title: 5-sulfonyl-benzimidazoles as selective CB2 agonists-part 2.
abstract: In a previous communication, the SAR of a series of potent and selective 5-sulfonyl-benzimidazole CB2-receptor agonists was described. The lack of in vivo activity of compounds from this series was attributed to their poor solubility and metabolic stability. In this Letter, we report on the further optimization of this series, leading to the relatively polar and peripherically acting CB2 agonists 41 and 49. Although both compounds were not active in acute pain models, the less selective compound 41 displayed good, sustained activity in a chronic model of neuropathic pain without the tolerance observed with morphine. In addition, both 41 and 49 delayed the onset of clinical symptoms in an experimental model for Multiple sclerosis.
authors: Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium. hgijsen@its.jnj.com
authors: Harrie J M
authors: HJ
authors: Gijsen
authors: Michel A J
authors: MA
authors: De Cleyn
authors: Michel
authors: M
authors: Surkyn
authors: Guy R E
authors: GR
authors: Van Lommen
authors: Bie M P
authors: BM
authors: Verbist
authors: Marjoleen J M A
authors: MJ
authors: Nijsen
authors: Theo
authors: T
authors: Meert
authors: Jean Van
authors: JV
authors: Wauwe
authors: Jeroen
authors: J
authors: Aerssens
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D015195:Drug Design; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D006801:Humans; D007249:Inflammation; D051379:Mice; D008956:Models, Chemical; D009103:Multiple Sclerosis / Q000188:drug therapy*; D009437:Neuralgia / Q000188:drug therapy; D051381:Rats; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D001562:Benzimidazoles; D043885:Receptor, Cannabinoid, CB2