US 7,482,370 B2
Compounds for the treatment of inflammatory disorders
Wensheng Yu, Edison, N.J. (US); Ling Tong, Warren, N.J. (US); Lei Chen, Roselle Park, N.J. (US); Joseph A. Kozlowski, Princeton, N.J. (US); Brian J. Lavey, New Providence, N.J. (US); Neng-Yang Shih, Warren, N.J. (US); Vincent S. Madison, Mountain Lakes, N.J. (US); Guowei Zhou, Livingston, N.J. (US); Peter Orth, New York, N.Y. (US); Zhuyan Guo, Scotch Plains, N.J. (US); Michael K. C. Wong, North Brunswick, N.J. (US); De-Yi Yang, Morris Plains, N.J. (US); Seong Heon Kim, Livingston, N.J. (US); and Bandarpalle B. Shankar, Branchburg, N.J. (US)
Assigned to Schering Corporation, Kenilworth, N.J. (US)
Filed on Jul. 13, 2005, as Appl. No. 11/180,863.
Claims priority of provisional application 60/588502, filed on Jul. 16, 2004.
Prior Publication US 2006/0205797 A1, Sep. 14, 2006
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/427 (2006.01); A61K 31/4164 (2006.01); A61K 31/4375 (2006.01); C07D 277/22 (2006.01); C07D 409/14 (2006.01); C07D 405/14 (2006.01); C07D 453/02 (2006.01)
U.S. Cl. 514—373  [514/405; 514/414; 548/209; 548/361.5; 548/465; 546/135] 79 Claims
 
1. A compound represented by Formula (I):

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt, solvate or isomer thereof, wherein:
X is selected from the group consisting of —S—, —C(R4)2— or —N(R4)—;
T is selected from the group consisting of H (with U and V being absent), alkyl, alkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, alkylaryl, and arylalkyl, said aryl, heteroaryl, heterocyclyl, cycloalkyl, alkylaryl and arylalkyl being optionally fused with one or more moieties selected from the group consisting of aryl, heteroaryl, heterocyclyl, cycloalkyl, alkylaryl and arylalkyl, wherein each of any of the aforementioned alkyl, alkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, alkylaryl and arylalkyl groups of T is unsubstituted or optionally independently substituted with one to four R10 moieties;
U is selected from the group consisting of a covalent bond, —N(R4)—, —N(R4)C(R4)2—, —N(R4)C(O)—, —O—, —N(R4)S(O)2—, —N(R4)C(O)N(R4)—, and —N(R4)C(S)N(R4)—;
V is absent or present, and if present V is selected from the group consisting of alkyl, aryl, heteroaryl, heterocyclyl and cycloalkyl, said aryl, heteroaryl, heterocyclyl, cycloalkyl, alkylaryl and arylalkyl being optionally fused with one or more moieties selected from the group consisting of aryl, heteroaryl, heterocyclyl, cycloalkyl, alkylaryl and arylalkyl, wherein each of any of the aforementioned alkyl, aryl, heteroaryl, heterocyclyl and cycloalkyl is unsubstituted or optionally independently substituted with one to four R10 moieties;
Y is selected from the group consisting of a covalent bond, —(C(R4)2)n—, —N(R4)—, —C(O)N(R4)—, —N(R4)C(O)—, —N(R4)C(O)N(R4)—, —S(O)2N(R4)—, —N(R4) —S(O)2, —O—, —S—, —C(O)—, —S(O)—, and —S(O)2—;
Z is selected from the group consisting of a covalent bond, —(C(R4)2)n—, —N(R4)—, —C(O)N(R4)—, —N(R4)C(O)—, —N(R4)C(O)N(R4)—, —S(O)2N(R4)—, —N(R4) —S(O)2—, —O—, —S—, —C(O)—, —S(O)—, and —S(O)2—;
n is 1 to 3;
R1 is selected from the group consisting of H, —OR4, halogen, alkyl, fluoroalkyl, aryl, heteroaryl, heterocyclyl, alkylaryl, alkylheteroaryl and arylalkyl, wherein each of the alkyl, fluoroalkyl, aryl, heteroaryl, heterocyclyl, alkylaryl, alkylheteroaryl and arylalkyl groups of R1 is unsubstituted or optionally independently substituted with one to four R20 moieties, with the proviso that when Y is present and Y is N, S or O, then R1 is not halogen;
R2 is selected from the group consisting of H, —OR4, halogen, alkyl, fluoroalkyl, aryl, heteroaryl, heterocyclyl, alkylaryl, alkylheteroaryl and arylalkyl, wherein each of the alkyl, fluoroalkyl, aryl, heteroaryl, heterocyclyl, alkylaryl, alkylheteroaryl and arylalkyl groups of R2 is unsubstituted or optionally independently substituted with one to four R20 moieties, with the proviso that when Z is present and Z is N, S or O, then R2 is not halogen;
each R4 is the same or different and is independently selected from the group consisting of H, alkyl, —CH2C≡CCH3, —CH2C≡CCH2OH, and —CH2-cyclopropyl;
R10 is selected from the group consisting of —OR4, —N(R4)2, —O(fluoroalkyl), halogen, alkyl, fluoroalkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, alkylaryl and arylalkyl, wherein each of the alkyl, fluoroalkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, alkylaryl and arylalkyl groups of R10 is unsubstituted or optionally independently substituted with one to four R30 moieties which can be the same or different, each R30 moiety being independently selected from the group of R30 moieties below;
R20 is selected from the group consisting of halogen, alkyl, fluoroalkyl; and
R30 is selected from the group consisting of halogen, alkyl, and fluoroalkyl.