2. Academic Validation
  3. Discovery, structure-activity relationships, pharmacokinetics, and efficacy of glucokinase activator (2R)-3-cyclopentyl-2-(4-methanesulfonylphenyl)-N-thiazol-2-yl-propionamide (RO0281675)

Discovery, structure-activity relationships, pharmacokinetics, and efficacy of glucokinase activator (2R)-3-cyclopentyl-2-(4-methanesulfonylphenyl)-N-thiazol-2-yl-propionamide (RO0281675)

  • J Med Chem. 2010 May 13;53(9):3618-25. doi: 10.1021/jm100039a.
Nancy-Ellen Haynes 1,  Wendy L Corbett,  Fred T Bizzarro,  Kevin R Guertin,  Darryl W Hilliard,  George W Holland,  Robert F Kester,  Paige E Mahaney,  Lida Qi,  Cheryl L Spence,  John Tengi,  Mark T Dvorozniak,  Aruna Railkar,  Franz M Matschinsky,  Joseph F Grippo,  Joseph Grimsby,  Ramakanth Sarabu
Affiliations

Affiliation

  • 1 Department of Discovery Chemistry, Hoffmann-La Roche Inc., 340 Kingsland Street, Nutley, New Jersey 07110, USA.
PMID: 20405948 DOI: 10.1021/jm100039a
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.

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