Design, synthesis and biological evaluation of pyrazolyl-thiazolinone derivatives as potential EGFR and HER-2 kinase inhibitors.

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Qiu KM, Wang HH, Wang LM, Luo Y, Yang XH, Wang XM, Zhu HL

Design, synthesis and biological evaluation of pyrazolyl-thiazolinone derivatives as potential EGFR and HER-2 kinase inhibitors.

Bioorg Med Chem. 2012 Mar 15;20(6):2010-8. doi: 10.1016/j.bmc.2012.01.051. Epub 2012 Feb 4.

PubMed ID

22361272 [ View in PubMed

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Abstract

A series of pyrazolyl-thiazolinone derivatives (E1-E36) have been designed and synthesized and their biological activities were also evaluated as potential EGFR and HER-2 kinase inhibitors. Thirty-four of the 36 compounds were reported for the first time. Among them, compound 2-(5-(4-bromophenyl)-3-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one (E28) displayed the most potent inhibitory activity (IC(50)=0.24muM for EGFR and IC(50)=1.07muM for HER-2). Antiproliferative assay results indicated that compound E28 owned high antiproliferative activity against MCF-7, B16-F10 and HCT-116 in vitro, with IC(50) value of 0.30, 0.54, and 0.70muM, respectively. Docking simulation was further performed to position compound E28 into the EGFR active site to determine the probable binding model. Based on the preliminary results, compound E28 with potent inhibitory activity in tumor growth would be a potential anticancer agent.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Erlotinib	Epidermal growth factor receptor	IC 50 (nM)	30	N/A	N/A	Details