Synthesis and pharmacological activity of angiotensin converting enzyme inhibitors: N-(mercaptoacyl)-4-substituted-(S)-prolines

E M Smith; G F Swiss; B R Neustadt; E H Gold; J A Sommer; A D Brown; P J Chiu; R Moran; E J Sybertz; T Baum

doi:10.1021/jm00399a033

Synthesis and pharmacological activity of angiotensin converting enzyme inhibitors: N-(mercaptoacyl)-4-substituted-(S)-prolines

J Med Chem. 1988 Apr;31(4):875-85. doi: 10.1021/jm00399a033.

Authors

E M Smith¹, G F Swiss, B R Neustadt, E H Gold, J A Sommer, A D Brown, P J Chiu, R Moran, E J Sybertz, T Baum

Affiliation

¹ Department of Medicinal Chemistry, Schering-Plough Corporation, Bloomfield, New Jersey 07003.

PMID: 2832605
DOI: 10.1021/jm00399a033

Abstract

The synthesis of a series of N-(mercaptoacyl)-4-substituted-(S)-prolines (2 and 3) is described. These compounds were evaluated in vitro for inhibition of angiotensin-converting enzyme (ACE), and selected compounds were evaluated in vivo for ACE inhibition. The most potent compounds in vitro are 108, 109, 111, 114, and 116, having relative potencies of 1.0, 1.0, 1.3, 1.1, and 2.6 as compared to the potency of captopril. The most potent compounds in vivo intravenously are 108, 111, 114, 116, 117, and 97.

MeSH terms

Angiotensin-Converting Enzyme Inhibitors / chemical synthesis*
Angiotensin-Converting Enzyme Inhibitors / pharmacology
Animals
Antihypertensive Agents / chemical synthesis*
Antihypertensive Agents / therapeutic use
Bradykinin / metabolism
Hypertension / drug therapy
Hypertension / enzymology
Peptidyl-Dipeptidase A / metabolism
Proline / analogs & derivatives*
Proline / chemical synthesis
Proline / pharmacology
Rats
Rats, Inbred SHR
Structure-Activity Relationship
Sulfhydryl Compounds / chemical synthesis*
Sulfhydryl Compounds / pharmacology

Substances

Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Agents
Sulfhydryl Compounds
Proline
Peptidyl-Dipeptidase A
Bradykinin