On May 1, 2017, Xu, Jiayi; Lin, Songnian; Myers, Robert W.; Trujillo, Maria E.; Pachanski, Michele J.; Malkani, Sunita; Chen, Hsuan-shen; Chen, Zhesheng; Campbell, Brian; Eiermann, George J.; Elowe, Nadine; Farrer, Brian T.; Feng, Wen; Fu, Qinghong; Kats-Kagan, Roman; Kavana, Michael; McMasters, Daniel R.; Mitra, Kaushik; Tong, Xinchun; Xu, Libo; Zhang, Fengqi; Zhang, Rui; Addona, George H.; Berger, Joel P.; Zhang, Bei; Parmee, Emma R. published an article.Recommanded Product: 98946-18-0 The title of the article was Discovery of orally active hepatoselective glucokinase activators for treatment of Type II Diabetes Mellitus. And the article contained the following:
Systemically acting glucokinase activators (GKA) have been demonstrated in clin. trials to effectively lower blood glucose in patients with type II diabetes. However, mechanism-based hypoglycemia is a major adverse effect that limits the therapeutic potential of these agents. The authors hypothesized that the predominant mechanism leading to hypoglycemia is GKA-induced excessive insulin secretion from pancreatic β-cells at (sub-)euglycemic levels. The authors further hypothesized that restricting GK activation to hepatocytes would maintain glucose-lowering efficacy while significantly reducing hypoglycemic risk. Here the authors report the discovery of a novel series of carboxylic acid substituted GKAs based on pyridine-2-carboxamide. These GKAs exhibit preferential distribution to the liver vs. the pancreas in mice. SAR studies led to the identification of a potent and orally active hepatoselective GKA, compound I. GKA I demonstrated robust glucose lowering efficacy in high fat diet-fed mice at doses ≥10 mpk, with ≥70-fold liver:pancreas distribution, minimal effects on plasma insulin levels, and significantly reduced risk of hypoglycemia. The experimental process involved the reaction of tert-Butyl trichloroacetimidate(cas: 98946-18-0).Recommanded Product: 98946-18-0
The Article related to glucokinase activator antidiabetic diabetes, diabetes, glucokinase, glucokinase activator (gka), glucose homeostasis, glucose metabolism, hepatoselective, hepatospecific, hexokinase iv, liver preferring, pyridine-2-carboxamide, type ii diabetes mellitus and other aspects.Recommanded Product: 98946-18-0
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