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

Zhejiang University

Research output: Contribution to journal › Journal article › Research › peer-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 language	English
Journal	Bioorganic & Medicinal Chemistry
Volume	20
Issue number	9
Pages (from-to)	2837-2844
ISSN	0968-0896
DOIs	https://doi.org/10.1016/j.bmc.2012.03.026
Publication status	Published - 2012
Externally published	Yes

Keywords

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

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10.1016/j.bmc.2012.03.026

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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 2.32μM, 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.",

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

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

year = "2012",

doi = "10.1016/j.bmc.2012.03.026",

language = "English",

volume = "20",

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journal = "Bioorganic & Medicinal Chemistry",

issn = "0968-0896",

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T1 - Discovery of novel 2-piperidinol-3-(arylsulfonyl)quinoxalines as phosphoinositide 3-kinase α (PI3Kα) inhibitors

AU - Wu, Peng

AU - Su, Yi

AU - Liu, Xiaowen

AU - Yang, Bo

AU - He, Qiaojun

AU - Hu, Yongzhou

PY - 2012

Y1 - 2012

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 2.32μM, 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.

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 2.32μM, 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.

KW - 2-Piperidinol-3-(arylsulfonyl)quinoxaline

KW - PI3Kα

KW - pAkt

KW - Antitumor activity

U2 - 10.1016/j.bmc.2012.03.026

DO - 10.1016/j.bmc.2012.03.026

M3 - Journal article

SN - 0968-0896

VL - 20

SP - 2837

EP - 2844

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 9

ER -

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

Abstract

Keywords

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