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Upstream product

• 20028-80-2 SR 4330 
• 27314-97-2 3-amino-1,2,4-benzotriazine-1,4-dioxide 

Relevant academic research and scientific papers

Time-resolved spectroscopy of the excited singlet states of tirapazamine and desoxytirapazamine

Laser flash photolysis (LFP, 400 nm excitation) of the anti-cancer drug tirapazamine (TPZ) in acetonitrile produces the singlet excited-state S 1 with λmax = 544 nm. The lifetime of this state is 130 ps, in good agreement with the reported fluorescence lifetime. The excited state is reduced to the corresponding radical anion by KSCN or KI. The spectrum of the radical anion is in good agreement with previously reported pulse radiolysis studies and time-dependent density functional theory (TD-DFT) calculations. LFP of desoxytirapazamine (dTPZ) also produces the first excited singlet state, S1. The fluorescence quantum yield and lifetime (5.4 ns) of the dTPZ singlet excited state are both much greater than the corresponding values of TPZ. This is explained by DFT calculations that predict that cyclization of TPZ to form an oxaziridine is thermodynamically facile but that cyclization of dTPZ to form an oxadiaziridine is not. Thus, the S 1 state of TPZ has a short lifetime and low fluorescence quantum yield due to ready cyclization whereas the cyclization of the S1 state of dTPZ is unimportant and does not limit either the fluorescence quantum yield or the fluorescence lifetime. This conclusion is confirmed by studies of dTPZ', an isomer of dTPZ containing the C=N-O moiety which has a low quantum yield and short fluorescence lifetime similar to that 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.

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.

3-amino-1,2,4-benzotriazine 4-oxide: Characterization of a new metabolite arising from bioreductive processing of the antitumor agent 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine)

Tirapazamine (1) is a promising antitumor agent that selectively causes DNA damage in hypoxic tumor cells, following one-electron bioreductive activation. Surprisingly, after more than 10 years of study, the products arising from bioreductive metabolism of tirapazamine have not been completely characterized. The two previously characterized metabolites are 3-amino-1,2,4-benzotriazine 1-oxide (3) and 3-amino-1,2,4-benzotriazine (5). In this work, 3-amino-1,2,4-benzotriazine 4-oxide (4) is identified for the first time as a product resulting from one-electron activation of the antitumor agent tirapazamine by the enzymes xanthine/xanthine oxidase and NADPH:cytochrome P450 oxidoreductase. As part of this work, the novel N-oxide (4) was unambiguously synthesized and characterized using NMR spectroscopy, UV-vis spectroscopy, LC/MS, and X-ray crystallography. Under conditions where the parent drug tirapazamine is enzymatically activated, the metabolite 4 is produced but readily undergoes further reduction to the benzotriazine (5). Thus, under circumstances where extensive reductive metabolism occurs, the yield of the 4-oxide (4) decreases. In contrast, the isomeric two-electron reduction product 3-amino-1,2,4-benzotriazine 1-oxide (3) does not readily undergo enzymatic reduction and, therefore, is found as a major bioreductive metabolite under all conditions. Finally, the ability of the 4-oxide metabolite (4) to participate in tirapazamine-mediated DNA damage is considered.