2,6-bis(methylthio)-7H-purin-8(9H)-one | 98277-22-6

• 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: 2,6-bis(methylthio)-7H-purin-8(9H)-one
• 英文别名: 2,6-bis-methylsulfanyl-7,9-dihydro-purin-8-one；2,6-Bis-methylmercapto-7,9-dihydro-purin-8-on；2,6-bis(methylsulfanyl)-7,9-dihydropurin-8-one
• CAS: 98277-22-6
• 化学式: C₇H₈N₄OS₂
• 分子量: 228.299
• InChiKey: FCYZEMBJGZTVBH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,6-bis(methylthio)-7H-purin-8(9H)-one 在 三氯氧磷 作用下， 生成 8-chloro-2,6-bis-methylsulfanyl-7(9)H-purine
  参考文献：
  名称：

  Potential Purine Antagonists. XX. The Preparation and Reactions of Some Methylthiopurines¹

  摘要：

  DOI：

  10.1021/ja01531a037
• 作为产物：
  描述：

  甲硫醇 、 6-chloro-2-methylsulfanyl-7,9-dihydro-purin-8-one 在 sodium hydroxide 作用下， 生成 2,6-bis(methylthio)-7H-purin-8(9H)-one
  参考文献：
  名称：

  Potential Purine Antagonists. XX. The Preparation and Reactions of Some Methylthiopurines¹

  摘要：

  DOI：

  10.1021/ja01531a037

文献信息

• Ray; Chakravarti; Bose, Journal of the Chemical Society, 1923, vol. 123, p. 1957,1959
  作者：Ray、Chakravarti、Bose

  DOI：——

  日期：——
• 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.