Dual acting antioxidant A1 adenosine receptor agonists

Alison Dianne Gregg, Steven Eric Bottle, Shane Devine, Heidi Figler, Joel Linden, Paul James White, Colin William Pouton, Vijay Urmaliya, Peter John Scammells

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16 Citations (Scopus)


Herein we report the synthesis and biological evaluation of some potent and selective A, adenosine receptor agonists, which incorporate a functionalised linker attached to an antioxidant moiety. N-6-(2,2,5,5-Tetramethylpyrrolidin-1-yloxyl-3-ylmethyl)-adenosine (VCP28, 2e) proved to be an agonist with high affinity (K-i = 50 nM) and good selectivity (A(3)/A(1) >= 400) for the A, adenosine receptor. N-6-[4-[2-[1,1,3,3-Tetramethylisoindolin-2-yloxyl-5-amido]ethyl]phenyl]adenosine (VCP102, 5a) has higher binding affinity (Ki = 7 nM), but lower selectivity (A(3)/A(1) = similar to 3). All compounds bind weakly (K-i > 1 mu M) to A(2A) and A(2B) receptors. The combination of-A, agonist activity and antioxidant activity has the potential to produce cardioprotective effects. (C) 2007 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)5437 - 5441
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number19
Publication statusPublished - 2007

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