8-(（苯并[D][1,3]二氧杂环戊烯-6 - 基）甲基）- 9H-嘌呤-2,6 - 二胺 | 873436-95-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 8-(（苯并[D][1,3]二氧杂环戊烯-6 - 基）甲基）- 9H-嘌呤-2,6 - 二胺
• 中文别名: 8-(（苯并[D][1,3]二氧杂环戊烯-6-基）甲基）-9H-嘌呤-2,6-二胺
• 英文名称: 8-(benzo[1,3]dioxol-5-ylmethyl)-2-aminoadenine
• 英文别名: 8-(benzo[d][1,3]dioxol-5-ylmethyl)-9H-purine-2,6-diamine；8-(3-[1,3]dioxolan-4-ylidene-propyl)-9H-purine-2,6-diamine；8-(1,3-benzodioxol-5-ylmethyl)-7H-purine-2,6-diamine
• CAS: 873436-95-4
• 化学式: C₁₃H₁₂N₆O₂
• 分子量: 284.277
• InChiKey: BSTSINXUGFGPQG-UHFFFAOYSA-N

物化性质

• 沸点：
  738.2±70.0 °C(Predicted)
• 密度：
  1.608±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 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：
  125
• 氢给体数：
  3
• 氢受体数：
  7

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  8-(（苯并[D][1,3]二氧杂环戊烯-6 - 基）甲基）- 9H-嘌呤-2,6 - 二胺 在 N-碘代丁二酰亚胺 、 caesium carbonate 、 氟化氢吡啶 、 三氟乙酸 、 sodium nitrite 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 吡啶 、 4-二甲氨基吡啶 、 三聚氟氰 、 异丁醇 、 sodium methylate 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 8-(（苯并[D][1,3]二氧杂环戊烯-6 - 基）甲基）- 9H-嘌呤-2,6 - 二胺
  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

• 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。
• Adenine derived inhibitors of the molecular chaperone HSP90—SAR explained through multiple X-ray structures
  作者：Brian Dymock、Xavier Barril、Mandy Beswick、Adam Collier、Nicholas Davies、Martin Drysdale、Alexandra Fink、Christophe Fromont、Roderick E. Hubbard、Andrew Massey、Allan Surgenor、Lisa Wright

  DOI：10.1016/j.bmcl.2003.11.011

  日期：2004.1

  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.
• Microwave-assisted one step synthesis of 8-arylmethyl-9H-purin-6-amines
  作者：Hui Tao、Yanlong Kang、Tony Taldone、Gabriela Chiosis

  DOI：10.1016/j.bmcl.2008.11.057

  日期：2009.1

  Molecular chaperone heat shock protein 90 (Hsp90) is an important target in cancer and neurodegenerative diseases, and has rapidly become the focus of several drug discovery efforts. Among small molecule Hsp90 inhibitors with clinical applicability are derivatives of 8-arylmethyl-9H-purin-6-amine class. Here we report the use of microwave-assisted chemistry for the successful one-pot delivery of 8-arylmethyl-9H-purin-6-amines. We discuss the applicability as well as the limitations of this method towards the creation of a large chemical diversity in the 8-arylmethyl-9H-purin-6-amine series. (C) 2008 Elsevier Ltd. All rights reserved.
• Identification of Potent Water Soluble Purine-Scaffold Inhibitors of the Heat Shock Protein 90
  作者：Huazhong He、Danuta Zatorska、Joungnam Kim、Julia Aguirre、Laura Llauger、Yuhong She、Nian Wu、Robert M. Immormino、Daniel T. Gewirth、Gabriela Chiosis

  DOI：10.1021/jm0508078

  日期：2006.1.1

  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.