N-Aralkyl-piperidyl Carbanilates as Hypocholesteremic Agents

Abstract

A number of N-aralkyl-N-methylaminoethyl carbanilates have been described in the literature as possessing hypocholesteremic activity. This series of compounds now has been extended to include 12 new o-[1-(substituted benzyl)-4-piperidyl]-N-(sub-stituted phenyl) urethans and six new o-[1-(substituted benzyl)-4-piperidylideneimino]-N-(substituted phenyl) urethans. Two new derivatives of N1-[(1-substituted benzyl)-4-piperidyl]-N3(p-chloro-phenyl)urea have been prepared. Eleven intermediate piperidine derivatives, that have not been previously described in the literature, have been prepared and characterized. Fifteen of these new compounds have been studied for their ability to inhibit the incorporation of mevalonate-2-14C into cholesterol by homogenates of rat liver. Six of the compounds exhibited greater than 50% inhibition when tested at a concentration of 2 × 10−5M. Appreciable incorporation of radioactivity into 7-dehydrocholesterol was observed with these six compounds. No significant reduction in serum cholesterol levels could be found in rats dosed at a level of 40 mg./ kg. of body weight over a period of 7 days.