Zheng Guangrong, Dwoskin Linda P, Deaciuc Agripina G, Crooks Peter A
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Rose Street, Lexington, KY 40536-0082, USA.
Bioorg Med Chem Lett. 2008 Dec 15;18(24):6509-12. doi: 10.1016/j.bmcl.2008.10.042. Epub 2008 Oct 14.
A series of lobelane homologues has been synthesized and evaluated for their [(3)H]DTBZ binding affinity at the vesicular monoamine transporter-2 (VMAT2). The structure-activity relationships (SAR) indicate that for retention of binding affinity at VMAT2, the lengths of the methylene linkers should be no shorter than one methylene unit at C-6 of the piperidine ring, and no shorter than two methylene units at C-2 of the piperidine ring. These results indicate that the intramolecular distances between the piperidine ring and two phenyl rings in lobelane analogues are an important criterion for retention of high affinity at VMAT2.
已合成了一系列洛贝林同系物，并评估了它们对囊泡单胺转运体2（VMAT2）的[(3)H]DTBZ结合亲和力。构效关系（SAR）表明，为了保持对VMAT2的结合亲和力，亚甲基连接体的长度在哌啶环的C-6处不应短于一个亚甲基单元，在哌啶环的C-2处不应短于两个亚甲基单元。这些结果表明，洛贝林类似物中哌啶环与两个苯环之间的分子内距离是保持对VMAT2高亲和力的重要标准。
