654671-78-0
654671-78-0 结构式
基本信息
西他列汀磷酸盐
无水磷酸西他列汀
磷酸西他列汀无水物
磷酸西他列汀/一水化物
磷酸西他列汀 磷酸西他列汀一水化物
4-氧代-4-(3-三氟甲基-5,6-二氢(1,2,4)三唑并[4,3-a]吡嗪-7(8H)-基)-1-(2,4,5-三氟苯基)丁-2-胺磷酸盐
Sitagliptin phosphate/Sitagliptin phosphate Monohydrate/Sitagliptin
(3R)-3-aMino-1-[3-(trifluoroMethyl)-5H,6H,7H,8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one
4-Oxo-4-(3-(trifluoromethyl)-5,6-dihydro(1,2,4)triazolo[4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-2-amine phosphate
7-[(3R)-3-Amino-1-oxo-4-(2,4,5-trifluorophenyl)butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-α]pyrazine-phosphate
Sitagliptin phosphate 4-Oxo-4-(3-(trifluoromethyl)-5,6-dihydro(1,2,4)triazolo[4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-2-amine phosphate
物理化学性质
常见问题列表
临床研究表明，磷酸西他列汀作为单药治疗2型糖尿病患者，可使糖化血红蛋白（HbA1c）水平显著降低。与二甲双胍或TZDs联合应用时，具有显著的辅助治疗作用，能针对2型糖尿病的三种主要缺陷：胰岛素抵抗，β细胞功能障碍（胰岛素的释放减少），以及α细胞功能障碍（未抑制肝葡萄糖的产生）发挥作用。但该药不宜用于1型糖尿病患者或者糖尿病性酮酸中毒的治疗。
磷酸西他列汀能够增强一种名为肠降血糖系统的人体生理性系统，产生生理性降糖功效。这个生理系统自身能够影响胰岛的β细胞和α细胞，有助于调节葡萄糖，而且只有β细胞功能紊乱造成胰岛素减少引起血糖升高，或因α细胞和β细胞功能紊乱造成肝脏葡萄糖合成失控进而引发血糖升高，DPP-4才会产生药效。
磷酸西他列汀存在葡萄糖水平依赖性，它不会一味地只知道降糖，更不会掠夺性地压榨胰岛，耗竭胰腺的功能。相反，试验证明，它具有长期保护人类β细胞的前景。此外，它不会导致体重增加、血糖降低等的副反应，患者对药物依从性也会大大提高。因此，理论上它的有效作用年限会大大超过目前的口服降糖药，患者的胰岛素依赖会大大延缓。
IC50: 19 nM (DPP4, in Caco-2 cell extracts)
Sitagliptin phosphate exhibits a potent inhibitory effect on DPP-4 with IC 50 of 19 nM from Caco-2 cell extracts. Sitagliptin reduces in vitro migration of isolated splenic CD4 T-cells through a pathway involving cAMP/PKA/Rac1 activation. A recent study demonstrates that sitagliptin exerts a novel, direct action in order to stimulate GLP-1 secretion by the intestinal L cell through a DPP-4-independent, protein kinase A- and MEK-ERK1/2-dependent pathway. It therefore reduces the effect of autoimmunity on graft survival.
In vivo, the ED 50 value of sitagliptin phosphate for inhibition of plasma DPP-4 activity is calculated to be 2.3 mg/kg 7 hour postdose and 30 mg/kg 24 hour postdose in freely fed Han-Wistar rats. The streptozotocin-induced type 1 diabetes mouse model exhibits elevated DPP-4 levels in the plasma that can be substantially inhibited in mice on an Sitagliptin phosphate diet. This is achieved by a positive effect on the regulation of hyperglycemia, potentially through prolongation of islet graft survival. The plasma clearance and volume of distribution of Sitagliptin phosphate are higher in rats (40-48 mL/min/kg, 7-9 L/kg) than in dogs (9 mL/min/kg, 3 L/kg); and its half-life is shorter in rats,2 hours compared with 4 hours in dogs.