N-(6-dimethylaminopyridin-3-yl)-2-methylquinazolin-4-amine | 898282-75-2

• 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-(6-dimethylaminopyridin-3-yl)-2-methylquinazolin-4-amine
• 英文别名: (2-dimethylamino-pyridine-5-yl)-(2-methyl-quinazolin-4-yl)-amine；2-N,2-N-dimethyl-5-N-(2-methylquinazolin-4-yl)pyridine-2,5-diamine
• CAS: 898282-75-2
• 化学式: C₁₆H₁₇N₅
• 分子量: 279.344
• InChiKey: UDBUIBPSSKNURG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 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：

  N-(6-dimethylaminopyridin-3-yl)-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47%的产率得到N-(6-dimethylaminopyridin-3-yl)-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：

  N,N-二甲基吡啶-2,5-二胺 、 4-氯-2-甲基喹唑啉 在 sodium acetate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 以21%的产率得到N-(6-dimethylaminopyridin-3-yl)-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

• 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。
• 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。
• Method of treating brain cancer
  申请人：Myrexis, Inc.

  公开号：US08258145B2

  公开（公告）日：2012-09-04

  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.

  本发明揭示了4-芳基氨基喹唑啉及其类似物，其作为caspase活化剂和诱导凋亡剂具有有效性。本发明的化合物在治疗各种临床病症中有用，其中发生异常细胞的不受控制的生长和扩散，特别是在治疗脑癌中使用这些化合物。
• US7989462B2
  申请人：——

  公开号：US7989462B2

  公开（公告）日：2011-08-02