(dimethylamino)ethyl 5,6-methylenedioxybenzothiophene-2-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: (dimethylamino)ethyl 5,6-methylenedioxybenzothiophene-2-carboxylate
• 英文别名: 2-(dimethylamino)ethyl thieno[20,3’:4,5]benzo[1,2-d][1,3]dioxole-6-carboxylate；2-(Dimethylamino)ethyl thieno[2,3-f][1,3]benzodioxole-6-carboxylate；2-(dimethylamino)ethyl thieno[2,3-f][1,3]benzodioxole-6-carboxylate
• 化学式: C₁₄H₁₅NO₄S
• 分子量: 293.343
• InChiKey: OYOMJSKQBWTYNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  76.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ethyl thieno[2’,3’:4,5]benzo[1,2-d][1,3]dioxole-6-carboxylate 在 氯化亚砜 、 三乙胺 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 1.5h， 生成 (dimethylamino)ethyl 5,6-methylenedioxybenzothiophene-2-carboxylate
  参考文献：
  名称：

  Substituted benzothiophene and benzofuran derivatives as a novel class of bone morphogenetic Protein-2 upregulators: Synthesis, anti-osteoporosis efficacies in ovariectomized rats and a zebrafish model, and ADME properties

  摘要：

  The bone morphogenetic protein (BMP) pathway is a promising new target for the design of therapeutic agents for the treatment of low bone mass. This study optimized the structure of the anti-osteoporosis compound 38 by balancing its lipophilicity and improving its stability. Twenty derivatives which were not reported in the literature were designed and synthesized. The ovariectomized rat model of osteoporosis was selected to evaluate the therapeutic effects. Compound 125 showed better therapeutic efficacy than that of 38. We verified the anti-osteoporosis activity and BMP-2 protein upregulation after treatment with 125 in a zebrafish osteoporosis model. We found that 125 improved the ADME properties, therapeutic efficacy, and pharmacokinetics of the drug. Overall, we evaluated the anti-osteoporosis effects of the compounds of this type, preliminarily determined the target patient population, verified the mechanism of action, clarified the level of toxicity, and provided preliminary ADME data. We believe that these compounds can both correct bone loss that is already occurring in patients and have broad clinical applicability. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112465

文献信息

• Substituted benzothiophene and benzofuran derivatives as a novel class of bone morphogenetic Protein-2 upregulators: Synthesis, anti-osteoporosis efficacies in ovariectomized rats and a zebrafish model, and ADME properties
  作者：Si-tu Xue、Lei Zhang、Zhuo-song Xie、Jie Jin、Hui-Fang Guo、Hong Yi、Zong-ying Liu、Zhuo-rong Li

  DOI：10.1016/j.ejmech.2020.112465

  日期：2020.8

  The bone morphogenetic protein (BMP) pathway is a promising new target for the design of therapeutic agents for the treatment of low bone mass. This study optimized the structure of the anti-osteoporosis compound 38 by balancing its lipophilicity and improving its stability. Twenty derivatives which were not reported in the literature were designed and synthesized. The ovariectomized rat model of osteoporosis was selected to evaluate the therapeutic effects. Compound 125 showed better therapeutic efficacy than that of 38. We verified the anti-osteoporosis activity and BMP-2 protein upregulation after treatment with 125 in a zebrafish osteoporosis model. We found that 125 improved the ADME properties, therapeutic efficacy, and pharmacokinetics of the drug. Overall, we evaluated the anti-osteoporosis effects of the compounds of this type, preliminarily determined the target patient population, verified the mechanism of action, clarified the level of toxicity, and provided preliminary ADME data. We believe that these compounds can both correct bone loss that is already occurring in patients and have broad clinical applicability. (C) 2020 Elsevier Masson SAS. All rights reserved.