MOLECULAR LIPOPHILICITY POTENTIAL, A TOOL IN 3D QSAR - METHOD AND APPLICATIONS

A new method is presented to calculate the Molecular Lipophilicity Pot ential (MLP). The method is validated by showing that the MLP thus gen erated on the solvent-accessible surface can be used to back-calculate log P. Because the MLP is shown to be sensitive to conformational eff ects, the MLP/log P relation is best sought by taking all conformers i nto account. The MLP method presented here can be used as a third held in CoMFA studies, as illustrated with two series of alpha(1)-adrenoce ptor ligands. In the first series, the steric, electrostatic and lipop hilic fields are highly intercorrelated, and taken separately yield co mparable models. In the second series of ligands, the best model is ob tained with the lipophilic field alone, allowing insights into ligand- receptor interactions.