title: Prediction of drug solubility from Monte Carlo simulations.
abstract: Monte Carlo statistical mechanics simulations have been carried out for 150 organic solutes in water. Physically significant descriptors such as the solvent-accessible surface area, numbers of hydrogen bonds, and indices for cohesive interactions in solids are correlated with pharmacologically important properties including octanol/water partition coefficient (log P) and aqueous solubility (log S). The regression equation for log S only requires five descriptors to provide a correlation coefficient, r2, of 0.9 and rms error of 0.7 for the 150 solutes. The descriptors can form a basis for structural modifications to guide an analogue's properties into desired ranges.
authors.affiliation: Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA. bill@adrik.chem.yale.edu
authors.forename: W L
authors.initials: WL
authors.lastname: Jorgensen
authors.forename: E M
authors.initials: EM
authors.lastname: Duffy
mesh_terms: D009010:Monte Carlo Method; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility
chemical_list: D004364:Pharmaceutical Preparations