| 摘要 |
Inhibitors of the Zn<+2>-metalloendopeptidases, enkephalinase, angiotensin-converting enzyme, and collagenase, intermediates for synthesizing the inhibitors, and methods of making and using the inhibitors, are provided. The enkephalinase inhibitors of the invention are useful as analgesics or antihypertensives. The angiotensin-converting enzyme inhibitors of the invention are useful as anti-hypertensives. The collagenase inhibitors of the invention are useful in treating diseases, such as corneal ulceration, periodontal disease, and arthritis, which involve undesirable collagen degradation. The inhibitors of the invention are peptide or peptide ester derivatives of the intermediates of the invention, whichare N-acyl derivatives of amino acids of the formula X10-NH-CHR9-(CO2H), wherein X10 is selected from the group consisting of N=C-CHR20-(C=O)- and X21(CR22R23)(CHR24)(C=O)-, wherein R20 is hydrogen or alkyl of 1 to 3 carbon atoms, R22, R23 and R24 are each independently hydrogen or alkyl of 1 to 3 carbon atoms, and X21 is fluoro, chloro or bromo; and R9 is benzyl, alkyl of 1-5 carbon atoms, or hydrogen. |
