8-(benzo[1,3]dioxol-5-ylsulfanyl)adenine | 873436-88-5

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 8-(benzo[1,3]dioxol-5-ylsulfanyl)adenine
• 英文别名: 8-(benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine；8-(benzo[d][1,3]dioxol-5-ylthio)-9H-purin-6-amine；8-(1,3-benzodioxol-5-ylthio)-9H-purin-6-amine；8-(1,3-benzodioxol-5-ylsulfanyl)-7H-purin-6-amine
• CAS: 873436-88-5
• 化学式: C₁₂H₉N₅O₂S
• 分子量: 287.302
• InChiKey: LGBDNSGYOVMKIT-UHFFFAOYSA-N

物化性质

• 沸点：
  605.6±65.0 °C(Predicted)
• 密度：
  1.70±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8-(benzo[1,3]dioxol-5-ylsulfanyl)adenine 在 N-碘代丁二酰亚胺 、 三氟乙酸 作用下， 以 乙腈 为溶剂， 以85%的产率得到8-(6-iodo-benzo[1,3]dioxol-5-ylsulfanyl)adenine
  参考文献：
  名称：

  A facile and efficient synthesis of d₆-labeled PU-H71, a purine-scaffold Hsp90 inhibitor

  摘要：

  PU-H71 是一种嘌呤支架 Hsp90 抑制剂，目前正在进行癌症治疗的后期临床前评估。在本研究中，我们提出了一种简单的 d6 标记 PU-H71 合成方法，用作内标，基于 LC-MS-MS 方法准确定量生物基质中的药物。 PU-H71-d6 使用现成的 1,3-二溴丙烷-d6 分五个步骤合成，是推进我们临床计划的重要化合物。版权所有 © 2009 约翰·威利父子有限公司

  DOI：

  10.1002/jlcr.1689
• 作为产物：
  描述：

  3,4-亚甲二氧基苯胺 在 盐酸 、 copper(l) iodide 、 新铜试剂 、 sodium t-butanolate 、 sodium nitrite 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.42h， 生成 8-(benzo[1,3]dioxol-5-ylsulfanyl)adenine
  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] NEW COMPOUNDS AS HSP90 INHIBITORS<br/>[FR] NOUVEAUX COMPOSÉS INHIBITEURS DE LA HSP90
  申请人：CRYSTAX PHARMACEUTICALS S L

  公开号：WO2009007399A1

  公开（公告）日：2009-01-15

  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 R3 is a radical selected from the group consisting of: -S-R14 and -CH2-R15.The compounds of formula (I) are useful for treating diseases mediated by a heat shock protein 90 (Hsp 90).

  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。
• THERAPEUTIC COMPOUNDS AND THEIR USE IN CANCER
  申请人：Bajji C. Ashok

  公开号：US20070299258A1

  公开（公告）日：2007-12-27

  The invention relates to compounds of Formulae I-III and their therapeutic uses.

  这项发明涉及到I-III式化合物及其治疗用途。
• 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。
• Therapeutic Compounds and Their Use in Treating Diseases and Disorders
  申请人：Bajji Ashok C.

  公开号：US20100292255A1

  公开（公告）日：2010-11-18

  The invention provides novel therapeutic compounds, pharmaceutical compositions comprising these compounds, and methods for using these compounds and compositions to treat diseases and disorders, such as cancer.

  该发明提供了新型治疗化合物、包含这些化合物的药物组合物以及使用这些化合物和组合物治疗疾病和疾病的方法，例如癌症。
• Development of a Mitochondria-Targeted Hsp90 Inhibitor Based on the Crystal Structures of Human TRAP1
  作者：Changwook Lee、Hye-Kyung Park、Hanbin Jeong、Jaehwa Lim、An-Jung Lee、Keun Young Cheon、Chul-Su Kim、Ajesh P. Thomas、Boram Bae、Nam Doo Kim、Seong Heon Kim、Pann-Ghill Suh、Ja-Hyoung Ryu、Byoung Heon Kang

  DOI：10.1021/ja511893n

  日期：2015.4.8

  The mitochondrial pool of Hsp90 and its mitochondrial paralogue, TRAP1, suppresses cell death and reprograms energy metabolism in cancer cells; therefore, Hsp90 and TRAP1 have been suggested as target proteins for anticancer drug development. Here, we report that the actual target protein in cancer cell mitochondria is TRAP1, and current Hsp90 inhibitors cannot effectively inactivate TRAP1 because of their insufficient accumulation in the mitochondria. To develop mitochondrial TRAP1 inhibitors, we determined the crystal structures of human TRAP1 complexed with Hsp90 inhibitors. The isopropyl amine of the Hsp90 inhibitor PU-H71 was replaced with the mitochondria-targeting moiety triphenylphosphonium to produce SMTIN-P01. SMTIN-P01 showed a different mode of action from the nontargeted PU-H71, as well as much improved cytotoxicity to cancer cells. In addition, we determined the structure of a TRAP1-adenylyl-imidodiphosphate (AMP-PNP) complex. On the basis of comparative analysis of TRAP1 structures, we propose a molecular mechanism of ATP hydrolysis that is crucial for chaperone function.