Document Report Card

ID: ALA1127433

Journal: J Med Chem

Title: N6-substituted adenosine receptor agonists. Synthesis and pharmacological activity as potent antinociceptive agents.

Authors: Güngör T, Malabre P, Teulon JM, Camborde F, Meignen J, Hertz F, Virone-Oddos A, Caussade F, Cloarec A.

Abstract: 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 (Ki = 110 nM) and A2 (Ki = 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.

CiteXplore: 7996542

DOI: 10.1021/jm00051a007