Inhibition of neuronal nitric oxide synthase by 7-methoxyindazole and related substituted indazoles.
The synthesis and pharmacological evaluation of methoxyindazoles as new inhibitors of neuronal nitric oxide synthase are presented. The 7-methoxyindazole, although less potent than 7-NI, is the most active compound of the series in an in vitro enzymatic assay of neuronal nitric oxide synthase activity. This result shows that the nitro-substitution is not indispensable to the biological activity of the indazole ring. 7-Methoxyindazole possesses in vivo NOS inhibitory as well and related antinociceptive properties.
Schumann
P
P
CNRS UMR 6551, Université de Caen, France. rault@pharmacie.unicaen.fr
Collot
V
V
Hommet
Y
Y
Gsell
W
W
Dauphin
F
F
Sopkova
J
J
MacKenzie
E T
ET
Duval
D
D
Boulouard
M
M
Rault
S
S
D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004583:Electrons; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007191:Indazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D051379:Mice; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship
C436345:7-methoxyindazole; D000700:Analgesics; D004791:Enzyme Inhibitors; D007191:Indazoles; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; C496322:Nos1 protein, rat