title: 5-Sulfonyl-benzimidazoles as selective CB2 agonists.
abstract: A novel series of benzimidazole CB2-receptor agonists was synthesized and the structure-activity relationship explored. The results showed agonistic activities with an EC(50) up to 0.5 nM and excellent selectivity (>4000-fold) over the CB1 receptor. The size of the substituent on the 2-position determined the level of agonism, ranging from inverse agonism to partial agonism to full agonism, which was more pronounced for the rat CB2 receptor. A wide variation of sulfonyl substituents at the benzimidazole 5-position was tolerated, which was used to optimize the drug-like properties. This resulted into lead compound 14j that can be used to investigate the potential of a selective, peripherically acting CB2 agonist. The in vitro profile of key compounds is displayed using pie bar charts (VlaaiVis).
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
authors.forename: Bie M P
authors.initials: BM
authors.lastname: Verbist
authors.forename: Michel A J
authors.initials: MA
authors.lastname: De Cleyn
authors.forename: Michel
authors.initials: M
authors.lastname: Surkyn
authors.forename: Erwin
authors.initials: E
authors.lastname: Fraiponts
authors.forename: Jeroen
authors.initials: J
authors.lastname: Aerssens
authors.forename: Marjoleen J M A
authors.initials: MJ
authors.lastname: Nijsen
authors.forename: Harrie J M
authors.initials: HJ
authors.lastname: Gijsen
mesh_terms: D000478:Alkylation; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D010084:Oxidation-Reduction; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013457:Sulfur Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001562:Benzimidazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D013457:Sulfur Compounds; C031000:benzimidazole