CYSTEIN PROTEASE INHIBITORS

摘要

This invention relates to compounds of formula (I), wherein A is C(O) or CH(OH); R<1> is (1), (2), (3) or (4); R<2> is H, C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar-C0-6alkyl, Het-C0-6alkyl, R<5>C(O)-, R<5>C(S)-, R<5>SO2-, R<5>OC(O)-, R<5>R'NC(O)-, R<5>R'NC(S)-, adamantyl-C(O)-, or (5); R" is H, C1-6alkyl, Ar-C0-6alkyl, or Het-C0-6alkyl; R"' is H, C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar-C0-6alkyl, or Het-C0-6alkyl; each R<3> independently is H, C2-6alkenyl, C2-6alkynyl, Het, Ar or C1-6alkyl optionally substituted by OR', SR', NR'2, R'NC(O)OR<5>, CO2R', CO2NR'2, N(C=NH)NH2, Het or Ar; R<4> is H, C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar-C0-6alkyl, Het-C0-6alkyl, R<5>C(O)-, R<5>C(S)-, R<5>SO2-, R<5>OC(O)-, R<5>R'NC(O)-, R<5>R'NC(S)-, R'HNCH(R')C(O)-, or R<5>OC(O)NR'CH(R')C(O)-; each R<5> independently is C3-6cycloalkyl-C0-6alkyl, Ar-C0-6alkyl, Het-C0-6alkyl, Ar-C0-6alkoxy, Het-C0-6alkoxy, or C1-6alkyl optionally substituted by OR', SR', NR'2, R'NC(O)OR<5>, CO2R', CO2NR'2, N(C=NH)NH2, Het or Ar; R<6> is H, C1-6alkyl, Ar-C0-6alkyl, or Het-C0-6alkyl and R<7> is H, C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar-C0-6alkyl, Het-C0-6alkyl, R<5>C(O)-, R<5>C(S)-, R<5>SO2-, R<5>OC(O)-, R<5>R'NC(O)-, R<5>R'NC(S)-, R'HNCH(R')C(O)-, or R<5>OC(O)NR'CH(R')C(O)-; or R<6> and R<7> are connected to form a pyrrolidine, a piperidine, or a morpholine ring; each R' independently is H, C1-6alkyl, Ar-C0-6alkyl, or Het-C0-6alkyl; R* is H, C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar-C0-6alkyl, or Het-C0-6alkyl; Y is a single bond or O; each Z independently is CO or CH2; and n is 0, 1, or 2; or a pharmaceutically acceptable salt thereof, which are inhibitors of cysteine proteases, particularly cathepsin K, and are useful in the treatment of diseases in which inhibition of bone loss is a factor.