654671-78-0
654671-78-0 結(jié)構(gòu)式
基本信息
西他列汀磷酸鹽
無(wú)水磷酸西他列汀
磷酸西他列汀無(wú)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-5,6-二氫(1,2,4)三唑并[4,3-a]吡嗪-7(8H)-基)-1-(2,4,5-三氟苯基)丁-2-胺磷酸鹽
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
物理化學(xué)性質(zhì)
常見(jiàn)問(wèn)題列表
臨床研究表明，磷酸西他列汀作為單藥治療2型糖尿病患者，可使糖化血紅蛋白（HbA1c）水平顯著降低。與二甲雙胍或TZDs聯(lián)合應(yīng)用時(shí)，具有顯著的輔助治療作用，能針對(duì)2型糖尿病的三種主要缺陷：胰島素抵抗，β細(xì)胞功能障礙（胰島素的釋放減少），以及α細(xì)胞功能障礙（未抑制肝葡萄糖的產(chǎn)生）發(fā)揮作用。但該藥不宜用于1型糖尿病患者或者糖尿病性酮酸中毒的治療。
磷酸西他列汀能夠增強(qiáng)一種名為腸降血糖系統(tǒng)的人體生理性系統(tǒng)，產(chǎn)生生理性降糖功效。這個(gè)生理系統(tǒng)自身能夠影響胰島的β細(xì)胞和α細(xì)胞，有助于調(diào)節(jié)葡萄糖，而且只有β細(xì)胞功能紊亂造成胰島素減少引起血糖升高，或因α細(xì)胞和β細(xì)胞功能紊亂造成肝臟葡萄糖合成失控進(jìn)而引發(fā)血糖升高，DPP-4才會(huì)產(chǎn)生藥效。
磷酸西他列汀存在葡萄糖水平依賴(lài)性，它不會(huì)一味地只知道降糖，更不會(huì)掠奪性地壓榨胰島，耗竭胰腺的功能。相反，試驗(yàn)證明，它具有長(zhǎng)期保護(hù)人類(lèi)β細(xì)胞的前景。此外，它不會(huì)導(dǎo)致體重增加、血糖降低等的副反應(yīng)，患者對(duì)藥物依從性也會(huì)大大提高。因此，理論上它的有效作用年限會(huì)大大超過(guò)目前的口服降糖藥，患者的胰島素依賴(lài)會(huì)大大延緩。
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.