(ARYLOXY)METHYLSILANE DERIVATIVES AS NEW CHOLESTEROL-BIOSYNTHESIS INHIBITORS - SYNTHESIS AND HYPOCHOLESTEROLEMIC ACTIVITY OF A NEW CLASS OFSQUALENE EPOXIDASE INHIBITORS

A series 3-substituted (aryloxy)silane derivatives of benzylamine (4, 4', or 4'') was synthetized and evaluated for hypocholesterolemic acti vity. Most of the new silane derivatives were identified as potent inh ibitors of pig liver squalene epoxidase with IC50 values in the submic romolar range. In vitro inhibition of cholesterol biosynthesis in Hep- G(2) cells was observed with a very good potency for the ene-yne deriv atives 4a, 4i, 4n, 4q, and 4u as well as for the yne-yne compound 4''. In, vivo, 4i, 4u, 4', and 4'' were found to decrease cholesterol bios ynthesis in rats upon oral administration with ED(50) values in the ra nge of 2-7 mg/kg. Therefore, these new (aryloxy)methylsilane derivativ es of benzylamine represent a new class of potent squalene epoxidase i nhibitors with promising hypocholesterolemic properties.