Derivatives of 4,6-diamino-1,2-dihydro-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-2H-1-one:: potential antagonist ligands for imaging the A2A adenosine receptor by positron emission tomography (PET)

被引：12

作者：

Holschbach, MH

Bier, D

Wutz, W

Sihver, W

Schüller, M

Olsson, RA ^{[1
]}

机构：

[1] Forschungszentrum Julich, Inst Nukl Chem, D-52425 Julich, Germany

[2] Univ S Florida, Dept Internal Med, Tampa, FL 33612 USA

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 40卷 / 05期

关键词：

PET; A(2A) adenosine receptor antagonists; triazolo[4,3-a]quitioxoline; radioligands;

D O I：

10.1016/j.ejmech.2004.12.005

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The importance of the brain A(2A) adenosine receptor (A(2A)AR) in movement disorders urges the development of radiolabeled ligands for imaging those receptors by positron emission tomography (PET). This study evaluated one class of A(2A)AR antagonists, derivatives of 4-amino-6-benzylamino- 1,2-dihydro-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-2H-1-one, 10a, as agents for imaging brain A(2A)ARs by PET.. Modifications of a literature synthesis of 10a efficiently generated analogs 10b-s for pharmacological evaluation. Radioligand binding experiments showed affinities for the rat brain A(2A)AR in the low nanomolar range but similar affinities for the A(1)AR and substantial unspecific binding. Autoradiography employing [H-3]10a, showing that high unspecific binding obscured specific binding to both the A(1) AR and A(2A)AR. Thus, compounds 10b-s are unsuitable as ligands for imaging brain A(2A)ARs by PET. (c) 2005 Elsevier SAS. All rights reserved.

引用

页码：421 / 437

页数：17

共 38 条

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