7-O-(methoxycarbamoyl)-17-[2-(dimethylamino)ethyl]amino-7-O-decarbamoyl-17-demethoxygeldanamycin

• 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: 7-O-(methoxycarbamoyl)-17-[2-(dimethylamino)ethyl]amino-7-O-decarbamoyl-17-demethoxygeldanamycin
• 英文别名: [(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-[2-(dimethylamino)ethylamino]-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] N-methoxycarbamate
• 化学式: C₃₃H₅₀N₄O₉
• 分子量: 646.781
• InChiKey: XHSXXMHOOVTJGW-COFSWBFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  46
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  165
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  格尔德霉素 在 4-二甲氨基吡啶 、 potassium tert-butylate 作用下， 以 二氯甲烷 、 二甲基亚砜 、 1,2-二氯乙烷 为溶剂， 反应 2.0h， 生成 7-O-(methoxycarbamoyl)-17-[2-(dimethylamino)ethyl]amino-7-O-decarbamoyl-17-demethoxygeldanamycin
  参考文献：
  名称：

  Structure-based design of 7-carbamate analogs of geldanamycin

  摘要：

  The 7-carbamate groups of geldanamycin and its 17-(2-dimethylaminoethyl)amino-17-demethoxy derivative (17-DMAG) bind the N-terminal domain of Hsp90 by establishing a network of hydrogen bonds which involve four buried water molecules. In this study, a structure-based approach was used to investigate the effects of displacing some of these waters by modification of the 7-carbamate. A general loss of binding to human Hsp90 was observed, except for replacement of the carbamate with a hydroxamate group which gave an analog with weak activity. Modeling of Hsp90-ligand interactions suggested that the hydroxamate was not able to displace the buried water molecules, while bulkier substituents able to do so proved inactive. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.013

文献信息

• Structure-based design of 7-carbamate analogs of geldanamycin
  作者：Giulio Rastelli、Zong-Qiang Tian、Zhan Wang、David Myles、Yaoquan Liu

  DOI：10.1016/j.bmcl.2005.08.013

  日期：2005.11

  The 7-carbamate groups of geldanamycin and its 17-(2-dimethylaminoethyl)amino-17-demethoxy derivative (17-DMAG) bind the N-terminal domain of Hsp90 by establishing a network of hydrogen bonds which involve four buried water molecules. In this study, a structure-based approach was used to investigate the effects of displacing some of these waters by modification of the 7-carbamate. A general loss of binding to human Hsp90 was observed, except for replacement of the carbamate with a hydroxamate group which gave an analog with weak activity. Modeling of Hsp90-ligand interactions suggested that the hydroxamate was not able to displace the buried water molecules, while bulkier substituents able to do so proved inactive. (c) 2005 Elsevier Ltd. All rights reserved.