Merck + Co., Inc.

John G MacConnell

Byron H Arison

Shieh-Shung T Chen

Leeyuan Huang

Raymond F White

George A Doss

Helmut H Mrozik

Richard L Monaghan

George M Garrity

Louis Kaplan

Laszlo R Treiber

Brian R Petuch

Gregory D Berger

Jon D Polishook

Kevin M Byrne

August J Kempf

Magda M Gagliardi

Cholesterol lowering compound

New cholesterol lowering compounds are formed from the photochemical treatment of zaragozic acid A.

Chemical compounds

New cholesterol lowering compounds are formed from the photochemical treatment of the zaragozic acids.

Cholesterol lowering compounds

Cholesterol lowering compounds and compositions are formed from the photochemical treatment of the Zaragozic Acids followed by esterification. These compounds and compositions are active squalene synthetase inhibitors useful in the treatment of hypercholesterolemia.

Compounds of Structural Formula (I) ##STR1## are produced by directed biosynthesis. These compounds are squalene synthetase inhibitors and thus useful as cholesterol lowering agents, antifungal agents and cancer treatment agents.

Cholesterol lowering compounds produced by directed biosynthesis

This invention relates to compounds of structural formula (I): ##STR1## which are squalene synthase inhibitors and thus useful as cholesterol lowering agents. The compounds also exhibit antifungal activity and are inhibitors of farnesyl-protein transferase.

Cholesteral lowering agents

Derivatives of C-076 compounds are described in which the C-076 molecule, a series of macrolides, has the 23-hydroxy group thereof oxidized to the 23-keto group. The 23-keto compounds are prepared by selectively oxidizing the suitably protected 23-hydroxy compound using such oxidizing agents as pyridinium dichromate, chromic acid-dimethyl pyrazole, chromic acid, chromic acid-acetic acid, and the like. Alternatively, selective oxidation of the unprotected 23-hydroxy compound may be accomplished by placing the compound in soil. Further reaction of the oxidized C-076 compounds is also possible. The compounds thus produced have profound anthelmintic, insecticidal, ectoparasiticidal, and acaricidal activity. Compositions containing the described C-076 derivatives as the active ingredient thereof are also disclosed.

23-Keto derivatives of C-076 compounds

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Westfield, NJ, United States of America

John G MacConnell