3-amino-N-(furan-2-ylmethyl)-6-(thiophen-2-yl)thieno[2,3-b]pyridine-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• 英文名称: 3-amino-N-(furan-2-ylmethyl)-6-(thiophen-2-yl)thieno[2,3-b]pyridine-2-carboxamide
• 英文别名: 3-amino-N-(furan-2-ylmethyl)-6-thiophen-2-ylthieno[2,3-b]pyridine-2-carboxamide
• 化学式: C₁₇H₁₃N₃O₂S₂
• 分子量: 355.441
• InChiKey: NQYMOTAWXUEQPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  138
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (E)-3-二甲基氨基-1-噻吩-2-丙酮 在 三乙烯二胺 、 potassium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 3-amino-N-(furan-2-ylmethyl)-6-(thiophen-2-yl)thieno[2,3-b]pyridine-2-carboxamide
  参考文献：
  名称：

  Discovery and structure-activity relationships study of thieno[2,3-b]pyridine analogues as hepatic gluconeogenesis inhibitors

  摘要：

  Type 2 diabetes mellitus (T2DM) is a chronic, complex and multifactorial metabolic disorder, and targeting gluconeogenesis inhibition is a promising strategy for anti-diabetic drug discovery. This study discovered a new class of thieno[2,3-b]pyridine derivatives as hepatic gluconeogenesis inhibitors. First, a hit compound (DMT: IC50 = 33.8 mu M) characterized by a thienopyridine core was identified in a cell based screening of our privileged small molecule library. Structure activity relationships (SARs) study showed that replaced the CF3 in the thienopyridine core could improve the potency and led to the discovery of 8e (IC50 = 16.8 mu M) and 9d (IC50 = 12.3 mu M) with potent inhibition of hepatic glucose production and good drug-like properties. Furthermore, the mechanism of 8e for the inhibition of hepatic glucose production was also identified, which could be effective through the reductive expression of the mRNA transcription level of gluconeogenic genes, including glucose-6-phosphatase (G6Pase) and hepatic phosphoenolpyruvate carboxykinase (PEPCK). Additionally, 8e could also reduce the fasting blood glucose and improve the oral glucose tolerance and pyruvate tolerance in db/db mice. The optimization of this class of derivatives had provided us a start point to develop new anti-hepatic gluconeogenesis agents. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.04.028

文献信息

• Discovery and structure-activity relationships study of thieno[2,3-b]pyridine analogues as hepatic gluconeogenesis inhibitors
  作者：Fei Ma、Jian Liu、Tingting Zhou、Min Lei、Jing Chen、Xiachang Wang、Yinan Zhang、Xu Shen、Lihong Hu

  DOI：10.1016/j.ejmech.2018.04.028

  日期：2018.5

  Type 2 diabetes mellitus (T2DM) is a chronic, complex and multifactorial metabolic disorder, and targeting gluconeogenesis inhibition is a promising strategy for anti-diabetic drug discovery. This study discovered a new class of thieno[2,3-b]pyridine derivatives as hepatic gluconeogenesis inhibitors. First, a hit compound (DMT: IC50 = 33.8 mu M) characterized by a thienopyridine core was identified in a cell based screening of our privileged small molecule library. Structure activity relationships (SARs) study showed that replaced the CF3 in the thienopyridine core could improve the potency and led to the discovery of 8e (IC50 = 16.8 mu M) and 9d (IC50 = 12.3 mu M) with potent inhibition of hepatic glucose production and good drug-like properties. Furthermore, the mechanism of 8e for the inhibition of hepatic glucose production was also identified, which could be effective through the reductive expression of the mRNA transcription level of gluconeogenic genes, including glucose-6-phosphatase (G6Pase) and hepatic phosphoenolpyruvate carboxykinase (PEPCK). Additionally, 8e could also reduce the fasting blood glucose and improve the oral glucose tolerance and pyruvate tolerance in db/db mice. The optimization of this class of derivatives had provided us a start point to develop new anti-hepatic gluconeogenesis agents. (C) 2018 Elsevier Masson SAS. All rights reserved.