Discovery of novel 2-piperidinol-3-(arylsulfonyl)quinoxalines as phosphoinositide 3-kinase α (PI3Kα) inhibitors

Peng Wu, Yi Su, Xiaowen Liu, Bo Yang, Qiaojun He, Yongzhou Hu

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

A series of novel 2-aliphatic cyclic amine-3-(arylsulfonyl)quinoxalines was synthesized based on the structural features of a previously identified lead, WR1. The 2-piperidinol-3-(arylsulfonyl)quinoxalines, which showed excellent antitumor activities against five human cell lines, with inhibitory activities ranging from 0.34 to 2.32μM, proved to be a promising class of novel PI3Kα inhibitors. The most potent compound 10d (WR23) showed an inhibitory IC50 value of 0.025μM against PI3Kα and significant pAkt suppression effect. Molecular docking analysis was performed to determine possible binding modes between PI3Kα and target compounds.
Original languageEnglish
JournalBioorganic & Medicinal Chemistry
Volume20
Issue number9
Pages (from-to)2837-2844
ISSN0968-0896
DOIs
Publication statusPublished - 2012
Externally publishedYes

Keywords

  • 2-Piperidinol-3-(arylsulfonyl)quinoxaline
  • PI3Kα
  • pAkt
  • Antitumor activity

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