| 405939-47-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• CAS: 405939-47-1
• 化学式: C₂₉H₃₂ClN₅O₇
• 分子量: 598.055
• InChiKey: VPZYRYRXHSPDHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  42.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  141.12
• 氢给体数：
  0.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  在 三氟乙酸 作用下， 反应 60.0h， 以26 mg的产率得到[2-[[5-[6-(3-Chloroanilino)pyrazin-2-yl]pyridin-3-yl]amino]-2-oxoethyl] acetate
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Pyrazine-Pyridine Biheteroaryls as Novel, Potent, and Selective Vascular Endothelial Growth Factor Receptor-2 Inhibitors

  摘要：

  There is much evidence that direct inhibition of the kinase activity of vascular endothelial growth factor receptor-2 (VEGFR-2) will result in the reduction of angiogenesis and the suppression of tumor growth. Palladium-catalyzed C-C bond, C-N bond formation reactions were used to assemble various pyrazine-pyridine biheteroaryls as potent VEGFR-2 inhibitors. Among them, 4-{5-[6-(3-chloro-phenylamino)-pyrazin-2-yl]-pyridin-3-ylamino}-butan-1-ol (39) and N-{5-[6-(3-chloro-phenylamino)-pyrazin-2-yl]-pyridin-3-yl}-N ',N '-dimethyl-ethane-1,2-diamine (41) exhibited the highest kinase selectivity against fibroblast growth factor receptor kinase, platelet-derived growth factor receptor kinase, and glycogen synthase kinase-3. All of these compounds showed good cellular potency to inhibit VEGF-stimulated proliferation of human umbilical vein endothelial cells (HUVEC) but with modest effects on the unstimulated growth of HUVEC. The low inhibition of these compounds to the growth of tumor cell lines, such as HeLa, HCT-116, and A375 further confirms that these VEGFR-2 inhibitors are not cytotoxic agents. The in vivo antitumor activity of 39 and 41 were demonstrated in the A375 human melanoma xenograft nude mice model. Molecular modeling (QSAR analysis) was conducted in an attempt to rationalize the observed structure-activity relationship.

  DOI：

  10.1021/jm058205b
• 作为产物：
  描述：

  5-{6-[tert-butoxycarbonyl-(3-chlorophenyl)amino]pyrazin-2-yl}nicotinic acid 在 二苯基膦叠氮化物 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 23.0h， 生成
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Pyrazine-Pyridine Biheteroaryls as Novel, Potent, and Selective Vascular Endothelial Growth Factor Receptor-2 Inhibitors

  摘要：

  There is much evidence that direct inhibition of the kinase activity of vascular endothelial growth factor receptor-2 (VEGFR-2) will result in the reduction of angiogenesis and the suppression of tumor growth. Palladium-catalyzed C-C bond, C-N bond formation reactions were used to assemble various pyrazine-pyridine biheteroaryls as potent VEGFR-2 inhibitors. Among them, 4-{5-[6-(3-chloro-phenylamino)-pyrazin-2-yl]-pyridin-3-ylamino}-butan-1-ol (39) and N-{5-[6-(3-chloro-phenylamino)-pyrazin-2-yl]-pyridin-3-yl}-N ',N '-dimethyl-ethane-1,2-diamine (41) exhibited the highest kinase selectivity against fibroblast growth factor receptor kinase, platelet-derived growth factor receptor kinase, and glycogen synthase kinase-3. All of these compounds showed good cellular potency to inhibit VEGF-stimulated proliferation of human umbilical vein endothelial cells (HUVEC) but with modest effects on the unstimulated growth of HUVEC. The low inhibition of these compounds to the growth of tumor cell lines, such as HeLa, HCT-116, and A375 further confirms that these VEGFR-2 inhibitors are not cytotoxic agents. The in vivo antitumor activity of 39 and 41 were demonstrated in the A375 human melanoma xenograft nude mice model. Molecular modeling (QSAR analysis) was conducted in an attempt to rationalize the observed structure-activity relationship.

  DOI：

  10.1021/jm058205b