N1-(3-(6-amino-8-(6-iodobenzo[d][1,3]dioxol-5-ylthio)-9H-purin-9-yl)propyl)hexane-1,6-diamine | 1301630-37-4

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: N1-(3-(6-amino-8-(6-iodobenzo[d][1,3]dioxol-5-ylthio)-9H-purin-9-yl)propyl)hexane-1,6-diamine
• 英文别名: N'-[3-[6-amino-8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]purin-9-yl]propyl]hexane-1,6-diamine
• CAS: 1301630-37-4
• 化学式: C₂₁H₂₈IN₇O₂S
• 分子量: 569.47
• InChiKey: JMCHBCHNIYQIRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  151
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N1-(3-(6-amino-8-(6-iodobenzo[d][1,3]dioxol-5-ylthio)-9H-purin-9-yl)propyl)hexane-1,6-diamine 、 磺基罗丹明101磺酰氯 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以61%的产率得到PU-H71-TR
  参考文献：
  名称：

  Synthesis of purine-scaffold fluorescent probes for heat shock protein 90 with use in flow cytometry and fluorescence microscopy

  摘要：

  Fluorescent ligands for the heat shock protein 90 (Hsp90) were synthesized containing either fluorescein isothiocyanate (FITC), 4-nitrobenzo[1,2,5] oxadiazole (NBD) or the red shifted dye sulforhodamine 101 (Texas Red) conjugated to PU-H71. Two of the compounds, PU-H71-FITC2 (9) and PU-H71-NBD1 (8), were shown to be suitable for fluorescence-activated flow cytometry and fluorescence microscopy. Thus these molecules serve as useful probes for studying Hsp90 in heterogeneous live cell populations. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.026
• 作为产物：
  描述：

  tert-butyl 6-(3-(6-amino-8-(6-iodobenzo[d][1,3]dioxol-5-ylthio)-9H-purin-9-yl)propylamino)hexylcarbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.75h， 以76%的产率得到N1-(3-(6-amino-8-(6-iodobenzo[d][1,3]dioxol-5-ylthio)-9H-purin-9-yl)propyl)hexane-1,6-diamine
  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

• 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
• HSP90 COMBINATION THERAPY
  申请人：Sloan-Kettering Institute for Cancer Research

  公开号：EP2701747A2

  公开（公告）日：2014-03-05
• US9555137B2
  申请人：——

  公开号：US9555137B2

  公开（公告）日：2017-01-31
• [EN] HSP90 COMBINATION THERAPY<br/>[FR] POLYTHÉRAPIE PAR HSP90
  申请人：SLOAN KETTERING INST CANCER

  公开号：WO2012149493A2

  公开（公告）日：2012-11-01

  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.