Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 2, Issue 12, Pages 890-895Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ml200189u
Keywords
A(2A) receptor agonist; inflammatory bowel disease; anti-inflammatory drug; nonabsorbable A(2A) receptor agonist; A(2B) receptor antagonist
Categories
Ask authors/readers for more resources
Adenosine A(2A) 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 A(2B)-selective antagonist. Thus, nonabsorbable, locally active A(2A) agonists, as a monotherapy or in combination with an A(2B) antagonist, may be an efficient novel treatment for IBS, preventing the severe systemic side effects of known A(2A) agonists.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available