5424-06-6Relevant articles and documents
Photochemical DNA cleavage by the antitumor agent 3-amino-1,2,4- benzotriazine 1,4-dioxide (tirapazamine, WIN 59075, SR4233)
Daniels, J. Scott,Chatterji, Tonika,MacGillivray, Leonard R.,Gates, Kent S.
, p. 10027 - 10030 (1998)
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Toward hypoxia-selective DNA-alkylating agents built by grafting nitrogen mustards onto the bioreductively activated, hypoxia-selective DNA-oxidizing agent 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine)
Johnson, Kevin M.,Parsons, Zachary D.,Barnes, Charles L.,Gates, Kent S.
, p. 7520 - 7531 (2014)
Tirapazamine (3-amino-1,2,4-benzotriazine 1,4-dioxide) is a heterocyclic di-N-oxide that undergoes enzymatic deoxygenation selectively in the oxygen-poor (hypoxic) cells found in solid tumors to generate a mono-N-oxide metabolite. This work explored the idea that the electronic changes resulting from the metabolic deoxygenation of tirapazamine analogues might be exploited to activate a DNA-alkylating species selectively in hypoxic tissue. Toward this end, tirapazamine analogues bearing nitrogen mustard units were prepared. In the case of the tirapazamine analogue 18a bearing a nitrogen mustard unit at the 6-position, it was found that removal of the 4-oxide from the parent di-N-oxide to generate the mono-N-oxide analogue 17a did indeed cause a substantial increase in reactivity of the mustard unit, as measured by hydrolysis rates and DNA-alkylation yields. Hammett sigma values were measured to quantitatively assess the magnitude of the electronic changes induced by metabolic deoxygenation of the 3-amino-1,2,4-benzotriazine 1,4-dioxide heterocycle. The results provide evidence that the 1,2,4-benzotiazine 1,4-dioxide unit can serve as an oxygen-sensing prodrug platform for the selective unmasking of bioactive agents in hypoxic cells.
Tirapazamine drug carrier with core-shell structure, and preparation method and application thereof
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Paragraph 0074; 0077-0079, (2020/06/02)
The invention relates to a tirapazamine drug carrier with a core-shell structure, and a preparation method and an application thereof, belonging to the technical field of drug preparation. According to the invention, hyaluronic acid, dithiodiacetic acid, tetraamino zinc phthalocyanine and L-carnitine are connected through a chemical action to form the tirapazamine drug carrier with the core-shellstructure, wherein a tetraamino zinc phthalocyanine-L-carnitine part is a core; a hyaluronic acid-dithiodiacetic acid part is a shell; the hyaluronic acid and the L-carnitine are used for improving the hydrophobicity of the tetramino zinc phthalocyanine; and a carrier micelle with hydrophilicity and cell-membrane and mitochondrion double-targeting effects is formed. A tirapazamine drug (TPZ) is loaded into the carrier to form a tirapazamine drug-loaded micelle with a core-shell structure, and oxygen is consumed through photodynamic treatment to activate the tirapazamine drug (TPZ), so a photodynamic and chemotherapy synergistic therapy is realized; the drug resistance of chemotherapy and the resistance of cells to photodynamic are avoided; and good application prospects are realized in preparation of anti-tumor drugs.
Synthesis, crystal structure and calculation of oxides of 2-methylamino-3-methyl quinoxaline
Li, Junjian,Wang, Rui,Wang, Wenfeng,Wang, Xucheng,Yuan, Yaofeng,Zhang, Min
, (2020/07/27)
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.