Tert-butyl 3-[3-(3-decoxyphenoxy)-2-oxopropyl]sulfanylpropanoate | 1026566-29-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: Tert-butyl 3-[3-(3-decoxyphenoxy)-2-oxopropyl]sulfanylpropanoate
• CAS: 1026566-29-9
• 化学式: C₂₆H₄₂O₅S
• 分子量: 466.682
• InChiKey: IIVKWYFXGPYNIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  32
• 可旋转键数：
  20
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  87.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Tert-butyl 3-[3-(3-decoxyphenoxy)-2-oxopropyl]sulfanylpropanoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 3-[3-(3-Decyloxy-phenoxy)-2-oxo-propylsulfanyl]-propionic 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：

  3-decyloxyphenol 在 三乙烯二胺 、 caesium carbonate 、 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 8.0h， 生成 Tert-butyl 3-[3-(3-decoxyphenoxy)-2-oxopropyl]sulfanylpropanoate
  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).