2,6-dimercapto-7Hpurin-8(9H)-one | 6703-93-1

• 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: 2,6-dimercapto-7Hpurin-8(9H)-one
• 英文别名: 2,6-bis(sulfanylidene)-7,9-dihydro-3H-purin-8-one
• CAS: 6703-93-1
• 化学式: C₅H₄N₄OS₂
• 分子量: 200.245
• InChiKey: SOQYJXVHBQVRDB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  129
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,6-dimercapto-7Hpurin-8(9H)-one 、 乙基溴苯 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 0.08h， 以49%的产率得到2,6-bis(phenethylthio)-7H-purin-8(9H)-one
  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：

  alkaline earth salt of/the/ methylsulfuric acid 在 potassium hydrosulfide 作用下， 生成 2,6-dimercapto-7Hpurin-8(9H)-one
  参考文献：
  名称：

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

  摘要：

  DOI：

文献信息

• Detoxication of Sulfur Half-Mustards by Nucleophilic Scavengers: Robust Activity of Thiopurines
  作者：Jinyun Liu、K. Leslie Powell、Howard D. Thames、Michael C. MacLeod

  DOI：10.1021/tx900190j

  日期：2010.3.15

  Sulfur mustard and monofunctional analogues (half-mustards, 2-[chloroethyl] alkyl sulfides) react as electrophiles, damaging cellular macromolecules, and thus are potentially subject to scavenging by nucleophilic agents. We have determined rate constants for the reaction of four purine derivatives that contain nucleophilic thiol moieties with several sulfur-half-mustards. Three of these compounds, 2,6-dithiopurine

  自第一次世界大战以来，硫芥（双（2-氯乙基）硫化物）一直用于化学战，是众所周知的剧毒起泡剂。在长期低水平暴露后，它被认为是一种致癌物质，并且已知会在 DNA 中形成链间交联。由于易于合成，硫和氮芥作为恐怖分子的潜在化学威胁剂目前受到关注。硫芥和单功能类似物（半芥末，2-[氯乙基] 烷基硫化物）作为亲电试剂反应，破坏细胞大分子，因此可能会被亲核试剂清除。我们已经确定了四种含有亲核硫醇部分的嘌呤衍生物与几种半硫芥的反应速率常数。这些化合物中的三种，2,6-二硫嘌呤、2,6-二硫脲酸、和 9-methyl-6-mercaptopurine，与亲电子芥子化合物表现出容易的反应。在接近中性的 pH 值下，这些硫嘌呤是芥末亲电试剂的亲核清除剂，比其他低分子量硫醇（如N-乙酰半胱氨酸和谷胱甘肽。通过数值积分技术计算的进展曲线表明，等摩尔浓度的硫嘌呤显着减少了对表锍离子的总体暴露，这是硫芥子气溶解在水溶液中时产生的主要反应性亲电子试剂。
• Garkuscha, Zhurnal Obshchei Khimii, 1957, vol. 27, p. 1712,1715;engl.Ausg.S.1783,1785
  作者：Garkuscha

  DOI：——

  日期：——
• Potential Purine Antagonists. XX. The Preparation and Reactions of Some Methylthiopurines¹
  作者：C. Wayne Noell、Roland K. Robins

  DOI：10.1021/ja01531a037

  日期：1959.11
• 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.