745053-46-7Relevant academic research and scientific papers
Design, synthesis, and pharmacological evaluation of N-(4-mono and 4,5-disubstituted thiazol-2-yl)-2-aryl-3-(tetrahydro-2H-pyran-4-yl)propanamides as glucokinase activators
Li, Fuying,Zhu, Qingzhang,Zhang, Yi,Feng, Ying,Leng, Ying,Zhang, Ao
scheme or table, p. 3875 - 3884 (2010/08/05)
A series of N-thiazole substituted arylacetamides were designed on the basis of metabolic mechanism of the aminothiazole fragment as glucokinase (GK) activators for the treatment of type 2 diabetes. Instead of introducing a substituent to block the metabolic sensitive C-5 position on the thiazole core directly, a wide variety of C-4 or both C-4 and C-5 substitutions were explored. Compound R-9k bearing an iso-propyl group as the C-4 substituent was found possessing the highest GK activation potency with an EC50 of 0.026 μM. This compound significantly increased both glucose uptake and glycogen synthesis in rat primary cultured hepatocytes. Moreover, single oral administration of compound R-9k exerted significant reduction of blood glucose levels in both ICR and ob/ob mice. These promising results indicated that compound R-9k is a potent orally active GK activator, and is warranted for further investigation as a new anti-diabetic treatment.
Highly enantioselective hydrogenation of α-aryl-β-substituted acrylic acids catalyzed by Ir-SpinPHOX
Zhang, Yi,Han, Zhaobin,Li, Fuying,Ding, Kuiling,Zhang, Ao
supporting information; experimental part, p. 156 - 158 (2010/04/02)
The enantioselective hydrogenation of a series of challenging substrates, α-aryl-β-substituted acrylic acids, was realized with high efficiency and enantioselectivity (up to 96%) under the catalysis of Ir(i) complex of Spiro-based P,N ligand, SpinPHOX.
SAR, pharmacokinetics, safety, and efficacy of glucokinase activating 2-(4-sulfonylphenyl)-N-thiazol-2-ylacetamides: Discovery of PSN-GK1
Bertram, Lisa S.,Black, Daniel,Briner, Paul H.,Chatfield, Rosemary,Cooke, Andrew,Fyfe, Matthew C. T.,Murray, P. John,Naud, Frédéric,Nawano, Masao,Procter, Martin J.,Rakipovski, Günaj,Rasamison, Chrystelle M.,Reynet, Christine,Schofield, Karen L.,Shah, Vilas K.,Spindler, Felix,Taylor, Amanda,Turton, Roy,Williams, Geoffrey M.,Wong-Kai-In, Philippe,Yasuda, Kosuke
supporting information; experimental part, p. 4340 - 4345 (2009/05/27)
Allosteric activators of the glucose-sensing enzyme glucokinase (GK) are currently attracting much interest as potential antidiabetic therapies because they can achieve powerful blood glucose lowering through actions in multiple organs. Here, the optimization of a weakly active high-throughput screening hit to (2R)-2-(4-cyclopropanesulfonylphenyl)-N-(5-fluorothiazol-2-yl)-3- (tetrahydropyran-4-yl)propionamide (PSN-GK1), a potent GK activator with an improved pharmacokinetic and safety profile, is described. Following oral administration, this compound elicited robust glucose lowering in rats.
TRI(CYCLO) SUBSTITUTED AMIDE COMPOUNDS
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Page 41-42, (2008/06/13)
Compounds of Formula (I): or pharmaceutically acceptable salts thereof, are useful in the prophylactic and therapeutic treatment of hyperglycemia and diabetes.
