Potent and selective adenosine A2A receptor antagonists: 1,2,4-Triazolo[1,5-c]pyrimidines

被引：38

作者：

Neustadt, Bernard R. ^{[1
,2
,3
,4
]}

Liu, Hong ^{[1
,2
,3
,4
]}

Hao, Jinsong ^{[1
,2
,3
,4
]}

Greenlee, William J. ^{[1
,2
,3
,4
]}

Stamford, Andrew W. ^{[1
,2
,3
,4
]}

Foster, Carolyn ^{[1
,2
,3
,4
]}

Arik, Leyla ^{[1
,2
,3
,4
]}

Lachowicz, Jean ^{[1
,2
,3
,4
]}

Zhang, Hongtao ^{[1
,2
,3
,4
]}

Bertorelli, Rosalia ^{[5
]}

Fredduzzi, Silva ^{[5
]}

Varty, Geoffrey ^{[1
,2
,3
,4
]}

Cohen-Williams, Mary ^{[1
,2
,3
,4
]}

Ng, Kwokei ^{[1
,2
,3
,4
]}

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, Kenilworth, NJ 07033 USA

[4] Schering Plough Res Inst, Dept Pharmacokinet, Kenilworth, NJ 07033 USA

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 03期

关键词：

Adenosine A(2a); Parkinson's disease; 1,2,4-Triazolo[1,5-c]pyrimidine; PARKINSONS-DISEASE; HIGHLY POTENT; HERG ACTIVITY; PART; DERIVATIVES; DISCOVERY; ANALOGS; DESIGN; 2-AMINO-N-PYRIMIDIN-4-YLACETAMIDES; TRIAZOLOTRIAZINE;

D O I：

10.1016/j.bmcl.2008.11.075

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. In the course of exploring pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine A(2A) antagonists, which led to clinical candidate SCH 420814, we prepared 1,2,4-triazolo[1,5-c]pyrimidines with potent and selective (vs A(1)) A(2a) antagonist activity, including oral activity in the rat haloperidol-induced catalepsy model. Structure-activity relationships and plasma levels are described for this series. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：967 / 971

页数：5

共 22 条

[1] 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

[2] Antagonists of the human adenosine A2A receptor.: Part 3:: Design and synthesis of pyrazolo[3,4-d]pyrimidines, pyrrolo[2,3-d] pyrimidines and 6-arylpurines [J].

Gillespie, Roger J. ;

Cliffe, Ian A. ;

Dawson, Claire E. ;

Dourish, Colin T. ;

Gaur, Suneel ;

Jordan, Allan M. ;

Knight, Antony R. ;

Lerpiniere, Joanne ;

Misra, Anil ;

Pratt, Robert M. ;

Roffey, Jonathan ;

Stratton, Gemma C. ;

Upton, Rebecca ;

Weiss, Scott M. ;

Williamson, Douglas S. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (09) :2924-2929

[3] Antagonists of the human adenosine A2A receptor.: Part 1:: Discovery and synthesis of thieno[3,2-d] pyrimidine-4-methanone derivatives [J].

Gillespie, Roger J. ;

Adams, David R. ;

Bebbington, David ;

Benwell, Karen ;

Cliffe, Ian A. ;

Dawson, Claire E. ;

Dourish, Colin T. ;

Fletcher, Allan ;

Gaur, Suneel ;

Giles, Paul R. ;

Jordan, Allan M. ;

Knight, Antony R. ;

Knutsen, Lars J. S. ;

Lawrence, Anthony ;

Lerpiniere, Joanne ;

Misra, Anil ;

Porter, Richard H. P. ;

Pratt, Robert M. ;

Shepherd, Robin ;

Upton, Rebecca ;

Ward, Simon E. ;

Weiss, Scott M. ;

Williamson, Douglas S. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (09) :2916-2919

[4] Antagonists of the human adenosine A2A receptor.: Part 2:: Design and synthesis of 4-arylthieno[3,2-d]pyrimidine derivatives [J].

Gillespie, Roger J. ;

Cliffe, Ian A. ;

Dawson, Claire E. ;

Dourish, Colin T. ;

Gaur, Suneel ;

Giles, Paul R. ;

Jordan, Allan M. ;

Knight, Antony R. ;

Lawrence, Anthony ;

Lerpiniere, Joanne ;

Misra, Anil ;

Pratt, Robert M. ;

Todd, Richard S. ;

Upton, Rebecca ;

Weiss, Scott M. ;

Williamson, Douglas S. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (09) :2920-2923

[5]

JACOBSON KA, 1992, J MED CHEM, V35, P4007

[6] Cassette-accelerated rapid rat screen: a systematic procedure for the dosing and liquid chromatography/atmospheric pressure ionization tandem mass spectrometric analysis of new chemical entities as part of new drug discovery [J].

Korfmacher, WA ;

Cox, KA ;

Ng, KJ ;

Veals, J ;

Hsieh, YS ;

Wainhaus, S ;

Broske, L ;

Prelusky, D ;

Nomeir, A ;

White, RE .

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, 2001, 15 (05) :335-340

[7] 2-(2-furanyl)-7-phenyl[1,2,4]triazolo[1,5-c]pyrimidin-5-amine analogs as adenosine A2A antagonists:: The successful reduction of hERG activity.: Part 2 [J].

Matasi, JJ ;

Caldwell, JP ;

Zhang, HT ;

Fawzi, A ;

Higgins, GA ;

Cohen-Williams, ME ;

Varty, GB ;

Tulshian, DB .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (16) :3675-3678

[8] 2-(2-furanyl)-7-phenyl[1,2,4]triazolo[1,5-c]pyrimidin-5-amine analogs:: Highly potent, orally active, adenosine A2A antagonists.: Part 1 [J].

Matasi, JJ ;

Caldwell, JP ;

Zhang, HT ;

Fawzi, A ;

Cohen-Williams, ME ;

Varty, GB ;

Tulshian, DB .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (16) :3670-3674

[9] The discovery and synthesis of novel adenosine receptor (A2A) antagonists [J].

Matasi, JJ ;

Caldwell, JP ;

Hao, JS ;

Neustadt, B ;

Arik, L ;

Foster, CJ ;

Lachowicz, J ;

Tulshian, DB .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (05) :1333-1336

[10] 2,6-Diaryl-4-phenacylaminopyrimidines as potent and selective adenosine A2A antagonists with reduced hERG liability [J].

Moorjani, Manisha ;

Zhang, Xiaohu ;

Chen, Yongsheng ;

Lin, Emily ;

Rueter, Jaimie K. ;

Gross, Raymond S. ;

Lanier, Marion C. ;

Tellew, John E. ;

Williams, John P. ;

Lechner, Sandra M. ;

Malany, Siobhan ;

Santos, Mark ;

Ekhlassi, Paddi ;

Castro-Palomino, Julio C. ;

Crespo, Maria I. ;

Prat, Maria ;

Gual, Silvia ;

Diaz, Jose-Luis ;

Saunders, John ;

Slee, Deborah H. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (04) :1269-1273

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