Anti-Cancer Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Michelle Prudhomme  
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex


Pyrrolidino Analogues of Gefitinib with Improved EGFR Inhibition, Cancer Cell Cytotoxicity, and Pharmacokinetic Properties

Author(s): Jing-Kun Fang, Zhimin Xu, Yingjun Zhang, Weihong Zhang, Bing Liu, Yu Fang, Tengxiao Sun.

Graphical Abstract:


The binding mode analysis of Gefitinib revealed that 6-propylmorpholino group (sidechain) shows no interactions due to its weak electron density. In order to modify the electron density of Gefitinib’s sidechain, novel pyrrolidino analogs of Gefitinib where morpholino groups were replaced by substituted pyrrolidino groups were synthesized. Gefitinib derivatives with high electronegativity atoms or groups in the pyrrolidino moiety always exhibit high potent activity against EGFR and human cancer cell lines, A431, MDA-MB-231 and A549. Among these derivatives, 16 displayed the best pharmacokinetic properties that make it to be a promising candidate for developing drugs to replace Gefitinib.

Keywords: Gefitinib, anticancer, EGFR, pyrrolidino analogue, pharmacokinetic property.

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Article Details

Year: 2016
Page: [1665 - 1672]
Pages: 8
DOI: 10.2174/1871520616666160622094153
Price: $58