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Journal of Enzyme Inhibition and Medicinal Chemistry

Journal of Enzyme Inhibition and Medicinal Chemistry

IF: 5.6
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Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3Kα inhibitors

Published:1 December 2023 DOI: 10.1080/14756366.2022.2155638 PMID: 36650905
Rui Chen, Zhongyuan Wang, Lijie Sima, Hu Cheng, Bilan Luo, Jianta Wang, Bing Guo, Shunyi Mao, Zhixu Zhou, Jingang Peng, Lei Tang, Xinfu Liu, Weike Liao

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 PI3Kα and a panel of PI3Kα-addicted cancer cells. Among them, compound 35 was identified as a PI3Kα 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.

Synthesis

Ethyl 8-bromo-6-methylimidazo[1,2-a]pyridine-2-carboxylate
8-BroMo-6-MethyliMidazo[1,2-a]pyridine-2-carboxylic acid

Substances (8)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Alpelisib (BYL719) 1217486-61-7 C19H22F3N5O2S 261 suppliers $10.00-$2691.10
Alpelisib (BYL719) 1217486-61-7 C19H22F3N5O2S 261 suppliers $10.00-$2691.10
Alpelisib (BYL719) 1217486-61-7 C19H22F3N5O2S 261 suppliers $10.00-$2691.10
Alpelisib (BYL719) 1217486-61-7 C19H22F3N5O2S 261 suppliers $10.00-$2691.10
PIK-75 372196-67-3 C16H14BrN5O4S 102 suppliers Inquiry
PIK-75 372196-67-3 C16H14BrN5O4S 102 suppliers Inquiry
PIK-75 372196-67-3 C16H14BrN5O4S 102 suppliers Inquiry
PIK-75 372196-67-3 C16H14BrN5O4S 102 suppliers Inquiry

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