A Quantitative Structure-Activity Relationship Study on Some Imidazoles and 2-Aminopyridines Acting as Nitric Oxide Synthase (NOS) Inhibitors

A quantitative structure-activity relationship study has been made on two different series of nitric oxide synthase (NOS) inhibitors. A series of imidazoles and some mono or bicyclic nitrogen-containing heterocycles was reported to potently act against neuronal NOS (nNOS) and a series of 2-aminopyridines to act against inducible NOS (iNOS). The QSAR model derived for the former suggested that nNOS inhibition activity of the compounds is basically controlled by electronic nature of the molecule and that the compounds having fused ring would have added advantage and the one derived for the latter suggested that iNOS inhibition activity of 2-aminopyridines is controlled by hydrophobic nature of 6- substituents and the steric nature of 4-substituents. A negative effect on activity in this series was however suggested to be produced by the polarizability of the molecule.