| Literature DB >> 22765894 |
Moon H Kim1, Amy Lew Tsuhako, Erick W Co, Dana T Aftab, Frauke Bentzien, Jason Chen, Wei Cheng, Stefan Engst, Levina Goon, Rhett R Klein, Donna T Le, Morrison Mac, Jason J Parks, Fawn Qian, Monica Rodriquez, Thomas J Stout, Jeffrey H Till, Kwang-Ai Won, Xiang Wu, F Michael Yakes, Peiwen Yu, Wentao Zhang, Yeping Zhao, Peter Lamb, John M Nuss, Wei Xu.
Abstract
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 CYP profile, acceptable pharmacokinetic and toxicity profiles, and robust efficacy in multiple xenograft tumor models.Entities:
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Year: 2012 PMID： 22765894 DOI： 10.1016/j.bmcl.2012.06.029
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823