当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Design, synthesis and biological evaluation of novel 6-phenyl-1,3a,4,10b-tetrahydro-2H-benzo[c]thiazolo[4,5-e]azepin-2-one derivatives as potential BRD4 inhibitors.

Design, synthesis and biological evaluation of novel 6-phenyl-1,3a,4,10b-tetrahydro-2H-benzo[c]thiazolo[4,5-e]azepin-2-one derivatives as potential BRD4 inhibitors.

Abstract：

:Bromodomain-containing protein 4 (BRD4) is a key epigenetic regulator in cancer, and inhibitors targeting BRD4 exhibit great anticancer activity. By replacing the methyltriazole ring of the BRD4 inhibitor I-BET-762 with an N-methylthiazolidone heterocyclic ring, fifteen novel BRD4 inhibitors were designed and synthesized. Compound 13f had a hydrophobic acetylcyclopentanyl side chain, showing the most potent BRD4 inhibitory activity in the BRD4-BD1 inhibition assay (IC50 value of 110 nM), it also significantly suppressed the proliferation of MV-4-11 cells with high BRD4 level (IC50 value of 0.42 μM). Furthermore, the potent apoptosis-promoting and G0/G1 cycle-arresting activity of compound 13f were indicated by flow cytometry. As the downstream-protein of BRD4, c-Myc was in significantly low expression by compound 13f treatment in a dose-dependent manner. All the findings supported that this novel compound 13f provided a perspective for developing effective BRD4 inhibitors.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Li Q,Li J,Cai Y,Zou Y,Chen B,Zou F,Mo J,Han T,Guo W,Huang W,Qiu Q,Qian H

doi

10.1016/j.bmc.2020.115601

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

115601

issue

15

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(20)30431-4

journal_volume

28

pub_type

杂志文章

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