Novel and highly potent histamine H3 receptor ligands. Part 1: withdrawing of hERG activity
Novel and highly potent histamine H3 receptor ligands. Part 1: withdrawing of hERG activity
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DOI：
10.1016/j.bmcl.2011.07.006
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发表时间：
2011-09-15
影响因子：
2.7
通讯作者：
Capet, Marc
中科院分区：
文献类型：
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作者：
Levoin, Nicolas;Labeeuw, Olivier;Capet, Marc
一些芳基-哌啶基醚组胺H3受体拮抗剂的临床前研究显示了较强的hERG结合。为了克服这个问题，我们已经开发了一个QSAR模型专门致力于H3受体配体。该模型被设计为直接适用于药物化学，而不需要分子建模。由此产生的递归划分树是鲁棒的（80-85%的准确率），但也很简单和易于理解。我们的工作中出现了一个新的有前途的线索，并提出了结构-活性关系。(C)2011爱思唯尔有限公司保留所有权利。
Pre-clinical investigation of some aryl-piperidinyl ether histamine H3 receptor antagonists revealed a strong hERG binding. To overcome this issue, we have developed a QSAR model specially dedicated to H3 receptor ligands. This model was designed to be directly applicable in medicinal chemistry with no need of molecular modeling. The resulting recursive partitioning trees are robust (80-85% accuracy), but also simple and comprehensible. A novel promising lead emerged from our work and the structure-activity relationships are presented. (C) 2011 Elsevier Ltd. All rights reserved.