(E)-1-(3,4-bis((tetrahydro-2H-pyran-2-yl)oxy)phenyl)-5-phenylpent-1-en-3-one | 1026226-73-2

• 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: (E)-1-(3,4-bis((tetrahydro-2H-pyran-2-yl)oxy)phenyl)-5-phenylpent-1-en-3-one
• 英文别名: (E)-1-[3,4-bis(oxan-2-yloxy)phenyl]-5-phenylpent-1-en-3-one
• CAS: 1026226-73-2
• 化学式: C₂₇H₃₂O₅
• 分子量: 436.548
• InChiKey: QOQIMGVAVSPELO-DTQAZKPQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E)-1-(3,4-bis((tetrahydro-2H-pyran-2-yl)oxy)phenyl)-5-phenylpent-1-en-3-one 在 甲醇 、 4-甲基苯磺酸吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 (E)-1-(3,4-dihydroxyphenyl)-5-phenyl-pent-1-en-3-one
  参考文献：
  名称：

  咖啡酸苯乙酯类似物作为新型5-脂氧合酶抑制剂的结构活性关系。

  摘要：

  白三烯（LTs）是一类脂质介体，与多种炎症性疾病有关。咖啡酸苯乙酯（CAPE）通过抑制5-脂氧合酶（5-LO）（LTs生物合成中的关键酶）而具有强大的抗LTs活性。在这项研究中，我们描述了作为自由基清除剂和5-LO抑制剂的CAPE类似物的设计和合成。通过Sonogashira和Heck交叉偶联反应合成了在咖啡酰基和芳基部分之间分别带有炔丙基和烯丙基连接基的咖啡酸酯（分别为4a-i和5a-i），以研究柔韧性和芳基取代对5-LO抑制的影响。合成了咖啡酰醇和醚（6，7a-b）以及咖啡酰醛和酮（8a-e），以阐明酯键对抑制活性的重要性。所有测试的化合物均被证明是良好的自由基清除剂（IC50为10-30μM）。在HEK293细胞模型中初步筛选抗LTs活性后，在人多形核白细胞（PMNL）中确定了所选化合物的5-LO抑制潜能。在PMNL的浓度依赖性测定中，大多数被筛选的化合物的性能均优于CAPE 3，其

  DOI：

  10.1111/cbdd.12874
• 作为产物：
  描述：

  TRANS-咖啡酸 在 硫酸 、 异丙基氯化镁 、 4-甲基苯磺酸吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 6.08h， 生成 (E)-1-(3,4-bis((tetrahydro-2H-pyran-2-yl)oxy)phenyl)-5-phenylpent-1-en-3-one
  参考文献：
  名称：

  咖啡酸苯乙酯类似物作为新型5-脂氧合酶抑制剂的结构活性关系。

  摘要：

  白三烯（LTs）是一类脂质介体，与多种炎症性疾病有关。咖啡酸苯乙酯（CAPE）通过抑制5-脂氧合酶（5-LO）（LTs生物合成中的关键酶）而具有强大的抗LTs活性。在这项研究中，我们描述了作为自由基清除剂和5-LO抑制剂的CAPE类似物的设计和合成。通过Sonogashira和Heck交叉偶联反应合成了在咖啡酰基和芳基部分之间分别带有炔丙基和烯丙基连接基的咖啡酸酯（分别为4a-i和5a-i），以研究柔韧性和芳基取代对5-LO抑制的影响。合成了咖啡酰醇和醚（6，7a-b）以及咖啡酰醛和酮（8a-e），以阐明酯键对抑制活性的重要性。所有测试的化合物均被证明是良好的自由基清除剂（IC50为10-30μM）。在HEK293细胞模型中初步筛选抗LTs活性后，在人多形核白细胞（PMNL）中确定了所选化合物的5-LO抑制潜能。在PMNL的浓度依赖性测定中，大多数被筛选的化合物的性能均优于CAPE 3，其

  DOI：

  10.1111/cbdd.12874

文献信息

• Geometrically and Conformationally Restrained Cinnamoyl Compounds as Inhibitors of HIV-1 Integrase:  Synthesis, Biological Evaluation, and Molecular Modeling
  作者：Marino Artico、Roberto Di Santo、Roberta Costi、Ettore Novellino、Giovanni Greco、Silvio Massa、Enzo Tramontano、Maria E. Marongiu、Antonella De Montis、Paolo La Colla

  DOI：10.1021/jm9707232

  日期：1998.10.1

  Various cinnammoyl-based structures were synthesized and tested in enzyme assays as inhibitors of the HIV-1 integrase (IN). The majority of compounds were designed as geometrically or conformationally constrained analogues of caffeic acid phenethyl ester (CAPE) and were characterized by a syn disposition of the carbonyl group with respect to the vinylic double bond. Since the cinnamoyl moiety present in flavones such as quercetin (inactive on HIV-1-infected cells) is frozen in an anti arrangement, it was hoped that fixing our compounds in a syn disposition could favor anti-HIV-1 activity in cell-based assays. Geometrical and conformational properties of the designed compounds were taken into account through analysis of X-ray structures available from the Cambridge Structural Database. The polyhydroxylated analogues were prepared by reacting 3,4-bis(tetrahydropyran-2-yloxy)benzaldehyde with various compounds having active methylene groups such as 2-propanone, cyclopentanone, cyclohexanone, 1,3-diacetylbenzene, 2,4-dihydroxyacetophenone, 2,3-dihydro-1-indanone, 2,3-dihydro-1,3-indandione, and others. While active against both 3'-processing and strand-transfer reactions, the new compounds, curcumin included, failed to inhibit the HIV-1 multiplication in acutely infected MT-4 cells. Nevertheless, they specifically inhibited the enzymatic reactions associated with IN, being totally inactive against other viral (HIV-1 reverse transcriptase) and cellular (RNA polymerase II) nucleic acid-processing enzymes. On the other hand, title compounds were endowed with remarkable antiproliferative activity, whose potency correlated neither with the presence of catechols (possible source of reactive quinones) nor with inhibition of topoisomerases. The SARs developed for our compounds led to novel findings concerning the molecular determinants of IN inhibitory activity within the class of cinnamoyl-based structures. We hypothesize that these compounds bind to IN featuring the cinnamoyl residue C=C-C=O in a syn disposition, differently from flavone derivatives characterized by an anti arrangement about the same fragment. Certain inhibitors, lacking one of the two pharmacophoric catechol hydroxyls, retain moderate potency thanks to nonpharmacophoric fragments (i.e., a m-methoxy group in curcumin) which favorably interact with an "accessory" region of IN. This region is supposed to be located adjacent to the binding site accommodating the pharmacophoric dihydroxycinnamoyl moiety. Disruption of coplanarity in the inhibitor structure abolishes activity owing to poor shape complementarity with the target or an exceedingly high strain energy of the coplanar conformation.
• Structure-activity relationship of caffeic acid phenethyl ester analogs as new 5-lipoxygenase inhibitors
  作者：Jérémie A. Doiron、Luc M. Leblanc、Martin J. G. Hébert、Natalie A. Levesque、Aurélie F. Paré、Jacques Jean-François、Marc Cormier、Marc E. Surette、Mohamed Touaibia

  DOI：10.1111/cbdd.12874

  日期：2017.4

  lipid mediators implicated in numerous inflammatory disorders. Caffeic acid phenethyl ester (CAPE) possesses potent anti-LTs activity through the inhibition of 5-lipoxygenase (5-LO), the key enzyme in the biosynthesis of LTs. In this study, we describe the design and synthesis of CAPE analogs as radical scavengers and 5-LO inhibitors. Caffeic esters bearing propargyl and allyl linkers between the caffeoyl

  白三烯（LTs）是一类脂质介体，与多种炎症性疾病有关。咖啡酸苯乙酯（CAPE）通过抑制5-脂氧合酶（5-LO）（LTs生物合成中的关键酶）而具有强大的抗LTs活性。在这项研究中，我们描述了作为自由基清除剂和5-LO抑制剂的CAPE类似物的设计和合成。通过Sonogashira和Heck交叉偶联反应合成了在咖啡酰基和芳基部分之间分别带有炔丙基和烯丙基连接基的咖啡酸酯（分别为4a-i和5a-i），以研究柔韧性和芳基取代对5-LO抑制的影响。合成了咖啡酰醇和醚（6，7a-b）以及咖啡酰醛和酮（8a-e），以阐明酯键对抑制活性的重要性。所有测试的化合物均被证明是良好的自由基清除剂（IC50为10-30μM）。在HEK293细胞模型中初步筛选抗LTs活性后，在人多形核白细胞（PMNL）中确定了所选化合物的5-LO抑制潜能。在PMNL的浓度依赖性测定中，大多数被筛选的化合物的性能均优于CAPE 3，其