N-Phenyl-4-hydroxy-2-quinolone-3-carboxamides as selective inhibitors of mutant H1047R phosphoinositide-3-kinase (PI3Kα)

  • Bioorg Med Chem. 2012 Dec 15;20(24):7175-83. doi: 10.1016/j.bmc.2012.09.059.
Dima A Sabbah  1 ,  Neka A Simms ,  Wang Wang ,  Yuxiang Dong ,  Edward L Ezell ,  Michael G Brattain ,  Jonathan L Vennerstrom ,  Haizhen A Zhong
Affiliations
  • 1. College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198-6025, USA.
PMID: 23121722 DOI: 10.1016/j.bmc.2012.09.059
Abstract

This work describes our efforts to optimize the lead PI3Kα Inhibitor N-benzyl 4-hydroxy-2-quinolone-3-carboxamide using structure-based design and molecular docking. We identified a series of N-phenyl 4-hydroxy-2-quinolone-3-carboxamides as selective inhibitors of mutant H1047R versus wild-type PI3Kα and we also showed that the cell growth inhibition by these compounds likely occurs by inhibiting the formation of pAKT and induction of Apoptosis.

Products