Abstract
A novel series of quinolinone-based adenosine A(2B) receptor antagonists was identified via high throughput screening of an encoded combinatorial compound collection. Synthesis and assay of a series of analogs highlighted essential structural features of the initial hit. Optimization resulted in an A(2B) antagonist (2i) which exhibited potent activity in a cAMP accumulation assay (5.1 nM) and an IL-8 release assay (0.4 nM).
Copyright © 2010 Elsevier Ltd. All rights reserved.
MeSH terms
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Adenosine A2 Receptor Antagonists / chemical synthesis
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Adenosine A2 Receptor Antagonists / chemistry*
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Adenosine A2 Receptor Antagonists / pharmacology
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Combinatorial Chemistry Techniques
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Drug Evaluation, Preclinical
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Humans
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Microsomes, Liver / metabolism
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Quinolones / chemical synthesis
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Quinolones / chemistry*
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Quinolones / pharmacology
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Receptor, Adenosine A2B / chemistry*
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Receptor, Adenosine A2B / metabolism
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Structure-Activity Relationship
Substances
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Adenosine A2 Receptor Antagonists
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Quinolones
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Receptor, Adenosine A2B