5-(1-naphthylsulfanyl)-9H-pyrimido[4,5-b]indole-2,4-diamine

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 5-(1-naphthylsulfanyl)-9H-pyrimido[4,5-b]indole-2,4-diamine
• 英文别名: 5-naphthalen-1-ylsulfanyl-9H-pyrimido[4,5-b]indole-2,4-diamine
• 化学式: C₂₀H₁₅N₅S
• 分子量: 357.439
• InChiKey: IUCBNZCMMDEDRD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-奈硫酚 、 5-chloro-9H-pyrimido[4,5-b]indole-2,4-diamine 在 potassium carbonate 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 0.5h， 以70%的产率得到5-(1-naphthylsulfanyl)-9H-pyrimido[4,5-b]indole-2,4-diamine
  参考文献：
  名称：

  Synthesis and evaluation of 5-(arylthio)-9 H -pyrimido[4,5- b ]indole-2,4-diamines as receptor tyrosine kinase and thymidylate synthase inhibitors and as antitumor agents

  摘要：

  In an effort to optimize the structural requirements for combined cytostatic and cytotoxic effects in single agents, a series of 5-(arylthio)-9H-pyrimido[4,5-b]indole-2,4-diamines 3-7 were synthesized and evaluated as inhibitors of receptor tyrosine kinases (RTKs) as well as thymidylate synthase (TS). The synthesis of these compounds involved the nucleophilic displacement of the common intermediate 5-bromo/5-chloro-9H-pyrimido[4,5-b]indole-2,4-diamine with appropriate aryl thiols. A novel four step synthetic scheme to the common intermediate was developed which is more efficient relative to the previously reported six-step sequence. Biological evaluation of these compounds indicated dual activity in RTKs and human TS (hTS). In the VEGFR-2 assay, compound 5 was equipotent to the standard compound semaxanib and was better than standard TS inhibitor pemetrexed, in the hTS assay. Compounds 3, 6 and 7 were nanomolar inhibitors of hTS and were several fold better than pemetrexed. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.02.018

文献信息

• Synthesis and evaluation of 5-(arylthio)-9 H -pyrimido[4,5- b ]indole-2,4-diamines as receptor tyrosine kinase and thymidylate synthase inhibitors and as antitumor agents
  作者：Nilesh Zaware、Roy Kisliuk、Anja Bastian、Michael A. Ihnat、Aleem Gangjee

  DOI：10.1016/j.bmcl.2017.02.018

  日期：2017.4

  In an effort to optimize the structural requirements for combined cytostatic and cytotoxic effects in single agents, a series of 5-(arylthio)-9H-pyrimido[4,5-b]indole-2,4-diamines 3-7 were synthesized and evaluated as inhibitors of receptor tyrosine kinases (RTKs) as well as thymidylate synthase (TS). The synthesis of these compounds involved the nucleophilic displacement of the common intermediate 5-bromo/5-chloro-9H-pyrimido[4,5-b]indole-2,4-diamine with appropriate aryl thiols. A novel four step synthetic scheme to the common intermediate was developed which is more efficient relative to the previously reported six-step sequence. Biological evaluation of these compounds indicated dual activity in RTKs and human TS (hTS). In the VEGFR-2 assay, compound 5 was equipotent to the standard compound semaxanib and was better than standard TS inhibitor pemetrexed, in the hTS assay. Compounds 3, 6 and 7 were nanomolar inhibitors of hTS and were several fold better than pemetrexed. (C) 2017 Elsevier Ltd. All rights reserved.