Development of fluorinated CB2 receptor agonists for PET studies

被引：21

作者：

Lueg, Corinna ^{[1
]}

Schepmann, Dirk ^{[1
]}

Guenther, Robert ^{[2
]}

Brust, Peter ^{[2
]}

Wuensch, Bernhard ^{[1
]}

机构：

[1] Univ Munster, Inst Pharmazeut & Med Chem, D-48149 Munster, Germany

[2] Inst Radiopharmazeut Krebsforsch Forsch Stelle Le, Helmholtz Zentrum Dresden Rossendorf, Abt Neuroradiopharm, D-04318 Leipzig, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2013年 / 21卷 / 23期

关键词：

CB2 receptor ligands; Carbazole derivatives; Fluorinated ligands; Structure affinity relationships; PET; Docking; TYPE-2 CANNABINOID RECEPTOR; IN-VITRO; ENDOCANNABINOID SYSTEM; IMMUNE CELLS; LIGANDS; BRAIN; MODELS; PROLIFERATION; EXPRESSION; TOLERANCE;

D O I：

10.1016/j.bmc.2013.09.040

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A convergent strategy was followed to modify systematically carbazole based CB2 receptor ligands. The length of the N-(fluoroalkyl) group (n in 7), the length of the alkanamide (m in 7) and the substitution pattern of the phenyl moiety (X and Y in 7) were varied systematically. The highest CB2 affinity was found for the 2-fluoroethyl substituted carbazole derivative 20a (K-i = 5.8 nM) containing the propionamide and the 2-bromo-4-fluorophenyl moiety. According to docking studies 20a fits nicely into the binding pocket of the CB2 receptor, but elongation of the fluoroethyl side chain leads to a different binding mode of the ligands. The high CB2 affinity together with the high selectivity over the CB2 subtype qualifies the fluoroethyl derivative 20a to be developed as a PET tracer. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：7481 / 7498

页数：18

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