Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3Kα inhibitors. (31st December 2023)

• Record Type: Journal Article
• Authors: Chen, Rui; Wang, Zhongyuan; Sima, Lijie; Cheng, Hu; Luo, Bilan; Wang, Jianta; Guo, Bing; Mao, Shunyi; Zhou, Zhixu; Peng, Jingang; Tang, Lei; Liu, Xinfu; Liao, Weike
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 38:Number 1(2023)
• Publication Date: 2023-12-31
• Subjects: PI3Kα -- synthesis -- Imidazo[12-a]pyridine derivatives -- antitumor activity; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2022.2155638
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: 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 α and a panel of PI3K α -addicted cancer cells. Among them, compound 35 was identified as a PI3K α 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.