(R,S)-(E)-ethyl 3-(4-benzyloxyphenyl)-2-butenoate | 129649-14-5

• 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: (R,S)-(E)-ethyl 3-(4-benzyloxyphenyl)-2-butenoate
• 英文别名: ethyl (E)-3-(4-phenylmethoxyphenyl)but-2-enoate
• CAS: 129649-14-5
• 化学式: C₁₉H₂₀O₃
• 分子量: 296.366
• InChiKey: BGZLGAKOWILIFW-FYWRMAATSA-N

物化性质

• 沸点：
  436.1±14.0 °C(predicted)
• 密度：
  1.091±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 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：

  (R,S)-(E)-ethyl 3-(4-benzyloxyphenyl)-2-butenoate 在 sodium hydroxide 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 (E)-N,N-diethyl-3-(4-phenylmethoxyphenyl)but-2-enamide
  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：

  4-苄氧基溴苯 、 2-丁烯酸乙酯 在 palladium diacetate 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 反应 5.0h， 生成 (R,S)-(E)-ethyl 3-(4-benzyloxyphenyl)-2-butenoate
  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

• Therapeutic uses of PPAR mediators
  申请人：——

  公开号：US20030220373A1

  公开（公告）日：2003-11-27

  Use of PPAR mediators, and their pharmaceutical compositions, as ATP binding cassette transporter 1 (ABC-1) expression modulators, wherein the PPAR ligand receptor agonists of this invention are useful as inducers of ABC-1 expression.

  使用PPAR介质及其制药组合物作为ATP结合盒转运蛋白1（ABC-1）表达调节剂，本发明的PPAR配体受体激动剂可作为ABC-1表达的诱导剂。
• Quinoline derivatives, their use in the treatment of hypersensitive ailments and a pharmaceutical composition containing the same
  申请人：RHONE-POULENC RORER INTERNATIONAL (HOLDINGS) INC.

  公开号：EP0315399A2

  公开（公告）日：1989-05-10

  This invention relates to quinoline derivatives, their use in the treatment of hypersensitive ailments and a pharmaceutical composition containing the same. The quinoline derivatives of the invention are a particular class of quinolinyl-diaryl compounds and they are especially valuable as lipoxygenase inhibitors and/or leukotriene antagonists, typically antagonists of leukotriene D4, possessing anti-inflammatory and anti-allergic properties.

  本发明涉及喹啉衍生物、它们在治疗过敏性疾病中的用途以及含有喹啉衍生物的药物组合物。 本发明的喹啉衍生物是一类特殊的喹啉基二元化合物，它们作为脂氧合酶抑制剂和/或白三烯拮抗剂（通常是白三烯 D4 拮抗剂）特别有价值，具有抗炎和抗过敏特性。
• GALEMMO, ROBERT A.;JOHNSON, WILLIAM H. (JR);LEARN, KEITH S.;LEE, THOMAS D+, J. MED. CHEM., 33,(1990) N0, C. 2828-2841
  作者：GALEMMO, ROBERT A.、JOHNSON, WILLIAM H. (JR)、LEARN, KEITH S.、LEE, THOMAS D+

  DOI：——

  日期：——
• QUINOLINYL ETHER OR THIOETHER TETRAZOLES AS AGENTS FOR THE TREATMENT OF HYPERSENSITIVE AILMENTS
  申请人：RORER INTERNATIONAL (OVERSEAS) INC. (a Delaware corporation)

  公开号：EP0260305A1

  公开（公告）日：1988-03-23
• EP0260305A4
  申请人：——

  公开号：EP0260305A4

  公开（公告）日：1988-07-04