220000-87-3Relevant articles and documents
A scaleable synthesis of BAY 43-9006: A potent Raf kinase inhibitor for the treatment of cancer
Bankston, Donald,Dumas, Jacques,Natero, Reina,Riedl, Bernd,Monahan, Mary-Katherine,Sibley, Robert
, p. 777 - 781 (2002)
Urea 3 (BAY 43-9006), a potent Raf kinase inhibitor, was prepared in four steps with an overall yield of 63%. Significant process research enabled isolation of each intermediate and target without chromatographic purification, and overall yield increases > 50% were observed compared to those from previous methods. This report focuses on improved synthetic strategies for production of scaled quantities of 3 for preclinical, toxicological studies. These improvements may be useful to assemble other urea targets as potential therapeutic agents to combat cancer.
An efficient and high-yielding protocol for the production of Regorafenib via a new synthetic strategy
Wang, Li-Mei,Du, Bao-Quan,Zuo, Da-Zhuang,Cheng, Ming-Ke,Zhao, Meng,Zhao, Si-Jia,Zhai, Xin,Gong, Ping
, p. 3209 - 3218 (2016)
An improved, high-yielding, and efficient protocol for the production of Regorafenib (1), a novel diaryl urea inhibitor of multiple protein kinases, is described. The highlight of the process chemistry design and development is an optimization of the route for preparing key intermediate 4-(4-amino-3-fluorophenoxy)-N-methylpicolinamide (7) by O-alkylation, nitration and reduction reactions. The developed process avoids using column chromatography to isolate 7, reduces the reaction requirements and is cost-saving, resulting in an increased overall yield from 35.0 to 57.0 % and purity from 97.0 to 99.8 %.
Synthesis and biological evaluation of novel 4-(4-formamidophenylamino)-N-methylpicolinamide derivatives as potential antitumor agents
Hu, Min,Meng, Nana,Xia, Yong,Xu, Youzhi,Yu, Luoting,Zeng, Xiuxiu,Zhou, Shuyan
, (2021/06/11)
A novel series of 4-(4-formamidophenylamino)-N-methylpicolinamide derivatives were synthesized and evaluated against different tumor cell lines. Experiments in vitro showed that these derivatives could inhibit the proliferation of two kinds of human cancer cell lines (HepG2, HCT116) at low micromolar concentrations and the most potent analog 5q possessed broad-spectrum antiproliferative activity. Experiments in vivo demonstrated that 5q could effectively prolong the longevity of colon carcinoma-burdened mice and slow down the progression of cancer cells by suppression of angiogenesis and the induction of apoptosis and necrosis.
Identification of Diarylurea Inhibitors of the Cardiac-Specific Kinase TNNI3K by Designing Selectivity against VEGFR2, p38α, and B-Raf
Cheung, Mui,Desai, Tina A.,Fries, Harvey,Gatto, Gregory J.,Graves, Alan P.,Holt, Dennis A.,Kallander, Lara S.,Patterson, Jaclyn R.,Shewchuk, Lisa,Stoy, Patrick,Totoritis, Rachel,Wang, Liping
, p. 15651 - 15670 (2021/11/16)
A series of diarylurea inhibitors of the cardiac-specific kinase TNNI3K were developed to elucidate the biological function of TNNI3K and evaluate TNNI3K as a therapeutic target for the treatment of cardiovascular diseases. Utilizing a structure-based design, enhancements in kinase selectivity were engineered into the series, capitalizing on the established X-ray crystal structures of TNNI3K, VEGFR2, p38α, and B-Raf. Our efforts culminated in the discovery of an in vivo tool compound 47 (GSK329), which exhibited desirable TNNI3K potency and rat pharmacokinetic properties as well as promising kinase selectivity against VEGFR2 (40-fold), p38α (80-fold), and B-Raf (>200-fold). Compound 47 demonstrated positive cardioprotective outcomes in a mouse model of ischemia/reperfusion cardiac injury, indicating that optimized exemplars from this series, such as 47, are favorable leads for discovering novel medicines for cardiac diseases.
4 -phenoxypyridine compound containing quinoxalinone and application thereof (by machine translation)
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, (2020/07/13)
The invention belongs to the field of medicines, and particularly relates to 4 -phenoxypyridine compounds containing quinoxalinone and application thereof. The 4 -phenoxypyridine compound containing quinoxalinone has the structure of the general formula (I). The invention also relates to the application of the compound of the general formula (I) to inhibit c-Met kinase and provide 4 -phenoxypyridine compounds containing quinoxalinone and pharmaceutically acceptable salts thereof in preparation of medicines for treating and/or preventing diseases caused by abnormal high expression c-Met kinase. (by machine translation)