Showing papers by "Miguel A. Ondetti published in 1987"

Use of enkephalinase inhibitors as analgesic agents

Abstract: Mercaptoalkanoyl and acylmercaptoalkanoyl compounds of the formula ##STR1## wherein n is an integer from one to fifteen possess enkephalinase inhibition activity and are useful as analgesic agents.

Angiotensin-Converting Enzyme Inhibitors: Accomplishments and Challenges

Abstract: Two different structural types were proposed in 1977 (1) as leads for the development of nonpeptidic angiotensin-converting enzyme (ACE) inhibitors: mercaptoalkanoyl amino acids and carboxyalkanoyl amino acids.The development of the first structural type led to the identification of captopril, the first orally active ACE inhibitor to reach clinical application in hypertension and congestive heart failure. Elaboration of the second structural type by Patchett and collaborators led to the development of a new class of potent ACE inhibitors; carboxyalkyl dipeptides, and to the identification of enalapril, the second orally active ACE inhibitor to reach clinical application. Detailed structure-activity investigations (2, 3) indicate that both types of inhibitors bind to the active site in similar manner. The electrostatic interaction through the proline carboxyl, hydrogen bonding through the amide carbonyl, and the hydrophobic and/or entropic contributions of the five member ring of proline and the α-methyl g...

Certain [(lower alkanoyl-thio)methyl-1-oxo-3-phenyl propyl amino]benzene lower alkanoic acid or ester derivatives which inhibit enkephalinase

Abstract: Acylmercaptoalkanoyl compounds of the formula ##STR1## wherein n is an integer from one to fifteen possess enkephalinase inhibition activity and are useful as analgesic agents.