Class 1 PI3K Clinical Candidates and Recent Inhibitor Design Strategies: A Medicinal Chemistry Perspective

被引：130

作者：

Garces, Aimie E. ^{[1
]}

Stocks, Michael J. ^{[1
]}

机构：

[1] Univ Pk Nottingham, Ctr Biomol Sci, Nottingham NG7 2RD, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2019年 / 62卷 / 10期

基金：

英国医学研究理事会;

关键词：

PHOSPHOINOSITIDE 3-KINASE DELTA; IN-VIVO EVALUATION; BIOLOGICAL EVALUATION; HIGHLY POTENT; PI3K-DELTA INHIBITORS; SELECTIVE INHIBITOR; ISOFORM SELECTIVITY; (PI3K)/MAMMALIAN TARGET; PI3-KINASE INHIBITORS; PI3K-BETA INHIBITORS;

D O I：

10.1021/acs.jmedchem.8b01492

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Phosphatidylinositol 3-kinases (PI3Ks) are a family of lipid kinases that phosphorylate the 3-OH of the inositol ring of phosphoinositides, and deregulation of this pathway has implications in many diseases. The search for novel PI3K inhibitors has been at the forefront of academic and industrial medicinal chemistry with over 600 medicinal chemistry-based publications and patents appearing to date, leading to 38 clinical candidates and the launch of two drugs, idelalisib in 2014 and copanlisib in 2017. This Perspective will discuss medicinal chemistry design approaches to novel isoform-selective inhibitors through consideration of brief case histories of compounds that have progressed into clinical development or that have revealed new structural motifs in this highly competitive area of research.

引用

页码：4815 / 4850

页数：36

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