(S)-methyl <5-bromo-2-(1-phenylethoxy)phenyl>acetate | 220801-67-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (S)-methyl <5-bromo-2-(1-phenylethoxy)phenyl>acetate
• 英文别名: Methyl 5-bromo-2-[(1S)-1-phenylethoxy]benzeneacetate；methyl 2-[5-bromo-2-[(1S)-1-phenylethoxy]phenyl]acetate
• CAS: 220801-67-2
• 化学式: C₁₇H₁₇BrO₃
• 分子量: 349.224
• InChiKey: XHWYVDVVEWQTDZ-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-methyl <5-bromo-2-(1-phenylethoxy)phenyl>acetate 在 sodium hydroxide 、 palladium diacetate 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 甲醇 为溶剂， 反应 7.0h， 生成 2-[5-[(E)-4-(diethylamino)-4-oxobut-2-en-2-yl]-2-[(1S)-1-phenylethoxy]phenyl]acetic acid
  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：

  邻羟基苯乙酸 在 tetra-N-butylammonium tribromide 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 甲苯 为溶剂， 反应 18.0h， 生成 (S)-methyl <5-bromo-2-(1-phenylethoxy)phenyl>acetate
  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

文献信息

• 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.