7-O-descarbamoyl-7-hydroxygeldanamycin | 156222-90-1

• 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-descarbamoyl-7-hydroxygeldanamycin
• 英文别名: 7-O-decarbamoylgeldanamycin；(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-9,13-dihydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaene-3,20,22-trione
• CAS: 156222-90-1
• 化学式: C₂₈H₃₉NO₈
• 分子量: 517.62
• InChiKey: AZMUWZBGFKDVCZ-XXAUIAHHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  37
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  131
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  7-O-descarbamoyl-7-hydroxygeldanamycin 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 7-O-carbazoyl-17-(2-fluoroethyl)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
• 作为产物：
  描述：

  格尔德霉素 在 potassium tert-butylate 作用下， 以 二甲基亚砜 为溶剂， 生成 7-O-descarbamoyl-7-hydroxygeldanamycin
  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

• [EN] SYNTHESIS OF RESORCYLIC ACID LACTONES USEFUL AS THERAPEUTIC AGENTS<br/>[FR] SYNTHÈSE DE LACTONES D'ACIDE RÉSORCYLIQUE UTILES EN TANT QU'AGENTS THÉRAPEUTIQUES
  申请人：UNIV STRASBOURG

  公开号：WO2009091921A1

  公开（公告）日：2009-07-23

  Disclosed are macrocyclic compounds of formulae I, I', II, II', III, III', IV, and V, which are analogs of the pochonin resorcylic acid lactones, pharmaceutical compositions comprising the compounds, and methods and uses comprising the compounds for the treatment of diseases mediated by kinases and Heat Shock Protein 90 HSP90.

  公开的是式I、I'、II、II'、III、III'、IV和V的大环化合物，它们是pochonin resorcylic acid lactones的类似物，包括这些化合物的药物组合物，以及包括这些化合物用于治疗由激酶和热休克蛋白90 HSP90介导的疾病的方法和用途。
• ANALOGS OF ANSAMYCIN AND PHARMACEUTICAL COMPOSITIONS THEREOF
  申请人：Tao Chunlin

  公开号：US20080234246A1

  公开（公告）日：2008-09-25

  Analogs of geldanamycin (an ansamycin), pharmaceutical formulations comprising such analogs, and methods of use (e.g., treating tumors).
• MICELLE COMPOSITION OF POLYMER AND PASSENGER DRUG
  申请人：Kwon Glen S.

  公开号：US20120309780A1

  公开（公告）日：2012-12-06

  Hydrophobic drugs become more practical for treatments by being encapsulated in micelle compositions for increasing solubility. Micelle compositions may include an excipient tocopherol and/or prodrug formulations of the drug. Micelles extend the time period the drug remains in the micelles to improve drug circulation time and thereby drug delivery. Hydrophobic drugs for micelle encapsulation may include rapamycin, geldanamycin, and paclitaxel. Administration of these micelle compositions does not require Cremophor EL or Tween 80, avoiding serious side effects associated with these products which would previously accompany such drug administration.
• US7816346B2
  申请人：——

  公开号：US7816346B2

  公开（公告）日：2010-10-19
• 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.