Prediction of drug solubility from Monte Carlo simulations

Monte Carlo statistical mechanics simulations have been carried out for 150 organic solutes in water. Physically significant descriptors such as the s olvent-accessible surface area, numbers of hydrogen bonds, and indices for cohesive interactions in solids are correlated with pharmacologically impor tant properties including octanol/water partition coefficient (log P) and a queous solubility (log S), The regression equation for log S only requires five descriptors to provide a correlation coefficient, r(2), of 0.9 and rms error of 0.7 for the 150 solutes. The descriptors can form a basis for str uctural modifications to guide an analogue's properties into desired ranges . (C) 2000 Elsevier Science Ltd. All rights reserved.