4-substituted indazoles as new inhibitors of neuronal nitric oxide synthase.

Michel Boulouard (1) , Pascale Schumann-Bard (2) , Sabrina Butt-Gueulle (3) , Elodie Lohou (3) , Silvia Stiebing (3) , Valérie Collot (3) , Sylvain Rault

1 GMPc - Groupe Mémoire et Plasticité comportementale
2 UNICAEN - Université de Caen Normandie
3 CERMN - Centre d'Etudes et de Recherche sur le Médicament de Normandie

A series of halo-1-H-indazoles has been synthesized and evaluated for its inhibitory activity on neuronal nitric oxide synthase. Introduction of bromine at the C4 position of the indazole ring system provided a compound almost as potent as the reference compound, that is, 7-nitroindazole (7-NI). The importance of position 4 is further demonstrated by the synthesis and pharmacological evaluation of the 4-nitroindazole which was also a potent inhibitor of NOS activity. These compounds also exhibited in vivo NOS inhibitory activity, as attested by potent antinociceptive effects following systemic administration.

Domaines: Neurosciences

Michel Boulouard, Pascale Schumann-Bard, Sabrina Butt-Gueulle, Elodie Lohou, Silvia Stiebing, et al.. 4-substituted indazoles as new inhibitors of neuronal nitric oxide synthase.. Bioorganic and Medicinal Chemistry Letters, 2007, 17 (11), pp.3177-80. ⟨10.1016/j.bmcl.2007.03.024⟩. ⟨hal-00864259⟩