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

Autor: Iwata Y; Research and Development, RaQualia Pharma Inc, 5-2 Taketoyo, Aichi 470-2341, Japan. Electronic address: yasuhiro.iwata@raqualia.com., Ando K; Research and Development, RaQualia Pharma Inc, 5-2 Taketoyo, Aichi 470-2341, Japan., Taniguchi K; Research and Development, RaQualia Pharma Inc, 5-2 Taketoyo, Aichi 470-2341, Japan., Koba N; Research and Development, RaQualia Pharma Inc, 5-2 Taketoyo, Aichi 470-2341, Japan., Sugiura A; Research and Development, RaQualia Pharma Inc, 5-2 Taketoyo, Aichi 470-2341, Japan., Sudo M; Research and Development, RaQualia Pharma Inc, 5-2 Taketoyo, Aichi 470-2341, Japan.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2015 Jan 15; Vol. 25 (2), pp. 236-40. Date of Electronic Publication: 2014 Dec 03.
DOI: 10.1016/j.bmcl.2014.11.062
Abstrakt: 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.
(Copyright © 2014 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: