5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[2-[2-[2-[2-[3-[6-amino-8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]purin-9-yl]propylamino]ethoxy]ethoxy]ethoxy]ethyl]pentanamide | 1301630-38-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• 英文名称: 5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[2-[2-[2-[2-[3-[6-amino-8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]purin-9-yl]propylamino]ethoxy]ethoxy]ethoxy]ethyl]pentanamide
• CAS: 1301630-38-5
• 化学式: C₃₃H₄₆IN₉O₇S₂
• 分子量: 871.821
• InChiKey: QYFKPGZCEVCGTK-ULNCZQIZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  52
• 可旋转键数：
  23
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  249
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  8-(6-iodo-benzo[1,3]dioxol-5-ylsulfanyl)adenine 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 25.5h， 生成 5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[2-[2-[2-[2-[3-[6-amino-8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]purin-9-yl]propylamino]ethoxy]ethoxy]ethoxy]ethyl]pentanamide
  参考文献：
  名称：

  Design, synthesis, and evaluation of small molecule Hsp90 probes

  摘要：

  A number of compounds from different chemical classes are known to bind competitively to the ATP-pocket of Hsp90 and inhibit its chaperone function. The natural product geldanamycin was the first reported inhibitor of Hsp90 and since then synthetic inhibitors from purine, isoxazole and indazol-4-one chemical classes have been discovered and are currently or soon to be in clinical trials for the treatment of cancer. In spite of a similar binding mode to Hsp90, distinct biological profiles were demonstrated among these molecules, both in vitro and in vivo. To better understand the molecular basis for these dissimilarities, we report here the synthesis of chemical tools for three Hsp90 inhibitor classes. These agents will be useful for probing tumor-by-tumor the Hsp90 complexes isolated by specific inhibitors. Such information will lead to better understanding of tumor specific molecular markers to aid in their clinical development. It will also help to elucidate the molecular basis for the biological differences observed among Hsp90 inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.03.013

文献信息

• HSP90 COMBINATION THERAPY
  申请人：Chiosis Gabriela

  公开号：US20140315929A1

  公开（公告）日：2014-10-23

  This invention concerns a method for selecting an inhibitor of a cancer-implicated pathway or of a component of a cancer-implicated pathway for coadministration, with an inhibitor of HSP90, to a subject suffering from a cancer which comprises the following steps: (a) contacting a sample containing cancer cells from a subject with an inhibitor of HSP90 or an analog, homolog or derivative of an inhibitor of HSP90 under conditions such that one or more cancer pathway components present in the sample bind to the HSP90 inhibitor or the analog, homolog or derivative of the HSP90 inhibitor; (b) detecting pathway components bound to the HSP90 inhibitor or to the analog, homolog or derivative of the HSP90 inhibitor; (c) analyzing the pathway components detected in step (b) so as to identify a pathway which includes the components detected in step (b) and additional components of such pathway; and (d) selecting an inhibitor of the pathway or of a pathway component identified in step (c). This invention further concerns a method of treating a cancer patient by coadministering an inhibitor of HSP90 and an inhibitor of a cancer-implicated pathway or component thereof.

  本发明涉及一种选择癌症相关通路或癌症相关通路组分的抑制剂的方法，用于与HSP90的抑制剂一起共同治疗患有癌症的受试者，包括以下步骤：(a)将含有受试者的癌细胞的样本与HSP90抑制剂或其类似物、同源物或衍生物接触，以使样本中的一个或多个癌症通路组分与HSP90抑制剂或其类似物、同源物或衍生物结合；(b)检测与HSP90抑制剂或其类似物、同源物或衍生物结合的通路组分；(c)分析在步骤(b)中检测到的通路组分，以识别包括步骤(b)中检测到的组分和该通路的其他组分的通路；(d)选择通路或步骤(c)中识别的通路组分的抑制剂。本发明还涉及一种通过共同给予HSP90抑制剂和癌症相关通路或其组分的抑制剂来治疗癌症患者的方法。
• USES OF LABELED HSP90 INHIBITORS
  申请人：Sloan Kettering Institute For Cancer Research

  公开号：EP3208615B1

  公开（公告）日：2019-10-09
• [EN] USES OF LABELED HSP90 INHIBITORS<br/>[FR] UTILISATIONS D'INHIBITEURS MARQUÉS DE HSP90
  申请人：SLOAN KETTERING INST CANCER

  公开号：WO2013009655A3

  公开（公告）日：2013-05-10
• US9555137B2
  申请人：——

  公开号：US9555137B2

  公开（公告）日：2017-01-31