(153c) Cosmo-Sac in Drug Design: Prediction of Partition Coefficients

The estimation of octanol-water and other partition coefficients is important in drug design. Quantitative structure-property relationships (QSPR) methods, such as LOGKOW, CLOGP, etc., that contain a large number of descriptors, are most widely used in this area. Among these descriptors, the electrostatic interactions due to the charge density distribution, are very important. An approach based on the conductor-like screening model (COSMO) can be used to calculate the charge density distribution for solutes from quantum mechanics. Then the COSMO segment activity coefficeint model (COSMO-SAC) can be used to quickly calculate the electrostatic interactions between solutes and solvents, and then the partition coefficients. The partition coefficients for more than 80 pharmaceutical compounds, including several steroids, have been computed, including the effects of conformational changes. The results are compared with QSPR methods and the results of statistical mechanical simulations.