The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors

…, F Bentzien, J Chen, W Cheng, S Engst, L Goon…

文献索引：Kim, Moon H.; Tsuhako, Amy Lew; Co, Erick W.; Aftab, Dana T.; Bentzien, Frauke; Chen, Jason; Cheng, Wei; Engst, Stefan; Goon, Levina; Klein, Rhett R.; Le, Donna T.; Mac, Morrison; Parks, Jason J.; Qian, Fawn; Rodriquez, Monica; Stout, Thomas J.; Till, Jeffrey H.; Won, Kwang-Ai; Wu, Xiang; Michael Yakes; Yu, Peiwen; Zhang, Wentao; Zhao, Yeping; Lamb, Peter; Nuss, John M.; Xu, Wei Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 15 p. 4979 - 4985

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被引用次数: 9

摘要

Variously substituted indolin-2-ones were synthesized and evaluated for activity against KDR, Flt-1, FGFR-1 and PDGFR. Extension at the 5-position of the oxindole ring with ethyl piperidine (compound 7i) proved to be the most beneficial for attaining both biochemical and cellular potencies. Further optimization of 7i to balance biochemical and cellular potencies with favorable ADME/PK properties led to the identification of 8h, a compound with a clean ...