8-benzo[1,3]dioxol-5-ylmethyl-2-fluoroadenine | 873436-96-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 8-benzo[1,3]dioxol-5-ylmethyl-2-fluoroadenine
• 英文别名: 8-Benzo[1,3]dioxol-5-ylmethyl-2-fluoro-9H-purin-6-ylamine；8-(1,3-benzodioxol-5-ylmethyl)-2-fluoro-7H-purin-6-amine
• CAS: 873436-96-5
• 化学式: C₁₃H₁₀FN₅O₂
• 分子量: 287.253
• InChiKey: KHYVIWASHBWTQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  98.9
• 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-ylmethyl-2-fluoroadenine 在 N-碘代丁二酰亚胺 、 caesium carbonate 、 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 2.0h， 生成 9-(3-Bromopropyl)-2-fluoro-8-[(6-iodo-1,3-benzodioxol-5-yl)methyl]purin-6-amine
  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：

  胡椒乙酸 在 sodium methylate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 氟化氢吡啶 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.08h， 生成 8-benzo[1,3]dioxol-5-ylmethyl-2-fluoroadenine
  参考文献：
  名称：

  Adenine derived inhibitors of the molecular chaperone HSP90—SAR explained through multiple X-ray structures

  摘要：

  Multiple co-crystal structures of an adenine-based series of inhibitors bound to the molecular chaperone Hsp90 have been determined. These structures explain the observed SAR for previously described compounds and new compounds, which possess up to 8-fold improved potency against the isolated enzyme. Anti-tumour cell potency and mechanism of action data is also described for the most potent compounds. These data should enable the design of more potent Hsp90 inhibitors. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.11.011

文献信息

• SULFAMOYL-CONTAINING DERIVATIVES AND USES THEREOF
  申请人：Chen Jianxin

  公开号：US20080096903A1

  公开（公告）日：2008-04-24

  Sulfamoyl-containing compounds are disclosed, having utility as inhibitors of disease-related targets, such as Heat Shock Protein 90 (HSP90), and which are useful for treating disorders, e.g., proliferative disorders, including HSP90-mediated disorders. Methods for preparing and using the disclosed compounds are also described.

  披露了含有磺酰氨基的化合物，这些化合物可用作疾病相关靶点的抑制剂，例如热休克蛋白90（HSP90），并且可用于治疗疾病，例如增殖性疾病，包括HSP90介导的疾病。还描述了制备和使用所披露化合物的方法。
• 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。
• Small-Molecule HSP90 Inhibitors
  申请人：Chiosis Gabriela

  公开号：US20110104054A1

  公开（公告）日：2011-05-05

  Hsp90 inhibitors having 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代表在芳基团上的4′和5′位置上排列的两个取代基，其中X1从卤素，烷基，烷氧基，卤代烷氧基，羟基烷基，吡咯基，可选择取代的芳氧基，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，而R2为烷基，NH2，NH-烷基或O-烷基，C1到C6烷基或烷氧基；或其中X1具有公式-0-（CH2）n-0-，其中n是从O到2的整数，优选为1或2，其中一个氧原子与芳环的5′位置连接，另一个氧原子与芳环的4′位置连接。这些化合物在癌症治疗和放射成像配体中有用。
• Small-molecule Hsp90 Inhibitors
  申请人：Chiosis Gabriela

  公开号：US20110312980A1

  公开（公告）日：2011-12-22

  Purine scaffold Hsp90 inhibitors are useful in therapeutic applications and as radioimaging ligands.

  嘌呤支架Hsp90抑制剂在治疗应用和放射性成像配体中很有用。
• Small-molecule Hsp90 inhibitors
  申请人：Slaon-Kettering Institute for Cancer Research

  公开号：US07834181B2

  公开（公告）日：2010-11-16

  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, SO2−alkyl, COO-alkyl, KH2, OH, CN, SO2X5, NO2, NO, C═SR2 NSO2X5, C═OR2, where X5 is F, NH2, alkyl or H, and R2 is alkyl, NH2, NH-alkyl or O-alkyl, C1 to C6 alkyl or alkoxy; or wherein X1 has the formula —O—(CH2)n—O—, wherein n is an integer from 0 to 2, preferably 1 or 2, and one of the oxygen 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从卤素，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═SR2，NSO2X5，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至C6烷基或烷氧基; 或者其中X1具有公式—O—（CH2）n—O—，其中n是整数0到2，优选为1或2，其中一个氧原子与芳环的5′位置键合，另一个与4′位置键合。该化合物在癌症治疗和放射性成像配体中有用。