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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 ACS+Med+Chem+Lett
2011 ; 2
(12
): 890-5
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Development of Polar Adenosine A2A Receptor Agonists for Inflammatory Bowel
Disease: Synergism with A2B Antagonists
#MMPMID24900277
El-Tayeb A
; Michael S
; Abdelrahman A
; Behrenswerth A
; Gollos S
; Nieber K
; Müller CE
ACS Med Chem Lett
2011[Dec]; 2
(12
): 890-5
PMID24900277
show ga
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.