Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3Kα inhibitors

被引：7

作者：

Chen, Rui ^{[1
]}

Wang, Zhongyuan ^{[2
]}

Sima, Lijie ^{[3
]}

Cheng, Hu ^{[1
]}

Luo, Bilan ^{[1
]}

Wang, Jianta ^{[1
]}

Guo, Bing ^{[4
]}

Mao, Shunyi ^{[5
]}

Zhou, Zhixu ^{[5
]}

Peng, Jingang ^{[1
]}

Tang, Lei ^{[1
]}

Liu, Xinfu ^{[3
]}

Liao, Weike ^{[1
]}

机构：

[1] Guizhou Med Univ, Guizhou Prov Engn Technol Res Ctr Chem Drug R&D, Guiyang 550004, Peoples R China

[2] Guizhou Prov Peoples Hosp, Dept Pharm, Guiyang, Peoples R China

[3] Univ South China, Dept Hematol & Oncol, Shaoyang Cent Hosp, Affiliated Shaoyang Hosp,Hengyang Med Sch, Guiyang 550004, Peoples R China

[4] Guizhou Med Univ, Guizhou Prov Key Lab Pathogenesis & Drug Res Commo, Guiyang, Peoples R China

[5] Guizhou Univ, Sch Pharmaceut Sci, Guiyang, Peoples R China

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2023年 / 38卷 / 01期

基金：

美国国家科学基金会;

关键词：

PI3K alpha; synthesis; Imidazo[12-a]pyridine derivatives; antitumor activity; I PI3 KINASE; DISCOVERY; IDENTIFICATION; CHALLENGES; 3-KINASES; PATHWAY;

D O I：

10.1080/14756366.2022.2155638

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Inhibition of PI3K pathway has become a desirable strategy for cancer treatment. In this work, a series of 2, 6, 8-substituted Imidazo[1,2-a]pyridine derivatives were designed and screened for their activities against PI3K alpha and a panel of PI3K alpha-addicted cancer cells. Among them, compound 35 was identified as a PI3K alpha inhibitor with nanomolar potency as well as acceptable antiproliferative activity. Flow cytometry analysis confirmed 35 induced cell cycle arrest and apoptosis in T47D cells. In addition, it also showed desirable in vitro ADME properties. The design, synthesis, and SAR exploration of 35 are described within.

引用

页数：13

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