17-methylamino-17-demethoxygeldanamycin | 71952-93-7

• 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: 17-methylamino-17-demethoxygeldanamycin
• 英文别名: [(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-19-(methylamino)-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] carbamate
• CAS: 71952-93-7
• 化学式: C₂₉H₄₁N₃O₈
• 分子量: 559.66
• InChiKey: AYIAJGNRKFNJHO-ZAYXLYBCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  40
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  166
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  17-methylamino-17-demethoxygeldanamycin 在 三乙酰氧基硼氢化钠 、 戴斯-马丁氧化剂 、 sodium sulfate 作用下， 以 氯仿 、 1,2-二氯乙烷 为溶剂， 反应 25.0h， 生成 11-(benzylamino)-17-(methylamino)geldanamycin
  参考文献：
  名称：

  格尔德霉素衍生物对erbB-2癌基因的抑制作用：合成，作用机理和构效关系。

  摘要：

  erbB-2癌基因的过度表达与乳腺癌，卵巢癌和胃癌的不良预后有关。人们发现，天然存在的苯并醌类安沙霉素抗生素除草霉素A，格尔德霉素（GDM）和二氢格尔德霉素会有效消耗培养的人乳腺癌SKBR-3细胞中的185 erbB-2癌蛋白p185。化学努力地选择性修饰GDM的ansa环，在体外和体内均提供了更高效能的衍生物。类似物证明，对带有人erbB-2转染的Fisher大鼠胚胎细胞的nu / nu裸鼠全身性给药后，在细胞培养物中和体内p185磷酸酪氨酸的抑制作用。ansa环中的官能团修饰是立体选择性和区域特异性的，无需保护策略。抗-erbB-2活性所需的基本官能团是7-氨基甲酸酯和2,3-双键。允许修改其他位置的官能团。描述了1-5、7-9、11、15和22取代的格尔德霉素的结构活性关系。

  DOI：

  10.1021/jm00019a011
• 作为产物：
  描述：

  格尔德霉素 、 甲胺 以 1,2-二氯乙烷 为溶剂， 反应 20.0h， 生成 17-methylamino-17-demethoxygeldanamycin
  参考文献：
  名称：

  Synthesis and biological activities of novel 17-aminogeldanamycin derivatives

  摘要：

  Geldanamycin interferes with the action of heat shock protein 90 (Hsp90) by binding to the N-terminal ATP binding site and inhibiting an essential ATPase activity. In a program directed toward finding potent, water soluble inhibitors of Hsp90, we prepared a library of over sixty 17-alkylamino-17-demethoxygeldanamycin analogs, and compared their affinity for Hsp90, ability to inhibit growth of SKBr3 mammalian cells, and in selected cases, water solubility. Over 20 analogs showed cell growth inhibition potencies similar to that of 17-allylamino-17-demethoxygeldanamycin (17-AAG), the front-runner geldanamycin analog that is currently in multiple clinical trials. Many of these analogs showed water solubility properties that were desirable for formulation. One of the most potent and water-soluble analogs in the series was 17-(2-dimethylaminoethyl)amino-17-demethoxygeldanamycin (17-DMAG), which was independently prepared by the NCI and will soon enter clinical trials. Importantly, the binding affinity of these analogs to the molecular target Hsp90 does not correlate well with their cytotoxicity in SKBr3 cells. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.07.053

文献信息

• ANALOGS OF BENZOQUINONE-CONTAINING ANSAMYCINS AND METHODS OF USE THEREOF
  申请人：Adams Julian

  公开号：US20090253653A1

  公开（公告）日：2009-10-08

  The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog.

  本发明提供了苯醌含有的ansamycins的类似物及其用于治疗和调节与高增殖相关的疾病，如癌症。本发明提供了苯醌含有的ansamycins的类似物，其中苯醌被还原为氢醌，并通过与适当酸反应被固定，优选那些增加所得到的17-铵氢醌ansamycin类似物的溶解度和空气稳定性的酸。
• Analogs of Benzoquinone-Containing Ansamycins and Methods of Use Thereof
  申请人：Adams Julian

  公开号：US20090062250A1

  公开（公告）日：2009-03-05

  The present invention provides analogs of benzoquinone-containing ansamycins and uses thereof for treating and modulating disorders associated with hyperproliferation, such as cancer. The present invention provides analogs of benzoquinone-containing ansamycins where the benzoquinone is reduced to a hydroquinone and trapped by reaction with a suitable acid, preferably ones that increase the solubility and air stability of the resulting 17-ammonium hydroquinone ansamycin analog.

  本发明提供了苯醌含量的ansamycins的类似物及其用于治疗和调节与过度增殖有关的疾病，如癌症。本发明提供了苯醌含量的ansamycins的类似物，其中苯醌被还原为一个氢醌，并通过与适当酸的反应被固定，优选增加所得到的17-铵盐氢醌ansamycin类似物的溶解性和空气稳定性的酸。
• Assays and Implements for Determining and Modulating HSP90 Binding Activity
  申请人：Kamal Adeela

  公开号：US20080318338A1

  公开（公告）日：2008-12-25

  Ligand binding assays as applied to HSP90s as receptors or ligands, and reagents useful therefore, are described and claimed, as are methods of assaying for HSP90 modulators and methods of using the resulting products identified thereby.
• METHODS, COMPOSITIONS, AND KITS FOR THE TREATMENT OF CANCER
  申请人：Haggerty Timothy J.

  公开号：US20140335050A1

  公开（公告）日：2014-11-13

  The invention features methods, compositions, and kits for the administration of an HSP90 inhibitor, OBAA, flunarizine, aphidicolin, damnacanthal, dantrolene, or an analog thereof, alone, or in combination with, e.g., a TAA, an antigen-binding scaffold (e.g., an antibody, a soluble T cell receptor, or a chimeric receptor) specific for a TAA, a cell (e.g., a white blood cell that targets a cancer cell), and/or an IFN-β receptor agonist or an IFN-γ receptor agonist, for the treatment of cancer.
• Phospholipid Ether Analogs as Cancer-Targeting Drug Vehicles
  申请人：Cellectar Biosciences, Inc.

  公开号：US20160136290A1

  公开（公告）日：2016-05-19

  The present invention is directed to therapeutic compounds capable of targeting cancer cells and cancer stem cells. The present invention is further directed to compositions comprising these therapeutic compounds and methods of treating cancer comprising administering these therapeutic compounds.