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ACS Med Chem Lett. 2011 Oct 10;2(12):890-5. doi: 10.1021/ml200189u. eCollection 2011 Dec 8.

Development of Polar Adenosine A2A Receptor Agonists for Inflammatory Bowel Disease: Synergism with A2B Antagonists.

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PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn , An der Immenburg 4, D-53121 Bonn, Germany.
University of Leipzig , Institute of Pharmacy, Talstrasse 33, D-04109 Leipzig, Germany.


Adenosine A2A receptor agonists for the local treatment of inflammatory bowel disease (IBS) were designed and synthesized. Polar groups were introduced to prevent peroral absorption and subsequent systemic, e.g., hypotensive, side effects. 4-(2-{6-Amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-9H-purin-2-ylthio}ethyl)benzenesulfonic acid (7, PSB-0777) was selected for further evaluation in rat ileum/jejunum preparations in ex vivo experiments. Compound 7 significantly improved impaired acetylcholine-induced contractions induced by 2,4,6-trinitrobenzenesulfonic acid and showed synergism with an A2B-selective antagonist. Thus, nonabsorbable, locally active A2A agonists, as a monotherapy or in combination with an A2B antagonist, may be an efficient novel treatment for IBS, preventing the severe systemic side effects of known A2A agonists.


A2A receptor agonist; A2B receptor antagonist; anti-inflammatory drug; inflammatory bowel disease; nonabsorbable A2A receptor agonist

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