2-氨基-6-[(1-甲基-3-哌啶基)氧基]苯腈 | 1104467-66-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 2-氨基-6-[(1-甲基-3-哌啶基)氧基]苯腈
• 英文名称: 6-amino-2-(1-methyl(3-piperidyloxy))benzenecarbonitrile
• 英文别名: 2-Amino-6-[(1-methyl-3-piperidinyl)oxy]benzonitrile；2-amino-6-(1-methylpiperidin-3-yl)oxybenzonitrile
• CAS: 1104467-66-4
• 化学式: C₁₃H₁₇N₃O
• 分子量: 231.297
• InChiKey: OHXJXNWOOLGAIJ-UHFFFAOYSA-N

物化性质

• 沸点：
  419.5±45.0 °C(Predicted)
• 密度：
  1.17

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  62.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(1H-1,3-苯并咪唑-2-基)乙酸乙酯 、 2-氨基-6-[(1-甲基-3-哌啶基)氧基]苯腈 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以8%的产率得到4-氨基-3-(1H-苯并咪唑-2-基)-5-[(1-甲基-3-哌啶基)氧基]-2(1H)-喹啉酮
  参考文献：
  名称：

  Design, Structure−Activity Relationships and in Vivo Characterization of 4-Amino-3-benzimidazol-2-ylhydroquinolin-2-ones: A Novel Class of Receptor Tyrosine Kinase Inhibitors

  摘要：

  The inhibition of key receptor tyrosine kinases (RTKs) that are implicated in tumor vasculature formation and maintenance, as well as tumor progression and metastasis, has been a major focus in oncology research over the last several years. Many potent small molecule inhibitors of vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) kinases have been evaluated. More recently, compounds that act through the complex inhibition of multiple kinase targets have been reported and may exhibit improved clinical efficacy. We report herein a series of potent, orally efficacious 4-amino3-benzimidazol-2-ylhydroquinolin-2-one analogues as inhibitors of VEGF, PDGF, and fibroblast growth factor (FGF) receptor tyrosine kinases. Compounds in this class, such as 5 (TK1258), are reversible ATP-competitive inhibitors of VEGFR-2, FGFR-1, and PDGFR beta with IC50 values <0.1 mu M. On the basis of its favorable in vitro and in vivo properties, compound 5 was selected for clinical evaluation and is currently in phase I clinical trials.

  DOI：

  10.1021/jm800790t
• 作为产物：
  描述：

  3-羟基-1-甲基哌啶 、 2-氨基-6-氟苯腈 在 sodium hydride 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 2.25h， 以49%的产率得到2-氨基-6-[(1-甲基-3-哌啶基)氧基]苯腈
  参考文献：
  名称：

  Design, Structure−Activity Relationships and in Vivo Characterization of 4-Amino-3-benzimidazol-2-ylhydroquinolin-2-ones: A Novel Class of Receptor Tyrosine Kinase Inhibitors

  摘要：

  The inhibition of key receptor tyrosine kinases (RTKs) that are implicated in tumor vasculature formation and maintenance, as well as tumor progression and metastasis, has been a major focus in oncology research over the last several years. Many potent small molecule inhibitors of vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) kinases have been evaluated. More recently, compounds that act through the complex inhibition of multiple kinase targets have been reported and may exhibit improved clinical efficacy. We report herein a series of potent, orally efficacious 4-amino3-benzimidazol-2-ylhydroquinolin-2-one analogues as inhibitors of VEGF, PDGF, and fibroblast growth factor (FGF) receptor tyrosine kinases. Compounds in this class, such as 5 (TK1258), are reversible ATP-competitive inhibitors of VEGFR-2, FGFR-1, and PDGFR beta with IC50 values <0.1 mu M. On the basis of its favorable in vitro and in vivo properties, compound 5 was selected for clinical evaluation and is currently in phase I clinical trials.

  DOI：

  10.1021/jm800790t

文献信息

• Design, Structure−Activity Relationships and in Vivo Characterization of 4-Amino-3-benzimidazol-2-ylhydroquinolin-2-ones: A Novel Class of Receptor Tyrosine Kinase Inhibitors
  作者：Paul A. Renhowe、Sabina Pecchi、Cynthia M. Shafer、Timothy D. Machajewski、Elisa M. Jazan、Clarke Taylor、William Antonios-McCrea、Christopher M. McBride、Kelly Frazier、Marion Wiesmann、Gena R. Lapointe、Paul H. Feucht、Robert L. Warne、Carla C. Heise、Daniel Menezes、Kimberly Aardalen、Helen Ye、Molly He、Vincent Le、Jayesh Vora、Johanna M. Jansen、Mary Ellen Wernette-Hammond、Alex L. Harris

  DOI：10.1021/jm800790t

  日期：2009.1.22

  The inhibition of key receptor tyrosine kinases (RTKs) that are implicated in tumor vasculature formation and maintenance, as well as tumor progression and metastasis, has been a major focus in oncology research over the last several years. Many potent small molecule inhibitors of vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) kinases have been evaluated. More recently, compounds that act through the complex inhibition of multiple kinase targets have been reported and may exhibit improved clinical efficacy. We report herein a series of potent, orally efficacious 4-amino3-benzimidazol-2-ylhydroquinolin-2-one analogues as inhibitors of VEGF, PDGF, and fibroblast growth factor (FGF) receptor tyrosine kinases. Compounds in this class, such as 5 (TK1258), are reversible ATP-competitive inhibitors of VEGFR-2, FGFR-1, and PDGFR beta with IC50 values <0.1 mu M. On the basis of its favorable in vitro and in vivo properties, compound 5 was selected for clinical evaluation and is currently in phase I clinical trials.