发现坎格列净，一种新型含噻吩环的 C-糖苷，作为钠依赖性葡萄糖共转运蛋白 2 抑制剂用于治疗 2 型糖尿病。
Discovery of canagliflozin, a novel C-glucoside with thiophene ring, as sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus.
机构信息
Medicinal Chemistry Research Laboratories, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama, Japan.
出版信息
J Med Chem. 2010 Sep 9;53(17):6355-60. doi: 10.1021/jm100332n.
PMID:20690635
Abstract
We discovered that C-glucosides 4 bearing a heteroaromatic ring formed metabolically more stable inhibitors for sodium-dependent glucose cotransporter 2 (SGLT2) than the O-glucoside, 2 (T-1095). A novel thiophene derivative 4b-3 (canagliflozin) was a highly potent and selective SGLT2 inhibitor and showed pronounced anti-hyperglycemic effects in high-fat diet fed KK (HF-KK) mice.
摘要
我们发现，与 O-糖苷 2（T-1095）相比，带有杂芳环的 C-糖苷 4 形成了代谢更稳定的钠依赖性葡萄糖共转运蛋白 2（SGLT2）抑制剂。一种新型噻吩衍生物 4b-3（卡格列净）是一种高效且选择性的 SGLT2 抑制剂，在高脂肪饮食喂养的 KK（HF-KK）小鼠中显示出显著的抗高血糖作用。
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