Derivatives of Dibenzothiophene for Positron Emission Tomography Imaging of 伪7-Nicotinic Acetylcholine Receptors

详细信息    查看全文

• 作者：Yongjun Gao ; Kenneth J. Kellar ; Robert P. Yasuda ; Thao Tran ; Yingxian Xiao ; Robert F. Dannals ; Andrew G. Horti
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：October 10, 2013
• 年：2013
• 卷：56
• 期：19
• 页码：7574-7589
• 全文大小：682K
• 年卷期：v.56,no.19(October 10, 2013)
• ISSN：1520-4804

文摘

A new series of derivatives of 3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)dibenzo[b,d]thiophene 5,5-dioxide with high binding affinities and selectivity for 伪7-nicotinic acetylcholine receptors (伪7-nAChRs) (K_i = 0.4鈥?0 nM) has been synthesized for positron emission tomography (PET) imaging of 伪7-nAChRs. Two radiolabeled members of the series [¹⁸F]7a (K_i = 0.4 nM) and [¹⁸F]7c (K_i = 1.3 nM) were synthesized. [¹⁸F]7a and [¹⁸F]7c readily entered the mouse brain and specifically labeled 伪7-nAChRs. The 伪7-nAChR selective ligand 1 (SSR180711) blocked the binding of [¹⁸F]7a in the mouse brain in a dose-dependent manner. The mouse blocking studies with non-伪7-nAChR central nervous system drugs demonstrated that [¹⁸F]7a is highly 伪7-nAChR selective. In agreement with its binding affinity the binding potential of [¹⁸F]7a (BP_ND = 5.3鈥?.0) in control mice is superior to previous 伪7-nAChR PET radioligands. Thus, [¹⁸F]7a displays excellent imaging properties in mice and has been chosen for further evaluation as a potential PET radioligand for imaging of 伪7-nAChR in non-human primates.