Design, Synthesis, and Biological Evaluation of 1,4-Bis(2,3-dihydro-5-oxopyrrol-4-yl)-1,3-butadienes as Potential Chk1 Inhibitors

作者：Ren, H.; Sun, L.; Yan, H.^*

来源：Russian Journal of General Chemistry, 2017, 87(12): 3029-3035.

DOI：10.1134/S1070363217120490

• Chk1 inhibitors
• 1,4-bis(2,3-dihydro-5-oxopyrrol-4-yl)-1,3-butadienes
• synthesis
• biological testing

A series of 1,4-bis(2,3-dihydro-5-oxopyrrol-4-yl)-1,3-butadienes were designed as inhibitors of checkpoint kinase 1 (Chk1), based on the structureaEuro'activity relationships for known inhibitors through docking simulations. The docking results suggested that the title compounds were similar to known inhibitors in interaction with the catalytic site of Chk1. Twelve compounds were synthesized by a one-pot procedure from amines, dimethyl acetylenedicarboxylate, and glyoxal in water in the presence of catalytic amounts of gamma-cyclodextrin. The inhibitory activities of the synthesized compounds were evaluated in vitro using EC9706 esophageal cancer cells. The results indicated that 1,4-bis(2,3-dihydro-5-oxopyrrol-4-yl)-1,3-butadienes significantly inhibited Chk1 (IC50 10.45 mu M).

• 出版日期2017-12
• 单位北京工业大学