Determination of the Lipophilicity of Pyrimido(5,4-c)quinoline derivatives by reserved-phase thin-layer chromatography. Part 1. Lipophilicity of pryrimido(5,4-c)quinolin-4(3H)-ones and 1,2,3,4-Tetrahydropyrimido(5,4-c)quinolin-2,4-diones

摘要

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 RM values of the compounds were linearly dependent on the concentration of DMF in the mobile phase. Experimental lipophilicity (log PTLC = log D7.4) 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 PTLC (log D7.4) and log Pneutral for the non-ionized molecules. The dissociation constant (pKa) 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 Pneutral) of the compounds which can ionize under the experimental conditions. To evaluate the validity of the pKa values obtained, experimental pKa values were determined for the quinoline nitrogen atom of the compounds by UV-visible spectroscopic measurements.