AI Article Synopsis
- A series of novel quinazoline derivatives were created and tested as inhibitors for the EGFR kinase, with many showing strong inhibitory effects.
- Compound 6g was particularly effective, demonstrating a low IC value of 5 nM against EGFR wild-type and strong activity against specific cancer cell lines.
- The promising attributes of 6g, including selectivity, metabolic stability, and pharmacokinetics, indicate it has potential for further development in cancer treatment.
Article Abstract
A series of novel quinazoline derivatives bearing various C-6 benzamide substituents were synthesized and evaluated as EGFR inhibitors, and most showed significant inhibitory potency against EGFR kinase. In particular, compound 6g possessed potent inhibitory activity against EGFR wild-type (IC = 5 nM), and strong antiproliferative activity against HCC827 and Ba/F3 (L858R) cell lines. Kinase profiling against a panel of 365 kinases showed that 6g was highly selective for EGFR. Furthermore, 6g showed desirable properties in assays of liver microsome metabolic stability and cytochromes P450 inhibition and preliminary pharmacokinetic study. The overall attractive profile of 6g made it an interesting compound for further development.
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| http://dx.doi.org/10.1016/j.bmc.2018.02.022 | DOI Listing |
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