Prop-2-enyl 4-[3-(4-octoxyphenoxy)-2-oxopropoxy]benzoate | 1026561-79-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Prop-2-enyl 4-[3-(4-octoxyphenoxy)-2-oxopropoxy]benzoate
• CAS: 1026561-79-4
• 化学式: C₂₇H₃₄O₆
• 分子量: 454.563
• InChiKey: AHPSMQBMUGLZJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  33
• 可旋转键数：
  18
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Prop-2-enyl 4-[3-(4-octoxyphenoxy)-2-oxopropoxy]benzoate 在 四(三苯基膦)钯 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 4-[3-(4-Octyloxy-phenoxy)-2-oxo-propoxy]-benzoic acid
  参考文献：
  名称：

  Design and Synthesis of a Novel and Potent Series of Inhibitors of Cytosolic Phospholipase A₂ Based on a 1,3-Disubstituted Propan-2-one Skeleton

  摘要：

  Using knowledge of the substrate specificity of cPLA(2) (phospliolipases A(2)), a novel series of inhibitors of this enzyme were designed based upon a three point model of inhibitor binding to the enzyme active site comprising a lipophilic anchor, an electrophilic serine "trap", and an acidic binding moiety. The resulting 1,3-diheteroatom-substituted propan-2-ones were evaluated as inhibitors of cPLA2 in both aggregated bilayer and soluble substrate assays. Systematic variation of the lipophilic, electrophilic, and acidic groups revealed a well-defined structure-activity relationship against the enzyme. Optimization of each group led to compound 22 (ARC70484XX), which contains a decyloxy lipophilic side chain, a 1,3-diaryloxypropan-2-one moiety as a unique serine trap, and a benzoic acid as the acidic binding group. AR-C70484XX was found to be among the most potent in vitro inhibitors of cPLA2, described to date being more than 20-fold more active against the isolated enzyme (IC50 = 0.03 muM) than the standard CPLA(2) inhibitor, arachidonyl trifluoromethyl ketone (AACOCF(3)), and also greater than 10-fold more active than AACOCF3 against the cellular production of arachidonic acid by HL60 cells (IC50 = 2.8 muM).

  DOI：

  10.1021/jm011050x
• 作为产物：
  描述：

  4-羟基苯甲酸烯丙酯 在 三乙烯二胺 、 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 Prop-2-enyl 4-[3-(4-octoxyphenoxy)-2-oxopropoxy]benzoate
  参考文献：
  名称：

  Design and Synthesis of a Novel and Potent Series of Inhibitors of Cytosolic Phospholipase A₂ Based on a 1,3-Disubstituted Propan-2-one Skeleton

  摘要：

  Using knowledge of the substrate specificity of cPLA(2) (phospliolipases A(2)), a novel series of inhibitors of this enzyme were designed based upon a three point model of inhibitor binding to the enzyme active site comprising a lipophilic anchor, an electrophilic serine "trap", and an acidic binding moiety. The resulting 1,3-diheteroatom-substituted propan-2-ones were evaluated as inhibitors of cPLA2 in both aggregated bilayer and soluble substrate assays. Systematic variation of the lipophilic, electrophilic, and acidic groups revealed a well-defined structure-activity relationship against the enzyme. Optimization of each group led to compound 22 (ARC70484XX), which contains a decyloxy lipophilic side chain, a 1,3-diaryloxypropan-2-one moiety as a unique serine trap, and a benzoic acid as the acidic binding group. AR-C70484XX was found to be among the most potent in vitro inhibitors of cPLA2, described to date being more than 20-fold more active against the isolated enzyme (IC50 = 0.03 muM) than the standard CPLA(2) inhibitor, arachidonyl trifluoromethyl ketone (AACOCF(3)), and also greater than 10-fold more active than AACOCF3 against the cellular production of arachidonic acid by HL60 cells (IC50 = 2.8 muM).

  DOI：

  10.1021/jm011050x

文献信息

• Design and Synthesis of a Novel and Potent Series of Inhibitors of Cytosolic Phospholipase A₂ Based on a 1,3-Disubstituted Propan-2-one Skeleton
  作者：Stephen Connolly、Colin Bennion、Sarah Botterell、Pamela J. Croshaw、Catherine Hallam、Kim Hardy、Paul Hartopp、Clive G. Jackson、Sarah J. King、Louise Lawrence、Antonio Mete、David Murray、David H. Robinson、Gillian M. Smith、Linda Stein、Iain Walters、Edward Wells、W. John Withnall

  DOI：10.1021/jm011050x

  日期：2002.3.1

  Using knowledge of the substrate specificity of cPLA(2) (phospliolipases A(2)), a novel series of inhibitors of this enzyme were designed based upon a three point model of inhibitor binding to the enzyme active site comprising a lipophilic anchor, an electrophilic serine "trap", and an acidic binding moiety. The resulting 1,3-diheteroatom-substituted propan-2-ones were evaluated as inhibitors of cPLA2 in both aggregated bilayer and soluble substrate assays. Systematic variation of the lipophilic, electrophilic, and acidic groups revealed a well-defined structure-activity relationship against the enzyme. Optimization of each group led to compound 22 (ARC70484XX), which contains a decyloxy lipophilic side chain, a 1,3-diaryloxypropan-2-one moiety as a unique serine trap, and a benzoic acid as the acidic binding group. AR-C70484XX was found to be among the most potent in vitro inhibitors of cPLA2, described to date being more than 20-fold more active against the isolated enzyme (IC50 = 0.03 muM) than the standard CPLA(2) inhibitor, arachidonyl trifluoromethyl ketone (AACOCF(3)), and also greater than 10-fold more active than AACOCF3 against the cellular production of arachidonic acid by HL60 cells (IC50 = 2.8 muM).