- Switching on prodrugs using radiotherapy
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Chemotherapy is a powerful tool in the armoury against cancer, but it is fraught with problems due to its global systemic toxicity. Here we report the proof of concept of a chemistry-based strategy, whereby gamma/X-ray irradiation mediates the activation of a cancer prodrug, thereby enabling simultaneous chemo-radiotherapy with radiotherapy locally activating a prodrug. In an initial demonstration, we show the activation of a fluorescent probe using this approach. Expanding on this, we show how sulfonyl azide- and phenyl azide-caged prodrugs of pazopanib and doxorubicin can be liberated using clinically relevant doses of ionizing radiation. This strategy is different to conventional chemo-radiotherapy radiation, where chemo-sensitization of the cancer takes place so that subsequent radiotherapy is more effective. This approach could enable site-directed chemotherapy, rather than systemic chemotherapy, with ‘real time’ drug decaging at the tumour site. As such, it opens up a new era in targeted and directed chemotherapy. [Figure not available: see fulltext.].
- Geng, Jin,Zhang, Yichuan,Gao, Quan,Neumann, Kevin,Dong, Hua,Porter, Hamish,Potter, Mark,Ren, Hua,Argyle, David,Bradley, Mark
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p. 805 - 810
(2021/06/14)
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- Preparation method and intermediate of Pazopanib
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The invention discloses a preparation method and an intermediate of Pazopanib. The preparation method comprises the steps of carrying out two-step condensation reaction on 2,4-dichloro-5-nitropyrimidine so as to obtain a compound of a formula 5 (shown in the description), and carrying out reduction on the compound of the formula 5, so as to obtain Pazopanib. The preparation method has the beneficial effects that the yield of Pazopanib is increased, reaction conditions are mild, column chromatography purification is not required, and the preparation method is applicable to industrial production.
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Paragraph 0017; 0029
(2018/04/03)
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- Pyrimidineamines as angiogenesis modulators
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Pyrimidine derivatives, which are useful as VEGFR2 inhibitors are described herein. The described invention also includes methods of making such pyrimidine derivatives as well as methods of using the same in the treatment of hyperproliferative diseases.
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- Design, synthesis and biological evaluation of pazopanib derivatives as antitumor agents
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A novel series of pazopanib derivatives were designed, synthesized, and evaluated for their inhibitory activity against a series of kinases including VEGFR-2, EGFR, AKT1, ALK1, and ABL1. The anti-angiogenic activities ex vivo of some compounds were also investigated. Compounds P2d and P2e demonstrated outstanding inhibitory activity against VEGFR-2 and ABL1 and higher anti-angiogenic activity compared with Pazopanib, the reference standard. These two compounds (P2d and P2e) could be used as novel lead compounds for further development of anticancer agents.
- Jia, Yuping,Zhang, Jian,Feng, Jinhong,Xu, Fuming,Pan, Huili,Xu, Wenfang
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p. 306 - 316
(2014/03/21)
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- A novel practical synthesis of pazopanib: An anticancer drug
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Abstract: This paper reports a novel approach to synthesize pazopanib. In our synthetic route, the potently mutagenic alkylating agents such as dimethyl sulfate and methyl iodide are avoided. A novel regioselective methylation of the 2- position of 3-methyl-6-nitro-1H-indazole was reported. This novel route is one step shorter than the previously reported route.
- Mei, Yi Cheng,Yang, Bao Wei,Chen, Wei,Huang, Dan Dan,Li, Ying,Deng, Xin,Liu, Bao Ming,Wang, Jing Jie,Qian, Hai,Huang, Wen Long
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p. 276 - 279
(2012/08/27)
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- PROCESS FOR THE PREPARATION OF PAZOPANIP HCL AND CRYSTALLINE FORMS OF PAZOPANIB HCL
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Various crystalline forms of Pazopanib HCl were prepared. In preferred embodiments the obtained Pazopanib HCl is essentially free from CPMI.
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Page/Page column 33
(2011/06/25)
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- 5- (4- (N- (2, 3 -DIMETHYL- 2H- INDAZOL- 6 -YL) -N-METHYLAMINO) PYRIMIDIN- 2 -YLAMINO) -2 -METHYLBENZENESULFONAMIDE
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The present invention relates to novel forms of Pazopanib and a process for their preparation.
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Page/Page column 9
(2011/06/16)
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