4-substituted indazoles as new inhibitors of neuronal nitric oxide synthase.
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.
Boulouard
Michel
M
UPRES-EA 3915, Centre d'Etudes et de Recherche sur le Médicament de Normandie, UFR des Sciences Pharmaceutiques, rue Vaubénard, Caen, France.
Schumann-Bard
Pascale
P
Butt-Gueulle
Sabrina
S
Lohou
Elodie
E
Stiebing
Silvia
S
Collot
Valérie
V
Rault
Sylvain
S
D000818:Animals; D001966:Bromine / Q000737:chemistry; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007191:Indazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D051381:Rats; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D007191:Indazoles; D052248:Nitric Oxide Synthase Type I; D001966:Bromine; C080122:7-nitroindazole