ethyl 2-(3-(4-chlorobenzamido)phenyl)-4-((4-(4-methylpiperazin-1-yl)phenyl)amino)thiazole-5-carboxylate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 2-(3-(4-chlorobenzamido)phenyl)-4-((4-(4-methylpiperazin-1-yl)phenyl)amino)thiazole-5-carboxylate
• 英文别名: Ethyl 2-[3-[(4-chlorobenzoyl)amino]phenyl]-4-[4-(4-methylpiperazin-1-yl)anilino]-1,3-thiazole-5-carboxylate；ethyl 2-[3-[(4-chlorobenzoyl)amino]phenyl]-4-[4-(4-methylpiperazin-1-yl)anilino]-1,3-thiazole-5-carboxylate
• 化学式: C₃₀H₃₀ClN₅O₃S
• 分子量: 576.119
• InChiKey: CVLSTVFOFHOBKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  40
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 2-(3-(4-chlorobenzamido)phenyl)-4-((4-(4-methylpiperazin-1-yl)phenyl)amino)thiazole-5-carboxylate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 以46%的产率得到2-(3-(4-chlorobenzamido)phenyl)-4-((4-(4-methylpiperazin-1-yl)phenyl)amino)thiazole-5-carboxylic acid
  参考文献：
  名称：

  Discovery and structure-activity relationship of novel diphenylthiazole derivatives as BTK inhibitor with potent activity against B cell lymphoma cell lines

  摘要：

  By the analysis of different binding modes with Bruton's tyrosine kinase (BTK), series of novel diphenylthiazole derivatives were rationally designed, synthesized and characterized. Biologically evaluation in biochemistry and cellular assay indicated that, compounds 5m, 5o, 6b, 6c, 6g, 6i, 7h, 7i, 7k, 7m, 7n, 7o and 7s exhibited improved potency against Ramos cell (IC₅₀ = 1.36-8.60 μM) and Raji cell (IC₅₀ = 1.20-14.04 μM) as compared with ibrutinib (IC₅₀ = 14.69 and 15.99 μM, respectively). Especially, compounds 7m and 7n showed 10-time improved potency against Ramos cell viability over ibrutinib. Compound 6b improved 13-fold activity against Raji cell viability than ibrutinib. In addition, active compound 7o potently inhibited C481S mutant BTK with IC₅₀ value of 0.061 μM. Apoptosis analysis of both Ramos and Raji cells indicated that 7o was remarkably more potent than CGI-1746 and ibrutinib. Compound 7o potently inhibited BTK Y223 phosphorylation in Raji cells, and arrested cell cycle progression in the G0/G1 phase in Raji and Ramos cells. This study expanded the structural diversity of BTK inhibitors and compound 7o was discovered as an active lead inhibitor with great potential for further studies.

  DOI：

  10.1016/j.ejmech.2019.06.035
• 作为产物：
  描述：

  在 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 16.0h， 生成 ethyl 2-(3-(4-chlorobenzamido)phenyl)-4-((4-(4-methylpiperazin-1-yl)phenyl)amino)thiazole-5-carboxylate
  参考文献：
  名称：

  Discovery and structure-activity relationship of novel diphenylthiazole derivatives as BTK inhibitor with potent activity against B cell lymphoma cell lines

  摘要：

  By the analysis of different binding modes with Bruton's tyrosine kinase (BTK), series of novel diphenylthiazole derivatives were rationally designed, synthesized and characterized. Biologically evaluation in biochemistry and cellular assay indicated that, compounds 5m, 5o, 6b, 6c, 6g, 6i, 7h, 7i, 7k, 7m, 7n, 7o and 7s exhibited improved potency against Ramos cell (IC₅₀ = 1.36-8.60 μM) and Raji cell (IC₅₀ = 1.20-14.04 μM) as compared with ibrutinib (IC₅₀ = 14.69 and 15.99 μM, respectively). Especially, compounds 7m and 7n showed 10-time improved potency against Ramos cell viability over ibrutinib. Compound 6b improved 13-fold activity against Raji cell viability than ibrutinib. In addition, active compound 7o potently inhibited C481S mutant BTK with IC₅₀ value of 0.061 μM. Apoptosis analysis of both Ramos and Raji cells indicated that 7o was remarkably more potent than CGI-1746 and ibrutinib. Compound 7o potently inhibited BTK Y223 phosphorylation in Raji cells, and arrested cell cycle progression in the G0/G1 phase in Raji and Ramos cells. This study expanded the structural diversity of BTK inhibitors and compound 7o was discovered as an active lead inhibitor with great potential for further studies.

  DOI：

  10.1016/j.ejmech.2019.06.035

文献信息

• Discovery and structure-activity relationship of novel diphenylthiazole derivatives as BTK inhibitor with potent activity against B cell lymphoma cell lines
  作者：Xiaofeng Guo、Dongyan Yang、Zhijin Fan、Nailou Zhang、Bin Zhao、Chun Huang、Fangjie Wang、Rongji Ma、Meng Meng、Youcai Deng

  DOI：10.1016/j.ejmech.2019.06.035

  日期：2019.9

  By the analysis of different binding modes with Bruton's tyrosine kinase (BTK), series of novel diphenylthiazole derivatives were rationally designed, synthesized and characterized. Biologically evaluation in biochemistry and cellular assay indicated that, compounds 5m, 5o, 6b, 6c, 6g, 6i, 7h, 7i, 7k, 7m, 7n, 7o and 7s exhibited improved potency against Ramos cell (IC₅₀ = 1.36-8.60 μM) and Raji cell (IC₅₀ = 1.20-14.04 μM) as compared with ibrutinib (IC₅₀ = 14.69 and 15.99 μM, respectively). Especially, compounds 7m and 7n showed 10-time improved potency against Ramos cell viability over ibrutinib. Compound 6b improved 13-fold activity against Raji cell viability than ibrutinib. In addition, active compound 7o potently inhibited C481S mutant BTK with IC₅₀ value of 0.061 μM. Apoptosis analysis of both Ramos and Raji cells indicated that 7o was remarkably more potent than CGI-1746 and ibrutinib. Compound 7o potently inhibited BTK Y223 phosphorylation in Raji cells, and arrested cell cycle progression in the G0/G1 phase in Raji and Ramos cells. This study expanded the structural diversity of BTK inhibitors and compound 7o was discovered as an active lead inhibitor with great potential for further studies.