Design and biological evaluation of a series of thiophene-based 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors

A series of highly functionalized thiophene-based 3,5-dihydroxyheptenoic acid derivatives ( 10) were prepared from aldehydes 6 by homologation, aldol condensation with ethyl acetoacetate dianion and stereoselective β-hydroxyketone reduction. High levels of HMG-CoA reductase inhibitory activity have...

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Bibliographic Details
Published inBioorganic & medicinal chemistry letters Vol. 7; no. 5; pp. 549 - 554
Main Authors Coppola, Gary M., Damon, Robert E., Yu, Harvey, Engstrom, Robert G., Scallen, Terrence J.
Format Journal Article
LanguageEnglish
Published Oxford Elsevier Ltd 04.03.1997
Elsevier
Subjects
Biological and medical sciences
General and cellular metabolism. Vitamins
Medical sciences
Pharmacology. Drug treatments
Diol
Enzyme
Enzyme inhibitor
In vitro
Aldol condensation
Chemical reduction
Stereoselectivity
In vivo
Thiophene derivatives
Sulfur heterocycle
Structure activity relation
Animal
Organic salt
Carboxylate
Chemical homologation
Oxidoreductases
Chemical synthesis
Antilipemic agent
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Summary:A series of highly functionalized thiophene-based 3,5-dihydroxyheptenoic acid derivatives ( 10) were prepared from aldehydes 6 by homologation, aldol condensation with ethyl acetoacetate dianion and stereoselective β-hydroxyketone reduction. High levels of HMG-CoA reductase inhibitory activity have been found within the series. The most active analog in vitro was 10i whereas in vivo, 10e, 10i, 10m, 10n, 10o, and 10v were approximately equipotent. A series of highly functionalized thiophene derivatives were synthesized and evaluated for in vitro and in vivo HMG-CoA Reductase activity.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(97)00065-6