17-Cyclopropylmethylamino-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: 17-Cyclopropylmethylamino-17-demethoxygeldanamycin
• 英文别名: 17-cyclopropylmethylaminogeldanamycin；[(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-(cyclopropylmethylamino)-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] carbamate
• 化学式: C₃₂H₄₅N₃O₈
• 分子量: 599.725
• InChiKey: QHYNONUOKKSQBB-JEPUBLIZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  43
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  166
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  格尔德霉素 、 环丙基甲胺 以 二氯甲烷 为溶剂， 反应 2.0h， 以84%的产率得到17-Cyclopropylmethylamino-17-demethoxygeldanamycin
  参考文献：
  名称：

  Ansamycin formulations and methods of use thereof

  摘要：

  本文提供了金黄霉素类似物的固态形式，其中包括制备和使用这些化合物的药物组合物和晶体生长抑制剂。此外，还提供了用于治疗癌症、肿瘤疾病状态和/或高增殖性疾病的方法，以及抑制热休克蛋白90（“Hsp90”）的方法。

  公开号：

  US20080221077A1

文献信息

• Synthesis and biological activities of novel 17-aminogeldanamycin derivatives
  作者：Zong-Qiang Tian、Yaoquan Liu、Dan Zhang、Zhan Wang、Steven D. Dong、Christopher W. Carreras、Yiqing Zhou、Giulio Rastelli、Daniel V. Santi、David C. Myles

  DOI：10.1016/j.bmc.2004.07.053

  日期：2004.10

  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.
• Ansamycin formulations and methods of use thereof
  申请人：Austad Brian C.

  公开号：US20090062528A1

  公开（公告）日：2009-03-05

  Provided herein, inter alia, are solid forms of geldanamycin analogs, pharmaceutical compositions comprising a geldanamycin analog and a crystallization inhibitor, methods of making and using such compositions. Additionally, provided are methods for the treatment of cancer, a neoplastic disease state and/or a hyperproliferative disorder, and methods of inhibiting Heat Shock Protein 90 (“Hsp90”).
• 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.
• US7947670B2
  申请人：——

  公开号：US7947670B2

  公开（公告）日：2011-05-24
• US8283343B2
  申请人：——

  公开号：US8283343B2

  公开（公告）日：2012-10-09