Synthesis and biological activity of a ketomethylene analog of a tripeptide inhibitor of angiotensin converting enzyme

An analogue of a tripeptide inhibitor of angiotensin converting enzyme, Bz-Phe-Gly-Pro, has been synthesized in which the amide bond connecting phenylalanine and glycine has been replaced by a ketomethylene group. This nonpeptide analogue, 20, shows more potent converting enzyme inhibiting activity,...

Full description

Saved in:
Bibliographic Details
Published inJournal of medicinal chemistry Vol. 23; no. 12; pp. 1392 - 1398
Main Authors Almquist, Ronald G, Chao, Wan-Ru, Ellis, Marie E, Johnson, Howard L
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 01.12.1980
Subjects
Angiotensin I - antagonists & inhibitors
Angiotensin-Converting Enzyme Inhibitors
Animals
Chemical Phenomena
Chemistry
Dipeptides - chemical synthesis
Dipeptides - pharmacology
Guinea Pigs
In Vitro Techniques
Kinetics
Male
Muscle Contraction - drug effects
Online AccessGet full text

Cover

More Information
Summary:An analogue of a tripeptide inhibitor of angiotensin converting enzyme, Bz-Phe-Gly-Pro, has been synthesized in which the amide bond connecting phenylalanine and glycine has been replaced by a ketomethylene group. This nonpeptide analogue, 20, shows more potent converting enzyme inhibiting activity, I50 = 0.07 microM, than Bz-Phe-Gly-Pro, I50 = 9.4 microM, or than the orally active D-3-mercapto-2-methylpropanoyl-L-proline (captopril, 1), I50 = 0.30 microM. Compound 20 has a Ki of 1.06 X 10(-7) and either competitive or noncompetitive enzyme kinetics depending on what substrate is used in the converting enzyme assay. In tests for inhibition of angiotensin I induced contractions in the guinea pig ileum, 20 has one-tenth the activity of 1.
Bibliography:istex:35D63F2BEFF17C5AC1B967A50F493F7659A0F053
ark:/67375/TPS-NP4H9MP5-F
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00186a020