2-(benzylsulfanyl)-4-(3-thienyl)-5,6,7,8-tetrahydroquinoline-3-carbonitrile | 1233536-78-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-(benzylsulfanyl)-4-(3-thienyl)-5,6,7,8-tetrahydroquinoline-3-carbonitrile
• 英文别名: 2-benzylsulfanyl-4-thiophen-3-yl-5,6,7,8-tetrahydroquinoline-3-carbonitrile
• CAS: 1233536-78-1
• 化学式: C₂₁H₁₈N₂S₂
• 分子量: 362.519
• InChiKey: WVNCYWHQSGTBQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  90.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-(3-thienyl)-2-thioxo-1,2,5,6,7,8-hexahydroquinoline-3-carbonitrile 、 溴甲苯 在 potassium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以48%的产率得到2-(benzylsulfanyl)-4-(3-thienyl)-5,6,7,8-tetrahydroquinoline-3-carbonitrile
  参考文献：
  名称：

  Inhibitors of the RET tyrosine kinase based on a 2-(alkylsulfanyl)-4-(3-thienyl)nicotinonitrile scaffold

  摘要：

  In an approach to optimize 2-(4-fluorobenzylsulfanyl)-4-(2-thienyl)-5,6,7,8-tetrahydroquinoline-3-carbonitrile (1a), a weak inhibitor of the cancer-related tyrosine kinase RET originating from a screening campaign, analogues with 3-thienyl substitution were prepared. Among the novel derivatives, 2-amino-6-{[2-(4-chlorophenyl)-2-oxoethyl]sulfanyl}-4-(3-thienyl)pyridine-3,5-dicarbonitrile (13g) was identified as a submicromolar RET inhibitor, displaying 3- and 100-fold selectivity versus ALK and ABL kinases, respectively. The novel inhibitor exhibited antiproliferative activity in the micromolar concentration range against both RET-dependent and RET-independent cancer cell lines. Docking experiments suggest a binding mode of the new inhibitors in the ATP binding pocket of the target kinase, explaining the observed structure activity relationships. (c) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.03.017

文献信息

• Inhibitors of the RET tyrosine kinase based on a 2-(alkylsulfanyl)-4-(3-thienyl)nicotinonitrile scaffold
  作者：Wiebke Brandt、Luca Mologni、Lutz Preu、Thomas Lemcke、Carlo Gambacorti-Passerini、Conrad Kunick

  DOI：10.1016/j.ejmech.2010.03.017

  日期：2010.7

  In an approach to optimize 2-(4-fluorobenzylsulfanyl)-4-(2-thienyl)-5,6,7,8-tetrahydroquinoline-3-carbonitrile (1a), a weak inhibitor of the cancer-related tyrosine kinase RET originating from a screening campaign, analogues with 3-thienyl substitution were prepared. Among the novel derivatives, 2-amino-6-[2-(4-chlorophenyl)-2-oxoethyl]sulfanyl}-4-(3-thienyl)pyridine-3,5-dicarbonitrile (13g) was identified as a submicromolar RET inhibitor, displaying 3- and 100-fold selectivity versus ALK and ABL kinases, respectively. The novel inhibitor exhibited antiproliferative activity in the micromolar concentration range against both RET-dependent and RET-independent cancer cell lines. Docking experiments suggest a binding mode of the new inhibitors in the ATP binding pocket of the target kinase, explaining the observed structure activity relationships. (c) 2010 Elsevier Masson SAS. All rights reserved.