5-amino-N-quinolin-8-ylfuran-2-carboxamide | 1368129-69-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 5-amino-N-quinolin-8-ylfuran-2-carboxamide
• CAS: 1368129-69-4
• 化学式: C₁₄H₁₁N₃O₂
• 分子量: 253.26
• InChiKey: DWBYFLMEINXSAR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  81.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-amino-N-quinolin-8-ylfuran-2-carboxamide 、 顺式-2,3-降冰片烷二羧酸酐 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以20%的产率得到5-(cis,endo-1,3-dioxooctahydro-2H-4,7-methanoisoindol-2-yl)-N-quinolin-8-ylfuran-2-carboxamide
  参考文献：
  名称：

  Wnt Inhibition Correlates with Human Embryonic Stem Cell Cardiomyogenesis: A Structure–Activity Relationship Study Based on Inhibitors for the Wnt Response

  摘要：

  Human embryonic stem cell-based high-content screening of 550 known signal transduction modulators showed that one "lead" (1, a recently described inhibitor of the proteolytic degradation of Axin) stimulated cardiomyogenesis. Because Axin controls canonical Wnt signaling, we conducted an investigation to determine whether the cardiogenic activity of 1 is Wnt-dependent, and we developed a structure-activity relationship to optimize the cardiogenic properties of 1. We prepared analogues with a range of potencies (low nanomolar to inactive) for Wnt/beta-catenin inhibition and for cardiogenic induction. Both functional activities correlated positively (r(2) = 0.72). The optimal compounds induced cardiogenesis 1.5-fold greater than 1 at 30-fold lower concentrations. In contrast, no correlation was observed for cardiogenesis and modulation of transforming growth factor beta (TGF beta)/Smad signaling that prominently influences cardiogenesis. Taken together, these data show that Wnt signaling inhibition is essential for cardiogenic activity and that the pathway can be targeted for the design of druglike cardiogenic molecules.

  DOI：

  10.1021/jm2010223
• 作为产物：
  描述：

  5-硝基-2-糠酸 在 吡啶 、 氯化亚砜 、 palladium on activated charcoal 、 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 21.0h， 生成 5-amino-N-quinolin-8-ylfuran-2-carboxamide
  参考文献：
  名称：

  Wnt Inhibition Correlates with Human Embryonic Stem Cell Cardiomyogenesis: A Structure–Activity Relationship Study Based on Inhibitors for the Wnt Response

  摘要：

  Human embryonic stem cell-based high-content screening of 550 known signal transduction modulators showed that one "lead" (1, a recently described inhibitor of the proteolytic degradation of Axin) stimulated cardiomyogenesis. Because Axin controls canonical Wnt signaling, we conducted an investigation to determine whether the cardiogenic activity of 1 is Wnt-dependent, and we developed a structure-activity relationship to optimize the cardiogenic properties of 1. We prepared analogues with a range of potencies (low nanomolar to inactive) for Wnt/beta-catenin inhibition and for cardiogenic induction. Both functional activities correlated positively (r(2) = 0.72). The optimal compounds induced cardiogenesis 1.5-fold greater than 1 at 30-fold lower concentrations. In contrast, no correlation was observed for cardiogenesis and modulation of transforming growth factor beta (TGF beta)/Smad signaling that prominently influences cardiogenesis. Taken together, these data show that Wnt signaling inhibition is essential for cardiogenic activity and that the pathway can be targeted for the design of druglike cardiogenic molecules.

  DOI：

  10.1021/jm2010223

文献信息

• Wnt Inhibition Correlates with Human Embryonic Stem Cell Cardiomyogenesis: A Structure–Activity Relationship Study Based on Inhibitors for the Wnt Response
  作者：Marion Lanier、Dennis Schade、Erik Willems、Masanao Tsuda、Sean Spiering、Jaroslaw Kalisiak、Mark Mercola、John R. Cashman

  DOI：10.1021/jm2010223

  日期：2012.1.26

  Human embryonic stem cell-based high-content screening of 550 known signal transduction modulators showed that one "lead" (1, a recently described inhibitor of the proteolytic degradation of Axin) stimulated cardiomyogenesis. Because Axin controls canonical Wnt signaling, we conducted an investigation to determine whether the cardiogenic activity of 1 is Wnt-dependent, and we developed a structure-activity relationship to optimize the cardiogenic properties of 1. We prepared analogues with a range of potencies (low nanomolar to inactive) for Wnt/beta-catenin inhibition and for cardiogenic induction. Both functional activities correlated positively (r(2) = 0.72). The optimal compounds induced cardiogenesis 1.5-fold greater than 1 at 30-fold lower concentrations. In contrast, no correlation was observed for cardiogenesis and modulation of transforming growth factor beta (TGF beta)/Smad signaling that prominently influences cardiogenesis. Taken together, these data show that Wnt signaling inhibition is essential for cardiogenic activity and that the pathway can be targeted for the design of druglike cardiogenic molecules.