Development of the First Potential Nonpeptidic Positron Emission Tomography Tracer for the Imaging of CCR2 Receptors

被引：6

作者：

Wagner, Stefan ^{[1
]}

Gatti, Fernando de Moura ^{[2
,10
]}

Silva, Daniel G. ^{[3
]}

Zacarias, Natalia V. Ortiz ^{[4
]}

Zweemer, Annelien J. M. ^{[4
]}

Hermann, Sven ^{[3
]}

De Maria, Monica ^{[5
]}

Koch, Michael ^{[6
]}

Weiss, Christina ^{[6
]}

Schepmann, Dirk ^{[2
]}

Heitman, Laura H. ^{[4
]}

Tschammer, Nuska ^{[7
]}

Kopka, Klaus ^{[8
,9
]}

Junker, Anna ^{[2
,3
]}

机构：

[1] Univ Hosp Munster, Dept Nucl Med, Albert Schweitzer Campus 1,Bldg A1, D-48149 Munster, Germany

[2] Univ Munster, Inst Pharmazeut & Med Chem, Corrensstr 48, D-48149 Munster, Germany

[3] European Inst Mol Imaging EIMI, Waldeyerstr 15, D-48149 Munster, Germany

[4] Leiden Univ, Leiden Acad Ctr Drug Res LACDR, Einsteinweg 55, NL-2333 CC Leiden, Netherlands

[5] Friedrich Alexander Univ, Dept Dev Biol, Staudtstr 5, D-91058 Erlangen, Germany

[6] Bayer AG, Res & Dev Lead Discovery Wuppertal, Aprather Weg 18a,Gebaude 456, D-42096 Wuppertal, Germany

[7] Friedrich Alexander Univ Erlangen Nurnberg, Emil Fischer Ctr, Dept Chem & Pharm, Schuhstr 19, D-91052 Erlangen, Germany

[8] Helmholtz Zentrum Dresden Rossendorf, Inst Radiopharmazeut Krebsforsch, Bautzner Landstr 400, D-01328 Dresden, Germany

[9] Tech Univ Dresden, Fac Chem & Food Chem, D-01062 Dresden, Germany

[10] Univ Sao Paulo, Fac Ciencias Farmaceut, Av Prof Lineu Prestes 580, BR-05508900 Sao Paulo, SP, Brazil

来源：

CHEMMEDCHEM | 2021年 / 16卷 / 04期

基金：

巴西圣保罗研究基金会;

关键词：

CCR2; CCR5; antagonists; chemokine receptors; molecular imaging; PET; radiolabeling; TAK-779; FUNCTIONAL EXPRESSION; BIOLOGICAL EVALUATION; CHEMOKINE; CLONING;

D O I：

10.1002/cmdc.202000728

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Herein we report the design and synthesis of a series of highly selective CCR2 antagonists as F-18-labeled PET tracers. The derivatives were evaluated extensively for their off-target profile at 48 different targets. The most potent and selective candidate was applied in vivo in a biodistribution study, demonstrating a promising profile for further preclinical development. This compound represents the first potential nonpeptidic PET tracer for the imaging of CCR2 receptors.

引用

页码：640 / 645

页数：6

共 17 条

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