(4S,5S)-13,16,16,4,5-pentamethyl-14-oxo-14,15,16,17-tetrahydro-11H-3,6-diaza-1(1,2)-indola-2(1,3)-benzenacyclononaphane-24-carbonitrile | 1330556-11-0

• 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: (4S,5S)-13,16,16,4,5-pentamethyl-14-oxo-14,15,16,17-tetrahydro-11H-3,6-diaza-1(1,2)-indola-2(1,3)-benzenacyclononaphane-24-carbonitrile
• CAS: 1330556-11-0
• 化学式: C₂₅H₃₂N₄O
• 分子量: 404.555
• InChiKey: HWSMTZNEOCCJTA-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.54
• 重原子数：
  30.0
• 可旋转键数：
  0.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  69.85
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (4S,5S)-13,16,16,4,5-pentamethyl-14-oxo-14,15,16,17-tetrahydro-11H-3,6-diaza-1(1,2)-indola-2(1,3)-benzenacyclononaphane-24-carbonitrile 在 乙醇 、 四丁基氟化铵 、 双氧水 、 三乙酰氧基硼氢化钠 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二甲基亚砜 、 1,2-二氯乙烷 为溶剂， 生成 (15S,16S)-14-(2-hydroxyethyl)-5,5,9,15,16-pentamethyl-7-oxo-2,14,17-triazatetracyclo[16.3.1.02,10.03,8]docosa-1(22),3(8),9,18,20-pentaene-19-carboxamide
  参考文献：
  名称：

  Discovery of a stable macrocyclic o-aminobenzamide Hsp90 inhibitor which significantly decreases tumor volume in a mouse xenograft model

  摘要：

  An extension of our previously reported series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. Addition of a second methyl group to the tether provided analogs that show increased potency in binding as well as cell-proliferation assays and, more importantly, are stable toward microsomes. We wish to disclose the discovery of a macrocycle which showed impressive biomarker activity 24-h post dosing and which demonstrated prolonged exposure in tumors. When studied in a lung cancer xenograft model, the compound demonstrated significant tumor size reduction. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.102
• 作为产物：
  描述：

  在 tris-(dibenzylideneacetone)dipalladium(0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 甲苯 为溶剂， 生成 (4S,5S)-13,16,16,4,5-pentamethyl-14-oxo-14,15,16,17-tetrahydro-11H-3,6-diaza-1(1,2)-indola-2(1,3)-benzenacyclononaphane-24-carbonitrile
  参考文献：
  名称：

  Discovery of a stable macrocyclic o-aminobenzamide Hsp90 inhibitor which significantly decreases tumor volume in a mouse xenograft model

  摘要：

  An extension of our previously reported series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. Addition of a second methyl group to the tether provided analogs that show increased potency in binding as well as cell-proliferation assays and, more importantly, are stable toward microsomes. We wish to disclose the discovery of a macrocycle which showed impressive biomarker activity 24-h post dosing and which demonstrated prolonged exposure in tumors. When studied in a lung cancer xenograft model, the compound demonstrated significant tumor size reduction. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.102