N1,N6-bis(8-methyl-7-(1-methylpiperidin-4-yloxy)-2-oxo-2H-chromen-3-yl)adipamide | 1332636-91-5

• 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: N1,N6-bis(8-methyl-7-(1-methylpiperidin-4-yloxy)-2-oxo-2H-chromen-3-yl)adipamide
• 英文别名: N,N'-bis[8-methyl-7-(1-methylpiperidin-4-yl)oxy-2-oxochromen-3-yl]hexanediamide
• CAS: 1332636-91-5
• 化学式: C₃₈H₄₆N₄O₈
• 分子量: 686.805
• InChiKey: YATRTMRBDCQDNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  50
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3-Amino-8-methyl-7-(1-methylpiperidin-4-yl)oxychromen-2-one 、 己二酰氯 在 吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 15.25h， 以89%的产率得到N1,N6-bis(8-methyl-7-(1-methylpiperidin-4-yloxy)-2-oxo-2H-chromen-3-yl)adipamide
  参考文献：
  名称：

  Targeting the Heat Shock Protein 90 Dimer with Dimeric Inhibitors

  摘要：

  The design, synthesis, and biological evaluation of conformationally constrained coumermycin Al analogues are reported. Compounds were evaluated against both breast cancer (SKBr3 and MCF7) and prostate cancer (PC3 mm2, A549, and HT29) cell lines. Non-noviosylated coumermycin Al analogues that manifest potent antiproliferative activity resulting from Hsp90 inhibition are provided, wherein replacement of the stereochemically complex noviose sugar with readily available piperidine rings resulted in similar to 100 fold increase in antiproliferative activities as compared to coumermycin Al, producing small molecule Hsp90 inhibitors that exhibit nanomolar activities.

  DOI：

  10.1021/jm200553w

文献信息

• DYNAMIC INHIBITORS OF HEAT SHOCK PROTEIN 90
  申请人：Blagg Brian S.J.

  公开号：US20120309702A1

  公开（公告）日：2012-12-06

  An inhibitor of heat shock protein 90 (HSP90) can include a coumermycin A1 analog having a structure that inhibits HSP90 greater than coumermycin A1. That is, the coumermycin A1 analog is not coumermycin A1. The coumermycin A1 analog can have an antiproliferative biological activity, which can be superior to coumermycin A1. The activity can include the coumermycin A1 analog inhibiting a C-terminus of HSP90.
• US9056104B2
  申请人：——

  公开号：US9056104B2

  公开（公告）日：2015-06-16
• Targeting the Heat Shock Protein 90 Dimer with Dimeric Inhibitors
  作者：Bhaskar Reddy Kusuma、Laura B. Peterson、Huiping Zhao、George Vielhauer、Jeffrey Holzbeierlein、Brian S. J. Blagg

  DOI：10.1021/jm200553w

  日期：2011.9.22

  The design, synthesis, and biological evaluation of conformationally constrained coumermycin Al analogues are reported. Compounds were evaluated against both breast cancer (SKBr3 and MCF7) and prostate cancer (PC3 mm2, A549, and HT29) cell lines. Non-noviosylated coumermycin Al analogues that manifest potent antiproliferative activity resulting from Hsp90 inhibition are provided, wherein replacement of the stereochemically complex noviose sugar with readily available piperidine rings resulted in similar to 100 fold increase in antiproliferative activities as compared to coumermycin Al, producing small molecule Hsp90 inhibitors that exhibit nanomolar activities.