2-Amino-6-chlor-9-(3-phenyl-propyl)-purin | 17400-49-6

• 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: 2-Amino-6-chlor-9-(3-phenyl-propyl)-purin
• 英文别名: 6-chloro-9-(3-phenyl-propyl)-9H-purin-2-ylamine；6-Chloro-9-(3-phenylpropyl)purin-2-amine
• CAS: 17400-49-6
• 化学式: C₁₄H₁₄ClN₅
• 分子量: 287.752
• InChiKey: XAFIDUJTHXEIMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-Amino-6-chlor-9-(3-phenyl-propyl)-purin 在 盐酸 、 水 、 溴 作用下， 以 溶剂黄146 为溶剂， 反应 21.0h， 生成 2-Amino-8-bromo-9-(3-phenylpropyl)-9h-purin-6-ol
  参考文献：
  名称：

  The discovery of purine-based agents targeting triple-negative breast cancer and the αB-crystallin/VEGF protein–protein interaction

  摘要：

  Oestrogen receptor-negative breast cancer, particularly subtypes such as triple-negative breast cancer (TNBC, around 10-15% of cases), are characterised by poor long-term survival, poor response to therapy and early progression to metastasis. Purine-based compounds represent a privileged scaffold in anticancer drug design, with several clinically approved and experimental agents in clinical development comprising a purine core structure. In this study, a series of new purine-based compounds were synthesised; seven of the new analogues were found to significantly reduce the in vitro viability of TNBC cell lines (MDA-MB-231 and MDA-MB-436) with IC50 values of 50M. In previous work, we have proposed a new concept for targeting angiogenesis driving TNBC progression, by disrupting the protein-protein interaction between the molecular chaperone B-crystallin (CRYAB) and VEGF. Since previous clinical studies applying anti-VEGF therapy to TNBC patients have met with limited success, we were interested to test our most promising purine analogues against CRYAB/VEGF, using a custom-designed cell-based CRYAB/VEGF(165) interaction assay platform. Analogues 4e and 4f significantly reduced the interaction between CRYAB/VEGF(165), and compound 4e (100M) was also found to decrease the levels of soluble VEGF expressed by MDA-MB-231 cells by 40%. In conclusion, these promising early activity profiles warrant further investigation to validate this concept.

  DOI：

  10.1007/s00044-018-2275-9
• 作为产物：
  描述：

  1-溴-3-苯基丙烷 、 2-氨基-6-氯嘌呤 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 、 2-Amino-6-chlor-9-(3-phenyl-propyl)-purin
  参考文献：
  名称：

  The discovery of purine-based agents targeting triple-negative breast cancer and the αB-crystallin/VEGF protein–protein interaction

  摘要：

  Oestrogen receptor-negative breast cancer, particularly subtypes such as triple-negative breast cancer (TNBC, around 10-15% of cases), are characterised by poor long-term survival, poor response to therapy and early progression to metastasis. Purine-based compounds represent a privileged scaffold in anticancer drug design, with several clinically approved and experimental agents in clinical development comprising a purine core structure. In this study, a series of new purine-based compounds were synthesised; seven of the new analogues were found to significantly reduce the in vitro viability of TNBC cell lines (MDA-MB-231 and MDA-MB-436) with IC50 values of 50M. In previous work, we have proposed a new concept for targeting angiogenesis driving TNBC progression, by disrupting the protein-protein interaction between the molecular chaperone B-crystallin (CRYAB) and VEGF. Since previous clinical studies applying anti-VEGF therapy to TNBC patients have met with limited success, we were interested to test our most promising purine analogues against CRYAB/VEGF, using a custom-designed cell-based CRYAB/VEGF(165) interaction assay platform. Analogues 4e and 4f significantly reduced the interaction between CRYAB/VEGF(165), and compound 4e (100M) was also found to decrease the levels of soluble VEGF expressed by MDA-MB-231 cells by 40%. In conclusion, these promising early activity profiles warrant further investigation to validate this concept.

  DOI：

  10.1007/s00044-018-2275-9