Novel Mps1 kinase inhibitors: From purine to pyrrolopyrimidine and quinazoline leads

被引：15

作者：

Bursavich, Matthew G. ^{[1
]}

Dastrup, David ^{[1
]}

Shenderovich, Mark ^{[1
]}

Yager, Kraig M. ^{[1
]}

Cimbora, Daniel M. ^{[2
]}

Williams, Brandi ^{[2
]}

Kumar, D. Vijay ^{[1
]}

机构：

[1] Myrexis Inc, Med Chem, Salt Lake City, UT 84108 USA

[2] Myrexis Inc, Vitro Pharmacol, Salt Lake City, UT 84108 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 24期

关键词：

Mps1; TTK; Protein kinase inhibitors; Scaffold hopping; Conformational restriction; Structure-based design; Cancer; Purines; Pyrrolopyrimidines; Quinazoline; POTENT;

D O I：

10.1016/j.bmcl.2013.10.008

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Mps1, also known as TTK, is a mitotic checkpoint protein kinase that has become a promising new target of cancer research. In an effort to improve the lead-likeness of our recent Mps1 purine lead compounds, a scaffold hopping exercise has been undertaken. Structure-based design, principles of conformational restriction, and subsequent scaffold hopping has led to novel pyrrolopyrimidine and quinazoline Mps1 inhibitors. These new single-digit nanomolar leads provide the basis for developing potent, novel Mps1 inhibitors with improved drug-like properties. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：6829 / 6833

页数：5

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