8-(7-bromo-2,3-dihydro-benzo[1,4]dioxin-6-ylsulfanyl)adenine | 852030-25-2

• 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-(7-bromo-2,3-dihydro-benzo[1,4]dioxin-6-ylsulfanyl)adenine
• 英文别名: 8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9H-purin-6-amine；8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)adenine；8-(6-bromo-3,4-methylenedioxyphenylthio)adenine；8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9H-purin-6-ylamine；8-(6-Bromobenzo[d][1,3]dioxol-5-ylthio)-9H-purin-6-amine；8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-7H-purin-6-amine
• CAS: 852030-25-2
• 化学式: C₁₂H₈BrN₅O₂S
• 分子量: 366.198
• InChiKey: HIXVNOZFOOVCLV-UHFFFAOYSA-N

物化性质

• 沸点：
  624.9±65.0 °C(Predicted)
• 密度：
  2.01±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 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-(7-bromo-2,3-dihydro-benzo[1,4]dioxin-6-ylsulfanyl)adenine 在 偶氮二甲酸二苄酯 、 三苯基膦 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 甲苯 为溶剂， 反应 2.83h， 生成 8-(6-bromo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(3-isopropylamino-propyl)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
• 作为产物：
  描述：

  8-(6-bromo-3,4-methylenedioxyphenylthio)-9-(2-deoxy-β-D-ribo-pentofuranosyl)adenine 在 三氟乙酸 、 碳酸氢钠 作用下， 以 水 为溶剂， 反应 1.0h， 以69%的产率得到8-(7-bromo-2,3-dihydro-benzo[1,4]dioxin-6-ylsulfanyl)adenine
  参考文献：
  名称：

  Efficient synthesis of Hsp90 inhibitor dimers as potential antitumor agents

  摘要：

  The PU-H58-dimers 13a-15b were efficiently synthesized and their biological properties were evaluated. The copper-catalyzed alkyne azide coupling was effective in simultaneously linking three components via a triazole formation to afford the target dimers. These synthesized dimers exhibited binding affinity to the N-terminal domain of Hsp90, cytotoxicity, and client degradation activity although these activities were comparative or weak comparable with that of the parent compound. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.05.075

文献信息

• HSP90 Inhibitors Containing a Zinc Binding Moiety
  申请人：Qian Changgeng

  公开号：US20080234297A1

  公开（公告）日：2008-09-25

  The present invention relates to HSP90 inhibitors and their use in the treatment of cell proliferative diseases such as cancer. The said derivatives may further act as HDAC inhibitors.

  本发明涉及HSP90抑制剂及其在治疗癌症等细胞增殖性疾病中的应用。所述衍生物还可能作为HDAC抑制剂。
• [EN] THERAPEUTIC COMPOUNDS AND THEIR USE IN TREATING DISEASES AND DISORDERS<br/>[FR] COMPOSÉS THÉRAPEUTIQUES ET LEUR UTILISATION DANS LE TRAITEMENT DE MALADIES ET DE TROUBLES
  申请人：MYRIAD GENETICS INC

  公开号：WO2009065035A1

  公开（公告）日：2009-05-22

  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.

  这项发明提供了新型治疗化合物，包括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，如癌症。
• 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。
• Multi-Functional Small Molecules as Anti-Proliferative Agents
  申请人：Cai Xiong

  公开号：US20080221132A1

  公开（公告）日：2008-09-11

  The present invention relates to the compositions, methods, and applications of a novel approach to selective inhibition of several cellular or molecular targets with a single small molecule. More specifically, the present invention relates to multi-functional small molecules wherein one functionality is capable of inhibiting histone deacetylases (HDAC) and the other functionality is capable of inhibiting a different cellular or molecular pathway involved in aberrant cell proliferation, differentiation or survival.

  本发明涉及一种新型选择性抑制多种细胞或分子靶点的组合物、方法和应用。更具体地说，本发明涉及多功能小分子，其中一种功能能够抑制组蛋白去乙酰化酶（HDAC），另一种功能能够抑制与异常细胞增殖、分化或存活有关的不同细胞或分子途径。
• Small-Molecule Hsp90 Inhibitors
  申请人：Chiosis Gabriela

  公开号：US20080253965A1

  公开（公告）日：2008-10-16

  Hsp90 inhibitors are provided having the formula: with a 2′,4′,5′-substitution pattern on the right-side aryl moiety. X1 represents two substituents, which may be the same or different, disposed in the 4′ and 5′ positions on the aryl group, wherein X1 is selected from halogen, alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, pyrollyl, optionally substituted aryloxy, alkylamino, dialkylamino, carbamyl, amido, alkylamido dialkylamido, acylamino, alkylsulfonylamido, trihalomethoxy, trihalocarbon, thioalkyl, SO 2 . alkyl, COO-alkyl, KH 2 , OH, CN, SO 2 X 5 , NO 2 , NO, C═SR 2 NSO 2 X 5 , C═OR 2 , where X 5 is F, NH2, alkyl or H, and R 2 is alkyl, NH 2 , NH-alkyl or O-alkyl, C 1 to C 6 alkyl or alkoxy; or wherein X 1 has the formula -0-(CH 2 ) n -0-, wherein n is an integer from O to 2, preferably 1 or 2, and one of the oxygens is bonded at the 5′-position and the other at the 4′-position of the aryl ring. The compounds are useful in cancer therapy and as radioimaging ligands.

  提供具有以下公式的Hsp90抑制剂：右侧芳基基团上具有2'、4'、5'取代模式。X1代表位于芳基团的4'和5'位置的两个取代基，可以相同或不同，其中X1选自卤素、烷基、烷氧基、卤代烷氧基、羟基烷基、吡咯基、可选取代的芳氧基、烷基氨基、二烷基氨基、氨基甲酰、酰胺、烷基酰胺、二烷基酰胺、酰胺基、烷基磺酰胺基、三卤甲氧基、三卤代碳基、硫代烷基、SO2.烷基、COO-烷基、KH2、OH、CN、SO2X5、NO2、NO、C═SR2NSO2X5、C═OR2，其中X5为F、NH2、烷基或H，R2为烷基、NH2、NH-烷基或O-烷基，C1到C6烷基或烷氧基；或X1具有公式-0-（CH2）n-0-，其中n是0到2的整数，优选为1或2，其中一个氧原子与芳环的5'位置键合，另一个氧原子键合于4'位置。这些化合物在癌症治疗和放射性成像配体方面有用。