Synthesis and evaluation of 7-amino-2-(2(3)-furyl)-5-phenylethylamino-oxazolo[5,4-d]pyrimidines as potential A2A adenosine receptor antagonists for positron emission tomography (PET)

被引：31

作者：

Holschbach, MH ^{[1
]}

Bier, D ^{[1
]}

Stüsgen, S ^{[1
]}

Wutz, W ^{[1
]}

Sihver, W ^{[1
]}

Coenen, HH ^{[1
]}

Olsson, RA ^{[1
]}

机构：

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

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 41卷 / 01期

关键词：

A(2A) adenosine receptor; PET; antagonist; oxazolo[5,4-d]pyrimidines;

D O I：

10.1016/j.ejmech.2005.07.018

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The brain A(2A) adenosine receptor (A(2A)AR) participates with the dopamine D, receptor in the control of movement and also might influence behavior. Because PET is an important tool for studying the roles of receptors in disease, a ligand for imaging the brain A(2A)AR is desirable. This report describes the synthesis and A(2A)AR antagonist activities of a panel of phenyl-substituted 7-amino-2-(2-furyl)-5-phenylethylamino-oxazolo [5,4-d]pyrimidines, 11aa-af, and their 3-furyl congeners, 11ba-bd. In competitive binding studies all compounds displaced [H-3]CGS21680 from the A(2A)AR with K-i values of 14-33 nM with selectivity for the A(2A)AR over the A(1)AR of 5- to 94-fold. Autoradiography of brain sections showed a high level of unspecific binding that obscured specific binding. Thus, these compounds are not promising PET ligands. (c) 2005 Elsevier SAS. All rights reserved.

引用

页码：7 / 15

页数：9

共 17 条

[1] 7-substituted 5-amino-2-(2-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as A2A adenosine receptor antagonists:: A study on the importance of modifications at the side chain on the activity and solubility [J].

Baraldi, PG ;

Cacciari, B ;

Romagnoli, R ;

Spalluto, G ;

Monopoli, A ;

Ongini, E ;

Varani, K ;

Borea, PA .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (01) :115-126

[2]

Block M.H, 1993, European Patent, Patent No. [EP544445A2, 544445]

[3] Medicinal chemistry of A2A adenosine receptor antagonists [J].

Caceiari, B ;

Pastorin, G ;

Spalluto, G .

CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2003, 3 (04) :403-411

[4]

Colotta V, 1999, ARCH PHARM, V332, P39

[5] THE PHYSIOLOGICAL-ROLE OF ADENOSINE IN THE CENTRAL NERVOUS-SYSTEM [J].

DUNWIDDIE, TV .

INTERNATIONAL REVIEW OF NEUROBIOLOGY, 1985, 27 :63-139

[6] STRUCTURE ACTIVITY PROFILE OF A SERIES OF NOVEL TRIAZOLOQUINAZOLINE ADENOSINE ANTAGONISTS [J].

FRANCIS, JE ;

CASH, WD ;

PSYCHOYOS, S ;

GHAI, G ;

WENK, P ;

FRIEDMANN, RC ;

ATKINS, C ;

WARREN, V ;

FURNESS, P ;

HYUN, JL ;

STONE, GA ;

DESAI, M ;

WILLIAMS, M .

JOURNAL OF MEDICINAL CHEMISTRY, 1988, 31 (05) :1014-1020

[7]

GILMAN H, 1987, J ORG CHEM, V55, P2903

[8] THE CHEMISTRY OF PYRIMIDINETHIOLS .3. THE SYNTHESIS OF SOME SUBSTITUTED PYRIMIDINTHIOLS AND SOME THIAZOLO[5,4-D]PYRIMIDINES [J].

HARNDEN, MR ;

HURST, DT .

AUSTRALIAN JOURNAL OF CHEMISTRY, 1990, 43 (01) :55-62

[9] ESSENTIAL ROLE OF ADENOSINE, ADENOSINE-A1-RECEPTORS, AND ATP-SENSITIVE K+ CHANNELS IN CEREBRAL ISCHEMIC PRECONDITIONING [J].

HEURTEAUX, C ;

LAURITZEN, I ;

WIDMANN, C ;

LAZDUNSKI, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (10) :4666-4670

[10] 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) [J].

Holschbach, MH ;

Bier, D ;

Wutz, W ;

Sihver, W ;

Schüller, M ;

Olsson, RA .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2005, 40 (05) :421-437

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