US 7,524,842 B2
Compounds for the treatment of inflammatory disorders
Brian J. Lavey, New Providence, N.J. (US); Joseph A. Kozlowski, Princeton, N.J. (US); Guowei Zhou, Livingston, N.J. (US); Ling Tong, Warren, N.J. (US); Wensheng Yu, Edison, N.J. (US); Michael K. C. Wong, North Brunswick, N.J. (US); Bandarpalle B. Shankar, Branchburg, N.J. (US); Neng-Yang Shih, Lexington, Mass. (US); M. Arshad Siddiqui, Newton, Mass. (US); Kristin E. Rosner, Watertown, Mass. (US); Chaoyang Dai, Acton, Mass. (US); Janeta Popovici-Muller, Waltham, Mass. (US); Vinay M. Girijavallabhan, Watertown, Mass. (US); Dansu Li, Watertown, Mass. (US); Razia Rizvi, Bloomfield, N.J. (US); Lei Chen, Roselle Park, N.J. (US); De-Yi Yang, Morris Plains, N.J. (US); Robert Feltz, Parsippany, N.J. (US); and Seong Heon Kim, Livingston, N.J. (US)
Assigned to Schering Corporation, Kenilworth, N.J. (US)
Filed on Jan. 16, 2007, as Appl. No. 11/653,511.
Claims priority of provisional application 60/759300, filed on Jan. 17, 2006.
Prior Publication US 2007/0197564 A1, Aug. 23, 2007
Int. Cl. A61K 31/428 (2006.01); A61K 31/4015 (2006.01); A61K 31/4166 (2006.01); C07D 209/04 (2006.01); C07D 233/24 (2006.01); C07D 277/34 (2006.01); C07D 417/06 (2006.01)
U.S. Cl. 514—227.8  [514/373; 514/405; 514/414; 544/60; 548/209; 548/361.5; 548/465] 34 Claims
 
1. A compound represented by Formula (I):

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt, solvate, ester or isomer thereof, wherein:
ring A is selected from the group consisting of aryl and heteroaryl, each of which is substituted with —Y—R1 and -Z-R2 as shown;
X is selected from the group consisting of —S—, —O—, —S(O)2—, S(O)—, —(C(R3)2)m— and —N(R3)—;
T is alkynyl;
V is selected from the group consisting H, alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, and N-oxides of said heteroaryl and heterocyclyl, wherein when each of said cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, and N oxides of said heteroaryl and heterocyclyl contains two radicals on same or adjacent carbon atoms, said radicals may optionally be taken together with the carbon atom(s) to which they are attached to form a five- to eight-membered cycloalkyl, cycloalkenyl, aryl, heterocyclyl or heteroaryl ring, wherein each of the aforementioned cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl, optionally with said five- to eight-membered cycloalkyl, cycloalkenyl, aryl, heterocyclyl, or heteroaryl is independently unsubstituted or substituted with one to four R10 moieties which can be the same or different;
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—;
m is 1 to 3;
n is 1 to 3;
R1 is selected from the group consisting of H, cyano, alkynyl, halogen, alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl, and heterocyclyl, wherein when each of said cycloalkyl, heterocyclyl, aryl and heteroaryl contains two radicals on adjacent carbon atoms, said radicals may optionally be taken together with the carbon atoms to which they are attached to form a five- to eight-membered cycloalkyl, aryl, heterocyclyl or heteroaryl ring; wherein each of the R1 alkyl, alkynyl, aryl, heteroaryl, and heterocyclyl, optionally with the five or six-membered cycloalkyl, aryl, heterocyclyl or heteroaryl ring is unsubstituted or optionally independently substituted with one to four R20 moieties which can be the same or different; with the proviso that when Y is —N(R4)—, —S— or —O—, then R1 is not halogen or cyano;
R2 is selected from the group consisting of H, cyano, alkynyl, halogen, alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl, and heterocyclyl, wherein when each of said cycloalkyl, heterocyclyl, aryl and heteroaryl contains two radicals on adjacent carbon atoms, said radicals may optionally be taken together with the carbon atoms to which they are attached to form a five- to eight-membered cycloalkyl, aryl, heterocyclyl or heteroaryl ring; wherein each of the R2 alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl, optionally with the five or six-membered cycloalkyl, aryl, heterocyclyl or heteroaryl ring is unsubstituted or optionally independently substituted with one to four R20 moieties which can be the same or different; with the proviso that when Y is —N(R4)—, —S— or —(O)—, then R2 is not halogen or cyano;
each R3 is the same of different and is independently selected from the group consisting of H, alkyl, and aryl;
each R4 is the same or different and is independently selected from the group consisting of H, alkyl, cycloalkyl, haloalkyl, hydroxy, -alkylcycloalkyl, -alkyl-N(alkyl)2, heterocyclyl, aryl, and heteroaryl;
R10 is selected from the group consisting of hydrogen, cyano, nitro, —C(R4)═N—OR4, —OR4, —SR4, —N(R4)2, —S(O)R4, —S(O)2R4, —N(R4)S(O)2R4, —N(R4)—C(O)—R4, —C(O)N(R4)—S(O)2R4, —S(O)2N(R4—C(O)—R4, —C(O)N(R4)C(O)R4, —C(O)N(R4)C(O)NR4—S(O)2N(R4)2, —N(R4)—C(O)OR4, —OC(O)N(R4)2, —N(R4)C(O)N(R4)2, —S(O)2N(R4)2, —S(O)2N(R4)—C(O)—R4, —N(R4)—C(═NR4)—N(R4)2, —N(R4)—C(═N—CN)—N(R4)2, -haloalkoxy, —C(O)OR4, —C(O)R4, —C(O)N(R4)2, halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocyclyl, and cycloalkyl, wherein each of the R10 alkyl, aryl, heteroaryl, heterocyclyl, and cycloalkyl is unsubstituted or optionally independently substituted with one to four R30 moieties which can be the same or different;
or wherein two R10 moieties, when attached to the same or adjacent carbon atoms may optionally be taken together with the carbon atom(s) to which they are attached to form a cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl ring;
R20 is selected from the group consisting of cyano, nitro, —C(R4)═N—(O)R4, —OR4, —SR4, —N(R4)2, —S(O)R4, —S(O)2R4, —N(R4)S(O)2R4, —N(R4)—C(O)—R4, —C(O)N(R4)—S(O)2R4, —S(O)2N(R4)—C(O)—R4, —C(O)N(R4)C(O)R4, —C(O)N(R4)C(O)NR4 —S(O)2N(R4)2, —N(R4)—C(O)OR4, —OC(O)N(R4)2, —N(R4)C(O)N(R4)2, —S(O)2N(R4)2, —S(O)2N(R4)—C(O)—R4, —N(R4)—C(═NR4)—N(R4)2, —N(R4)—C(═N—CN)—N(R4)2, -haloalkoxy, —C(O)OR4, —C(O)R4, —C(O)N(R4)2, halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocyclyl, and cycloalkyl; wherein when each of said R20 aryl, heteroaryl, heterocyclyl and cycloalkyl contains two radicals on adjacent carbon atoms, said radicals may optionally be taken together with the carbon atoms to which they are attached to form a five- to eight-membered cycloalkyl, aryl, heterocyclyl or heteroaryl ring; wherein each of said R20 alkyl, aryl, heteroaryl, heterocyclyl, and cycloalkyl, optionally with said five- to eight-membered cycloalkyl, aryl, heterocyclyl or heteroaryl ring is unsubstituted or substituted with one to four moieties selected independently from the group consisting of alkyl, halo, haloalkyl, hydroxy, alkoxy, haloalkoxy, hydroxyalkyl, cyano, nitro, —NH2, —NH(alkyl), and —N(alkyl)2;
or when two R20 moieties when attached to the same or adjacent carbon atoms may optionally be taken together with the carbon atom(s) to which they are attached to form a cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl ring;
R30is selected from the group consisting of cyano, nitro, —C(R4)═N—(O)R4, —OR4, —SR4, —N(R4)2, —S(O)R4, —S(O)2R4, —N(R4)S(O)2R4, —N(R4)—C(O)—R4, —C(O)N(R4)—S(O)2R4, —S(O)2N(R4)—C(O)—R4, —C(O)N(R4)C(O)R4, —C(O)N(R4)C(O)NR4 —S(O)2N(R4)2, —N(R4)—C(O)OR4, —OC(O)N(R4)2, —N(R4)C(O)N(R4)2, —S(O)2N(R4)2, —S(O)2N(R4)—C(O)—R4, —N(R4)—C(═NR4)—N(R4)2, —N(R4)—C(═N—CN)—N(R4)2, -haloalkoxy, —C(O)OR4, —C(O)R4, —C(O)N(R4)2, halogen, alkyl, haloalkyl, aryl, heteroaryl, heterocyclyl, and cycloalkyl; wherein when each of said R30 aryl, heteroaryl, heterocyclyl and cycloalkyl contains two radicals on adjacent carbon atoms, said radicals may optionally be taken together with the carbon atoms to which they are attached to form a five- to eight-membered cycloalkyl, aryl, heterocyclyl or heteroaryl ring; wherein each of said R30 alkyl, aryl, heteroaryl, heterocyclyl, and cycloalkyl, optionally with said five- to eight-membered cycloalkyl, aryl, heterocyclyl or heteroaryl ring is unsubstituted or substituted with one to four moieties selected independently from the group consisting of alkyl, halo, haloalkyl, hydroxy, alkoxy, haloalkoxy, cyano, nitro, —NH2, —NH(alkyl), and —N(alkyl)2;
or when two R30 moieties when attached to the same or adjacent carbon atoms may optionally be taken together with the carbon atom(s) to which they are attached to form a cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl ring.