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    • 5. 发明授权
    • Sulfamide and bis-sulfamide amino acid derivatives as inhibitors of proteolytic enzymes
    • 磺酰胺和双磺酰胺氨基酸衍生物作为蛋白水解酶的抑制剂
    • US06495358B1
    • 2002-12-17
    • US09552554
    • 2000-04-19
    • William C. Groutas
    • William C. Groutas
    • C12N948
    • C07C307/06Y02P20/55
    • 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 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.
    • 提供通式I的化合物及其药学上可接受的盐,其中Z是能够在蛋白酶的主要特异性位点结合的化学物质或R 1; Y是与特定类别的蛋白酶反应的化学物质;每个 R2,R3,R5和R7独立地选自氢,烷基,芳基,取代的芳基,烷基芳基和芳基烷基; R4和R6独立地选自:(a)H,烷基,芳基,芳烷基 烷基芳基,取代的衍生物和R 1;(b)-C(O)OH及其衍生物,所述衍生物选自-C(O)OQ,-C(O)NRYRZ,-C(O) [NHCHRi(q)C(O)] qOQ和-C(O)[NHCHRi(q)C(O)] qNRYRZ; 所述衍生物选自-CHRiNHW,-CHRiNHC(O)OQ,-CHR1NHC(O)R,-CHR1NHC(O)NRYRZ,-CHR1NHC(O)[NHCHRi(O) q)C(O)] qOQ,-CHR 1 NHSO 2 R和-CHR 1 NH [C(O)CHR 1(r)NH] rW,其中q和r独立地为1至10的整数; J为羧基保护基; G是氨基保护基; Q是H,R或J; W是H,R或G; 每个R 1独立地选自天然或非天然存在的氨基酸侧链; R是烷基,芳基,取代的芳基,烷基芳基,芳烷基或杂环基; 并且每个RY和RZ独立地为H,烷基,芳基,取代的芳基,烷基芳基,芳基烷基或杂环基。