INHIBITORS OF STEROL SYNTHESIS - EFFECTS OF A NEW FLUORINATED ANALOG OF 3-BETA-HYDROXY-5-ALPHA-CHOLEST-8(14)EN-15-ONE IN RATS

3 beta-Hydroxy-25,26,26,26,27,27,27-heptafluoro-5 alpha- cholest-8(14) -en-15-one (VII), an analog of 3 beta-hydroxy-5 alpha-cholest-8(14)-en -15-one (I) in which conversion to 26- and 25-oxygenated metabolites i s blocked by the F-7-substitution, was administered to male Sprague-Da wley rats at levels of from 0.025 to 0.15% by weight in a ground chow diet. Administration of VII resulted in lowering of the levels of seru m cholesterol at dosages as low as 0.025% by weight in diet. In marked contrast to I, VII had little or no effect on food consumption. Where as administration of I at a level of 0.1% by weight in diet resulted i n a cessation of growth, VII, at approximately the same molar concentr ation in diet, had only slight or no effect on changes in total body w eight. Significant levels of 25,26,26,26,27,27,27-heptafluorocholester ol (VIII) were observed in serum and liver, indicating the conversion of VII to VIII. Characterization of VIII in liver was based upon the r esults of gas chromatography, low and high resolution mass spectral st udies, infrared spectroscopy, and H-1 and C-13 nuclear magnetic resona nce spectroscopy. The levels of VIII in serum appeared to be related t o dosage and duration of administration of VII.