2. Academic Validation
  3. Design, synthesis, and biological evaluation of novel 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors

Design, synthesis, and biological evaluation of novel 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors

  • Bioorg Med Chem Lett. 2013 Oct 15;23(20):5630-3. doi: 10.1016/j.bmcl.2013.08.037.
Lei Ding 1,  Feng Tang,  Wei Huang,  Qiu Jin,  Han Shen,  Ping Wei
Affiliations

Affiliation

  • 1 The College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, No. 30 Puzhu Road(S), Nanjing 211800, China; Jiangsu Simcere Pharmaceutical Co., Ltd, Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No. 699-18 Xuan Wu Avenue, Nanjing 210042, China. Electronic address: dinglei@simcere.com.
PMID: 23999040 DOI: 10.1016/j.bmcl.2013.08.037
Abstract

A novel series of 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives targeting VEGFR-2, PDGFR-β and c-Kit kinases were designed and synthesized. The molecular design was based on the SAR features of indolin-2-ones as kinase inhibitors. SAR study of the series allowed us to identify compounds possessing more potent inhibitory activities against the three kinases than sunitinb with IC50 values in the low nanomolar range in vitro. Additionally, some compounds also showed favorable antiproliferative activities against a panel of Cancer cell lines (BXPC-3, T24, BGC, HEPG2 and HT29).

Keywords

2-Dihydroindolinone derivatives; Antiproliferative; Inhibitor; Molecular docking; Receptor tyrosine kinase.

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