N6-Substituted Adenosine Receptor Agonists. Synthesis and Pharmacological Activity as Potent Antinociceptive Agents

Article abstract of DOI:10.1021/jm00051a007

Novel N⁶-(indol-3-yl)alkyl derivatives of adenosine were synthesized.The adenosine receptor affinity and the antinociceptive activity of these compounds were assessed in binding studies and the phenylbenzoquinone-induced writhing test.Most of these analogues exhibited a potent analgesic activity without side effects.Among them, compound 3c (UP 202-32) bound to A₁ (K_i = 110 nM) and A₂ (K_i = 350 nM) adenosine receptors in a specific manner since it did not interact with many other receptors, especially opioid binding sites.The antinociceptive activity in the phenylbenzoquinone assay (ED50 = 3.3 mg/kg po) was antagonized by 8-cyclopentyltheophylline, suggesting that an adenosinergic mechanism underlies the analgesic activity observed with this compound.The data obtained with these new N⁶-substituted adenosine receptor agonists emphasize the interest of such compounds in the treatment of pain.