6 alkylene is preferably methylene or ethylene at Y.

[1136] 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.

[1137] The C2-6 alkenylene is preferably vinylene at Y.

[1138] 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.

[1139] The C1-6 alkoxy is particularly preferably methoxy at Ra2, Ra3, Ra27, Ra28, Ra33, group A and group C.

[1140] 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.

[1141] The group A is particularly preferably methoxyethoxy.

[1142] 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.

[1143] The C1-6 alkanoyl is particularly preferably acetyl at R1, R2, R3, R4, Ra5, Ra29, Rb7 and group B.

[1144] 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.

[1145] The C1-6 alkoxycarbonyl is particularly preferably methoxycarbonyl or ethoxycarbonyl at Ra10 and group A.

[1146] 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.

[1147] 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.

[1148] 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.

[1149] The C1-6 alkanoylamino is particularly preferably acetylamino at X and Ra10.

[1150] The C1-6 alkylsulfonyl is alkylsulfonyl wherein the alkyl moiety thereof is the above-defined C-1-6 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.

[1151] The C1-6 alkylsulfonyl is particularly preferably methylsulfonyl at X and Ra5.

[1152] 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.

[1153] The C6-14 aryl is preferably phenyl or naphthyl, particularly preferably phenyl at the ring A, ring A′, ring B and ring B′.

[1154] 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.

[1155] The C3-8 cycloalkyl is particularly preferably cyclohexyl at the ring A, ring A′, ring B and ring B′.

[1156] 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.

[1157] The C3-8 cycloalkenyl is preferably cyclohexenyl at the ring A and ring A′.

[1158] 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.

[1159] 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.

[1160] The heterocyclic group includes the groups of the following formulas.

[1161] 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.

[1162] Specific examples of the heterocyclic group include

[1163] and the like.

[1164] 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.

[1165] 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

[1166] and the like.

[1167] At R1, R2, R3, R4, Z and group D, tetrazolyl and 5-oxo-Δ2-1,2,4-oxadiazolin-3-yl are particularly preferable.

[1168] 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′.

[1169] 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.

[1170] 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.

[1171] The C6-14 aryl C1-6 alkyl is particularly preferably benzyl at Ra8 and Rb6.

[1172] The glucuronic acid residue is glucuronic acid less any hydroxyl group, preferably β-D-glucuronic acid substituted at 1-position.

[1173] 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.

[1174] The C6-14 aryl C1-6 alkyloxycarbonyl is particularly preferably benzyloxycarbonyl at Rb7.

[1175] 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.

[1176] 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, Ra31 and Rb5, methyl, ethyl or isopropyl at Ra24, methyl or isopropyl at Ra18, methyl or ethyl at Ra1, Ra19 and Ra25, 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 Ra23, 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.

[1177] 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.

[1178] 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.

[1179] 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.

[1180] 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.

[1181] The optionally substituted C2-6 alkynyl is preferably 2-propynyl at Ra20.

[1182] 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)rSRb1, —(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).

[1183] 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.

[1184] 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.

[1185] 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, 4-chlorophenyl, 4-methoxyphenyl or 4-trifluoromethylphenyl at Ra12, Ra27 and 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, 3-nitro-4-methoxyphenyl or 4-nitro-3-methoxyphenyl at Ra24, and phenyl or 4-methylphenyl at Ra25.

[1186] It is particularly preferably phenyl at other substituents.

[1187] 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)).

[1188] 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.

[1189] 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.

[1190] At Z and Z′, the aryl moiety is preferably phenyl.

[1191] 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.

[1192] 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.

[1193] 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, particularly preferably 4-chlorophenyl.

[1194] 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, —(CH2r—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.

[1195] 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, 2,2,6,6-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,

[1196] and the like.

[1197] 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.

[1198] 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,

[1199] 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 Ra26 and at Ra27 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.

[1200] 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)).

[1201] 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.

[1202] 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, indolyl, benzimidazolyl, indolinyl, benzofuranyl, benzothienyl, benzoxazolyl, benzothiazolyl

[1203] and the like.

[1204] 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-pyridyl, 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.

[1205] 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.

[1206] 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, 3methyl-1,2,4-oxadiazol-5-yl, 1,1-dioxoisothiazolidin-2-yl, 4,4dimethyl-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.

[1207] 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-oxopiperidin-1-yl, 2-oxopyrrolidin-1-yl, 2-oxoimidazolidin-1-yl, 2-oxooxazolidin-1-yl, or 1,1-dioxoisothiazolidin-2-yl, most preferably 2-oxopyrrolidin-1-yl.

[1208] 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.

[1209] The cycloalkyl moiety is preferably cyclopentyl or cyclohexyl, particularly preferably cyclohexyl.

[1210] 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.

[1211] 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.

[1212] 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.

[1213] 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.

[1214] 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. 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)).

[1215] 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.

[1216] 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.

[1217] 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.

[1218] The cycloalkyl moiety is preferably cyclopentyl or cyclohexyl, and at Z and Z′, it is particularly preferably cyclohexyl.

[1219] 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.

[1220] The optionally substituted C3-8 cycloalkenyl is particularly preferably cyclohexenyl at the ring Cy.

[1221] 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.

[1222] 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, 4acetylbenzyl, 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.

[1223] 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), —ORb1. Examples thereof include fluorine atom, chlorine atom, nitro, methyl, tert-butyl, trifluoromethyl, methoxy or trifluoromethyloxy, particularly preferably fluorine atom or chlorine atom.

[1224] 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.

[1225] It is particularly preferably benzyl at other substituents.

[1226] 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)).

[1227] 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.

[1228] 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.

[1229] 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)tCONRa27Ra28, —(CH2)t—ORa20, —(CH2)t—NRa29CO—Ra24, —(CH2)t—S(O)q—Ra25 or —(CH2)t—SO2—NHRa26.

[1230] 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.

[1231] 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.

[1232] 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.

[1233] 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.

[1234] 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.

[1235] Examples of heterocycle C1-6 alkyl optionally substituted 5 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.

[1236] 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)).

[1237] 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.

[1238] 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, 4methylthiazol-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.

[1239] 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).

[1240] Preferable group D is the above-defined halogen atom, nitro, the above-defined optionally substituted C1-6 alkyl, —(CH2)t—COORa19, —(CH2)tCONRa27Ra28, —(CH2)tORa20, —(CH2)t—NRa29CO—Ra24, —(CH2)t—S(O)q—Ra25 or —(CH2)t—SO2—NHRa26.

[1241] 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.

[1242] Particularly preferred is 4-hydroxypiperidinomethyl.

[1243] 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.

[1244] 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.

[1245] 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.

[1246] At C3-8 cycloalkyl C1-6 alkyl moiety, it is preferably cyclopentylmethyl or cyclohexylmethyl, and at Ra20, Ra27 and Ra28, it is particularly preferably cyclohexylmethyl.

[1247] 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.

[1248] Preferred are industrially effective protecting groups and specifically preferred as Ra36 are methyl and ethyl.

[1249] In formula [I], X is preferably

[1250] wherein each symbol is as defined above.

[1251] 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.

[1252] 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.

[1253] In formulas [I] and [II], 1 to 4 of G1 to G9 in the moiety

[1254] is(are) preferably a nitrogen atom, specifically preferably

[1255] It is also a preferable embodiment wherein the

[1256] moiety is aromatic ring.

[1257] R1 and R3 are preferably hydrogen atom or —ORa6 (Ra6 is as defined above), particularly 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. R4 is preferably hydrogen atom.

[1258] Ra1 is preferably optionally substituted C1-6 alkyl.

[1259] 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).

[1260] The ring Cy and ring Cy′ are preferably cyclopentyl, cyclohexyl, cycloheptyl, tetrahydrothiopyranyl or piperidino, particularly preferably cyclopentyl, cyclohexyl or cycloheptyl, more preferably cyclohexyl.

[1261] 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.

[1262] 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.

[1263] 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 are preferably 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′.

[1264] 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—NRa12CHRa15— (each symbol is as defined above), more preferably, —(CH2)m—O—(CH2)n— or —O—(CH2)n—CRa15Ra16—(CH2)n—, most preferably —(CH2)m—O—(CH2)n—.

[1265] 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=0 and n=1. 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=0 and n=1.

[1266] When Y is —O—(CH2)m—CRa15Ra16—(CH2)n—, Ra16 is preferably hydrogen atom, Ra15 is preferably

[1267] 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.

[1268] 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.

[1269] When ring B is bonded to Y as pyridin-2-yl, Z is preferably substituted at the 3-position and 6-position of pyridyl; when it is bonded to Y as pyridin-3-yl, Z is preferably substituted at the 2-position and 5-position of pyridyl; and when it is bonded to Y as pyridin-4-yl, Z is preferably substituted at the 2-position and 5-position of pyridyl.

[1270] 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.

[1271] 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”.

[1272] More preferably, they are the above-defined halogen atom, nitro, the above-defined optionally substituted C1-6 alkyl, —(CH2)t—CORa18, —(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.

[1273] 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.

[1274] 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, N-acetyl-N-ethylamino, N-acetyl-N-propylamino, N-acetyl-N-isopropylamino, N-ethylcarbonyl-N-methylamino, N-ethyl-N-(ethylcarbonyl)amino, 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-(methylsulfonyl)-N-methylamino, N-(ethylsulfonyl)-N-methylamino, N-(isopropylsulfonyl)-N-methylamino, N-(methylsulfonyl)-N-ethylamino, N-(methylsulfonyl)-N-propylamino, N-(ethylsulfonyl)-N-ethylamino, methylthio, methylsulfonyl, isopropylsulfonyl, isobutylsulfonyl, methylsulfinyl, isopropylsulfinyl, aminosulfonyl, methylaminosulfonyl, dimethylaminosulfonyl, isopropylaminosulfonyl, tert-butylaminosulfonyl, 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, N-acetyl-N-methylamino, 4-(N-acetyl-N-methylamino)phenyl, 4-(N-acetyl-N-ethylamino)phenyl, 4-(N-acetyl-N-propylamino)phenyl, 4-(N-acetyl-N-isopropylamino)phenyl, 4-(N-ethylcarbonyl-N-methylamino)phenyl, 4-[N-ethyl-N-(ethylcarbonyl)amino]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-hydroxypiperidino-carbonylmethyloxy, 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-hydroxypiperidinosulfonyl, 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.

[1275] 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, N-acetyl-N-methylamino, N-acetyl-N-ethylamino, N-acetyl-N-propylamino, N-acetyl-N-isopropylamino, N-ethylcarbonyl-N-methylamino, N-ethyl-N-(ethylcarbonyl)amino, 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.

[1276] 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.

[1277] 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.

[1278] In formula [I], when X is

[1279] 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.

[1280] When ring B is phenyl, w is 2 and phenyl is bonded to Y at the 1-position, one of the most preferable embodiments is that wherein Z is bonded to the 2-position and 5-position of phenyl, Z at the 2-position is “C6-14 aryl optionally substituted by 1 to 5 substituent(s) selected from group D” and Z at the 5-position is “heterocyclic group optionally substituted by 1 to 5 substituent(s) selected from group D”.

[1281] 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, lactic acid, malic acid, succinic acid, tartaric acid, acetic acid, trifluoroacetic acid, gluconic acid, ascorbic acid, methylsulfonic acid, benzylsulfonic acid, meglumine 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.

[1282] 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.

[1283] The present invention also encompasses prodrug and metabolite of each compound.

[1284] 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.

[1285] 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, injections, eye drops, liquids, capsules, troches, aerosols, elixirs, suspensions, emulsions, syrups and the like, which can be administered systemically or topically and orally or parenterally.

[1286] 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.

[1287] 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.

[1288] The therapeutic agent for hepatitis C of the present invention is expected to provide a synergestic effect when concurrently used with other antiviral agents, antiinflammatory agents or immunostimulants.

[1289] The medicaments with the prospect of synergestic effect include, for example, interferon-α, interferon-β, interferon-γ, interleukin-2, interleukin-8, interleukin-10, interleukin-12, TNFα, recombinant or modified products thereof, agonists, antibodies, vaccines, ribozymes, antisense nucleotides and the like.

[1290] As evidenced in the combination therapy of anti-HIV agents, which is also called a cocktail therapy, the combined use of various anti-virus agents againt viruses showing frequent genetic mutations is expected to show effect for suppressing emergence and increase of drug tolerant viruses. For example, 2 or 3 agents from HCV-IRES inhibitors, HCV-NS3 protease inhibitors, HCV-NS2NS3 protease inhibitors, HCV-NS5A inhibitors and HCV polymerase inhibitor may be used in combination. Specifically, the combined use with Ribavirin(R), interferon-α (IFN-α, Roferon(R), Intron A(R), Sumiferon(R), MultiFeron(R), Infergen(R), Omniferon(R), Pegasys(R), PEG-Intron A(R)), interferon-β (Frone(R), Rebif(R), AvoneX(R), IFNβMOCHIDA(R)), interferon-ω, 1-β-L-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide, 16α-bromo-3β-hydroxy-5α-androstan-17-one, 1H-imidazole-4-ethanamide dihydrochloride, HCV ribozyme Heptazyme(R), polyclonal antibody Civacir(R), lactoferrin GPX-400, (1S,2R,8R,8aR)-1,2,8-trihydroxyoctahydroindolizidinium chloride, HCV vaccine (MTH-68/B, Innivax C(R), Engerix B(R)), antisense oligonucleotide ISIS-14803, HCV-RNA transcriptase inhibitor VP-50406, tetrachlorodecaoxide (high concentration Oxoferin(R)), tetrahydrofuran-3-yl (S)—N-3-[3-(3-methoxy-4-oxazol-5-ylphenyl)ureido]benzylcarbamate, 4-amino-2-ethoxymethyl-α,α-dimethyl-1H-imidazo[4,5-c]quinoline-1-ethanol, interleukin-2 (Proleukin(R)), thymosin α1 and the like is exemplified, wherein (R) shows product names.

[1291] Furthermore, the combined use with the compounds disclosed in JP-A-08-268890, JP-A-10-101591, JP-A-07-069899, WO99/61613 and the like as HCV IRES inhibitors; the compounds disclosed in WO98/22496, WO99/07733, WO99/07734, WO00/09543, WO00/09558, WO01/59929, WO98/17679, EP932617, WO99/50230, WO00/74768, WO97/43310, U.S. Pat. No. 5,990,276, WO01/58929, WO01/77113, WO02/8198, WO02/8187, WO02/8244, WO02/8256, WO01/07407, WO01/40262, WO01/64678, WO98/46630, JP-A-11-292840, JP-A-10-298151, JP-A-11-127861, JP-A-2001-103993, WO98/46597, WO99/64442, WO00/31129, WO01/32961, WO93/15730, U.S. Pat. No. 7,832,236, WO00/200400, WO02/8251, WO01/16379, WO02/7761 and the like as HCV protease inhibitors; the compounds disclosed in WO97/36554, U.S. Pat. No. 5,830,905, WO97/36866, U.S. Pat. No. 5,633,388, WO01/07027, WO00/24725 and the like as HCV helicase inhibitors; the compounds disclosed in WO00/10573, WO00/13708, WO00/18231, WO00/06529, WO02/06246, WO01/32153, WO01/60315, WO01/77091, WO02/04425, WO02/20497, WO00/04141 and the like as HCV polymerase inhibitors; the compounds disclosed in WO01/58877, JP-A-11-180981, WO01/12214 and the like as interferon agonists or enhancers; and the like is also exemplified.

[1292] 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.

[1293] 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.

[1294] 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.

[1295] 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.

[1296] Production Method 1

[1297] In this Production Method, a benzimidazole compound is formed from a nitrobenzene compound.

[1298] Production Method 1-1

[1299] wherein Hal is halogen atom, such as chlorine atom, bromine atom and the like, Rcl is halogen atom, such as chlorine atom, bromine atom and the like, or hydroxyl group, and other symbols are as defined above.

[1300] Step 1

[1301] 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].

[1302] Step 2

[1303] 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]. The compound [4] can be also obtained by reacting compound (3] with sodium hydrosulfite under alkaline conditions.

[1304] Step 3

[1305] 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].

[1306] Step 4

[1307] 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].

[1308] Production Method 1-2

[1309] This Production Method is an alternative method for producing compound [I-2].

[1310] wherein each symbol is as defined above.

[1311] Step 1

[1312] 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].

[1313] Step 2

[1314] The compound [7] is reduced in the same manner as in Step 2 of Production Method 1-1 to give compound [8].

[1315] Step 3

[1316] 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].

[1317] Production Method 1-3

[1318] wherein Rc2 is alkyl such as methyl, ethyl and the like, and other symbols are as defined above.

[1319] 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).

[1320] 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].

[1321] 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].

[1322] Production Method 2

[1323] 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.

[1324] Production Method 2-1

[1325] Conversion of Carboxylic Acid Ester Moiety to Amide

[1326] wherein E is a single bond, —(CH2)s—, —O—(CH2)s— or —NH—(CH2)s— (wherein s is an integer of 1 to 6), Rc3, Rc4 and Rc5 are C1-6 alkyl, and other symbols are as defined above.

[1327] Step 1

[1328] 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].

[1329] Step 2

[1330] 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].

[1331] Production Method 2-2

[1332] Conversion of Cyano Group to Substituted Amidino Group

[1333] wherein each symbol is as defined above.

[1334] 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.

[1335] Production Method 2-3

[1336] Conversion of Sulfonic Acid Ester Moiety to Sulfonic Acid

[1337] wherein Rc6 is C1-6 alkyl, and other symbols are as defined above.

[1338] The compound [I-2-6] obtained in the same manner as in the 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].

[1339] Production Method 3

[1340] 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.

[1341] Production Method 3-1

[1342] Conversion of Hydroxyl Group to Ether

[1343] 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.

[1344] 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].

[1345] 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].

[1346] The compound [I-2-9] can be obtained in the same manner from compound [I-2-8] and compound [14].

[1347] Production Method 3-2

[1348] Conversion of Nitro to Substituted Amino Group

[1349] 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.

[1350] Step 1

[1351] 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 [I2-11].

[1352] Step 2

[1353] 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].

[1354] Step 3

[1355] 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].

[1356] 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].

[1357] The compound [I-2-11] is acylated with compound [17] in the same manner as above to give compound [I-2-12].

[1358] 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 [I-2-12].

[1359] Production Method 3-3

[1360] Conversion of Carboxylic Acid Ester Moiety to Amide

[1361] 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.

[1362] Step 1

[1363] 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].

[1364] Step 2

[1365] The compound [1-2-14] is reacted with compound [18] in the same manner as in Step 2 of Production Method 2-1 to give compound [II-2-4].

[1366] The compound [I-2-15] is obtained from compound [1-2-14] and compound [19] in the same manner as above.

[1367] Production Method 4

[1368] 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.

[1369] Production Method 4-1

[1370] Direct Bonding of Ring Z″ to Ring B

[1371] 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 and 4-chlorophenylboronic acid, w″ is 0, 1 or 2, and other symbols are as defined above.

[1372] 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 hydrogencarbonate, potassium phosphate, triethylamine and the like at room temperature or with heating, to give compound [II-2-6].

[1373] Production Method 4-2

[1374] Conversion of Hydroxyl Group to Ether

[1375] wherein Rc10 is —Ra20 or —(CH2)p—CORa21 corresponding to substituent Z, and other symbols are as defined above.

[1376] 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].

[1377] Production Method 4-3

[1378] Synthesis in Advance of Ring B Part such as Compound [13] in Production Method 3-1

[1379] wherein Rc11 is leaving group such as chlorine atom, 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.

[1380] Step 1

[1381] 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].

[1382] Step 2

[1383] 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].

[1384] 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].

[1385] Step 3

[1386] 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, to give compound [25]. For an accerelated reaction, the reaction may be carried out in the presence of a tertiary amine such as DMF, pyridine and the like, or under heating.

[1387] Step 4

[1388] 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].

[1389] Production Method 4-4

[1390] wherein M′ is a metal such as magnesium, lithium, zinc and the like, and other symbols are as defined above.

[1391] Step 1

[1392] 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].

[1393] 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].

[1394] Step 2

[1395] The compound [42] obtained in the same manner as in the above-mentioned Production Method is reacted with compound [43] to give compound [44].

[1396] 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].

[1397] Step 3

[1398] 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].

[1399] The compound [44] is reacted with thionyl chloride and pyridine preferably in toluene solvent to give compound [45].

[1400] 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].

[1401] Production Method 4-5

[1402] Method Including Steps to Introduce a Protecting Group into a Functional Group

[1403] wherein Rc13 is carboxylic acid protecting group such as tertbutyl and the like, Rc14 is carboxylic acid protecting group such as methyl and the like and other symbols are as defined above.

[1404] Step 1

[1405] Commercially available compound (26] or compound [26] obtained by a conventional method is protected by a conventional method to give compound [27].

[1406] 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].

[1407] 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.

[1408] Step 2

[1409] 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].

[1410] Step 3

[1411] 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].

[1412] Step 4

[1413] 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].

[1414] 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].

[1415] Step 5

[1416] 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].

[1417] Step 6

[1418] 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].

[1419] 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.

[1420] 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].

[1421] Production Method 4-6

[1422] wherein g is an integer of 1 to 5, and other sumbols are as defined above.

[1423] Step 1

[1424] 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].

[1425] Step 2

[1426] 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].

[1427] Step 3

[1428] 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].

[1429] Step 4

[1430] 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].

[1431] Step 5

[1432] 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].

[1433] Production Method 4-7

[1434] wherein each symbol is as defined above.

[1435] Step 1

[1436] Commercially available product or compound [46] obtained by a conventional method is reacted with compound [20] in the same manner as in Production Method 4-1 to give compound [47].

[1437] Step 2

[1438] The compound [47] obtained in the same manner as in the above-mentioned Production Method is reduced in the same manner as in the above-mentioned Production Method 4-3 Step 2 to give compound [48].

[1439] Step 3

[1440] The compound [48] obtained in the same manner as in the above-mentioned Production Method is reduced in the same manner as in the above-mentioned Production Method 1-1 Step 2 to give compound [49].

[1441] Step 4

[1442] The compound [49] obtained in the same manner as in the above-mentioned Production Method is reacted with compound [42] in a solvent such as DMF, acetonitrile, THF, chloroform, ethyl acetate, methylene chloride and toluene to give compound [50]. To enhance the reaction selectivity for amino group, acetic acid and sodium acetate may be added in an equivalent amount ratio.

[1443] Step 5

[1444] The compound [50] obtained in the same manner as in the above-mentioned Production Method is subjected to cyclization reaction in the same manner as in the above-mentioned Production Method 1-1 Step 1 to give compound [51].

[1445] Step 6

[1446] The compound [51] obtained in the same manner as in the above-mentioned Production Method is halogenated in the same manner as in the above-mentioned Production Method 4-3 Step 3 to give compound [52].

[1447] Step 7

[1448] The compound [52] obtained in the same manner as in the above-mentioned Production Method is reacted in the same manner as in the above-mentioned Production Method 3-1 with compound [I-2-16] obtained in the same manner as in the above-mentioned Production Method to give compound [II-2-20].

[1449] Step 8

[1450] The compound [II-2-20] obtained in the same manner as in the above-mentioned Production Method is hydrolyzed in the same manner as in the above-mentioned Production Method 2-1 Step 1 to give compound [II-2-21].

[1451] Production Method 5

[1452] Formation of Indole Ring

[1453] wherein Rc15 is protecting group such as trimethylsilyl, tertbutyldimethylsilyl, tert-butyldiphenylsilyl and the like, and other symbols are as defined above.

[1454] Step 1

[1455] 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].

[1456] Step 2

[1457] 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].

[1458] Step 3

[1459] 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].

[1460] Production Method 6

[1461] Formation of imidazo[1,2-a]pyridine Ring

[1462] wherein Rc16 and Rc17 are each independently alkyl, such as methyl, ethyl and the like, and other symbols are as defined above.

[1463] Step 1

[1464] 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].

[1465] Step 2

[1466] 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].

[1467] Alternatively, an acid halide of compound [34] may be used instead of compound [36].

[1468] Step 3

[1469] The compound [38] obtained by the above-mentioned Production Method is subjected to halogenation by a conventional method to give compound [39].

[1470] 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].

[1471] 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.

[1472] Step 4

[1473] 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].

[1474] 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.

[1475] 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,

[1476] 5-oxo-Δ2-1,2,4-triazolin-3-yl: J Org Chem, 61(24), 8397-8401, 1996,

[1477] 1-oxo-Δ3-1,2,3,5-thiatriazolin-4-yl: Liebigs Ann Chem, 1376, 1980,

[1478] 3-oxo-Δ4-1,2,4-oxadiazolin-5-yl: EP145095,

[1479] 5-oxo-Δ2-1,3,4-oxadiazolin-2-yl: J Org Chem, 20, 412, 1955,

[1480] 5-oxo-Δ3-1,2,4-dioxazolin-3-yl: J Prakt Chem, 314, 145, 1972,

[1481] 3-oxo-Δ4-1,2,4-thiadiazolin-5-yl: JP-A-61-275271,

[1482] 5-oxo-Δ3-1,2,4-dithiazolin-3-yl: J Org Chem, 61(19), 6639-6645, 1996,

[1483] 2-oxo-Δ4-1,3,4-dioxazolin-5-yl: J Org Chem, 39, 2472, 1974,

[1484] 2-oxo-Δ4-1,3,4-oxathiazolin-5-yl: J Med Chem, 35(20), 3691-98, 1992,

[1485] 5-oxo-Δ2-1,3,4-thiadiazolin-2-yl: J Prakt Chem, 332(1), 55, 1990,

[1486] 5-oxo-Δ2-1,4,2-oxathiazolin-3-yl: J Org Chem, 31, 2417, 1966,

[1487] 2-oxo-Δ4-1,3,4-dithiazolin-5-yl: Tetrahedron Lett, 23, 5453, 1982,

[1488] 2-oxo-Δ4-1,3,2,4-dioxathiazolin-5-yl: Tetrahedron Lett, 319, 1968,

[1489] 3,5-dioxoisooxazolidin-4-yl: Helv Chim Acta, 1973, 48, 1965,

[1490] 2,5-dioxoimidazolidin-4-yl: Heterocycles, 43(1), 49-52, 1996,

[1491] 5-oxo-2-thioxoimidazolidin-4-yl: Heterocycles, 5, 391, 1983,

[1492] 2,4-dioxooxazolidin-5-yl: J Am Chem Soc, 73, 4752, 1951,

[1493] 4-oxo-2-thioxooxazolidin-5-yl: Chem Ber, 91, 300, 1958,

[1494] 2,4-dioxothiazolidin-5-yl: JP-A-57-123175,

[1495] 4-oxo-2-thioxothiazolidin-5-yl: Chem Pharm Bull, 30, 3563, 1982,

[1496] 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].

[1497] 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

[1498] Production of ethyl 2-(4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1499] Step 1: Production of ethyl 4-chloro-3-nitrobenzoate

[1500] 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%).

[1501]

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)

[1502] Step 2: Production of ethyl 4-cyclohexylamino-3-nitrobenzoate

[1503] 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%).

[1504]

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)

[1505] Step 3: Production of ethyl 3-amino-4-cyclohexylaminobenzoate

[1506] 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%).

[1507]

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)

[1508] Step 4: Production of ethyl 3-[4-(3-bromophenoxy)benzoyl]amino-4-cyclohexylaminobenzoate

[1509] 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%).

[1510]

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)

[1511] Step 5: Production of ethyl 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1512] Ethyl 3-[4-(3-bromophenoxy)benzoyl]amino-4cyclohexylaminobenzoate (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%).

[1513]

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

[1514] Production of 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid

[1515] Ethyl 2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-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%).

[1516] melting point: 255-256° C.

[1517] FAB-Ms: 491(MH+)

[1518]

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

[1519] Production of ethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate

[1520] 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%).

[1521]

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

[1522] Production of ethyl 2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1523] 2-Bromo-5-chlorobenzyl bromide prepared from 2-bromo-5chlorotoluene (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%).

[1524]

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

[1525] Production of ethyl 2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1526] 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%).

[1527]

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

[1528] Production of 2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxylphenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid

[1529] 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%).

[1530] melting point: 243-244° C.

[1531] FAB-Ms: 571(MH+)

[1532]

1
H-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

[1533] Production of ethyl 2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1534] 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

[1535] Production of ethyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1536] 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%).

[1537]

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

[1538] Production of 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid

[1539] 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%).

[1540] melting point: 248-249° C.

[1541] FAB-Ms: 568(MH+)

[1542]

1
H-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

[1543] Production of ethyl 1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}-benzimidazole-5-carboxylate

[1544] 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 (0.1 ml) 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%).

[1545]

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

[1546] Production of 1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}-benzimidazole-5-carboxylic acid

[1547] 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%).

[1548] melting point: not lower than 300° C.

[1549] FAB-Ms: 423(MH+)

[1550]

1
H-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

[1551] Production of 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid

[1552] In the same manner as in Examples 1 and 2, the title compound (700 mg) was obtained.

[1553] FAB-Ms: 413(MH+)

[1554]

1
H-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

[1555] Production of 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide

[1556] 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%).

[1557] melting point: 232-233° C.

[1558] FAB-Ms: 412(MH+)

[1559]

1
H-NMR (300 MHz, CDCl3): 8.23(1H, d, =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

[1560] Production of 2-(4-benzyloxyphenyl)-5-cyano-1-cyclopentylbenzimidazole

[1561] In the same manner as in Example 1, the title compound (400 mg) was obtained.

[1562] FAB-Ms: 394(MH+)

[1563]

1
H-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

[1564] Production of 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide oxime

[1565] 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%).

[1566] melting point: 225-226° C.

[1567] FAB-Ms: 456(MH+)

[1568]

1
H-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

[1569] Production of ethyl 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylate

[1570] Step 1: Production of 4-(4-fluorophenyl)-5-hydroxymethyl-2-methylthiazole

[1571] 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%).

[1572]

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)

[1573] Step 2: Production of 5-chloromethyl-4-(4-fluorophenyl)-2-methylthiazole

[1574] 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%).

[1575]

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)

[1576] Step 3: Production of ethyl 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-4-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole -5-carboxylate

[1577] 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%).

[1578] APCI-Ms: 570(MH+)

[1579]

1
H-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

[1580] Production of 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic acid

[1581] Ethyl 1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-4-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 (39g, yield 69%).

[1582] melting point: 196-198° C.

[1583] FAB-Ms: 542(MH+)

[1584]

1
H-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

[1585] Production of ethyl 1-cyclohexyl-2-(2-fluoro-4-hydroxyphenyl)-benzimidazole-5-carboxylate

[1586] In the same manner as in Example 3, the title compound (50 g) was obtained.

EXAMPLE 19

[1587] Production of ethyl 2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1588] Step 1 : Production of 3,3′-difluorobenzhydrol

[1589] 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%).

[1590]

1
H-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)

[1591] Step 2: Production of 3,3′-difluorobenzhydryl chloride

[1592] 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%).

[1593]

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)

[1594] Step 3: Production of ethyl 2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1595] 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%).

[1596] FAB-Ms: 585(MH+)

[1597]

1
H-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

[1598] Production of 2-{4-(bis[3-fluorophenyl]methoxy)-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid

[1599] 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%).

[1600] melting point: 242-243° C.

[1601] FAB-Ms: 557(MH+)

[1602]

1
H-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

[1603] Production of ethyl 1-cyclopentyl-2-(4-nitrophenyl)benzimidazole-5-carboxylate

[1604] In the same manner as in Example 1, the title compound (12 g) was obtained.

EXAMPLE 22

[1605] Production of ethyl 2-(4-aminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate

[1606] 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%).

[1607]

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

[1608] Production of ethyl 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate

[1609] 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%).

[1610]

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

[1611] Production of 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid

[1612] 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%).

[1613] melting point: not lower than 300° C.

[1614] FMB-Ms: 426(MH+)

[1615]

1
H-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

[1616] Production of ethyl 2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1617] 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%).

[1618]

1
H-NMR (300 MHz, CDCl3): 8.51(1H, d, J=1.8Hz), 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

[1619] Production of 2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid

[1620] 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%).

[1621] melting point: 253-254° C.

[1622] FAB-Ms: 523(MH+)

[1623]

1
H-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

[1624] Production of ethyl 2-[4-(3-acetoxyphenyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1625] In the same manner as in Example 1, the title compound (87 g) was obtained.

EXAMPLE 28

[1626] Production of ethyl 1-cyclohexyl-2-[4-(3-hydroxyphenyloxy)-phenyl]benzimidazole-5-carboxylate

[1627] 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%).

[1628]

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=6.9Hz), 2.36−2.18(2H, 20 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

[1629] Production of ethyl 1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)-phenyloxy]phenyl}benzimidazole-5-carboxylate

[1630] 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%).

[1631]

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(3m), 1.42(3H, t, J=7.0 Hz)

EXAMPLE 30

[1632] Production of 1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]-phenyl}benzimidazole-5-carboxylic acid

[1633] 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%).

[1634] melting point: 235-237° C.

[1635] FAB-Ms: 520(MH+)

[1636]

1
H-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

[1637] Production of methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1638] Step 1: Production of 2-bromo-5-methoxybenzaldehyde

[1639] 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%).

[1640]

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)

[1641] Step 2: Production of 2-(4-chlorophenyl)-5-methoxybenzaldehyde

[1642] 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%).

[1643]

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)

[1644] Step 3: Production of 2-(4-chlorophenyl)-5-methoxybenzyl alcohol

[1645] 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%).

[1646]

1
H-NMR (300 MHz, CDCl3): 7.37(2H, d, J=B8.6 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)

[1647] Step 4: Production of 2-(4-chlorophenyl)-5-methoxybenzyl chloride

[1648] 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%).

[1649]

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)

[1650] Step 5: Production of methyl 2-{4-[2-(4-chlorophenyl)-5methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1651] 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%).

[1652]

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

[1653] Production of 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride

[1654] 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%).

[1655] APCI-Ms: 568(MH+)

[1656]

1
H-NMR (300MHz, DMSO-d6): 8.30(1H, d, J=1.4Hz), 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

[1657] Production of ethyl 2-{4-[3-(4-chlorophenyl)pyridin-2-ylmethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1658] Step 1: Production of methyl 3-hydroxypicolinate

[1659] 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%).

[1660]

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)

[1661] Step 2: Production of methyl 3-(trifluoromethylsulfonyloxy)-pyridine-2-carboxylate

[1662] 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%).

[1663]

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)

[1664] Step 3: Production of methyl 3-(4-chlorophenyl)pyridine-2-carboxylate

[1665] 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%).

[1666]

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)

[1667] Step 4: Production of [3-(4-chlorophenyl)pyridin-2-yl]methanol.

[1668] 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%).

[1669]

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)

[1670] Step 5: Production of ethyl 2-{4-[3-(4-chlorophenyl)pyridin-2-ylmethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1671] [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%).

[1672]

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(11H, m)

EXAMPLE 244

[1673] Production of methyl 2-[4-(2-bromo-5-tert-butoxycarbonyl-benzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1674] Step 1: Production of tert-butyl 4-bromo-3-methylbenzoate

[1675] 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%).

[1676]

1
H-NMR (300 MHz, CDCl3): 7.83(1H, d, J=2.2 Hz), 7.67−7.53(2H, m), 2.43(3H, s), 1.58(9H, s) Step 2: Production of methyl 2-[4-(2-bromo-5-tert-butoxycarbonylbenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1677] 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%).

[1678]

1
H-NMR (300 MHz, CDCl3): 8.49(1H, d, J=1l.5Hz), 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

[1679] Production of methyl 2-{4-[5-tert-butoxycarbonyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1680] Methyl 2-[4-(2-bromo-5-tert-butoxycarbonylbenzyloxy)phenyl]-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%).

[1681]

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

[1682] Production of methyl 2-{4-[5-carboxy-2-(4-chlorophenyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride

[1683] 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%).

[1684]

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

[1685] Production of methyl 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoyl-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[1686] 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%).

[1687]

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

[1688] Production of 2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate hydrochloride

[1689] 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%).

[1690] APCI-Ms: 594(MH+)

[1691]

1
H-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

[1692] Production of methyl 2-[4-(2-bromo-5-nitrobenzyloxy)-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1693] 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%).

[1694]

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

[1695] Production of methyl 2-[4-{2-(4-chlorophenyl)-5-nitrobenzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxlate

[1696] 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%).

[1697]

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

[1698] Production of methyl 2-(4-{5-amino-2-(4-chlorophenyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1699] 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%).

[1700]

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

[1701] Production of methyl 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate

[1702] 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%).

[1703]

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(6m), 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

[1704] Production of 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride

[1705] 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%).

[1706] Ms:638(M+1)

[1707]

1
H-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)

EXAMPLE 340-2

[1708] Step 1: Production of 4′-chloro-4-nitro-biphenyl-2-carbaldehyde

[1709] To a solution of 2-chloro-5-nitrobenzaldehyde (100 g) in 1,2-dimethoxyethane (1000 ml) were added 4-chlorophenylboronic acid (93 g), bistriphenylphosphine palladium(II) dichloride (380 mg), sodium hydrogencarbonate (68 g) and water (500 ml), and the mixture was refluxed for 1 hr. The reaction mixture was cooled to 50° C., ethyl acetate (1000 ml) was added thereto and the mixture was stirred. The aqueous layer was separated and the organic layer was washed with water (500 ml), 1N aqueous sodium hydroxide solution (500 ml), water (500 ml), 28% aqueous ammonia (500 ml), water (500 ml), 2N hydrochloric acid (500 ml) and saturated brine (500 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was suspended in diisopropyl ether (500 ml), filtrated and vacuum dried to give the title compound (120 g, yield 85%).

[1710]

1
H-NMR (300 MHz, DMSO-d6): 9.92(1H, s), 8.61 (1H, d, J=2.5 Hz), 8.53(1H, dd, J=2.6 Hz, 8.5 Hz), 7.82(1H, d, J=8.5 Hz), 7.64(2H, d, J=8.7 Hz), 7.59(2H, d, J=8.7 Hz)

[1711] Step 2: Production of (4′-chloro-4-nitro-biphenyl-2-yl)methanol

[1712] A solution of 4′-chloro-4-nitro-biphenyl-2-carbaldehyde (120 g) obtained in the previous step in tetrahydrofuran (900 ml) was added dropwise to a suspension of sodium borohydride (47 g) in 2propanol (600 ml), over 70 min under water-cooling. The reaction mixture was stirred at room temperature for 1 hr, and 2N hydrochloric acid (185 ml) was dropwise added thereto over 40 min under water-cooling. The mixture was stirred at room temperature for 30 min and concentrated under reduced pressure. The residue was suspended in 2-propanol (300 ml), and water (1000 ml) was added with stirring. After stirring the mixture for 30 min, the crystals were collected by filtration and vacuum dried to give the title compound (116 g, yield 96%).

[1713]

1
H-NMR (300MHz, DMSO-d6): 8.43(1H, d, J=2.5 Hz), 8.19(1H, dd, J=2.6 Hz, 8.4 Hz), 7.57(2H, d, J=8.5 Hz), 7.52(1H, d, J=8.4 Hz), 7.47(2H, d, J=8.6 Hz), 5.59(1H, brs), 4.48(2H, s)

[1714] Step 3: Production of (4-amino-4′-chloro-biphenyl-2-yl)methanol

[1715] To a suspension of (4′-chloro-4-nitro-biphenyl-2-yl)methanol (1.0 g) obtained in the previous step and sodium hydrosulfite (2.0 g) in N,N-dimethylformamide (4 ml) and methanol (1 ml) was added water (0.3 ml, 50 μl each time in 6 portions) every 20 min at 100° C. Water (5 ml) was added threto at room temperature. Conc. hydrochloric acid (2.5 ml) was added threto at room temperature. The mixture was stirred at 55° C. for 2.5 hr, and a solution of sodium hydroxide (1.2 g) in water (3 ml) was added under ice-cooling. Water (5 ml) was added and the mixture was stirred at room temperature for 1 hr. The precipitate was filtrated and washed with water (3 ml). The crystals were vacuum dried to give the title compound (700 mg, yield 79%).

[1716]

1
H-NMR (400 MHz, DMSO-d6): 7.39(2H, d, J=8.5 Hz), 7.35(2H, d, J=8.5 Hz), 6.90(1H, d, J=8.4 Hz), 6.82(1H, s), 6.56(1H, d, J=8.4 Hz), 5.20(2H, brs), 5.04(1H, t, J=5.4 Hz), 4.29(2H, d, J=5.4 Hz)

[1717] Step 4: Production of 4-chloro-N-(4′-chloro-2-hydroxymethyl-biphenyl-4-yl)butyramide

[1718] To a solution of (4-amino-4′-chloro-biphenyl-2-yl)-methanol (1.0 g) obtained in the previous step in tetrahydrofuran (10 ml) were added sodium acetate (390 mg) and acetic acid (0.27 ml) at room temperature.

[1719] 4-Chlorobutyryl chloride (0.48 ml) was gradually added dropwise under ice-cooling. After stirring the mixture at room temperature for 30 min, water (20 ml) and ethyl acetate (20 ml) were added to the reaction mixture and the organic layer was separated. The organic layer was washed with saturated aqueous sodium hydrogencarbonate (20 ml) and saturated brine (20 ml). The organic layer was dried over sodium sulfate, filtrated and the solvent was evaporated to give the title compound (1.44 g, yield 99%).

[1720]

1
H-NMR (300 MHz, CDCl3): 7.68(1H, s), 7.55(1H, d, J=8.4 Hz), 7.39(2H, d, J=8.5 Hz), 7.28(2H, d, J=8.5 Hz), 7.22(1H, d, J=8.3 Hz), 4.58(2H, s), 3.69(2H, t, J=6.1 Hz), 2.60(2H, t, J=7.0 Hz), 2.22(2H, m)

[1721] Step 5: Production of 1-(4′-chloro-2-hydroxymethyl-biphenyl-4yl)-2-pyrrolidinone

[1722] To a solution of 4-chloro-N-(4′-chloro-2-hydroxymethylbiphenyl-4-yl)butyramide (1.44 g) obtained in the previous step in N,N-dimethylformamide (15 ml) was added potassium carbonate (710 mg) at room temperature. After stirring the mixture at 100° C. for 90 min, 1N hydrochloric acid (5 ml) and water (20 ml) were added at room temperature and the precipitated crystals were collected by filtration and washed with water (5 ml). The crystals were vacuum dried to give the title compound (970 mg, yield 76%).

[1723]

1
H-NMR (300 MHz, CDCl3): 7.76(1H, d, J=2.3 Hz), 7.62(1H, dd, J=2.4 Hz, 8.3 Hz), 7.38(2H, d, J=8.5 Hz), 7.29(2H, d, J=8.5 Hz), 7.25(1H, d, J=8.3 Hz), 4.61(2H, s), 3.91(2H, t, J=7.0 Hz), 2.62(2H, t, J=7.8 Hz), 2.18(2H, m)

[1724] Step 6: Production of 1-(4′-chloro-2-chloromethyl-biphenyl-4-yl)2-pyrrolidinone

[1725] To a mixed solution of 1-(4′-chloro-2-hydroxymethyl-biphenyl-4-yl)-2-pyrrolidinone (900 mg) obtained in the previous step in N,N-dimethylformamide (2 ml) and toluene (7 ml) was dropwise added thionyl chloride (0.26 ml) under ice-cooling. After stirring the mixture at room temperature for 3 hr, the reaction mixture was diluted with ethyl acetate (20 ml) and washed with water (20 ml), saturated aqueous sodium hydrogencarbonate (20 ml) and saturated brine (20 ml). The organic layer was dried over sodium sulfate, filtrated and the solvent was evaporated under reduced pressure to give the title compound (954 mg, yield 99%).

[1726]

1
H-NMR (300 MHz, CDCl3): 7.77(1H, d, J=2.3 Hz), 7.69(1H, dd, J=2.4 Hz, 8.5 Hz),7.42(2H, d, J=8.6 Hz), 7.34(2H, d, J=8.6 Hz), 7.26(1H, d, J=8.4 Hz), 4.50(2H, s), 3.92(2H, t, J=7.0 Hz), 2.65(2H, t, J=7.8 Hz), 2.20(2H, m)

[1727] Step 7: Production of methyl 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}cyclohexylbenzimidazole-5-carboxylate

[1728] To a suspension of methyl 1-cyclohexyl-2-(2-fluoro-4-hydroxyphenyl)benzimidazole-5-carboxylate (915 mg) obtained in Example 18 in N,N-dimethylformamide (6 ml) was added 1-(4′-chloro-2-chloromethyl-biphenyl-4-yl)-2-pyrrolidinone (954 mg) obtained in the previous step and potassium carbonate (415 mg) at room temperature. After stirring the mixture at 100° C. for 1 hr, 1N hydrochloric acid (3 ml) and water (8 ml) were added at room temperature and the precipitated crystals were collected by filtration and washed with water (5 ml). The crystals were vacuum dried to give the title compound (1.6 g, yield 100%).

[1729]

1
H-NMR (300 MHz, CDCl3): 8.49(1H, d, J=1.5 Hz), 7.98(1H, dd, J=1.6 Hz, 8.6 Hz), 7.90(1H, d, J=2.2 Hz), 7.72−7.65(2H, m), 7.49(1H, t, J=8.3 Hz), 7.40(2H, d, J=8.5 Hz), 7.34(1H, d, J=8.7 Hz), 7.31(2H, d, J=8.6 Hz), 6.80 (1H, d, J=8.6 Hz), 6.71(1H, d, J=11.6 Hz), 4.99(2H, s), 4.04(1H, m), 3.95(3H, s), 3.93(2H, t, J=7.1 Hz), 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)

[1730] Step 8: Production of 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid

[1731] Methyl 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5carboxylate (2.0 g) obtained in the previous step was suspended in methanol (4.0 ml) and tetrahydrofuran (8.0 ml), and 2N aqueous sodium hydroxide solution (2.3 ml) was added. The mixture was heated under reflux for 3 hr. The reaction mixture was allowed to cool and tetrahydrofuran (1.0 ml) and water (5.0 ml) were added. 2N Hydrochloric acid (2.3 ml) was gradually added at room temperature. After stirring the mixture at room temperature for 2 hr, the precipitated crystals were collected by filtration and washed successively with methanol-water (1:1) mixed solution (6.0 ml), water (6.0 ml) and methanol-water (1:1) mixed solution (6.0 ml), and vacuum dried to give the title compound (1.84 g, yield 94%).

[1732]

1
H-NMR (300 MHz, DMSO-d6): 12.75(1H, brs), 8.26(1H, s), 7.99(1H, s), 7.96(1H, d, J=9.0 Hz), 7.89(1H, d, J=9.0 Hz), 7.78(1H, dd, J=2.1 Hz, 8.4 Hz), 7.54(1H, t, J=9.0 Hz), 7.49(2H, d, J=8.7 Hz), 7.45(2H, d, J=8.4 Hz), 7.38(1H, d, J=8.4 Hz), 7.08(1H, dd, J=2.1 Hz, 12.0 Hz), 6.96(1H, dd, J=2.1 Hz, 8.7 Hz), 5.09(2H, s), 3.99(1H, m), 3.91(2H, t, J=6.6 Hz), 2.54(2H, t, J=7.8 Hz), 2.30−2.00(4H, m), 1.95−1.50(5H, m), 1.45−1.20(3H, m)

[1733] Step 9: Production of 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidine-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid hydrochloride To 4N hydrochloric acid (50 ml) were successively added 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzoyl}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic acid (10.0 g) obtained in the previous step and acetone-methyl ethyl ketone (3:2) mixed solution (20 ml). The mixture was stirfed at 60° C. for 3 hr and at room temperature for 1 hr. The crystals were collected by filtration, washed twice with acetone (10 ml) and vacuum dried to give the title compound (9.62 g, yield 91%).

[1734] melting point: 243-246° C.

[1735] Ms: 638(M+1)

[1736]

1
H-NMR (300 MHz, DMSO-d6): 8.33(1H, d, J=1.1 Hz), 8.21(1H, d, J=8.8 Hz), 8.02(1H, d, J=8.8 Hz), 8.00(1H, d, J=2.2 Hz), 7.77(1H, dd, J=2.2 Hz, 8.4 Hz), 7.68(1H, t, J=8.4 Hz), 7.50(2H, d, J=8.4 Hz), 7.45(2H, d, J=8.4 Hz), 7.39(1H, d, J=8.4 Hz), 7.20(1H, dd, J=2.2 Hz, 12.1 Hz), 7.06(1H, dd, J=2.2 Hz, 8.8 Hz), 5.11(2H, s), 4.13(1H, m), 3.91(2H, t, J=7.0 Hz), 2.54(2H, t, J=8.1 Hz), 2.40−2.05(4H, m), 2.00−1.75(4H, m), 1.70−1.55(1H, m), 1.50−1.20(3H, m)

[1737] 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, 341-471, 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 269.

EXAMPLE 501

[1738] Production of methyl 2-{4-[2-(4-chlorophenyl)-5methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylate

[1739] Step 1: Production of methyl 3-bromo-4-cyclohexylaminobenzoate

[1740] 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%).

[1741]

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)

[1742] Step 2: Production of 4′-chloro-2-(4-iodophenoxymethyl)-4methoxybiphenyl

[1743] 4-Iodophenol (5.0 g) was dissolved in acetone (50 ml), and potassium carbonate (4.7 g) and 4′-chloro-2-chloromethyl-4methoxybiphenyl (6.0 g) 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%).

[1744]

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)

[1745] Step 3: Production of [4-(4′-chloro-4-methoxybiphenyl-2ylmethoxy)phenylethynyl]trimethylsilane

[1746] 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%).

[1747]

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) Step 4: Production of methyl 3-[4-(4′-chloro-4-methoxybiphenyl-2ylmethoxy)phenylethynyl]-4-cyclohexlaminobenzoate

[1748] [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-cyclohexylaminobenzoate (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%).

[1749]

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)

[1750] Step 5: Production of methyl 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylate

[1751] 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%).

[1752]

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

[1753] Production of 2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylate acid

[1754] 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%).

[1755] APCI-Ms: 566(MH+)

[1756]

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)

[1757] 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

[1758] Production of ethyl 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo-[1,2-a]pyridine-7-carboxylate

[1759] Step 1: Production of 4-benzyloxy-N-methoxy-N-methylbenzamide

[1760] 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%).

[1761]

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)

[1762] Step 2: Production of 1-(4-benzyloxyphenyl)-2-cyclohexylethanone

[1763] 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%).

[1764]

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(10H, m)

[1765] Step 3: Production of 1-(4-benzyloxyphenyl)-2-bromo-2cyclohexylethanone

[1766] 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%).

[1767]

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(11H, m)

[1768] Step 4: Production of ethyl 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylate

[1769] Ethyl 2-aminopyridine-4-carboxylate (214 mg) prepared according to JP-A-8-48651, 1-(4-benzyloxyphenyl)-2-bromo-2cyclohexylethanone (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%).

[1770] APCI-MS: 455(MH+)

[1771]

1
H-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

[1772] Production of 2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylic acid

[1773] 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%).

[1774] APCI-MS: 427(MH+)

[1775]

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(10H, m)

[1776] The compounds shown in Tables 213 to 218 can be further obtained in the same manner as in Examples 1 to 703 or by other conventional method employed as necessary.

[1777] 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]

[1778] i) Preparation of Enzyme (HCV Polymerase)

[1779] 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 Mar, 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.

[1780] ii) Synthesis of Substrate RNA

[1781] 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.

[1782] 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.

[1783] This RNA was applied to formaldehyde denaturation agarose gel electrophoresis to confirm the quality thereof and preserved at −80° C.

[1784] iii) Assay of Enzyme (HCV Polymerase) Inhibitory Activity

[1785] 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.

[1786] 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.

[1787] 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.

[1788] The results are shown in Tables 178-184 and 222-224.

[1789] 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%)

[1790] Formulation Example is given in the following. This example is merely for the purpose of exemplification and does not limit the invention.

[1791] Formulation Example

1(a) compound of Example 110 g(b) lactose50 g(c) corn starch15 g(d) sodium carboxymethylcellulose44 g(e) magnesium stearate 1 g

[1792] 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).

2TABLE 1Example No.311H NMR(δ) ppm

300MHz, CDCl3 7.81(2H, d, J=6.6Hz), 7.60(2H, d, J=8.8Hz), 7.51-7.21(8H, m), 7.11(2H, d, J=8.8Hz), 5.15(2H, s), 4.93(1H, quint, J=8.8Hz), 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) ppm

300MHz, CDCl3 8.51(1H, d, J=1.5Hz), 7.98(1H, d, J=8.4Hz), 7.61(2H, d, J=8.7Hz), 7.56-7.10(6H, m), 7.12(2H, d, J=8.7Hz), 5.15(2H, s), 4.94(1H, quint, J=9.3Hz), 4.41(2H, q, J=7.5Hz), 2.40-1.50(8H, m), 1.41(3H, t, J=7.5Hz)Purity>90% (NMR)MS441(M + 1)Example No.331H NMR(δ) ppm

300MHz, CDCl3 7.84(1H, s), 7.61(2H, d, J=9.0Hz), 7.58-7.30(7H, m), 7.12(2H, d, J=9.0Hz), 5.15(2H, s), 4.94(1H, quint, J=8.7Hz), 3.10(6H, brs), 2.40-1.50(8H, m)Purity>90% (NMR)MS440(M + 1)

[1793]

3

TABLE 2

Example No.
34
1H NMR(δ) ppm

300MHz, CDCl3 8.20(1H, s), 7.50-7.31(9H, m), 7.12(2H, d, J=8.7Hz), 5.15(2H, s), 4.94(1H, quint, J=8.7Hz), 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

300MHz, CDCl3 7.91(1H. s), 7.59(2H, d, J=8.7Hz), 7.49-7.30(7H, m), 7.11(2H, d, J=8.8Hz), 5.15(2H, s), 4.19(1H, quint, J=8.8Hz), 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

300MHz, CDCl3 8.40(1H, d, J=1.4Hz), 7.95(1H, dd, J=8.6, 1.4Hz), 7.61(2H, d, J=8.7Hz), 7.57-7.30(6H, m), 7.13(2H, d, J=8.7Hz), 5.16(2H, s), 4.95(1H, quint, J=8.8Hz), 2.64(3H, s), 2.40-1.54(8H, m)

Purity
>90% (NMR)

MS
411(M + 1)

[1794]

4

TABLE 3

Example No.
37
1H NMR(δ) ppm

300MHz, DMSO-d6 10.47(1H, brs,), 9.15(1H, brs), 8.40(1H, s), 8.07(1H, d, J=9.0Hz), 7.93(1H, d, J=8.7Hz), 7.77(2H, d, J=8.7Hz), 7.55-7.29(7H, m), 5.26(2H, s), 4.93(1H, quint, J=9.0Hz), 3.77-3.63(2H, m), 3.39-3.23(2H, m), 2.84(6H, d, J=4.8Hz), 2.32-1.60(8H, m)

Purity
>90% (NMR)

MS
483(M + 1)

Example No.
38
1H NMR(δ) ppm

300MHz, CDCl3 8.69(1H, s), 8.19(1H, d, J=9.0Hz), 7.62(2H, d, J=8.7Hz), 7.54(1H, d, J=9.0Hz), 7.48-7.36(5H, m), 7.15(2H, d, J=8.7Hz), 5.17(2H, s), 4.98(1H, quint, J=9.0Hz), 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

300MHz, DMSO-d6 7.84(1H, d, J=9.0Hz), 7.79(2H, d, J=8.7Hz), 7.52-7.33(8H, m), 7.26(1H, d, J=9.0Hz), 5.27(2H, s), 4.92(1H, quint, J=9.3Hz), 2.19-1.70(8H, m).

Purity
>90% (NMR)

MS
384(M + 1)

[1795]

5

TABLE 4

Example No.
40
1H NMR(δ) ppm

300MHz, CDCl3 7.72(1H, s), 7.60-7.35(10H, m), 7.10(2H, d, J=8.7Hz), 5.14(2H, s), 4.90(1H, quint, J=8.8Hz), 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

300MHz, CDCl3 7.66(1H, s), 7.61(2H, d, J=8.8Hz), 7.50-7.28(7H, m), 7.12(2H, d, J=8.8Hz), 6.86(1H, brs), 5.15(2H, s), 4.94(1H, quint, J=8.8Hz), 2.97(3H, s), 2.29-1.76(8H, m).

Purity
>90% (NMR)

MS
462(M + 1)

Example No.
42
1H NMR(δ) ppm

300MHz, DMSO-d6 8.11(1H, s), 7.81(1H, d, J=8.4Hz), 7.72(1H, d, J=8.4Hz), 7.65(2H, d, J=8.4Hz), 7.51(2H, m), 7.43(2H, m), 7.37(1H, m), 7.29(2H, s), 7.23(2H, d, J=8.4Hz), 5.22(2H, s), 4.89(1H, quintet, J=9.2Hz), 2.2-2.0(6H, m), 1.7(2H, m).

Purity
>90% (NMR)

MS
448(M+)

[1796]

6

TABLE 5

Example No.
43
1H NMR(δ) ppm

300MHz, DMSO-d6 8.33(1H, 5), 8.08(1H, d, J=9.0Hz), 7.99(1H, d, J=9.0Hz), 7.47-7.41(4H, m), 7.33(2H, d, J=8.4Hz), 5.22(2H, s), 4.96(1H, quint, J=9.0Hz), 2.25-1.60(8H, m), 1.30(9H, s).

Purity
>90% (NMR)

MS
469(M + 1)

Example No.
44
1H NMR(δ) ppm

300MHz, DMSO-d6 12.9(2H, brs), 8.25(1H, s), 8.00(2H, d, J=7.8Hz), 7.90(1H, d, J=8.4Hz), 7.74(1H, d, J=8.7Hz), 7.67(2H, d, J=9.0Hz), 7.62(2H, d, J=8.1Hz), 7.24(2H, d, J=8.4Hz), 5.32(2H, s), 4.88(1H, quint, J=9.0Hz, 2.25-1.60(8H, m).

Purity
>90% (NMR)

MS
457(M + 1)

Example No.
45
1H NMR(δ) ppm

300MHz, DMSO-d6 13.4(1H, brs), 8.32(1H, s), 8.06(1H, d, J=8.7Hz), 7.97(1H, d, J=8.7Hz), 7.79(2H, d, J=8.8Hz), 7.56-7.48(4H, m), 7.33(2H, d, J=8.8Hz), 5.27(2H, s), 4.95(1H, quint, J=8.9Hz), 2.30-1.60(8H, m).

Purity
>90% (NMR)

MS
447(M + 1)

[1797]

7

TABLE 6

Example No.
46
1H NMR(δ) ppm

300MHz, DMSO-d6 8.33(1H, s), 8.07(1H, d, J=8.7Hz), 7.98(1H, d, J=8.7Hz), 7.80(2H, d, J=8.4Hz), 7.34(2H, d, 8.4Hz), 7.19(1H, d, J=3.6Hz), 7.09(1H, d, J=3.6Hz), 5.41(2H, s), 4.95(1H, quint, J=8.7Hz), 2.30-1.60(8H, m).

Purity
>90% (NMR)

MS
453(M + 1)

Example No.
47
1H NMR(δ) ppm

300MHz, DMSO-d6 8.33(1H, s), 8.07(1H, d, J=8.4Hz), 7.98(1H, d, J=9.0Hz), 7.82-7.72(6H, m), 7.35(2H, d, J=9.0Hz), 5.40(2H, s), 4.95(1H, quint, J=8.7Hz), 2.35-1.60(8H, m).

Purity
>90% (NMR)

MS
481(M + 1)

Example No.
48
1H NMR(δ) ppm

300MHz, DMSO-d6 8.23(1H, s), 7.88(1H, d, J=8.4Hz), 7.70(1H, d, J=8.4Hz), 7.64(2H, d, J=8.4Hz), 7.43(2H, d, J=8.4Hz), 7.20(2H, d, J=8.4Hz), 6.98(2H, d, J=8.4Hz), 5.13(2H, s), 4.88(1H, quint, J=8.7Hz), 3.77(3H, s), 2.35-1.60(8H, m).

Purity
>90% (NMR)

MS
443(M + 1)

[1798]

8

TABLE 7

Example No.
49
1H NMR(δ) ppm

300MHz, DMSO-d6 8.93(2H, d, J=6.6Hz), 8.35(1H, s), 8.06-8.04(3H, m), 7.97(1H, d, J=8.7Hz), 7.83(2H, d, J=8.7Hz), 7.38(2H, d, J=8.7Hz), 5.61(2H, s), 4.94(1H, quint, J=8.7Hz), 2.40-1.60(8H, m).

Purity
>90% (NMR)

MS
414(M + 1)

Example No.
50
1H NMR(δ) ppm

300MHz, DMSO-d6 8.33(1H, s), 8.08(1H, d, J=8.7Hz), 7.99(1H, d, J=9.0Hz), 7.78(2H, d, J=8.4Hz), 7.39(2H, d, J=8.1Hz), 7.32(2H, d, J=8.7Hz), 7.23(2H, d, J=7.8Hz), 5.22(2H, s), 4.96(1H, quint, J=9.0Hz), 2.32(3H, s), 2.30-1.60(8H, m).

Purity
>90% (NMR)

MS
427(M + 1)

Example No.
51
1H NMR(δ) ppm

300MHz, DMSO-d6 8.31(1H, s), 8.03(1H, d, J=9.0Hz), 7.93(1H, d, J=9.0Hz), 7.77(2H, d, J=8.4Hz), 7.31(2H, d, J=8.7Hz), 5.07(2H, s), 4.94(1H, quint, J=8.7Hz), 2.45(3H, s), 2.26(3H, s), 2.26-1.60(8H, m).

Purity
>90% (NMR)

MS
432(M + 1)

[1799]

9

TABLE 8

Example No.
52
1H NMR(δ) ppm

300MHz, DMSO-d6 12.7(1H, brs), 10.0(1H, s), 8.22(1H, s), 7.87(1H, d, J=8.6Hz), 7.69(1H, d, J=8.6Hz), 7.53(2H, d, J=8.6Hz), 6.96(2H, d, J=8.6Hz), 4.89(1H, qiunt, J=9.0Hz), 2.30-1.60(8H, m).

Purity
>90% (NMR)

MS
323(M + 1)

Example No.
53
1H NMR(δ) ppm

300MHz, DMSO-d6 9.18(1H, t, J=5.6Hz), 8.34(1H, s), 8.04(1H, d, J=9.6Hz), 7.98(1H, d, J=8.7Hz), 7.80(2H, d, J=8.7Hz), 7.52-7.32(7H, m), 5.27(2H, s), 4.95(1H, quint, J=9.0Hz), 3.99(2H, d, J=5.7Hz), 2.40-1.60(8H, m).

Purity
>90% (NMR)

MS
470(M + 1)

Example No.
54
1H NMR(δ) ppm

300MHz, DMSO-d6 8.32(1H, s), 8.05(1H, d, J=8.7Hz), 7.95(1H, d, J=8.7Hz), 7.80(2H, d, J=8.4Hz), 7.67(1H, t, J=4.5Hz), 7.56(1H, t, J=4.5Hz), 7.45-7.42(2H, m), 7.35(2H, d, J=8.4Hz), 5.31(2H, s), 4.96(1H, quint, J=9.0Hz), 2.30-1.60(8H, m).

Purity
>90% (NMR)

MS
447(M + 1)

[1800]

10

TABLE 9

Example No.
55
1H NMR(δ) ppm

300MHz, DMSO-d6 12.78(1H, brs), 8.24(1H, s), 7.88 and 7.72(2H, ABq, J=8.6Hz), 7.66 and 7.23(4H, A′B′q, J=8.6Hz), 7.58(1H, s), 7.48-7.42(3H, m), 5.24(1H, s), 4.88(1H, quint, J=8.8Hz), 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

100

300MHz, DMSO-d6 12.89(1H, broad), 8.18(1H, s), 7.87(1H, d, J=8.4Hz), 7.74(1H, d, J=9.2Hz), 7.67(2H, d, J=8.8Hz), 7.52(2H, m), 7.45(2H, m), 7.38(1H, m), 7.23(2H, d, J=8.8Hz), 5.22(2H, s), 4.94(1H, quintet, J=8.9Hz), 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

101

300MHz, 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=8.7Hz), 4.86(1H, quint, J=8.7Hz), 2.12-1.90(6H, m), 1.72-1.59(2H, m)

Purity
>90% (NMR)

MS
462(M + 1)

[1801]

11

TABLE 10

Example No.
58
1H NMR(δ) ppm

102

300MHz, DMSO-d6 12.78(1H, s), 10.69(1H, s), 8.26-7.72(9H, m), 4.92(1H, quint, J=9.0Hz), 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

103

300MHz, DMSO-d6 10.82(1H, s), 8.34(1H, s), 8.14 and 7.84(4H, ABq, J=8.4Hz), 8.06 and 7.66(4H, A′B′q, J=8.6Hz), 8.06-7.98(4H, m), 5.01(1H, quint, J=9.3Hz), 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

104

300MHz, DMSO-d6 10.61(1H, s), 8.32(1H, s), 8.12 and 7.81(4H, ABq, J=8.9Hz), 8.03 and 7.93(2H, A′B′q, J=8.7Hz), 7.95 and 7.59(4H, A″B″q, J=8.4Hz), 4.99(1H, quint, J=9.0Hz), 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)

[1802]

12

TABLE 11

Example No.
61
1H NMR (δ) ppm

105

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

106

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

107

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), 12.60-1.95 (6H, m), 1.25-1.05 (2H, m)

Purity
about 90% (NMR)

MS
457 (M + 1)

[1803]

13

TABLE 12

Example No.
64
1H NMR (δ) ppm

108

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

109

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

110

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)

[1804]

14

TABLE 13

Example No.
67
1H NMR (δ) ppm

111

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

112

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

113

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)

[1805]

15

TABLE 14

Example No.
70
1H NMR (δ) ppm

114

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

115

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

116

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)

[1806]

16

TABLE 15

Example No.
73
1H NMR (δ) ppm

117

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 (1H, 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

118

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

119

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
476 (M + 1)

[1807]

17

TABLE 16

Example No.
76
1H NMR (δ) ppm

120

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

121

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

122

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)

[1808]

18

TABLE 17

Example No.
79
1H NMR (δ) ppm

123

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

124

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

125

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)

[1809]

19

TABLE 18

Example No.
82
1H NMR (δ) ppm

126

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

127

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

128

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)

[1810]

20

TABLE 19

Example No.
85
1H NMR (δ) ppm

129

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

130

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

131

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)

[1811]

21

TABLE 20

Example No.
88
111 NMR(6) ppm

132

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

133

Purity
91% (HPLC)

MS
427 (M + 1)

Example No.
90
1H NMR (δ) ppm

134

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)

[1812]

22

TABLE 21

Example No.
91
1H NMR (δ) ppm

135

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

136

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

137

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)

[1813]

23

TABLE 22

Example No.
94
1H NMR (δ) ppm

138

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

139

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

140

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)

[1814]

24

TABLE 23

Example No.
97
1H NMR (δ) ppm

141

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

142

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

143

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)

[1815]

25

TABLE 24

Example No.
100
1H NMR (δ) ppm

144

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

145

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

146

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)

[1816]

26

TABLE 25

Example No.
103
1H NMR (δ) ppm

147

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

148

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

149

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)

[1817]

27

TABLE 26

Example No.
106
1H NMR (δ) ppm

150

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

151

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

152

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)

[1818]

28

TABLE 27

Example No.
109
1H NMR (δ) ppm

153

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

154

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

155

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)

[1819]

29

TABLE 28

Example No.
112
1H NMR (δ) ppm

156

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

157

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

158

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)

[1820]

30

TABLE 29

Example No.
115
1H NMR (δ) ppm

159

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

160

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

161

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)

[1821]

31

TABLE 30

Example No.
118
1H NMR (δ) ppm

162

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

163

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

164

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)

[1822]

32

TABLE 31

Example No.
121
1H NMR(δ) ppm

165

300MHz, DMSO-d6 12.85(1H, brs), 8.24(1H, s), 8.01 (1H, d, J=8.7Hz), 7.90(1H, d, J=8.6Hz), 7.62 and, 7.17(4H, ABq, J=8.7Hz), 7.24(1H, m), 6.94(2H, m), 6.82(1H, m), 4.32(2H, t, J=6.7Hz), 3.76(3H, s), 3.07(2H, t, J=6.7Hz), 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

166

300MHz, DMSO-d6 12.8(1H, brs), 8.22(1H, s), 7.87(2H, m), 7.62(2H, d, J=8.1Hz), 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

167

300MHz, DMSO-d6 8.24(1H, s), 7.97(1H, d, J=9.0Hz), 7.87(1H, d, J=8.4Hz), 7.65(2H, d, J=8.7Hz), 7.40-7.05(9H, m), 7.03(2H, d, J=8.4Hz), 4.31(1H, m), 4.18(2H, t, J=6.6Hz), 2.81(2H, t, J=6.3Hz), 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)

[1823]

33

TABLE 32

Example No.
124
1H NMR(δ) ppm

168

300MHz, DMSO-d6 13.1(1H, brs), 8.29(1H, s), 8.17(1H, d, J=8.7Hz), 7.99(1H, d, J=8.7Hz), 7.77(2H, d, J=8.7Hz), 7.40-7.20(8H, m), 6.84(1H, d, J=9.3Hz), 6.75-6.72(2H, m), 4.36(1H, m), 4.22(2H, t, J=6.8Hz), 3.04(2H, t, J=6.7Hz), 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

169

300MHz, DMSO-d6 8.32(1H, s), 8.28(1H, d, J=8.7Hz), 8.05(1H, d, J=9.0Hz), 7.73(2H,

# d, J=9.0Hz), 7.43(4H, d, J=7.2Hz), 7.36-7.20(8H, m), 4.74(2H, d, J=7.5Hz), 4.57(1H, t, J=7.5Hz), 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

170

300MHz, DMSO-d6 8.32(1H, s), 8.14(1H, d, J=8.7Hz), 8.03(1H, d, J=8.7Hz), 7.77(2H, d, J=9.0Hz), 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).

Purity
>90% (NMR)

MS
425(M + 1)

[1824]

34

TABLE 33

Example No.
127
1H NMR(δ) ppm

171

300Mhz, DMSO-d6 13.2(1H, brs), 8.33(1H, s), 8.12(1H, d, J=8.7Hz), 7.96(1H, d, J=8.8Hz), 7.79(2H, d, J=8.7Hz), 7.52-7.32(7H, m), 5.26(2H, s), 4.92(1H, d, J=49.4Hz), 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

172

300Mhz, DMSO-d6 8.21(1H, s), 7.92 and 7.85(2H, ABq, J=8.6Hz), 7.61 and 7.06(4H, A′B′q, J=8.6Hz), 7.36-6.91(9H, m), 4.24(1H, brt, J=12.2Hz), 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

173

300MHz, DMSO-d6 8.21(1H, s), 7.92 and 7.86(2H, ABq, J=8.6Hz), 7.69 and 7.22(4H, A′B′q, J=8.6Hz), 7.52-7.39(1H, m), 7.47 and 7.41(2H, A″B″q, J=8.1Hz), 6.91(1H, d, J=8.0Hz), 6.89(1H, d, J=8.2Hz), 6.75(1H, s), 4.36-4.18(1H, 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)

[1825]

35

TABLE 34

Example No.
130
1H NMR(δ) ppm

174

300MHz, DMSO-d6 8.27(1H, s), 7.69(2H, d, J=8.6Hz), 7.49-7.21(11H, m), 5.08 and 5.03(2H, ABq, J=12.6Hz), 5.07-4.99(1H, m), 4.26(2H, d, J=6.6Hz), 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

175

300MHz, DMSO-d6 8.29(1H, s), 8.11(1H, d, J=9.0Hz), 7.96(1H, d, J=8.4Hz), 7.80(2H, d, J=8.1Hz), 7.72-7.41(7H, m), 7.12(1H, d, J=12.6Hz), 7.01(1H, d, J=8.4Hz), 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

176

300MHz, DMSO-d6 12.8(1H, brs), 8.23(1H, s), 7.97(1H, d, J=8.7Hz), 7.87(1H, d, J=8.6Hz), 7.66(2H, d, J=8.6Hz), 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)

[1826]

36

TABLE 35

Example No.
133
1H NMR(δ) ppm

177

300MHz, DMSO-d6 8.57(1H, s), 8.01(1H, d, J=8.7Hz), 7.66(1H, d, J=8.7Hz), 7.51(2H, d, J=8.7Hz), 7.31(4H, d,

# J=8.0Hz), 7.16(4H, d, J=8.0Hz), 7.09(2H, d, J=8.7Hz), 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

178

8.59(1H, d, J=1.5Hz), 8.02(1H, dd, J=8.7, 1.5Hz), 7.68(1H, d, J=8.7Hz), 7.54(2H, d, J=8.8Hz), 7.39(4H,

# dd, J=8.7, 5.3Hz), 7.08(4H, d, J=8.7Hz), 7.05(2H, d, J=8.8Hz), 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

179

300MHz, DMSO-d6 12.34(1H, brs), 7.93(1H, s), 7.55(1H, d, J=8.6Hz), 7.33-7.15(6H, m), 7.11(2H, d, J=8.6Hz), 4.30-4.20(1H, m), 4.07(2H, t, J=6.3Hz), 3.93(3H, s), 2.78(2H, t, J=7.4Hz), 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)

[1827]

37

TABLE 36

Example No.
136
1H NMR(δ) ppm

180

300MHz, DMSO-d6 8.13(1H, s), 7.65(2H, d, J=8.7Hz), 7.63(1H, s), 7.35-7.12(7H, m), 4.35-4.20(1H, m), 4.10(1H, t, J=6.3Hz), 2.78(2H, t, J=7.5Hz), 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

181

300MHz, DMSO-d6 8.24(1H, s), 8.11(1H, s), 7.76(2H, d, J=9.0Hz), 7.37-7.16(7H, m), 4.43-4.30(1H, m), 4.13(2H, t, J=6.3Hz), 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

182

300MHz, DMSO-d6 12.73(1H, brs), 8.22(1H, s), 7.76(1H, d, J=8.7Hz), 7.85(1H, d, J=8.7Hz), 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)

[1828]

38

TABLE 37

Example No.
139
1H NMR(δ) ppm

183

300MHz, DMSO-d6 12.73(1H, brs), 8.22(1H, s), 7.93(1H, d, J=8.7Hz), 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=6.7Hz), 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

184

300MHz, DMSO-d6 12.83(2H, brs), 8.22(1H, s), 7.94(1H, d, J=8.7Hz), 7.85(1H, d, J=8.4Hz), 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

185

300MHz, DMSO-d6 12.87(1H, brs), 8.24(1H, s), 7.97(1H, d, J=9.0Hz), 7.87(1H, d, J=8.7Hz), 7.69 and 7.19(4H, ABq, J=8.7Hz), 7.36(1H, t, J=8.7Hz), 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)

[1829]

39

TABLE 38

Example No.
142
1H NMR(δ) ppm

186

300MHz, DMSO-d6 8.32(1H, s), 8.27(1H, d, J=8.7Hz), 8.05(1H, d, J=9.0Hz), 7.76-7.72(3H, m), 7.54(1H, d, J=8.4Hz), 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

187

300MHz, DMSO-d6 13.1(1H, brs), 8.30(1H, s), 8.24(1H, d, J=8.8Hz), 8.03(1H, d, J=8.7Hz), 7.74-7.71(3H, m), 7.52(1H, d, J=8.3Hz), 7.40-7.36(3H, m), 7.23(2H, d, J=8.8Hz), 7.01(2H, d, J=8.7Hz), 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

188

300MHz, DMSO-d6 13.0(1H, brs), 8.31(1H, s), 8.23(1H, d, J=8.7Hz), 8.04(1H, d, J=8.7Hz),

# 7.80(2H, d, J=8.3Hz), 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(1H, m), 1.50-1.10(3H, m).

Purity
>90% (NMR)

MS
585(M + 1)

[1830]

40

TABLE 39

Example No.
145
1H NMR(δ) ppm

189

300MHz, DMSO-d6 8.31(1H, s), 8.23(1H, d, J=8.8Hz), 8.02(1H, d, J=8.7Hz), 7.73-7.71(3H,

# m), 7.54(1H, d, J=8.3Hz), 7.48(2H, d, J=8.4Hz), 7.41-7.37(3H, m), 7.22(2H, d, J=8.7Hz), 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

190

300MHz, DMSO-d6 8.29(1H, s), 8.13(1H, d, J=8.7Hz), 7.97(1H, d, J=8.6Hz), 7.76(1H, d, J=2.1Hz), 7.63(1H, t, J=8.5Hz), 7.57(1H, dd, J=8.2, 2.2Hz), 7.55-7.35(6H, m), 7.15(1H, d, J=12.1Hz), 7.02(1H, d, J=8.6Hz), 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

191

300MHz, CDCl3 8.61(1H, s), 8.04(1H, d, J=8.7Hz), 7.69(1H, d, J=8.7Hz), 7.66(1H, d, J=2.4Hz), 7.59(2H, d, J=8.7Hz), 7.42(1H, dd, J=8.0, 2.4Hz), 7.38(1H, t, J=1.8Hz), 7.28(2H, d, J=1.8Hz), 7.26(1H, d, J=8.0Hz), 7.03(2H, d, J=8.7Hz), 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)

[1831]

41

TABLE 40

Example No.
148
1H NMR(δ) ppm

192

300MHz, DMSO-d6 8.21(s, 1H), 7.89(1H, d, J=8.7Hz), 7.87(1H, d, J=8.7Hz), 7.63-7.46(5H, m), 7.30-7.12(5H, m), 7.08(1H, d, J=11.0Hz), 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

193

300MHz, DMSO-d6 8.24(1H, d, J=1.5Hz), 7.96(1H, d, J=9.0Hz), 7.88(1H, dd, J=9.0, 1.5Hz), 7.58(1H, d, J=8.7Hz), 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

194

300MHz, DMSO-d6 8.23(1H, s), 8.95(1H, d, J=8.4Hz), 7.88(1H, d, J=8.7Hz), 7.66(1H, d, J=8.4Hz), 7.52-7.28(7H, m), 7.23(2H, d, J=9.3Hz), 7.14(2H, d, J=8.7Hz), 5.14(2H, s), 3.90-3.72(1H, m), 2.20-1.10(10H, m)

Purity
>90% (NMR)

MS
587(M + 1)

[1832]

42

TABLE 41

Example No.
151
1H NMR (δ) ppm

195

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

196

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

197

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)

[1833]

43

TABLE 42

Example No.
154
1H NMR (δ) ppm

198

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

199

300 MHz, DMSO-d6 8.21 (1H, s), 7.85 and 7.61 (2H, ABq, J=8.7 Hz), 7.61 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

200

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, 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)

[1834]

44

TABLE 43

Example No.
157
1H NMR (δ) ppm

201

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

202

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

203

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)

[1835]

45

TABLE 44

Example No.
160
1H NMR (δ) ppm

204

300 MHz, DMSO-d6 8.90 (1H, brs), 8.59 (lh, 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 (δ5) ppm

205

300 MHz, DMSO-d6 9.05 (1H, brs), 8.76 (lh, 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

206

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)

[1836]

46

TABLE 45

Example No.
163
1H NMR (δ) ppm

207

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=3.7 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

208

300 MHz, DMSO-d6 8.20 (1H, s), 7.87 (2H, s), 7.68 and 7.18 (4H, ABq, J=8.7 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

209

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 (1H, m), 3.42-3.10 (2H, m), 2.45-1.23 (14H, m)

Purity
>90% (NMR)

MS

[1837]

47

TABLE 46

Example No.
166
1H NMR (δ) ppm

210

300 MHz, DMSO-d6 8.27 (1H, s), 8.13 (1H, d, J=8.4 Hz), 7.97 (1H, d, J=9.0 Hz), 7.73 (1H, d, J=1.8 Hz), 7.68 (2H, d, J=8.4 Hz), 7.54 (1H, dd, J=8.4, 2.1 Hz), 7.41-7.31 (5H, m), 7.19 (2H, d, J=8.4 Hz), 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

211

300 MHz, DMSO-d6 8.25 (1H, s), 8.09 (1H, d, J=8.4 Hz), 8.00 (2H, d, J=8.4 Hz), 7.94 (1H, d, J=8.7 Hz), 7.80 (1H, d, J=2.1 Hz), 7.73 (2H, d, J=8.1 Hz), 7.65 (2H, d, J=8.7 Hz), 7.60 (1H, dd, J=8.1, 2.1 Hz), 7.44 (1H, d, J=8.1 Hz), 7.16 (2H, d, J=8.7 Hz), 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

212

300 MHz, DMSO-d6 13.1 (1H, brs), 8.32 (1H, s), 8.28 (1H, d, J=8.8 Hz), 8.05 (1H, d, J=8.7 Hz), 7.80-7.75 (3H, m), 7.69 (1H, d, J=4.1 Hz), 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)

[1838]

48

TABLE 47

Example No.
169
1H NMR (δ) ppm

213

300 MHz, DMSO-d6 8.31 (1H, s), 8.26 (1H, d, J=8.7 Hz), 8.05 (1H, d, J=8.7 Hz), 7.78-7.71 (3H, m), 7.59-7.41 (6H, m), 7.23 (2H, d, J=9.0 Hz), 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

214

300 MHz, 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=8.7 Hz), 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

215

300 MHz, DMS0-d6 8.31 (1H, s), 8.25 (1H, d, J=8.7 Hz), 8.04 (1H, d, J=8.7 Hz), 7.74-7.71 (3H, m), 7.57-7.46 (3H, m), 7.39 (1H, d, J=8.1 Hz), 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)

[1839]

49

TABLE 48

Example No.
172
1H NMR (δ) ppm

216

300 MHz, DMSO-d6 8.24 (1H, s), 7.99 (1H, d, J=8.7 Hz), 7.88 (1H, d, J=10.5 Hz), 7.70 (1H, dd, J=11.4, 1.8 Hz), 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

217

300 MHz, DMSO-d6 8.33 (1H, s), 8.29 (1H, d, J=8.7 Hz), 8.06 (1H, d, J=8.7 Hz), 7.82-7.74 (4H, m), 7.45 (1H, dd, J=8.4, 3.0 Hz), 7.39 (2H, d, J=8.7 Hz), 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

218

300 MHz, DMSO-d6 12.80 (1H, brs), 8.26 (1H, s), 8.01 (1H, d, J=8.7 Hz), 7.85 (1H, d, J=8.7 Hz), 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)

[1840]

50

TABLE 49

Example No.
175
1H NMR (δ) ppm

219

300 MHz, DMSO-d6 12.75 (1H, s), 8.21 (1H, s), 7.94 and 7.85 (2H, ABq, J=8.7 Hz), 7.61 and 7.00 (4H, A′ B′ q, J=8.5 Hz), 7.31-6.91 (2H, m), 7.25 (2H, d, J=7.7 Hz), 5.41 (2H, brs), 4.54 (2H, d, J=6.6 Hz), 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

220

300 MHz, DMSO-d6 8.24 (1H, s), 7.97 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=8.1 Hz), 6.81 (1H, d, J=9.2 Hz), 6.72 (1H, s), 6.71 (1H, d, J=6.5 Hz), 4.48-4.20 (2H, m), 3.95-3.75 (3H, m), 3.03 (1H, t, J=12.3 Hz), 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

221

300 MHz, DMSO-d6 12.76 (1H, s), 8.23 (1H, s), 7.96 and 7.86 (2H, ABq, J=8.6 Hz), 7.69 and 7.20 (4H, A′ B′ q, J=8.6 Hz), 7.39 (1H, t, J=8.2 Hz), 6.86 (1H, d, J=8.3 Hz), 6.81 (1H, s), 6.76 (1h, d, J=8.0 Hz), 4.83 (2H, s), 4.31 (1H, brt, J=12.2 Hz), 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)

[1841]

51

TABLE 50

Example No.
178
1H NMR (δ) ppm

222

300 MHz, DMSO-d6 12.85 (1H, s), 8.75 (1H, s), 8.63 (2H, d, J=3.8 Hz), 8.25 (1H, s), 8.04-8.01 (2H, m), 8.02 and 7.90 (2H, ABq, J=8.6 Hz), 7.72 and 7.20 (4H, A′ B′ q, J=8.6 Hz), 7.57 (2H, dd, J=7.8, 5.0 Hz), 7.40 (1H, t, J=8.2 Hz), 6.93 (1H, d, J=8.2 Hz), 6.87 (1H, s), 6.77 (1H, d, J=8.2 Hz), 5.23 (2H, s), 4.33 (1H, brt, J=12.2 Hz), 2.40-2.18 (2H, m), 2.00-1.55

# (5H, m), 150-1.15 (3H, m)

Purity
>90% (NMR)

MS
520 (M + 1)

Example No.
179
1H NMR (δ) ppm

223

300 MHz, DMSO-d6 8.32 (1H, s), 8.29 (1H, d, J=9.0 Hz), 8.06 (1H, d, J=8.7 Hz), 7.61 (1H, d, J=8.4 Hz), 7.58-7.32 (5H, m), 6.98 (1H, d, J=2.1 Hz), 6.93 (1H, dd, J=8.7, 2.1 Hz), 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

224

300 MHz, DMSO-d6 8.21 (1H, s), 7.91 (1H, d, J=8.6 Hz), 7.85 (1H, d, J=8.6 Hz), 7.63 (2H, d, J=8.4 Hz), 7.60 (1H, d, J=9.0 Hz), 7.25 (2H, d, J=8.4 Hz), 7.23 (1H, d, J=3.0 Hz), 6.95 (1H, dd, J=9.0, 3.0 Hz), 5.19 (2H, s), 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)

[1842]

52

TABLE 51

Example No.
181
1H NMR (δ) ppm

225

300 MHz, DMSO-d6 8.19 (1H, s), 7.95 (1H, d, J=8.7 Hz), 7.86 (1H, d, J=8.7 Hz), 7.65 (4H, d, J=7.4 Hz), 7.47 (2H, d, J=8.7 Hz), 7.44-7.27 (6H, m), 6.99 (2H, d, J=8.7 Hz), 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

226

300 MHz, DMSO-d6 8.55 (1H, d, J=2.1 Hz), 8.32 (1H, m), 8.21 (1H, s), 7.95 (1H, d, J=8.4 Hz), 7.86 (1H, d, J=7.8 Hz), 7.68-7.56 (7H, m), 7.14 (2H, d, J=8.7 Hz), 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

227

300 MHz, DMSO-d6 10.16 (1H, s), 8.25 (1H, s), 8.07 (1H, d, J=8.7 Hz), 7.94-7.87 (2H, m), 7.71-7.62 (3H, m), 7.50-7.42 (4H, m), 7.30 (1H, d, J=8.4 Hz), 7.14 (2H, d, J=8.4 Hz), 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+)

[1843]

53

TABLE 52

Example No.
184
1H NMR (δ) ppm

228

300 MHz, DMSO-d6 13.2 (2H, brs), 8.30 (1H, s), 8.26 (1H, d, J=8.8 Hz), 8.04 (1H, d, J=8.8 Hz), 8.00 (2H, d, J=8.2 Hz), 7.79 (1H, s), 7.73 (2H, d, J=8.7 Hz), 7.61-7.56 (3H, m), 7.44 (1H, d, J=8.3 Hz), 7.23 (2H, d, J=8.8 Hz), 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

229

300 MHz, DMSO-d6 8.30 (1H, m), 8.24 (1H, d, J=9.0 Hz), 8.03 (1H, d, J=9.0 Hz), 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

230

(DMSO-d6) δ: 8.29 (1H, brs), 8.10 (1H, d, J=8.4 Hz), 7.97 (1H, d, J=8.4 Hz), 7.79 (2H, d, J=8.4 Hz), 7.74-7.67 (1H, m), 7.68 (2H, d, J=8.4 Hz), 7.61 (1H, d, J=8.4 Hz), 7.57-7.50 (2H, m), 7.46-7.39 (1H, m), 7.29 (1H, d, J=2.4 Hz), 7.11 (1H, dd, J=2.4, 8.4 Hz), 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)

[1844]

54

TABLE 53

Example No.
187
1H NMR (δ) ppm

231

300 MHz, DMSO-d6 12.76 (1H, s), 8.57 (1H, d, J=4.4 Hz), 8.23 (1H, s), 7.96 and 7.86 (2H, ABq, J=8.2 Hz), 7.87-7.82 (1H, m), 7.68 and 7.12 (4H, A′ B′ q, J=8.6 Hz), 7.53 (2H, d, J=7.8 Hz), 7.37 (1H, t, J=8.3 Hz), 7.36-7.33 (1H, m), 6.90 (1H, d, J=8.3 Hz), 6.83 (1H, s), 6.74 (1H, d, J=8.0 Hz), 5.20 (2H, s), 4.31 (1H, brt, J=12.2 Hz), 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

232

300 MHz, DMSO-d6 12.77 (1H, brs), 8.21 (1H, d, J=1, 4 Hz), 7.92 (1H, d, J=8.7 Hz), 7.88 (1H, dd, J=8.7, 1.4 Hz), 7.57 (2H, d, J=8.7 Hz), 7.57-7.27 (7H, m), 7.11 (2H, d, J=8.7 Hz), 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

233

300 MHz, DMSO-d6 8.32(1H, s), 8.30-8.20 (2H, m), 8.10-7.98 (2H, m), 7.74 (2H, d, J=9.0 Hz), 7.60-7.46 (5H, m), 7.24 (2H, d, J=9.0 Hz), 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)

[1845]

55

TABLE 54

Example No.
190
1H NMR (δ) ppm

234

300 MHz, DMSO-d6 8.36-7.90 (5H, m), 7.74 (2H, d, J=8.6 Hz), 7.60-7.40 (5H, m), 7.25 (2H, d, J=8.7 Hz), 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

235

300 MHz, DMSO-d6 8.22 (1H, s), 7.94 (1H, d, J=8.4 Hz), 7.85 (1H, d, J=8.7 Hz), 7.61 (2H, d, J=8.7 Hz), 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

236

300 MHz, DMSO-d6 8.22 (1H, s), 7.94 (1H, d, J=8.4 Hz), 7.85 (1H, d, J=8.7 Hz), 7.61 (2H, d, J=8.7 Hz), 7.26-7.01 (6H, m), 4.84 (2H, s), 4.1 (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)

[1846]

56

TABLE 55

Example No.
193
1H NMR (δ) ppm

237

300 MHz, DMSO-d6 13.00 (1H, brs), 8.29 (1H, d, J=1.4 Hz), 8.15 (1H, d, J=8.8 Hz), 7.97 (1H, dd, J=1.4 Hz, 8.8 Hz), 7.89 (2H, d, J=8.8 Hz), 7.80-7.60 (5H, m) 7.25 (2H, d, J=8.8 Hz), 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

238

300 MHz, DMSO-d6 12.80 (1H, brs), 8.23 (1H, s), 7.97 (1H, d, J=8.5 Hz), 7.87 (1H, d, J=8.5 Hz), 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

239

300 MHz, DMSO-d6 8.25 (1H, s), 8.09-7.92 (5H, m), 7.77 (1H, s), 7.65 (2H, d, J=8.4 Hz), 7.59-7.51 (3H, m), 7.43 (2H, d, J=8.4 Hz), 7.17 (2H, d, J=8.7 Hz), 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)

[1847]

57

TABLE 56

Example No.
196
1H NMR (δ) ppm

240

300 MHz, DMSO-d6 8.22 (1H, s), 7.95 (1H, d, J=8.4 Hz), 7.86 (1H, d, J=8.4 Hz), 7.69 and 7.18 (4H, ABq, J=8.7 Hz), 7.34 (1H, t, J=8.0 Hz), 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

241

300 MHz, DMSO-d6 8.23 (1H, s), 7.95 (1H, d, J=8.4 Hz), 7.86 (1H, d, J=8.7 Hz), 7.69 and 7.18 (4H, ABq, J=8.7 Hz), 7.35 (1H, t, J=8.4 Hz), 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

242

300 MHz, DMSO-d6 12.75 (1H, s), 8.23 (1H, d, J=4.4 Hz), 7.95 and 7.86 (2H, ABq, J=8.6 Hz), 7.69 and 7.19 (4H, A′ B′ q, J=8.6 Hz), 7.36 (1H, t, J=7.8 Hz), 6.82 (1H, d, J=9.3 Hz), 6.73 (1H, s), 6.71 (1H, d, J=7.2 Hz), 4.30 (1H, brt, J=12.2 Hz), 3.89 (2H, d, J=6.0 Hz), 3.59 (2H, d, J=11.7 Hz), 2.85 (3H, s), 2.73 (2H, t, J=10.5 Hz), 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)

[1848]

58

TABLE 57

Example No.
199
1H NMR (δ) ppm

243

300 MHz, DMSO-d6 8.33 (1H, s), 8.30 (1H, d, J=8.9 Hz), 8.06 (1H, d, J=8.7 Hz), 7.79 (2H, d, J=8.7 Hz), 7.70 (2H, d, J=8.7 Hz), 7.61 (2H, d, J=8.7 Hz), 7.39 (2H, d, J=8.8 Hz), 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

244

(DMSO-d6) δ: 8.23(1H, s), 7.96 (1H, d, J=8.6 Hz), 7.86 (1H, d, J=8.6 Hz), 7.69 (2H, d, J=8.4 Hz), 7.52 (1H, s) 7.50-7.30 (4H, m), 7.18 (2H, d, J=8.4 Hz), 6.90 (1H, d, J=8.3 Hz), 6.84 (1H, s), 6.74 (1H, d, J=8.3 Hz), 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

245

(DMSO-d6) δ: 8.26 (1H, s), 8.06 (1H, d, J=8.7 Hz), 7.92 (1H, d, J=8.7 Hz), 7.72 (2H, d, J=8.7 Hz), 7.47 (4H, s), 7.38 (1H, t, J=8.2 Hz), 7.20 (2H, d, J=8.7 Hz), 6.90 (1H, d, J=8.2 Hz), 6.83 (1H, s), 6.74 (1H, d, J=8.2 Hz), 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)

[1849]

59

TABLE 58

Example No.
202
1H NMR (δ) ppm

246

(DMS0-d6) δ: 12.81 (1H, brs), 8.24 (1H, s), 7.99 (1H, d, J=8.7 Hz), 7.87 (1H, d, J=8.7 Hz), 7.69 (2H, d, J=8.6 Hz), 7.53-7.47 (2H, m), 7.38 (1H, t, J=8.2 Hz), 7.26-7.16 (4H, m), 6.89 (1H, d, J=8.2 Hz), 6.82 (1H, s), 6.73 (1H, d, J=8.2 Hz), 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

247

300 MHz, DMSO-d6 12.74 (1H, brs), 8.21 (1H, s), 8.08 (2H, d, J=9.0 Hz), 7.93 (1H, d, J=8.7 Hz), 7.85 (2h, d, J=8.7 Hz), 7.58 (2H, d, J=8.7 Hz), 7.13 (2H, d, J=8.7 Hz), 6.83 (2H, d, J=9.0 Hz), 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

248

300 MHz, DMSO-d6 8.39-8.28 (2H, m), 8.08 (1H, d, J=8.8 Hz), 7.76 (2H, d, J=8.7 Hz), 7.29 (2H, d, J=8.7 Hz), 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

[1850]

60

TABLE 59

Example No.
205
1H NMR (δ) ppm

249

300 MHz, DMSO-d6 9.59 (1H, brs), 8.23 (1H, s), 8.04 (1H, d, J=8.4 Hz), 7.90 (1H, d, J=8.4 Hz), 7.62 (2H, d, J=8.7 Hz), 7.39 (2H, 2H, d, J=8.7 Hz) 7.18 (2H, d, J=8.7 Hz), 6.63 (2H, d, J=8.7 Hz), 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

250

300 MHz, DMSO-d6 13.1 (1H, brs), 8.33 (1H, s), 8.29 (1H, d, J=8.8 Hz), 8.06 (1H, d, J=8.7 Hz), 7.77 (2H, d, J=8.7 Hz), 7.59-7.52 (4H, m), 7.35 (2H, d, J=8.8 Hz), 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

251

300 MHz, DMSO-d6 8.29 (1H, s) 8.26 (1H, d, J=8.8 Hz), 8.04 (1H, d, J=8.7 Hz), 7.73 (2H, d, J=8.8 Hz), 7.50-7.41 (6H, m), 7.36 (2H, d, J=8.8 Hz), 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)

[1851]

61

TABLE 60

Example No.
208
1H NMR (δ) ppm

252

300 MHz, DMSO-d6 8.32 (1H, s), 8.27 (1H, d, J=9.0 Hz) 8.07-8.00 (3H, m), 7.79-7.70 (3H, m), 7.51 (2H, d, J=8.1 Hz), 7.40 (2H, d, J=8.4 Hz), 7.18 (2H, d, J=8.7 Hz), 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

253

300 MHz, DMSO-d6 8.24 (1H, d, J=4.4 Hz), 7.98 and 7.88 (2H, ABq, J=8.6 Hz), 7.70 and 7.19 (4H, A′ B′ q, J=8.4 Hz), 7.35(1H, t, J=8.4 Hz), 6.86 (1H, d, J=8.1 Hz), 6.79 (1H, s), 6.71 (1H, d, J=8.1 Hz), 4.65-4.53 (1H, m), 4.31 (1H, brt, J=12.2 Hz), 3.88-3.78 (2H, m), 3.48 (2H, t, J=9.0 Hz), 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

254

300 MHz, DMSO-d6 12.75 (1H, s), 8.23 (1H, s), 7.96 and 7.87 (2H, ABq, J=8.7 Hz), 7.84-7.66 (6H, m), 7.38 (1H, t, J=8.4 Hz), 7.18 (2H, d, J=8.4 Hz), 6.91 (1H, d, J=9.0 Hz), 6.84 (1H, s), 6.74 (1H, d, J=8.1 Hz), 5.26 (2H, s), 4.31 (1H, brt, J=12.2 Hz), 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)

[1852]

62

TABLE 61

Example No.
211
1H NMR (δ) ppm

255

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), 2.07-1.80 (7H, m), 1.70-1.20 (5H, m)

Purity
>90% (NMR)

MS
540 (M + 1)

Example No.
212
1H NMR (δ) ppm

256

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

257

300 MHz, DMSO-d6 8.23 (1H, s), 7.95 and 7.86 (2H, AB1, J=8.4 Hz), 7.69 and 7.19 (4H, A′B′1, 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)

[1853]

63

TABLE 62

Example No.
214
1H NMR (δ) ppm

258

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=8.7 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

259

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), 7.18 (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

260

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)

[1854]

64

TABLE 63

Example No.
217
1H NMR (δ) ppm

261

(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

262

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

263

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)

[1855]

65

TABLE 64

Example No.
220
1H NMR (δ) ppm

264

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, 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

265

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

266

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)

[1856]

66

TABLE 65

Example No.
223
1H NMR (δ) ppm

267

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

268

(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

269

(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)

[1857]

67

TABLE 66

Example No.
226
1H NMR (δ) ppm

270

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

271

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.
219
1H NMR (δ) ppm

272

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)

[1858]

68

TABLE 67

Example No.
229
1H NMR (δ) ppm

273

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

274

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, m0, 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
>90% (NMR)

MS
481 (M + 1)

Example No.
231
1H NMR (δ) ppm

275

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, s, 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
>90% (NMR)

MS
595 (M + 1)

[1859]

69

TABLE 68

Example No.
232
1H NMR (δ) ppm

276

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

277

DMSO-d6 13.20 (1H, brs), 8.99 (1H, s), 8.32 (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, d), 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)

Example No.
234
1H NMR (δ) ppm

278

DMSO-d6 8.21 (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)

[1860]

70

TABLE 69

Example No.
235
1H NMR (δ) ppm

279

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, d, J=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

280

300 MHz, DMSO-d6 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, m0

Purity
>90% (NMR)

MS
APCI-Ms 555 (M + 1)

Example No.
237
1H NMR (δ) ppm

281

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)

[1861]

71

TABLE 70

Example No.
238
1H NMR (δ) ppm

282

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

283

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

284

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, M0, 1.5-1.2 (3H, m)

Purity
>90% (NMR)

MS
APCI-Ms 525 (M + 1)

[1862]

72

TABLE 71

Ex. No.
Formula
MS

1001

285

364 (M + H)

1002

286

454 (M + H)

1003

287

398 (M + H)

1004

288

357 (M + H)

1005

289

322 (M + H)

1006

290

385 (M + H)

[1863]

73

TABLE 72

Ex. No.
Formula
MS

1007

291

357 (M + H)

1008

292

416 (M + H)

1009

293

310 (M + H)

1010

294

390 (M + H)

1011

295

395 (M + H)

1012

296

366 (M + H)

[1864]

74

TABLE 73

Ex. No.
Formula
MS

1013

297

374 (M + H)

1014

298

382 (M + H)

1015

299

350 (M + H)

1016

300

402 (M + H)

1017

301

414 (M + H)

1018

302

340 (M + H)

[1865]

75

TABLE 74

Ex. No.
Formula
MS

1019

303

350 (M + H)

1020

304

380 (M + H)

1021

305

366 (M + H)

1022

306

378 (M + H)

1023

307

402 (M + H)

[1866]

76

TABLE 75

Ex. No.
Formula
MS

1024

308

518 (M + H)

1025

309

408 (M + H)

1026

310

336 (M + H)

1027

311

408 (M + H)

1028

312

366 (M + H)

1029

313

362 (M + H)

[1867]

77

TABLE 76

Ex. No.
Formula
MS

1030

314

473 (M + H)

1031

315

338 (M + H)

1032

316

307 (M + H)

1033

317

406 (M + H)

1034

318

466 (M + H)

1035

319

412 (M + H)

[1868]

78

TABLE 77

Ex. No.
Formula
MS

1036

320

412 (M + H)

1037

321

428 (M + H)

1038

322

466 (M + H)

1039

323

406 (M + H)

1040

324

417 (M + H)

1041

325

440 (M + H)

[1869]

79

TABLE 78

Ex. No.
Formula
MS

1042

326

417 (M + H)

1043

327

440 (M + H)

1044

328

312 (M + H)

1045

329

423 (M + H)

1046

330

352 (M + H)

1047

331

307 (M + H)

[1870]

80

TABLE 79

Ex. No.
Formula
MS

1048

332

374 (M + H)

1049

333

398 (M + H)

1050

334

326 (M + H)

1051

335

442 (M + H)

1052

336

518 (M + H)

[1871]

81

TABLE 80

Ex. No.
Formula
MS

1053

337

442 (M + H)

1054

338

376 (M + H)

1055

339

442 (M + H)

1056

340

352 (M + H)

1057

341

367 (M + H)

1058

342

367 (M + H)

[1872]

82

TABLE 81

Ex. No.
Formula
MS

1059

343

364 (M + H)

1060

344

324 (M + H)

1061

345

352 (M + H)

1062

346

357 (M + H)

1063

347

360 (M + H)

1064

348

351 (M + H)

[1873]

83

TABLE 82

Ex. No.
Formula
MS

1065

349

351 (M + H)

1066

350

366 (M + H)

1067

351

367 (M + H)

1068

352

364 (M + H)

1069

353

350 (M + H)

1070

354

306 (M + H)

[1874]

84

TABLE 83

Ex. No.
Formula
MS

1071

355

365 (M + H)

1072

356

455 (M + H)

1073

357

399 (M + H)

1074

358

358 (M + H)

1075

359

337 (M + H)

1076

360

386 (M + H)

[1875]

85

TABLE 84

Ex. No.
Formula
MS

1077

361

358 (M + H)

1078

362

417 (M + H)

1079

363

311 (M + H)

1080

364

391 (M + H)

1081

365

396 (M + H)

1082

366

367 (M + H)

[1876]

86

TABLE 85

Ex. No.
Formula
MS

1083

367

375 (M + H)

1084

368

351 (M + H)

1085

369

383 (M + H)

1086

370

403 (M + H)

1087

371

415 (M + H)

1088

372

341 (M + H)

[1877]

87

TABLE 86

Ex. No.
Formula
MS

1089

373

351 (M + H)

1090

374

381 (M + H)

1091

375

367 (M + H)

1092

376

379 (M + H)

1093

377

403 (M + H)

[1878]

88

TABLE 87

Ex. No.
Formula
MS

1094

378

519 (M + H)

1095

379

409 (M + H)

1096

380

337 (M + H)

1097

381

409 (M + H)

1098

382

367 (M + H)

1099

383

363 (M + H)

[1879]

89

TABLE 88

Ex. No.
Formula
MS

1100

384

474 (M + H)

1101

385

339 (M + H)

1102

386

308 (M + H)

1103

387

467 (M + H)

1104

388

413 (M + H)

1105

389

413 (M + H)

[1880]

90

TABLE 89

Ex. No.
Formula
MS

1106

390

429 (M + H)

1107

391

467 (M + H)

1108

392

1109

393

1110

394

441 (M + H)

1111

395

418 (M + H)

[1881]

91

TABLE 90

Ex. No.
Formula
MS

1112

396

313 (M + H)

1113

397

308 (M + H)

1114

398

375 (M + H)

1115

399

399 (M + H)

1116

400

327 (M + H)

1117

401

443 (M + H)

[1882]

92

TABLE 91

Ex. No.
Formula
MS

1118

402

519 (M + H)

1119

403

443 (M + H)

1120

404

377 (M + H)

1121

405

443 (M + H)

1122

406

353 (M + H)

[1883]

93

TABLE 92

Ex. No.
Formula
MS

1123

407

368 (M + H)

1124

408

368 (M + H)

1125

409

365 (M + H)

1126

410

325 (M + H)

1127

411

353 (M + H)

1128

412

358 (M + H)

[1884]

94

TABLE 93

Ex. No.
Formula
MS

1129

413

361 (M + H)

1130

414

352 (M + H)

1131

415

352 (M + H)

1132

416

367 (M + H)

1133

417

368 (M + H)

1134

418

365 (M + H)

[1885]

95

TABLE 94

Ex. No.
Formula
MS

1135

419

351 (M + H)

1136

420

307 (M + H)

1137

421

385 (M + H)

1138

422

365 (M + H)

1139

423

467 (M + H)

1140

424

387 (M + H)

[1886]

96

TABLE 95

Ex. No.
Formula
MS

1141

425

322 (M + H)

1142

426

364 (M + H)

1143

427

323 (M + H)

1144

428

363 (M + H)

1145

429

484 (M + H)

1146

430

385 (M + H)

[1887]

97

TABLE 96

Ex. No.
Formula
MS

1147

431

427 (M + H)

1148

432

420 (M + H)

1149

433

508 (M + H)

1150

434

458 (M + H)

1151

435

458 (M + H)

[1888]

98

TABLE 97

Ex. No.
Formula
MS

1152

436

474 (M + H)

1153

437

458 (M + H)

1154

438

508 (M + H)

1155

439

454 (M + H)

[1889]

99

TABLE 98

Ex. No.
Formula
MS

1156

440

470 (M + H)

1157

441

496 (M + H)

1158

442

482 (M + H)

1159

443

448 (M + H)

1160

444

488 (M + H)

[1890]

100

TABLE 99

Ex. No.
Formula
MS

1161

445

468 (M + H)

1162

446

447 (M + H)

1163

447

466 (M + H)

1164

448

526 (M + H)

1165

449

420 (M + H)

[1891]

101

TABLE 100

Ex. No.
Formula
MS

1166

450

490 (M + H)

1167

451

435 (M + H)

1168

452

436 (M + H)

1169

453

436 (M + H)

1170

454

404 (M + H)

1171

455

406 (M + H)

[1892]

102

TABLE 101

Ex. No.
Formula
MS

1172

456

392 (M + H)

1173

457

420 (M + H)

1174

458

406 (M + H)

1175

459

420 (M + H)

1176

460

523 (M + H)

1177

461

406 (M + H)

[1893]

103

TABLE 102

Ex. No.
Formula
MS

1178

462

447 (M + H)

1179

463

433 (M + H)

1180

464

509 (M + H)

1181

465

513 (M + H)

[1894]

104

TABLE 103

Ex. No.
Formula
MS

1182

466

497 (M + H)

1183

467

496 (M + H)

1184

468

418 (M + H)

1185

469

508 (M + H)

1186

470

490 (M + H)

[1895]

105

TABLE 104

Ex. No.
Formula
MS

1187

471

441 (M + H)

1188

472

455 (M + H)

1189

473

455 (M + H)

1190

474

513 (M + H)

1191

475

504 (M + H)

1192

476

494 (M + H)

[1896]

106

TABLE 105

Ex. No.
Formula
MS

1193

477

512 (M + H)

1194

478

504 (M + H)

1195

479

516 (M + H)

1196

480

497 (M + H)

1197

481

456 (M + H)

1198

482

509 (M + H)

[1897]

107

TABLE 106

Ex. No.
Formula
MS

1199

483

483 (M + H)

1200

484

427 (M + H)

1201

485

427 (M + H)

1202

486

477 (M + H)

1203

487

519 (M + H)

1204

488

440 (M + H)

[1898]

108

TABLE 107

Ex. No.
Formula
MS

1205

489

454 (M + H)

1206

490

325 (M + H)

1207

491

341 (M + H)

1208

492

385 (M + H)

1209

493

363 (M + H)

1210

494

332 (M + H)

[1899]

109

TABLE 108

Ex. No.
Formula
MS

1211

495

351 (M + H)

1212

496

335 (M + H)

1213

497

349 (M + H)

1214

498

321 (M + H)

1215

499

375 (M + H)

1216

500

367 (M + H)

[1900]

110

TABLE 109

Ex. No.
Formula
MS

1217

501

433 (M + H)

1218

502

391 (M + H)

1219

503

337 (M + H)

1220

504

385 (M + H)

1221

505

341 (M + H)

1222

506

332 (M + H)

[1901]

111

TABLE 110

Ex. No.
Formula
MS

1223

507

395 (M + H)

1224

508

375 (M + H)

1225

509

351 (M + H)

1226

510

321 (M + H)

1227

511

426 (M + H)

1228

512

460 (M + H)

[1902]

112

TABLE 111

Ex. No.
Formula
MS

1229

513

442 (M + H)

1230

514

468 (M + H)

1231

515

456 (M + H)

1232

516

494 (M + H)

1233

517

451 (M + H)

1234

518

468 (M + H)

[1903]

113

TABLE 112

Ex. No.
Formula
MS

1235

519

498 (M + H)

1236

520

476 (M + H)

1237

521

502 (M + H)

1238

522

505 (M + H)

1239

523

469 (M + H)

[1904]

114

TABLE 113

Ex. No.
Formula
MS

1240

524

483 (M + H)

1241

525

408 (M + H)

1242

526

460 (M + H)

1243

527

468 (M + H)

1244

528

494 (M + H)

1245

529

454 (M + H)

[1905]

115

TABLE 114

Ex. No.
Formula
MS

1246

530

468 (M + H)

1247

531

498 (M + H)

1248

532

482 (M + H)

1249

533

468 (M + H)

1250

534

460 (M + H)

[1906]

116

TABLE 115

Ex. No.
Formula
MS

1251

535

442 (M + H)

1252

536

468 (M + H)

1253

537

456 (M + H)

1254

538

494 (M + H)

[1907]

117

TABLE 116

Ex. No.
Formula
MS

1255

539

451 (M + H)

1256

540

468 (M + H)

1257

541

498 (M + H)

1258

542

470 (M + H)

[1908]

118

TABLE 117

Ex. No.
Formula
MS

1259

543

476 (M + H)

1260

544

502 (M + H)

1261

545

505 (M + H)

1262

546

469 (M + H)

[1909]

119

TABLE 118

Ex. No.
Formula
MS

1263

547

483 (M + H)

1264

548

408 (M + H)

1265

549

460 (M + H)

1266

550

468 (M + H)

[1910]

120

TABLE 119

Ex. No.
Formula
MS

1267

551

494 (M + H)

1268

552

454 (M + H)

1269

553

468 (M + H)

1270

554

498 (M + H)

[1911]

121

TABLE 120

Ex. No.
Formula
MS

1271

555

482 (M + H)

1272

556

468 (M + H)

1273

557

494 (M + H)

1274

558

484 (M + H)

[1912]

122

TABLE 121

Ex. No.
Formula
MS

1275

559

519 (M + H)

1276

560

427 (M + H)

1277

561

456 (M + H)

1278

562

516 (M + H)

[1913]

123

TABLE 122

Ex. No.
Formula
MS

1279

563

436 (M + H)

1280

564

426 (M + H)

1281

565

440 (M + H)

1282

566

454 (M + H)

1283

567

468 (M + H)

[1914]

124

TABLE 123

Ex. No.
Formula
MS

1284

568

482 (M + H)

1285

569

406 (M + H)

1286

570

420 (M + H)

1287

571

508 (M + H)

1288

572

508 (M + H)

[1915]

125

TABLE 124

Ex. No.
Formula
MS

1289

573

509 (M + H)

1290

574

455 (M + H)

1291

575

494 (M + H)

1292

576

418 (M + H)

[1916]

126

TABLE 125

Ex. No.
Formula
MS

1293

577

490 (M + H)

1294

578

496 (M + H)

1295

579

477 (M + H)

1296

580

508 (M + H)

1297

581

470 (M + H)

[1917]

127

TABLE 126

Ex. No.
Formula
MS

1298

582

435 (M + H)

1299

583

488 (M + H)

1300

584

454 (M + H)

1301

585

504 (M + H)

[1918]

128

TABLE 127

Ex. No.
Formula
MS

1302

586

513 (M + H)

1303

587

399 (M + H)

1304

588

530 (M + H)

1305

589

504 (M + H)

1306

590

440 (M + H)

[1919]

129

TABLE 128

Ex. No.
Formula
MS

1307

591

494 (M + H)

1308

592

508 (M + H)

1309

593

518 (M + H)

1310

594

532 (M + H)

1311

595

522 (M + H)

[1920]

130

TABLE 129

Ex. No.
Formula
MS

1312

596

546 (M + H)

1313

597

484 (M + H)

1314

598

517 (M + H)

1315

599

488 (M + H)

1316

600

481 (M + H)

[1921]

131

TABLE 130

Ex. No.
Formula
MS

1317

601

413 (M + H)

1318

602

423 (M + H)

1319

603

504 (M + H)

1320

604

510 (M + H)

1321

605

522 (M + H)

1322

606

522 (M + H)

[1922]

132

TABLE 131

Ex. No.
Formula
MS

1323

607

484 (M + H)

1324

608

449 (M + H)

1325

609

502 (M + H)

1326

610

491 (M + H)

1327

611

496 (M + H)

[1923]

133

TABLE 132

Ex. No.
Formula
MS

1328

612

497 (M + H)

1329

613

470 (M + H)

1330

614

530 (M + H)

1331

615

502 (M + H)

1332

616

522 (M + H)

[1924]

134

TABLE 133

Ex. No.
Formula
MS

1333

617

491 (M + H)

1334

618

536 (M + H)

1335

619

547 (M + H)

1336

620

484 (M + H)

1337

621

484 (M + H)

1338

622

498 (M + H)

[1925]

135

TABLE 134

Ex. No.
Formula
MS

1339

623

528 (M + H)

1340

624

498 (M + H)

1341

625

514 (M + H)

1342

626

513 (M + H)

1343

627

488 (M + H)

1344

628

502 (M + H)

[1926]

136

TABLE 135

Ex. No.
Formula
MS

1345

629

488 (M + H)

1346

630

502 (M + H)

1347

631

499 (M + H)

1348

632

480 (M + H)

1349

633

522 (M + H)

1350

634

546 (M + H)

[1927]

137

TABLE 136

Ex. No.
Formula
MS

1351

635

482 (M + H)

1352

636

484 (M + H)

1353

637

609 (M + H)

1354

638

532 (M + H)

1355

639

480 (M + H)

1356

640

566 (M + H)

[1928]

138

TABLE 137

Ex. No.
Formula
MS

1357

641

602 (M + H)

1358

642

596 (M + H)

1359

643

491 (M + H)

1360

644

491 (M + H)

1361

645

491 (M + H)

1362

646

496 (M + H)

[1929]

139

TABLE 138

Ex. No.
Formula
MS

1363

647

512 (M + H)

1364

648

494 (M + H)

1365

649

488 (M + H)

1366

650

481 (M + H)

1367

651

524 (M + H)

1368

652

497 (M + H)

[1930]

140

TABLE 139

Ex. No.
Formula
MS

1369

653

472 (M + H)

1370

654

469 (M + H)

1371

655

470 (M + H)

1372

656

469 (M + H)

1373

657

494 (M + H)

1374

658

458 (M + H)

[1931]

141

TABLE 140

Ex. No.
Formula
MS

1375

659

612 (M + H)

1376

660

554 (M + H)

1377

661

542 (M + H)

1378

662

526 (M + H)

1379

663

496 (M + H)

1380

664

510 (M + H)

[1932]

142

TABLE 141

Ex. No.
Formula
MS

1381

665

540 (M + H)

1382

666

525 (M + H)

1383

667

558 (M + H)

1384

668

523 (M + H)

1385

669

539 (M + H)

[1933]

143

TABLE 142

Ex. No.
Formula
MS

1386

670

533 (M + H)

1387

671

500 (M + H)

1388

672

485 (M + H)

1389

673

523 (M + H)

1390

674

512 (M + H)

[1934]

144

TABLE 143

Ex. No.
Formula
MS

1391

675

540 (M + H)

1392

676

527 (M + H)

1393

677

525 (M + H)

1394

678

507 (M + H)

1395

679

491 (M + H)

1396

680

506 (M + H)

[1935]

145

TABLE 144

Ex. No.
Formula
MS

1397

681

522 (M + H)

1398

682

538 (M + H)

1399

683

522 (M + H)

1400

684

530 (M + H)

1401

685

600 (M + H)

1402

686

504 (M + H)

[1936]

146

TABLE 145

Ex. No.
Formula
MS

1403

687

534 (M + H)

1404

688

475 (M + H)

1405

689

472 (M + H)

1406

690

455 (M + H)

1407

691

469 (M + H)

1408

692

547 (M + H)

[1937]

147

TABLE 146

Ex. No.
Formula
MS

1409

693

529 (M + H)

1410

694

435 (M + H)

1411

695

504 (M + H)

1412

696

469 (M + H)

1413

697

522 (M + H)

1414

698

488 (M + H)

[1938]

148

TABLE 147

Ex. No.
Formula
MS

1415

699

502 (M + H)

1416

700

488 (M + H)

1417

701

502 (M + H)

1418

702

455 (M + H)

1419

703

455 (M + H)

1420

704

522 (M + H)

[1939]

149

TABLE 148

Ex. No.
Formula
MS

1421

705

469 (M + H)

1422

706

536 (M + H)

1423

707

510 (M + H)

1424

708

494 (M + H)

1425

709

458 (M + H)

[1940]

150

TABLE 149

Ex. No.
Formula
MS

1426

710

612 (M + H)

1427

711

526 (M + H)

1428

712

480 (M + H)

1429

713

441 (M + H)

1430

714

511 (M + H)

[1941]

151

TABLE 150

Ex. No.
Formula
MS

1431

715

530 (M + H)

1432

716

497 (M + H)

1433

717

441 (M + H)

1434

718

491 (M + H)

1435

719

491 (M + H)

1436

720

491 (M + H)

[1942]

152

TABLE 151

Ex. No.
Formula
MS

1437

721

524 (M + H)

1438

722

508 (M + H)

1439

723

474 (M + H)

1440

724

490 (M + H)

1441

725

508 (M + H)

1442

726

474 (M + H)

[1943]

153

TABLE 152

Ex. No.
Formula
MS

1443

727

516 (M + H)

1444

728

600 (M + H)

1445

729

504 (M + H)

1446

730

534 (M + H)

1447

731

475 (M + H)

[1944]

154

TABLE 153

Ex. No.
Formula
MS

1448

732

530 (M + H)

1449

733

440 (M + H)

1450

734

490 (M + H)

1451

735

474 (M + H)

1452

736

441 (M + H)

1453

737

508 (M + H)

[1945]

155

TABLE 154

Ex. No.
Formula
MS

1454

738

455 (M + H)

1455

739

522 (M + H)

1456

740

496 (M + H)

1457

741

516 (M + H)

1458

742

426 (M + H)

1459

743

482 (M + H)

[1946]

156

TABLE 155

Ex. No.
Formula
MS

1460

744

486 (M + H)

1461

745

516 (M + H)

1462

746

427 (M + H)

1463

747

476 (M + H)

1464

748

460 (M + H)

1465

749

502 (M + H)

[1947]

157

TABLE 156

Ex. No.
Formula
MS

1466

750

586 (M + H)

1467

751

518 (M + H)

1468

752

530 (M + H)

1469

753

598 (M + H)

1470

754

512 (M + H)

1471

755

544 (M + H)

[1948]

158

TABLE 157

Ex. No.
Formula
MS

1472

756

440 (M + H)

1473

757

490 (M + H)

1474

758

474 (M + H)

1475

759

441 (M + H)

1476

760

508 (M + H)

1477

761

455 (M + H)

[1949]

159

TABLE 158

Ex. No.
Formula
MS

1478
522 (M + H)

1479
496 (M + H)

1480
516 (M + H)

1481
426 (M + H)

1482
482 (M + H)

[1950]

160

TABLE 159

Ex. No.
Formula
MS

1483

762

486 (M + H)

1484

763

516 (M + H)

1485

764

427 (M + H)

1486

765

476 (M + H)

[1951]

161

TABLE 160

Ex. No.
Formula
MS

1487

766

460 (M + H)

1488

767

502 (M + H)

1489

768

586 (M + H)

1490

769

518 (M + H)

[1952]

162

TABLE 161

Ex. No.
Formula
MS

1491

770

530 (M + H)

1492

771

598 (M + H)

1493

772

512 (M + H)

1494

773

544 (M + H)

[1953]

163

TABLE 162

Ex. No.
Formula
MS

1495

774

580 (M + H)

1496

775

550 (M + H)

1497

776

606 (M + H)

1498

777

580 (M + H)

1499

778

550 (M + H)

[1954]

164

TABLE 163

Ex. No.
Formula
MS

1500

779

606 (M + H)

1501

780

630 (M + H)

1502

781

600 (M + H)

1503

782

656 (M + H)

[1955]

165

TABLE 164

Ex. No.
Formula
MS

1504

783

630 (M + H)

1505

784

600 (M + H)

1506

785

656 (M + H)

1507

786

580 (M + H)

[1956]

166

TABLE 165

Ex. No.
Formula
MS

1508

787

550 (M + H)

1509

788

606 (M + H)

1510

789

580 (M + H)

1511

790

550 (M + H)

1512

791

546 (M + H)

[1957]

167

TABLE 166

Ex. No.
Formula
MS

1513

792

516 (M + H)

1514

793

572 (M + H)

1515

794

546 (M + H)

1516

795

516 (M + H)

1517

796

572 (M + H)

[1958]

168

TABLE 167

Ex. No.
Formula
MS

1518

797

602 (M + H)

1519

798

572 (M + H)

1520

799

628 (M + H)

1521

800

606 (M + H)

[1959]

169

TABLE 168

Ex. No.
Formula
MS

1522

801

573 (M + H)

1523

802

606 (M + H)

1524

803

602 (M + H)

1525

804

572 (M + H)

[1960]

170

TABLE 169

Ex. No.
Formula
MS

1526

805

628 (M + H)

1527

806

606 (M + H)

1528

807

606 (M + H)

1529

808

614 (M + H)

[1961]

171

TABLE 170

Ex. No.
Formula
MS

1530

809

584 (M + H)

1531

810

640 (M + H)

1532

811

618 (M + H)

1533

812

614 (M + H)

1534

813

584 (M + H)

[1962]

172

TABLE 171

Ex. No.
Formula
MS

1535

814

640 (M + H)

1536

815

627 (M + H)

1537

816

627 (M + H)

[1963]

173

TABLE 172

Ex. No.
Formula
MS

1538

817

560 (M + H)

1539

818

634 (M + H)

5640

819

593 (M + H)

1541

820

627 (M + H)

[1964]

174

TABLE 173

Ex. No.
Formula
MS

1542

821

627 (M + H)

1543

822

560 (M + H)

1544

823

634 (M + H)

1545

824

593 (M + H)

[1965]

175

TABLE 174

Ex. No.
Formula
MS

1546

825

627 (M + H)

1547

826

627 (M + H)

1548

827

560 (M + H)

1549

828

634 (M + H)

[1966]

176

TABLE 175

Ex. No.
Formula
MS

1550

829

627 (M + H)

1551

830

560 (M + H)

1552

831

532 (M + H)

1553

832

565 (M + H)

[1967]

177

TABLE 176

Ex. No.
Formula
MS

1554

833

599 (M + H)

1555

834

599 (M + H)

1556

835

532 (M + H)

1557

836

532 (M + H)

[1968]

178

TABLE 177

Ex. No.
Formula
MS

1558

837

584 (M + H)

1559

838

570 (M + H)

[1969]

179

TABLE 178

HCV polymerase

Ex.
inhibitory activity

No.
IC50 [μM]

2
0.079

6
0.034

9
0.019

11
0.53

12
0.60

17
0.047

20
0.042

26
0.033

30
0.052

43
0.58

44
0.95

45
0.40

46
0.47

47
0.54

48
0.44

49
0.94

50
0.54

51
1.0

54
0.56

55
0.36

67
0.26

68
0.28

70
0.19

71
0.62

77
0.51

81
0.18

82
0.097

83
0.52

85
0.17

86
0.13

87
0.80

88
0.092

89
0.34

90
0.20

91
0.53

93
0.16

94
0.084

96
0.25

97
0.16

98
0.30

[1970]

180

TABLE 179

HCV polymerase

Ex.
inhibitory activity

No.
IC50 [μM]

99
0.53

100
0.78

101
0.14

103
0.17

104
0.073

105
0.076

106
0.40

107
0.11

108
0.21

109
0.11

110
0.24

111
0.14

112
0.11

113
0.071

114
0.56

115
0.17

116
0.37

117
0.075

118
0.14

119
0.13

120
0.16

121
0.19

122
0.51

123
0.10

124
0.091

125
0.12

128
0.14

129
0.12

130
0.16

131
0.046

132
0.055

133
0.12

134
0.071

139
0.26

140
0.11

141
0.43

142
0.055

143
0.053

144
0.19

145
0.088

[1971]

181

TABLE 180

HCV polymerase

Ex.
inhibitory activity

No.
IC50 [μM]

146
0.043

147
0.31

148
0.038

149
0.15

150
0.24

151
0.20

153
0.19

154
0.076

155
0.53

156
0.23

157
0.16

158
0.11

159
0.13

160
0.24

161
0.062

162
0.43

163
0.15

164
0.16

165
0.58

166
0.055

167
0.033

168
0.078

169
0.15

170
0.048

171
0.050

172
0.10

173
0.14

174
0.030

175
0.29

176
0.053

177
0.077

178
0.052

179
0.63

180
0.11

181
0.71

182
0.021

183
0.017

184
0.018

185
0.11

186
0.37

[1972]

182

TABLE 181

HCV polymerase

Ex.
inhibitory activity

No.
IC50 [μM]

187
0.056

188
0.038

189
0.017

190
0.020

191
0.43

192
0.22

193
0.13

194
0.52

195
0.023

196
0.20

197
0.11

198
0.044

199
0.11

200
0.10

201
0.14

202
0.095

203
0.063

204
0.16

205
0.077

206
0.05

207
0.081

208
0.039

209
0.12

210
0.31

211
0.059

212
0.23

213
0.10

214
0.059

215
0.078

216
0.084

217
0.058

218
0.033

219
0.13

220
0.073

221
0.058

222
0.041

223
0.21

225
0.014

227
0.045

228
0.18

[1973]

183

TABLE 182

HCV polymerase

Ex.
inhibitory activity

No.
IC50 [μM]

229
0.022

230
0.17

231
0.073

232
0.015

233
0.028

234
0.022

235
0.036

236
0.075

237
0.015

238
0.19

239
0.17

240
0.055

248
0.012

249
0.022

250
0.018

252
0.32

253
0.65

254
0.038

255
0.038

256
0.079

257
0.074

259
0.10

260
0.27

262
0.013

263
0.035

264
<0.01

265
0.014

266
0.018

267
0.014

268
0.012

269
0.013

270
0.012

271
0.024

272
0.066

273
0.041

276
0.023

279
0.017

280
0.016

281
0.052

282
0.019

[1974]

184

TABLE 183

HCV polymerase

Ex.
inhibitory activity

No.
IC50 [μM]

283
0.014

284
0.014

285
0.012

286
0.014

287
0.012

288
0.013

289
<0.01

290
0.012

291
0.016

292
0.015

293
0.034

294
0.032

295
0.045

296
0.034

297
0.022

298
0.011

299
0.018

300
0.045

301
0.017

303
0.10

304
0.017

305
0.01

306
0.013

307
0.022

308
0.023

311
0.16

312
0.023

313
0.025

314
0.097

315
0.028

316
0.022

317
0.032

318
0.012

319
0.030

[1975]

185

TABLE 184

HCV polymerase

Ex.
inhibitory activity

No.
IC50 [μM]

320
0.036

321
0.015

322
0.016

323
0.018

324
0.027

325
0.019

326
0.018

327
0.019

328
0.015

329
0.047

330
0.011

331
0.017

332
0.023

333
0.016

334
0.016

335
0.013

[1976]

186

TABLE 185

Example No. 249
1H NMR(δ) ppm

839

300MHz, DMSO-d6 8.02(1H, d, 1.5Hz), 8.11 (1H, d, J=1.8Hz), 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

840

300MHz, DMSO-d6 8.25(1H, d, J=1.5Hz), 8.16-8.08(2H, m), 7.99-7.88(2H, m), 7.66(2H, d, J=8.6Hz), 7.60-7.48(5H, m), 7.19(2H, d, J=8.6Hz), 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

841

300MHz, 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)

[1977]

187

TABLE 186

Example No. 252
1H NMR(δ) ppm

842

300MHz, DMSO-d6 8.20(1H, d, J=1.5Hz), 7.96 (1H, d, J=8.6Hz), 7.84(1H, dd, J=8.6, 1.5Hz), 7.54(2H, d, J=6.9Hz), 7.48-7.26(8H, m), 7.09(1H, t, J=7.3Hz), 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

843

300MHz, DMSO-d6 8.21(1H, d, J=1.5Hz), 7.93 (1H, d, J=8.7Hz), 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=3.6Hz), 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

844

300MHz, DMSO-d6 8.15(1H, s), 8.02(1H, d, J=8.7Hz), 7.90(1H, dd, J=8.4, 1.4Hz), 7.80-7.71(2H, m), 7.67(2H, d, J=8.7Hz), 7.33(2H, t, J=8.7Hz), 7.26(2H, d, J=8.7Hz), 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)

[1978]

188

TABLE 187

Example No. 255
1H NMR(δ) ppm

845

300MHz, DMSO-d6 8.34(1H, s), 8.32(1H, d, J=8.8Hz), 8.09-8.03(3H, m), 7.83(2H, d, J=8.3Hz), 7.79(2H, d, J=8.8Hz), 7.36(2H, d, J=8.8Hz), 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

846

300MHz, 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, 2.3Hz), 6.69(1H, dd, J=8.1, 2.1Hz), 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 (M + 1)

Example No. 257
1H NMR(δ) ppm

847

300MHz, DMSO-d6 8.19(1H, d, J=8.7Hz), 7.93 (1H, 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, 2.9Hz), 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)

[1979]

189

TABLE 188

Example No.
258
1H NMR (δ) ppm

848

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

849

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

850

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)

[1980]

190

TABLE 189

Example No.
261
1H NMR (δ) ppm

851

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

852

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

853

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)

[1981]

191

TABLE 190

Example No.
264
1H NMR (δ) ppm

854

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

855

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

856

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)

[1982]

192

TABLE 191

Example No.
267
1H NMR (δ) ppm

857

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

858

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

859

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)

[1983]

193

TABLE 192

Example No.
270
1H NMR (δ) ppm

860

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

861

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

862

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)

[1984]

194

TABLE 193

Example No.
273
1H NMR (δ) ppm

863

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

864

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

865

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)

[1985]

195

TABLE 194

Example No.
276
1H NMR (δ) ppm

866

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

867

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

868

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)

[1986]

196

TABLE 195

Example No.
279
1H NMR (δ) ppm

869

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

870

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

871

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

[1987]

197

TABLE 196

Example No.
282
1H NMR (δ) ppm

872

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

873

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

874

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)

[1988]

198

TABLE 197

Example No.
285
1H NMR (δ) ppm

875

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

876

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

877

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)

[1989]

199

TABLE 198

Example No.
288
1H NMR (δ) ppm

878

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

879

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

880

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)

[1990]

200

TABLE 199

Example No.
291
1H NMR (δ) ppm

881

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

882

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

883

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)

[1991]

201

TABLE 200

Example No.
294
1H NMR (δ) ppm

884

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

885

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

886

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)

[1992]

202

TABLE 201

Example No.
297
1H NMR (δ) ppm

887

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

888

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

889

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)

[1993]

203

TABLE 202

Example No.
300
1H NMR (δ) ppm

890

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

891

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

892

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)

[1994]

204

TABLE 203

Example No.
303
1H NMR (δ) ppm

893

300 MHz, CDCl3 8.49 (1H, s), 7.98(1H, dd, J=8.6, 1.5 Hz), 7.71 (1H, d, J=1.8 Hz), 7.66 (1H, d, J=8.6 Hz), 7.55-7.29 (7H, m), 6.80 (1H, dd, J=8.2, 2.2 Hz), 6.69 (1H, dd, J=11.2, 2.2 Hz), 4.99 (2H, s), 4.10-3.92 (1H, m), 3.95 (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
1H NMR (δ) ppm

894

300 MHz, DMSO-d6 8.21 (1H, s), 7.94 (1H, d, J=8.7 Hz), 7.84 (1H, d, J=9.1 Hz), 7.70 (1H, s), 7.26-7.39 (9H, m), 7.11 (2H, d, J=8.4 Hz), 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
1H NMR (δ) ppm

895

300 MHz, DMSO-d6 8.24 (2H. s), 8.03 (1H, d, J=8.0 Hz), 7.96 (1H, d, J=8.8 Hz), 7.87 (1H, d, J=9.1 Hz), 7.60-7.46 (6H, m), 7.09 (1H, dd, J=12.0, 1.8 Hz), 6.97 (1H, dd, J=8.4, 1.8 Hz), 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)

[1995]

205

TABLE 204

Example No.
306
1H NMR (δ) ppm

896

300 MHz, DMSO-d6 12.84 (1H, brs), 8.21 (1H s), 7.98-7.84 (5H, m), 7.58 (2H, d, J=8.7 Hz), 7.54 (2H, d, J=7.8 Hz), 7.34 (1H,, d, J=8.7 Hz), 7.26 (1H, d, J=2.4 Hz), 7.13-7.06 (3H, m), 5.06 (2H, s), 4.26 (1H, brt, J=12.7 Hz), 3.84 (3H, s), 2.36-2.17 (2H, brm), 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
1H NMR (δ) ppm

897

300 MHz, DMSO-d6 8.22 (1H, s), 8.04 (1H, s), 7.96 (2H, d, J=8.1 Hz), 7.87 (2H, s), 7.72 (1H, d, J=1.2 Hz), 7.59-7.41 (7H, m), 5.12 (2H, s), 4.25 (1H, brt, J=11.8 Hz), 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
1H NMR (δ) ppm

898

300 MHz, DMSO-d6 8.27 (1H, s), 8.08 (1H, d, J=9.0 Hz), 7.93 (1H, d, J=8.7 Hz), 7.65 (2H, d, J=8.7 Hz), 7.46 (2H, d, J=8.1 Hz), 7.42 (2H, d, J=8.4 Hz), 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)

[1996]

206

TABLE 205

Example No.
309
1H NMR (δ) ppm

899

300 MHz, DMSO-d6 8.33 (1H, s), 8.15 and 7.99 (2H, ABq, J=8.9 Hz), 7.84 and 7.59 (4H, A′ B′ q, J=8.3 Hz), 7.46 (2H, d, J=8.4 Hz), 7.22-7.16 (3H, m), 7.01-6.98 (2H, m), 4.27 and 4.23 (2H, A″B″q, J=12.9 Hz), 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
1H NMR (δ) ppm

900

300 MHz, DMSO-d6 8.33 (1H, s), 8.09 and 7.95 (2H, ABq, J=8.7 Hz), 7.87 and 7.71 (4H, A′ B′ q, J=8.0 Hz), 7.43 (2H, d, J=7.8 Hz), 7.15 (1H, d, J=8.7 Hz), 7.07-7.02 (4H, m), 4.66 (2H, s), 4.23 (1H, brt, J=11.8 Hz), 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
1H NMR (δ) ppm

901

300 MHz, DMSO-d6 8.30 (1H, s), 8.21 and 8.01 (2H, ABq, J=8.7 Hz), 7.65 (2H, d, J=8.4 Hz), 7.52-7.41 (6H, m), 7.20 (1H, d, J=8.4 Hz), 7.14 (1H, d, J=2.7 Hz), 6.97 (1H, dd, J=8.4, 2.4 Hz), 4.31 (1H, brt, J=9.8 Hz), 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)

Purity
>90% (NMR)

MS
583 (M + 1)

[1997]

207

TABLE 206

Example No.
312
1H NMR (δ) ppm

902

300 MHz, DMSO-d6 8.22 (1H, s), 8.12 (1H, d, J=8.4 Hz), 8.00-7.84 (5H, m), 7.70 (4H, d, J=8.4 Hz), 7.56 (1H, t, J=8.6 Hz), 7.23 (1H, d, J=12.0 Hz), 7.13 (1H, d, J=8.6 Hz), 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
1H NMR (δ) ppm

903

300 MHz, DMSO-d6 8.89 (1H, brs), 8.63 (1H, brs), 8.24 (1H, s), 8.11 (1H, d, J=7.8 Hz), 7.99 (1H, d, J=8.8 Hz), 7.89 (1H, d, J=9.9 Hz), 7.61-7.55 (4H, m), 7.43 (2H, t, J=7.7 Hz), 7.34 (1H, t, J=7.2 Hz), 7.24 (1H, d, J=12.0 Hz), 7.14 (1H, d, J=8.6 Hz), 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
1H NMR (δ) ppm

904

300 MHz, CDCl3 8.48 (1H, d, J=1.4 Hz), 8.05 (1H, d, J=1.8 Hz), 8.98 (1H, d, J=8.6 Hz), 7.82 (1H, d, J=7.9 Hz), 7.66 (1H, d, J=8.6 Hz), 7.55-7.24 (6H, m), 6.78 (1H, dd, J=8.6, 2.6 Hz), 6.69 (1H, dd, J=11.6 Hz), 2.2 Hz), 6.40-6.30 (1H, m), 4.99 (2H, s), 4.02 (1H, m), 3.95 (3H, s), 3.05 (3H, d, J=4.8 Hz), 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)

[1998]

208

TABLE 207

Example No.
503
1H NMR (δ) ppm

905

300 MHz, DMSO-d6 8.23 (1H, s), 7.76 (1H, d, J=8.7 Hz), 7.58 (1H, d, J=8.8 Hz), 7.51-7.32 (7H, m), 7.17 (2H, d, J=8.7 Hz), 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
1H NMR (δ) ppm

906

300 MHz, DMSO-d6 8.96 (1H, s), 8.50 (1H, s), 7.77 (2H, d, J=8.7 Hz), 7.50-7.40 (4H, m), 7.30 (1H, d, J=8.4 Hz), 7.24 (1H, d, J=2.4 Hz), 7.16 (2H, d, J=8.4 Hz), 7.06 (1H, dd, J=2.4 Hz, 8.1 Hz), 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)

[1999]

209

TABLE 208

Example No. 315
1H NMR(γ) ppm

907

300MHz, DMSO-d6 8.84(2H, d, J=6.3Hz), 8.28(1H, s), 8.17 and 7.99(2H, ABq, J=8.7 Hz), 7.87-7.85(3H, m), 7.70-7.50(3H, m), 7.52(1H, d, J=8.3Hz), 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 8(1H, m), 1.50-1.23(3H, m)

Purity > 90% (NMR)

MS 538(M + 1)

Example No. 316
1H NMR(γ) ppm

908

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
1H NMR(γ) ppm

909

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 t, J=12.8Hz), 3.14(2H, t, J=6.3 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)

[2000]

210

TABLE 209

Example No. 318
1H NMR(δ) ppm

910

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
1H NMR(δ) ppm

911

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
1H NMR(δ) ppm

912

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)

[2001]

211

TABLE 210

Example No. 321
1H NMR(δ) ppm

913

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
1H NMR(δ) ppm

914

300MHz, DMSO-d6 9.54(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
1H NMR(δ) ppm

915

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, J=7.9Hz), 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)

[2002]

212

TABLE 211

Example No. 324
1H NMR(δ) ppm

916

300MHz, DMSO-d6 8.36(1H, d, J=7.9Hz), 8.30(1H, s), 8.28 and 8.05(2H, ABq, J=8.8 Hz), 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
1H NMR(δ) ppm

917

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=

# 6.8, 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
1H NMR(δ) ppm

MS 685 (M +1)

918

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)

[2003]

213

TABLE 212

Example No. 327
1H NMR(δ) ppm

919

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)

[2004]

214

TABLE 213

920

Ex.

No.
R
R′

2001
—H
4-C-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-)

921

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)

922

2021
5-(-F)

923

2022
4-(-Cl)
—H

2023
4-(-Cl)
4-(-F)

2024
4-(-Cl)
4-(-Cl)

2025
4-(-Cl)
4-(-Me)

2026
5-(-Cl)
4-C-CF3)

2027
4-(-Cl)
4-(-CO2H)

2028
5-(-Cl)
4-(-CO2Me)

2029
5-(-Cl)

924

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)

925

2035
4-(-Cl)

926

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)

927

2043
5-(-CF3)
4-C-CO2H)

2044
5-(-CF3)
4-(-CO2Me)

2045
5-(-CF3)

928

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

929

—H

2053

930

4-(-F)

2054

931

4-(-Cl)

2055

932

4-(-CN)

2056

933

4-(-NO2)

2057

934

4-(-Me)

2058

935

4-(-CF3)

2059

936

4-(-Ac)

2060

937

4-(-CO2H)

2061

938

4-(-CO2Me)

2062

939

940

2063

941

4-(-CONH2)

2064

942

4-{-CON(Me)2}

2065

943

4-{-C(═NH)NH2}

2066

944

4-(-OMe)

2067

945

946

2068

947

4-(-NHMe)

2069

948

4-(-NHAc)

2070

949

950

2071

951

4-(-SMe)

2072

952

953

2073

954

955

2074

956

957

2075

958

959

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-(-Cl)

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)

960

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)

961

2107
5-(-CONH2)
4-(-NHMe)

2108
5(-CONH2)
4-(-NHAc)

2109
5(CONH2)

962

2110
5-(-CONH2)
4-(-SMe)

2111
5-(-CONH2)

963

2112
5-(-CONH2)

964

2113
5-(-CONH2)

965

2114
5-(-CONH2)

966

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)2}
4-(-CO2Me)

2125
5-{-CON(Me)2}

967

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}

968

2131
5-{-CON(Me)2}
4-(-NHMe)

2132
5-{-CON(Me)2}
4-(-NHAc)

2133
5-{-CON(Me)2}

969

2134
4-{-CON(Me)2}
4-(-SMe)

2135
5-{-CON(Me)2}

970

2136
4-{-CON(Me)2}

971

2137
5-{-CON(Me)2}

972

2138
5-{-CON(Me)2}

973

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-(-CMe)
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)

974

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)

975

2160
5-(-OMe)
4-(-NHMe)

2161
5-(-OMe)
4-(-NHAc)

2162
5-(-OMe)

976

2163
5-(-OMe)
4-(-SMe)

2164
5-(-OMe)

977

2165
5-(-OMe)

978

2166
5-(-OMe)

979

2167
5-(-OMe)

980

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

981

4-(-F)

2176

982

4-(-Cl)

2177

983

4-(-Me)

2178

984

4-(-CF3)

2179

985

4-(-CO2H)

2180

986

4-(-CO2Me)

2181

987

988

2182

989

4-(-SMe)

2183

990

991

2184

992

993

2185
5-(-SMe)
4-(-F)

2186
4HSMe)
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

994

4-(-F)

2193

995

4-(-Cl)

2194

996

4-(-Me)

2195

997

4-(-CF3)

2196

998

4-(-Ac)

2197

999

4-(-CONH2)

2198

1000

4-{-CON(Me)2}

2199

1001

4-(-F)

2200

1002

4-(-Cl)

2201

1003

4-(-Me)

2202

1004

4-(-CF3)

2203

1005

4-(-Ac)

2204

1006

4-(-CONH2)

2205

1007

4-{-CON(Me)2}

2206

1008

4-(-F)

2207

1009

4-(-Cl)

2208

1010

2,4-di-(-Cl)

2209

1011

4-(-Me)

2210

1012

3-(-CF3)

2211

1013

4-(-CF3)

2212

1014

4-(-CONH2)

2213

1015

4-{-CON(Me)2}

2214

1016

4-(-SMe)

2215

1017

1018

2216

1019

1020

2217

1021

4-(-F)

2218

1022

4-(-Cl)

2219

1023

4-(-Me)

2220

1024

4-(-CF3)

2221

1025

4-(-CONH2)

2222

1026

4-{-CON(Me)2}

2223

1027

4-(-SMe)

2224

1028

1029

2225

1030

1031

2226
5-{-O-(CH2)2-OH}
4-(-Cl)

2227
5-{-O-(CH3)3-OH}
4-(-Cl)

2228

1032

4-(-Cl)

2229

1033

4-(-Cl)

2230

1034

4-(-Cl)

2231

1035

4-(-Cl)

2232

1036

4-(-Cl)

2233

1037

4-(-Cl)

2234

1038

4-(-Cl)

2235

1039

4-(-Cl)

2236

1040

4-(-Cl)

2237

1041

4-(-Cl)

2238

1042

4-(-Cl)

2239

1043

4-(-Cl)

2240

1044

4-(-Cl)

2241

1045

4-(-Cl)

2242

1046

4-(-Cl)

2243

1047

4-(-Cl)

2244

1048

4-(-Cl)

2245

1049

4-(-Cl)

2246

1050

4-(-Cl)

2247

1051

4-(-Cl)

2248

1052

4-(-Cl)

2249

1053

4-(-Cl)

2250

1054

4-(-Cl)

2251

1055

4-(-Cl)

2252

1056

4-(-Cl)

2253

1057

4-(-Cl)

2254

1058

4-(-Cl)

[2005]

215

TABLE 214

1059

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)
1 4-(-CF3)

2263
5-(-F)
4-(-CO2H)

2264
5-(-F)
4-(-CO2Me)

2265
5-(-F)

1060

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)

1061

2271
5-(-F)

1062

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)

1063

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)

1064

2285
5-(-Cl)

1065

2286
5-(-CN)
4-(-F)

2287
5-(-CN)
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)

1066

2293
5-(-CF3)
4-(-CO2H)

2294
5-(-CF3)
4-(-CO2Me)

2295
5-(-CF3)

1067

2296
5-(-CO2H)
4-(-F)

2297
4-(-CO2H)
4-(-F)

2299
5-(-CO2Me)
4-(-Cl)

2300
5-(-Ac)
4-(-F)

2301
5-(-Ac)
4-(-Cl)

2302

1068

—H

2303

1069

4-(-F)

2304

1070

4-(-Cl)

2305

1071

4-(CN)

2306

1072

4-(-NO2)

2307

1073

4-(-Me)

2308

1074

4-(-CF3)

2309

1075

4-(-Ac)

2310

1076

4-(-CO2H)

2311

1077

4-(-CO2Me)

2312

1078

1079

2313

1080

4-(-CONH2)

2314

1081

4-{-CON(Me)2}

2315

1082

4-{-C(=NH)NH2}

2316

1083

4-(-OMe)

2317

1084

1085

2318

1086

4-(-NHMe)

2319

1087

4-(-NHAc)

2320

1088

1089

2321

1090

4-(-SMe)

2322

1091

1092

2323

1093

1094

2324

1095

1096

2325

1097

1098

2326
5-(-CONH2)
—H

2327
5-(-CONH2)
4-(-F)

2328
4-(-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)

1099

2337
5-(-CONH2)
4-(-CONH2)

2338
5-(-CONH2)
4-{-CON(Me)

2339
5-(-CONH2)
4-{-C(=NH)NH2}

2340
5-(-CONH2)
4-(-OMe)

2341
5-(-CONH2)

1100

2342
5-(-CONH2)
4-(-NHMe)

2343
5-(-CONH2)
4-(-NHAc)

2344
5-(-CONH2)

1101

2345
5-(-CONH2)
4-(-SMe)

2346
5-(-CONH2)

1102

2347
5-(-CONH2)

1103

2348
5-(-CONH2)

1104

2349
5-(-CONH2)

1105

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}

1106

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}

1107

2366
5-{-CON(Me)2}
4-(-NHMe)

2367
5-{-CON(Me)2}
4-(-NHAc)

2368
5-{-CON(Me)2}

1108

2369
5-{-CON(Me)2}
4-(-SMe)

2370
5-{-CON(Me)21

1109

2371
5-{-CON(Me)2}

1110

2372
5-{-CON(Me)2}

1111

2373
5-{-CON(Me)2}

1112

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)

1113

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)

1114

2390
5-(-OMe)
4-(-NHMe)

2391
5-(-OMe)
4-(-NHAc)

2392
5-(-OMe)

1115

2393
5-(-OMe)
4-(-SMe)

2394
5-(-OMe)

1116

2395
5-(-OMe)

1117

2396
5-(-OMe)

1118

2397
5-(-OMe)

1119

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

1120

4-(-F)

2406

1121

4-(-Cl)

2407

1122

4-(-Me)

2408

1123

4-(-CF3)

2409

1124

4-(-CO2H)

2410

1125

4-(-CO2Me)

2411

1126

1127

2412

1128

4-(-SMe)

2413

1129

1130

2414

1131

1132

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)
14-{-CON(Me)2}

2422

1133

4-(-F)

2424

1134

4-(-Me)

2425

1135

4-(-CF3)

2426

1136

4-(-Ac)

2427

1137

4-(-CONH2)

2428

1138

4-{-CON(Me)2}

2429

1139

4-(-F)

2430

1140

4-(-Cl)

2431

1141

4-(-Me)

2432

1142

4-(-CF3)

2433

1143

4-(-Ac)

2434

1144

4-(-CONH2)

2435

1145

4-{-CON(Me)2}

2436

1146

4-(-F)

2437

1147

4-(-Cl)

2438

1148

4-(-Me)

2439

1149

4-(-CF3)

2440

1150

4-(-CONH2)

2441

1151

4-{-CON(Me)2}

2442

1152

4-(-SMe)

2443

1153

1154

2444

1155

1156

2445

1157

4-(-F)

2446

1158

4-(-Cl)

2447

1159

4-(-Me)

2448

1160

4-(-CF3)

2449

1161

4-(-CONH2)

2450

1162

4-{-CON(Me)2}

2451

1163

2452

1164

1165

2453

1166

1167

[2006]

216

TABLE 215

1168

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

1169

1170

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

1171

1172

2476
3-(—NHMe)
3-(—NHMe)

2477
3-(—NHAc)
3-(—NHAc)

2478

1173

1174

2479
3-(—SMe)
3-(—SMe)

2480

1175

1176

2481

1177

1178

2482

1179

1180

2483

1181

1182

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

1183

1184

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

1185

1186

2507
4-(—NHMe)
4-(—NHNe)

2508
4-(—NHAc)
4-(—NHAc)

2509

1187

1188

2510
4-(—SMe)
4-(—SMe)

2511

1189

1190

2512

1191

1192

2513

1193

1194

2514

1195

1196

[2007]

217

TABLE 216

1197

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

1198

1199

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

1200

1201

2535
3-(—NHMe)
3-(—NHMe)

2536
3-(—NHAc)
3-(—NHAc)

2537

1202

1203

2538
3-(—SMe)
3-(—SMe)

2539

1204

1205

2540

1206

1207

2541

1208

1209

2542

1210

1211

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

1212

1213

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

1214

1215

2562
4-(—NHMe)
4-(—NHMe)

2563
4-(—NHAc)
4-(—NHAc)

2564

1216

1217

2565
4-(—SMe)
4-(—SMe)

2566

1218

1219

2567

1220

1221

2568

1222

1223

2569

1224

1225

[2008]

218

TABLE 217

1226

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

1227

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

1228

2589
4-Py
4-(—CONH2)

2590
3-Py
4-{—CON(Me)2}

[2009]

219

TABLE 218

1229

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

1230

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

1231

2610
3-Py
4-(—CONH2)

2611
3-Py
4-{—CON(Me)2}

[2010]

220

TABLE 219

Example No.
328
1H NMR (δ) ppm

1232

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), 4.2-3.40 (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

1233

400MHz, DMSO-d6 9.80(1H, brs), 8.32(1H, s), 8.3O (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

1234

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)

[2011]

221

TABLE 220

Example No.
331
1H NMR (δ) ppm

1235

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

1236

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, br t, 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

1237

300MHz, DMSO-d6 8.30(1H, s), 8.24 and 8.03(2H, A Bq, 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, br t, J=12.1Hz), 4.05-3.15(5H, br m), 3.27(3H, s), 2.39-2.20(2H, m), 2.07-1.75(6H, m), 1.70-1.5 8(1H, m)1.55-1.20(5H, m)

Purity
>90% (NMR)

MS
678(M + 1)

[2012]

222

TABLE 221

Example No.
334
1H NMR (δ) ppm

1238

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

1239

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)

[2013]

223

TABLE 222

HCV polymerase

Ex.
inhibitory activity

No.
IC50 [μM]

340
0.017

341
0.025

342
0.015

343
0.017

344
0.016

345
0.012

346
0.025

347
0.022

348
0.013

349
0.021

350
0.020

351
0.019

352
0.013

353
0.023

354
0.013

355
0.015

356
0.016

357
0.019

358
0.017

359
0.015

360
0.014

361
0.028

362
0.020

363
0.11

364
0.12

365
0.020

366
0.024

367
0.011

368
0.024

369
0.022

370
0.017

371
0.015

372
0.033

373
0.013

374
0.013

375
0.012

376
0.014

377
0.012

378
0.018

379
0.021

[2014]

224

TABLE 223

HCV polymerase

Ex.
inhibitory activity

No.
IC50 [μM]

380
0.023

381
0.011

382
0.015

383
0.013

384
0.016

385
0.019

386
0.018

387
0.025

388
0.020

389
0.012

390
0.014

391
0.017

392
0.014

393
0.011

394
0.019

395
0.016

396
0.025

397
0.037

398
0.077

399
0.032

409
0.020

410
0.018

411
0.015

412
0.019

413
0.026

414
0.024

415
0.019

416
0.024

417
0.029

418
0.016

419
0.021

420
0.015

421
0.017

422
0.017

423
0.017

424
0.020

425
0.026

426
0.053

427
0.020

428
0.026

[2015]

225

TABLE 224

HCV polymerase

inhibitory

Ex.
activity

No.
IC50 [μM]

429
0.017

430
0.017

431
0.015

432
0.022

433
0.014

434
0.011

435
0.012

436
0.026

440
0.070

442
0.024

443
0.030

445
0.33

446
0.016

447
0.12

448
0.20

449
0.025

450
0.040

451
0.031

452
0.028

454
0.013

455
0.015

456
0.017

457
0.015

458
0.015

459
0.014

460
0.017

461
0.021

462
0.028

463
0.026

464
0.030

465
0.033

466
0.023

467
0.032

468
0.028

469
0.024

502
0.024

503
0.196

601
0.32

701
0.052

[2016]

226

TABLE 225

Example No.

341
1H NMR (δ) ppm

1240

300MHz, DMSO-d6 8.29(1H, d, J=1.5Hz), 8.25(1H, d, J=8.7Hz, 8.03(1H, dd, J=8.7Hz), 7.72and7.22(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), 0.94and0.92 (total3H, each s)

Purity
>90% (NMR)

MS
662 (M + 1)

342
1H NMR (δ) ppm

1241

300MHz, 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), 7.70and7.22(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

1242

300 MHz, 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, 2), 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)

[2017]

227

TABLE 226

Example No.

344
1H NMR (δ) ppm

1243

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

1244

300MHz, DMSO-d6 8.29(1H, d, =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

1245

300Mz, DMSO-d6 8.26(1H, d, J=1.9Hz), 8.23(1H, d, J=1.5Hz), 8.08-9.02(2H, m), 7.91(1H, dd, J=8.7, 1.5Hz), 7.63and7.16(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),0.97and0.95(total6H, each s)

Purity
>90% (NMR)

MS
621 (M + 1)

[2018]

228

TABLE 227

Example No.

347
1H NMR (δ) ppm

1246

300Mz, DMSO-d6 8.26(1H, s), 8.22(1H, s), 8.06 (1H, s), 8.05(1H, d, J=8.0Hz), 7.94and7.85(2H, ABq, J=8.8Hz), 7.59and7.15(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

1247

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, J8.7Hz), 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

1248

300MHz, DMSO-d6 8.41(1H, d, J=1.5Hz), 8.33 (1H, d, J=4.5Hz), 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)

[2019]

229

TABLE 228

Example No.
350
1H NMR (δ) ppm

1249

300 MHz, DMSO-d6 8.36 (1H, d, J=7.7 Hz), 8.29 (1H, s), 8.23 (1H, d, J=8.8 Hz), 8.02 (1H, d, J=8.6 Hz), 7.94 (1H, d, J=7.9 Hz), 7.84 (1H, d, J=1.6 Hz), 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=6.5 Hz)

Purity
>90% (NMR)

MS
622 (M + 1)

Example No.
351
1H NMR (δ) ppm

1250

300 MHz, DMSO-d6 8.29 (1H, s), 8.24 (1H, d, J=8.8 Hz), 8.02 (1H, d, J=8.6 Hz), 7.80-7.65 (3H, m), 7.55-7.45 (5H, m), 7.32 (1H, d, J=1.5 Hz), 7.22 (2H, d, J=8.8 Hz), 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

1251

300 MHZ, DMSO-d6 13.20 (1H, brs), 8.30-8.24 (2H, m), 8.13 (1H, s), 8.04 (1H, d, J=8.7 Hz), 7.94 (1H, d, J=8.0 Hz), 7.75-7.70 (3H, m), 7.55-7.43 (5H, m), 7.25 (2H, d, J=8.7 Hz), 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)

[2020]

230

TABLE 229

Example No.
353
1H NMR (δ) ppm

1252

300 MHz, DMSO-d6 8.41 (1H, s), 8.33-8.29 (2H, m), 8.16 (1H, d, J=8.2 Hz), 8.07 (1H, d, J=8.6 Hz), 7.77 (2H, d, J=8.7 Hz), 7.62 (1H, d, J=8.0 Hz), 7.59-7.51 (4H, m), 7.28 (2H, d, J=8.8 Hz), 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
about 90% (NMR)

MS
634 (M + 1)

Example No.
354
1H NMR (δ) ppm

1253

300 MHz, DMSO-d6 8.31 (1H, s), 8.25 (1H, d, J=9.0 Hz), 8.03 (1H, d, J=8.7 Hz), 7.76-7.71 (3H, m), 7.51-7.47 (5H, m), 7.33 (1H, s), 7.23 (2H, d, J=9.0 Hz), 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

1254

300 MHz, DMSO-d6 8.62 (1H, t, J=5.7 Hz), 8.32-8.30 (2H, m), 8.25 (1H, d, J=8.7 Hz), 8.03 (1H, d, J=8.7 Hz), 7.96(1H, d, J=8.1 Hz), 7.86 (1H, s), 7.75 (1H, d, J=9.0 Hz), 7.72 (2H, d, J=9.0 Hz), 7.55-7.50 (4H, m), 7.22 (2H, d, J=9.0 Hz), 5.17 (2H, s), 4.35 (1H, m), 3.52 (2H, t, J=6.0 Hz), 3.36 (2H, t, J=6.0 Hz), 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)

[2021]

231

TABLE 230

Example No.
356
1H NMR (δ) ppm

1255

300 Mz, DMSO-d6 9.30 (1H, t, J=5.9 Hz), 8.54 (2H, d, J=5.9 Hz), 8.22 (1H, s), 8.02-7.79 (5H, m), 7.59 and 7.12 (4H, ABq, J=8.6 Hz), 7.55 (4H, s), 7.37 (2H, d, J=5.9 Hz), 5.15 (2H, s), 4.54 (2H, d, J=5.7 Hz), 4.26 (m, brt, J=12.8 Hz), 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

1256

300 Mz, DMS0-d6 8.31 (1H, d, J=1.5 Hz), 8.43 (1H, d, J=8.4 Hz), 8.03 (1H, dd, J=8.4, 1.5 Hz), 7.74 (1H, d, J=8.1 Hz), 7.73 and 7.23 (4H, ABq, J=9.0 Hz), 7.54-7.51 (5H, m), 7.37 (1H, d, J=1.8 Hz), 5.14 (2H, s), 4.36 (1H, brt, J=12.1 Hz), 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

1257

300 MHz, DMSO-d6 8.33 (1H, s), 8.31 (1H, d, J=8.7 Hz), 8.14 (1H, s), 8.07(1H, d, J=8.7 Hz), 7.92 (1H, d, J=8.0 Hz), 7.76 (2H, d, J=8.7 Hz), 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
about 90% (NMR)

MS
635 (M + 1)

[2022]

232

TABLE 231

Example No.
359
1H NMR (δ) ppm

1258

300 MHz, DMSO-d6 8.31 (1H, s), 8.25 (1H, d, J=8.7 Hz), 8.10-7.90 (2H, m), 7.82 (1H, dd, J=7.8 Hz, 1.8 Hz), 7.72 (2H, d, J=9.0 Hz), 7.63 (1H, d, J=8.1 Hz), 7.23 (2H, d, J=9.0 Hz), 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

1259

300 MHz, DMSO-d6 8.33 (1H, s), 8.30 (1H, d, J=8.5 Hz), 8.06 (1H, d, J=10.1 Hz), 8.80-8.65 (3H, m), 8.60-8.45 (3H, m), 7.42 (1H, d, J=7.8 Hz), 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

1260

300 MHz, DMSO-d6 8.35-8.20 (2H, m), 8.05 (1H, d, J=8.7 Hz), 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)

[2023]

233

TABLE 232

Example No.
362
1H NMR (δ) ppm

1261

300 MHz, DMSO-d6 8.33 (1H, s), 8.29 (1H, d, J=8.7 Hz), 8.06 (1H, d, J=8.7 Hz), 7.79 (2H, d, J=9.0 Hz), 7.76 (1H, d, J=9.0 Hz), 7.60 (1H, d, J=8.1Hz), 7.53 (1H, dd, J=1.7 Hz, 8.0 Hz), 7.35 (2H, d, J=8.7 Hz), 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

1262

300 MHz, DMSO-d6 8.28 (1H, d, J=1.3 Hz), 8.20-8.10 (2H, m), 8.98 (1H, d, J=8.6 Hz), 7.90-7.80 (2H, m), 7.75 (2H, d, J=8.7 Hz), 7.36 (2H, d, J=8.7 Hz), 7.04 (1H, d, J=1.3 Hz), 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

1263

300 MHz, DMSO-d6 8.31 (1H, s), 8.26 (1H, d, J=8.7 Hz), 8.13 (1H, s), 8.04 (1H, d, J=9.0 Hz), 7.90-7.70 (4H, m), 7.65 (1H, s), 7.39 (2H, d, J=9.0 Hz), 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)

[2024]

234

TABLE 233

Example No.
365
1H NMR (δ) ppm

1264

300 MHz, DMSO-d6 8.28 (1H, s), 8.23 (1H, s), 8.17 (1H, d, J=8.7 Hz), 8.00 (2H, t, J=6.9 Hz), 7.69 (2H, d, J=8.4 Hz), 7.60-7.45 (5H, m), 7.21 (2H, d, J=8.4 Hz), 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

1265

300 MHz, DMSO-d6 8.26 (1H, s), 8.17 (1H, s), 8.11 (1H, d, J=8.7 Hz), 7.95 (2H, d, J=9.6 Hz), 7.70-7.40 (8H, m), 7.19 (2H, d, J=8.4 Hz), 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

1266

300 Mz, DMSO-d6 8.42 (1H, d, J=1.9 Hz), 8.30 (1H, J=, 1.5 Hz), 8.27 (1H, d, J=8.7 Hz), 8.18 (1H, dd, J=7.9, 1.9 Hz), 8.04 (1H, dd, J=8.7, 1.5 Hz), 7.75 and 7.29 (4H, ABq, J=8.9 Hz) 7.63 (1H, d, J=7.9 Hz), 5.23 (2H, s), 4.36 (1H, brt, J=12.3 Hz) 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)

[2025]

235

TABLE 234

Example No.
368
1H NMR (δ) ppm

1267

300 Mz, DMSO-d6 8.30 (1H, d, J=1.5 Hz), 8.25 (1H, d, J=8.6 Hz), 8.04 (1H, dd, J=8.6, 1.5 Hz), 7.93 and 7.67 (4H, ABq, J=8.1 Hz), 7.80 (1H, d, J=2.2 Hz), 7.72 and 7.21 (4H, A′ B′ q, J=8.6 Hz), 7.60 (1H, dd, J=8.1, 2.2 Hz), 7.44 (1H, d, J=8.1 Hz), 5.13 (2H, s), 4.34 (1H, brt, J=11.7 Hz), 2.37-2.19 (2H, brm), 2.09-1.80 (4H, brm), 1.72-

#1.60 (1H,brm), 150-1.21 (3H, brm)

Purity
>90% (NMR)

MS
562 (M + 1)

Example No.
369
1H NMR (δ) ppm

1268

300 Mz, DMSO-d6 8.30 (1H, d, J=1.5 Hz), 8.25 (1H, d, J=8.6 Hz), 8.16 and 7.72 (4H, ABq, J=8.4 Hz), 8.13 (1H, dd, J=8.6, 1.5 Hz), 7.80 (1Hd, J=2.2 Hz), 7.70 and 7.24 (4H, A′ B′ q, J=8.8 Hz), 7.61 (1H, dd, J=8.1, 2.2 Hz), 7.48 (1H, d, J=8.1 Hz), 5.17 (2H, s), 4.33 (1H, brt, J=12.1 Hz), 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

1269

300 MHz, DMSO-d6 10.94 (1H, brs), 8.33 (1H, s), 8.27 (1H, d, J=8.7 Hz), 8.04 (1H, d, J=8.7 Hz), 7.74 (2H, d, J=8.4 Hz), 7.56-7.29 (6H, m), 7.23 (2H, d, J=8.7 Hz), 7.13 (1H, d, J=8.7 Hz), 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)

[2026]

236

TABLE 235

Example No.
371
1H NMR (δ) ppm

1270

300 MHz, DMSO-d6 8.31 (1H, d, J=1.5 Hz), 8.17 (1H, d, J=9.0 Hz), 7.99 (1H, dd, J=8.7 Hz, 1.4 Hz), 7.70-7.55 (2H, m), 7.50-7.30 (6H, m), 7.19 (1H, dd, J=12.0 Hz, 2.2 Hz), 7.06 (1H, dd, J=8.6 Hz, 2.2 Hz), 5.08 (2H, 4.10 (1H, m), 3.68 (2H, brt, J=5.2), 2.50 (2H, brt, J=1.8 Hz), 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

1271

300 Mz, DMSO-d6 8.29 (1H, d, J=1.5 Hz), 8.11 (1H, d, J=8.6 Hz), 7.96 (1H, dd, J=8.6, 1.5 Hz), 7.89 (1H, s), 7.78 and 7.56 (4H, ABq, J=8.4 Hz), 7.69 (1H, s), 7.66 (1H, t, J=8.8 Hz), 7.31 (1H, dd, J=12.1, 2.2 Hz), 7.18 (1H, dd, J=8.8, 2.2 Hz), 5.37 (2H, s), 4.08 (1H, brt, J=11.0 Hz), 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

1272

300 MHz, DMSO-d6 11.40 (1H, brs), 9.25 (2H, brs), 8.29 (1H, d, J=1.3 Hz), 8.12-8.09 (2H, m), 7.96 (1H, d, J=8.7 Hz), 7.88 (1H, dd, J=1.8 Hz, 8.1 Hz), 7.67-7.63 (2H, m), 7.56 (2H, d, J=8.7 Hz), 7.51 (2H, d, J=8.7 Hz), 7.17 (1H, d, J=12.0 Hz), 7.05 (1H, d, J=8.6 Hz), 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)

[2027]

237

TABLE 236

Example No.
374 1H NMR (δ) ppm

1273

300 MHz, DMSO-d6 13.21 (1H, brs), 8.31 (1H, d, J=1.4 Hz), 8.18-8.15 (2H, m), 7.99 (1H, d, J=8.7 Hz), 7.94 (1H, dd, J=1.8 Hz, 8.0 Hz) 7.70-7.53 (6H, m), 7.17 (1H, d, J=12.0 Hz), 7.05 (1H, d, J=8.6 Hz), 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

1274

300 MHz, DMSO-d6 8.32 (1H, d, J=1.5 Hz), 8.23 (1H, d, J=1.5 Hz), 8.19 (1H, d, J=9.0 Hz), 8.03-7.98 (2H, m), 7.68 (1H, t, J=8.4 Hz), 7.60 (1H, d, J=8.1 Hz), 7.56 (2H, d, J=9.3 Hz), 7.53 (2H, d, J=9.0 Hz), 7.22 (1H, dd, J=2.1 Hz, 12.0 Hz), 7.09 (1H, dd, J=2.1 Hz, 8.4 Hz), 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

1275

300 MHz, DMSO-d6 13.61 (1H, brs), 8.34-8.30 (2H, m), 8.21 (1H, d, J=8.7 Hz), 8.07 (1H, dd, J=1.8 Hz, 8.1 Hz), 8.02 (1H, dd, J=1.5 Hz, 8.7 Hz), 7.69 (1H, t, J=8.4 Hz), 7.57-7.49 (5H, m), 7.22 (1H, dd, J=2.7 Hz, 12.0 Hz), 7.09 (1H, dd, J=2.4 Hz, 9.0 Hz), 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)

[2028]

238

TABLE 237

Example No.
377
1H NMR (δ) ppm

1276

300 Mz, DMSO-d6 8.60 (1H, d, J=4.5 Hz), 8.29 (1H, d, J=1.5 Hz), 8.14 (1H, d, J=8.9 Hz), 8.13 (1H, d, J=1.5 Hz), 7.98 (1H, dd, J=8.9, 1.5 Hz), 7.94 (1H, dd, J=8.1, 1.5 Hz), 7.64 (1H, t, J=8.7 Hz), 7.52 and 7.49 (4H, ABq, J=9.0 Hz), 7.46 (1H, d, J=8.1 Hz), 7.18 (1H, dd, J=12.1, 2.3 Hz), 7.05 (1H, dd, J=8.7, 2.3 Hz), 5.13 (2H, s), 4.08 (1H, brt, J=12.1 H), 2.95-

#2.84 (1H, m), 2.31-2.14 (2H, brm), 1.97-1.78

Purity
>90% (NMR)

MS
638 (M + 1)

Example No.
378
1H NMR (δ) ppm

1277

300 Mz, DMSO-d6 8.77 (1H, d, J=1.4 Hz), 8.30 (1H, d, J=1.4 Hz), 8.16 (1H, d, J=1.8 Hz), 8.13 (1H, d, J=8.4 Hz), 7.98 (2H, dd, J=8.4, 1.8 Hz), 7.65 (1H, t, J=8.4 Hz), 7.53 and 7.49 (4H, ABq, J=8.8 Hz), 7.47 (1H, d, J=7.7 Hz), 7.18 (1H, dd, J=12.1, 2.2 Hz), 7.05 (1H, dd, J=8.4, 2.2 Hz), 5.13 (2H, s), 4.53-4.40 (1H, m), 4.09 (1H, brt, J=12.8 Hz),

# 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

1278

300 Mz, DMSO-d6 8.29 (1H, d, J=1.1 Hz), 8.11 (1H, d, J=4.5 Hz), 8.11 (1H, d, J=8.8 Hz), 7.98-7.91 (2H, m), 7.89 (1H, s), 7.63 (1H, t, J=8.8 Hz), 7.52 and 7.48 (4H, ABq, J=8.6 Hz), 7.44 (1H, d, J=8.1 Hz), 7.17 (1H, dd, J=12.1, 2.2 Hz), 7.04 (1H, dd, J=8.8, 2.2 Hz), 5.12 (2H, s), 4.07 (1H, brt, J=12.4 Hz), 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)

[2029]

239

TABLE 238

Example No.
380
1H NMR(67 ) ppm

1279

300 Mz, DMSO-d6 8.62(1H, t, J = 5.5 Hz), 8.30(1H, d, J = 1.5 Hz), 8.17 (1H, d, J = 1.8 Hz), 8.14(1H, d, J = 8.8 Hz),7.98 (1H, dd, J = 8.1, 1.8 Hz), 7.64(1H, t, J = 8.8 Hz), 7.52 and 7.50(4H, ABq, J = 8.8 Hz), 7.48(1H, d, J = 8.1 Hz), 7.18(1H, dd, J = 12.1, 2.2 Hz), 7.05(1H, dd, J = 8.8, 2.2 Hz), 5.14(2H, s), 4.08(1H, brt, J = 12.1 Hz), 3.13(1H, t, J = 6.2 Hz), 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

1280

300 Mz, DMSO-d6 8.29(1H, d, J = 1.5 Hz), 8.27 (1H, d, J = 8.3 Hz), 8.18(1H, d, J = 1.9 Hz), 8.13 (1H, d, J = 8.7 Hz), 8.01-7.96(2H, m), 7.64(1H, t, J = 8.7 Hz), 7.52 and 7.49(1H, ABq, J = 8.8 Hz), 7.49(1H, d, J = 7.9 Hz), 7.18 (1H, dd, J = 12.1, 2.3 Hz), 7.05 1H, dd, J = 8.7, 2.3 Hz), 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(total3H, each s)

Purity
>90% (NMR)

MS
656 (M + 1)

Example No.
382
1H NMR(δ) ppm

1281

300 Mz, DMSO-d6 8.30(1H, d, J = 1.5 Hz), 8.13(1H, d, J = 8.8 Hz), 8.09(1H, d, J = 1.5 Hz), 7.98(1H, dd, J = 8.8, 1.5 Hz), 7.86(1H, dd, J = 8.1, 1.5 Hz), 7.64(1H, J = 8.8 Hz), 7.55-7.47(5H, m), 7.17(1H, dd, J = 12.1, 2.2 Hz), 7.05(1H, dd, J = 8.8, 2.2 Hz), 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)

[2030]

240

TABLE 239

Example No.
383
1H NMR(δ) ppm

1282

300 Mz, DMSO-d6 8.57(1H, t, J = 5.5 Hz), 8.29(1H, d, J = 1.4 Hz), 8.19(1H, d, J = 1.5 Hz), 8.12(1H, d, J = 9.2 Hz), 8.01-7.95(2H, m), 7.64(1H, t, J = 8.8 Hz), 7.53 and 7.50(4H, ABq, J = 8.8 Hz), 7.48(1H, d, J = 7.7 Hz), 7.17 (1H, dd, J = 12.1, 2.2 Hz), 7.04(1H, dd, J = 8.8, 2.2 Hz), 5.14(2H, s), 4.08(1H, brt, J = 13.9 Hz), 3.70-3.66(1M, 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

1283

300 Mz, DMSO-d6 8.30(1H, d, J = 1.5 Hz), 8.14(1H, d, J = 8.4 Hz), 7.98(1H, dd, J = 8.4, 1.5 Hz), 7.68(1H, brs), 7.63(1H, t, J = 8.4 Hz), 7.51(5H, s), 7.43 (1H, d, J = 8.1 Hz), 7.17(1H, dd, J = 12.5, 1.8 Hz), 7.03(1H, dd, J = 8.4, 1.8 Hz), 4.08(1H, brt, J = 11.4 Hz), 3.50 and 3.30 (total2H, 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

1284

300 Mz, DMSO-d6 8.29(1H, d, J = 1.5 Hz), 8.12(1H, d, J = 8.8 Hz), 7.97(1H, dd, J = 8.8, 1.5 Hz), 772-7.60(2H, m), 7.55-7.42(6H, m), 7.16(1H, d, J = 11.1 Hz), 7.03(1H, d, J = 8.4 Hz), 5.15(2H, s), 4.07(1H, brt, J = 12.5 Hz), 3.44 and 3.22(total2H, 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(total3H, each brs)

Purity
>90% (NMR)

MS
654 (M + 1)

[2031]

241

TABLE 240

Example No.
386
1H NMR(δ) ppm

1285

300 Mz, DMSO-d6 8.29(1H, d, J = 1.5 Hz), 8.12(1H, d, J = 8.7 Hz), 7.97(1H, dd, J = 8.7, 1.5 Hz) 7.74-7.60(2H, m), 7.54-7.42(6H, m), 7.17(1H, dd, J = 12.1, 2.2 Hz), 7.02(1H, dd, J = 8.3, 2.2 Hz), 5.15(2H, s), 4.06(1H, brt, J = 12.8 Hz), 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

1286

300 Mz, DMSO-d6 8.29(1H, s), 8.14 and 7.97(2H, ABq, J = 8.7 Hz), 7.63 (1H, s),7.63 (1H, t, J = 8.7 Hz), 7.51-7.41 (6H, m), 7.16(1H, dd, J = 12.1, 1.9 Hz), 7.02(1H, dd, J = 8.7, 1.9 Hz), 5.16(2H, s), 4.26(2H, brs), 4.07(1H, brt, J = 12.1 Hz), 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

1287

300 MHz, DMSO-d6 8.58(1H, m), 8.29(1H, s), 8.20-7.90(2H, m), 7.64(1H < t, J = 8.4 Hz), 7.60-7.40 (5H, m), 7.15(1H, d, J = 12.3 Hz), 7.04(1H, d, J = 8.4 Hz), 5.13(2H, 1s), 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 = 6.9 Hz)

Purity
>90% (NMR)

MS
654 (M + 1)

[2032]

242

TABLE 241

Example No.
389
1H NMR(δ) ppm

1288

300 MHz, DMSO-d6 8.60(1H, m), 8.29(1H, s), 8.20-7.90(4H, m), 7.64(1H, t, J = 9.0 Hz), 7.60-7.40(5H, m), 7.17(1H, d, J = 12.0 Hz), 7.04(1H, d, J = 8.7 Hz), 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 = 7.5 Hz)

Purity
>90% (NMR)

MS
640 (M + 1)

Example No.
390
1H NMR(δ) ppm

1289

300 MHz, 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 = 8.4 Hz), 7.60-7.40(5H, m), 7.18(1H, d, J = 12.0 Hz), 7.05(1H, d, J = 8.4 Hz), 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 = 7.2 Hz)

Purity
>90% (NMR)

MS
626 (M + 1)

Example No.
391
1H NMR(δ) ppm

1290

400 NHz, DMSO-d6 8.54(1H, s), 8.31(1H, s), 8.19(1H, d, J = 8.6 Hz), 8.01(1H, d, J = 8.6 Hz), 7.81(1H, d, J = 2.1 Hz), 7.64(1H, t, J = 8.4 Hz), 7.61(1H, dd, J = 2, 3 Hz, 8.4 Hz), 7.47(2H, d, J = 8.6 Hz), 7.43(2H, d, J = 8.8 Hz), 7.25(1H, d, J = 8.4 Hz), 7.17 (1H, dd, J = 2.3 Hz, 12.1 Hz), 7.05(1H, dd, J = 2.3 Hz, 8.6 Hz), 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)

[2033]

243

TABLE 242

Example No.
392
1H NMR(δ) ppm

1291

300 Mz, DMSO-d6 8.79(1H, s), 8.29(1H, d, J = 1.5 Hz), 8.13(1H, d, J = 8.8 Hz), 7.98(1H, dd, J = 8.8, 1.5 Hz), 7.80(1H, d, 2.2 Hz), 7.63(1H, t, J = 8.4 Hz), 7.61(1H, dd, J = 8.2, 2.2 Hz), 7.47 and 7.43(4H, ABq, J = 8.8 Hz), 7.26(1H, d, J = 8.2 Hz), 7.14 (1H, dd, J = 12.1, 2.2 Hz), 7.02(1H, dd, J = 8.4, 2.2 Hz), 5.05(2H, s), 4.08(1H, brt, J = 12.1 Hz), 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

1292

400 MHz, DMSO-d6 8.94(1H, s), 8.31(1H, d, J = 1.0 Hz), 8.18(1H, d, J = 8.6 Hz), 8.00(1H, dd, J = 1.4 Hz, 8.8 Hz),7.71(1H, d, J = 2.2 Hz), 7.66(1H, t, J = 8.6 Hz), 7.52(1H, dd, J = 2.4 Hz, 8.6 Hz), 7.46(2H, d, J = 8.6 Hz), 7.42(2H, d, J = 8.2 Hz), 7.24(1H, d, J = 8.4Hz), 7.16(1H, d, J = 12.1 Hz), 7.04(1H, dd, J = 2.4 Hz, 8.8 Hz), 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

1293

300 MHz, DMSO-d6 8.93(1H, s), 8.31(1H, d, J = 1.4 Hz), 8.19(1H, d, J = 8.8 Hz), 8.01(1H, d, J = 8.7 Hz), 7.71(1H, d, J = 2.2 Hz), 7.66(1H, t, J = 8.5 Hz), 7.51(1H, dd, J = 2.2 Hz, 8.4 Hz), 7.46(2H, d, J = 8.6 Hz), 7.41(2H, d, J = 8.7 Hz), 7.23(1H, d, J = 8.4 Hz), 7.16(1H, d, J = 12.2 Hz), 7.05(1H, d, J = 8.7 Hz), 5.05(2H, s), 4.13(1H, m), 3.12(2H, q, J = 7.2 Hz), 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 = = 7.2 Hz)

Purity
>90% (NMR)

MS
641 (M + 1)

[2034]

244

TABLE 243

Example No.
395
1H NMR(δ) ppm

1294

300 MHz, DMSO-d6 8.83(1H, s), 8.32(1H, d, J = 1.4 Hz), 8.21(1H, d, J = 8.8 Hz), 8.02(1H, dd, J = 1.4 Hz, 8.7 Hz), 7.71 (1H, d, J = 2.1 Hz), 7.68(1H, t, J = 8.6 Hz), 7.49(1H, dd, J = 2.2 Hz, 8.4 Hz), 7.46(2H, d, J = 8.4 Hz), 7.41 (2H, d, J = 8.6 Hz), 7.23(1IH, d, J = 8.4 Hz), 7.17(1H, d, J = 12.2 Hz), 7.06(1H, d, J = 8.7 Hz), 6.30(1H, brs), 5.05(2H, s), 4.14(1H, m), 3.77(1H, sept, J = 6.5 Hz),

# 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 = 6.5 Hz)

Purity
>90% (NMR)

MS
655 (M + 1)

Example No.
396
1H NMR(δ) ppm

1295

300 MHz, DMSO-d6 8.37(1H, d, J = 7.3 Hz), 8.25 (1H, s), 8.15(1H, s), 7.97(2H, d, J = 8.8 Hz), 7.88(1H, d, J = 8.8 Hz), 7.58-7.47(4H, m), 7.31(1H, m), 7.11(1H, dd, J = 8.4, 2.2 Hz), 6.98(1H, dd, = 8.4, 2.2), 5.13(2H, s), 4.13(1H, q, J = 6.6 Hz), 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 = 6.6 Hz)

Purity
>90% (NMR)

MS
642 (M + 1)

Example No.
397
1H NMR(δ) ppm

1296

300 MHz, DMSO-d6 8.40(1H, d, J = 37.9 Hz), 8.28(1H, d, J = 1.9 Hz), 8.15(1H, d, J = 1.9 Hz), 8.11(1H, d, J = 8.7 Hz), 7.96(2H, m), 7.56(1H, t, J = 8.7 Hz), 7.45(3H, m), 7.18(1H, m), 7.08(1H, dd, J = 12.1, 1.9 Hz), 6.96(1H, dd, J = 8.3, 2.3 Hz), 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 = 6.4 Hz)

Purity
>90% (NMR)

MS
642 (M + 1)

[2035]

245

TABLE 244

Example No.
398
1H NMR(δ) ppm

1297

8.41(1H, d, J = 8.1 Hz), 8.29(1H, d, J = 1.5 Hz), 8.17(1H, d, J = 1.8 Hz), 8.12(1H, d, J = 8.4 Hz), 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, 2.2 Hz), 7.05(1H, dd, J = 8.8 2.2 Hz), 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

1298

300 Mz, DMSO-d6 8.39(1H, d, J = 7.7 Hz), 8.29(1H, d, J = 1.5 Hz), 8.16(1H, d, J = 1.8 Hz), 8.11(1H, d, J = 8.8 Hz), 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, 2.2 Hz), 7.04(1H, dd, J = 8.8, 2.2 Hz), 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.
399
1H NMR(δ) ppm

1299

300 MHz, DMSO-d6 8.39(1H, d, J = 7.7 Hz), 8.29(1H, s), 8.17(1H, d, J = 1.5 Hz), 8.11(1H, d, J = 8.8 Hz), 7.98(2H, m), 7.73(2H, m), 7.64(1H, t, J = 8.4 Hz), 7.52(1H, d, J = 8.0 Hz), 7.46(1H, dd, J = 8.4, 1.8 Hz), 7.18(1H, dd, J = 11.9, 2.0 Hz), 7.05(1H, dd, J = 8.6, 2.4 Hz), 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 = 6.6 Hz)

Purity
>90% (NMR)

MS
642 (M + 1)

[2036]

246

TABLE 245

Example No.
401
1H NMR(δ) ppm

1300

300 MHz, DMSO-d6 8.38(1H, d, J = 7.8 Hz), 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 = 12.3 Hz), 6.97(1H, d, J = 10.2 Hz), 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 = 6.6 Hz)

Purity
>90% (NMR)

MS
658 (M + 1)

Example No.
402
1H NMR(6) ppm

1301

300 MHz, DMSO-d6 8.25(1H, s), 8.03(1H, d, J = 8.7 Hz), 7.91(1H, d, J = 8.7 Hz), 7.83(1H, s), 7.70-7.35(6H, m), 7.04(1H, d, J = 12.0 Hz), 6.93(1H, d, J = 8.4 Hz), 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

1302

400 MHz, DMSO-d6 8.25(1H, s), 8.08(1H, d, J = 8.4 Hz), 7.92(1H, d, J = 9.2 Hz), 7.79(1H, s), 7.66-7.49(4H, m), 7.42(1H, d, J = 7.6 Hz), 7.31-7.28(1H, m), 7.14(1H, d, J = 11.3 Hz), 6.99(1H, d, J = 8.8 Hz), 5.13(2H, s), 4.02(1H, m) 3.45-3.33(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)

[2037]

247

TABLE 246

Example No.
404
1H NMR(δ) ppm

1303

400 MHz, DMSO-d6 8.41(1H, d, J = 7.6 Hz), 8.32(1H, d, J = 1.5 Hz), 8.20(1H, d, J = 8.6 Hz), 8.17(1H, d, J = 1.7 Hz), 8.00(1H, dt, J = 8.8 Hz, 1.5 Hz), 7.71-7.64(2H, m), 7.54(1H, dd, J = 10.3 Hz, 1.9 Hz), 7.32(1H, dd, J = 8.2 Hz, 1.9 Hz), 7.22(1H, dd, J = 12.1 Hz, 2.3 Hz), 7.08(1H, dd, J = 8.6 Hz), 2.3 Hz), 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 = 6.6 Hz)

Purity
>90% (NMR)

MS
658 (M + 1)

Example No.
405
1H NMR(δ) ppm

1304

300 MHz, DMSO-d6 8.32(1H, s), 8.19(1H, d, J = 9.0 Hz), 8.03-7.98(2H, m), 7.75(1H, dd, J = 2.1 Hz, 8.4 Hz), 7.67(1H, t, J = 8.6 Hz), 7.40-7.36(3H, m), 7.32(2H, d, J = 8.4 Hz), 7.19(1H, dd, J = 2.1 Hz, 12.3 Hz), 7.07(1H, dd, J = 2.1 Hz, 8.7 Hz), 5.11(2H, s), 4.12(1H, m), 4.12(1H, m), 3.90(2H, t, J = 6.9 Hz), 2.54(2H, t, J = 8.1 Hz), 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

1305

300 MHz, DMSO-d6 8.34(1H, d, J = 7.7 Hz), 8.29(1H, s), 8.15(1H, s), 8.11(1H, d, J = 8.8 Hz), 7.97(2H, d, J = 9.2 Hz), 7.63(1H, t, J = 8.8 Hz), 7.47-7.31(5H, m), 7.18(1H, dd, J = 12.4, 2.Example No.
404
2 Hz), 7.06(1H, dd, J = 12.4, 2.2 Hz), 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 = 6.2 Hz)

Purity
>90% (NMR)

MS
652 (M + 1)

[2038]

248

TABLE 247

Example No.
407
1H NMR(δ) ppm

1306

400 MHz, DMSO-d6 8.32(1H, d, J = 1.4 Hz), 8.20(1H, d, J = 8.8 Hz), 8.01(1H, dd, J = 1.6 Hz, 8.8 Hz), 7.90(1H, s), 7.67(1H, t, J = 8.4 Hz), 7.61(1H, s), 7.55-7.21(1H, dd, J ==2.3 Hz, 8.7 Hz), 5.10(2H, s), 4.11(1H, m), 3.78 (2H, t, J = 6.7 Hz), 3.47(2H, t, J = 7.4 Hz), 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

1307

400 MHz, DMSO-d6 8.32(1H, d, J = 1.6 Hz), 8.21(1H, d, J = 8.8 Hz), 8.02(1H, dd, J = 1.6 Hz, 8.8 Hz), 7.76(1H, s), 7.68(1H, t, J = 8.5 Hz), 7.59(1H, s), 7.54-7.51(4H, m), 7.21(1H, dd, J = 2.4 Hz, 12.1 Hz), 7.07(1H, dd, J = 2.4 Hz, 8.8 Hz), 5.08(2H, s), 4.11 (1H, m), 3.77(2H, t, J = 6.9 Hz), 2.47(2H, t, J = 8.0 Hz), 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

300 MHz, DMSO-d68.28(1H, d, J = 1.5 Hz), 8.20-8.85(4H, m), 7.75(1H, d, J = 6.9 Hz), 7.70-7.45(6H, m), 7.13(1H, dd, J = 12.0 Hz, 2.1 Hz), 7.00(1H, dd, J = 8.7 Hz), 2.1 Hz), 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 = 6.6 Hz)

Purity
>90% (NMR)

MS
676 (M + 1)

[2039]

249

TABLE 248

Example No.
410
1H NMR(δ) ppm

1308

300 MHz, DMSO-d6 8.31(1H, s), 8.00(1H, d, J = 8.7 Hz), 7.88(1H, d, J = 8.7 Hz), 7.70(1H, s), 7.65 (1H, t, J = 8.4 Hz), 7.53 (2H, d, J = 8.4 Hz), 7.49 (2H, d, J = 8.7 Hz), 7.45-7.41(2H, m), 7.16(1H, d, J = 12.0 Hz), 7.04(1H, d, J = 8.7 Hz), 5.14(2H, s), 4.68(1H, quint, J = 8.4 Hz), 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

1309

300 MHz, DMSO-d6 8.30(1H, s), 7.99(1H, d, 1 = 9.0 Hz), 7.87(1H, d, J = 8.7 Hz), 7.67(1H, s), 7.64(1H, t, J = 8.7 Hz), 7.53(2H, d, J = 8.7 Hz), 7.49(2H, d, J = 7.5 Hz), 7.45-7.41(2H, m), 7.15(1H, d, J = 12.3 Hz), 7.02(1H, d, J = 18.4 Hz), 5.15(2H, 5), 4.67(1H, quint, J = 8.7 Hz), 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

1310

300 MHz, DMSO-d6 8.38(1H, d, J = 7.5 Hz), 8.33(1H, s), 8.16(1H, s), 8.02(1H, d, J = 8.7 Hz), 7.98(1H, d, J = 9.0 Hz), 7.91(1H, d, J = 8.4 Hz), 7.67(1H, t, J = 8.4 Hz), 7.53(2H, d, J = 8.7 Hz), 7.48(2H, d, J = 8.7 Hz), 7.46(1H, d, J = 8.1 Hz), 7.18(1H, d, J = 11.7 Hz), 7.06(1H, d, J = 8.7 Hz), 5.13(2H, s), 4.70(1H, quint, J = 8.4 Hz), 4.13(1H, sept, J = 6.6 Hz), 2.30-1.85(6H, m), 1.80-1.50(2H, m),

# 1.16(6H, d, J = 6.3 Hz)

Purity
>90% (NMR)

MS
626(M + 1)

[2040]

250

TABLE 249

Example No.
413
1H NMR(δ) ppm

1311

300 Mz, DMSO-d6 8.39(1H, d, J = 7.5 Hz), 8.31(1H, d, J = 1.5 Hz), 8.16(1H, d, J = 1.9 Hz), 8.06(1H, dd, J = 8.8, 1.5 Hz), 7.99-7.95 (2H, m), 7.76 and 7.24 (4H, ABq, J = 8.9 Hz), 7.53 and 7.50(4H, A′ B′q, J = 9.1 Hz), 7.46(1H, d, J = 8.3 Hz), 5.14(2H, s), 4.94(1H, quint, J = 9.0 Hz), 4.19-4.08(1H, m), 2.32-2.11(4H, brm), 210-1.95(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

1312

300 Mz, DMSO-d6 8.31(1H, d, J = 1.5 Hz), 8.06(1H, dd, J = 8.7, 1.5 Hz), 7.97(1H, d, J = 8.7 Hz), 7.75 and 7.22(4H, ABq, J = 8.9 Hz), 7.70(1H, d, J = 1.9 Hz), 7.53(1H, dd, J = 7.9, 1.9 Hz), 7.52(4H, s), 7.43(1H, d, J = 7.9 Hz), 5.15(2H, s), 4.93(1H, quint, J = 8.9 Hz), 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

1313

300 Mz, DMSO-d6 8.31(1H, d, J = 1.5 Hz), 8.06(1H, dd, J = 8.7, 1.5 Hz), 7.98(1H, d, J = 8.7 Hz), 7.75 and 7.22(4H, ABq, J = 8.9 Hz), 7.67(1H, d, J = 1.5 Hz), 7.52(4H, s), 7.49(1H, dd, J =7.9, 1.5 Hz), 7.43(1H, d, J = 8.9 Hz), 5.16(2H, s), 4.93(1H, quint, J = 8.9 Hz), 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)

[2041]

251

TABLE 250

Example No.
416
1H NMR(δ) ppm

1314

300 MHz, DMSO-d6 8.38(1H, d, J = 7.7 Hz), 8.30(1H, s), 8.20-7.90(4H, m), 7.72 (2H, d, J = 8.7 Hz), 7.60-7.40(5H, m), 7.22(2H, d, J = 8.7 Hz), 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 = 6.5 Hz)

Purity
22 90% (NMR)

MS
640(M + 1)

Example No.
417
1H NMR(δ) ppm

1315

400 MHz, DMSO-d6 8.33(1H, s), 8.17(1H, d, J = 8.6 Hz), 8.10(1H, d, J = 8.6 Hz), 7.82(1H, d, J = 1.4 Hz), 7.74(2H, d, J = 8.7 Hz), 7.64(1H, dd, J = 8.0 Hz, 1.7 Hz), 7.55-7.50(4H, m), 7.43(1H, d, J = 7.8 Hz), 7.24(1H, d, J = 8.7 Hz), 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
22 90% (NMR)

MS
652(M + 1)

Example No.
418
1H NMR(δ) ppm

1316

400 MHz, DMSO-d6 8.34(1H, d, J = 7.6 Hz), 8.25 (1H, s), 8.11(1H, d, J = 1.3 Hz), 7.90-8.00(3H, m), 7.59(1H, t, J = 8.6 Hz), 7.40-7.55(5H, m), 7.12(1H, d, J = 11.9 Hz), 7.00(1H, d, J = 8.6 Hz), 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 = 4.8 Hz)

Purity
22 90% (NMR)

MS
658(M + 1)

[2042]

252

TABLE 251

Example No.
419
1H NMR(δ) ppm

1317

400 MHz, DMSO-d6 8.30(1H, s), 8.05-7.95(3H, m), 7.80-7.75(1H, m), 7.63(1H, t, J = 8.6 Hz), 7.55-7.35(5H, m), 7.15(1H, dd, J = 12.1 Hz, 2.1 Hz), 7.03(1H, dd, J = 8.7 Hz, 2.3 Hz), 5.10(2H, s), 4.23(1H, m), 3.90(2H, t, J = 7.0 Hz), 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

1318

300 Mz, DMSO-d6 8.37(1H, d, J = 7.5 Hz), 8.28(1H, d, J = 1.5 Hz), 8.17(1H, d, J = 1.5 Hz), 8.13(1H, d, J = 8.7 Hz), 7.97(1H, dd, J = 8.1, 1.5 Hz), 7.94(1H, dd, J = 8.7, 1.5 Hz), 7.61(1H, t, J = 8.7 Hz), 7.51 and 7.49(4H, ABq, J = 8.9 Hz), 7.46(1H, d, J = 8.1 Hz), 7.08(1H, dd, J = 12.4, 2.3 Hz), 6.97(1H, dd, J = 8.7, 2.3 Hz), 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, s), 1.18(3H, s)

Purity
>90% (NMR)

MS
641(M + 1)

Example No.
421
1H NMR(δ) ppm

1319

300 Mz, DMSO-d6 8.24(1H, d, J = 1.5 Hz), 8.02(1H, d, J = 8.7 Hz), 7.88(1H, dd, J = 8.7, 1.5 Hz), 7.82(1H, d, J = 1.9 Hz), 7.63(1H, dd, J = 7.9, 1.9 Hz),7.54(1H, t, J = 8.7 Hz), 7.50(4H, s), 7.42(1H, d, J = 7.9 Hz), 7.01(1H, dd, J = 12.0, 2.3 Hz), 6.91 (1H, dd, J = 8.7, 2.3 Hz), 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)

[2043]

253

TABLE 252

Example No.
422
1H NMR(δ) ppm

1320

300 MHz, DMSO-d6 10.99(2H, s), 8.44(1H, s), 8.30(1H, s), 8.18(1H, d, J = 8.7 Hz), 8.14(1H, d, J = 8.7 Hz), 7.98(1H, d, J = 9.0 Hz), 7.70-7.66(2H, m), 7.57(2H, d, J = 8.7 Hz), 7.54(2H, d, J = 8.7 Hz), 7.21(1H, d, J = 12.0 Hz), 7.09(1H,d,J8.4Hz), 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

1321

300 MHz, DMSO-d6 8.27(1H, s), 8.05(1H, d, J = 8.7 Hz), 7.93 (1H, d, J = 8.7 Hz), 7.90(1H, s), 7.70(1H, d, J = 8.4 Hz), 7.59(1H, t, J = 8.4 Hz), 7.50(2H, d, J = 9.0 Hz), 7.45(2H, d, J = 8.7 Hz), 7.41(1H, d, J = 8.4 Hz), 7.12(1H, d, J = 12.0 Hz), 7.00(1H, d, J = 8.7 Hz), 5.10(2H, s), 4.49(2H, t, J = 7.8 Hz), 4.14(2H, t, J = 8.0 Hz), 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

1322

300 MHz, DMSO-d6 8.30(1H, s), 8.14(1H, d, J = 8.4 Hz), 7.98(1H, d, J = 9.3 Hz), 7.89(1H, s), 7.68(1H, d, J = 8.4 Hz), 7.62(1H, d, J = 9.0 Hz), 7.48(2H, d, J = 8.4 Hz), 7.43(2H, d, J = 8.4 Hz), 7.33(1H, d, J = 8.4 Hz), 7.16(1H, d, J = 12.0 Hz), 7.04(1H, d, J = 9.0 Hz), 5.07(2H, s), 4.10(1H, m), 3.92(2H, t, J = 8.0 Hz), 3.45(2H, t, J = 8.0 Hz), 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)

[2044]

254

TABLE 253

Example No.
425
1H NMR(δ) ppm

1323

300 MHz, DMSO-d6 9.05(1H, 5), 8.30(1H, s), 8.16(1H, d, J = 8.8 Hz), 7.99(1H, d, J = 8.6 Hz), 7.72(1H, s), 7.64(1H, t, J = 8.6 Hz), 7.52 (1H, d, J = 8.4 Hz), 7.47(2H, d, J = 8.7 Hz), 7.42(2H, d, J = 8.6 Hz), 7.25(1H, d, J = 8.4 Hz), 7.15(1H, d, J = 12.2 Hz), 7.04(1H, d, J = 8.6 Hz), 6.60(1H, brs), 5.05(2H, s), 4.10(1H, m), 3.68(2H, t, J = 6.1 Hz), 3.45(2H, t, J = 6.1 Hz), 2.40-2.10(2H, m), 2.00-1.55(5m, m),

#1.50-1.20(3H, m)

Purity
>90% (NMR)

MS
639(M + 1)

Example No.
426
1H NMR(δ) ppm

1324

300 MHz, DMSO-d6 8.32(1H, s), 8.24(1H, d, J = 8.7 Hz), 8.03 (1H, d, J = 8.7 Hz), 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

1325

300 MHz, DMSO-d6 11.26(1H, brs), 8.35(1H, s), 8.27(1H, d, J = 9.0 Hz), 8.05(1H, d, J = 8.4 Hz), 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)

[2045]

255

TABLE 254

Example No.
428
1H NMR(δ) ppm

1326

300 MHz, DMSO-d6 8.31(1H, s), 8.26(1H, d, J = 9.0 Hz), 8.04(1H, d, J = 8.7 Hz), 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

1327

300MHz, DMSO-d6 8.88(1H, q, J = 4.5 Hz), 8.33(1H, d, J = 1.5 Hz), 8.18(1H, d, J = 8.7 Hz), 8.01(1H, dd, J = 1.5 Hz, 8.7 Hz), 7.89-7.83(2H, m), 7.50-7.34(3H, m), 7.20(1H, dd, J = 2.1 Hz, 8.4 Hz), 5.61(2H, s), 4.13(1H, m), 2.84(3H, d, J = 4.8 Hz), 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

1328

400 MHz, DMSO-d6 8.79(1H, t, J = 5.9 Hz), 8.31(1H, s), 8.15(1H, d, J = 8.7 Hz), 7.99(1H, d, J = 8.8 Hz), 7.87(1H, d, J = 8.1 Hz), 7.85(1H, d, J = 8.7 Hz), 7.70(1H, t, J = 8.4 Hz), 7.42-7.33(3H, m), 7.18(1H, d, J = 8.8 Hz), 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)

[2046]

256

TABLE 255

Example No.
431
1H NMR(δ) ppm

1329

300MHz, DMSO-d6 8.31(1H, s), 8.16(1H, d, J = 8.8 Hz), 7.99(1H, d, J = 8.7 Hz), 7.74-7.60(4H, m), 7.37(2H, t, J = 8.8 Hz), 7.28(1H, dd, J = 2.2 Hz, 12.2 Hz), 7.14(1H, dd, J = 2.2 Hz, 8.6 Hz), 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

1330

300 MHz, DMSO-d6 8.45(1H, d, J = 7.7 Hz), 8.32(1H, s), 8.19(1H, d, J = 8.8 Hz), 8.02-7.99(2H, m), 7.70(1H, t, J = 8.6 Hz), 7.60(2H, dd, J = 5.4 Hz, 8.7 Hz), 7.37(2H, t, J = 8.8 Hz), 7.27(1H, dd, J = 2.3 Hz, 12.2 Hz), 7.14(1H, dd, J = 2.2 Hz, 8.7 Hz), 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 = 6.6 Hz)

Purity
>90% (NMR)

MS
630(M + 1)

Example No.
433
1H NMR(δ) ppm

1331

300 MHz, DMSO-d6 8.31(1H, d, J = 1.4 Hz), 8.15(1H, d, J = 8.8 Hz), 7.98(1H, dd, J = 1.4 Hz, 8.7 Hz), 7.68-7.60(4H, m), 7.36(2H, t, J = 8.8 Hz), 7.28 (1H, dd, J = 2.2 Hz, 12.2 Hz), 7.15(1H, d, J = 2.2 Hz, 8.6 Hz), 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)

[2047]

257

TABLE 256

Example No.
434
1H NMR(δ) ppm

1332

300 Mz, DMSO-d6 8.45(1H, d, J = 1.5 Hz), 8.26(1H, d, J = 8.8 Hz), 8.10(1H, dd, J = 8.8, 1.5 Hz), 7.72(1H, d, J = 1.5 Hz), 7.64(1H, t, J = 8.6 Hz), 7.56-7.48(5H, m), 7.44(1H, d, J = J = 7.7 Hz), 7.18(1H, dd, J = 12.3, 2.4 Hz), 7.04(1H, dd, J = 8.6, 2.4 Hz), 5.15(2H, s), 4.08(1H, brt, 11.7 Hz), 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

1333

300 Mz, DMSO-d6 8.42(1H, d, J = 1.5 Hz), 8.24(1H, d, J = 8.8 Hz), 8.08(1H, dd, J = 8.8, 1.5 Hz), 8.00(2H, d, J = 8.8 Hz), 7.79(1H, d, J = 7.8 Hz), 7.62(1H, t, J = 8.4 Hz), 7.61-7.55(3H, m), 7.44(1H, d, J = 8.1 Hz), 7.16(1H, dd, J = 12.1, 2.6 Hz), 7.02(1H, dd, J = 8.4, 2.6 Hz), 5.12(2H, s), 4.07(1H, brt, J = 12.5 Hz), 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

1334

300 MHz, DMSO-d6 8.41(1H, d, J = 7.7 Hz), 8.30-8.26(2H, m), 8.18(1H, d, J = 1.4 Hz), 7.99(1H, dd, J = 1.7 Hz, 8.0 Hz), 7.89(1H, d, J = 10.1 Hz), 7.67(1H, t, J = 8.8 Hz), 7.55-7.45(5H, m), 7.20(1H, d, J = 12.2 Hz), 7.07(1H, dd, J = 2.1 Hz, 8.7 Hz), 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 = 6.6 Hz)

Purity
>90% (NMR)

MS
680(M + 1)

[2048]

258

TABLE 257

Example No.
437
1H NMR(δ) ppm

1335

Purity
>90% (NMR)

MS
580(M + 1)

Example No.
438
1H NMR(δ) ppm

1336

Purity
>90% (NMR)

MS
607(M + 1)

Example No.
437
1H NMR(δ) ppm

1337

300 MHz, CDCl3 8.60(1H, d, J = 1.5 Hz), 8.05(1H, dd, J = 1.6 Hz, 8.7 Hz), 7.70(1H, d, J = 8.7 Hz), 7.62(2H, d, J = 8.2 Hz), 7.49(2H, d, J = 8.2 Hz), 7.13(2H, d, J = 8.8 Hz), 7.27-7.23(2H, m), 7.06(2H, t, J = 8.6 Hz), 6.80(2H, d, J = 8.8 Hz), 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)

[2049]

259

TABLE 258

Example No.
440
1H NMR(δ) ppm

1338

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

1339

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

1340

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)

[2050]

260

TABLE 259

Example No.
443
1H NMR(δ) ppm

1341

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

1342

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=8.4Hz), 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

1343

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)

[2051]

261

TABLE 260

Example No.
446
1H NMR(δ) ppm

1344

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.
447
1H NMR(δ) ppm

1345

300MHz, DMSO-d6 8.36(1H, d, J=7.7Hz), 8.14(2H, d, J=12.1Hz), 8.08(1H, d, J=8.5Hz), 7.97(1H, dd,

# J=1.7Hz, 8.3Hz), 7.74(1H, dd, J=1.8Hz, 8.4Hz), 7.58-7.45(6H, m), 7.31(2H, s), 7.12(1H, dd, J=2.2Hz, 12.1Hz), 7.00(1H, dd, J=2.4Hz, 8.6Hz), 5.11(2H, s), 4.16(1H, m), 4.02(1H, m), 2.20(2H, m), 1.86(4H, m), 1.62(1H, m), 1.21(9H, m)

Purity
>90% (NMR)

MS
675(M + 1)

Example No.
448
1H NMR(δ) ppm

1346

300MHz, DMSO-d6 8.29(2H, m), 8.04(1H, d, J=8.5Hz), 7.93(1H, dd, J=1.5Hz, 8.8Hz), 7.60-7.42(8H, m), 7.05(1H, dd, J=2.2Hz, 12.1Hz), 6.95(1H, dd, J=2.4Hz, 8.6Hz), 5.11(2H, s), 4.07-3.90(2H, m), 2.28-2.19(2H, m), 1.88-1.84(4H, m), 1.67-1.62(1H, m), 1.40-1.26(3H, m), 1.04(6H, d, J=6.6Hz)

Purity
>90% (NMR)

MS
640(M + 1)

[2052]

262

TABLE 261

Example No.
449
1H NMR(δ) ppm

1347

300MHz, DMSO-d6 8.31(1H, s), 8.17(1H, d, J=8.7Hz), 8.00(1H,

# d, J=8.7Hz), 7.78(1H, d, J=8.1Hz), 7.66(1H, t, J=8.7Hz), 7.55-7.45(4H, m), 7.40(1H, d, J=11.7Hz), 7.19(1H, d, J=12.3Hz),7.05(1H, d, J=8.7Hz), 5.07(2H, s), 4.10(1H, m), 3.85(2H, t, J=6.6Hz), 3.47(2H, t, J=7.5z) 2.60-2.50(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
692(M + 1)

Example No.
450
1H NMR(δ) ppm

1348

300MHz, DMSO-d6 8.37(1H, d, J=7.8Hz), 8.15(1H, s), 7.97(1H, d, J=9.8Hz), 7.64-7.45(8H, m),

# 7.12(1H, d, J=12.1Hz), 7.00(1H, d, J=8.6Hz), 5.11(2H, s), 4.21(3H, s), 4.18-4.05(1H, m), 4.04-3.89(1H, m), 2.29-2.08(2H, m), 1.90-1.74(4H, m), 1.68-1.58(1H, m), 1.40-1.17(3H, m), 1.20(6H, d, J=6.6Hz)

Purity
>90% (NMR)

MS
670(M + 1)

Example No.
451
1H NMR(δ) ppm

1349

300MHz, DMSO-d6 8.29(1H, s), 8.12(1H, d, J=8.8Hz), 7.97(1H, d, J=10.2Hz), 7.65-7.59(2H, m), 7.51(4H, s), 7.46(2H, s), 7.15(1H, d,

# J=12.2Hz), 7.01(1H, d, J=8.6Hz), 5.15(2H, s), 4.13-3.98(1H, m), 3.21(3H, s), 2.56-2.42(1H, m), 2.30-2.15(2H, m), 1.95-1.77(4H, m), 1.69-1.59(1H, m), 1.45-1.17(3H, m), 0.96(6H, d, J=6.5Hz)

Purity
>90% (NMR)

MS
654(M + 1)

[2053]

263

TABLE 262

Example No.
452
1H NMR(δ) ppm

1350

300MHz, DMSO-d6 10.1(1H, s), 8.28(1H, s), 8.11(1H, d, J=8.7Hz), 7.96(1H, d, J=11.4Hz), 7.95(1H, s), 7.72(1H, d, J=8.7Hz), 7.62(1H, t, J=9.0Hz), 7.48

# and 7.43(4H, ABq, J=8.4Hz), 7.31(1H, d, J=8.4Hz), 7.13(1H, d, J=12.0Hz), 7.02 (1H, d, J=9.0Hz), 5.07(2H, s), 4.14-4.00(1H, m), 2.69-2.59(1H, m), 2.30-2.12(2H, m), 1.95-1.77(4H, m), 1.71-1.57(1H, m), 1.45-1.20(3H, m), 1.12(6H, d, J=6.9Hz)

Purity
>90% (NMR)

MS
640(M + 1)

Example No.
453
1H NMR(δ) ppm

1351

300MHz, DMSO-d6 11.1(1H, brs), 8.31(1H, d, J=9.4Hz), 8.29(1H, s), 8.07(1H, d, J=10.2Hz), 7.70-7.62(3H, m), 7.31-7.23(3H, m), 4.40-4.23(1H, m), 4.24(2H, s), 2.61(3H, s), 2.34-2.14(2H, m), 1.99-1.72(4H, m), 1.66-1.54(1H, m), 1.46-1.30(1H, m), 1.27-1.08(2H, m)

Purity
>90% (NMR)

MS
542(M + 1)

Example No.
454
1H NMR(δ) ppm

1352

300MHz, DMSO-d6 8.27(1H, d, J=1.4Hz), 8.05(1H, d, J=8.7Hz), 7.92(1H, d, J=8.7Hz), 7.79(1H, d, J=7.8Hz), 7.59(1H, t, J=8.6Hz), 7.55-7.45(4H, m), 7.37(1H, d, J=11.4Hz), 7.14(1H, d, J=12.1Hz), 7.01(1H, d, J=8.6Hz), 5.04(2H, s), 4.10(1H, m), 3.84(2H, t, J=6.9Hz), 2.55-2.45(2H, m), 2.40-2.10(4H, m), 2.00-1.80(4H, m), 1.75-1.55(1H, m), 1.50-1.20(3H, m)

Purity
>90% (NMR)

MS
656(M + 1)

[2054]

264

TABLE 263

Example No.
455
1H NMR(δ) ppm

1353

300MHz, DMSO-d6 10.05(1H, brs), 8.32(1H, d, J=1.3Hz), 8.19(1H, d, J=8.8Hz), 8.01(1H, d, J=8.7Hz), 7.67(1H, t, J=8.6Hz), 7.50-7.41(5H, m), 7.38-7.33(2H, m), 7.17(1H, dd, J=2.2Hz, 12.2Hz), 7.05(1H, dd, J=2.2Hz, 8.7Hz), 5.10(2H, s), 4.12(1H, m), 3.07(3H, s), 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
648(M + 1)

Example No.
456
1H NMR(δ) ppm

1354

300MHz, DMSO-d6 8.31(1H, d, J=1.4Hz), 8.17(1H, d, J=8.8Hz), 8.00(1H, dd, J=1.5Hz, 8.7Hz), 7.73(1H,

# d, J=2.3Hz), 7.66(1H, t, J=8.6Hz), 7.56(1H, dd, J=2.3Hz, 8.3Hz), 7.50-7.47(4H, m), 7.42(1H, d, J=8.3Hz), 7.19(1H, d, J=12.2Hz), 7.06(1H, dd, J=2.2Hz, 8.6Hz), 5.11(2H, s), 4.10(1H, m), 3.31(3H, s), 3.03(3H, s), 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
662(M + 1)

Example No.
457
1H NMR(δ) ppm

1355

300MHz, DMSO-d6 8.41(1H, d, J=8.8Hz), 8.28(1H, s), 8.10(1H, d, J=9.2Hz), 7.96(1H, d, J=8.8Hz), 7.87(1H, d, J=8.8Hz), 7.61(1H, dd, J=8.5Hz,

# 8.5Hz), 7.56-7.49(4H, m), 7.19(1H, dd, J=2.4Hz, 12.2Hz), 7.05(1H, dd, J=2.4Hz, 8.7Hz), 5.18(2H, s), 4.06-3.97(4H, m), 2.62(2H, t, J=8.1Hz), 2.28-2.15(2H, m), 2.11-2.01(4H, m), 1.91-1.87(4H, m), 1.64(1H, m), 1.43-1.23(3H, m)

Purity
>90% (NMR)

MS
639(M + 1)

[2055]

265

TABLE 264

Example No.
458
1H NMR(δ) ppm

1356

300MHz, DMSO-d6 10.19(1H, s), 8.29(1H, s), 8.14(1H, d, J=8.8Hz), 7.98(1H, dd, J=1.7Hz,

# 8.7Hz), 7.90(1H, d, J=2.2Hz), 7.69(1H, dd, J=2.2Hz, 8.4Hz), 7.64(1H, dd, J=8.5Hz, 8.5Hz), 7.50-7.42(4H, m), 7.32(1H, d, J=8.4Hz), 7.14(1H, dd, J=2.5Hz, 12.1Hz), 7.02(1H, dd, J=2.4Hz, 8.6Hz), 5.08(2H, s), 4.17-4.02(1H, m), 2.30-2.18(2H, m), 2.08(3H, s), 1.87-1.79(4H, m), 1.68-1.59(1H, m), 1.35-1.23(3H, m)

Purity
>90% (NMR)

MS
612(M + 1)

Example No.
459
1H NMR(δ) ppm

1357

300MHz, DMSO-d6 8.29(1H, s), 8.11(1H, d, J=8.8Hz), 7.96(1H, d, J=8.6Hz), 7.64-7.58(2H, m), 7.51(4H, s), 7.44(2H, s), 7.15(1H, d, J=12.2Hz), 7.02(1H, d, J=8.5H), 5.14(2H, s), 4.12-3.95(1H, m), 3.70(2H, q, J=7.1Hz), 2.50(3H, s), 2.31-2.12(2H, m), 1.92-1.82(4H, m), 1.69-1.57(1H, m), 1.43-1.16(3H, m), 1.05(3H, t, J=7.1Hz)

Purity
>90% (NMR)

MS
640(M + 1)

Example No.
460
1H NMR(δ) ppm

1358

300MHz, DMSO-d6 8.28(1H, s), 8.09(1H, d, J=8.8Hz), 7.95(1H, d, J=10.1Hz), 7.64-7.56(2H, m), 7.51(4H, ws), 7.44(2H, s), 7.14(1H, d, J=12.2Hz), 7.01(1H, d, J=8.6Hz), 5.14(2H, s), 4.12-3.95(1H, m), 3.64(2H, t, J=7.2Hz), 2.50(3H, s), 2.31-2.12(2H, m), 1.93-1.84(4H, m), 1.69-1.59(1H, m), 1.52-1.17(5H, m), 0.84(3H, t, J−7.3Hz)

Purity
>90% (NMR)

MS
654(M + 1)

[2056]

266

TABLE 265

Example No.
461
1H NMR(δ) ppm

1359

400MHz, DMSO-d6 8.30(1H, s), 8.13(1H, d, J=8.8Hz), 7.99(1H, d, J=8.8Hz), 7.69(1H, s), 7.62(1H, t, J=8.4Hz), 7.96-7.50(4H, m), 7.45(1H, d,

# J=8.7Hz), 7.17(1H, dd, J=2.3Hz, 12.0Hz), 7.05(1H, dd, J=2.2Hz, 8.7Hz), 5.14(2H, s), 4.07(1H, m), 3.73(2H, q, J=7.2Hz), 3.05(3H, s), 2.40-2.10(2H, m), 2.00-1.80(4H, m), 1.75-1.55(1H, m), 1.50-1.20(3H, m), 1.06(3H, t, J=7.2Hz)

Purity
>90% (NMR)

MS
676(M + 1)

Example No.
462
1H NMR(δ) ppm

1360

300MHz, DMSO-d6 8.30(1H, s), 8.13(1H, d, J=8.7Hz), 7.98(1H, d, J=8.7Hz), 7.70(1H, d, J=1.8Hz), 7.63(1H, t, J=8.4Hz), 7.55-7.50(5H, m), 7.43(1H,

# d, J=8.1Hz), 7.15(1H, d, J=12.0Hz), 7.02(1H, d, J=8.7Hz), 5.13(2H, s), 4.07(1H, m), 3.65(2H, t, J=6.6Hz), 3.03(3H, s), 2.40-2.10(2H, m), 2.00-1.75(4H, m), 1.70-1.60(1H, m), 1.50-1.20(5H, m), 0.87(3H, t, J=7.5Hz)

Purity
>90% (NMR)

MS
690(M + 1)

Example No.
463
1H NMR(δ) ppm

1361

300MHz, DMSO-d6 8.29(1H, s), 8.11(1H, d, J=8.5Hz), 7.97(1H, d, J=9.9Hz), 7.65(1H, br), 7.61(1H, d, J=8.4Hz), 7.53-7.42(6H, m), 7.16(1H, dd, J=2.2Hz, 12.1Hz), 7.03(1H, dd, J=2.0Hz, 9.0Hz), 5.12(2H, s), 4.04-4.00(1H, m), 3.24(3H, s), 2.20(2H, m), 1.87(7H, m), 1.64(1H, m), 1.41-1.28(3H, m)

Purity
>90% (NMR)

MS
626(M + 1)

[2057]

267

TABLE 266

Example No.
464
1H NMR(δ) ppm

1362

300MHz, DMSO-d6 8.28(1H, s), 8.09(1H, d, J=8.8Hz), 7.95(1H, d, J=8.8Hz), 7.73(1H, d, J=2.2Hz), 7.63-7.39(7H, m), 7.15(1H, dd, J=2.2Hz, 12.1Hz), 7.01(1H, dd, J=2.0Hz, 8.6Hz), 5.10(2H, s), 4.05-3.99(1H, m), 3.34(3H, s), 3.23(2H, q, J=7.2Hz), 2.20(2H, m), 1.87(4H, m), 1.62(1H, m), 1.33(3H, m), 1.24(3H, t, J=7.3Hz)

Purity
>90% (NMR)

MS
676(M + 1)

Example No.
465
1H NMR(δ) ppm

1363

300MHz, DMSO-d6 8.29(1H, d, J=1.5Hz), 8.11(1H, d, J=8.8Hz), 7.98(1H, dd, J=1.4Hz, 8.4Hz), 7.69(1H, d, J=2.2Hz), 7.62(1H, dd, J=8.6Hz,

# 8.6Hz), 7.56-7.47(5H, m), 7.43(1H, d, J=8.1Hz), 7.16(1H, dd, J=2.2Hz, 12.1Hz), 7.02(1H, dd, J=2.4Hz, 8.7Hz), 5.13(2H, s), 4.09-4.02(1H, m), 3.77(2H, q, J=6.8Hz), 3.19(2H, q, J=7.4Hz), 2.25-2.21(2H, m), 1.90-1.87(4H, m), 1.63(1H, m), 1.39-1.33(3H, m), 1.27(3H, t, J=7.4Hz), 1.06(3H, t, J=6.9Hz)

Purity
>90% (NMR)

MS
690(M + 1)

Example No.
466
1H NMR(δ) ppm

1364

300MHz, DMSO-d6 8.28(1H, s), 8.10(1H, d, J=8.4Hz), 7.96(1H, d, J=8.4Hz), 7.64(1H, s), 7.61(1H, d, J=8.4Hz), 7.50(4H, s), 7.44(2H, s), 7.14(1H, d, J=12.0Hz), 7.02(1H, d, J=8.4Hz), 5.12(2H, s), 4.12-3.95(1H, m), 3.23(3H, s), 2.32-2.06(4H, m), 1.94-1.77(4H, m), 1.70-1.59(1H, m), 1.42-1.18(3H, m), 0.96(3H, t, J=7.2Hz)

Purity
>90% (NMR)

MS
640(M + 1)

[2058]

268

TABLE 267

Example No.
467
1H NMR(δ) ppm

1365

300MHz, DMSO-d6 8.28(1H, s), 8.08(1H, d, J=8.7Hz), 7.95(1H, d, J=8.4Hz), 7.60(1H, t, J=8.4Hz), 7.59(1H, s), 7.51(4H, s), 7.45 and 7.42(2H, ABq,

# J=8.1Hz), 7.14(1H, d, J=12.0Hz), 7.00(1H, d, J=8.4Hz), 5.14(2H, s), 4.12-3.95(1H, m), 3.70(2H, q, J=6.9Hz), 2.30-1.98(4H, m), 1.94-1.79(4H, m), 1.69-1.59(1H, m), 1.45-1.17(3H, m), 1.05(3H, t, J=6.9Hz), 0.94(3H, t, J=7.5Hz)

Purity
>90% (NMR)

MS
654(M + 1)

Example No.
468
1H NMR(δ) ppm

1366

400MHz, DMSO-d6 8.25(1H, s), 7.96(1H, d, J=8.8Hz), 7.90(1H, d, J=8.8Hz), 7.55(1H, t, J=8.4Hz), 7.46(2H, d, J=8.7Hz), 7.41(2H, d, J=8.7Hz),

# 7.10-7.00(2H, m), 6.98(1H, dd, J=2.2Hz, 8.7Hz), 5.05(2H, s), 3.98(1H, m), 3.84(3H, s), 2.30-2.10(2H, m), 1.90-1.75(4H, m), 1.70-1.60(1H, m), 1.50-1.20(3H, m)

Purity
>90% (NMR)

MS
585(M + 1)

Example No.
469
1H NMR(δ) ppm

1367

400MHz, DMSO-d6 8.26(1H, s), 8.02(1H, d, J=8.8Hz), 7.93(1H, d, J=8.8Hz), 7.60-7.50(6H, m), 7.45(1H,

# d, J=8.7Hz), 7.08(1H, dd, J=2.3Hz, 12.0Hz), 6.97(1H, dd, J=2.2Hz, 8.7Hz), 5.18(2H, s), 4.85(1H, sept, J=6.6Hz), 3.98(1H, m), 2.40-2.10(2H, m), 2.00-1.80(4H, m), 1.75-1.55(4H, m), 1.50-1.20(3H, m), 1.02(6H, d, J=6.6Hz)

Purity
>90% (NMR)

MS
654(M + 1)

[2059]

269

TABLE 268

Example No.
470
1H NMR(δ) ppm

1368

300MHz, DMSO-d6 8.39(1H, d, J=1.4Hz), 8.04(1H, d, J=8.8Hz), 7.98(1H, d, J=2.2Hz), 7.95(1H, d, J=8.8Hz), 7.78(1H, dd, J=2.3Hz, 8.5Hz), 7.57(1H, t, J=8.6Hz), 7.50(2H, d, J=8.8Hz), 7.45 (2H, d, J=8.8Hz), 7.39(1H, d, J=8.4Hz), 7.10(1H, d, J=12.1Hz), 6.98 (1H, d, J=8.6Hz), 5.65-5.60(2H, m), 5.35(1H, d, J=4.2Hz), 5.08(2H, s), 4.00(1H, m), 3.93-3.84(3H, m),

# 3.50-3.30(4H, m), 2.54(2H, t, J=7.8Hz), 2.40-2.00(4H, m), 1.95-1.75(4H, m), 1.70-1.55(1H, m), 1.45-1.15(3H, m)

Purity
>90% (NMR)

MS
814 (M + 1)

Example No.
471
1H NMR (δ) ppm

1369

300MHz, DMSO-d6 12.78(1H, brs), 8.30(1H, dd, J=0.9Hz, 1.5Hz), 8.22(1H, d, J=1.5Hz), 7.95 (1H, d, J=1.8Hz), 7.94(1H, d, J=8.4Hz), 7.85(1H, dd, J=1.2Hz, 8.4Hz), 6.96(1H, dd, J=0.9 Hz, 1.8Hz), 4.46(1H, m), 2.40-2.10(2H, m), 2.00-1.20(8H, m)

Purity
>90% (NMR)

MS
311 (M + 1)

[2060]

270

TABLE 269

Example No.
702
1H NMR(δ) ppm

1370

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

1371

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)

[2061] Industrial Applicability

[2062] As is evident from the above-mentioned results, the compound of the present invention shows a high inhibitory activity against HCV polymerase.

[2063] 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.

[2064] This application is based on patent application Nos. 193786/2001 and 351537/2001 filed in Japan, the contents of which are hereby incorporated by reference.

Number	Date	Country	Kind
2001-193786	Jun 2001	JP
2001-351537	Nov 2001	JP

Fused cyclic compounds and medicinal use thereof

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