2-[(2-Chloro-4-quinazolinyl)amino]-N-methylbenzamide | 1097921-30-6

• 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: 2-[(2-Chloro-4-quinazolinyl)amino]-N-methylbenzamide
• 英文别名: 2-[(2-chloroquinazolin-4-yl)amino]-N-methylbenzamide
• CAS: 1097921-30-6
• 化学式: C₁₆H₁₃ClN₄O
• 分子量: 312.758
• InChiKey: BLQULGYKDCLLFX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  66.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  rac-8-amino-1,3-dimethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine 、 2-[(2-Chloro-4-quinazolinyl)amino]-N-methylbenzamide 在 palladium diacetate 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以74%的产率得到2-((2-((3,5-dimethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)amino)quinazolin-4-yl)amino)-N-methylbenzamide
  参考文献：
  名称：

  Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent c-Met/ALK Multikinase Inhibitory Activities

  摘要：

  By repurposing a typical dopamine D-1/D-5 receptor agonist motif, C1-substituted-N3-benzazepine or benzazecine, into the classical RTK inhibitor 2,4-diaminopyrimidine skeleton, a series of new 2,4-diarylaminopyrimidine analogues (DAAPalogues) were developed. Compounds 7 and 8a were identified possessing high potency against both c-Met and ALK kinases. Compound 8a displayed appreciable antitumor efficacy at the dose of 1 mg/kg in the ALK-driven BF3/EML4-ALK xenograft mice model.

  DOI：

  10.1021/ml400373j
• 作为产物：
  描述：

  2,4-二氯喹唑啉 、 2-氨基-N-甲基苯甲酰胺 在 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 反应 3.0h， 以53%的产率得到2-[(2-Chloro-4-quinazolinyl)amino]-N-methylbenzamide
  参考文献：
  名称：

  Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent c-Met/ALK Multikinase Inhibitory Activities

  摘要：

  By repurposing a typical dopamine D-1/D-5 receptor agonist motif, C1-substituted-N3-benzazepine or benzazecine, into the classical RTK inhibitor 2,4-diaminopyrimidine skeleton, a series of new 2,4-diarylaminopyrimidine analogues (DAAPalogues) were developed. Compounds 7 and 8a were identified possessing high potency against both c-Met and ALK kinases. Compound 8a displayed appreciable antitumor efficacy at the dose of 1 mg/kg in the ALK-driven BF3/EML4-ALK xenograft mice model.

  DOI：

  10.1021/ml400373j

文献信息

• DI(ARYLAMINO)ARYL COMPOUND
  申请人：Kondoh Yutaka

  公开号：US20100099658A1

  公开（公告）日：2010-04-22

  The present invention provides a compound which is useful as an inhibitor against the kinase activity of EML4-ALK fusion proteins and mutant EGFR proteins. As a result of extensive and intensive studies on compounds having an inhibitory effect against the kinase activity of EML4-ALK fusion proteins and mutant EGFR proteins, the inventors of the present invention have found that the di(arylamino)aryl compound of the present invention has inhibitory activity against the kinase activity of EML4-ALK fusion proteins and mutant EGFR proteins. This finding led to the completion of the present invention. The compound of the present invention can be used as a pharmaceutical composition for preventing and/or treating cancer, lung cancer, non-small cell lung cancer, small cell lung cancer, EML4-ALK fusion polynucleotide-positive and/or mutant EGFR polynucleotide-positive cancer, EML4-ALK fusion polynucleotide-positive and/or mutant EGFR polynucleotide-positive lung cancer, or EML4-ALK fusion polynucleotide-positive and/or mutant EGFR polynucleotide-positive non-small cell lung cancer, etc.

  本发明提供了一种化合物，可用作抑制EML4-ALK融合蛋白和突变EGFR蛋白的激酶活性的抑制剂。在广泛而深入的研究EML4-ALK融合蛋白和突变EGFR蛋白的激酶活性的化合物的基础上，本发明的发明人发现本发明的二(芳基氨基)芳基化合物具有抑制EML4-ALK融合蛋白和突变EGFR蛋白的激酶活性的活性。这一发现导致了本发明的完成。本发明的化合物可用作预防和/或治疗癌症、肺癌、非小细胞肺癌、小细胞肺癌、EML4-ALK融合多核苷酸阳性和/或突变EGFR多核苷酸阳性癌症、EML4-ALK融合多核苷酸阳性和/或突变EGFR多核苷酸阳性肺癌，或EML4-ALK融合多核苷酸阳性和/或突变EGFR多核苷酸阳性非小细胞肺癌等的药物组合物。
• US8318702B2
  申请人：——

  公开号：US8318702B2

  公开（公告）日：2012-11-27
• Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent c-Met/ALK Multikinase Inhibitory Activities
  作者：Zhiqing Liu、Jing Ai、Xia Peng、Zilan Song、Kui Wu、Jing Zhang、Qizheng Yao、Yi Chen、Yinchun Ji、Yanhong Yang、Meiyu Geng、Ao Zhang

  DOI：10.1021/ml400373j

  日期：2014.4.10

  By repurposing a typical dopamine D-1/D-5 receptor agonist motif, C1-substituted-N3-benzazepine or benzazecine, into the classical RTK inhibitor 2,4-diaminopyrimidine skeleton, a series of new 2,4-diarylaminopyrimidine analogues (DAAPalogues) were developed. Compounds 7 and 8a were identified possessing high potency against both c-Met and ALK kinases. Compound 8a displayed appreciable antitumor efficacy at the dose of 1 mg/kg in the ALK-driven BF3/EML4-ALK xenograft mice model.