Synthesis and biological activity of carboxylic acid replacement analogs of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline

The carboxylic acid group on the proline of 1 was replaced by a phosphoric acid, a hydroxamic acid, and a tetrazole to give compounds 2-4, respectively. Testing of 2-4 as angiotensin converting enzyme (ACE) inhibitors gave I50 values of 100, 1.6, and 22 microM, respectively, compared to 0.07 microM...

Full description

Saved in:
Bibliographic Details
Published inJournal of medicinal chemistry Vol. 28; no. 8; pp. 1067 - 1071
Main Authors Almquist, Ronald G, Chao, Wan Ru, Jennings-White, Clive
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 01.08.1985
Subjects
Angiotensin-Converting Enzyme Inhibitors
Animals
Antihypertensive Agents - chemical synthesis
Dipeptides - chemical synthesis
Dipeptides - metabolism
Dipeptides - pharmacology
Hypertension, Renovascular - drug therapy
Rats
Structure-Activity Relationship
Online AccessGet full text

Cover

More Information
Summary:The carboxylic acid group on the proline of 1 was replaced by a phosphoric acid, a hydroxamic acid, and a tetrazole to give compounds 2-4, respectively. Testing of 2-4 as angiotensin converting enzyme (ACE) inhibitors gave I50 values of 100, 1.6, and 22 microM, respectively, compared to 0.07 microM for 1. A hydroxamic acid derivative of the ketomethylene pentapeptide analogue 18 was then synthesized. This compound, 17, had an ACE I50 of 0.011 microM compared to 0.0076 microM for 18. Oral administration of 10 mg/kg of 17 to renal hypertensive rats had no effect on blood pressure or heart rate.
Bibliography:istex:AED7C6AE3BB73FA9510E36C499D507247401D160
ark:/67375/TPS-7SXWC4R2-D
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00146a015