| 摘要 |
This invention relates to analogs of peptidase substrates in which the nitrogen atom of the scissile amide gorup of the substrate peptide has been replaced by H or a substituted carbonyl moiety. The contemplated peptidase inhibitors of the foregoing enzymes are selected from the generic formula R1NHCHR2C(O)X the hydrates, isosteres or the pharmaceutically acceptable salts thereof, wherein X is H or C(O)R3, R3 is H, methyl, ethyl, OH, methoxy or ethoxy, R1 is H, a protecting group, an alpha -amino acid or a peptide having 2 to 4 alpha -amino acids, optionally bearing a protecting group, R2 is a residue of an alpha -amino acid responsible for directing the inhibitor to the active site of the enzyme or is -A-SiR7R8R9, C1-10 alkyl, aralkyl or aryl, with A being a C1-6 alkylene, and each of R7, R8 and R9 being C1-10 alkyl, benzyl or phenethyl. These analogs of the peptidase substrates provide specific enzyme inhibitors for a variety of proteases, the inhibition of which will have useful physiological consequences in a variety of disease states. |
