Determination of the lipophilicity of pyrimido[5,4-c]quinoline derivatives by reversed-phase thin-layer chromatography. Part 1. Lipophilicity of pyrimido[5,4-c]quinolin-4(3H)-ones and 1,2,3,4-tetrahydropyrimido[5,4-c]quinolin-2,4-diones

Abstract

The lipophilicity of new bioactive pyrimido[5,4- c ]quinolin-4(3 H )-ones and 1,2,3,4-tetrahydropyrimido[5,4- c ]quinolin-2,4-diones has been determined by reversed-phase thin-layer chromatography with DMF-TRIS buffer as mobile phase. The R M values of the compounds were linearly dependent on the concentration of DMF in the mobile phase. Experimental lipophilicity (log P TLC = log D 7.4 ) was determined by use of a calibration curve prepared by chromatography of six standards. The partition coefficients (log P ) were calculated by use of software and compared with experimental values of log P TLC (log D 7.4 ) and log P neutral , for the non-ionized molecules. The dissociation constant (p K a ) was calculated for all the compounds by use of the pKalc 3.1 prediction module of the Pallas system and used to define the partition coefficient (log P neutral ) of the compounds which can ionize under the experimental conditions. To evaluate the validity of the p K a values obtained, experimental p K a values were ...