Design and Synthesis of a Novel Photoaffinity Ligand for the Dopamine and Serotonin Transporters Based on 2-Carbometh

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• 作者：Amy Hauck Newman ; Joo Hwan Cha ; Jianjing Cao ; Theresa Kopajtic ; Jonathan L. Katz ; M. Laura Parnas ; Roxanne Vaughan ; John R. Lever
• 刊名：Journal of Medicinal Chemistry
• 出版年：2006
• 出版时间：November 2, 2006
• 年：2006
• 卷：49
• 期：22
• 页码：6621 - 6625
• 全文大小：153K
• 年卷期：v.49,no.22(November 2, 2006)
• ISSN：1520-4804

文摘

Tropane-based photoaffinity ligands covalently bind to discrete points of attachment on the dopaminetransporter (DAT). To further explore structure-activity relations, a ligand in which the photoactivatedgroup was extended from the 3-position of the tropane ring was synthesized from cocaine via a Stille orSuzuki coupling strategy. 3-(4'-Azido-3'-iodo-biphenyl-4-yl)-8-methyl-8-aza-bicyclo[3.2.1]octane-2-carboxylicacid methyl ester (11; K_i = 15.1 ± 2.2 nM) demonstrated high binding affinity for the DAT. Moreover, thiscompound showed moderate binding affinity for the serotonin transporter (SERT, K_i = 109 ± 14 nM),suggesting the potential utility of [¹²⁵I]11 in both DAT and SERT protein structure studies.