9-(3-aminopropyl)-8-((6-iodobenzo[d][1,3]dioxol-5-yl)thio)-9H-purin-6-amine | 1333155-97-7

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 9-(3-aminopropyl)-8-((6-iodobenzo[d][1,3]dioxol-5-yl)thio)-9H-purin-6-amine
• 英文别名: 9-(3-Aminopropyl)-8-((6-iodobenzo-[d][1,3]dioxol-5-yl)thio)-9H-purin-6-amine；9-(3-aminopropyl)-8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]purin-6-amine
• CAS: 1333155-97-7
• 化学式: C₁₅H₁₅IN₆O₂S
• 分子量: 470.294
• InChiKey: XFOCPNJERGAMSB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  139
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  9-(3-aminopropyl)-8-((6-iodobenzo[d][1,3]dioxol-5-yl)thio)-9H-purin-6-amine 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Intracellular Protein-Responsive Supramolecules: Protein Sensing and In-Cell Construction of Inhibitor Assay System

  摘要：

  Supramolecular nanomaterials responsive to specific intracellular proteins should be greatly promising for protein sensing and imaging, controlled drug release or dynamic regulation of cellular processes. However, valid design strategies to create useful probes are poorly developed, particularly for proteins inside living cells as targets. We recently reported a unique supramolecular strategy for specific protein detection using self-assembling fluorescent probes consisting of a protein ligand and a fluorophore on the live cell surface, as well as in test tube settings. Herein, we discovered that our self-assembled supramolecular probes having a rhodamine derivative (tetramethylrhodamine or rhodamine-green) can incorporate and stay as less-fluorescent aggregates inside the living cells, so as to sense the protein activity in a reversible manner. Using the overexpressed model protein (dihydrofolate reductase), we demonstrated that this turn-on/off mode is controlled by selective ligandprotein recognition inside the live cells. Not only such a model protein, but also endogenous human carbonic anhydrase and heat shock protein 90 were specifically visualized in living mammalian cells, by use of the similar ligand-tethered supramolecular probes. Furthermore, such reversibility allowed us to intracellularly construct a unique system to evaluate the inhibitors affinity toward specific endogenous proteins in live cells, highlighting the potential of dynamic supramolecules as novel intelligent biomaterials.

  DOI：

  10.1021/ja508955y
• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以145 mg的产率得到9-(3-aminopropyl)-8-((6-iodobenzo[d][1,3]dioxol-5-yl)thio)-9H-purin-6-amine
  参考文献：
  名称：

  配体构象偏差驱动 Hsp90 表面暴露赖氨酸的对映选择性修饰

  摘要：

  由于其低内在反应性和整个蛋白质组中的高流行率，对表面暴露的赖氨酸进行靶向共价修饰具有挑战性。通过可逆结合抑制剂 (kinact) 优化共价键形成速率的策略通常涉及增加亲电子试剂的反应性，这会增加脱靶修饰的风险。在这里，我们采用另一种方法来增加赖氨酸靶向共价 Hsp90 抑制剂的 kinact，独立于可逆结合亲和力 (Ki) 或内在亲电性。从非共价配体开始，我们附加了一个手性的、构象受限的接头，它使芳基磺酰氟定向以与 Hsp90 表面上的 Lys58 快速和对映选择性反应。共价和非共价配体/Hsp90 复合物的生化实验和高分辨率晶体结构为配体构象在观察到的对映选择性中的作用提供了机械见解。最后，我们证明了细胞 Hsp90 的选择性共价靶向，尽管共价配体/Hsp90 复合物同时降解，但仍会导致延长的热休克反应。我们的工作突出了工程配体构象约束的潜力，可显着加速蛋白质靶标表面上远端、亲核性差的赖

  DOI：

  10.1021/jacs.9b09684

文献信息

• Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes
  作者：Tony Taldone、Anna Rodina、Erica M DaGama Gomes、Matthew Riolo、Hardik J Patel、Raul Alonso-Sabadell、Danuta Zatorska、Maulik R Patel、Sarah Kishinevsky、Gabriela Chiosis

  DOI：10.3762/bjoc.9.60

  日期：——

  The attachment of biotin to a small molecule provides a powerful tool in biology. Here, we present a systematic approach to identify biotinylated analogues of the Hsp90 inhibitor PU-H71 that are capable of permeating cell membranes so as to enable the investigation of Hsp90 complexes in live cells. The identified derivative 2g can isolate Hsp90 through affinity purification and, as we show, represents a unique and useful tool to probe tumor Hsp90 biology in live cells by affinity capture, flow cytometry and confocal microscopy. To our knowledge, 2g is the only reported biotinylated Hsp90 probe to have such combined characteristics.

  将生物素连接到小分子上提供了生物学中的强大工具。在这里，我们提出了一种系统的方法，以识别能够渗透细胞膜的Hsp90抑制剂PU-H71的生物素化类似物，从而使得在活细胞中能够研究Hsp90复合物。鉴定出的衍生物2g可以通过亲和纯化分离Hsp90，并且，正如我们所展示的，代表了一种独特而有用的工具，通过亲和捕获、流式细胞术和共聚焦显微镜来探索肿瘤Hsp90生物学。据我们所知，2g是唯一报道的具有这些综合特性的生物素化Hsp90探针。
• 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。
• SELECTIVE GRP94 INHIBITORS AND USES THEREOF
  申请人：Memorial Sloan-Kettering Cancer Center

  公开号：US20160194328A1

  公开（公告）日：2016-07-07

  The disclosure relates to novel selective Grp94 inhibitors, compositions comprising an effective amount of such compounds, and methods to treat or prevent a condition, such as cancer, comprising administering to an animal in need thereof an effective amount of such compounds.

  本公开涉及新型选择性Grp94抑制剂，包括含有有效量此类化合物的组合物，以及治疗或预防疾病的方法，例如癌症，包括向需要此类化合物的动物施用有效量此类化合物。
• Selective Grp94 inhibitors and uses thereof
  申请人：Memorial Sloan-Kettering Cancer Center

  公开号：US10421758B2

  公开（公告）日：2019-09-24

  The disclosure relates to novel selective Grp94 inhibitors, compositions comprising an effective amount of such compounds, and methods to treat or prevent a condition, such as cancer, comprising administering to an animal in need thereof an effective amount of such compounds.

  本公开涉及新型选择性 Grp94 抑制剂、包含有效量此类化合物的组合物，以及治疗或预防癌症等疾病的方法，包括向有需要的动物施用有效量的此类化合物。
• 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