Potent, selective, and orally active adenosine A2A receptor antagonists:: Arylpiperazine derivatives of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines

被引：131

作者：

Neustadt, Bernard R.

Hao, Jinsong

Lindo, Neil

Greenlee, William J.

Stamford, Andrew W.

Tulshian, Deen

Ongini, Ennio

Hunter, John

Monopoli, Angela

Bertorelli, Rosalia

Foster, Carolyn

Arik, Leyla

Lachowicz, Jean

Ng, Kwokei

Feng, Kung-I

机构：

[1] Schering Plough Res Inst, Dept Chem Res, Kenilworth, NJ 07033 USA

[2] Schering Plough Res Inst, Dept CNS Pharmacol, Kenilworth, NJ 07033 USA

[3] Schering Plough Res Inst, Dept Drug Metab & Pharmacokinet, Kenilworth, NJ 07033 USA

[4] Schering Plough Res Inst, I-20132 Milan, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 05期

关键词：

adenosine A(2A); Parkinson's; catalepsy; pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine;

D O I：

10.1016/j.bmcl.2006.11.083

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Antagonism of the adenosine A(2A) receptor offers great promise in the treatment of Parkinson's disease. Employing the known pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine A(2A) antagonist SCH 58261 as a starting point, we identified the Potent and selective (vs. A1) antagonist 11 h, orally active in the rat haloperidol-induced catalepsy model. We further optimized this lead to the methoxyethoxyethyl ether 12a (SCH 420814), which shows broad selectivity, good pharmacokinetic properties, and excellent in vivo activity. (c) 2006 Elsevier Ltd. All rights reserved.

引用

收藏

页码：1376 / 1380

页数：5

相关论文

共 27 条

[1]

*ACS, 2006, AM CHEM SOC 231 NAT

[2] Adenosine A2A receptor antagonist treatment of Parkinson's disease [J].

Bara-Jimenez, W ;

Sherzai, A ;

Dimitrova, T ;

Favit, A ;

Bibbiani, F ;

Gillespie, M ;

Morris, MJ ;

Mouradian, MM ;

Chase, TN .

NEUROLOGY, 2003, 61 (03) :293-296

[3] Recent developments in the field of A2A and A3 adenosine receptor antagonists [J].

Baraldi, PG ;

Tabrizi, MA ;

Bovero, A ;

Avitabile, B ;

Preti, D ;

Fruttarolo, F ;

Romagnoli, R ;

Varani, K ;

Borea, PA .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2003, 38 (04) :367-382

[4] Design, synthesis, and biological evaluation of C9- and C2-substituted pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c] pyrimidines as new A2A and A3 adenosine receptors antagonists [J].

Baraldi, PG ;

Fruttarolo, F ;

Tabrizi, MA ;

Preti, D ;

Romagnoli, R ;

El-Kashef, H ;

Moorman, A ;

Varani, K ;

Gessi, S ;

Merighi, S ;

Borea, PA .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (07) :1229-1241

[5] SYNTHESIS OF NEW PYRAZOLO[4,3-E]1,2,4-TRIAZOLO[1,5-C] PYRIMIDINE AND 1,2,3-TRIAZOLO[4,5-E]1,2,4-TRIAZOLO[1,5-C] PYRIMIDINE DISPLAYING POTENT AND SELECTIVE ACTIVITY AS A(2A) ADENOSINE RECEPTOR ANTAGONISTS [J].

BARALDI, PG ;

MANFREDINI, S ;

SIMONI, D ;

ZAPPATERRA, L ;

ZOCCHI, C ;

DIONISOTTI, S ;

ONGINI, E .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1994, 4 (21) :2539-2544

[6] Design, synthesis, and biological evaluation of a second generation of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as potent and selective A2A adenosine receptor antagonists [J].

Baraldi, PG ;

Cacciari, B ;

Spalluto, G ;

Bergonzoni, M ;

Dionisotti, S ;

Ongini, E ;

Varani, K ;

Borea, PA .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (12) :2126-2133

[7] 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

[8] Synthesis of [1,2,4]triazolo[1,5-a]pyrazines as adenosine A2A receptor antagonists [J].

Dowling, JE ;

Vessels, JT ;

Haque, S ;

Chang, HX ;

van Vloten, K ;

Kumaravel, G ;

Engber, T ;

Jin, XW ;

Phadke, D ;

Wang, J ;

Ayyub, M ;

Petter, RC .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (21) :4809-4813

[9]

El Ashry ESH, 2000, ADV HETEROCYCL CHEM, V75, P79

[10] 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