Synthesis and biological evaluation of indazole derivatives

Rosa M Claramunt; Concepción López; Ana López; Carlos Pérez-Medina; Marta Pérez-Torralba; Ibon Alkorta; José Elguero; Germaine Escames; Darío Acuña-Castroviejo

doi:10.1016/j.ejmech.2011.01.027

Synthesis and biological evaluation of indazole derivatives

Eur J Med Chem. 2011 Apr;46(4):1439-47. doi: 10.1016/j.ejmech.2011.01.027. Epub 2011 Jan 28.

Authors

Rosa M Claramunt¹, Concepción López, Ana López, Carlos Pérez-Medina, Marta Pérez-Torralba, Ibon Alkorta, José Elguero, Germaine Escames, Darío Acuña-Castroviejo

Affiliation

¹ Departamento de Química Orgánica y Bio-Orgánica, Facultad de Ciencias, UNED, Senda del Rey 9, E-28040 Madrid, Spain. rclaramunt@ccia.uned.es

PMID: 21334118
DOI: 10.1016/j.ejmech.2011.01.027

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dose-Response Relationship, Drug
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Indazoles / chemical synthesis*
Indazoles / chemistry
Indazoles / pharmacology*
Nitric Oxide Synthase Type I / antagonists & inhibitors
Nitric Oxide Synthase Type II / antagonists & inhibitors

Substances

Enzyme Inhibitors
Indazoles
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type II