Estimation of the lipophilicity of antiarrhythmic and antihypertensive active 1-substituted pyrrolidin-2-one and pyrrolidine derivatives.

Department of Pharmaceutical Chemistry, Medical College, Jagiellonian University 30-688 Kraków, Medyczna 9, Poland.
Biomedical Chromatography (Impact Factor: 1.66). 08/2003; 17(5):318-24. DOI: 10.1002/bmc.246
Source: PubMed

ABSTRACT The lipophilicity of some antiarrhythmic and antihypertensive active 1-[2-hydroxy- or 1-[2-acetoxy-3-(4-aryl-1-piperazinyl)propyl]pyrrolidin-2-one derivatives (1-12) has been investigated. Their lipophilicity (R(MO) and log k') was determined by reversed-phase thin-layer chromatography and reversed-phase high-performance liquid chromatography with mixtures of acetonitrile and Tris buffer as mobile phases. The partition coefficients of compounds 1-12 (log P(ScilogP)) were also calculated with the ScilogP program. Comparison of R(MO), log k' and calculated log D(7.0 ScilogP) values enabled calculation of clog D(7.0 TLC) and clog D(7.0 HPLC) values. Preliminary quantitative structure-activity relationship studies indicated that for active compounds there is a dependence between affinity for alpha(2)-adrenoceptors and their clog D(7.0 HPLC) values.