Discovery of diarylurea P2Y1 antagonists with improved aqueous solubility
Discovery of diarylurea P2Y1 antagonists with improved aqueous solubility
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DOI：
10.1016/j.bmcl.2013.03.125
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发表时间：
2013-06-01
影响因子：
2.7
通讯作者：
Lam, Patrick Y. S.
中科院分区：
文献类型：
--
作者：
Wang, Tammy C.;Qia, Jennifer X.;Lam, Patrick Y. S.
临床前数据表明，P2 Y（1）拮抗剂，例如二芳基脲化合物1，可以提供与P2 Y（12）拮抗剂类似的抗血栓形成功效，并且可能具有减少出血倾向的潜力。本文描述了一系列带有增溶胺侧链的二芳基脲类化合物作为有效的P2Y（1）拮抗剂。其中，化合物2l和3h与化合物1相比具有改善的水溶性，并保持抗血小板活性。化合物21在大鼠和兔血栓形成模型中均适度有效，并且具有与化合物1类似的大鼠出血时间的适度延长。(C)2013爱思唯尔有限公司保留所有权利。
Preclinical data suggests that P2Y(1) antagonists, such as diarylurea compound 1, may provide antithrombotic efficacy similar to P2Y(12) antagonists and may have the potential of providing reduced bleeding liabilities. This manuscript describes a series of diarylureas bearing solublizing amine side chains as potent P2Y(1) antagonists. Among them, compounds 2l and 3h had improved aqueous solubility and maintained antiplatelet activity compared with compound 1. Compound 2l was moderately efficacious in both rat and rabbit thrombosis models and had a moderate prolongation of bleeding time in rats similar to that of compound 1. (C) 2013 Elsevier Ltd. All rights reserved.