Caspase inhibitors and uses thereof

摘要

This invention provides novel compounds, and pharmaceutically acceptable derivatives thereof, that are useful as caspase inhibitors. These compounds have the general formula (IE):
where R 1 is hydrogen, CN, CHN 2 , R, -CH 2 Y;
R is an aliphatic group, a substituted aliphatic group, an aryl group, a substituted aryl group, an aralkyl group, a substituted aralkyl group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group;
Y is an electronegative leaving group or -OR, -SR, -OC=O (R), or -OPO(R 8 ) (R 9 );
R 8 and R 9 are independently selected from R or OR;
R 2 is CO 2 H, CH 2 CO 2 H, or esters or isosteres thereof;
R 3 is hydrogen or a C 1-6 straight chained or branched alkyl;
X 2 is selected from a valence bond, oxygen, sulfur, nitrogen or carbon;
R 4 and R 5 are each independently selected from hydrogen, halo, R, OR, SR, aryl, substituted aryl, OH, NO 2 , CN, NH 2 , NHR, N(R) 2 , NHCOR, NHCONHR, NHCON(R) 2 , NRCOR, NHCO 2 R, CO 2 R, CO 2 H, COR, CONHR, CON(R) 2 , S(O) 2 R, SONH 2 , S(O)R, SO 2 NHR, or NHS(O) 2 R; and
the fused ring is an aromatic or non-aromatic heterocyclic ring.