论文信息 - Design, synthesis and biological evaluation of novel glucokinase activators

Design, synthesis and biological evaluation of novel glucokinase activators

Abstract A new series of benzamide derivatives as glucokinase activators (GKAs) were designed and synthesized, and their activation for glucokinase were evaluated by the preliminary glucokinase activity assay. The structure–activity relationship (SAR) is discussed. The result shows that compound 12d and 12h have potent activity reference drug RO-28-1675.

[1] R. Taub,et al. Glucokinase activation – a strategy for T2D therapy: recent developments , 2007 .

[2] Craig S Donald,et al. Design of a potent, soluble glucokinase activator with excellent in vivo efficacy. , 2006, Bioorganic & medicinal chemistry letters.

[3] M. Chiba,et al. Discovery of potent and orally active 3-alkoxy-5-phenoxy-N-thiazolyl benzamides as novel allosteric glucokinase activators. , 2009, Bioorganic & medicinal chemistry.

[4] J. Gromada,et al. A novel glucokinase activator modulates pancreatic islet and hepatocyte function. , 2005, Endocrinology.

[5] Teruyuki Nishimura,et al. Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase. , 2004, Structure.

[6] F. Matschinsky. Regulation of Pancreatic β-Cell Glucokinase: From Basics to Therapeutics , 2002 .

[7] H. Najafi,et al. Glucokinase and glucose homeostasis: proven concepts and new ideas. , 2005, Biochemical Society transactions.

[8] Scott Boyd,et al. Discovery, synthesis and biological evaluation of novel glucokinase activators. , 2005, Bioorganic & medicinal chemistry letters.

[9] M. Tschöp,et al. Two birds with one stone: novel glucokinase activator stimulates glucose-induced pancreatic insulin secretion and augments hepatic glucose metabolism. , 2003, Molecular interventions.