Structure-activity relationship studies: study of the analgesic properties of a series of synthesized esters of 3- (4-benzyl-1-piperazinyl) 1-phenylpropanols.

Abstract

Four previously stynthesized derivatives of 3- (4-benzyl-1-piperazinyl)-1-phenylpropanol were screened for analgesic activity in albino mice using a variation of the Eddy and Lambach hot plate method. The result showed that the most significant analgesic effect was elicited by the parent secondary 3-piperazinylpropanol, namely 3-(4-benzyl-1-piperazinyl)-1-phenylpropanol. Its esterification products with propanoyl, benzoyl and phenylacetyl chlorides exhibited reduced analgesic properties. The percent maximum protection against thermal pain produced by Aspirin (71.43%) was twice as high as that produced by the most active of the four derivatives (43.65%). The analgesic effect of the compounds was dose dependent. From acute toxicity studies in mice, the LD50 values were estimated to be in range of moderate toxicity (89.74 to 243 mg/kg). The most active of the compounds studied, namely, 3-(4-benzyl-1-piperazinyl-1-phenylpropanols, was also found to be the most toxic. The margin between its safe doses and its LD50 (89.74 mg/kg) was found to be very narrow. Esterification of the 3-(4-benzyl-1-piperazinyl)-1-phenylpropanol led to decrease in its analgesic activity and also a decrease in its toxicity.