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Bioorg Med Chem Lett. 2015 Jan 15;25(2):236-40. doi: 10.1016/j.bmcl.2014.11.062. Epub 2014 Dec 3.

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

Author information

1
Research and Development, RaQualia Pharma Inc, 5-2 Taketoyo, Aichi 470-2341, Japan. Electronic address: yasuhiro.iwata@raqualia.com.
2
Research and Development, RaQualia Pharma Inc, 5-2 Taketoyo, Aichi 470-2341, Japan.

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.

KEYWORDS:

Benzimidazole; CB2 agonist; Cannabinoid receptor; Irritable bowel syndrome

PMID:
25499880
DOI:
10.1016/j.bmcl.2014.11.062
[Indexed for MEDLINE]

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