1032823-75-8
中文名稱
GSK1292263
英文名稱
GSK1292263
CAS
1032823-75-8
分子式
C23H28N4O4S
分子量
456.558
MOL 文件
1032823-75-8.mol
更新日期
2024/12/26 09:13:31
1032823-75-8 結構式
基本信息
中文別名
化合物GSK12922635-[[[1-(3-異丙基-1,2,4-二唑-5-基)-4-哌啶基]甲基]氧基]-2-[4-(甲磺?；?苯基]吡啶
3-異丙基-5-(4-(((6-(4-(甲基磺酰)苯基)吡啶-3-基)氧基)甲基)哌啶-1-基)-1,2,4-惡二唑
5-[[[1-(3-異丙基-1,2,4-噁二唑-5-基)-4-哌啶基]甲基]氧基]-2-[4-(甲磺?；?苯基]吡啶
5-[[[1-(3-異丙基-1,2,4-惡二唑-5-基)-4-哌啶基]甲基]氧基]-2-[4-(甲磺酰基)苯基]吡啶
英文別名
CS-417GSK1292263
GSK1292263 USP/EP/BP
GSK-1292263
GSK 1292263
GPR119 receptor agonist GS1292263
3-Isopropyl-5-(4-(((6-(4-(methylsulfonyl)phenyl)pyridin-3-yl)oxy)methyl)piperidin-1-yl)-1,2,4-
3-Isopropyl-5-(4-(((6-(4-(methylsulfonyl)phenyl)pyridin-3-yl)oxy)methyl)piperidin-1-yl)-1,2,4-oxa
5-((1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)methoxy)-2-(4-(methylsulfonyl)phenyl)pyridine
3-isopropyl-5-(4-(((6-(4-(Methylsulfonyl)phenyl)pyridin-3-yl)oxy)Methyl)piperidin-1-yl)-1,2,4-oxadiazole
Pyridine, 5-[[1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl]methoxy]-2-[4-(methylsulfonyl)phenyl]-
所屬類別
生物化工：GPR 激動劑物理化學性質
沸點655.1±65.0 °C(Predicted)
密度1.23
儲存條件-20°C儲存
溶解度≥21.1 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH
酸度系數(pKa)4.75±0.32(Predicted)
形態(tài)固體
顏色White to off-white
常見問題列表
生物活性
GSK1292263是一種新型GPR119激動劑，用于治療2型糖尿病。Phase 2。體外研究
GSK-1292263 is selected from 1538 compounds by using Hypo1, the Fit-Value and Estimate of GSK-1292263 that is aligned in Hypo1 are 8.8 and 7.7 (nM), respectively.體內研究
GSK-1292263 administrated at a single dose of 3-30 mg/kg in the absence of nutrients correlates with increased levels of circulating gastrointestinal peptides, including glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY) and glucagon in male Sprague-Dawley rats, the increase is enhanced following administration of glucose in the oral glucose tolerance test (OGTT). GSK-129226 significant increases in the peak insulin response and insulin AUC(0-15 min) of 30-60% compared with values in the vehicle control cohort in the intravenous glucose tolerance test in rats, this insulin upregulation correlated with a significant increase in the glucose disposal rate. GSK-1292263 is associated with a statistically significant increase in insulin immunoreactivity in pancreatic sections in a 6-week study performed in Zucker diabetic fatty rats, compared with insulin immunoreactivity in samples obtained from rats receiving vehicle control. GSK-1292263 administrated at dose of 10 or 30 mg/kg or vehicle control at 2 hours prior to insulin infusion in hyperinsulinemic-euglycemic clamps stimulates glucagon secretion without increasing blood glucose levels Sprague-Dawley rats.靶點
| Target | Value |
|
GPR119
() |
體外研究
GSK-1292263通過使用Hypo1從1538種化合物中被選出，與Hypo1中一致的GSK-1292263的擬合值和估計值分別為8.8和7.7 (nM)。
體內研究
在雄性Sprague-Dawley大鼠體內，GSK-1292263(3-30 mg/kg)以單劑量給藥在營養(yǎng)素不存在時，與循環(huán)胃腸肽，包括胰高血糖素樣多肽1(GLP-1)，腸抑胃肽(GIP)，多肽YY (PYY)和胰高血糖素的增加水平相關，在口服葡萄糖耐量測試(OGTT)中，葡萄糖給藥會加強循環(huán)胃腸肽的增加。在大鼠靜脈內葡萄糖耐量測試中，GSK-129226顯著增加胰島素反應的峰值，并且與載體對照組相比，增加30-60%的胰島素AUC(0-15 min)，此處胰島素的上調與葡萄糖清除率的顯著增加相關。在Zucker糖尿病肥胖大鼠的6周研究中，與空白對照大鼠樣本中胰島素免疫反應性相比，GSK-1292263與胰腺切片中胰島素免疫反應性在統(tǒng)計學上的顯著增加相關。Sprague-Dawley大鼠體內，高胰島素-正常血糖鉗夾實驗中，胰島素注射2小時前，GSK-1292263以10 或30 mg/kg的劑量給藥或與載體對照相比，刺激胰高血糖素分泌，而不增加血糖水平。