N-(3,4-dimethoxyphenyl)-2-methylquinazolin-4-amine | 898282-73-0

• 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: N-(3,4-dimethoxyphenyl)-2-methylquinazolin-4-amine
• 英文别名: (3,4-dimethoxy-phenyl)-(2-methyl-quinazolin-4-yl)-amine
• CAS: 898282-73-0
• 化学式: C₁₇H₁₇N₃O₂
• 分子量: 295.341
• InChiKey: KPHHIMSRHNPCTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 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：
  56.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(3,4-dimethoxyphenyl)-2-methylquinazolin-4-amine 、 碘甲烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 oil 为溶剂， 以23%的产率得到N-(3,4-dimethoxyphenyl)-N,2-dimethylquinazolin-4-amine
  参考文献：
  名称：

  Discovery of N-(4-Methoxyphenyl)-N,2-dimethylquinazolin-4-amine, a Potent Apoptosis Inducer and Efficacious Anticancer Agent with High Blood Brain Barrier Penetration

  摘要：

  As a continuation of our structure-activity relationship (SAR) studies on 4-anilinoquinazolines as potent apoptosis inducers and to identify anticancer development candidates, we explored the replacement of the 2-Cl group in our lead compound 2-chloro-N-(4-methoxyphenyl)-N-methylquinazolin-4-amine (6b, EP 128265, MPI-0441138) by other functional groups. This SAR study and lead optimization resulted in the identification of N-(4-methoxyphenyl)-N,2-dimethylquinazolin-4-amine (6h EP128495, MPC-6827) as an anticancer clinical candidate. Compound 6h was found to be a potent apoptosis inducer with EC50 of 2 nM in our cell-based apoptosis induction assay. It also has excellent blood brain barrier penetration, and is highly efficacious in human MX-1 breast and other mouse xenograft cancer models.

  DOI：

  10.1021/jm801315b
• 作为产物：
  描述：

  4-氯-2-甲基喹唑啉 、 3,4-二甲氧基苯胺 在 sodium acetate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 以100%的产率得到N-(3,4-dimethoxyphenyl)-2-methylquinazolin-4-amine
  参考文献：
  名称：

  Discovery of N-(4-Methoxyphenyl)-N,2-dimethylquinazolin-4-amine, a Potent Apoptosis Inducer and Efficacious Anticancer Agent with High Blood Brain Barrier Penetration

  摘要：

  As a continuation of our structure-activity relationship (SAR) studies on 4-anilinoquinazolines as potent apoptosis inducers and to identify anticancer development candidates, we explored the replacement of the 2-Cl group in our lead compound 2-chloro-N-(4-methoxyphenyl)-N-methylquinazolin-4-amine (6b, EP 128265, MPI-0441138) by other functional groups. This SAR study and lead optimization resulted in the identification of N-(4-methoxyphenyl)-N,2-dimethylquinazolin-4-amine (6h EP128495, MPC-6827) as an anticancer clinical candidate. Compound 6h was found to be a potent apoptosis inducer with EC50 of 2 nM in our cell-based apoptosis induction assay. It also has excellent blood brain barrier penetration, and is highly efficacious in human MX-1 breast and other mouse xenograft cancer models.

  DOI：

  10.1021/jm801315b

文献信息

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

  公开号：US20080004297A1

  公开（公告）日：2008-01-03

  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.

  本发明涉及4-芳胺基喹唑啉及其类似物，其作为caspase激活剂和凋亡诱导剂具有有效性。本发明的化合物在治疗各种临床情况中有用，其中发生异常细胞的不受控制的生长和扩散。
• 4-arylamin-or-4-heteroarylamino-quinazolines and analogs as activators of caspases and inducers of apoptosis and the use thereof
  申请人：Myrexis, Inc.

  公开号：US07989462B2

  公开（公告）日：2011-08-02

  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.

  本发明涉及4-芳基氨基喹唑啉及其类似物，可作为caspase激活剂和凋亡诱导剂。该发明的化合物可用于治疗多种临床情况，其中发生异常细胞的不受控制的生长和扩散。
• US7989462B2
  申请人：——

  公开号：US7989462B2

  公开（公告）日：2011-08-02
• [EN] COMPOUNDS AND THERAPEUTICAL USE THEREOF<br/>[FR] COMPOSES ET UTILISATION THERAPEUTIQUE ASSOCIEE
  申请人：MYRIAD GENETICS INC

  公开号：WO2006074147A2

  公开（公告）日：2006-07-13

  [EN] 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.
  [FR] L'invention concerne des 4-arylamino-quinazolines et des analogues de celles-ci, efficaces en tant qu'activateurs de caspases et inducteurs d'apoptose. Les composés selon l'invention sont utiles dans le traitement de divers états cliniques caractérisés par une croissance et une propagation incontrôlées de cellules anormales.
• Discovery of <i>N</i>-(4-Methoxyphenyl)-<i>N</i>,2-dimethylquinazolin-4-amine, a Potent Apoptosis Inducer and Efficacious Anticancer Agent with High Blood Brain Barrier Penetration
  作者：Nilantha Sirisoma、Azra Pervin、Hong Zhang、Songchun Jiang、J. Adam Willardsen、Mark B. Anderson、Gary Mather、Christopher M. Pleiman、Shailaja Kasibhatla、Ben Tseng、John Drewe、Sui Xiong Cai

  DOI：10.1021/jm801315b

  日期：2009.4.23

  As a continuation of our structure-activity relationship (SAR) studies on 4-anilinoquinazolines as potent apoptosis inducers and to identify anticancer development candidates, we explored the replacement of the 2-Cl group in our lead compound 2-chloro-N-(4-methoxyphenyl)-N-methylquinazolin-4-amine (6b, EP 128265, MPI-0441138) by other functional groups. This SAR study and lead optimization resulted in the identification of N-(4-methoxyphenyl)-N,2-dimethylquinazolin-4-amine (6h EP128495, MPC-6827) as an anticancer clinical candidate. Compound 6h was found to be a potent apoptosis inducer with EC50 of 2 nM in our cell-based apoptosis induction assay. It also has excellent blood brain barrier penetration, and is highly efficacious in human MX-1 breast and other mouse xenograft cancer models.