(15R,16S)-13-acetyl-5,5,9,15,16-pentamethyl-7-oxo-2,13,17-triazatetracyclo[16.3.1.02,10.03,8]docosa-1(22),3(8),9,18,20-pentaene-19-carboxamide | 1330555-95-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (15R,16S)-13-acetyl-5,5,9,15,16-pentamethyl-7-oxo-2,13,17-triazatetracyclo[16.3.1.02,10.03,8]docosa-1(22),3(8),9,18,20-pentaene-19-carboxamide
• CAS: 1330555-95-7
• 化学式: C₂₇H₃₆N₄O₃
• 分子量: 464.608
• InChiKey: JNXQZEQTCNUMCM-WBVHZDCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  34
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  97.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (2S,3S)-3-amino-2-methyl butyric acid 在 N-甲基吗啉 、 ammonium hydroxide 、 tris-(dibenzylideneacetone)dipalladium(0) 、 lithium aluminium tetrahydride 、 乙醇 、 双氧水 、 三乙酰氧基硼氢化钠 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三乙胺 、 三氟乙酸 、 sodium hydroxide 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 二甲基亚砜 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 (15R,16S)-13-acetyl-5,5,9,15,16-pentamethyl-7-oxo-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：

  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

文献信息

• Discovery of a stable macrocyclic o-aminobenzamide Hsp90 inhibitor which significantly decreases tumor volume in a mouse xenograft model
  作者：Christoph W. Zapf、Jonathan D. Bloom、Zhong Li、Russell G. Dushin、Thomas Nittoli、Mercy Otteng、Antonia Nikitenko、Jennifer M. Golas、Hao Liu、Judy Lucas、Frank Boschelli、Erik Vogan、Andrea Olland、Mark Johnson、Jeremy I. Levin

  DOI：10.1016/j.bmcl.2011.05.102

  日期：2011.8

  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.