4-(3-chloro-2-fluorophenylamino)-7-methoxyquinazoline-6-carbaldehyde | 848488-65-3

• 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-2-fluorophenylamino)-7-methoxyquinazoline-6-carbaldehyde
• 英文别名: 4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazoline-6-carbaldehyde；4-(3-chloro-2-fluoroanilino)-6-carbaldehyde-7-methoxy quinazoline；4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline-6-carbaldehyde
• CAS: 848488-65-3
• 化学式: C₁₆H₁₁ClFN₃O₂
• 分子量: 331.734
• InChiKey: XWHXIIWBTYYFQA-UHFFFAOYSA-N

物化性质

• 沸点：
  478.6±45.0 °C(Predicted)
• 密度：
  1.455±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  64.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(3-chloro-2-fluorophenylamino)-7-methoxyquinazoline-6-carbaldehyde 在 吡啶 、 magnesium bromide 、 水 作用下， 反应 16.0h， 以100%的产率得到4-[(3-chloro-2-fluorophenyl)amino]-7-hydroxyquinazoline-6-carbaldehyde
  参考文献：
  名称：

  [EN] QUINAZOLINE DERIVATIVES
  [FR] DERIVES DE QUINAZOLINE

  摘要：

  一种式(I)的喹唑啉衍生物，其中：R1、R2、R3、R3a、R4、R5、R5a、R6、R7、a、m和p如描述中所定义。还声明含有该喹唑啉衍生物的药物组合物，以及将该喹唑啉衍生物用作药物和制备该喹唑啉衍生物的方法。式(I)的喹唑啉衍生物在治疗高增殖性疾病如癌症方面具有用途。

  公开号：

  WO2005075439A1
• 作为产物：
  描述：

  4-(3-chloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yl trifluoromethanesulfonate 在 1,1'-双(二苯基膦)二茂铁 、 四丁基溴化铵 、 palladium diacetate 、 臭氧 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 生成 4-(3-chloro-2-fluorophenylamino)-7-methoxyquinazoline-6-carbaldehyde
  参考文献：
  名称：

  Discovery and Evaluation of Clinical Candidate AZD3759, a Potent, Oral Active, Central Nervous System-Penetrant, Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor

  摘要：

  Recent reports suggest that an increasing number of patients with lung cancer, especially those with activating mutations of the epidermal growth factor receptor (EGFR), also present with brain metastases and leptomeningeal metastases. These patients have poor prognosis as there are no approved drugs for these indications. Available agents have poor efficacy for these patients even at well above their standard dose. Herein, we report the discovery of (4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl (2R)-2,4-dimethylpiperazine-1-carboxylate 1m (AZD3759), an investigational drug currently in Phase 1 clinical trial, which has excellent central nervous system penetration and which induces profound regression of brain metastases in a mouse model.

  DOI：

  10.1021/acs.jmedchem.5b01073

文献信息

• Quinazoline Derivatives
  申请人：Hennequin Laurent Francois Andre

  公开号：US20080234263A1

  公开（公告）日：2008-09-25

  The invention concerns quinazoline derivatives of Formula (I) wherein each of R 1 , R 3 , R 20 , X 1 , X 2 , Z, W, (a) and (q) 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 antiproliferative agent in the prevention or treatment of turnours which are sensitive to inhibition of erbB receptor tyrosine kinases, particularly EGFR tyrosine kinase.

  本发明涉及公式(I)的喹嗪衍生物，其中R1、R3、R20、X1、X2、Z、W、(a)和(q)中的每一个具有在说明书中定义的任何含义；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作抗增殖剂的药物中的用途，用于预防或治疗对erbB受体酪氨酸激酶抑制敏感的肿瘤，特别是EGFR酪氨酸激酶。
• Quinazoline compounds for the treatment of hyperproliferative disorders
  申请人：AstraZeneca AB

  公开号：US07632840B2

  公开（公告）日：2009-12-15

  A quinazoline derivative of the formula I: wherein: R1, R2, R3, R3a, R4, R5, R5a R6, R7, a, m and p are as defined in the description. Also claimed are pharmaceutical compositions containing the quinazoline derivative, the use of the quinazoline derivatives as medicaments and processes for the preparation of the quinazoline derivative. The quinazoline derivatives of formula I, are useful in the treatment of hyperproliferative disorders such as a cancer.

  公式I的喹唑啉衍生物，其中：R1、R2、R3、R3a、R4、R5、R5a、R6、R7、a、m和p如描述中所定义。还声明了含有喹唑啉衍生物的制药组合物，以及将喹唑啉衍生物用作药物和制备喹唑啉衍生物的过程。公式I的喹唑啉衍生物在治疗高增殖性疾病（如癌症）方面具有用途。
• QUINAZOLINE DERIVATIVES
  申请人：AstraZeneca AB

  公开号：EP1664030A1

  公开（公告）日：2006-06-07
• US7632840B2
  申请人：——

  公开号：US7632840B2

  公开（公告）日：2009-12-15
• Discovery and Evaluation of Clinical Candidate AZD3759, a Potent, Oral Active, Central Nervous System-Penetrant, Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor
  作者：Qingbei Zeng、Jiabing Wang、Ziqiang Cheng、Kan Chen、Peter Johnström、Katarina Varnäs、David Yunzhi Li、Zhen Fan Yang、Xiaolin Zhang

  DOI：10.1021/acs.jmedchem.5b01073

  日期：2015.10.22

  Recent reports suggest that an increasing number of patients with lung cancer, especially those with activating mutations of the epidermal growth factor receptor (EGFR), also present with brain metastases and leptomeningeal metastases. These patients have poor prognosis as there are no approved drugs for these indications. Available agents have poor efficacy for these patients even at well above their standard dose. Herein, we report the discovery of (4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl (2R)-2,4-dimethylpiperazine-1-carboxylate 1m (AZD3759), an investigational drug currently in Phase 1 clinical trial, which has excellent central nervous system penetration and which induces profound regression of brain metastases in a mouse model.