Inhibitors of cysteine and serine proteases particularly cathepsin K that are useful in the treatment of diseases that cause bone loss

摘要

The specification describes compounds of formula (I) which have the property of inhibiting cysteine proteases of papain and cathepsin K wherein: A is C(O) or CH(OH); R is H, C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar-C0-6alkyl, Het-C0-6alkyl, R5C(O)-, R5C(S)-, R5SO2-, R50C(O)-, R5R'NC(O)-, R5R'NC(S)-, adamantyl-C(O)-, or 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 R3 independently is H, C2 6alkenyl, C2-6alkynyl, Het, Ar or C1-6alkyl optionally substituted by OR', SR. NR'2, R'NC(O)OR5, C02R', C02NR'2, N(C=NH)NH2, Het or Ar; R4 is H, C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar-C0-6alkyl, Het-C0-6alkyl, R5C(O)-, R5C(S)-, R5SO2-, R50C(O)-, R5R'NC(O)-, R5R'NC(S)-, R'HNCH(R')C(O)-, or R5OC(O)NR'CH(R')C(O)-; each R5 independently is C3-6cycloalkyl-C0-6alkyl, Ar-C0-6alkyl, Het-C0-6alkyl, Ar-C0-6alkoxy, Het-Co 6alkoxy, or C1-6alkyl optionally substituted by OR', SR', NR'2, R'NC(O)OR5, C02R', C02NR'2, N(C=NH)NH2, Het or Ar; R6 is H, C1-6alkyl, Ar-C0-6alkyl, or Het-C0-6alkyl and R7 is H, C1-6alkyl, C36cycloalkyl-C0-6alkyl, Ar-C0-6alkyl, Het-C0-6alkyl, R5C(O)-, R5C(S)-, R5SO2-, R5OC(O)-, R5R'NC(O)-, R5R'NC(S)-, R'HNCH(R')C(O)-, or R5OC(O)NR'CH(R')C(O)-; or R6 and R7 are connected to form a pyrrolidine, a piperidine, or a morpholine ring; each R' independently is H, C1-6alkyl, Ar-C0-6alkyl, or Het-Co 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 isO, 1, or2; or a pharmaceutically acceptable salt thereof. Specific representative compounds are named in Examples 1 - 198.