2-[(4-Hexoxyphenoxy)methyl]oxirane | 168832-21-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-[(4-Hexoxyphenoxy)methyl]oxirane
• CAS: 168832-21-1
• 化学式: C₁₅H₂₂O₃
• 分子量: 250.338
• InChiKey: BYHYWOKQTSGLOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  18
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  31
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[(4-Hexoxyphenoxy)methyl]oxirane 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-hexoxyphenoxy)-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
• 作为产物：
  描述：

  溴己烷 在 sodium hydride 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.33h， 生成 2-[(4-Hexoxyphenoxy)methyl]oxirane
  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

• Synthesis, activity and metabolic stability of propan-2-one substituted tetrazolylalkanoic acids as dual inhibitors of cytosolic phospholipase A₂α and fatty acid amide hydrolase
  作者：Merlin Ekodo Voundi、Walburga Hanekamp、Matthias Lehr

  DOI：10.1039/d3md00224a

  日期：——

  The serine hydrolases cytosolic phospholipase A2α (cPLA2α) and fatty acid amide hydrolase (FAAH) are interesting targets for the development of new anti-inflammatory and analgesic drugs. Structural modifications of a potent dual inhibitor with a propan-2-one substituted tetrazolylpropionic acid moiety led to compounds with also nanomolar activity against both enzymes but better physicochemical properties

  丝氨酸水解酶胞浆磷脂酶 A 2 α (cPLA 2 α) 和脂肪酸酰胺水解酶 (FAAH) 是开发新型抗炎和镇痛药物的有趣靶点。用丙-2-酮取代的四唑基丙酸部分对强效双重抑制剂进行结构修饰，得到的化合物对两种酶也具有纳摩尔级活性，但具有更好的理化性质。结构-活性关系表明，这些变化对化合物对 cPLA 2 α 和 FAAH 的抑制活性具有部分不同的影响，反映了与酶的结合模式的差异。此外，还对目标结构的代谢稳定性进行了体外研究。
• [EN] PCRA HELICASE INHIBITORS<br/>[FR] INHIBITEURS D'HELICASE PCRA
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2002072760A2

  公开（公告）日：2002-09-19

  This invention relates to the novel PcrA helicase inhibitors useful as broad-spectrum antibacterials.