- Stille coupling reactions in the synthesis of hypoxia-selective 3-alkyl-1,2,4-benzotriazine 1,4-dioxide anticancer agents
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The introduction of a 3-alkyl substituent is a key step in the synthesis of 1,2,4-benzotriazine 1,4-dioxide hypoxia-selective anticancer agents, such as SN29751. The Stille reaction of 3-chloro-1,2,4-benzotriazine 1-oxides (BTOs) 5 was inhibited by the presence of electron donating substituents on the benzo ring, thus limiting the range of compounds available for SAR studies. The use of 3-iodo-BTOs 8 did not provide a significant improvement in the yields of 3-ethyl-BTOs 6. Microwave-assisted Stille coupling of chlorides 5 gave dramatically improved yields, which were consistently superior to those from the corresponding iodides 8. The application of microwave-assisted synthesis extended the range of substituted BTOs available for SAR studies and provided an efficient, scalable synthesis of the investigational anticancer agent, SN29751 (1).
- Pchalek, Karin,Hay, Michael P.
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Read Online
- Synthesis, structure and hypoxic cytotoxicity of 3-amino-1,2,4- benzotriazine-1,4-dioxide derivatives
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A series of novel 3-amino-1,2,4-benzotriazine-1,4-dioxide derivatives were synthesized and screened for their in vitro cytotoxicity against promyelocyte leukemia HL-60, androgen-independent prostate tumor PC3, hepatocellular carcinoma Bel-7402, human esop
- Jiang, Faqin,Weng, Qinjie,Sheng, Rong,Xia, Qing,He, Qiaojun,Yang, Bo,Hu, Yongzhou
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p. 258 - 263
(2008/02/09)
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- NOVEL 1,2,4-BENZOTRIAZINE-1,4-DIOXIDES
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The present invention provides a simplified set of characteristics that can be used to select 1,2,4 benzotriazine 1,4 dioxide compounds (TPZ analogues) with therapeutic activity against hypoxic cells in human tumour xenografts, and to further provide a no
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Page/Page column 47
(2010/02/13)
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- Benzoazine mono-N-oxides and benzoazine 1,4 dioxides and compositions therefrom for the therapeutic use in cancer treatments
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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.
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Page/Page column 32; 66
(2010/02/08)
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- DNA-TARGETED BENZOTRIAZINE 1,4-DIOXIDES AND THEIR USE IN CANCER THERAPY
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The present invention relates to DNA-targeted 1,2,4-benzotriazine- 1,4-dioxides and related analogues, to their preparation, and to their use as hypoxia-selective drugs and radiosensitizers for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.
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- Benzoazine mono-N-oxides and benzoazine 1,4 dioxides and compositions therefrom for the therapeutic use in cancer treatments
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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.
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