18671-92-6

Basic information

• Product Name: 3-AMINO-7-CHLORO-1,2,4-BENZOTRIAZINE-1-OXIDE
• Synonyms: 3-AMINO-7-CHLORO-1,2,4-BENZOTRIAZINE-1-OXIDE;7-chloro-1,2,4-Benzotriazin-3-amine 1-oxide
• CAS NO: 18671-92-6
• Molecular Formula: C₇H₅ClN₄O
• Molecular Weight: 196.5938
• Mol File: 18671-92-6.mol

Chemical Properties

• Melting Point: 302 °C (decomp)
• Boiling Point: 426.7°Cat760mmHg
• Flash Point: 211.9°C
• Appearance: /
• Density: 1.77g/cm³
• Vapor Pressure: 9.86E-09mmHg at 25°C
• Refractive Index: 1.785
• PKA: 3.00±0.50(Predicted)
• CAS DataBase Reference: 3-AMINO-7-CHLORO-1,2,4-BENZOTRIAZINE-1-OXIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 3-AMINO-7-CHLORO-1,2,4-BENZOTRIAZINE-1-OXIDE(18671-92-6)
• EPA Substance Registry System: 3-AMINO-7-CHLORO-1,2,4-BENZOTRIAZINE-1-OXIDE(18671-92-6)

Safety Data

• Hazardous Substances Data: 18671-92-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
3-Amino-7-chloro-1,2,4-benzotriazine-1-oxide is used as a potential pharmaceutical agent for its possible pharmacological and biological activities. The presence of the amino and chlorine groups may contribute to its unique properties, making it a candidate for further research and development in drug discovery and therapeutic applications.
Used in Chemical Industry:
In the chemical industry, 3-amino-7-chloro-1,2,4-benzotriazine-1-oxide may be utilized as a building block or intermediate in the synthesis of various chemical compounds. Its unique structure and functional groups can be exploited in the development of new materials, dyes, or other specialty chemicals.

InChI:InChI=1/C7H5ClN4O/c8-4-1-2-5-6(3-4)12(13)11-7(9)10-5/h1-3H,(H2,9,10,11)

Upstream product

• 420-04-2 CYANAMID 
• 89-63-4 4-Chloro-2-nitroaniline 
• 80527-69-1 2-nitro-4-chlorophenylguanidine 
• 881-51-6 N-(4-chloro-2-nitrophenyl)-acetamide 
• 106-47-8 4-chloro-aniline 
• 539-03-7 N-(4-chlorophenyl)acetamide 
• 20611-81-8 disodium cyanamide 

Downstream Products

• 5423-53-0 3-amino-7-chloro-1,2,4-benzotriazine 
• 27315-00-0 7-Cl-tirapazamine 
• 875843-75-7 4-nitro-benzenesulfonic acid-(7-chloro-benzo[e][1,2,4]triazin-3-ylamide) 
• 921933-36-0 C₁₃H₁₅ClN₄O 
• 18671-94-8 3,7-dichloro-1-oxido-1,2,4-benzotriazin-1-ium 

Relevant articles and documents

Application of Suzuki–Miyaura and Buchwald–Hartwig Cross-coupling Reactions to the Preparation of Substituted 1,2,4-Benzotriazine 1-Oxides Related to the Antitumor Agent Tirapazamine

Many 1,2,4-benzotriazine 1,4-dioxides display the ability to selectively kill the oxygen-poor cells found in solid tumors. As a result, there is a desire for synthetic routes that afford access to substituted 1,2,4-benzotriazine 1-oxides that can be used as direct precursors in the synthesis of 1,2,4-benzotriazine 1,4-dioxides. Here we describe the use of Suzuki–Miyaura and Buchwald–Hartwig cross-coupling reactions for the construction of various 1,2,4-benzotriazine 1-oxide analogs bearing substituents at the 3-position, 6-position, and 7-position.

MODULATORS OF THE P70S6 KINASE FOR USE IN THE TREATMENT OF BRAIN DISORDERS AND TRIPLE-NEGATIVE BREAST CANCER

The invention provides compounds for use in the treatment of a disease or condition selected from brain disorders and triple-negative breast cancer, the compounds being of the formula (1) or a salt or tautomer thereof; wherein: X1 is N or N+(O'

Discovery and optimization of benzotriazine Di-N-oxides targeting replicating and nonreplicating mycobacterium tuberculosis

Compounds bactericidal against both replicating and nonreplicating Mtb may shorten the length of TB treatment regimens by eliminating infections more rapidly. Screening of a panel of antimicrobial and anticancer drug classes that are bioreduced into cytotoxic species revealed that 1,2,4-benzotriazine di-N-oxides (BTOs) are potently bactericidal against replicating and nonreplicating Mtb. Medicinal chemistry optimization, guided by semiempirical molecular orbital calculations, identified a new lead compound (20q) from this series with an MIC of 0.31 μg/mL against H37Rv and a cytotoxicity (CC 50) against Vero cells of 25 μg/mL. 20q also had equivalent potency against a panel of single-drug resistant strains of Mtb and remarkably selective activity for Mtb over a panel of other pathogenic bacterial strains. 20q was also negative in a L5178Y MOLY assay, indicating low potential for genetic toxicity. These data along with measurements of the physiochemical properties and pharmacokinetic profile demonstrate that BTOs have the potential to be developed into a new class of antitubercular drugs.

SUBSTITUTED BENZOTRIAZINES AND QUINOXALINES AS INHIBITORS OF P7OS6 KINASE

The invention provides compounds of the formula (1): or salts or tautomers thereof; wherein X1 is N or N+(O ); X2 is N or CH; Q is a C1-3 alkylene group; R1 is selected from hydrogen, C1-4 hydrocarbyl and hydroxy-C2-4 hydrocarbyl; R2, R3 and R4 are the same or different and each is selected from hydrogen, fluorine, chlorine and methyl; Ar1 is an optionally substituted monocyclic 5 or 6-membered aryl or heteroaryl ring containing 0, 1 or 2 heteroatom ring members selected from O, N and S, or a naphthyl ring and Ar2 is an optionally substituted monocyclic 5 or 6-membered heteroaryl ring containing 1, 2 or 3 heteroatom ring members selected from O, N and S. The compounds of formula (1) are inhibitors of p70S6 kinase and are useful in the treatment of proliferative diseases.

Radical properties governing the hypoxia-selective cytotoxicity of antitumor 3-amino-1,2,4-benzotriazine 1,4-dioxidest

Revealing the free radical mechanism by which the anticancer drug tirapazamine (3-amino-1,2,4-benzotriazine 1,4-dioxide) induces hypoxia-selective cytotoxicity, is seen as a way forward to develop clinically useful bioreductive drugs against chemo- and radiation-resistant hypoxic tumor cells. Our previous studies point to the formation of an active benzotriazinyl radical following the one-electron reduction of tirapazamine and its elimination of water from the initial reduction intermediate, and have suggested that this species is a cytotoxin. In this paper we have used pulse radiolysis to measure the one-electron reduction potentials of the benzotriazinyl radicals E(B ?,H+/B) of 30 analogues of tirapazamine as well as the one-electron reduction potentials of their two-electron reduced metabolites, benzotriazine 1-oxides E(B/B?-. The redox dependencies of the back-oxidation of the one-electron reduced benzotriazine 1,4-dioxides by oxygen, their radical prototropic properties and water elimination reactions were found to be tracked in the main by the one-electron reduction potentials of the benzotriazine 1,4-dioxides E(A/A?-). Multiple regression analysis of published aerobic and hypoxic clonogenic cytotoxicity data for the SCCVII murine tumor cell line with the physical chemistry parameters measured in this study, revealed that hypoxic cytotoxicity is dependent on E(B ?, H-/B) thus providing strong evidence that the benzotriazinyl radicals are the active cytotoxic species in hypoxia, while aerobic cytotoxicity is dependent on E(B/B?-). It is concluded that maximizing the differential ratio between these two controlling parameters, in combination with necessary pharmacological aspects, will lead to more efficacious anticancer bioreductive drugs. The Royal Society of Chemistry 2005.

Benzoazine mono-N-oxides and benzoazine 1,4 dioxides and compositions therefrom for the therapeutic use in cancer treatments

The present invention relates to a synergetistic composition comprising one or more benzoazine-mono-N-oxides, and one or more benzoazine 1,4 dioxides for use in cancer therapy. The invention also provides a range of novel 1,2,4 benzoazine-mono-N-oxides and related analogues. These can be used as potentiators of the cytotoxicity of existing anticancer drugs and therapies for cancer treatment.

Benzoazine mono-N-oxides and benzoazine 1,4 dioxides and compositions therefrom for the therapeutic use in cancer treatments

The present invention relates to a synergetistic composition comprising one or more benzoazine-mono-N-oxides, and one or more benzoazine 1,4 dioxides for use in cancer therapy. The invention also provides a range of novel 1,2,4 benzoazine-mono-N-oxides and related analogues. These can be used as potentiators of the cytotoxicity of existing anticancer drugs and therapies for cancer treatment.

Structure-activity relationships of 1,2,4-benzotriazine 1,4-dioxides as hypoxia-selective analogues of tirapazamine

Tirapazamine (TPZ, 1,2,4-benzotriazin-3-amine 1,4-dioxide) is a bioreductive hypoxic cytotoxin currently in Phase II/III clinical trials in combination with radiotherapy and with cisplatin-based chemotherapy. As part of a program to develop TPZ analogues with improved solubility/potency and therapeutic indices, we synthesized 34 1,2,4-benzotriazin-3-amine 1,4-dioxides (BTO) to examine structure-activity relationships (SAR) for ring substitution. The electronic, hydrophobic, and steric parameters of substituents at the 5-, 6-, 7-, and 8-positions were systematically varied, and the aqueous solubility and one-electron reduction potentials [E(1)] of the analogues were determined. For each compound, we determined cell killing of mouse SCCVII tumor cells in vitro under aerobic and hypoxic conditions by clonogenic survival and determined their relative hypoxic toxicity (RHT; relative to TPZ) and hypoxic cytotoxicity ratio (HCR). A subset of compounds was independently evaluated using a 96-well SRB proliferation assay, the data from which correlated well with that derived by the clonogenic endpoint. Most substituents, except 5- and 8-dimethylamino and 8-diethylamino, gave analogues less soluble than TPZ. E(1) values ranged from -240 mV through -670 mV (with TPZ having a value of -456 mV) and correlated well with the electronic parameter σ for substituents at the 5-, 6-, 7-, and 8-positions. Aerobic cytotoxic potency showed a strong positive correlation with E(1) (i.e., electron-withdrawing substituents increased aerobic toxicity). Hypoxic cytotoxicity also generally increased with increasing E(1), with a maximum (RHT up to 3.9-fold) seen in halo- and trifluoromethyl-substituted BTO derivatives having E(1) between ca. -370 to -400 mV. Analogues with high HCRs (>50) all had E(1)s in the range -450 to -510 mV (weakly electron-donating substituents) with the exception of the 8-CF3 analogue, which had an HCR of 112 against SCCVII despite a high E(1) of -372 mV). The results suggest that ring-A substituents in BTO analogues can be used to predictably vary one-electron reduction potentials and also provide a much better definition than previously of the optimum range of these reduction potentials for a desirable biological activity profile (high HCR, RHT, and solubility).