Abstract
A number of novel xanthines bearing a variety of substituents at positions 1, 3, 7 and 8 were prepared and evaluated for their binding affinity to the human adenosine receptor A(1), A(2A), A(2B) and A(3) subtypes. Several of the 1,3,8- and 1,3,7,8-substituted xanthines showed moderate-to-high affinity at human A(2B) and A(1) receptors, with the most active compound (14q) having a pK(i) of 7.57 nM for hA(2B) receptors and a selectivity over hA(2A) receptors of 8.1-fold and hA(1) receptors of 3.7-fold.
Copyright 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine A1 Receptor Antagonists
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Adenosine A2 Receptor Antagonists
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Adenosine A3 Receptor Antagonists
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Anti-Inflammatory Agents / chemical synthesis*
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / pharmacology
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Cell Line
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HeLa Cells
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Humans
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Purinergic P1 Receptor Antagonists*
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Receptor, Adenosine A1 / metabolism
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Receptor, Adenosine A2A / metabolism
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Receptor, Adenosine A2B / metabolism
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Receptor, Adenosine A3 / metabolism
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Receptors, Purinergic P1 / metabolism
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Structure-Activity Relationship
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Xanthines / chemical synthesis
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Xanthines / chemistry*
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Xanthines / pharmacology
Substances
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Adenosine A1 Receptor Antagonists
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Adenosine A2 Receptor Antagonists
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Adenosine A3 Receptor Antagonists
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Anti-Inflammatory Agents
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Purinergic P1 Receptor Antagonists
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Receptor, Adenosine A1
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Receptor, Adenosine A2A
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Receptor, Adenosine A2B
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Receptor, Adenosine A3
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Receptors, Purinergic P1
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Xanthines