Inhibition of oxidosqualene cyclase by substituted quinolizidines

Substituted hydroxyquinolizidines have been synthesized as conformationally restricted analogs of the type II high-energy intermediate formed during the cyclization of 2,3-oxidosqualene to lanosterol. Compounds 4a and 4b were found to be potent inhibitors of rat liver oxidosqualene cyclase (OSC) with K(i) values of 0.51 muM and 0.11 muM, respectively.