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发现一系列丙烯酸及其衍生物作为选择性EP3受体拮抗剂的化学先导物。

Discovery of a series of acrylic acids and their derivatives as chemical leads for selective EP3 receptor antagonists.

作者信息

Asada Masaki, Obitsu Tetsuo, Nagase Toshihiko, Sugimoto Isamu, Yamaura Yoshiyuki, Sato Kazutoyo, Narita Masami, Ohuchida Shuichi, Nakai Hisao, Toda Masaaki

机构信息

Minase Research Institute, Ono Pharmaceutical Co., Ltd, Shimamoto, Mishima, Osaka 618-8585, Japan.

出版信息

Bioorg Med Chem. 2009 Sep 15;17(18):6567-82. doi: 10.1016/j.bmc.2009.08.007. Epub 2009 Aug 8.

Abstract

A series of acrylic acids and their structurally related compounds were evaluated for their binding affinity to four EP receptor subtypes (EP1-4). Starting from the initial hit 3, which was discovered in our in-house library, compounds 4 and 5 were identified as new chemical leads as candidates for further optimization towards a selective EP3 receptor antagonist. The identification process of these compounds and their pharmacokinetic profiles are presented.

摘要

对一系列丙烯酸及其结构相关化合物与四种EP受体亚型(EP1 - 4)的结合亲和力进行了评估。从我们内部库中发现的初始活性化合物3开始,化合物4和5被确定为新的化学先导物,作为进一步优化以获得选择性EP3受体拮抗剂的候选物。介绍了这些化合物的鉴定过程及其药代动力学概况。

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