Sulfamide and bis-sulfamide amino acid derivatives as inhibitors of proteolytic enzymes
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Compounds of the general formula (I) are provided, and pharmaceutically acceptable salts thereof, wherein, Z is a chemical species or Ri 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 of 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 Ri; (b) --C(O)OH and derivatives thereof, said derivatives selected from the group consisting of --C(O)OQ, --C(O)NRYRZ, --C(O)[NHCHRi(q)C(O)]qOQ, and --C(O)[NHCHRi(q)C(O)]qNRYRZ; and (c) --CHRiNH2 and derivatives thereof, said derivatives selected from the group consisting of --CHRiNHW, --CHRiNHC(O)OQ, --CHRiNHC(O)R, --CHRiNHC(O)NRYRZ, --CHRiNHC(O)[NHCHRi(q)C(O)]qOQ, --CHRiNHSO2R, and --CHRiNH[C(O)CHRi(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 Ri 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 RY and RZ is independently H, alkyl, aryl, substituted aryl, alkylaryl, arylalkyl, or heterocyclic radical.
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International Application No: PCT/US2001/012588 filed April 18, 2001. Patent No: WO/2001/081561 granted November 1, 2001.