Sulfamide and bis-sulfamide amino acid derivatives as inhibitors of proteolytic enzymes

摘要

Compounds of the general formula I are provided: ;and pharmaceutically acceptable salts thereof, wherein,;Z is a chemical species or R_i capable of binding at a primary specificity site of a protease;;Y is a chemical species reactive to a specific class of protease;;each of R₂, R₃, R₅ and R₇ is independently selected from the group consisting hydrogen, alkyls, aryls, substituted aryls, alkylaryls and arylalkyls;;R₄ and R₆ are independently selected from the group consisting of:;(a) H, alkyl, aryl, arylalkyl, alkylaryl, substituted derivatives thereof, and R_i;;(b) —C(O)OH and derivatives thereof, said derivatives selected from the group consisting of —C(O)OQ, —C(O)NR_YR_Z, —C(O)[NHCHR_i(q)C(O)]_qOQ, and —C(O)[NHCHR_i(q)C(O)]_qNR_YR_Z; and;(c) —CHR_iNH₂ and derivatives thereof, said derivatives selected from the group consisting of —CHR_iNHW, —CHR_iNHC(O)OQ, —CHR_iNHC(O)R, —CHR_iNHC(O)NR_YR_Z, —CHR_iNHC(O)[NHCHR_i(q)C(O)]_qOQ, —CHR_iNHSO₂R, and —CHR_iNH[C(O)CHR_i(r)NH]_rW, where q and r independently are integers from 1 to 10 inclusive; J is a carboxyl protecting group; G is an amino protecting group; Q is H, R or J; W is H, R or G; each R_i is independently selected from naturally or non-naturally occurring amino acid side chains; R is alkyl, aryl, substituted aryl, alkylaryl, arylalkyl, or heterocyclic radical; and each R_Y and R_Z is independently H, alkyl, aryl, substituted aryl, alkylaryl, arylalkyl, or heterocyclic radical.