3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 9. The synthesis and biological evaluation of novel simvastatin analogs.
J Med Chem
; 35(21): 3813-21, 1992 Oct 16.
Article
em En
| MEDLINE
| ID: mdl-1433193
ABSTRACT
Substitution of hydroxy and hydroxyalkyl functionality at C-7 of the hexahydronaphthalene nucleus of simvastatin has provided novel analogs. The synthetic strategy employed epoxidation or Lewis acid-catalyzed aldol reaction of the 8-keto silyl enol ether as a key reactive intermediate. These analogs were evaluated as potential hypocholesterolemic agents via initial determination of their ability to inhibit HMG-CoA reductase in vitro. Oral activity of these compounds was determined in an acute rat model and a three-week study in cholestyramine-primed dogs. Compounds were identified that possessed in vitro and in vivo activity comparable to that of simvastatin.
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Base de dados:
MEDLINE
Assunto principal:
Lovastatina
/
Inibidores de Hidroximetilglutaril-CoA Redutases
/
Anticolesterolemiantes
Idioma:
En
Ano de publicação:
1992
Tipo de documento:
Article