Synthesis,Pharmacological Study and Modeling of 7-Methoxyindazole and Related Substituted Indazoles as Neuronal Nitric Oxide Synthase Inhibitors

The synthesis, pharmacological evaluation and modelisation of 7-methoxyindazole (7-MI) and related alkoxy-indazoles as novel inhibitors of neuronal nitric oxide synthase are presented. 7-MI remains the most active compound of this series in an in vitro enzymatic assay of neuronal nitric oxide synthase activity. Modeling studies of the interaction of 7-substituted indazole derivatives complexed with nNOS and the relationship with their respective biological activities suggest that a bulky substitution on position-7 is responsible for a steric hindrance effect which does not allow these compounds to interact with nNOS in the same way as 7-NI and 7-MI.