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鉴定具有光学活性的嘧啶衍生物为选择性 5-HT 调节剂。

Identification of Optically Active Pyrimidine Derivatives as Selective 5-HT Modulators.

机构信息

Center for Neuro-Medicine, Korea Institute of Science and Technology (KIST), 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 02792, Korea.

Department of Chemistry, Korea University, Seoul 02841, Korea.

出版信息

Molecules. 2017 Aug 26;22(9):1416. doi: 10.3390/molecules22091416.

DOI:10.3390/molecules22091416
PMID:28846591
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6151589/
Abstract

A series of pyrimidine derivatives - were synthesized and evaluated for their binding affinities towards 5-HT receptors. With regard to designed molecules -, the influence of the size of alkyl ether and the absolute configuration of a stereogenic center on the 5-HT binding affinity and selectivity was studied. The most promising diasteromeric mixtures and were selected in the initial radioligand binding assay and they were further synthesized as optically active forms starting from optically active alcohols and , prepared by an enzymatic kinetic resolution. Pyrimidine analogue ()- displayed an excellent 5-HT binding affinity with good selectivity values against a broad range of other 5-HT receptor subtypes.

摘要

一系列嘧啶衍生物被合成并评估了它们与 5-HT 受体的结合亲和力。就设计的分子而言，研究了烷基醚的大小和手性中心的绝对构型对 5-HT 结合亲和力和选择性的影响。在最初的放射性配体结合测定中，选择了最有前途的非对映混合物和，并进一步从光学活性醇和合成了它们的光学活性形式，这些醇和是通过酶促动力学拆分制备的。嘧啶类似物（）-显示出优异的 5-HT 结合亲和力，并对广泛的其他 5-HT 受体亚型具有良好的选择性值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edea/6151589/9c0972708549/molecules-22-01416-sch003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edea/6151589/a7a274c1ea6b/molecules-22-01416-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edea/6151589/773e464382da/molecules-22-01416-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edea/6151589/a567cc2ac03d/molecules-22-01416-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edea/6151589/643d10e6bf99/molecules-22-01416-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edea/6151589/9c0972708549/molecules-22-01416-sch003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edea/6151589/a7a274c1ea6b/molecules-22-01416-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edea/6151589/773e464382da/molecules-22-01416-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edea/6151589/a567cc2ac03d/molecules-22-01416-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edea/6151589/643d10e6bf99/molecules-22-01416-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edea/6151589/9c0972708549/molecules-22-01416-sch003.jpg

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2
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3
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5
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8
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J Clin Invest. 2013 Dec;123(12):4986-91. doi: 10.1172/JCI70678. Epub 2013 Dec 2.
9
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J Pharmacol Exp Ther. 2011 Jun;337(3):673-80. doi: 10.1124/jpet.111.179572. Epub 2011 Mar 14.
10
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J Chem Educ. 2011 Mar;88(3):334-336. doi: 10.1021/ed100325p.