Drug Lipophilicity in QSAR Practice: II. Aspects of R_M‐Determinations; Critics of R_M‐Corrections; Interrelations with Partition Coefficients

Abstract

Abstract Experimental conditions for the derivation of precise R M ‐values are examined; the importance and the theoretical background of the extrapolation to modifyer‐free conditions as well as the generally proposed pK‐correction for R M are discussed. Compounds included in this study stem from the following four classes of drugs: antiarrhythmics, β‐blockers, phenothiazines and benzamides. R M ‐values of these compounds (determined in acetonitrile/buffer) are compared with experimentally determined (log P obs , log P*) as well as calculated log P values (∑f, C log P). Best interrelation is found with non‐pK corrected data derived in a buffer to modifyer mixture 50/50. Comparison of the calculative approaches indicates a slight superiority of ∑f over C log P.