Design and synthesis of a novel class EGFR/HER2 dual inhibitors containing tricyclic oxazine fused quinazolines scaffold.

Min Sun, Jianmin Jia, Huanliang Sun, Feidong Wang

Bioorganic & medicinal chemistry letters 2020 May 01

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Two series of novel tricyclic oxazine and oxazepine fused quinazolines have been designed, synthesized and evaluated for their inhibitory activity against EGFR and HER2. Structure-activity relationship (SAR) of these compounds was discussed. From the SAR studies, we found that intramolecular cyclization which possessed a functional Michael acceptor group can enhance the antitumor activities. Compounds 1e and 1h were identified as lead compounds which displayed almost 3-4 times more potent inhibition of EGFR and HER2 than the approved drug lapatinib. The satisfactory physicochemical properties of these compounds were also supported by ACD labs. The results presented here will promote the development of newer dual inhibitors of EGFR and HER2. Copyright © 2020 Elsevier Ltd. All rights reserved.

Citation

Min Sun, Jianmin Jia, Huanliang Sun, Feidong Wang. Design and synthesis of a novel class EGFR/HER2 dual inhibitors containing tricyclic oxazine fused quinazolines scaffold. Bioorganic & medicinal chemistry letters. 2020 May 01;30(9):127045