title: Novel thioamide derivatives as neutral CB1 receptor antagonists.
abstract: A novel class of cannabinoid-1 (CB1) receptor antagonists for the treatment of obesity is presented. The carboxamide linker in a set of 5,6-diaryl-pyrazine-2-amide derivatives was transformed into the corresponding thioamide, by using a one-pot synthesis. The structural series of thioamides not only showed retained CB1 potency (below 10nM), but also showed improved solubility. In addition, the neutral antagonist 2c significantly reduced body weight in cafeteria diet obese mice.
authors.affiliation: Lead Generation Department, AstraZeneca R&D Mölndal, S-431 83 Mölndal, Sweden. dr.jonas.bostrom@gmail.com
authors.forename: Jonas
authors.initials: J
authors.lastname: Boström
authors.forename: Roine I
authors.initials: RI
authors.lastname: Olsson
authors.forename: Joakim
authors.initials: J
authors.lastname: Tholander
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Greasley
authors.forename: Erik
authors.initials: E
authors.lastname: Ryberg
authors.forename: Henrik
authors.initials: H
authors.lastname: Nordberg
authors.forename: Stephan
authors.initials: S
authors.lastname: Hjorth
authors.forename: Leifeng
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy; D011719:Pyrazines / Q000737:chemistry* / Q000493:pharmacokinetics; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013854:Thioamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D019440:Anti-Obesity Agents; D011719:Pyrazines; D043884:Receptor, Cannabinoid, CB1; D013854:Thioamides