The study of the lipophilicity of some aminoalkanol derivatives with anticonvulsant activity

Abstract

A series of new (phenoxyethyl)aminoalkanol derivatives were synthesized and evaluated for their anticonvulsant activity. The most promising compound seemed to be (R,S)-1N-[(2,6-dimethyl)phenoxyethyl]amino-2-butanol, which displayed anti-MES activity (in mice, i.p.) with protective index (TD(50) /ED(50) ) of 5.712, corresponding to that of phenytoin (6.6), carbamazepine (4.9) and valproate (1.7). The lipophilicity of compounds 1-17 exhibiting anticonvulsant activity was investigated. Their lipophilicities (R(M0) ) were determined using reversed-phase thin-layer chromatography (RP-TLC) with a mixture of acetone and water as mobile phases. The partition coefficients of 1-17 (logP) were also calculated using two computer programs (Pallas and ALOGPS) and compared with R(M0) . The relationship between anticonvulsant activity and lipophilicity of the tested substances was estimated.