DRUG LIPOPHILICITY IN QSAR PRACTICE .2. ASPECTS OF RM-DETERMINATIONS - CRITICS OF RM-CORRECTIONS - INTERRELATIONS WITH PARTITION-COEFFICIENTS

Experimental conditions for the derivation of precise R(M)-values are examined; the importance and the theoretical background of the extrapolation to modifier-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, beta-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 (SIGMA-f, C log P). Best interrelation is found with non-pK corrected data derived in a buffer to modifier mixture 50/50. Comparison of the calculative approaches indicates a slight superiority of SIGMA-f over C log P.