Current trends in QSAR on NO donors and inhibitors of nitric oxide synthase (NOS)*

Abstract

This article evaluates the quantitative structure-activity relationships (QSAR) of nitric oxide (NO) radical donors and nitric oxide synthases (NOS) inhibitors, using the C-QSAR program of Biobyte. Furoxans, triazines, amidoximes, tetrazoles, imidazoles and N(omega)-2-nitroarylamino acid analogues were included in this survey. In nine out of seventeen cases, the clog P plays a significant part in the QSAR of the NO radical donors and of the NOS inhibition. Many of the compounds must be interacting with a hydrophobic space in a non-specific way. In some cases molecular refractivity CMR/MR as well as sterimol parameters (B(1) and L) are important. Electronic effects, with the exception of the Hammett's constant sigma and the Swain-Lupton parameter F, are not found to govern the biological activity. Stereochemical and electronic features are also found to be important. Indicator variables were used after the best model was found to account for the usual structural features.