7-Nitroindazole

7-Nitroindazole
Names
Preferred IUPAC name
7-Nitro-1H-indazole
Identifiers
CAS Number
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.019.032
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PubChem CID
UNII
InChI
  • InChI=1S/C7H5N3O2/c11-10(12)6-3-1-2-5-4-8-9-7(5)6/h1-4H,(H,8,9) checkY
    Key: PQCAUHUKTBHUSA-UHFFFAOYSA-N checkY
  • InChI=1/C7H5N3O2/c11-10(12)6-3-1-2-5-4-8-9-7(5)6/h1-4H,(H,8,9)
    Key: PQCAUHUKTBHUSA-UHFFFAOYAE
SMILES
  • [O-][N+](=O)c1cccc2c1[nH]nc2
Properties
Chemical formula
 C7H5N3O2
Molar mass 163.1335
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

7-Nitroindazole, or 7-NI, is a heterocyclic small molecule containing an indazole ring that has been nitrated at the 7 position. Nitroindazole acts as a selective inhibitor for neuronal nitric oxide synthase, a hemoprotein enzyme that, in neuronal tissue, converts arginine to citrulline and nitric oxide (NO).[1] Nitric oxide can diffuse through the plasma membrane into neighbouring cells, allowing cell signalling, so nitroindazole indirectly inhibits this signalling process.[2][3][4] Other inhibitors exist such as 3-bromo-7-nitroindazole, which is more potent but less specific,[5] or NPA (N-propyl-L-arginine), which acts on a different site.[6]

Pharmacology

7-Nitroindazole is under investigation as a possible protective agent against nerve damage caused by excitotoxicity or neurodegenerative diseases.[1][7] It may act by reducing oxidative stress or by decreasing the amount of peroxynitrite formed in these tissues. These effects are related to the inhibition of type 1 nitric oxide synthase. However, anticonvulsive effect is derived from some other mechanisms.[8]

See also

  • Dizocilpine (MK-801) a non-competitive antagonist of the NMDA receptor
  • Sildenafil a drug for impotence, which inhibits cGMP specific phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP, which is produced by guanylate cyclase, which is activated by nitric oxide produced by eNOS
  • tetrahydrobiopterin, cofactor to several enzymes including nitric oxide synthase (NOS)
  • protein kinase A (PKA) and protein kinase C (PKC)

References

  1. 1 2 Southan GJ; Szabó C (February 1996). "Selective pharmacological inhibition of distinct nitric oxide synthase isoforms". Biochem. Pharmacol. 51 (4): 383–94. doi:10.1016/0006-2952(95)02099-3. PMID 8619882.
  2. ↑ Moore PK; Wallace P; Gaffen Z; Hart SL; Babbedge RC (September 1993). "Characterization of the novel nitric oxide synthase inhibitor 7-nitro indazole and related indazoles: antinociceptive and cardiovascular effects". Br. J. Pharmacol. 110 (1): 219–24. doi:10.1111/j.1476-5381.1993.tb13795.x. PMC 2175981. PMID 7693278.
  3. ↑ Babbedge RC; Bland-Ward PA; Hart SL; Moore PK (September 1993). "Inhibition of rat cerebellar nitric oxide synthase by 7-nitro indazole and related substituted indazoles". Br. J. Pharmacol. 110 (1): 225–8. doi:10.1111/j.1476-5381.1993.tb13796.x. PMC 2175991. PMID 7693279.
  4. ↑ Moore PK; Babbedge RC; Wallace P; Gaffen ZA; Hart SL (February 1993). "7-Nitro indazole, an inhibitor of nitric oxide synthase, exhibits anti-nociceptive activity in the mouse without increasing blood pressure". Br. J. Pharmacol. 108 (2): 296–7. doi:10.1111/j.1476-5381.1993.tb12798.x. PMC 1907983. PMID 7680591.
  5. ↑ Gammie SC; Olaghere-da Silva UB; Nelson RJ (July 2000). "3-bromo-7-nitroindazole, a neuronal nitric oxide synthase inhibitor, impairs maternal aggression and citrulline immunoreactivity in prairie voles". Brain Res. 870 (1–2): 80–6. doi:10.1016/S0006-8993(00)02404-5. PMID 10869504.
  6. ↑ Kampf C; Roomans GM (May 2001). "Effects of hypochlorite on cultured respiratory epithelial cells". Free Radic. Res. 34 (5): 499–511. doi:10.1080/10715760100300441. PMID 11378533.
  7. ↑ Schulz JB; Matthews RT; Klockgether T; Dichgans J; Beal MF (September 1997). "The role of mitochondrial dysfunction and neuronal nitric oxide in animal models of neurodegenerative diseases". Mol. Cell. Biochem. 174 (1–2): 193–7. doi:10.1023/A:1006852306789. PMID 9309687.
  8. ↑ Matsumura, N.; Kikuchi-Utsumi, K.; Nakaki, T. (2008). "Activities of 7-nitroindazole and 1-(2-(trifluoromethylphenyl)-imidazole independent of neuronal nitric-oxide synthase inhibition". J Pharmacol Exp Ther. 325 (2): 357–62. doi:10.1124/jpet.107.135160. PMID 18270316.
  • 7-nitroindazole at the US National Library of Medicine Medical Subject Headings (MeSH)


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