Synthesis and antiinflammatory evaluation of substituted isophthalonitriles, trimesonitriles, benzonitriles, and terephthalonitriles.

In an effort to develop nonacidic, nonsteroidal, antiinflammatory agents without gastrointestinal complications, a series of cyanobenzenes was synthesized for antiinflammatory evaluation. Twenty-seven substituted isophthalonitriles, 19 trimesonitriles, 30 benzonitriles, and 16 terephthalonitriles were tested in the rat utilizing the carrageenan-induced pedal edema assay. Based on the performance of phenylbutazone in this assay (43.

Application of SCAP to drug design. 1. Prediction of octanol-water partition coefficients using solvent-dependent conformational analyses.

The solvent-dependent conformational analysis procedure (SCAP) has been used to predict the octanol-water partition coefficients of 20 different compounds with an average absolute error of 9%. SCAP predicts partition coefficients almost as well as the Hansch procedure using pi constants where the absolute error for the 20 compounds is 5%. In addition to estimating partition coefficients, SCAP allows direct calculation of the corresponding solute-solvent interaction free energies.