1152311-98-2Relevant articles and documents
Identification and hit-to-lead optimization of a novel class of CB1 antagonists
Letourneau, Jeffrey J.,Jokiel, Patrick,Olson, John,Riviello, Christopher M.,Ho, Koc-Kan,McAleer, Lihong,Yang, Jingchun,Swanson, Robert N.,Baker, James,Cowley, Phillip,Edwards, Darren,Ward, Nick,Ohlmeyer, Michael H.J.,Webb, Maria L.
scheme or table, p. 5449 - 5453 (2011/01/03)
The discovery, synthesis and preliminary structure-activity relationships (SARs) of a novel class of CB1 antagonists is described. Initial optimization of benzimidazole-based screening hit 4 led to the identification of 'inverted' indole-based lead compound 18c with improved properties versus compound 4 including reduced A log P, improved microsomal stability and improved aqueous solubility. Compound 18c demonstrates in vivo CB1 antagonist efficacy (CB1 agonist induced hypothermia model) and is orally bioavailable in rat.
