6-(isobutylthio)-7H-purine | 82499-06-7

• 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: 6-(isobutylthio)-7H-purine
• 英文别名: 6-iso-butylthiopurine；6-isobutylmercapto-7(9)H-purine；6-Isobutylmercapto-7(9)H-purin；1H-Purine, 6-[(2-methylpropyl)thio]-；6-(2-methylpropylsulfanyl)-7H-purine
• CAS: 82499-06-7
• 化学式: C₉H₁₂N₄S
• mdl: MFCD01694202
• 分子量: 208.287
• InChiKey: HBFAIQHZZSJMFS-UHFFFAOYSA-N

物化性质

• 熔点：
  199 °C
• 沸点：
  303.8±52.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.444
• 拓扑面积：
  79.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  溴代异丁烷 、 6-mercaptopurine 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.08h， 以37%的产率得到6-(isobutylthio)-7H-purine
  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

文献信息

• The discovery of purine-based agents targeting triple-negative breast cancer and the αB-crystallin/VEGF protein–protein interaction
  作者：Nelly A. Fosu-Mensah、Wen Jiang、Andrea Brancale、Jun Cai、Andrew D. Westwell

  DOI：10.1007/s00044-018-2275-9

  日期：2019.2

  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.