Indazole

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Names
Preferred IUPAC name

1H-Indazole[1]

Identifiers

CAS Number

* 271-44-3 Y

3D model (JSmol)

* Interactive image

ChEBI |

* CHEBI:36670 Y

ChEMBL |

* ChEMBL86795 Y

ChemSpider |

* 8866 Y

ECHA InfoCard | 100.005.436

PubChem CID

* 9221

UNII |

* 7C4VQE5C03 Y

CompTox Dashboard (EPA)

* DTXSID4075374

InChI

* InChI=1S/C7H6N2/c1-2-4-7-6(3-1)5-8-9-7/h1-5H,(H,8,9) Y

Key: BAXOFTOLAUCFNW-UHFFFAOYSA-N Y

* InChI=1/C7H6N2/c1-2-4-7-6(3-1)5-8-9-7/h1-5H,(H,8,9)

Key: BAXOFTOLAUCFNW-UHFFFAOYAQ

SMILES

* c2ccc1[nH]ncc1c2

Properties

Chemical formula

| C7H6N2
Molar mass | 118.14 g/mol
Melting point | 147 to 149 °C (297 to 300 °F; 420 to 422 K)
Boiling point | 270 °C (518 °F; 543 K)

Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Infobox references

Chemical compound

Indazole, also called isoindazole, is a heterocyclic aromatic organic compound. This bicyclic compound consists of the fusion of benzene and pyrazole.

Indazole is an amphoteric molecule which can be protonated to an indazolium cation or deprotonated to an indazolate anion. The corresponding pKa values are 1.04 for the equilibrium between indazolium cation and indazole and 13.86 for the equilibrium between indazole and indazolate anion.[2]

Indazole derivatives display a broad variety of biological activities.

Indazoles are rare in nature. The alkaloids nigellicine, nigeglanine, and nigellidine are indazoles. Nigellicine was isolated from the widely distributed plant Nigella sativa L. (black cumin). Nigeglanine was isolated from extracts of Nigella glandulifera.

The Davis–Beirut reaction can generate 2H-indazoles.[3]

Indazole, C7H6N2, was obtained by E. Fischer (Ann. 1883, 221, p. 280) by heating ortho-hydrazine cinnamic acid,[4]

## Drugs made from Indazole

[edit]

Marsanidine [1034875-38-1][5][6]

## See also

[edit]

* Indole, an analog with only one nitrogen atom in position 1.
* Benzimidazole, an analog with the nitrogen atoms in positions 1 and 3.
* Simple aromatic rings
* 7-Nitroindazole, an indazole-based nitric oxide synthase inhibitor

## References

[edit]

1. ^ International Union of Pure and Applied Chemistry (2014). Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013. The Royal Society of Chemistry. p. 213\. doi:10.1039/9781849733069. ISBN 978-0-85404-182-4.
2. ^ Catalan, Javier; Elguero, Jose (1987). "Basicity and Acidity of Azoles". Advances in Heterocyclic Chemistry Volume 41. Vol. 41\. Elsevier. pp. 187–274\. doi:10.1016/s0065-2725(08)60162-2. ISBN 9780120206414.187-274&rft.pub=Elsevier&rft.date=1987&rft_id=info:doi/10.1016/s0065-2725(08)60162-2&rft.isbn=9780120206414&rft.aulast=Catalan&rft.aufirst=Javier&rft.au=Elguero,+Jose&rfr_id=info:sid/en.wikipedia.org:Indazole" class="Z3988">
3. ^ Zhu, Jie S.; Haddadin, Makhluf J.; Kurth, Mark J. (22 July 2019). "Davis–Beirut Reaction: Diverse Chemistries of Highly Reactive Nitroso Intermediates in Heterocycle Synthesis". Accounts of Chemical Research. 52 (8): 2256–2265\. doi:10.1021/acs.accounts.9b00220. PMC 6702092. PMID 31328502.2256-2265&rft.date=2019-07-22&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702092#id-name=PMC&rft_id=info:pmid/31328502&rft_id=info:doi/10.1021/acs.accounts.9b00220&rft.aulast=Zhu&rft.aufirst=Jie+S.&rft.au=Haddadin,+Makhluf+J.&rft.au=Kurth,+Mark+J.&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702092&rfr_id=info:sid/en.wikipedia.org:Indazole" class="Z3988">
4. ^ Chisholm, Hugh, ed. (1911). "Indazoles" . Encyclopædia Britannica. Vol. 14 (11th ed.). Cambridge University Press. p. 371.
5. ^ Saczewski F, Kornicka A, Rybczyńska A, Hudson AL, Miao SS, Gdaniec M, Boblewski K, Lehmann A. 1-[(Imidazolidin-2-yl)imino]indazole. Highly alpha 2/I1 selective agonist: synthesis, X-ray structure, and biological activity. J Med Chem. 2008 Jun 26;51(12):3599-608. doi: 10.1021/jm800112s. Epub 2008 Jun 3. PMID 18517187.
6. ^ Franciszek Saczewski, et al. WO2009071906 (to Ip2ipo Innovations Ltd, Medical University of Gdansk).

* Synthesis: Stadlbauer, W. (2002). "Product Class 2: 1H- and 2H-Indazoles". In Neier; Bellus (eds.). Category 2, Hetarenes and Related Ring Systems. Science of Synthesis. Houben-Weyl. doi:10.1055/sos-SD-012-00277. ISBN 9783131122711.
* Review: Schmidt, Andreas; Beutler, Ariane; Snovydovych, Bohdan (2008). "Recent Advances in the Chemistry of Indazoles". European Journal of Organic Chemistry. 2008 (24): 4073–4095\. doi:10.1002/ejoc.200800227.4073-4095&rft.date=2008&rft_id=info:doi/10.1002/ejoc.200800227&rft.aulast=Schmidt&rft.aufirst=Andreas&rft.au=Beutler,+Ariane&rft.au=Snovydovych,+Bohdan&rfr_id=info:sid/en.wikipedia.org:Indazole" class="Z3988">

* v
* t
* e

Simple aromatic rings

1 ring|

| Three-membered|

* Borirene
* Cyclopropenone

|

Five-membered|

* Furan
* Pyrrole
* Imidazole
* Thiophene
* Phosphole
* Pyrazole
* Oxazole
* Isoxazole
* Thiazole
* Isothiazole
* Triazole
* Tetrazole
* Pentazole

Six-membered|

* Benzene
* Pyridine
* Pyrazine
* Pyrimidine
* Pyridazine
* Triazine
* Tetrazine
* Pentazine
* Hexazine

Seven-membered|

* Borepin
* Tropone

Nine-membered|

* Azonine

18-membered|

* Cyclooctadecanonaene

2 rings|

| Five + Five|

* Diazapentalene
* Thienothiophene
* Trithiapentalene

|

Five + Six|

* Benzofuran
* Isobenzofuran
* Indole
* Isoindole
* Benzothiophene
* Benzo(c)thiophene
* Benzophosphole
* Benzimidazole
* Purine
* Indazole
* Benzoxazole
* Benzisoxazole
* Benzothiazole
* 5-Aza-7-deazapurine

Six + Six|

* Naphthalene
* Quinoline
* Isoquinoline
* Quinoxaline
* Quinazoline
* Cinnoline
* Phthalazine

Five + Seven|

* Azulene

* v
* t
* e

Nitric oxide signaling modulators

Forms|

* Nitroxyl anion (NO−; oxonitrate(1-), hyponitrite anion)
* Nitric oxide (NO⋅; nitrogen monoxide)
* Nitrosonium (NO+; nitrosyl cation)

Targets|

| sGC|

* Activators/stimulators: Ataciguat
* BAY 41-2272
* BAY 41-8543
* BAY 60-4552
* BI-703704
* Cinaciguat (BAY 58-2667)
* GSK-2181236A
* Praliciguat
* Riociguat
* Vericiguat

* Inhibitors: ODQ

|

NO donors
(prodrugs)|

* Nitrates: Diethylene glycol dinitrate (DEGDN)
* Erythritol tetranitrate (ETN)
* Ethylene glycol dinitrate (EGDN; nitroglycol)
* Isosorbide mononitrate (ISMN)
* Isosorbide dinitrate (ISDN)
* Itramin tosilate
* Mannitol hexanitrate
* Naproxcinod (nitronaproxen; AZD-3582, HCT-3012)
* NCX-466
* NCX-2216
* NCX-4016
* NCX 4040
* NCX-4215
* Nicorandil
* Nipradilol (K-351)
* Nitrate (NO−

* Nitroatorvastatin (NCX-6560)
* Nitroflurbiprofen (HCT-1026)
* Nitrofluvastatin
* Nitroglycerin (glyceryl trinitrate (GTN))
* Nitropravastatin (NCX-6550)
* Pentaerithrityl tetranitrate (PETN)
* Propatylnitrate
* Propylene glycol dinitrate (PGDN)
* Sodium trioxodinitrate (Angeli's salt)
* Tenitramine
* Trolnitrate

* Nitroso compounds/nitrites: Nitrite (NO−
2); O-Nitroso compounds (alkyl nitrites): Amyl nitrite (isoamyl nitrite, isopentyl nitrite)
* Cyclohexyl nitrite
* Ethyl nitrite
* Hexyl nitrite
* Isobutyl nitrite (2-methylpropyl nitrite)
* Isopropyl nitrite
* Methyl nitrite
* n-Butyl nitrite
* Pentyl nitrite
* tert-Butyl nitrite; S-Nitroso compounds (thionitrites): LA810
* S-Nitrosoalbumin (SNALB)
* S-Nitrosated AR545C
* S-Nitroso-N-acetylcysteine (SNAC)
* S-Nitroso-N-acetylpenicillamine (SNAP)
* S-Nitroso-N-valerylpenicillamine (SNVP)
* S-Nitrosocaptopril (SNO-Cap)
* S-Nitrosocysteine (SNC, CysNO, SNO-Cys)
* S-Nitrosodiclofenac
* S-Nitrosoglutathione (GSNO, SNOG)
* SNO-t-PA
* SNO-vWF; N-Nitroso compounds (e.g., nitrosamines): SIN-1A

* Nitrosyl compounds: Metal nitrosyl complexes: Roussin's black salt
* Roussin's red salt
* Sodium nitroprusside (SNP)

* NONOates (diazeniumdiolates): Diethylamine/NO (DEA/NO)
* Diethylenetriamine/NO (DETA/NO)
* GLO/NO
* JS-K
* Methylamine hexamethylene methylamine/NO (MAHMA/NO)
* PROLI/NO
* Spermine/NO (SPER/NO)
* V-PYRRO/NO

* Heterocyclic compounds: Furoxans: Furoxan
* REC15/2739; Sydnonimines: Feprosidnine
* Linsidomine (SIN-1)
* Molsidomine (SIN-10)
* Sydnonimine

* Unsorted: Cimlanod
* FK-409
* FR144220
* FR146881
* N-Acetyl-N-acetoxy-4-chlorobenzenesulfonamide

Enzyme
(inhibitors)|

| NOS|

| nNOS|

* 3-Bromo-7-nitroindazole
* 3-Chloroindazole
* 3-Chloro-5-nitroindazole
* 5-Nitroindazole
* 6-Nitroindazole
* 7-Nitroindazole
* A-84643
* Aminoguanidine (pimagedine)
* ARL-17477
* Indazole
* N5-(1-Iminoethyl)-L-ornithine (L-NIO)
* Nω-Methyl-L-arginine (L-NMA)
* Nω-Propyl-L-arginine (L-NPA)
* Nitroarginine (NNA, NOARG)
* Pentamidine isethionate
* TRIM

|

iNOS|

* 1-Amino-2-hydroxyguanidine
* 2-Ethylaminoguanidine
* 2-Iminopiperidine
* 1400W
* AEITU
* Aminoguanidine (pimagedine)
* AMT
* AR-C 102222
* BYK-191023
* Canavanine
* Cindunistat (SD-6010)
* EITU
* IPTU
* MITU
* N5-(1-Iminoethyl)-L-ornithine (L-NIO)
* N6-(1-Iminoethyl)-L-lysine (L-NIL)
* Nω-Methyl-L-arginine (L-NMA)
* Ronopterin (VAS-203)
* TRIM

eNOS|

* Aminoguanidine (pimagedine)
* N5-(1-Iminoethyl)-L-ornithine (L-NIO)
* Nω-Methyl-L-arginine (L-NMA)
* Nitroarginine (NNA, NOARG)

Unsorted|

* Asymmetric dimethylarginine (ADMA)
* CKD-712
* Guanidinoethyldisulfide (GED)
* GW-273629
* Indospicine
* KD-7040
* Nitroarginine methyl ester (NAME)
* NCX-456
* NXN-462
* ONO-1714
* VAS-2381

Arginase|

* ABH
* Nω-Hydroxy-L-arginine (NOHA)
* chlorogenic acid
* ginseng
* epicatechin
* ornithine
* norvaline
* lysine
* alpha aminoacids

CAMK|

* Calmidazolium
* W-7

Others|

* Precursors: L-Arginine
* Nω-Hydroxy-L-arginine (NOHA)

* Cofactors: NADPH
* FAD
* FMN
* Heme
* BH4
* CaM
* O2
* Ca2+

* Indirect/downstream NO modulators: ACE inhibitors/AT-II receptor antagonists (e.g., captopril, losartan)
* ETB receptor antagonists (e.g., bosentan)
* L-Type calcium channel blockers (e.g., dihydropyridines: nifedipine)
* Nebivolol (beta blocker)
* PDE5 inhibitors (e.g., sildenafil)
* non-selective PDE inhibitors (e.g., caffeine)
* PDE9 inhibitors (e.g., paraxanthine)
* cGMP preferring PDE inhibitors (e.g., sildenafil, paraxanthine, tadalafil)
* Statins (e.g., simvastatin)

See also: Receptor/signaling modulators
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