嘧啶类 h-MCH-R1 拮抗剂 ATC0175 的衍生：体外分析和体内评价。
Pyrimidine-based antagonists of h-MCH-R1 derived from ATC0175: in vitro profiling and in vivo evaluation.
机构信息
Medicinal Chemistry, Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, CA 92121, USA.
出版信息
Bioorg Med Chem Lett. 2009 Nov 1;19(21):6166-71. doi: 10.1016/j.bmcl.2009.09.003. Epub 2009 Sep 6.
A series of pyrimidine analogues derived from ATC0175 were potent antagonists of human MCH-R1 in vitro. Significantly improved receptor selectivity was achieved with several analogues from this series, but no improvement in brain partitioning was noted. One example from this series was shown to inhibit food intake and decrease body weight in a chronic study. However no clear correlation between the pharmacodynamic effect and the pharmacokinetic data with respect to brain concentration was discernible leading us to conclude that the observed effect was most likely not due to interaction with the MCH-R1.
一系列源自 ATC0175 的嘧啶类似物在体外对人 MCH-R1 具有很强的拮抗作用。该系列的几种类似物显著提高了受体选择性，但脑分配方面没有改善。该系列中的一个例子被证明可以在慢性研究中抑制食物摄入和降低体重。然而，在药效学效应和脑浓度方面的药代动力学数据之间没有明显的相关性，这使我们得出结论，观察到的效应很可能不是由于与 MCH-R1 的相互作用。
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