(E)-3-<3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl>-2-propenoic acid 2-<(methylthio)thioxomethyl>hydrazide | 130116-81-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-<3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl>-2-propenoic acid 2-<(methylthio)thioxomethyl>hydrazide
• 英文别名: (E)-3-(3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl)-2-propenoic acid 2-[(methylthio)thioxomethyl]hydrazide；methyl N-[[(E)-3-(3,5-ditert-butyl-4-hydroxyphenyl)prop-2-enoyl]amino]carbamodithioate
• CAS: 130116-81-3
• 化学式: C₁₉H₂₈N₂O₂S₂
• 分子量: 380.576
• InChiKey: BECDAWFINARJNM-CMDGGOBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-3-<3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl>-2-propenoic acid 2-<(methylthio)thioxomethyl>hydrazide 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 1.0h， 以66%的产率得到(E)-2,6-bis(1,1-dimethylethyl)-4-{2-[5-(methylthio)-1,3,4-thiadiazol-2-yl]ethenyl}phenol
  参考文献：
  名称：

  Design of 5-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3,4-thiadiazoles, -1,3,4-oxadiazoles, and -1,2,4-triazoles as orally active, nonulcerogenic antiinflammatory agents

  摘要：

  To discover dual inhibitors of 5-lipoxygenase (LO) and cyclooxygenase (CO) with improved pharmacokinetic properties, we have designed and synthesized series of 1,2,4-triazole, 1,3,4-oxadiazole, and 1,3,4-thiadiazole di-tert-butylphenol derivatives which exhibit a wide range of log P (2.3 to >4) and pK(a) (5.5-12) values. From this work 5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-1,3,4-thiadiazole-2(3H)-thione, choline salt (12a, CI-986) was found to be a potent inhibitor of 5-LO (IC50 = 2.8 muM) and CO (IC50= 0.8 muM), orally active in rat models of inflammation and nonulcerogenic.

  DOI：

  10.1021/jm00060a017
• 作为产物：
  描述：

  3,5-二叔丁基-4-羟基肉桂酸 在 草酰氯 、 TEA 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 (E)-3-<3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl>-2-propenoic acid 2-<(methylthio)thioxomethyl>hydrazide
  参考文献：
  名称：

  Design of 5-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3,4-thiadiazoles, -1,3,4-oxadiazoles, and -1,2,4-triazoles as orally active, nonulcerogenic antiinflammatory agents

  摘要：

  To discover dual inhibitors of 5-lipoxygenase (LO) and cyclooxygenase (CO) with improved pharmacokinetic properties, we have designed and synthesized series of 1,2,4-triazole, 1,3,4-oxadiazole, and 1,3,4-thiadiazole di-tert-butylphenol derivatives which exhibit a wide range of log P (2.3 to >4) and pK(a) (5.5-12) values. From this work 5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-1,3,4-thiadiazole-2(3H)-thione, choline salt (12a, CI-986) was found to be a potent inhibitor of 5-LO (IC50 = 2.8 muM) and CO (IC50= 0.8 muM), orally active in rat models of inflammation and nonulcerogenic.

  DOI：

  10.1021/jm00060a017

文献信息

• Design of 5-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3,4-thiadiazoles, -1,3,4-oxadiazoles, and -1,2,4-triazoles as orally active, nonulcerogenic antiinflammatory agents
  作者：Michael D. Mullican、Michael W. Wilson、David T. Conner、Catherine R. Kostlan、Denis J. Schrier、Richard D. Dyer

  DOI：10.1021/jm00060a017

  日期：1993.4

  To discover dual inhibitors of 5-lipoxygenase (LO) and cyclooxygenase (CO) with improved pharmacokinetic properties, we have designed and synthesized series of 1,2,4-triazole, 1,3,4-oxadiazole, and 1,3,4-thiadiazole di-tert-butylphenol derivatives which exhibit a wide range of log P (2.3 to >4) and pK(a) (5.5-12) values. From this work 5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-1,3,4-thiadiazole-2(3H)-thione, choline salt (12a, CI-986) was found to be a potent inhibitor of 5-LO (IC50 = 2.8 muM) and CO (IC50= 0.8 muM), orally active in rat models of inflammation and nonulcerogenic.