Description
7-
Nitroindazole is a non-
selective inhibitor of NOS isoforms
in vitro. However, it shows good anti-
nociceptive effects
in vivo without affecting blood pressure
via inhibition of eNOS.
1 The IC
50 values for inhibition of rat nNOS, bovine eNOS, and rat iNOS are 0.71, 0.78, and 5.8 μM, respectively.
2
Definition
7-Nitroindazole is a heterocyclic small molecule containing an indazole ring that has been nitrated at the 7 position. It is a potent, selective brain inhibitor of mouse cerebellar Nitric Oxide Synthase, a hemoprotein enzyme that, in neuronal tissue, converts arginine to citrulline and nitric oxide (NO).
Synthesis
General procedure for the synthesis of 7-nitroindazole from 2-methyl-6-nitroaniline: To a stirred solution of 2-methyl-6-nitroaniline (10 g, 0.065 mol) in acetic acid (470 ml, 47 times the volume) was slowly added an aqueous solution (9 ml) of sodium nitrite (1.54 g, 0.06 mol, 1.1 equiv). The reaction mixture was stirred at room temperature for 30-45 min. The progress of the reaction was monitored by thin layer chromatography (TLC, unfolding agent 30% ethyl acetate/hexane, Rf=0.7). After completion of the reaction, acetic acid was removed by distillation under reduced pressure. The obtained residue was dissolved in ice water (200 ml), the precipitated solid was filtered, washed with cold water and dried under vacuum to afford the target product 7-nitroindazole as a yellow solid (10 g, 98% yield).
References
[1] Synlett, 2007, # 8, p. 1203 - 1206
[2] Patent: WO2010/127855, 2010, A1. Location in patent: Page/Page column 124; 125
[3] Archives of Pharmacal Research, 2018, vol. 41, # 1, p. 46 - 56
[4] European Journal of Medicinal Chemistry, 1986, vol. 21, # 4, p. 359 - 362
[5] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2000, vol. 39, # 5, p. 339 - 345
