121135-31-7

Basic information

• Product Name: 4-oxo-1,2,4-benzotriazin-4-ium-1(4H)-olate
• CAS NO: 121135-31-7
• Molecular Formula: C₇H₅N₃O₂
• Molecular Weight: 163.1335
• Mol File: 121135-31-7.mol

Chemical Properties

• CAS DataBase Reference: 4-oxo-1,2,4-benzotriazin-4-ium-1(4H)-olate(CAS DataBase Reference)
• NIST Chemistry Reference: 4-oxo-1,2,4-benzotriazin-4-ium-1(4H)-olate(121135-31-7)
• EPA Substance Registry System: 4-oxo-1,2,4-benzotriazin-4-ium-1(4H)-olate(121135-31-7)

Safety Data

• Hazardous Substances Data: 121135-31-7(Hazardous Substances Data)

Upstream product

• 59323-44-3 benzo[e][1,2,4]triazine-1-oxide 
• 27314-97-2 3-amino-1,2,4-benzotriazine-1,4-dioxide 

Relevant articles and documents

Characterization of radicals formed following enzymatic reduction of 3-substituted analogues of the hypoxia-selective cytotoxin 3-amino-1,2,4- benzotriazine 1,4-dioxide (tirapazamine)

The mechanism by which the 1,2,4-benzotriazine 1,4-dioxide (BTO) class of bioreductive hypoxiaselective prodrugs (HSPs) form reactive radicals that kill cancer cells has been investigated by steadystate radiolysis, pulse radiolysis (PR), electron paramagnetic resonance (EPR), and density functional theory (DFT) calculations. Tirapazamine (TPZ, 3-amino BTO, 1) and a series of 3-substituted analogues, -H (2), -methyl (3), -ethyl (4), -methoxy (5), -ethoxymethoxy (6), and -phenyl (7), were reduced in aqueous solution under anaerobic steady-state radiolysis conditions, and their radicals were found to remove the substrates by short chain reactions of different lengths in the presence of formate ions. Multiple carbon-centered radical intermediates, produced upon anaerobic incubation of the compounds with cytochrome P450 reductase enriched microsomes, were trapped by N-tert-butyl-α-phenylnitrone and observed using EPR. The highly oxidizing oxymethyl radical, from compound 5, was identified, and experimental spectra obtained for compounds 1, 2, 3, and 7 were well simulated after the inclusion of aryl radicals. The identification of a range of oxidizing radicals in the metabolism of the BTO compounds gives a new insight into the mechanism by which these HSPs can cause a wide variety of damage to biological targets such as DNA.

Isotopic labeling experiments that elucidate the mechanism of DNA strand cleavage by the hypoxia-selective antitumor agent 1,2,4-benzotriazine 1,4-Di- N -oxide

The 1,2,4-benzotriazine 1,4-dioxides are an important class of potential anticancer drugs that selectively kill the low-oxygen (hypoxic) cells found in solid tumors. These compounds undergo intracellular one-electron enzymatic reduction to yield an oxygen-sensitive drug radical intermediate that partitions forward, under hypoxic conditions, to generate a highly reactive secondary radical that causes cell killing DNA damage. Here, we characterized bioreductively activated, hypoxia-selective DNA-strand cleavage by 1,2,4-benzotriazine 1,4-dioxide. We found that one-electron enzymatic activation of 1,2,4-benzotriazine 1,4-dioxide under hypoxic conditions in the presence of the deuterium atom donor methanol-d4 produced nondeuterated mono-N-oxide metabolites. This and the results of other isotopic labeling studies provided evidence against the generation of atom-abstracting drug radical intermediates and are consistent with a DNA-damage mechanism involving the release of hydroxyl radical from enzymatically activated 1,2,4-benzotriazine 1,4-dioxides.

Transferring oxygen isotopes to 1,2,4-benzotriazine 1-oxides forming the corresponding 1,4-dioxides by using the HOF·CH3CN complex

Heterocyclic benzotriazine N-oxides are an interesting class of experimental anticancer and antibacterial agents. Analogs with 18O incorporated into the N-oxide group may offer useful mechanistic tools. We describe the use of H218OF·CH3CN in a fast, readily executed and high-yielding preparation of 1,2,4-benzotriazine 1,4-dioxides containing an 18O-label at the 4-oxide position.

Process for preparing 1,2,4-benzotriazine oxides

A method of using 1,2,4-benzotriazine oxides, some of which are novel compounds, as radiosensitizers and selective cytotoxic agents is disclosed. These compounds are shown to specifically radiosensitize hypoxic tumor cells. Some are additionally disclosed to be useful as specific cytotoxic agents for these cells. They also show an unexpected ability to radiosensitize aerobic cells following or preceding a hypoxic incubation of the cells with the drug. This provides a basis for selective radiosensitization of tumors compared to normal cells. A novel method for preparing the 1,2,4-benzotriazine oxides is also disclosed.