5-(1-Cyclohexen-1-yl)-2-thiophenecarboxylic acid | 476342-38-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 5-(1-Cyclohexen-1-yl)-2-thiophenecarboxylic acid
• 英文别名: 5-(cyclohexen-1-yl)thiophene-2-carboxylic acid
• CAS: 476342-38-8
• 化学式: C₁₁H₁₂O₂S
• 分子量: 208.281
• InChiKey: FTISOSGSOGRDGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  65.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N¹-(2-((3S,5R)-3,5-dimethyl-1-piperazinyl)-5-fluoro-4-pyrimidinyl)-3-methoxy-benzene-1,4-diamine 、 5-(1-Cyclohexen-1-yl)-2-thiophenecarboxylic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5-(1-cyclohexenyl)-N-(4-((2-((3S,5R)-3,5-dimethyl-1-piperazinyl)-5-fluoro-4-pyrimidinyl)amino)-2-methoxyphenyl)thiophene-2-carboxamide
  参考文献：
  名称：

  Synthesis and Biological Evaluation of B-Cell Lymphoma 6 Inhibitors ofN-Phenyl-4-pyrimidinamine Derivatives Bearing Potent Activities against Tumor Growth

  摘要：

  The transcriptional repressor B-cell lymphoma 6 (BCL6) is frequently misregulated in diffuse large B-cell lymphoma (DLBCL) and has emerged as an attractive drug target for the treatments of lymphoma. In this article, a series of N-phenyl-4-pyrimidinamine derivatives were designed and synthesized as potent BCL6 inhibitors by optimizing hit compound N-4-(3-chloro-4-methoxyphenyl)-N-2-isobutyl-5-fluoro-2,4-pyrimidinediamine on the basis of the structure-activity relationship. Among them, compound 14j displayed the most potent activities, which significantly blocked the interaction of BCL6 with its corepressors, reactivated BCL6 target genes in a dose-dependent manner, and had better effects compared with the two positive controls. Further studies indicated that a low dose of 14j could effectively inhibit germinal center formation. More importantly, 14j not only showed potent inhibition of DLBCL cell proliferation in vitro but also strongly suppressed the growth of DLBCL in vivo.

  DOI：

  10.1021/acs.jmedchem.9b01618
• 作为产物：
  描述：

  5-溴噻吩-2-甲酸甲酯 、 环己烯-1-基硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 0.08h， 生成 5-(1-Cyclohexen-1-yl)-2-thiophenecarboxylic acid
  参考文献：
  名称：

  Synthesis and Biological Evaluation of B-Cell Lymphoma 6 Inhibitors ofN-Phenyl-4-pyrimidinamine Derivatives Bearing Potent Activities against Tumor Growth

  摘要：

  The transcriptional repressor B-cell lymphoma 6 (BCL6) is frequently misregulated in diffuse large B-cell lymphoma (DLBCL) and has emerged as an attractive drug target for the treatments of lymphoma. In this article, a series of N-phenyl-4-pyrimidinamine derivatives were designed and synthesized as potent BCL6 inhibitors by optimizing hit compound N-4-(3-chloro-4-methoxyphenyl)-N-2-isobutyl-5-fluoro-2,4-pyrimidinediamine on the basis of the structure-activity relationship. Among them, compound 14j displayed the most potent activities, which significantly blocked the interaction of BCL6 with its corepressors, reactivated BCL6 target genes in a dose-dependent manner, and had better effects compared with the two positive controls. Further studies indicated that a low dose of 14j could effectively inhibit germinal center formation. More importantly, 14j not only showed potent inhibition of DLBCL cell proliferation in vitro but also strongly suppressed the growth of DLBCL in vivo.

  DOI：

  10.1021/acs.jmedchem.9b01618

文献信息

• Synthesis and Biological Evaluation of B-Cell Lymphoma 6 Inhibitors of<i>N</i>-Phenyl-4-pyrimidinamine Derivatives Bearing Potent Activities against Tumor Growth
  作者：Weikai Guo、Yajing Xing、Qiansen Zhang、Jiuqing Xie、Dongxia Huang、Haijun Gu、Peng He、Miaoran Zhou、Shifen Xu、Xiufeng Pang、Mingyao Liu、Zhengfang Yi、Yihua Chen

  DOI：10.1021/acs.jmedchem.9b01618

  日期：2020.1.23

  The transcriptional repressor B-cell lymphoma 6 (BCL6) is frequently misregulated in diffuse large B-cell lymphoma (DLBCL) and has emerged as an attractive drug target for the treatments of lymphoma. In this article, a series of N-phenyl-4-pyrimidinamine derivatives were designed and synthesized as potent BCL6 inhibitors by optimizing hit compound N-4-(3-chloro-4-methoxyphenyl)-N-2-isobutyl-5-fluoro-2,4-pyrimidinediamine on the basis of the structure-activity relationship. Among them, compound 14j displayed the most potent activities, which significantly blocked the interaction of BCL6 with its corepressors, reactivated BCL6 target genes in a dose-dependent manner, and had better effects compared with the two positive controls. Further studies indicated that a low dose of 14j could effectively inhibit germinal center formation. More importantly, 14j not only showed potent inhibition of DLBCL cell proliferation in vitro but also strongly suppressed the growth of DLBCL in vivo.