US 7,612,065 B2
Inhibitors of c-JUN N-terminal kinases (JNK)
Jeremy Green, Waltham, Mass. (US); Susanne Wilke, Norwich, Conn. (US); Francesco Salituro, Marlborough, Mass. (US); Edmund Harrington, Plymouth, Mass. (US); Jingrong Cao, Newton, Mass. (US); Guy Bemis, Arlington, Mass. (US); and Huai Gao, Arlington, Mass. (US)
Assigned to Vertex Pharmaceuticals Incorporated, Cambridge, Mass. (US)
Filed on Mar. 28, 2007, as Appl. No. 11/729,420.
Prior Publication US 2008/0033022 A1, Feb. 07, 2008
Int. Cl. A61K 31/535 (2006.01); A61K 31/445 (2006.01); A61K 31/44 (2006.01); A61K 31/405 (2006.01); C07D 413/12 (2006.01); C07D 401/12 (2006.01); C07D 211/22 (2006.01); C07D 213/26 (2006.01); C07D 209/34 (2006.01)
U.S. Cl. 514—231.5  [514/320; 514/415; 514/416; 544/143; 546/196; 546/197; 546/258; 548/469; 548/483; 548/484; 548/486; 548/491] 22 Claims
 
1. A compound of the formula:

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt thereof; wherein
Y is selected from —(CH2)-Q1; —(CO)-Q1; —(CO)NH-Q1; —(CO)—O-Q1; —(SO2)-Q1 or —(SO2)NH-Q1;
Q1 is a C1-C6 straight chain or branched alkyl or alkenyl group; a 5-7 membered aromatic or non-aromatic heterocyclic ring; or a 9-14 membered bicyclic or tricyclic aromatic or non-aromatic carbocyclic or heterocyclic ring system, wherein said alkyl, alkenyl, ring or ring system is optionally substituted with one to four substituents, each of which is independently selected from NH2, NH—R, N(R)2, NO2, OH, OR, CF3, halo, CN, CO2H, C(O)—NH2, C(O)—NH—R, C(O)—N(R)2, C(O)—R, SR, S(O)—R, S(O)2—R, S(O)2—NH—R or —R;
W is N;
R8 is a lone pair of electrons;
A1 is CR1;
A2 is CR2;
A3 is CR3;
A4 is CR4;
R1 is —NHR5, —OR5, —SR5, or —R5;
R2, R3, and R4 are independently selected from —(CO)NH2, —(CO)NHR, —(CO)N(R)2, —NHR5, —NHCH2R5, —OR5, —SR5, —R5, —NH(CO)—R6, —NH(CO)—NHR6, —NH(CO)—NH(CO)R6, —NH(CO)—OR6, —NH(SO2)—R6, —NH(SO2)—NHR6, —C(O)OH, —C(O)OR, —(CO)-Q1, —(CO)NH-Q1, —(CO)NR-Q1, —(CO)—O-Q1, —(SO2)-Q1 or —(SO2)NH-Q1;
R5 and R6 are each independently selected from H; N(R)2, NHOH, NO2, C(O)OR or halo; a C1-C6 straight chain or branched alkyl, alkenyl or alkynyl group; a 5-7 membered aromatic or non-aromatic carbocyclic or heterocyclic ring; or a 9-14 membered bicyclic or tricyclic aromatic or non-aromatic carbocyclic or heterocyclic ring; wherein said alkyl, alkenyl, ring or ring system is optionally substituted with one to four substituents, each of which is independently selected from NH2, NHR, NHC(O)OR, N(R)2, NO2, OH, OR, CF3, halo, CN, Si(R)3, CO2H, COOR, CONH2, CONHR, CON(R)2, COR, SR, S(O)R, S(O)2R, S(O)2NHR or R;
R is a C1-C6 straight chain or branched alkyl or alkenyl group, a 5-7 membered aromatic or non-aromatic carbocyclic or heterocyclic ring, or a 9-10 membered bicyclic aromatic or non-aromatic carbocyclic or heterocyclic ring system.