title: 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.affiliation: Research and Development, RaQualia Pharma Inc, 5-2 Taketoyo, Aichi 470-2341, Japan. Electronic address: yasuhiro.iwata@raqualia.com.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Iwata
authors.affiliation: Research and Development, RaQualia Pharma Inc, 5-2 Taketoyo, Aichi 470-2341, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ando
authors.affiliation: Research and Development, RaQualia Pharma Inc, 5-2 Taketoyo, Aichi 470-2341, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Taniguchi
authors.affiliation: Research and Development, RaQualia Pharma Inc, 5-2 Taketoyo, Aichi 470-2341, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Koba
authors.affiliation: Research and Development, RaQualia Pharma Inc, 5-2 Taketoyo, Aichi 470-2341, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Sugiura
authors.affiliation: Research and Development, RaQualia Pharma Inc, 5-2 Taketoyo, Aichi 470-2341, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Sudo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D063386:Cannabinoid Receptor Agonists / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D043183:Irritable Bowel Syndrome / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051381:Rats; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D063386:Cannabinoid Receptor Agonists; D043885:Receptor, Cannabinoid, CB2
keywords: Benzimidazole; CB2 agonist; Cannabinoid receptor; Irritable bowel syndrome