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

被引：27

作者：

Gillespie, Roger J. ^{[2
]}

Cliffe, Ian A. ^{[2
]}

Dawson, Claire E. ^{[2
]}

Dourish, Colin T. ^{[2
]}

Gaur, Suneel ^{[2
]}

Giles, Paul R. ^{[2
]}

Jordan, Allan M. ^{[1
]}

Knight, Antony R. ^{[2
]}

Lawrence, Anthony ^{[2
]}

Lerpiniere, Joanne ^{[2
]}

Misra, Anil ^{[2
]}

Pratt, Robert M. ^{[2
]}

Todd, Richard S. ^{[2
]}

Upton, Rebecca ^{[2
]}

Weiss, Scott M. ^{[2
]}

Williamson, Douglas S. ^{[1
]}

机构：

[1] Vernalis R&D Ltd, Cambridge CB21 6GB, England

[2] Vernalis R&D Ltd, Winnersh RG41 5UA, Wokingham, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 09期

关键词：

adenosine A(2A) receptor; Parkinson's disease; thienopyrimidine; in vivo activity;

D O I：

10.1016/j.bmcl.2008.03.076

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We describe herein the discovery and development of a series of 4-arylthieno[3,2-d]pyrimidines which are potent adenosine A(2A) receptor antagonists. These novel compounds show high degrees of selectivity against the human A(1), A(2B) and A(3) receptor sub-types. Moreover, a number of these compounds show promising activity in vivo, suggesting potential utility in the treatment of Parkinson's disease. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：2920 / 2923

页数：4

共 9 条

[1]

Bezard E, 1998, REV NEUROSCIENCE, V9, P71

[2]

GILLESPIE RJ, 2002, Patent No. 2002055524

[3] 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

[4] 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

[5] Adenosine A(2) receptors modulate haloperidol-induced catalepsy in rats [J].

Mandhane, SN ;

Chopde, CT ;

Ghosh, AK .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1997, 328 (2-3) :135-141

[6] Aroylation of fused pyrimidines; Synthesis of 4-aroylfuro[2,3-d]-, 4-aroylthieno[2,3-d]-, and 4-aroylisoxazolo[5,4-d]pyrimidines [J].

Miyashita, A ;

Obae, K ;

Suzuki, Y ;

Oishi, E ;

Iwamoto, K ;

Higashino, T .

HETEROCYCLES, 1997, 45 (11) :2159-2173

[7] Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells [J].

Porter, RHP ;

Benwell, KR ;

Lamb, H ;

Malcolm, CS ;

Allen, NH ;

Revell, DF ;

Adams, DR ;

Sheardown, MJ .

BRITISH JOURNAL OF PHARMACOLOGY, 1999, 128 (01) :13-20

[8]

Weiss S. M., 2003, Neurology, V61, pS101

[9] Therapeutic potential of adenosine A2A receptor antagonists in Parkinson's disease [J].

Xu, K ;

Bastia, E ;

Schwarzschild, M .

PHARMACOLOGY & THERAPEUTICS, 2005, 105 (03) :267-310

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