2,6-bis(propylthio)pyrimidine-4,5-diamine | 187668-70-8

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2,6-bis(propylthio)pyrimidine-4,5-diamine
• 英文别名: 2,6-Bis(propylthio)-4,5-pyrimidinediamine；2,6-bis(propylsulfanyl)pyrimidine-4,5-diamine
• CAS: 187668-70-8
• 化学式: C₁₀H₁₈N₄S₂
• 分子量: 258.412
• InChiKey: SODVEDDQLXKHHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,6-bis(propylthio)pyrimidine-4,5-diamine 在 sodium nitrite 作用下， 以 水 、 溶剂黄146 为溶剂， 生成 5,7-Bis(propylthio)-1H-1,2,3-triazolo[4,5-d]pyrimidine
  参考文献：
  名称：

  Inhibitors of platelet aggregation

  摘要：

  公式（I）的化合物##STR1##其中B为O或CH.sub.2；X选自NR.sup.1R.sup.2、SR.sup.1和C.sub.1-C.sub.7烷基；Y选自SR.sup.1、NR.sup.1R.sup.2和C.sub.1-C.sub.7烷基；R.sup.1和R.sup.2分别且独立地选自H，或C.sub.1-C.sub.7烷基，该烷基可选在或在烷基链内部由一个或多个O、S、N或卤素取代；R.sup.3和R.sup.4均为H，或R.sup.3和R.sup.4一起形成键；A为COOH、C(O)NH(CH.sub.2).sub.pCOOH、C(O)N\x9b(CH.sub.2).sub.qCOOH!.sub.2、C(O)NHCH(COOH)(CH.sub.2).sub.rCOOH或5-四唑基，其中p、q和r各自且独立地为1、2或3；以及其药学上可接受的盐和前药，包括含有这些新化合物的药物组合物以及这些化合物在治疗中的用途。此外，该发明范围还包括新化合物的新中间体。这些新化合物特别适用于预防血小板聚集。

  公开号：

  US05747496A1
• 作为产物：
  描述：

  溴丙烷 、 2,4-二巯基-5,6-二氨基嘧啶 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.08h， 以63%的产率得到2,6-bis(propylthio)pyrimidine-4,5-diamine
  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

• US5747496A
  申请人：——

  公开号：US5747496A

  公开（公告）日：1998-05-05
• Inhibitors of platelet aggregation
  申请人：Astra Pharmaceuticals Limited

  公开号：US05747496A1

  公开（公告）日：1998-05-05

  Compounds of the formula (I) ##STR1## wherein B is O or CH.sub.2 ; X is selected from NR.sup.1 R.sup.2, SR.sup.1, and C.sub.1 -C.sub.7 alkyl; Y is selected SR.sup.1, NR.sup.1 R.sup.2, and C.sub.1 -C.sub.7 alkyl; R.sup.1 and R.sup.2 is each and independently selected from H, or C.sub.1 -C.sub.7 alkyl optionally substituted upon or within the alkyl chain by one or more of O, S, N or halogen; R.sup.3 and R.sup.4 are both H, or R.sup.3 and R.sup.4 together form a bond; A is COOH, C(O)NH(CH.sub.2).sub.p COOH, C(O)N\x9b(CH.sub.2).sub.q COOH!.sub.2, C(O)NHCH(COOH)(CH.sub.2).sub.r COOH, or 5-tetrazolyl, wherein p, q and r is each and independently 1, 2 or 3; as well as pharmaceutically acceptable salts and prodrugs thereof, pharmaceutical compositions comprising the novel compounds and use of the compounds in therapy. Also within the scope of the invention are novel intermediates to the novel compounds. The novel compounds are in particular useful in the prevention of platelet aggregation.

  公式（I）的化合物##STR1##其中B为O或CH.sub.2；X选自NR.sup.1R.sup.2、SR.sup.1和C.sub.1-C.sub.7烷基；Y选自SR.sup.1、NR.sup.1R.sup.2和C.sub.1-C.sub.7烷基；R.sup.1和R.sup.2分别且独立地选自H，或C.sub.1-C.sub.7烷基，该烷基可选在或在烷基链内部由一个或多个O、S、N或卤素取代；R.sup.3和R.sup.4均为H，或R.sup.3和R.sup.4一起形成键；A为COOH、C(O)NH(CH.sub.2).sub.pCOOH、C(O)N\x9b(CH.sub.2).sub.qCOOH!.sub.2、C(O)NHCH(COOH)(CH.sub.2).sub.rCOOH或5-四唑基，其中p、q和r各自且独立地为1、2或3；以及其药学上可接受的盐和前药，包括含有这些新化合物的药物组合物以及这些化合物在治疗中的用途。此外，该发明范围还包括新化合物的新中间体。这些新化合物特别适用于预防血小板聚集。
• 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.