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.
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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)
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Copyright | Copyright © 2014 Elsevier Ltd. All rights reserved. |
Chemical References |
- Cannabinoid Receptor Agonists
- Receptor, Cannabinoid, CB2
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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
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