6-(3-amino-1H-indazol-4-yl)-N-ethyl-1-naphthamide | 1571111-57-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-(3-amino-1H-indazol-4-yl)-N-ethyl-1-naphthamide
• 英文别名: 6-(3-amino-1H-indazol-4-yl)-N-ethyl-1-naphthalenecarboxamide；6-(3-amino-1H-indazol-4-yl)-N-ethylnaphthalene-1-carboxamide
• CAS: 1571111-57-3
• 化学式: C₂₀H₁₈N₄O
• 分子量: 330.389
• InChiKey: NLNWDQZXNMUIRE-UHFFFAOYSA-N

物化性质

• 熔点：
  206 °C
• 沸点：
  700.0±50.0 °C(predicted)
• 密度：
  1.302±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  83.8
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  6-羟基-1-萘甲酸 在 4-二甲氨基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 1,1'-双(二苯基膦)二茂铁 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 氯化亚砜 、 lithium hydroxide monohydrate 、 水 、 potassium acetate 、 sodium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 21.25h， 生成 6-(3-amino-1H-indazol-4-yl)-N-ethyl-1-naphthamide
  参考文献：
  名称：

  Discovery of a New Series of Naphthamides as Potent VEGFR-2 Kinase Inhibitors

  摘要：

  Inhibition of VEGFR-2 signaling pathway has already become one of the most promising approaches for the treatment of cancer. In this study, we describe the design, synthesis, and biological evaluation of a new series of naphthamides as potent inhibitors of VEGFR-2. Among these compounds, 14c exhibited high VEGFR-2 inhibitory potency in both enzymatic and HUVEC cellular proliferation assays, with IC50 values of 1.5 and 0.9 nM, respectively. Kinase selectivity profiling revealed that 14c was a multitargeted inhibitor, and it also exhibited good potency against VEGFR-1, PDGFR-beta, and RET. Furthermore, 14c effectively blocked tube formation of HUVEC at nanomolar level. Overall, 14c might be a promising candidate for the treatment of cancer.

  DOI：

  10.1021/ml5000417

文献信息

• [EN] NAPHTHYLAMIDE COMPOUND, PREPARATION METHOD AND USE THEREOF<br/>[FR] COMPOSÉ NAPHTYLAMIDE, PROCÉDÉ DE PRÉPARATION ET UTILISATION DE CELUI-CI<br/>[ZH] 萘酰胺类化合物、其制备方法和用途
  申请人：SHANGHAI INST MATERIA MEDICA

  公开号：WO2015124101A1

  公开（公告）日：2015-08-27

  本发明涉及如式(I)所示结构的萘酰胺类化合物、其药用盐、其前药及其水合物或溶剂合物，也涉及所述化合物的制备方法、包含所述化合物的药物组合物以及其作为蛋白酪氨酸激酶抑制剂，特别是作为VEGFR-2抑制剂，在制备预防和/或治疗与异常血管新生相关疾病的药物中的用途。
• NAPHTHYLAMIDE COMPOUND, PREPARATION METHOD AND USE THEREOF
  申请人：Shanghai Institute Of Materia Medica Chinese Academy of Sciences

  公开号：EP3112351B1

  公开（公告）日：2022-03-30
• US9914707B2
  申请人：——

  公开号：US9914707B2

  公开（公告）日：2018-03-13
• Discovery of a New Series of Naphthamides as Potent VEGFR-2 Kinase Inhibitors
  作者：Yongcong Lv、Mengyuan Li、Ting Liu、Linjiang Tong、Ting Peng、Lixin Wei、Jian Ding、Hua Xie、Wenhu Duan

  DOI：10.1021/ml5000417

  日期：2014.5.8

  Inhibition of VEGFR-2 signaling pathway has already become one of the most promising approaches for the treatment of cancer. In this study, we describe the design, synthesis, and biological evaluation of a new series of naphthamides as potent inhibitors of VEGFR-2. Among these compounds, 14c exhibited high VEGFR-2 inhibitory potency in both enzymatic and HUVEC cellular proliferation assays, with IC50 values of 1.5 and 0.9 nM, respectively. Kinase selectivity profiling revealed that 14c was a multitargeted inhibitor, and it also exhibited good potency against VEGFR-1, PDGFR-beta, and RET. Furthermore, 14c effectively blocked tube formation of HUVEC at nanomolar level. Overall, 14c might be a promising candidate for the treatment of cancer.