Synthesis and characterization of a series of chiral alkoxymethyl morpholine analogs as dopamine receptor 4 (D4R) antagonists.
Synthesis and characterization of a series of chiral alkoxymethyl morpholine analogs as dopamine receptor 4 (D4R) antagonists.
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DOI：
10.1016/j.bmcl.2016.03.102
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发表时间：
2016-05-15
影响因子：
2.7
通讯作者：
Hopkins CR
中科院分区：
文献类型：
--
作者：
Witt JO;McCollum AL;Hurtado MA;Huseman ED;Jeffries DE;Temple KJ;Plumley HC;Blobaum AL;Lindsley CW;Hopkins CR
本文报道了一系列手性烷氧甲基吗啉类似物的合成及其构效关系。我们的努力最终确定了(S)-2-(6-氯吡啶-2-基)oxy)methyl)-4-((6-fluoro-1H-indol-3-yl)methyl)morpholine)是一种新的有效和选择性的多巴胺D4受体拮抗剂，对其他受试的多巴胺受体具有选择性(1µM时对D1、D2L、D2S、D3和D5的抑制率为10%)。
Herein, we report the synthesis and structure–activity relationship of a series of chiral alkoxymethyl morpholine analogs. Our efforts have culminated in the identification of (S)-2-(((6-chloropyridin-2-yl) oxy)methyl)-4-((6-fluoro-1H-indol-3-yl)methyl)morpholine as a novel potent and selective dopamine D4 receptor antagonist with selectivity against the other dopamine receptors tested (<10% inhibition at 1 µM against D1, D2L, D2S, D3, and D5).