Discovery of 3,6-dihydro-2H-pyran as a morpholine replacement in 6-aryl-1H-pyrazolo[3,4-d]pyrimidines and 2-arylthieno[3,2-d]pyrimidines: ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR)

被引：49

作者：

Kaplan, Joshua ^{[1
]}

Verheijen, Jeroen C. ^{[1
]}

Brooijmans, Natasja ^{[1
]}

Toral-Barza, Lourdes ^{[2
]}

Hollander, Irwin ^{[2
]}

Yu, Ker ^{[2
]}

Zask, Arie ^{[1
]}

机构：

[1] Wyeth Res, Chem Sci, Pearl River, NY 10965 USA

[2] Wyeth Res, Oncol Res, Pearl River, NY 10965 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 02期

关键词：

SELECTIVE INHIBITORS; PATHWAY; CANCER; POTENT;

D O I：

10.1016/j.bmcl.2009.11.050

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The morpholine hinge-region binding group on a series of pyrazolopyrimidine and thienopyrimidine mammalian target of rapamycin ( mTOR) inhibitors was replaced with 3,6-dihydro-2H-pyran (DHP), giving compounds of equivalent potency and selectivity versus PI3K. These results establish the DHP group as a hinge-region binding motif for the preparation of highly potent and selective mTOR inhibitors. (C) 2009 Elsevier Ltd. All rights reserved.

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页码：640 / 643

页数：4

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