Adenosine A2A Prodrugs – Phosphorylated A2A receptor agonist prodrugs as anti-inflammatory agents with improved tolerance
A2A agonists are well known for their anti-inflammatory
action. A new class of compounds is presented that allows systemic and local application with reduced side effects due to activation of the prodrug at the site of inflammation. The invention discloses phosphorylated A2A receptor agonists and covers medicaments containing such compounds. It further discloses a method for identification of phosphorylated A2A receptor agonists. The disclosed compounds are applicable for the treatment of acute and chronic inflammation. Phosphorylated A2A receptor agonists can be considered as prodrugs, which are activated by dephosphorylation. The compounds are hydrolysed specifically by ecto-5’- nucleotidase (CD73), which is represented on the outer surface of endothelial cells of large and small arteries as well as on immune cells such as macrophages and Tlymphocytes. CD73 is also upregulated on the surfaces of inflamed tissues. Upregulation of CD73 has also been demonstrated for arteriosclerotic plaques. Therefore, activation of the prodrug directly at the site of inflammation reduced side effects can be expected.
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