{3-[6-amino-8-(6-iodo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-propyl}-isopropyl-carbamic acid tert-butyl ester | 873437-14-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: {3-[6-amino-8-(6-iodo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-propyl}-isopropyl-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[3-[6-amino-8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]purin-9-yl]propyl]-N-propan-2-ylcarbamate
• CAS: 873437-14-0
• 化学式: C₂₃H₂₉IN₆O₄S
• 分子量: 612.492
• InChiKey: QQRAGUZKJYWYEB-UHFFFAOYSA-N

物化性质

• 沸点：
  698.6±65.0 °C(Predicted)
• 密度：
  1.65±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  143
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  {3-[6-amino-8-(6-iodo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-propyl}-isopropyl-carbamic acid tert-butyl ester 在 sodium nitrite 作用下， 以 水 、 溶剂黄146 为溶剂， 反应 16.0h， 以67%的产率得到{3-[8-(6-iodo-benzo[1,3]dioxol-5-ylsulfanyl)-6-oxo-1,6-dihydro-purin-9-yl]-propyl}-isopropyl-carbamic acid tert-butyl ester
  参考文献：
  名称：

  [EN] NEW COMPOUNDS AS HSP90 INHIBITORS
  [FR] NOUVEAUX COMPOSÉS INHIBITEURS DE LA HSP90

  摘要：

  该发明提供了式（I）的新化合物，其中：a、b、c或d成员中的一个是氮原子，其余成员是碳原子；R3是从以下组成的基团中选择的：-S-R14和-CH2-R15。式（I）的化合物对于治疗由热休克蛋白90（Hsp 90）介导的疾病是有用的。

  公开号：

  WO2009007399A1
• 作为产物：
  描述：

  8-(benzo[1,3]dioxol-5-ylsulfanyl)adenine 在 N-碘代丁二酰亚胺 、 caesium carbonate 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 48.0h， 生成 {3-[6-amino-8-(6-iodo-benzo[1,3]dioxol-5-ylsulfanyl)-purin-9-yl]-propyl}-isopropyl-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Identification of Potent Water Soluble Purine-Scaffold Inhibitors of the Heat Shock Protein 90

  摘要：

  Hsp90 is a chaperone protein that allows cancer cells to tolerate the many components of dysregulated pathways. Its inactivation may result in targeting multiple molecular alterations and, thus, in reverting the transformed phenotype. The PU-class, a purine-scaffold Hsp90 inhibitor series, has been reported to be potent and selective against Hsp90 both in vitro and in vivo models of cancer. Here, a series of this class was synthesized and evaluated as inhibitors of the chaperone. The structure-activity relationship and selectivity for tumor Hsp90 of compounds within the series is presented. The study identifies water soluble derivatives (> 5 mM in PBS pH 7.4) of nanomolar potency (IC50 similar to 50 nM) in cellular and animal models of cancer. Binding affinities of these compounds for Hsp90 correlate well with their biological activities. When administered in vivo to mice bearing MDA-MB-468 human breast cancer xenocyrafted tumors, these agents result in pharmacologically relevant concentrations and, accordingly, in modulation of Hsp90-client proteins in tumors.

  DOI：

  10.1021/jm0508078

文献信息

• [EN] METHODS AND REAGENTS FOR RADIOLABELING<br/>[FR] PROCÉDÉS ET RÉACTIFS DE RADIOMARQUAGE
  申请人：SLOAN KETTERING INST CANCER

  公开号：WO2015138039A1

  公开（公告）日：2015-09-17

  The present invention provides methods for radiolabeling compounds useful as Hsp90 inhibitors. The present invention also provides intermediates useful in such methods, and compositions of radiolabeled compounds. The present invention provides, among other things, novel methods for the synthesis of radiolabeled compounds. In certain embodiments, the present invention provides compounds of formula I.

  本发明提供了用作Hsp90抑制剂的化合物放射性标记的方法。本发明还提供了在这些方法中有用的中间体和放射性标记化合物的组成。本发明提供了包括合成放射性标记化合物的新方法在内的其他内容。在某些实施例中，本发明提供了I式化合物。
• COMPOUNDS AS HSP90 INHIBITORS
  申请人：Pedemonte Marc Martinell

  公开号：US20100240656A1

  公开（公告）日：2010-09-23

  The invention provides novel compounds of formula (I) wherein: one of the a, b, c or d members is a nitrogen atom and the remaining members are carbon atoms; and R 3 is a radical selected from the group consisting of: —S—R 14 and —CH 2 —R 15 . The compounds of formula (I) are useful for treating diseases mediated by a heat shock protein 90 (Hsp 90).

  本发明提供了公式（I）的新化合物，其中：a、b、c或d成员中的一个是氮原子，其余成员是碳原子；R3是从以下组中选择的基团：—S—R14和—CH2—R15。公式（I）的化合物可用于治疗由热休克蛋白90（Hsp90）介导的疾病。
• Methods and reagents for radiolabeling
  申请人：Memorial Sloan-Kettering Cancer Center

  公开号：US10329293B2

  公开（公告）日：2019-06-25

  The present invention provides methods for radiolabeling compounds useful as Hsp90 inhibitors. The present invention also provides intermediates useful in such methods, and compositions of radiolabeled compounds. The present invention provides, among other things novel methods for the synthesis of radiolabeled compounds. In certain embodiments, the present invention provides compounds of formula I.

  本发明提供了对用作 Hsp90 抑制剂的化合物进行放射性标记的方法。本发明还提供了在此类方法中有用的中间体，以及放射性标记化合物的组合物。本发明主要提供了合成放射性标记化合物的新方法。在某些实施方案中，本发明提供了式 I 的化合物。
• J. Med. Chem. 2006, 49, 381-390
  作者：

  DOI：——

  日期：——
• NEW COMPOUNDS AS HSP90 INHIBITORS
  申请人：Crystax Pharmaceuticals, S.L.

  公开号：EP2183221A1

  公开（公告）日：2010-05-12