1,1-dimethylethyl 2-<3-<3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl>-1-oxo-2-propenyl>hydrazinecarboxylate | 148794-22-3

• 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: 1,1-dimethylethyl 2-<3-<3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl>-1-oxo-2-propenyl>hydrazinecarboxylate
• 英文别名: 1,1-dimethylethyl 2-[3-(3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl)-1-oxo-2-propenyl]hydrazinecarboxylate；tert-butyl N-[[(E)-3-(3,5-ditert-butyl-4-hydroxyphenyl)prop-2-enoyl]amino]carbamate
• CAS: 148794-22-3
• 化学式: C₂₂H₃₄N₂O₄
• 分子量: 390.523
• InChiKey: NYPHTCKBRVGJAI-ZHACJKMWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl 2-<3-<3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl>-1-oxo-2-propenyl>hydrazinecarboxylate 在 盐酸 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 3.0h， 生成 (E)-4-[2-(5-amino-1,3,4-oxadiazol-2-yl)ethenyl]-2,6-bis-(1,1'-dimethylethyl)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 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 1,1-dimethylethyl 2-<3-<3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl>-1-oxo-2-propenyl>hydrazinecarboxylate
  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

• 3,5-Di-tertiary-butyl-4-hydroxyphenyl-1,3,4-thiadiazoles, and oxadiazoles and 3,5-di-tertiary-butyl-4-hydroxiphenyl- 1,2,4-thiadiazoles, -oxadiazoles as antiinflammatory agents
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0371438A2

  公开（公告）日：1990-06-06

  The present invention is novel compounds which are 3,5-di-tertiary-butyl-4-hydroxyphenyl substituted 1,2,4-and 1,3,4-thiadazoles and oxadiazoles, and 1,2,4-triazoles, and pharmaceutically acceptable additions and base salts thereof, pharmaceutical compositions and methods of use therefor. The invention compounds are now found to have activity as inhibitors of 5-lipoxygenase and/or cyclooxygenase providing treatment of conditions advantageously affected by such inhibition including inflammation, arthritis, pain, fever, and the like.

  本发明是3,5-二叔丁基-4-羟基苯基取代的1,2,4和1,3,4-噻二唑和噁二唑以及1,2,4-三唑的新型化合物及其药学上可接受的添加剂和基盐、药物组合物和使用方法。现在发现，本发明化合物具有作为 5-脂氧合酶和/或环氧合酶抑制剂的活性，可治疗受这种抑制影响的有利病症，包括炎症、关节炎、疼痛、发热等。
• US5155122A
  申请人：——

  公开号：US5155122A

  公开（公告）日：1992-10-13
• US5256680A
  申请人：——

  公开号：US5256680A

  公开（公告）日：1993-10-26
• US5376670A
  申请人：——

  公开号：US5376670A

  公开（公告）日：1994-12-27
• 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.