Identification of a highly potent and selective CB2 agonist, RQ-00202730, for the treatment of irritable bowel syndrome.

Abstract

Herein we report the identification of a highly potent and selective CB2 agonist, RQ-00202730 (40), obtained by lead optimization of the benzimidazole scaffold. Compound 40 showed strong agonistic activity with an EC50 of 19nM and excellent selectivity (>1300-fold) over the CB1 receptor. Compound 40 displayed a dose dependent analgesic effect on TNBS-induced visceral hypersensitivity in rats by oral administration (ED50 0.66mg/kg at 2.5h after oral administration). In addition, 40 did not show a significant effect on body temperature in rats after oral administration at 300mg/kg. These findings suggest that highly selective CB2 agonists will be effective agents for IBS therapy.

• Authors: Yasuhiro Iwata, Kazuo Ando, Kana Taniguchi, Naomi Koba, Akemi Sugiura, Masaki Sudo
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 25 Issue 2 Pg. 236-40 (Jan 15 2015) ISSN: 1464-3405 [Electronic] England
• PMID: 25499880 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Cannabinoid Receptor Agonists
• Receptor, Cannabinoid, CB2

Topics

• Administration, Oral
• Animals
• Cannabinoid Receptor Agonists (administration & dosage, chemistry, metabolism)
• Dose-Response Relationship, Drug
• Irritable Bowel Syndrome (drug therapy, metabolism)
• Male
• Rats
• Receptor, Cannabinoid, CB2 (agonists, metabolism)
• Treatment Outcome