Caspase inhibitors

摘要

A compound, or a pharmaceutically acceptable salt or ester thereof, of formula I:
X—W
wherein X is a caspase-selective structure and W has the structure of
—NH—CH(Y)(Z)
wherein Y is a structure that can form a reversible covalent bond with a caspase; and

Z is selected from a carboxyl moiety or a carboxylic acid mimetic.

主权项

1. A compound, or a pharmaceutically acceptable salt, hydrate or ester thereof, of formula II:wherein
R1 is H, —C(O)R8, —C(O)C(O)R8, —S(O)2R8, —S(O)R8, —C(O)OR8, —C(O)N(H)R8, —S(O)2N(H)—R8, —S(O)N(H)—R8, —C(O)C(O)N(H)R8, —C(O)CH═CHR8, —C(O)CH2OR8, —C(O)CH2N(H)R8, —C(O)N(R8)2, —S(O)2N(R8)2, —S(O)N(R8)2, —C(O)C(O)N(R8)2, —C(O)CH2N(R8)2, —CH2R8, —CH2-alkenyl-R8, or —CH2-alkynyl-R8; R2 is H and each R6 is independently —H, or —R8; or R2 and R6 together with the atoms to which they are bound, form a 3 to 7 membered heterocyclic ring system; R22 is —C(R6)2—; R3 and a first R4 together with the atoms to which they are bound, form a 3 to 7 membered heterocyclic ring system, and a second R4 is independently —H or —R8; R5 is —H; each R8 is independently alkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, alkylcycloalkyl, alkylaryl, alkylheteroaryl or alkylheterocyclyl; R21 is —CN or —C(O)OR9; R20 is —C(O)OR9, or a heteroaryl; R9 is —H, alkyl, or —CN; and m is 0 or 1; provided that at least R21 is —CN or —C(O)OCN, or R20 is —C(O)OCN.