Conformational studies of a family of related antimalarial phenanthrene amino alcohols

Abstract

A comformational study utilizing quantum chemical methods was performed on a family of antimalarial .alpha.-(piperidyl)-3,6-bis(trifluoromethyl)-9-phenanthrenemethanols whose structures differ by the placement of the substituent on either the 2, 3 or 4 position of the piperidyl ring. The antimalarial activity of these 3-substituted compounds was shown experimentally to be highly stereospecific while the 2-substituted compounds are not and the 4-substituted compounds are inactive. Such observed differences in behavior are correlated with conformational results and a pharmacophore is postulated. The identity of the active racemate of the 3-piperidyl compound is predicted.