Structure-activity relationships of 3,5-disubstituted benzamides as glucokinase activators with potent in vivo efficacy
2009
Abstract The optimization of our lead GK activator 2a to 3-[(1 S )-2-hydroxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]- N -1,3-thiazol-2-ylbenzamide ( 6g ), a potent GK activator with good oral availability, is described, including to uncouple the relationship between potency and hydrophobicity. Following oral administration, this compound exhibited robust glucose lowering in diabetic model rodents.
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