Determination of the lipophilicity of antiarrhythmic and antihypertensive 1-[2-hydroxy- or 1-[2-acetoxy-3-(4-aryl-1-piperazinyl)propyl]-pyrrolidin-2-one derivatives

The lipophilicity of some antiarrhythmic and antihypertensive [2-hydroxy- o r 1- [2-acetoxy-3-(4-aryl-1-piperazinyl)propyl] pyrrolidin-2-one derivative s [1-11] has been investigated. The relative lipophilicity (R-M of the comp ounds was determined by reversed-phase thin-layer chromatography with a mix ture of acetone, methanol and water as the mobile phase. The R-M of each co mpound decreased linearly with increasing concentration of acetone, The par tition coefficients (log P-SYBYL) of the compounds were calculated by use o f the Sybyl program. Comparison of R-M0 and logP(SYBYL) enabled calculation of clog P values. The distribution coefficient at a given pH (log D) value was calculated by use of experimental pK(a) and clog P values.