4-[(3-chloro-4-fluoro-phenyl)amino]-6-amino-[(S)-(tetrahydrofuran-3-yl)oxy]-quinazoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-[(3-chloro-4-fluoro-phenyl)amino]-6-amino-[(S)-(tetrahydrofuran-3-yl)oxy]-quinazoline
• 英文别名: 4-N-(3-chloro-4-fluorophenyl)-2-[(3S)-oxolan-3-yl]oxyquinazoline-4,6-diamine
• 化学式: C₁₈H₁₆ClFN₄O₂
• 分子量: 374.802
• InChiKey: VHFKRQZPEXUJIA-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  82.3
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  二乙基磷乙酸 、 4-[(3-chloro-4-fluoro-phenyl)amino]-6-amino-[(S)-(tetrahydrofuran-3-yl)oxy]-quinazoline 在 N,N'-羰基二咪唑 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 5.0h， 以88%的产率得到{[4-((3-氯-4-氟苯基)氨基)-7-(((S)-四氢呋喃-3-氧基)-6-喹啉)氨基甲酰基]甲基}膦酸二乙酯
  参考文献：
  名称：

  Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them

  摘要：

  本发明涉及一般式的双环杂环化合物 其中 R a ，R b ，R c ，R d ，R e 和X的定义如权利要求书中所述， 其互变异构体、立体异构体、它们的混合物及其盐，特别是其与无机或有机酸形成的生理上可接受的盐，具有有价值的药理特性，特别是对酪氨酸激酶介导的信号传导具有抑制作用，其用于治疗疾病，特别是肿瘤性疾病和良性前列腺增生（BPH），肺部和呼吸道疾病，以及其制备。

  公开号：

  US20050107358A1

文献信息

• Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for the preparation thereof
  申请人：Himmelsbach Frank

  公开号：US20050159436A1

  公开（公告）日：2005-07-21

  The present invention relates to bicyclic heterocycles of general formula wherein R a , R b , R c , A, B, C, D, E and X are defined as in claim 1, the tautomers, the stereoisomers, the mixtures and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids which have valuable pharmacological properties, particularly an inhibitory effect on signal transduction mediated by tyrosine kinases, the use thereof for treating diseases, particularly tumoral diseases, as well as benign prostatic hyperplasia (BPH), diseases of the lungs and respiratory tract, and the preparation thereof.

  本发明涉及一般式为的双环杂环化合物， 其中Ra，Rb，Rc，A，B，C，D，E和X如权利要求1所定义，其互变异构体、立体异构体、混合物及其与无机或有机酸形成的生理上可接受的盐，具有有价值的药理学特性，特别是对酪氨酸激酶介导的信号转导具有抑制作用，其用于治疗疾病，特别是肿瘤性疾病、良性前列腺增生（BPH）、肺和呼吸道疾病，以及其制备方法。
• BICYCLIC HETEROCYCLES, PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS, THEIR USE AND PROCESSES FOR THE PREPARATION THEREOF
  申请人：Himmelsbach Frank

  公开号：US20080103161A1

  公开（公告）日：2008-05-01

  The present invention relates to bicyclic heterocycles of general formula wherein R a , R b , R c , A, B, C, D, E and X are defined as in claim 1 , the tautomers, the stereoisomers, the mixtures and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids which have valuable pharmacological properties, particularly an inhibitory effect on signal transduction mediated by tyrosine kinases, the use thereof for treating diseases, particularly tumoral diseases, as well as benign prostatic hyperplasia (BPH), diseases of the lungs and respiratory tract, and the preparation thereof.

  本发明涉及一般式为的双环杂环化合物 其中Ra，Rb，Rc，A，B，C，D，E和X如权利要求1中所定义，其互变异构体，立体异构体，混合物和盐，特别是其与无机或有机酸的生理上可接受的盐，具有有价值的药理特性，特别是对由酪氨酸激酶介导的信号转导具有抑制作用，其用于治疗疾病，特别是肿瘤性疾病，以及良性前列腺增生症（BPH），肺和呼吸道疾病，以及其制备方法。
• Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells, or angiogenesis
  申请人：BOEHRINGER INGELHEIM INTERNATIONAL GMBH

  公开号：EP2361626A1

  公开（公告）日：2011-08-31

  The present invention relates to a pharmaceutical combination for the treatment of diseases which involves cell proliferation, migration or apoptosis of myeloma cells, or angiogenesis. The invention also relates to a method for the treatment of said diseases, comprising co-administration of effective amounts of specific active compounds and/or co-treatment with radiation therapy, in a ratio which provides an additive and synergistic effect, and to the combined use of these specific compounds and/or radiotherapy for the manufacture of corresponding pharmaceutical combination preparations.

  本发明涉及一种药物组合，用于治疗涉及骨髓瘤细胞增殖、迁移或凋亡或血管生成的疾病。本发明还涉及一种治疗上述疾病的方法，包括以提供相加和协同效应的比例联合给药有效量的特定活性化合物和/或联合放射治疗，以及联合使用这些特定化合物和/或放射治疗来制造相应的药物组合制剂。
• Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis
  申请人：BOEHRINGER INGELHEIM INTERNATIONAL GMBH

  公开号：EP2409705A1

  公开（公告）日：2012-01-25

  The present invention relates to a pharmaceutical combination for the treatment of diseases which involves cell proliferation, migration or apoptosis of myeloma cells, or angiogenesis. The invention also relates to a method for the treatment of said diseases, comprising co-administration of effective amounts of specific active compounds and/or co-treatment with radiation therapy, in a ratio which provides an additive and synergistic effect, and to the combined use of these specific compounds and/or radiotherapy for the manufacture of corresponding pharmaceutical combination preparations.

  本发明涉及一种药物组合，用于治疗涉及骨髓瘤细胞增殖、迁移或凋亡或血管生成的疾病。本发明还涉及一种治疗上述疾病的方法，包括以提供相加和协同效应的比例联合给药有效量的特定活性化合物和/或联合放射治疗，以及联合使用这些特定化合物和/或放射治疗来制造相应的药物组合制剂。
• BICYCLISCHE HETEROCYCLEN, DIESE VERBINDUNGEN ENTHALTENDE ARZNEIMITTEL, IHRE VERWENDUNG UND VERFAHREN ZU IHRER HERSTELLUNG
  申请人：BOEHRINGER INGELHEIM PHARMA GMBH & CO. KG

  公开号：EP1499619A1

  公开（公告）日：2005-01-26