(E)-3-<3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl>-2-propenoic acid hydrazide | 148773-22-2

• 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 hydrazide
• 英文别名: (E)-3-(3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl)-2-propenoic acid hydrazide；(E)-3-(3,5-ditert-butyl-4-hydroxyphenyl)prop-2-enehydrazide
• CAS: 148773-22-2
• 化学式: C₁₇H₂₆N₂O₂
• 分子量: 290.406
• InChiKey: VFNQNLCSCOWJAP-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  75.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  溴化氰 、 (E)-3-<3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl>-2-propenoic acid hydrazide 在 碳酸氢钠 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 以52%的产率得到(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 盐酸 、 草酰氯 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (E)-3-<3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl>-2-propenoic acid 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

• Multipurpose polymer bound stabilizers
  申请人：ATOCHEM NORTH AMERICA, INC.

  公开号：EP0303986A2

  公开（公告）日：1989-02-22

  These are provided polymer bound stabilizers with recurring units selected from the formulas or both wherein the units occur, e.g., in the polymer back­bone, x is 0 or 1, R¹ and R² are, e.g., hydrogen, and each -- is the residue of a primary amino or hydrazido substituted stabilizer group selected from (a) hindered phenols, (b) hindered amine light stabilizers, (c) 2-hydroxybenzophenones, (d) 2-(2-hydroxyphenyl)-2H-benzotriazoles, (e) secondary aromatic amines, (f) benzothiazoles or benzimidazoles, (g) aryl salicylates, (h) salicylic acid derivatives (i) oxamide derivatives and (j) dialkyl sulfides, with the proviso that at least two different groups from (a) through (j) are attahced to the polymer. The polymeric stabilizers are prepared by the reaction of primary amino or hydrazido substituted stabilizers with some or all of the anhydride groups of the polymer or copolymer. They are not lost from the polymer by volatilization, migration or extraction, even at high temperature and may be used as concentrates to stabilize other polymers.

  这些聚合物结合稳定剂具有选自下列公式的重复单元 或两者，其中单元出现在聚合物骨架等处，x 为 0 或 1，R¹ 和 R² 为氢等，且每 -- 是伯氨基或肼基取代的稳定剂基团的残基，选自 (a) 受阻酚，(b) 受阻胺光稳定剂，(c) 2-羟基二苯甲酮，(d) 2-(2-羟基苯基)-2H-苯并三唑，(e) 仲芳香胺、(f) 苯并噻唑或苯并咪唑； (g) 芳基水杨酸盐； (h) 水杨酸衍生物； (i) 草酰胺衍生物；以及 (j) 二烷基硫化物，但聚合物中至少含有两个不同的(a)至(j)基团。聚合物稳定剂是通过伯氨基或肼基取代的稳定剂与聚合物或共聚物的部分或全部酸酐基团反应制备的。即使在高温条件下，它们也不会因挥发、迁移或萃取而从聚合物中流失，可用作稳定其他聚合物的浓缩物。
• Dianhydride coupled polymer stabilizers
  申请人：ATOCHEM NORTH AMERICA, INC.

  公开号：EP0308886A2

  公开（公告）日：1989-03-29

  There are provided polymer stabilizers having the formula wherein A is an organic tetravalent radical of 2 to 48 carbons, D is a divalent radical -C(=O)-N(G)-C(=O)-(CH₂)x-, where x is 0 or 1, E is a monovalent radical -(CH₂)x-C(=O)NH-G, where x is 0 or 1, d is 0, 1 or 2 and G is the residue of a stabilizer group, e.g., a hydrazido-substituted hindered phenol or a hydrazido-­substituted hindered amine light stabilizers The polymer stabilizers are prepared by the reaction of hydrazido-substituted or certain amino-substituted polymer stabilizers and cyclic dianhydrides. The polymer stabilizers of the invention are useful for protecting a large variety of synthetic polymeric organic materials from the degradative effects of heat, light and oxygen. Some of the modifiers are flame retardants and many more metal deactivators in addition to their primary activity.

  聚合物稳定剂的结构式为 其中 A 是 2 至 48 个碳原子的有机四价基、 D 是二价基-C(=O)-N(G)-C(=O)-(CH₂)x-，其中 x 为 0 或 1、 E 是单价基-(CH₂)x-C(=O)NH-G，其中 x 为 0 或 1、 d 是 0、1 或 2，以及 G 是稳定剂基团的残基，如肼基取代的受阻酚或肼基取代的受阻胺光稳定剂。 通过肼基取代或某些氨基取代的聚合物稳定剂与环状二酐反应制备聚合物稳定剂。本发明的聚合物稳定剂可用于保护各种合成高分子有机材料免受热、光和氧的降解作用。其中一些改性剂是阻燃剂，而更多的改性剂除了其主要活性外，还是金属失活剂。
• 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。
• US4863999A
  申请人：——

  公开号：US4863999A

  公开（公告）日：1989-09-05
• US4874803A
  申请人：——

  公开号：US4874803A

  公开（公告）日：1989-10-17