| US 7,479,564 B2 | ||
| Aryl or heteroaryl fused imidazole compounds as anti-inflammatory and analgesic agents | ||
| Kazunari Nakao, Chita-gun (Japan); Yoshiyuki Okumura, Chita-gun (Japan); Miyako Matsumizu, Chita-gun (Japan); Naomi Ueno, Chita-gun (Japan); Yoshinobu Hashizume, Chita-gun (Japan); Tomoki Kato, Chita-gun (Japan); Akiyoshi Kawai, Chita-gun (Japan); Yoriko Miyake, Chita-gun (Japan); Seiji Nukui, Chita-gun (Japan); Katsuhiro Shinjyo, Chita-gun (Japan); and Kana Taniguchi, Chita-gun (Japan) | ||
| Assigned to RaQualia Pharma Inc., Aichi-ken (Japan) | ||
| Filed on Nov. 03, 2006, as Appl. No. 11/556,523. | ||
| Application 11/556523 is a division of application No. 10/771696, filed on Feb. 04, 2004, granted, now 7,141,580. | ||
| Application 10/771696 is a division of application No. 09/977621, filed on Oct. 15, 2001, granted, now 6,710,054. | ||
| Claims priority of provisional application 60/241825, filed on Oct. 19, 2000. | ||
| Prior Publication US 2007/0155732 A1, Jul. 05, 2007 | ||
| Int. Cl. A61K 31/4184 (2006.01); C07D 235/06 (2006.01) | ||
| U.S. Cl. 548—304.4 [514/394] | 13 Claims |
1. A compound of the following formula:
 Y1, Y2, Y3 and Y4 are independently selected from CH or C(L);
R1 is H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-7 cycloalkyl, C1-8 alkoxy, halo-substituted C1-8 alkoxy, C1-8 alkyl-S(O)m-, Q1-, pyrrolidinyl, piperidyl, oxopyrrolidinyl, oxopiperidyl, amino, mono- or di-(C1-8 alkyl)amino, C1-4alkyl-C(═O)—N(R3)— or C1-4alkyl-S(O)m-N(R3)—, wherein said C1-8 alkyl, C2-8 alkenyl and C2-8 alkynyl are optionally substituted with halo, C1-3 alkyl, hydroxy, oxo, C1-4 alkoxy-, C1-4 alkyl-S(O)m-, C3-7 cycloalkyl-, cyano, indanyl, 1,2,3,4-tetrahydronaphtyl, 1,2-dihydronaphtyl, pyrrolidinyl, piperidyl, oxopyrrolidinyl, oxopiperidyl,
Q1-, Q1-C(═O)—, Q1-O—, Q1-S(O)m-, Q1-C1-4alkyl-O—, Q1-C1-4alkyl-S(O)m—, Q1-C1-4alkyl-C(O)—N(R3)—, Q1-C1-4alkyl-N(R3)— or C1-4 alkyl-C(O)-N(R3)—;
Q1 is a 5-12 membered monocyclic or bicycle aromatic ring optionally containing up to 4 heteroatoms selected from O, N and S,
and is optionally substituted with halo, C1-4 alkyl, halo-substituted C1-4alkyl, hydroxy, C1-4alkoxy, halo-substituted C1-4alkoxy, C1-4 alkylthio, nitro, amino, mono- or di-(C1-4alkyl)amino, cyano, HO—C1-4 alkyl, C1-4 alkoxy-C1-4alkyl, C1-4 alkylsulfonyl, aminosulfonyl, C1-4 alkylC(═O)—, HO(O═)C—, C1-4 alkyl-O(O═)C—, R3N(R4)C(═O)—, C1-4 alkylsulfonylamino, C3-7 cycloalkyl, R3C(═O)N(R4)— or NH2(HN═)C—;
A is a 5-6 membered monocyclic aromatic ring optionally containing up to 3 heteroatoms selected from O, N and S, wherein said
5-6 membered monocyclic aromatic ring is optionally substituted with up to 3 substituents selected from halo, C1-4 alkyl, halo-substituted C1-4 alkyl, hydroxy, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4alkylthio, nitro, amino, mono- or di-(C1-4 alkyl)amino, cyano, HO—C1-4 alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, acetyl, R3N(R4)C(═O)—, HO(O═)C—, C1-4alkyl-O(O═)C—, C1-4 alkylsulfonylamino, C3-7 cycloalkyl, R3C(═O)N(R4)— and NH2(HN═)C—;
B is halo-substituted C1-6 alkylene, C3-7 cycloalkylene, C2-6 alkenylene, C2-6 alkynylene, —O—C1-5 alkylene, C1-2 alkylene-O—C1-2 alkylene or C1-6 alkylene optionally substituted with an oxo group or C1-3 alkyl;
W is NH, N—C1-4 alkyl, O, S, N—OR5 or a covalent bond;
R2 is H, C1-4 alkyl, OH or C1-4 alkoxy;
Z is a 5-12 membered monocyclic or bicyclic aromatic ring optionally containing up to 3 heteroatoms selected from O, N and
S, wherein said 5-12 membered monocyclic or bicyclic aromatic ring is optionally substituted with halo, C1-4 alkyl, halo-substituted C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, hydroxy, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, nitro, amino, mono- or di-(C1-4 alkyl)amino, cyano, HO—C1-4 alkyl, C1-4 alkoxy-C1-4alkyl, C1-4 alkylsulfonyl, aminosulfonyl, C1-4alkylC(═O)—, R3C(═O)N(R4)—, HO(O═)C—, C1-4alkyl-O(O═)C—, C1-4 alkylsulfonylamino, C3-7 cycloalkyl, NH2(HN═)C—, Q2-S(O)m-, Q2-O—, Q2-N(R3)— or Q2-;
L is halo, C1-4 alkyl, halo-substituted C1-4 alkyl, hydroxy, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, nitro, amino, mono- or di-(C1-4 alkyl)amino, cyano, HO—C1-4 alkyl, C1-4 alkoxy-C1-4alkyl, C1-4 alkylsulfonyl, aminosulfonyl, C1-4alkylC(═O)—, HO(O═)C—, C1-4alkyl-O(O═)C—, C1-4 alkylsulfonylamino, C3-7 cycloalkyl, R3C(═O)N(R4), NH2(HN═)C—, R3N(R4)C(═O), R3N(R4)S(O)m-, Q2-, Q2-C(═O)—, Q2-O—, Q2-C1-4alkyl-O—, or two adjacent L groups are joined together to form an alkylene chain having 3 or 4 members in which one or two
(non-adjacent) carbon atoms are optionally replaced by oxygen atoms;
m is 0, 1 or 2;
R3 and R4 are independently selected from H and C1-4 alkyl;
R5 is H, C1-4 alkyl, C1-4 alkyl-(O═)C— or C1-4 alkyl-O—(O═)C—; and
Q2 is a 5-12 membered monocyclic or bicyclic aromatic ring, or a 5-12 membered tricyclic ring optionally containing up to 3 heteroatoms
selected from O, N and S, wherein said 5-12 membered monocyclic or bicyclic aromatic ring is optionally substituted with halo,
C1-4 alkyl, halo-substituted C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, hydroxy, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, nitro, amino, mono- or di-(C1-4 alkyl)amino, cyano, HO—C1-4alkyl, C1-4 alkoxy-C1-4 alkyl, C1-4 alkylsulfonyl, aminosulfonyl, C1-4 alkyl-(O═)C—, R3(R4)C(═O)N—, HO(O═)C—, C1-4 alkyl-O(O═)C—, C1-4 alkylsulfonylamino, C3-7 cycloalkyl, C1-4 alkyl-C(═O)NH— or NH2(HN═)C—.
|