7-fluoro-5-morpholin-4-ylquinazolin-4(3H)-one | 379230-65-6

• 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: 7-fluoro-5-morpholin-4-ylquinazolin-4(3H)-one
• 英文别名: 7-fluoro-5-morpholino-3,4-dihydroquinazolin-4-one；7-fluoro-5-morpholin-4-yl-3H-quinazolin-4-one
• CAS: 379230-65-6
• 化学式: C₁₂H₁₂FN₃O₂
• 分子量: 249.245
• InChiKey: NLYGZTRFILSHCL-UHFFFAOYSA-N

物化性质

• 沸点：
  455.7±55.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  53.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-fluoro-5-morpholin-4-ylquinazolin-4(3H)-one 在 sodium hydride 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.25h， 生成 4-chloro-5-morpholino-7-(2-pyrrolidin-1-ylethoxy)quinazoline
  参考文献：
  名称：

  N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a Novel, Highly Selective, Orally Available, Dual-Specific c-Src/Abl Kinase Inhibitor

  摘要：

  Src family kinases (SFKs) are nonreceptor tyrosine kinases that are reported to be critical for cancer progression. We report here a novel subseries of C-5-substituted anilinoquinazolines that display high affinity and specificity for the tyrosine kinase domain of the c-Src and Abl enzymes. These compounds exhibit high selectivity for SFKs over a panel of recombinant protein kinases, excellent pharmacokinetics, and in vivo activity following oral dosing. N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine (AZD0530) inhibits c-Src and Abl enzymes at low nanomolar concentrations and is highly selective over a range of kinases. AZD0530 displays excellent pharmacokinetic parameters in animal preclinically and in man (t(1/2) = 40 h). AZD0530 is a potent inhibitor of tumor growth in a c-Src-transfected 3T3-fibroblast xenograft model in vivo and led to a significant increase in survival in a highly aggressive, orthotopic model of human pancreatic cancer when dosed orally once daily. AZD0530 is currently undergoing clinical evaluation in man.

  DOI：

  10.1021/jm060434q
• 作为产物：
  描述：

  4,6-二氟靛红 在 sodium hydroxide 、 双氧水 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 二氯甲烷 、 乙二醇甲醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.5h， 生成 7-fluoro-5-morpholin-4-ylquinazolin-4(3H)-one
  参考文献：
  名称：

  N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a Novel, Highly Selective, Orally Available, Dual-Specific c-Src/Abl Kinase Inhibitor

  摘要：

  Src family kinases (SFKs) are nonreceptor tyrosine kinases that are reported to be critical for cancer progression. We report here a novel subseries of C-5-substituted anilinoquinazolines that display high affinity and specificity for the tyrosine kinase domain of the c-Src and Abl enzymes. These compounds exhibit high selectivity for SFKs over a panel of recombinant protein kinases, excellent pharmacokinetics, and in vivo activity following oral dosing. N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine (AZD0530) inhibits c-Src and Abl enzymes at low nanomolar concentrations and is highly selective over a range of kinases. AZD0530 displays excellent pharmacokinetic parameters in animal preclinically and in man (t(1/2) = 40 h). AZD0530 is a potent inhibitor of tumor growth in a c-Src-transfected 3T3-fibroblast xenograft model in vivo and led to a significant increase in survival in a highly aggressive, orthotopic model of human pancreatic cancer when dosed orally once daily. AZD0530 is currently undergoing clinical evaluation in man.

  DOI：

  10.1021/jm060434q

文献信息

• [EN] QUINAZOLINE DERIVATIVES FOR THE TREATMENT OF TUMOURS<br/>[FR] DERIVES DE LA QUINAZOLINE POUR LE TRAITEMENT DE TUMEURS
  申请人：ASTRAZENECA AB

  公开号：WO2001094341A1

  公开（公告）日：2001-12-13

  The invention concerns quinazoline derivatives of Formula (I) wherein each of Q1, Z, m, R?1, R2, R3 and Q2¿ have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an anti-invasive agent in the containment and/or treatment of solid tumour disease.

  本发明涉及公式（I）的喹唑啉衍生物，其中Q1，Z，m，R?1，R2，R3和Q2¿中的每一个都具有描述中定义的任何含义；制备它们的过程，含有它们的制药组合物以及它们在制造用于抗侵袭剂的药物，用于包含和/或治疗实体肿瘤疾病。
• Quinazoline derivatives for treatment of tumours
  申请人：——

  公开号：US20040214841A1

  公开（公告）日：2004-10-28

  The invention concerns quinazoline derivatives of Formula (I) wherein each of Q 1 , Z, m, R 1 , R 2 , R 3 and Q 2 have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an anti-invasive agent in the containment and/or treatment of solid tumour disease. 1

  本发明涉及公式（I）的喹嗪衍生物，其中Q1、Z、m、R1、R2、R3和Q2中的每个都具有描述中定义的任何含义；制备它们的过程，包含它们的制药组合物以及它们在制造用于抗侵袭剂以限制和/或治疗实体肿瘤疾病的药物中的使用。
• Quinazoline derivatives for the treatment of t cell mediated diseases
  申请人：Moore Corine Nelly

  公开号：US20050038050A1

  公开（公告）日：2005-02-17

  The invention concerns the use of the quinazoline derivatives of Formula (I) wherein each of Q 1 , Z, m, R 1 , R 2 , R 3 and Q 2 have any of the meanings defined in the description in the manufacture of a medicament for use in the prevention or treatment of T cell mediated diseases or medical conditions in a warm-blooded animal.

  本发明涉及在温血动物中预防或治疗T细胞介导的疾病或医疗状况的药物制剂的制造中使用公式（I）的喹唑啉衍生物，其中Q1，Z，m，R1，R2，R3和Q2中的每一个都具有描述中定义的任何含义。
• Quinazoline derivatives for the treatment of tumours
  申请人：Hennequin Francois Andre Laurent

  公开号：US20060258642A1

  公开（公告）日：2006-11-16

  The invention concerns quinazoline derivatives of Formula (I) wherein each of Q 1 , Z, m, R 1 , R 2 , R 3 and Q 2 have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an anti-invasive agent in the containment and/or treatment of solid tumour disease.

  本发明涉及公式（I）的喹唑啉衍生物，其中Q1，Z，m，R1，R2，R3和Q2中的每一个都具有描述中定义的任何含义；其制备过程，含有它们的制药组合物以及它们在制造用于抗侵袭剂在包含和/或治疗实体肿瘤疾病的药物中的应用。
• QUINAZOLINE DERIVATIVES FOR THE TREATMENT OF TUMOURS
  申请人：AstraZeneca AB

  公开号：EP1292594B1

  公开（公告）日：2004-09-01