4-(1-phenylethoxy)-3-hydroxyacetophenone | 205318-14-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(1-phenylethoxy)-3-hydroxyacetophenone
• 英文别名: 1-[3-Hydroxy-4-(1-phenylethoxy)phenyl]ethanone
• CAS: 205318-14-5
• 化学式: C₁₆H₁₆O₃
• 分子量: 256.301
• InChiKey: JUBGKNNKYYOWQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 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)-3-hydroxyacetophenone 在 sodium hydride 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 36.0h， 生成 ethyl 2-[5-[(E)-4-(diethylamino)-4-oxobut-2-en-2-yl]-2-(1-phenylethoxy)phenoxy]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
• 作为产物：
  描述：

  3,4-二羟基苯乙酮 、 (1-溴乙基)苯 在 lithium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 4-(1-phenylethoxy)-3-hydroxyacetophenone
  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

• Aryl-substituted acrylamides with Leukotriene B4 (LTB-4) receptor antagonist activity
  申请人：Novartis AG

  公开号：US06291530B1

  公开（公告）日：2001-09-18

  Disclosed are compounds of formula (I) wherein W is CH or N; R is (mono- or di cabocyclic or heterocyclic aryl)-lower alkyl; R1 is hydrogen or lower alkyl; R2 and R3 are hydrogen, lower alkyl, lower alkoxy-lower alkyl or aryl-lower alkyl; or R2 and R3 joined together represent lower alkylene optionally interrupted by O, NH, N-lower alkyl or S so as to form a ring with the amide nitrogen; X is O, S, SO, S2 or a direct bond; X1 is O, S, SO, SO2 or a direct bond; Y is a direct bond, lower alkylene or lower alkylidene; and Z is carboxyl, 5-tetrazolyl,, hydroxymethyl or carboxyl derivatized in the form of a pharmaceutically acceptable ester, and pharmaceutically acceptable salts thereof; which arm useful as LTB-4 antagonists.

  本发明涉及一种式子（I）的化合物，其中W为CH或N；R为（单环或双环芳基或杂环芳基）-较低烷基；R1为氢或较低烷基；R2和R3为氢、较低烷基、较低烷氧基-较低烷基或芳基-较低烷基；或者R2和R3结合在一起，用较低烷基烷基可选地中断的O、NH、N-较低烷基或S表示，以形成与酰胺氮原子形成环的环；X为O、S、SO、S2或直接键；X1为O、S、SO、SO2或直接键；Y为直接键、较低烷基或较低烷基亚甲基；Z为羧基、5-四唑基、羟甲基或以药学上可接受的酯形式衍生的羧基，并且其药学上可接受的盐；它们有用作LTB-4拮抗剂。
• ARYL-SUBSTITUTED ACRYLAMIDES WITH LEUKOTRIENE B4 (LTB-4) RECEPTOR ANTAGONIST ACTIVITY
  申请人：Novartis AG

  公开号：EP0942903A1

  公开（公告）日：1999-09-22
• US6291530B1
  申请人：——

  公开号：US6291530B1

  公开（公告）日：2001-09-18
• [EN] ARYL-SUBSTITUTED ACRYLAMIDES WITH LEUKOTRIENE B4 (LTB-4) RECEPTOR ANTAGONIST ACTIVITY<br/>[FR] ACRYLAMIDES SUBSTITUES PAR DE L'ARYLE AYANT UNE ACTIVITE ANTAGONISTE DU RECEPTEUR LEUCOTRIENE B4 (LTB-4)
  申请人：NOVARTIS AG

  公开号：WO1998013347A1

  公开（公告）日：1998-04-02

  (EN) Disclosed are compounds of formula (I) wherein W is CH or N; R is (mono- or di-carbocyclic or heterocyclic aryl)-lower alkyl; R1 is hydrogen or lower alkyl; R2 and R3 are hydrogen, lower alkyl, lower alkoxy-lower alkyl or aryl-lower alkyl; or R2 and R3 joined together represent lower alkylene optionally interrupted by O, NH, N-lower alkyl or S so as to form a ring with the amide nitrogen; X is O, S, SO, SO2 or a direct bond; X1 is O, S, SO, SO2 or a direct bond; Y is a direct bond, lower alkylene or lower alkylidene; and Z is carboxyl, 5-tetrazolyl, hydroxymethyl or carboxyl derivatized in the form of a pharmaceutically acceptable ester; and pharmaceutically acceptable salts thereof; which are useful as LTB-4 antagonists.(FR) L'invention concerne les composés présentant la formule (I). Dans cette dernière, W représente CH ou N; R est (aryle mono- ou di-carbocyclique ou hétérocyclique)-alkyle inférieur; R1 est hydrogène ou alkyle inférieur; R2 et R3 sont hydrogène, alkyle inférieur, alcoxy inférieur-alkyle inférieur ou aryle-alkyle inférieur; ou R2 et R3 assemblés représentent de l'alkylène inférieur éventuellement interrompu par O, NH, N-alkyle inférieur ou S pour former une chaîne avec l'azote d'amide; X est O, S, SO, SO2 ou une liaison directe; X1 est O, S, SO, SO2 ou une liaison directe; Y est une liaison directe, de l'alkylène inférieure ou de l'alkylidène inférieur, et Z est carboxyle, 5-tétrazolyle, hydroxyméthyle ou du carboxyle dérivé sous forme d'un ester pharmaceutiquement acceptable. L'invention traite aussi de sels pharmaceutiquement acceptables de ces derniers qui sont utiles comme antagonistes de la leucotriène B-4.
• 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.