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, E rel, between stacking and apical interaction energies of indazoles with the active site of the NOS enzyme has been established. [Display omitted] ► 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.