8-(sulfostyryl)xanthines:: Water-soluble A2A-selective adenosine receptor antagonists

被引：43

作者：

Muller, CE ^{[1
]}

Sandoval-Ramirez, J

Schobert, U

Geis, U

Frobenius, W

Klotz, KN

机构：

[1] Univ Wurzburg, Inst Pharm & Lebensmittelchem, D-97074 Wurzburg, Germany

[2] Univ Wurzburg, Inst Pharmakol & Toxikol, D-97078 Wurzburg, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 1998年 / 6卷 / 06期

关键词：

xanthines; sulfonic acids; A(1)-; A(2A)-; A(2B)-; A(3)-adenosine receptors; A(2A)-antagonists; water-solubility;

D O I：

10.1016/S0968-0896(98)00025-X

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：

8-(Sulfostyryl)xanthine derivatives were synthesized as water-soluble A(2A)-selective adenosine receptor (AR) antagonists, meta- and para-sulfostyryl-DMPX (3,7-dimethyl-1-propargylxanthine) derivatives 11a and 11b exhibited high affinity to rat AZA-AR in submicromolar concentrations, and were 20- to 30-fold selective versus rat A(1)-AR. Styryl-DMPX derivatives were inactive at human A(2B)- and A(3)-AR. 1,3-Dipropyl-8-p-sulfostyrylxanthine (13) and its 7-methyl derivative (14) showed similar (13) or higher (14) A(2A) affinity than 11a and 11b but showed no (13) or only a low degree (14) of selectivity versus A(1)-, A(2B)-, and A(3)-AR. The A(2A)-selective sulfostyryl-DMPX derivatives exhibit high water-solubility and may be useful research tools for in vivo studies. (C) 1998 Elsevier Science Ltd. All rights reserved.

引用

页码：707 / 719

页数：13

共 43 条

[1] Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives: Potent and selective A(2A) adenosine antagonists [J].

Baraldi, PG ;

Cacciari, B ;

Spalluto, G ;

Villatoro, MJPDIY ;

Zocchi, C ;

Dionisotti, S ;

Ongini, E .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (05) :1164-1171

[2]

Baraldi PG, 1995, CURR MED CHEM, V2, P707

[3] PENETRATION OF ADENOSINE ANTAGONISTS INTO MOUSE-BRAIN AS DETERMINED BY EXVIVO BINDING [J].

BAUMGOLD, J ;

NIKODIJEVIC, O ;

JACOBSON, KA .

BIOCHEMICAL PHARMACOLOGY, 1992, 43 (04) :889-894

[4] ADENOSINE ANTAGONISM BY PURINES, PTERIDINES AND BENZOPTERIDINES IN HUMAN-FIBROBLASTS [J].

BRUNS, RF .

BIOCHEMICAL PHARMACOLOGY, 1981, 30 (04) :325-333

[5] SOLUBILITIES OF ADENOSINE ANTAGONISTS DETERMINED BY RADIORECEPTOR ASSAY [J].

BRUNS, RF ;

FERGUS, JH .

JOURNAL OF PHARMACY AND PHARMACOLOGY, 1989, 41 (09) :590-594

[6]

CERFONTAIN H, 1975, TETRAHEDRON LETT, P3639

[7]

CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099

[8]

COLLIS MG, 1993, TRENDS PHARMACOL SCI, V14, P360

[9] CAFFEINE ANALOGS - STRUCTURE-ACTIVITY-RELATIONSHIPS AT ADENOSINE RECEPTORS [J].

DALY, JW ;

HIDE, I ;

MULLER, CE ;

SHAMIM, M .

PHARMACOLOGY, 1991, 42 (06) :309-321

[10] 1,3-DIALKYL-8-(PARA-SULFOPHENYL)XANTHINES - POTENT WATER-SOLUBLE ANTAGONISTS FOR A1-ADENOSINE AND A2-ADENOSINE RECEPTORS [J].

DALY, JW ;

PADGETT, W ;

SHAMIM, MT ;

BUTTSLAMB, P ;

WATERS, J .

JOURNAL OF MEDICINAL CHEMISTRY, 1985, 28 (04) :487-492

← 1 2 3 4 5 →