N-(8-methyl-7-(1-methylpiperidin-4-yloxy)-2-oxo-2H-chromen-3-yl)-3-(3-methylbut-2-enyl)-4-(prop-2-ynyloxy)benzamide | 1415574-37-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: N-(8-methyl-7-(1-methylpiperidin-4-yloxy)-2-oxo-2H-chromen-3-yl)-3-(3-methylbut-2-enyl)-4-(prop-2-ynyloxy)benzamide
• 英文别名: 3-(3-methylbut-2-enyl)-N-[8-methyl-7-(1-methylpiperidin-4-yl)oxy-2-oxochromen-3-yl]-4-prop-2-ynoxybenzamide
• CAS: 1415574-37-6
• 化学式: C₃₁H₃₄N₂O₅
• 分子量: 514.621
• InChiKey: JCRBEZBTQOUTPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-hydroxy-N-(8-methyl-7-(1-methylpiperidin-4-yloxy)-2-oxo-2H-chromen-3-yl)-3-(3-methylbut-2-enyl)benzamide 、 2-丙炔-1-醇 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以27%的产率得到N-(8-methyl-7-(1-methylpiperidin-4-yloxy)-2-oxo-2H-chromen-3-yl)-3-(3-methylbut-2-enyl)-4-(prop-2-ynyloxy)benzamide
  参考文献：
  名称：

  3D-QSAR-Assisted Design, Synthesis, and Evaluation of Novobiocin Analogues

  摘要：

  Hsp90 is an attractive therapeutic target for the treatment of cancer. Extensive structural modifications to novobiocin, the first Hsp90 C-terminal inhibitor discovered, have produced a library of novobiocin analogues and revealed some structure activity relationships. On the basis of the most potent novobiocin analogues generated from prior studies, a three-dimensional quantitative structure activity (3D QSAR) model was built. In addition, a new set of novobiocin analogues containing various structural features supported by the 3D QSAR model were synthesized and evaluated against two breast cancer cell lines. Several new inhibitors produced antiproliferative activity at midnanomolar concentrations, which results through Hsp90 inhibition.

  DOI：

  10.1021/ml300275g

文献信息

• Coumarin based Hsp90 inhibitors with urea and ether substituents
  申请人：University of Kansas

  公开号：US10030006B2

  公开（公告）日：2018-07-24

  Compounds of the formulas: wherein: R1-R4, X1, Y1, and A are as defined herein are provided. Pharmaceutical compositions of the compounds are also provided. In some aspects, these compounds are are useful for the treatment of a disease or disorder. In some embodiments, the disease or disorder is a proliferative disease such as cancer.

  提供了以下式子的化合物： 其中：提供了 R1-R4、X1、Y1 和 A 如本文所定义的化合物。还提供了这些化合物的药物组合物。在某些方面，这些化合物可用于治疗疾病或紊乱。在某些实施方案中，疾病或紊乱是增殖性疾病，如癌症。
• Coumarin based HSP90 inhibitors with urea and ether substituents
  申请人：University of Kansas

  公开号：US10745386B2

  公开（公告）日：2020-08-18

  Compounds of the formulas: wherein: R1-R4, X1, Y1, and A are as defined herein are provided. Pharmaceutical compositions of the compounds are also provided. In some aspects, these compounds are useful for the treatment of a disease or disorder. In some embodiments, the disease or disorder is a proliferative disease such as cancer.

  下列公式的化合物：.....： 其中提供了 R1-R4、X1、Y1 和 A 如本文所定义的化合物。还提供了这些化合物的药物组合物。在某些方面，这些化合物可用于治疗疾病或紊乱。在某些实施方案中，疾病或紊乱是增殖性疾病，如癌症。
• [EN] COUMARIN BASED HSP90 INHIBITORS WITH UREA AND ETHER SUBSTITUENTS<br/>[FR] INHIBITEURS HSP90 À BASE DE COUMARINE À SUBSTITUANTS D'URÉE ET D'ÉTHER
  申请人：UNIV KANSAS

  公开号：WO2015070238A3

  公开（公告）日：2015-07-16
• COUMARIN BASED HSP90 INHIBITORS WITH UREA AND ETHER SUBSTITUENTS
  申请人：The University of Kansas

  公开号：EP3068778A2

  公开（公告）日：2016-09-21
• 3D-QSAR-Assisted Design, Synthesis, and Evaluation of Novobiocin Analogues
  作者：Huiping Zhao、Elisabetta Moroni、Bin Yan、Giorgio Colombo、Brian S. J. Blagg

  DOI：10.1021/ml300275g

  日期：2013.1.10

  Hsp90 is an attractive therapeutic target for the treatment of cancer. Extensive structural modifications to novobiocin, the first Hsp90 C-terminal inhibitor discovered, have produced a library of novobiocin analogues and revealed some structure activity relationships. On the basis of the most potent novobiocin analogues generated from prior studies, a three-dimensional quantitative structure activity (3D QSAR) model was built. In addition, a new set of novobiocin analogues containing various structural features supported by the 3D QSAR model were synthesized and evaluated against two breast cancer cell lines. Several new inhibitors produced antiproliferative activity at midnanomolar concentrations, which results through Hsp90 inhibition.