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

The lipophilicity of new bioactive pyrimido[5,4-c]quinolin-4(3H)-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, 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 (pK(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 pK(a) values obtained, experimental pK(a) values were determined for the quinoline nitrogen atom of the compounds by UV-visible spectroscopic measurements.