(6s)-6,15,15,18-Tetramethyl-17-Oxo-2,3,4,5,6,7,14,15,16,17-Decahydro-1h-8,12-(Metheno)[1,4,9]triazacyclotetradecino[9,8-A]indole-9-Carboxamide | 1301177-33-2

• 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: (6s)-6,15,15,18-Tetramethyl-17-Oxo-2,3,4,5,6,7,14,15,16,17-Decahydro-1h-8,12-(Metheno)[1,4,9]triazacyclotetradecino[9,8-A]indole-9-Carboxamide
• 英文别名: (16S)-5,5,9,16-tetramethyl-7-oxo-2,14,17-triazatetracyclo[16.3.1.02,10.03,8]docosa-1(22),3(8),9,18,20-pentaene-19-carboxamide
• CAS: 1301177-33-2
• 化学式: C₂₄H₃₂N₄O₂
• 分子量: 408.544
• InChiKey: DGOVAFNEOBXFEF-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  30
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  89.2
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (6s)-6,15,15,18-Tetramethyl-17-Oxo-2,3,4,5,6,7,14,15,16,17-Decahydro-1h-8,12-(Metheno)[1,4,9]triazacyclotetradecino[9,8-A]indole-9-Carboxamide 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 C₂₇H₃₇N₅O₃
  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

文献信息

• Design and SAR of macrocyclic Hsp90 inhibitors with increased metabolic stability and potent cell-proliferation activity
  作者：Christoph W. Zapf、Jonathan D. Bloom、Jamie L. McBean、Russell G. Dushin、Thomas Nittoli、Charles Ingalls、Alan G. Sutherland、John P. Sonye、Clark N. Eid、Jennifer Golas、Hao Liu、Frank Boschelli、Yongbo Hu、Erik Vogan、Jeremy I. Levin

  DOI：10.1016/j.bmcl.2011.02.101

  日期：2011.4

  A novel series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. A basic nitrogen within the tether linking the aniline nitrogen atom to a tetrahydroindolone moiety allowed access to compounds with good physical properties. Important structure-activity relationship information was obtained from this series which led to the discovery of a soluble and stable compound which is potent in an Hsp90 binding and cell-proliferation assay. (C) 2011 Elsevier Ltd. All rights reserved.
• Macrocyclic lactams as potent Hsp90 inhibitors with excellent tumor exposure and extended biomarker activity
  作者：Christoph W. Zapf、Jonathan D. Bloom、Jamie L. McBean、Russell G. Dushin、Thomas Nittoli、Mercy Otteng、Charles Ingalls、Jennifer M. Golas、Hao Liu、Judy Lucas、Frank Boschelli、Yongbo Hu、Erik Vogan、Jeremy I. Levin

  DOI：10.1016/j.bmcl.2011.03.112

  日期：2011.6

  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.