New Highly Potent and Selective Adenosine A3 Receptor Antagonists

Author(s): Neil J. Press, Thomas H. Keller, Pamela Tranter, David Beer, Ken Jones, Alexander Faessler, Richard Heng, Christine Lewis, Trevor Howe, Peter Gedeck

Journal Name: Current Topics in Medicinal Chemistry

Volume 4 , Issue 8 , 2004

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Abstract:

A class of potent, selective adenosine A3 receptor antagonists was obtained via optimisation of the screening hit N-[4-(4-methoxyphenyl)-thiazol-2-yl]-acetamide. Structural modifications of this hit revealed very quickly that a 5-(pyridin-4-yl) substituent on the 2- aminothiazole ring was optimal for high potency at the adenosine A3 receptor. Structure activity relationship studies led to both potent and selective A3 receptor antagonists, including N-[5-pyridin-4-yl-4-(3,4,5-trimethoxyphenyl)-thiazol-2-yl]-acetamide, a highly potent aden-osine A3 receptor antagonist with greater than 100- fold selectivity against the related adenosine receptors. As well as demonstrating selective in vitro binding on the human A3 adenosine receptor, this compound was also shown to selectively block the rat A3 receptor in vivo. This important new compound can be readily synthesised in four steps from commercially available starting materials.

Keywords: adenosine a3 receptor antagonists, n-[4-(4-methoxyphenyl)-thiazol-2-yl]-acetamide, n-[5-pyridin-4-yl-4-(3,4,5-trimethoxyphenyl)-thiazol-2-yl]-acetamide

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Article Details

VOLUME: 4
ISSUE: 8
Year: 2004
Page: [863 - 870]
Pages: 8
DOI: 10.2174/1568026043451023
Price: $65

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