Hydrogen bond and other descriptors for thalidomide and its N-alkyl analogs; prediction of physicochemical and biological properties.

Abstract

Descriptors for thalidomide and its N-alkyl derivatives have been obtained from solubilities reported by Goosen et al. It I shown that thalidomide and the three N-alkylthalidomides are reasonably strong hydrogen bond bases, and that thalidomide is a hydrogen bond acid. From the obtained descriptors, a large number of physicochemical and biochemical properties of the four thalidomides were predicted, including several water-solvent partition coefficients. Predictions of skin permeation of the four thalidomides are in excellent agreement with experiment. Thalidomide is predicted to be only moderately to poorly distributed to the brain, but N-pentylthalidomide, is predicted to be very well distributed to the brain. All four thalidomides have very high predicted % human intestinal absorption.