An extension of the f-fragment method for the calculation of hydrophobic constants (log P) of conformationally defined systems

An extension of the popular fragment methods for the calculation of octanol--water partition coefficient (log P) values of conformationally defined compounds is presented. Correction factors for both trans-antiperiplanar and gauche conformational isomers have been developed for both the Rekker and Leo fragment methods and successfully applied to a large, diverse group of conformationally defined phenethylamines. This approach is easy to use and only requires one additional correction factor per isomer. This method thus allows, for the first time, conformation to be taken into account for the fragment calculation of log P values.