2-amino-5-methoxycarbonyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-amino-5-methoxycarbonyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine
• 英文别名: methyl 2-amino-6,7-dihydrothiazolo[5,4-c]pyridine-5(4H)-carboxylate；methyl 2-amino-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridine-5-carboxylate
• 化学式: C₈H₁₁N₃O₂S
• 分子量: 213.26
• InChiKey: HBRLUAXDUCJKGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  96.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino-5-methoxycarbonyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine 、 (S)-3-(4-(azetidine-1-carbonyl)phenoxy)-5-((1-methoxypropan-2-yl)oxy)benzoic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以36%的产率得到methyl (S)-2-(3-(4-(azetidine-1-carbonyl)phenoxy)-5-((1-methoxypropan-2-yl)oxy)benzamido)-6,7-dihydrothiazolo[5,4-c]pyridine-5(4H)-carboxylate
  参考文献：
  名称：

  Discovery of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific glucokinase activators: Design, synthesis, and biological evaluation

  摘要：

  Glucokinase (GK) activators are being developed for the treatment of type 2 diabetes mellitus (T2DM). However, existing GK activators have risks of hypoglycemia caused by over-activation of GK in islet cells and dyslipidemia caused by over-activation of intrahepatic GK. In the effort to mitigate risks of hypoglycemia and dyslipidemia while maintaining the promising efficacy of GK activator, we investigated a series of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific partial GK activators, which led to the identification of compound 72 that showed a good balance between in vitro potency and enzyme kinetic parameters, and protected beta-cells from streptozotocin-induced apoptosis. Chronic treatment of compound 72 demonstrated its potent activity in regulation of glucose homeostasis and low risk of dyslipidemia with diabetic db/db mice in oral glucose tolerance test (OGTT). Moreover, acute treatment of compound 72 did not induce hypoglycemia in C57BL/6J mice even at 200 mg/kg via oral administration. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.07.051
• 作为产物：
  描述：

  4-氧代哌啶-1-羧酸甲酯 、 氰胺 在 四氢吡咯 、 sulfur 作用下， 以 异丙醇 为溶剂， 反应 8.0h， 以71%的产率得到2-amino-5-methoxycarbonyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine
  参考文献：
  名称：

  Discovery of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific glucokinase activators: Design, synthesis, and biological evaluation

  摘要：

  Glucokinase (GK) activators are being developed for the treatment of type 2 diabetes mellitus (T2DM). However, existing GK activators have risks of hypoglycemia caused by over-activation of GK in islet cells and dyslipidemia caused by over-activation of intrahepatic GK. In the effort to mitigate risks of hypoglycemia and dyslipidemia while maintaining the promising efficacy of GK activator, we investigated a series of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific partial GK activators, which led to the identification of compound 72 that showed a good balance between in vitro potency and enzyme kinetic parameters, and protected beta-cells from streptozotocin-induced apoptosis. Chronic treatment of compound 72 demonstrated its potent activity in regulation of glucose homeostasis and low risk of dyslipidemia with diabetic db/db mice in oral glucose tolerance test (OGTT). Moreover, acute treatment of compound 72 did not induce hypoglycemia in C57BL/6J mice even at 200 mg/kg via oral administration. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.07.051

文献信息

• [EN] N-SUBSTITUTED-3,5-DISUBSTITUTED BENZAMIDE COMPOUND AND PREPARATION METHOD AND APPLICATION THEREOF<br/>[FR] COMPOSÉ BENZAMIDE N-SUBSTITUÉ-3,5-DISUBSTITUÉ ET SES PROCÉDÉ DE PRÉPARATION ET APPLICATION<br/>[ZH] N-取代-3,5-二取代苯甲酰胺类化合物及其制备方法和应用
  申请人：SHANGHAI INST MATERIA MEDICA

  公开号：WO2016112863A1

  公开（公告）日：2016-07-21

  本发明公开一种N-取代-3,5-二取代苯甲酰胺类化合物及其制备方法和应用，该化合物结构如通式I所示，式中，m、X、Y、R1、R2和R3如权利要求书和说明书所示。本发明还公开了包含通式I所示化合的药物组合物。本发明的化合物可以作为葡萄糖激酶激动剂，用于预防和/或治疗与葡萄糖代谢异常相关的疾病。
• Discovery of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific glucokinase activators: Design, synthesis, and biological evaluation
  作者：Zhengyu Wang、Xiaofan Shi、Huan Zhang、Liang Yu、Yanhua Cheng、Hefeng Zhang、Huibin Zhang、Jinpei Zhou、Jing Chen、Xu Shen、Wenhu Duan

  DOI：10.1016/j.ejmech.2017.07.051

  日期：2017.10

  Glucokinase (GK) activators are being developed for the treatment of type 2 diabetes mellitus (T2DM). However, existing GK activators have risks of hypoglycemia caused by over-activation of GK in islet cells and dyslipidemia caused by over-activation of intrahepatic GK. In the effort to mitigate risks of hypoglycemia and dyslipidemia while maintaining the promising efficacy of GK activator, we investigated a series of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific partial GK activators, which led to the identification of compound 72 that showed a good balance between in vitro potency and enzyme kinetic parameters, and protected beta-cells from streptozotocin-induced apoptosis. Chronic treatment of compound 72 demonstrated its potent activity in regulation of glucose homeostasis and low risk of dyslipidemia with diabetic db/db mice in oral glucose tolerance test (OGTT). Moreover, acute treatment of compound 72 did not induce hypoglycemia in C57BL/6J mice even at 200 mg/kg via oral administration. (C) 2017 Elsevier Masson SAS. All rights reserved.