Design, synthesis and antitumor activities of novel bis-aryl ureas derivatives as Raf kinase inhibitors.
A series of novel bis-aryl ureas containing trifluoromethyl imidazolyl group targeting Raf kinase were designed and synthesized based on the lead compound of Sorafenib. All the prepared compounds were evaluated for their in vitro antiproliferative activities against three human cancer cell lines including MDA-MB-231 (breast), BGC-823 (gastric), and SMMC-7721 (liver). Several compounds from the series exhibited excellent antitumor activities against all three tested cancer lines. Further their inhibitory activities against Raf kinase were investigated, and three compounds (11c, 11d, and 11p) demonstrated better activities than contrast drug Sorafenib. Especially compound 11c was found to be a potent and selective Raf kinase inhibitor and could be considered as a candidate compound for further development.
Institute of Radiation and Irradiation Medicine, Academy of Military Medical Science, Beijing 100850, China.
Wenhu
W
Zhan
Yanyang
Y
Li
Weiping
W
Huang
Yanjin
Y
Zhao
Zhenglin
Z
Yao
Shanyou
S
Yu
Shoujun
S
Yuan
Falong
F
Jiang
Shan
S
Yao
Shuxin
S
Li
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000633:toxicity; D001557:Benzenesulfonates / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D011725:Pyridines / Q000737:chemistry; D000077157:Sorafenib; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity; D048490:raf Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D014508:Urea; D000077157:Sorafenib; D048490:raf Kinases