2-chloro-N-(3,4-dimethoxyphenyl)-N-methylquinazolin-4-amine | 827030-98-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-chloro-N-(3,4-dimethoxyphenyl)-N-methylquinazolin-4-amine
• 英文别名: (2-chloro-quinazolin-4-yl)-(3,4-dimethoxy-phenyl)-methyl-amine
• CAS: 827030-98-8
• 化学式: C₁₇H₁₆ClN₃O₂
• 分子量: 329.786
• InChiKey: REQTXYJALZRJCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  47.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2-{4-[(3,4-dimethoxy-phenyl)-methyl-amino]-quinazolin-2-ylamino}-ethyl)-carbamic acid tert-butyl ester 、 2-chloro-N-(3,4-dimethoxyphenyl)-N-methylquinazolin-4-amine 、 N,N-二异丙基乙胺 、 N-叔丁氧羰基-1,2-乙二胺 在 crude material 、 氯仿 、 碳酸氢钠 、 水 、 magnesium sulfate 、 silica 、 甲醇 、 ammonium hydroxide 、 amine 、 异丙醇 作用下， 以 正丁醇 为溶剂， 反应 29.0h， 以yielding the title compound as a tan solid (550 mg; 91%)的产率得到N2-(2-amino-ethyl)-N4-(3,4-dimethoxy-phenyl)-N4-methyl-quinazoline-2,4-diamine
  参考文献：
  名称：

  Compounds and therapeutical use thereof

  摘要：

  本发明公开了4-芳基氨基喹唑啉及其类似物，可以有效激活半胱氨酸蛋白酶和诱导细胞凋亡。本发明的化合物在治疗各种出现异常细胞不受控制的临床情况中非常有用。

  公开号：

  US08309562B2
• 作为产物：
  描述：

  2-氯-N-(3,4-二甲氧基苯基)喹唑啉-4-胺 、 碘甲烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 以54%的产率得到2-chloro-N-(3,4-dimethoxyphenyl)-N-methylquinazolin-4-amine
  参考文献：
  名称：

  Discovery of 2-Chloro-N-(4-methoxyphenyl)-N-methylquinazolin-4-amine (EP128265, MPI-0441138) as a Potent Inducer of Apoptosis with High In Vivo Activity

  摘要：

  Using a live cell, high-throughput caspase-3 activator assay, we have identified a novel series of 4-anilinoquinazolines as inducers of apoptosis. In this report, we discuss the discovery of 2-chloro-N-(4-methoxyphenyl)-N-methylquinazolin-4-amine, compound 2b (EP128265, MPI-0441138) as a highly active inducer of apoptosis (EC(50) for caspase activation of 2 nM) and as a potent inhibitor of cell proliferation (GI(50) of 2 nM) in T47D cells. Compound 2b inhibited tubulin polymerization, was effective in cells overexpressing ABC transporter Pgp-1, and was efficacious in the MX-1 human breast and PC-3 prostate cancer mouse models. In contrast to the SAR of 4-anilinoquinazolines as EGFR kinase inhibitors, the methyl group on the nitrogen linker was essential for the apoptosis-inducing activity of 4-anilinoquinazolines and substitution in the 6- and 7-positions of the quinazoline core structure decreased potency.

  DOI：

  10.1021/jm8003653

文献信息

• COMPOUNDS AND THERAPEUTICAL USE THEREOF
  申请人：Cai Xiong Sui

  公开号：US20070244113A1

  公开（公告）日：2007-10-18

  Disclosed are 4-arylamino-quinazolines and analogs thereof effective as activators of caspases and inducers of apoptosis. The compounds of this invention are useful in the treatment of a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  本发明揭示了4-芳氨基喹唑啉及其类似物，可有效激活半胱氨酸蛋白酶并诱导细胞凋亡。本发明的化合物在治疗各种临床情况中具有用途，其中异常细胞的不受控制的生长和扩散。
• Compounds and therapeutical use thereof
  申请人：Cai Xiong Sui

  公开号：US20050137213A1

  公开（公告）日：2005-06-23

  Disclosed are 4-arylamino-quinazolines and analogs thereof effective as activators of caspases and inducers of apoptosis. The compounds of this invention are useful in the treatment of a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  本发明揭示了4-芳基氨基喹唑啉及其类似物，它们有效地激活半胱氨酸蛋白酶并诱导细胞凋亡。本发明的化合物在治疗各种临床病症中具有用途，其中发生异常细胞的不受控制的生长和扩散。
• METHOD OF TREATING BRAIN CANCER
  申请人：Cai Sui Xiong

  公开号：US20080051398A1

  公开（公告）日：2008-02-28

  Disclosed are 4-arylamino-quinazolines and analogs thereof effective as activators of caspases and inducers of apoptosis. The compounds of this invention are useful in the treatment of a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs, and in particular to the use of these compounds in treating brain cancer.

  本发明涉及4-芳基氨基喹唑啉及其类似物，其有效激活caspases并诱导细胞凋亡。本发明的化合物可用于治疗各种临床病症，其中发生异常细胞的不受控制的生长和扩散，特别是用于治疗脑癌。
• 4-ARYLAMINO-QUINAZOLINES AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS
  申请人：MYRIAD GENETICS, INC.

  公开号：EP1660092A2

  公开（公告）日：2006-05-31
• JP2007524637A
  申请人：——

  公开号：JP2007524637A

  公开（公告）日：2007-08-30