Discovery, structure-activity relationships, pharmacokinetics, and efficacy of glucokinase activator (2R)-3-cyclopentyl-2-(4-methanesulfonylphenyl)-N-...
Basic Information
ID: ALA1157747
Journal: J Med Chem
Title: Discovery, structure-activity relationships, pharmacokinetics, and efficacy of glucokinase activator (2R)-3-cyclopentyl-2-(4-methanesulfonylphenyl)-N-thiazol-2-yl-propionamide (RO0281675).
Authors: Haynes NE, Corbett WL, Bizzarro FT, Guertin KR, Hilliard DW, Holland GW, Kester RF, Mahaney PE, Qi L, Spence CL, Tengi J, Dvorozniak MT, Railkar A, Matschinsky FM, Grippo JF, Grimsby J, Sarabu R.
Abstract: Glucokinase (GK) is a glucose sensor that couples glucose metabolism to insulin release. The important role of GK in maintaining glucose homeostasis is illustrated in patients with GK mutations. In this publication, identification of the hit molecule 1 and its SAR development, which led to the discovery of potent allosteric GK activators 9a and 21a, is described. Compound 21a (RO0281675) was used to validate the clinical relevance of targeting GK to treat type 2 diabetes.
CiteXplore: 20405948
DOI: 10.1021/jm100039a
Patent ID: ┄