US 7,553,873 B2
Glutamate aggrecanase inhibitors
Phaik-Eng Sum, Pomona, N.Y. (US); Jerauld Stanley Skotnicki, Westfield, N.J. (US); Steve Yik-Kai Tam, Wellesley, Mass. (US); Tarek Suhayl Mansour, New City, N.Y. (US); David Brian How, Nyack, N.Y. (US); Joshua James Sabatini, White Plains, N.Y. (US); Jason Shaoyun Xiang, Winchester, Mass. (US); and Eric Feyfant, Lexington, Mass. (US)
Assigned to Wyeth, Madison, N.J. (US)
Filed on Jul. 11, 2006, as Appl. No. 11/484,005.
Claims priority of provisional application 60/697590, filed on Jul. 11, 2005.
Prior Publication US 2007/0043066 A1, Feb. 22, 2007
Int. Cl. A61K 31/166 (2006.01); A61K 31/192 (2006.01); C07C 63/06 (2006.01); C07C 237/28 (2006.01)
U.S. Cl. 514—563  [514/616; 562/435; 562/450; 564/155] 37 Claims
 
1. A compound of the formula (I):

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt thereof,
wherein
W is —C(O);
R1 is biphenyl optionally substituted with one or more of R5 or R6, and when R1 is substituted with more than one of R5 or R6, the substituents can be identical or different;
R2 is hydrogen;
R3 is —CO2H, —CONHOH, —CONHR7, or —COOR7;
R4 is —CONR9R10;
R5 is aryl, —NHCO-aryl, —NHCO-heteroaryl, (C1-C6)alkyl, —O—(C1-C6)alkyl, or —NHCO—(C1-C6)alkyl, each alkyl, aryl, or heteroaryl optionally substituted with one or more of R6, and when R5 is substituted with more than one R6, the substituents can be identical or different;
R6 is hydrogen, halogen, —CF3, —OH, —CO2R7, —COR7, (C2-C6)alkynyl, (C2-C6)alkenyl, —O—(C1-C6)alkyl-(C3-C6)cycloalkyl, —O—(C1-C6)alkyl substituted with aryl or O-aryl, each aryl, optionally substituted with one or more of R13;
R12 is aryl optionally substituted with one or more of R13;
R7 is hydrogen or (C1-C6)alkyl;
R9 is hydrogen or (C1-C6)alkyl optionally substituted with one or more R12;
R10 is (C1-C6)alkyl substituted with one or more R12;
R13 is halogen, —O—(C1-C6)alkyl, —CO2H, —OH, —CF3, hydrogen, (C1-C6)alkyl, aryl, heteroaryl, (C2-C6)alkenyl, (C2-C6)alkynyl, cycloalkyl, cycloalkyl substituted with —OH, aryl substituted with —NH2, aryl substituted with —O—(C1-C6)alkyl, —(CH2)n-aryl, or —(CH2)n-heteroaryl;
m is 0;
n is 0-4; and
p is 2.