9-(3-Bromopropyl)-2-fluoro-8-[(6-iodo-1,3-benzodioxol-5-yl)methyl]purin-6-amine | 873437-15-1

• 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: 9-(3-Bromopropyl)-2-fluoro-8-[(6-iodo-1,3-benzodioxol-5-yl)methyl]purin-6-amine
• CAS: 873437-15-1
• 化学式: C₁₆H₁₄BrFIN₅O₂
• 分子量: 534.126
• InChiKey: UWKIYEXSJJUHBI-UHFFFAOYSA-N

物化性质

• 沸点：
  715.7±70.0 °C(Predicted)
• 密度：
  2.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  88.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  9-(3-Bromopropyl)-2-fluoro-8-[(6-iodo-1,3-benzodioxol-5-yl)methyl]purin-6-amine 、 异丙胺 反应 1.0h， 以75%的产率得到2-fluoro-8-(6-iodo-benzo[1,3]dioxol-5-ylmethyl)-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：

  Benzo[1,3]dioxol-5-yl-acetyl fluoride 在 4-二甲氨基吡啶 、 N-碘代丁二酰亚胺 、 异丁醇 、 sodium methylate 、 potassium carbonate 、 caesium carbonate 、 氟化氢吡啶 、 三氟乙酸 、 sodium nitrite 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 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

文献信息

• [EN] SMALL-MOLECULE HSP90 INHIBITORS<br/>[FR] PETITES MOLECULES INHIBITRICES DU HSP90
  申请人：SLOAN KETTERING INST CANCER

  公开号：WO2006084030A3

  公开（公告）日：2007-01-25