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

doi:10.1016/j.bmc.2012.03.026

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

Experimental Radiation Oncology

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

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 0.025 μM against PI3Kα and significant pAkt suppression effect. Molecular docking analysis was performed to determine possible binding modes between PI3Kα and target compounds.

Original language	English (US)
Pages (from-to)	2837-2844
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	20
Issue number	9
DOIs	https://doi.org/10.1016/j.bmc.2012.03.026
State	Published - May 1 2012

Keywords

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

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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

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 0.025 μM against PI3Kα and significant pAkt suppression effect. Molecular docking analysis was performed to determine possible binding modes between PI3Kα and target compounds.",

keywords = "2-Piperidinol-3-(arylsulfonyl)quinoxaline, Antitumor activity, PI3Kα, pAkt",

author = "Peng Wu and Yi Su and Xiaowen Liu and Bo Yang and Qiaojun He and Yongzhou Hu",

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AU - Wu, Peng

AU - Su, Yi

AU - Liu, Xiaowen

AU - Yang, Bo

AU - He, Qiaojun

AU - Hu, Yongzhou

PY - 2012/5/1

Y1 - 2012/5/1

N2 - 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 0.025 μM against PI3Kα and significant pAkt suppression effect. Molecular docking analysis was performed to determine possible binding modes between PI3Kα and target compounds.

AB - 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 0.025 μM against PI3Kα and significant pAkt suppression effect. Molecular docking analysis was performed to determine possible binding modes between PI3Kα and target compounds.

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KW - Antitumor activity

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KW - pAkt

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

Abstract

Keywords

ASJC Scopus subject areas

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