Computer-Assisted Prediction of Favorable Substituents for High Bioactivity in Congeners

Abstract

A computer program called PREHAC was developed. This aids in the prediction of highly bioactive compounds among congeners in series of aliphatic monosubstituted derivatives and aromatic mono-, di-and tri-substituted ones, based on the Hansch-Fujita method. The PREHAC program is applicable to two phases included in the computer-assisted lead optimization: the development of a QSAR equation and the decision about the direction of structural modification based on the correlation, that is, the selection of substituent. This program was designed to search the Master Data file of 13 sets of physicochemical parameter values for 408 useful substituents. From the input of substituent names, activity values, and information on the combination of parameters, or from the input of the coefficients and intercept of the QSAR equation, the predicted high-ranking derivatives will be printed out. An example is given.