Analogs of JHU75528, a PET ligand for imaging of cerebral cannabinoid receptors (CBI): Development of ligands with optimized lipophilicity and binding affinity
Analogs of JHU75528, a PET ligand for imaging of cerebral cannabinoid receptors (CBI): Development of ligands with optimized lipophilicity and binding affinity
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DOI：
10.1016/j.ejmech.2008.03.040
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发表时间：
2009-02-01
影响因子：
6.7
通讯作者：
Horti, Andrew G.
中科院分区：
文献类型：
--
作者：
Fan, Hong;Kotsikorou, Evangelia;Horti, Andrew G.
利莫那班的氰基类似物与大脑大麻素受体（CB1）的结合亲和力高，并与优化的亲脂性已被合成为潜在的正电子发射断层扫描（PET）配体。该系列的最佳配体是未来PET同位素放射性标记的最佳靶点，并作为具有增强特性的放射性配体在人类受试者中进行CB1受体PET成像的体内评价。啮齿动物脑切片的细胞外电生理记录表明，新系列的先导化合物JHU75528，4具有与其与利莫那班的结构关系一致的功能性CB拮抗剂特性。分子模拟分析揭示了氰基与CB1结合口袋结合的重要作用。(C)2008年，Elsevier Masson SAS。All rights reserved.
Cyano analogs of Rimonabant with high binding affinity for the cerebral cannabinoid receptor (CB1) and with optimized lipophilicity have been synthesized as potential positron emission tomography (PET) ligands. The best ligands of the series are optimal targets for the future radiolabeling with PET isotopes and in vivo evaluation as radioligands with enhanced properties for PET imaging of CB1 receptors in human subjects. Extracellular electrophysiological recordings in rodent brain slices demonstrated that JHU75528, 4, the lead compound of the new series, has functional CB antagonist properties that are consistent with its structural relationship to Rimonabant. Molecular modeling analysis revealed an important role of the binding of the cyano group with the CB1 binding pocket. (C) 2008 Elsevier Masson SAS. All rights reserved.