Novel Mps1 kinase inhibitors: From purine to pyrrolopyrimidine and quinazoline leads
Novel Mps1 kinase inhibitors: From purine to pyrrolopyrimidine and quinazoline leads
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DOI：
10.1016/j.bmcl.2013.10.008
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发表时间：
2013-12-15
影响因子：
2.7
通讯作者：
Kumar, D. Vijay
中科院分区：
文献类型：
--
作者：
Bursavich, Matthew G.;Dastrup, David;Kumar, D. Vijay
Mps1，也被称为TTK，是一种有丝分裂检查点蛋白激酶，已成为癌症研究的一个有希望的新靶点。为了提高我们最近的Mps1嘌呤先导化合物的铅的相似性，我们进行了一个支架跳跃练习。基于结构的设计，构象限制原理，以及随后的支架跳跃导致了新的吡咯嘧啶和喹唑啉类Mps1抑制剂。这些新的个位数纳摩尔导联为开发有效的新型Mps1抑制剂提供了基础，这些抑制剂具有改进的药物样特性。(C) 2013 Elsevier Ltd.版权所有。
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.