当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Structure-Activity Relationship Studies of Pyridine-Based Ligands and Identification of a Fluorinated Derivative for Positron Emission Tomography Imaging of Cannabinoid Type 2 Receptors.

Structure-Activity Relationship Studies of Pyridine-Based Ligands and Identification of a Fluorinated Derivative for Positron Emission Tomography Imaging of Cannabinoid Type 2 Receptors.

Abstract：

:The cannabinoid type 2 (CB2) receptor has emerged as a valuable target for therapy and imaging of immune-mediated pathologies. With the aim to find a suitable radiofluorinated analogue of the previously reported CB2 positron emission tomography (PET) radioligand [11C]RSR-056, 38 fluorinated derivatives were synthesized and tested by in vitro binding assays. With a Ki (hCB2) of 6 nM and a selectivity factor of nearly 700 over cannabinoid type 1 receptors, target compound 3 exhibited optimal in vitro properties and was selected for evaluation as a PET radioligand. [18F]3 was obtained in an average radiochemical yield of 11 ± 4% and molar activities between 33 and 114 GBq/μmol. Specific binding of [18F]3 to CB2 was demonstrated by in vitro autoradiography and in vivo PET experiments using the CB2 ligand GW-405 833. Metabolite analysis revealed only intact [18F]3 in the rat brain. [18F]3 detected CB2 upregulation in human amyotrophic lateral sclerosis spinal cord tissue and may thus become a candidate for diagnostic use in humans.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Haider A,Kretz J,Gobbi L,Ahmed H,Atz K,Bürkler M,Bartelmus C,Fingerle J,Guba W,Ullmer C,Honer M,Knuesel I,Weber M,Brink A,Herde AM,Keller C,Schibli R,Mu L,Grether U,Ametamey SM

doi

10.1021/acs.jmedchem.9b01280

subject

Has Abstract

pub_date

2019-12-26 00:00:00

pages

11165-11181

issue

24

eissn

0022-2623

issn

1520-4804

journal_volume

62

pub_type

杂志文章

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