27314-97-2

Basic information

• Product Name: 3-AMINO-1,2,4-BENZOTRIAZINE-1,4-DIOXIDE
• Synonyms: 3-AMINO-1,2,4-BENZOTRIAZINE-1,4-DIOXIDE;SR-4233, Tirapazamine;SR-4233, Tirapazamine, TPZ;SR 259075;Tirazone;4-Hydroxy-1-oxido-1,2,4-benzotriazin-1-ium-3-imine;TPZ;Tirapazamine(SR259075
• CAS NO: 27314-97-2
• Molecular Formula: C₇H₆N₄O₂
• Molecular Weight: 178.15
• EINECS: 1533716-785-6
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Amines;Heterocycles;WMH
• Mol File: 27314-97-2.mol
• Article Data: 13

Chemical Properties

• Melting Point: 220°C dec.
• Boiling Point: 493.6 °C at 760 mmHg
• Flash Point: 252.3 °C
• Appearance: , orange to dark orange-red/
• Density: 1.68 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.777
• Storage Temp.: 2-8°C
• Solubility: DMSO: soluble10mg/mL, clear
• PKA: 1.51±0.30(Predicted)
• CAS DataBase Reference: 3-AMINO-1,2,4-BENZOTRIAZINE-1,4-DIOXIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 3-AMINO-1,2,4-BENZOTRIAZINE-1,4-DIOXIDE(27314-97-2)
• EPA Substance Registry System: 3-AMINO-1,2,4-BENZOTRIAZINE-1,4-DIOXIDE(27314-97-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: DM0671500
• Hazardous Substances Data: 27314-97-2(Hazardous Substances Data)

Usage

Description

Tirapazamine is a hypoxia-activated anticancer agent. It is converted to an oxidizing radical under hypoxic conditions and can induce single- and double-strand breaks in DNA, formation of trapped topoisomerase I- and II-DNA complexes, and other chromosomal aberrations, leading to cytotoxicity. Tirapazamine induces hypoxia-enhanced cytotoxicity in DT40 cells (IC50s = 1.02 and 4.34 μM in hypoxic and normoxic conditions, respectively). It also induces cytotoxicity in HT-1080 and A549 cells in a concentration-dependent manner under hypoxic conditions. In vivo, tirapazamine sensitizes tumors to cisplatin in a mouse RIF-1 fibrosarcoma tumor model. Tirapazamine (0.08 mmol/kg) also sensitizes tumors to fractionated irradiation in a FaDu hypopharyngeal squamous cell carcinoma mouse xenograft model.

Chemical Properties

Orange Needles

Uses

Different sources of media describe the Uses of 27314-97-2 differently. You can refer to the following data:
1. A bioreductive anticancer agent. Selectively toxic to cells under hypoxic conditions. An antineoplastic
2. Tirapazamine has been used to evaluate its cytotoxic effect on U-251 MG (glioblastoma cell line) cell viability.

Definition

ChEBI: A member of the class of benzotriazines that is 1,2,4-benzotriazine carrying an amino substituent at position 3 and two oxido substituents at positions 1 and 4.

Biochem/physiol Actions

Under hypoxic conditions, tirapazamine is a potent cytotoxic agent that induces apoptosis by inducing breaks in single and double stranded DNA, as well as chromosomal breaks. The compound sensitizes cells to other ionizing radiation and other cytotoxic agents like cisplatin.

InChI:InChI=1/C7H6N4O2/c8-7-9-11(13)6-4-2-1-3-5(6)10(7)12/h1-4H,(H2,8,9)

Upstream product

• 5424-06-6 3-amino-1,2,4-benzotriazine 1-oxide 
• 20028-80-2 SR 4330 
• 480-96-6 benzofurazan oxide 
• 420-04-2 CYANAMID 
• 112970-44-2 2-bromo-3-methoxyaniline 
• 27446-08-8 3-oxo-3,4-dihydrobenzo-1,2,4-triazine 1-oxide 
• 67692-91-5 3-chloro-1,2,4-benzotriazine 1-oxide 
• 528-29-0 1,2-Dinitrobenzene 
• 1493-27-2 ortho-nitrofluorobenzene 
• 88-74-4 2-nitro-aniline 
• 20028-79-9 3-CH₃CONH-1,2,4-benzotriazine-1-oxide 

Downstream Products

• 121135-31-7 1,2,4-benzotriazine-1,4-dioxide 
• 27315-02-2 3-acetylamino-1,2,4-benzotriazine-1,4-dioxide 
• 39132-82-6 2H-<1,2,4>oxadiazolo<3,2-c><1,2,4>benzotriazin-2-one-5-oxide 
• 59399-03-0 4-benzoyloxy-1-oxy-4H-benzo[1,2,4]triazin-3-ylideneamine 
• 59399-02-9 4-acetoxy-1-oxy-4H-benzo[1,2,4]triazin-3-ylideneamine 
• 59399-05-2 phenylacetic acid 3-imino-1-oxy-3H-benzo[1,2,4]triazin-4-yl ester 
• 59399-06-3 7-methoxy-1-oxy-4-propionyloxy-4H-benzo[e][1,2,4]triazin-3-ylideneamine 
• 20028-80-2 SR 4330 
• 5424-06-6 3-amino-1,2,4-benzotriazine 1-oxide 
• 34371-14-7 2-deoxy-D-ribonolactone 
• 251322-95-9 3-amino-1,2,4-benzotriazine 4-oxide 

Relevant articles and documents

A redox-activatable biopolymer-based micelle for sequentially enhanced mitochondria-targeted photodynamic therapy and hypoxia-dependent chemotherapy

A tumor redox-activatable micellar nanoplatform based on the naturally occurring biomacromolecule hyaluronic acid (HA) was developed for complementary photodynamic/chemotherapy against CD44-positive tumors. Here HA was first conjugated with l-carnitine (Lc)-modified zinc phthalocyanine (ZnPc) via disulfide linkage and then co-assembled with tirapazamine (TPZ) to afford the physiologically stable micellar nanostructure. The mitochondria-targeted photodynamic activity of ZnPc-Lc could efficiently activate the mitochondrial apoptosis cascade and deplete the oxygen in the tumor intracellular environment to amplify the hypoxia-dependent cytotoxic effect of TPZ.

Synthesis, crystal structure and calculation of oxides of 2-methylamino-3-methyl quinoxaline

Monoxide and dioxide of animo quinoxaline were synthesized and characterized by 1H NMR, 13C NMR and HRMS. The result shows that monoxide is main product. 1H NMR analysis, quantum calculation and crystal structure all indicate that the monoxide is 4-oxide structure but not 1-oxide structure. The subsequent discussions of electronic effect and steric effect of 1-oxide and 4-oxide support the conclusion that 4-oxide is dominant product, which is consistent with 1H NMR analysis and crystal structure. At last, the calculated structure is in good agreement with the crystal structure in this paper, which indicates that the calculation result in this paper is credible.

Exploiting the Inherent Photophysical Properties of the Major Tirapazamine Metabolite in the Development of Profluorescent Substrates for Enzymes That Catalyze the Bioreductive Activation of Hypoxia-Selective Anticancer Prodrugs

Hypoxia-selective cytotoxins (HSCs) seek to exploit the oxygen-poor nature of tumor tissue for therapeutic gain. Typically, HSCs require activation by one-electron bioreductive enzymes such as NADPH:cytochrome P450 reductase (CYPOR). Thus, successful clinical deployment of HSCs may be facilitated by the development and implementation of diagnostic probes that detect the presence of relevant bioreductive enzymes in tumor tissue. The work described here develops analogues of the well-studied HSC tirapazamine (3-amino-1,2,4-benzotriazine 1,4-di-N-oxide, TPZ) as profluorescent substrates of the one-electron reductases involved in bioactivation of HSCs. Hypoxic metabolism of TPZ or 7-fluoro-TPZ by one-electron reductases releases inherently fluorescent mono-N-oxide metabolites that may serve as indicators, probes, markers, or stains for the detection of the enzymes involved in the bioactivation of HSCs. In particular, profluorescent compounds of this type can provide a foundation for fluorescence-based bioassays that help identify tumors responsive to HSCs.