- Bicyclic derivative of heterocyclic glucoside as well as preparation method and application of bicyclic derivative
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The invention relates to a bicyclic derivative of heterocyclic glucoside as well as a preparation method and application of the bicyclic derivative, in particular to a compound shown in a formula I, a stereoisomer or pharmaceutically acceptable salt or es
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- Design, Synthesis and in vivo Evaluation of Novel C-Aryl Glucosides as Potent Sodium-Dependent Glucose Cotransporters Inhibitors for the Treatment of Diabetes
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A series of novel C-aryl glucosides with substituents at the 3′-position or cyclization at 3′, 4′-positions of the distal aryl ring were designed and synthesized, which might decrease the oxidative metabolism of dapagliflozin. Preliminary evaluation for hypoglycemic effect and the risk of hypoglycemia were carried out both in normal and in streptozotocin-induced diabetic mice. Among the synthesized compounds, compound 19a exerted potency-similarity with dapagliflozin and triggered the hypoglycemic effect in a dose-dependent manner. Besides, compound 19a, even at the high dose of 10 mg/kg, revealed a low risk of hypoglycemia. In further studies, 19a exhibited sustained antihyperglycemic effect without particular side-effects in 30-day chronic diabetic mice studies. Moreover, histological changes in the pancreas of diabetic mice indicated 19a might protect pancreatic β-cell from apoptosis by reducing the damage of glucotoxicity. All of these results demonstrated that compound 19a, with excellent in vivo pharmacological activity and safety profile, was considered to be a promising drug candidate for the treatment of diabetes mellitus.
- Li, Zheng,Wang, Xuekun,Xu, Xue,Qiu, Qianqian,Jiao, Lei,Huang, Wenlong,Qian, Hai
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p. 764 - 775
(2015/03/30)
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- C-ARYL GLUCOSIDE DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF
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C-aryl glucoside derivatives, preparation processes and pharmaceutical uses thereof are disclosed. In particular, C-aryl glucoside derivatives represented by formula (I), with each substituent defined in the application, pharmaceutically acceptable salts or stereoisomers thereof, their preparation methods, and pharmaceutical compositions containing the derivatives as well as their uses as therapeutic agents, particularly as sodium-dependent glucose cotransporter (SGLT)-1 inhibitors, are disclosed.
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