Synthesis and biological evaluation of indazole derivatives

The inhibition of neuronal and inducible nitric oxide synthases (nNOS and iNOS) by a series of 36 indazoles has been evaluated, showing that most of the assayed derivatives are better iNOS than nNOS inhibitors. A parabolic model relating the iNOS inhibition percentage with the difference, Erel, between stacking and apical interaction energies of indazoles with the active site of the NOS enzyme has been established.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► synthetic indazoles are good inhibitors of NOS isoforms. ► fluorine atoms in the molecule increase the inhibitory potency against NOS. ► 4,5,6,7-tetrafluoroindazole is a potent and selective iNOS inhibitor. ► a parabolic model relates the interaction between inhibitory indazoles and iNOS.