Abstract
A series of adenosine-5'-N-alkylcarboxamides and N(6)-(2,2-diphenylethyl)adenosine-5'-N-alkylcarboxamides bearing antioxidant moieties in the 2-position were synthesized from the versatile intermediate, O(6)-(benzotriazol-1-yl)-2-fluoro-2',3'-O-isopropylideneinosine-5'-N-alkylcarboxamide (1). These compounds were evaluated as A(2A) adenosine receptor (A(2A)R) agonists in a cAMP accumulation assay, and a number of potent and selective agonists were identified. Three of these compounds were evaluated further in an ischemic injury cell survival assay and a reactive oxygen species (ROS) production assay whereby 15b and 15c were shown to reduce ROS activity and cell death due to ischemia.
© 2012 American Chemical Society
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine / analogs & derivatives*
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Adenosine / chemical synthesis*
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Adenosine / pharmacology
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Adenosine A2 Receptor Agonists / chemical synthesis*
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Adenosine A2 Receptor Agonists / pharmacology
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Amides / chemical synthesis*
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Amides / pharmacology
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Animals
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Antioxidants / chemical synthesis*
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Antioxidants / pharmacology
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CHO Cells
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Cell Hypoxia
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Cell Line
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Cell Survival / drug effects
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Cricetinae
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Cricetulus
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Cyclic AMP / biosynthesis
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Humans
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Models, Molecular
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Myoblasts / cytology
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Myoblasts / drug effects
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Myoblasts / metabolism
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Myocytes, Cardiac / cytology
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Myocytes, Cardiac / drug effects
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Myocytes, Cardiac / metabolism
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Rats
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Reactive Oxygen Species / metabolism
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Receptor, Adenosine A2A / metabolism*
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Reperfusion Injury / pathology
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Structure-Activity Relationship
Substances
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Adenosine A2 Receptor Agonists
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Amides
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Antioxidants
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Reactive Oxygen Species
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Receptor, Adenosine A2A
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Cyclic AMP
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Adenosine