1. Discovery of novel 2-piperidinol-3-(arylsulfonyl)quinoxalines as phosphoinositide 3-kinase α (PI3Kα) inhibitors.
- Author
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Wu P, Su Y, Liu X, Yang B, He Q, and Hu Y
- Subjects
- Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Binding Sites, Catalytic Domain, Cell Line, Tumor, Cell Proliferation drug effects, Computer Simulation, Drug Evaluation, Preclinical, Drug Screening Assays, Antitumor, Enzyme Inhibitors chemical synthesis, Humans, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Quinoxalines chemical synthesis, Quinoxalines pharmacology, Structure-Activity Relationship, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Phosphoinositide-3 Kinase Inhibitors, Piperidines chemistry, Piperidines pharmacology, Quinoxalines chemistry
- 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 2.32 μM, proved to be a promising class of novel PI3Kα inhibitors. The most potent compound 10d (WR23) showed an inhibitory IC(50) 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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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