13,16,16-trimethyl-14,8-dioxo-14,15,16,17-tetrahydro-11H-3,7-diaza-1(1,2)-indola-2(1,3)-benzenacyclononaphane-24-carbonitrile | 1327336-91-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: 13,16,16-trimethyl-14,8-dioxo-14,15,16,17-tetrahydro-11H-3,7-diaza-1(1,2)-indola-2(1,3)-benzenacyclononaphane-24-carbonitrile
• CAS: 1327336-91-3
• 化学式: C₂₃H₂₆N₄O₂
• 分子量: 390.485
• InChiKey: UBPZLEHYBFRPCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.29
• 重原子数：
  29.0
• 可旋转键数：
  0.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  86.92
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  13,16,16-trimethyl-14,8-dioxo-14,15,16,17-tetrahydro-11H-3,7-diaza-1(1,2)-indola-2(1,3)-benzenacyclononaphane-24-carbonitrile 在 双氧水 、 sodium hydroxide 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 生成 5,5,9-Trimethyl-7,12-dioxo-2,13,17-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：

  Macrocyclic lactams as potent Hsp90 inhibitors with excellent tumor exposure and extended biomarker activity

  摘要：

  A novel series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. In continuation of our research in this area, macrocyclic amides and lactams were explored to reduce the risk of hERG liabilities. This effort culminated in the discovery of compound 38, which showed a favorable in vitro profile, and efficiently suppressed proliferation of several relevant cell lines. This compound showed prolonged Hsp90-inhibitory activity at least 24 h post-administration, consistent with elevated and prolonged exposure in the tumor. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.112
• 作为产物：
  描述：

  在 tris-(dibenzylideneacetone)dipalladium(0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三氟乙酸 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 甲苯 为溶剂， 生成 13,16,16-trimethyl-14,8-dioxo-14,15,16,17-tetrahydro-11H-3,7-diaza-1(1,2)-indola-2(1,3)-benzenacyclononaphane-24-carbonitrile
  参考文献：
  名称：

  Macrocyclic lactams as potent Hsp90 inhibitors with excellent tumor exposure and extended biomarker activity

  摘要：

  A novel series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. In continuation of our research in this area, macrocyclic amides and lactams were explored to reduce the risk of hERG liabilities. This effort culminated in the discovery of compound 38, which showed a favorable in vitro profile, and efficiently suppressed proliferation of several relevant cell lines. This compound showed prolonged Hsp90-inhibitory activity at least 24 h post-administration, consistent with elevated and prolonged exposure in the tumor. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.112