Synthesis and monoamine transporter affinity of 3'-analogs of 2-β-carbomethoxy-3-β-(4'-iodophenyl)tropane (β-CIT)

被引：21

作者：

Bois, F

Baldwin, RM

Kula, NS

Baldessarini, RJ

Innis, RB

Tamagnan, G

机构：

[1] Yale Univ, Sch Med, VA Connecticut HCS, West Haven, CT 06516 USA

[2] Harvard Univ, Sch Med, Massachusetts Gen Hosp, McLean Div,Mailman Res Ctr,Dep Psychiat, Belmont, MA 02478 USA

[3] Harvard Univ, Sch Med, Massachusetts Gen Hosp, McLean Div,Mailman Res Ctr,Neurosci Program, Belmont, MA 02478 USA

[4] Inst Neurodegenerat Disorders, New Haven, CT 06510 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 09期

关键词：

tropane; cocaine; DAT; SERT; monoamine;

D O I：

10.1016/j.bmcl.2004.02.043

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The 3'-iodo positional isomer of 2-beta-carbomethoxy-3-beta-(4'-iodophenyl)tropane (beta-CIT) and other 3'-substituted analogs were synthesized and evaluated for binding to momoamine transporters in rat forebrain and membranes of cell lines selectively expressing human transporter genes. All 3'-substituted compounds displayed affinity for both serotonin (SERT) and dopamine (DAT), but much less for norepinephrine transporters (NET), with selectivity for rat (r) or human (h) SERT over NET, but only 3'-iodo-substituted phenyltropanes showed selectivity for SERT versus DAT. The 3'-iodo, N-methyl analog of beta-CIT (7) displayed 9-fold selectivity and high affinity for hSERT (K-i = 9.6 nM) over hDAT (K-i = 279 nM), and its nor-congener (8) showed even higher hSERT potency (K-i = 1.2 nM) and selectivity over DAT (415-fold). (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：2117 / 2120

页数：4

共 31 条

[11] Synthesis and characterization of iodine-123 labeled 2β-carbomethoxy-3β-(4′-((Z)-2-iodoethenyl)phenyl)nortropane.: A ligand for in vivo Imaging of serotonin transporters by single-photon-emission tomography [J].