4-(1-phenylethoxy)-2-hydroxyacetophenone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(1-phenylethoxy)-2-hydroxyacetophenone
• 英文别名: 1-[2-Hydroxy-4-(1-phenylethoxy)phenyl]ethanone
• 化学式: C₁₆H₁₆O₃
• 分子量: 256.301
• InChiKey: TXJHNOVESMZFRR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(1-phenylethoxy)-2-hydroxyacetophenone 在 sodium hydride 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 36.0h， 生成
  参考文献：
  名称：

  Carboxy-Substituted Cinnamides:  A Novel Series of Potent, Orally Active LTB₄ Receptor Antagonists

  摘要：

  A series of carboxy-substituted cinnamides were investigated as antagonists of the human cell surface leukotriene B-4 (LTB4) receptor. Binding was determined through measurement of [H-3]-LTB4 displacement from human neutrophils. Receptor antagonism was confirmed through a functional assay, which measures inhibition of Ca2+ release in human neutrophils. Potent antagonists were discovered through optimization of a random screening hit, a p-(alpha-methylbenzyloxy)cinnamide, having low-micromolar activity. Substantial improvement of in vitro potency was realized by the attachment of a carboxylic acid moiety to the cinnamide phenyl ring through a flexible tether, leading to identification of compounds with low-nanomolar potency. Modification of the benzyloxy substituent, either through ortho-substitution on the benzyloxy phenyl group or through replacement of the ether oxygen with a methylene or sulfur atom, produced achiral antagonists of equal or greater potency. The most potent compounds in vitro were assayed for oral activity using the arachidonic acid-induced mouse ear edema model of inflammation. Several compounds in this series were found to significantly inhibit edema formation and myeloperoxidase activity in this model up to 17 h after oral administration. Representatives of this series have been shown to be potent and long-acting orally active inhibitors of the LTB4 receptor.

  DOI：

  10.1021/jm980540v
• 作为产物：
  描述：

  2,4-二羟基苯乙酮 、 (1-溴乙基)苯 在 potassium carbonate 作用下， 以 正己烷 、 丙酮 为溶剂， 生成 4-(1-phenylethoxy)-2-hydroxyacetophenone
  参考文献：
  名称：

  Lipoxygenase inhibiting compounds

  摘要：

  具有5-和12-脂氧酶抑制活性的化合物具有以下结构##STR1##其中A是直链或支链的二价碳原子数为1至4的烷基，R.sub.1是甲基、氨基或碳原子数为1至6的烷基氨基，取代基R.sub.2是C.sub.1-C.sub.2烷基。基团R.sub.3是氢、碳原子数为1至6的烷基、碳原子数为1至6的烷氧基、碳原子数为1至6的硫代烷氧基、卤素、氰基和三卤甲基中选择的一个或多个取代基，R.sub.4是氢、碳原子数为1至6的烷基、碳原子数为1至6的烷氧基、碳原子数为1至6的硫代烷氧基、羟基、卤素、氰基和三卤甲基中选择的一个或多个取代基，但当R.sub.1为氨基且A为>CHCH.sub.3时，R.sub.3和R.sub.4不能同时为氢。指定为M的基团是氢、药用可接受的阳离子或代谢可裂解基团。还公开了制备药物组合物和抑制5-和12-脂氧酶活性的方法。

  公开号：

  US05026729A1

文献信息

• US5026729A
  申请人：——

  公开号：US5026729A

  公开（公告）日：1991-06-25
• Carboxy-Substituted Cinnamides:  A Novel Series of Potent, Orally Active LTB₄ Receptor Antagonists
  作者：Paul D. Greenspan、Roger A. Fujimoto、Paul J. Marshall、Anil Raychaudhuri、Kenneth E. Lipson、Huanghai Zhou、Robert A. Doti、David E. Coppa、Lijuan Zhu、Roberta Pelletier、Susan Uziel-Fusi、Robert H. Jackson、Michael H. Chin、Bernard L. Kotyuk、John J. Fitt

  DOI：10.1021/jm980540v

  日期：1999.1.1

  A series of carboxy-substituted cinnamides were investigated as antagonists of the human cell surface leukotriene B-4 (LTB4) receptor. Binding was determined through measurement of [H-3]-LTB4 displacement from human neutrophils. Receptor antagonism was confirmed through a functional assay, which measures inhibition of Ca2+ release in human neutrophils. Potent antagonists were discovered through optimization of a random screening hit, a p-(alpha-methylbenzyloxy)cinnamide, having low-micromolar activity. Substantial improvement of in vitro potency was realized by the attachment of a carboxylic acid moiety to the cinnamide phenyl ring through a flexible tether, leading to identification of compounds with low-nanomolar potency. Modification of the benzyloxy substituent, either through ortho-substitution on the benzyloxy phenyl group or through replacement of the ether oxygen with a methylene or sulfur atom, produced achiral antagonists of equal or greater potency. The most potent compounds in vitro were assayed for oral activity using the arachidonic acid-induced mouse ear edema model of inflammation. Several compounds in this series were found to significantly inhibit edema formation and myeloperoxidase activity in this model up to 17 h after oral administration. Representatives of this series have been shown to be potent and long-acting orally active inhibitors of the LTB4 receptor.
• Lipoxygenase inhibiting compounds
  申请人：Abbott Laboratories

  公开号：US05026729A1

  公开（公告）日：1991-06-25

  Compounds having 5- and 12-lipoxygenase inhibitory activity have the structure ##STR1## where A is straight or branched divalent alkylene of from one to four carbon atoms, R.sub.1 is methyl, amino, or alkylamino of from one to six carbon atoms and the substituent group R.sub.2 is C.sub.1 -C.sub.2 alkyl. The group R.sub.3 is one or more substituents selected from hydrogen, alkyl of from one to six carbon atoms, alkoxy of from one to six carbon atoms, thioalkoxy of from one to six carbon atoms, halogen, cyano, and trihalomethyl, and R.sub.4 is one or more substituents selected from hydrogen, alkyl of from one to six carbon atoms, alkoxy of from one to six carbon atoms, thioalkoxy of from one to six carbon atoms, hydroxy, halogen, cyano, and trihalomethyl, with the proviso that when R.sub.1 is amino and A is >CHCH.sub.3, R.sub.3 and R.sub.4 may not both be hydrogen. The group designated M is hydrogen, a pharmaceutically acceptable cation, or a metabolically cleavable group. Pharmaceutical compositions and a method of inhibiting 5- and 12-lipoxygenase activity are also disclosed.

  具有5-和12-脂氧酶抑制活性的化合物具有以下结构##STR1##其中A是直链或支链的二价碳原子数为1至4的烷基，R.sub.1是甲基、氨基或碳原子数为1至6的烷基氨基，取代基R.sub.2是C.sub.1-C.sub.2烷基。基团R.sub.3是氢、碳原子数为1至6的烷基、碳原子数为1至6的烷氧基、碳原子数为1至6的硫代烷氧基、卤素、氰基和三卤甲基中选择的一个或多个取代基，R.sub.4是氢、碳原子数为1至6的烷基、碳原子数为1至6的烷氧基、碳原子数为1至6的硫代烷氧基、羟基、卤素、氰基和三卤甲基中选择的一个或多个取代基，但当R.sub.1为氨基且A为>CHCH.sub.3时，R.sub.3和R.sub.4不能同时为氢。指定为M的基团是氢、药用可接受的阳离子或代谢可裂解基团。还公开了制备药物组合物和抑制5-和12-脂氧酶活性的方法。