Theoretical calculation and prediction of intestinal absorption of drugs in humans using MolSurf parametrization and PLS statistics

A method for modeling and prediction of the intestinal absorption of drugs in humans using theoretically computed molecular descriptors and multivaria te statistics has been investigated using 20 diverse drug-like compounds. T he program MolSurf was used to compute theoretical molecular descriptors re lated to physicochemical properties such as lipophilicity, polarity, polari zability and hydrogen bonding. The multivariate Partial Least Squares Proje ctions to Latent Structures (PLS) method was used to delineate the relation ship between the intestinal absorption of drugs in humans and the theoretic ally computed molecular descriptors. Good statistical models were derived. Properties associated with hydrogen b onding had the largest impact on absorption and should be kept to a minimum to promote high absorption. High charge-transfer properties and the presen ce of surface electrons, i.e. valence electrons, which are not tightly bond ed to the molecule, were also found to promote high absorption. (C) 1999 El sevier Science B.V. All rights reserved.