Discovery of (S)-6-(3-cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic acid as a hepatoselective glucokinase activator clinical candidate for treating type 2 diabetes mellitus.

  title={Discovery of (S)-6-(3-cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic acid as a hepatoselective glucokinase activator clinical candidate for treating type 2 diabetes mellitus.},
  author={Jeffrey A. Pfefferkorn and Angel Guzman-Perez and John H. Litchfield and Robert J. Aiello and Judith L. Treadway and John C. Pettersen and Martha L Minich and Kevin J Filipski and Christopher S Jones and Meihua Tu and Gary E Aspnes and Hud Risley and Jianwei Bian and Benjamin D. Stevens and Patricia Bourassa and Theresa D'Aquila and Levenia Baker and Nicole Barucci and Alan G.S. Robertson and Francis Bourbonais and Dawa Derksen and Margit Macdougall and Over Cabrera and Jing Chen and Amanda Lee Lapworth and James A Landro and William J. Zavadoski and Karen E. Atkinson and Nahor Haddish-Berhane and Beijing Tan and Lili Yao and Rachel E. Kosa and Manthena V S Varma and Bo Feng and David B. Duignan and Ayman El-Kattan and Sharad B. Murdande and Shenping Liu and Mark J Ammirati and John D. Knafels and Paul A. DaSilva-Jardine and Laurel J. Sweet and Spiros Liras and Timothy P. Rolph},
  journal={Journal of medicinal chemistry},
  volume={55 3},
Glucokinase is a key regulator of glucose homeostasis, and small molecule allosteric activators of this enzyme represent a promising opportunity for the treatment of type 2 diabetes. Systemically acting glucokinase activators (liver and pancreas) have been reported to be efficacious but in many cases present hypoglycaemia risk due to activation of the enzyme at low glucose levels in the pancreas, leading to inappropriately excessive insulin secretion. It was therefore postulated that a liver… CONTINUE READING
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