N-[5-amino-2-(dimethylamino)phenyl]thiophene-2-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[5-amino-2-(dimethylamino)phenyl]thiophene-2-carboxamide
• 化学式: C₁₃H₁₅N₃OS
• 分子量: 261.348
• InChiKey: SEQJTHCUVYUQHG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  86.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[5-amino-2-(dimethylamino)phenyl]thiophene-2-carboxamide 在 盐酸 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 0.5h， 生成 N-(2-(dimethylamino)-5-((7-isonicotinoyl-5,6,7,8-tetrahydropyrido[4’,3’:4,5]thieno[2,3-d]pyrimidin-4-yl)amino)phenyl)thiophene-2-carboxamide
  参考文献：
  名称：

  Discovery of novel TNNI3K inhibitor suppresses pyroptosis and apoptosis in murine myocardial infarction injury

  摘要：

  Myocardial infarction (MI) injury is a highly lethal syndrome that has, until recently, suffered from a lack of clinically efficient targeted therapeutics. The cardiac troponin I interacting kinase (TNNI3K) exacerbates ischemia-reperfusion (IR) injury via oxidative stress, thereby promoting cardiomyocyte death. In this current study, we designed and synthesized 35 novel TNNI3K inhibitors with a pyrido[4,5]thieno [2,3-d] pyrimidine scaffold. In vitro results indicated that some of the inhibitors exhibited sub-micromolar TNNI3K inhibitory capacity and good kinase selectivity, as well as cytoprotective activity, in an oxygen-glucose deprivation (OGD) injury cardiomyocyte model. Furthermore, investigation of the mechanism of the representative derivative compound 6o suggested it suppresses pyroptosis and apoptosis in cardiomyocytes by interfering with p38MAPK activation, which was further confirmed in a murine myocardial infarction injury model. In vivo results indicate that compound 6o can markedly reduce myocardial infarction size and alleviate cardiac tissue damage in rats. In brief, our results provide the basis for further development of novel TNNI3K inhibitors for targeted MI therapy. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112314
• 作为产物：
  描述：

  N~1~,N~1~-二甲基-4-硝基-1,2-苯二胺 在 氯化铵 、 溶剂黄146 、 三乙胺 、 锌 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 N-[5-amino-2-(dimethylamino)phenyl]thiophene-2-carboxamide
  参考文献：
  名称：

  Discovery of novel TNNI3K inhibitor suppresses pyroptosis and apoptosis in murine myocardial infarction injury

  摘要：

  Myocardial infarction (MI) injury is a highly lethal syndrome that has, until recently, suffered from a lack of clinically efficient targeted therapeutics. The cardiac troponin I interacting kinase (TNNI3K) exacerbates ischemia-reperfusion (IR) injury via oxidative stress, thereby promoting cardiomyocyte death. In this current study, we designed and synthesized 35 novel TNNI3K inhibitors with a pyrido[4,5]thieno [2,3-d] pyrimidine scaffold. In vitro results indicated that some of the inhibitors exhibited sub-micromolar TNNI3K inhibitory capacity and good kinase selectivity, as well as cytoprotective activity, in an oxygen-glucose deprivation (OGD) injury cardiomyocyte model. Furthermore, investigation of the mechanism of the representative derivative compound 6o suggested it suppresses pyroptosis and apoptosis in cardiomyocytes by interfering with p38MAPK activation, which was further confirmed in a murine myocardial infarction injury model. In vivo results indicate that compound 6o can markedly reduce myocardial infarction size and alleviate cardiac tissue damage in rats. In brief, our results provide the basis for further development of novel TNNI3K inhibitors for targeted MI therapy. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112314

文献信息

• Discovery of novel TNNI3K inhibitor suppresses pyroptosis and apoptosis in murine myocardial infarction injury
  作者：Haiying Pang、Ning Wang、Jinlong Chai、Xiaoyun Wang、Yuehua Zhang、Zhiang Bi、Wenbin Wu、Gu He

  DOI：10.1016/j.ejmech.2020.112314

  日期：2020.7

  Myocardial infarction (MI) injury is a highly lethal syndrome that has, until recently, suffered from a lack of clinically efficient targeted therapeutics. The cardiac troponin I interacting kinase (TNNI3K) exacerbates ischemia-reperfusion (IR) injury via oxidative stress, thereby promoting cardiomyocyte death. In this current study, we designed and synthesized 35 novel TNNI3K inhibitors with a pyrido[4,5]thieno [2,3-d] pyrimidine scaffold. In vitro results indicated that some of the inhibitors exhibited sub-micromolar TNNI3K inhibitory capacity and good kinase selectivity, as well as cytoprotective activity, in an oxygen-glucose deprivation (OGD) injury cardiomyocyte model. Furthermore, investigation of the mechanism of the representative derivative compound 6o suggested it suppresses pyroptosis and apoptosis in cardiomyocytes by interfering with p38MAPK activation, which was further confirmed in a murine myocardial infarction injury model. In vivo results indicate that compound 6o can markedly reduce myocardial infarction size and alleviate cardiac tissue damage in rats. In brief, our results provide the basis for further development of novel TNNI3K inhibitors for targeted MI therapy. (C) 2020 Elsevier Masson SAS. All rights reserved.