论文信息 - On the Reliability of Calculated Log P-values: Rekker, Hansch/Leo and Suzuki Approach

On the Reliability of Calculated Log P-values: Rekker, Hansch/Leo and Suzuki Approach

A number of fragmental approaches for calculation of drug lipophilicity (log P) have been developed in recent years. Among these the procedures of Rekker, Hansch and Leo and that of Suzuki and Kudo offer good possibilities for setting up computerized versions of log-P calculation. This paper presents a comparative overview of the results of these three approaches for two series of hydrocarbon structures as well as for 36 selected drugs as tabulated by Rekker and Mannhold in their monograph “Calculation of Drug Lipophilicity”. The presented data demonstrate quite clearly that in a number of cases unexpected and unacceptable artefacts show up. Our final conclusion is that – at least for the series we chose for demonstration – the ultimate goal for faultless log P-calculations, although within reach, has not yet been fully realized.

[1] A. Ghose,et al. Atomic Physicochemical Parameters for Three‐Dimensional Structure‐Directed Quantitative Structure‐Activity Relationships I. Partition Coefficients as a Measure of Hydrophobicity , 1986 .

[2] P. Broto,et al. Molecular structures: perception, autocorrelation descriptor and sar studies: system of atomic contributions for the calculation of the n-octanol/water partition coefficients , 1984 .

[3] Yoshihiro Kudo,et al. Automatic log P estimation based on combined additive modeling methods , 1990, J. Comput. Aided Mol. Des..

[4] Albert J. Leo,et al. [25] Hydrophobic parameter: Measurement and calculation , 1991 .

[5] Calculated log P values: Are they reliable? , 1993 .

[6] Gilles Klopman,et al. Simple method of computing the partition coefficient , 1985 .

[7] Rf Rekker,et al. THE HYDROPHOBIC FRAGMENTAL CONSTANT; AN EXTENSION TO A 1000 DATA POINT SET , 1979 .