methyl 5-(2-formylphenyl)-2-methylthiophene-3-carboxylate | 1353018-93-5

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: methyl 5-(2-formylphenyl)-2-methylthiophene-3-carboxylate
• 英文别名: 3-Thiophenecarboxylic acid, 5-(2-formylphenyl)-2-methyl-, methyl ester
• CAS: 1353018-93-5
• 化学式: C₁₄H₁₂O₃S
• 分子量: 260.313
• InChiKey: IAFDZDDPIGJBBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  71.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 5-(2-formylphenyl)-2-methylthiophene-3-carboxylate 在 sodium chlorite 、 disodium hydrogenphosphate 、 2-甲基-2-丁烯 作用下， 以 水 、 叔丁醇 为溶剂， 反应 60.0h， 以68%的产率得到2-(4-(methoxycarbonyl)-5-methylthiophen-2-yl)benzoic acid
  参考文献：
  名称：

  Discovery of a potent glucokinase activator with a favorable liver and pancreas distribution pattern for the treatment of type 2 diabetes mellitus

  摘要：

  Glucokinase (GK) is an enzyme that plays an important role as a glucose sensor while maintaining whole body glucose homeostasis. Allosteric activators of GK (GKAs) have the potential to treat type 2 diabetes mellitus. To identify novel GKAs, a series of compounds based on a thiophenyl-pyrrolidine scaffold were designed and synthesized. In this series, compound 38 was found to inhibit glucose excursion in an oral glucose tolerance test (OGTT) in mice. Optimization of 38 using a zwitterion approach led to the identification of the novel GKA 59. GKA 59 exhibited potent blood glucose control in the OGTT test as well as a favorable safety profile. Owing to low pancreatic distribution, compound 59 primarily activates GK in the liver. This characteristic could overcome limitations of other GKAs, such as hypoglycemia, increased plasma triglycerides, and loss of efficacy. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.06.060
• 作为产物：
  描述：

  2-甲基-3-噻吩甲酸甲酯 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 methyl 5-(2-formylphenyl)-2-methylthiophene-3-carboxylate
  参考文献：
  名称：

  Discovery of a potent glucokinase activator with a favorable liver and pancreas distribution pattern for the treatment of type 2 diabetes mellitus

  摘要：

  Glucokinase (GK) is an enzyme that plays an important role as a glucose sensor while maintaining whole body glucose homeostasis. Allosteric activators of GK (GKAs) have the potential to treat type 2 diabetes mellitus. To identify novel GKAs, a series of compounds based on a thiophenyl-pyrrolidine scaffold were designed and synthesized. In this series, compound 38 was found to inhibit glucose excursion in an oral glucose tolerance test (OGTT) in mice. Optimization of 38 using a zwitterion approach led to the identification of the novel GKA 59. GKA 59 exhibited potent blood glucose control in the OGTT test as well as a favorable safety profile. Owing to low pancreatic distribution, compound 59 primarily activates GK in the liver. This characteristic could overcome limitations of other GKAs, such as hypoglycemia, increased plasma triglycerides, and loss of efficacy. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.06.060