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

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.

• Authors: T Güngör, P Malabre, J M Teulon, F Camborde, J Meignen, F Hertz, A Virone-Oddos, F Caussade, A Cloarec
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 37 Issue 25 Pg. 4307-16 (Dec 09 1994) ISSN: 0022-2623 [Print] United States
• PMID: 7996542 (Publication Type: Journal Article)

Chemical References

• Analgesics
• Indoles
• Purinergic P1 Receptor Agonists
• Receptors, Purinergic P1
• UP 202-32
• 8-cyclopentyl-1,3-dimethylxanthine
• Theophylline
• Adenosine
• Nitrogen

Topics

• Adenosine (analogs & derivatives, antagonists & inhibitors, chemical synthesis, metabolism)
• Analgesia
• Analgesics (chemical synthesis, metabolism)
• Animals
• Indoles (antagonists & inhibitors, chemical synthesis, metabolism)
• Methylation
• Mice
• Molecular Structure
• Nitrogen (chemistry)
• Purinergic P1 Receptor Agonists
• Rats
• Receptors, Purinergic P1 (metabolism)
• Structure-Activity Relationship
• Theophylline (analogs & derivatives, pharmacology)