6-(Morpholin-4-ylmethyl)-5-(4-nitrophenyl)thieno[2,3-d]pyrimidin-4-amine | 866584-50-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 6-(Morpholin-4-ylmethyl)-5-(4-nitrophenyl)thieno[2,3-d]pyrimidin-4-amine
• CAS: 866584-50-1
• 化学式: C₁₇H₁₇N₅O₃S
• 分子量: 371.42
• InChiKey: ANNXTKUFMHGGEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-(Morpholin-4-ylmethyl)-5-(4-nitrophenyl)thieno[2,3-d]pyrimidin-4-amine 在 铁粉 、 氯化铵 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 N-{4-[4-amino-6-(morpholin-4-yl-methyl)thieno[2,3-d]primidin-5-yl]phenyl}-N'-(3-methylphenyl)urea
  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：

  6-methyl-5-(4-nitrophenyl)thieno[2,3-d]pyrimidin-4-amine 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 sodium hydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 6.67h， 生成 6-(Morpholin-4-ylmethyl)-5-(4-nitrophenyl)thieno[2,3-d]pyrimidin-4-amine
  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)).