This invention relates to acetylenic esters that are useful in the treatment of fungal diseases and hypercholesterolemic conditions.
Fermentation broths of certain strains of Streptoverticillium hiroshimense and Nocardia have been shown to produce the triyne carbonate 5-(1-hydroxy-2,4,6-heptatriynyl)-2-oxo-1,3-dioxolane-4-heptanoic acid, Formula A, ##STR1## wherein R is hydrogen, or salts thereof. M. D. Lewis and R. Menes, Tetrahedron Lett., 28, 5129-5132 (1987); See also U.S. patent application Ser. Nos. 07/053,920 (now U.S. Pat. No. 4,806,565), 07/053,921 (now U.S. Pat. No. 4,806,566), 07/053,926, and 07/053,973 (now U.S. Pat. No. 4,780,311), all filed May 26, 1987. The triyne carbonate A is a potent inhibitor of cytosolic .beta.-ketothiolase, the initial enzyme of cholesterol biosynthesis, and is also active against certain fungal and bacterial strains. Utility against hypercholesterolemia and infectious diseases is limited, however, by the relative instability of the compound in vivo. The compounds of the present invention have been prepared as part of a program to improve both inherent biological activity and in vivo stability relative to the triyne carbonate of Formula A.
USPTO Backgrounds
USPTO Backgrounds