Synthesis, pharmacological study and modeling of 7-methoxyindazole and related substituted indazoles as neuronal nitric oxide synthase inhibitors

J Enzyme Inhib Med Chem. 2003 Apr;18(2):195-9. doi: 10.1080/1475636032000069864.

Abstract

The synthesis, pharmacological evaluation and modelisation of 7-methoxyindazole (7-MI) and related alkoxyindazoles 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebellum / enzymology
  • Enzyme Inhibitors* / chemical synthesis
  • Enzyme Inhibitors* / chemistry
  • Enzyme Inhibitors* / pharmacology
  • In Vitro Techniques
  • Indazoles* / chemical synthesis
  • Indazoles* / chemistry
  • Indazoles* / pharmacology
  • Models, Chemical
  • Molecular Structure
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase Type I
  • Rats
  • Structure-Activity Relationship

Substances

  • 7-methoxyindazole
  • Enzyme Inhibitors
  • Indazoles
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nos1 protein, rat