6,6-dicyano-5-phenylhex-5-enoic acid methylamide | 866581-23-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 6,6-dicyano-5-phenylhex-5-enoic acid methylamide
• 英文别名: 6,6-dicyano-N-methyl-5-phenylhex-5-enamide
• CAS: 866581-23-9
• 化学式: C₁₅H₁₅N₃O
• 分子量: 253.304
• InChiKey: GLPIBUYZIMUKIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  76.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6,6-dicyano-5-phenylhex-5-enoic acid methylamide 在 硫酸 、 硝酸 、 铁粉 、 氯化铵 、 sulfur 、 二乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 22.25h， 生成 3-[4-amino-5-(4-aminophenyl)thieno[2,3-d]pyrimidin-6-yl]-N-methylpropanamide
  参考文献：
  名称：

  Thienopyrimidine Ureas as Novel and Potent Multitargeted Receptor Tyrosine Kinase Inhibitors

  摘要：

  A series of novel thienopyrimidine-based receptor tyrosine kinase inhibitors has been discovered. Investigation of structure-activity relationships at the 5- and 6-positions of the thienopyrimidine nucleus led to a series of N,N '-diaryl ureas that potently inhibit all of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor tyrosine kinases. A kinase insert domain-containing receptor (KDR) homology model suggests that these compounds bind to the "inactive conformation" of the enzyme with the urea portion extending into the back hydrophobic pocket adjacent to the adenosine 5 '-triphosphate (ATP) binding site. A number of compounds have been identified as displaying excellent in vivo potency. In particular, compounds 28 and 76 possess favorable pharmacokinetic (PK) profiles and demonstrate potent antitumor efficacy against the HT1080 human fibrosarcoma xenograft tumor growth model (tumor growth inhibition (TGI) = 75% at 25 mg/kg-day, per os (po)).

  DOI：

  10.1021/jm050458h
• 作为产物：
  描述：

  4-苯甲酰基丁酸 在 N-甲基吗啉 、 ammonium acetate 、 1-羟基苯并三唑 、 溶剂黄146 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 18.0h， 生成 6,6-dicyano-5-phenylhex-5-enoic acid methylamide
  参考文献：
  名称：

  Thienopyrimidine Ureas as Novel and Potent Multitargeted Receptor Tyrosine Kinase Inhibitors

  摘要：

  A series of novel thienopyrimidine-based receptor tyrosine kinase inhibitors has been discovered. Investigation of structure-activity relationships at the 5- and 6-positions of the thienopyrimidine nucleus led to a series of N,N '-diaryl ureas that potently inhibit all of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor tyrosine kinases. A kinase insert domain-containing receptor (KDR) homology model suggests that these compounds bind to the "inactive conformation" of the enzyme with the urea portion extending into the back hydrophobic pocket adjacent to the adenosine 5 '-triphosphate (ATP) binding site. A number of compounds have been identified as displaying excellent in vivo potency. In particular, compounds 28 and 76 possess favorable pharmacokinetic (PK) profiles and demonstrate potent antitumor efficacy against the HT1080 human fibrosarcoma xenograft tumor growth model (tumor growth inhibition (TGI) = 75% at 25 mg/kg-day, per os (po)).

  DOI：

  10.1021/jm050458h

文献信息

• Thienopyrimidine Ureas as Novel and Potent Multitargeted Receptor Tyrosine Kinase Inhibitors
  作者：Yujia Dai、Yan Guo、Robin R. Frey、Zhiqin Ji、Michael L. Curtin、Asma A. Ahmed、Daniel H. Albert、Lee Arnold、Shannon S. Arries、Teresa Barlozzari、Joy L. Bauch、Jennifer J. Bouska、Peter F. Bousquet、George A. Cunha、Keith B. Glaser、Jun Guo、Junling Li、Patrick A. Marcotte、Kennan C. Marsh、Maria D. Moskey、Lori J. Pease、Kent D. Stewart、Vincent S. Stoll、Paul Tapang、Neil Wishart、Steven K. Davidsen、Michael R. Michaelides

  DOI：10.1021/jm050458h

  日期：2005.9.1

  A series of novel thienopyrimidine-based receptor tyrosine kinase inhibitors has been discovered. Investigation of structure-activity relationships at the 5- and 6-positions of the thienopyrimidine nucleus led to a series of N,N '-diaryl ureas that potently inhibit all of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor tyrosine kinases. A kinase insert domain-containing receptor (KDR) homology model suggests that these compounds bind to the "inactive conformation" of the enzyme with the urea portion extending into the back hydrophobic pocket adjacent to the adenosine 5 '-triphosphate (ATP) binding site. A number of compounds have been identified as displaying excellent in vivo potency. In particular, compounds 28 and 76 possess favorable pharmacokinetic (PK) profiles and demonstrate potent antitumor efficacy against the HT1080 human fibrosarcoma xenograft tumor growth model (tumor growth inhibition (TGI) = 75% at 25 mg/kg-day, per os (po)).