(2E,4E)-5-(3,4-methylenedioxyphenyl)-2,4-pentadienoic acid N-(n-butyl)amide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: (2E,4E)-5-(3,4-methylenedioxyphenyl)-2,4-pentadienoic acid N-(n-butyl)amide
• 英文别名: (2E,4E)-5-(1,3-benzodioxol-5-yl)-N-butyl-2,4-pentadienamide；N-butyl-5-(3,4-methylenedioxyphenyl)-2E,4E-pentadienamide；(2E,4E)-5-(1,3-benzodioxol-5-yl)-N-butylpenta-2,4-dienamide
• 化学式: C₁₆H₁₉NO₃
• 分子量: 273.332
• InChiKey: GLSARSFOAIORLO-YDFGWWAZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2E,4E)-5-(3,4-methylenedioxyphenyl)-2,4-pentadienoic acid N-(n-butyl)amide 在 palladium on activated charcoal 、 氢气 作用下， 反应 2.0h， 生成 5-(1,3-benzodioxol-5-yl)-N-butylpentanamide
  参考文献：
  名称：

  Synthesis and inhibitory effect of piperine derivates on monoamine oxidase

  摘要：

  A series of piperine derivates (1-19) have been designed, synthesized and evaluated in vitro for their monoamine oxidase (MAO) A and B inhibitory activity and selectivity. It is worth noting that most of the small amine moieties substituted on the piperidine ring proved to be potent and selective inhibitors of MAO-B rather than of MAO-A. 5-(3,4-methylenedioxyphenyl)-2E,4E-pentadienoic acid n-propyl amide (3) showed the greatest MAO-B inhibitory activity (IC50(MAO-B) = 0.045 mu M) and good selectivity (IC50(MAO-A) = 3.66 mu M). The conjugated double bond and carbonyl group of piperine are proved to be an essential feature for piperine and related alkylamides to exhibit MAO-inhibitory activity. Binding mode of the titled compounds was predicted using FlexX algorithm. The design and optimization of novel small molecule monoamine oxidase inhibitors will be guided by the results of this report. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.090
• 作为产物：
  描述：

  胡椒碱 在 草酰氯 、 三乙胺 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 30.0h， 生成 (2E,4E)-5-(3,4-methylenedioxyphenyl)-2,4-pentadienoic acid N-(n-butyl)amide
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Piperic Acid Amides as Free Radical Scavengers and α-Glucosidase Inhibitors

  摘要：

  合成了一系列胡椒酸酰胺（4–24, 29, 30），并评估了它们对1,1-二苯基-2-苦苷肼（DPPH）自由基的清除活性及α-葡萄糖苷酶的抑制活性。在合成的化合物中，含有邻甲氧基苯酚、儿茶酚或5-羟基吲哚基团的酰胺11、13和15表现出强效的DPPH自由基清除活性（11: EC50 140 µM; 13: EC50 28 µM; 15: EC50 20 µM）。酰胺10、18和23则展现出更高的α-葡萄糖苷酶抑制活性（10: IC50 21 µM; 18: IC50 21 µM; 23: IC50 12 µM）。这些数据显示，结合胺的疏水性是α-葡萄糖苷酶抑制活性的一个重要决定因素。此外，酰胺13和15同时表现出强效的DPPH自由基清除活性和α-葡萄糖苷酶抑制活性（13: IC50 46 µM; 15: IC50 46 µM）。这是首次报告胡椒酸酰胺的DPPH自由基清除活性和α-葡萄糖苷酶抑制活性，并暗示这些酰胺可能作为开发具有抗氧化活性的新型α-葡萄糖苷酶抑制剂的先导化合物。

  DOI：

  10.1248/cpb.c14-00874

文献信息

• Efficient Modulation of γ-Aminobutyric Acid Type A Receptors by Piperine Derivatives
  作者：Angela Schöffmann、Laurin Wimmer、Daria Goldmann、Sophia Khom、Juliane Hintersteiner、Igor Baburin、Thomas Schwarz、Michael Hintersteininger、Peter Pakfeifer、Mouhssin Oufir、Matthias Hamburger、Thomas Erker、Gerhard F. Ecker、Marko D. Mihovilovic、Steffen Hering

  DOI：10.1021/jm5002277

  日期：2014.7.10

  Piperine activates TRPV1 (transient receptor potential vanilloid type 1 receptor) receptors and modulates gamma-aminobutyric acid type A receptors (GABA(A)R). We have synthesized a library of 76 piperine analogues and analyzed their effects on GABA(A)R by means of a two-microelectrode voltage-clamp technique. GABA(A)R were expressed in Xenopus laevis oocytes. Structure-activity relationships (SARs) were established to identify structural elements essential for efficiency and potency. Efficiency of piperine derivatives was significantly increased by exchanging the piperidine moiety with either N,N-dipropyl, N,N-diisopropyl, N,N-dibutyl, p-methylpiperidine, or N,N-bis(trifluoroethyl) groups. Potency was enhanced by replacing the piperidine moiety by N,N-dibutyl, N,N-diisobutyl, or N,N-bistrifluoroethyl groups. Linker modifications did not substantially enhance the effect on GABA(A)R. Compound 23 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dipropyl-2,4-pentadienamide] induced the strongest modulation of GABA(A) (maximal GABA-induced chloride current modulation (IGABA-max = 1673% +/- 146%, EC50 = 51.7 +/- 9.5 mu M), while 25 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dibutyl-2,4-pentadienamide] displayed the highest potency (EC50 = 13.8 +/- 1.8 mu M, IGABA-max = 760% +/- 47%). Compound 23 induced significantly stronger anxiolysis in mice than piperine and thus may serve as a starting point for developing novel GABA(A)R modulators.
• Structure–activity relationship of piperine and its synthetic analogues for their inhibitory potentials of rat hepatic microsomal constitutive and inducible cytochrome P450 activities
  作者：Surrinder Koul、Jawahir L. Koul、Subhash C. Taneja、Kanaya L. Dhar、Deshvir S. Jamwal、Kuldeep Singh、Rashmeet K. Reen、Jaswant Singh

  DOI：10.1016/s0968-0896(99)00273-4

  日期：2000.1

  Inhibitors of drug metabolism have important implications in pharmaco-toxicology and agriculture. We have reported earlier that piperine, a major alkaloid of black and long peppers inhibits both constitutive and inducible cytochrome P450 (CYP)dependent drug metabolising enzymes. In the present study, an attempt has been made to prepare several novel synthetic analogues so as to relate various modifications in the parent molecule to the inhibition of CYP activities. Two types of mono-oxygenase reactions arylhydrocarbon hydroxylase (AHH) and 7-methoxycoumarin-O-demethylase (MOCD) have been studied. Inhibition studies were investigated in rat microsomal fraction prepared from untreated, 3MC- and PB- treated rat liver in vitro. Modifications were introduced into the piperine molecule: (i) in the phenyl nucleus, (ii) in the side chain and (iii) in the basic moiety. Thus, 38 compounds have been subjected to such studies, and simultaneously an attempt has also been made to arrive at the structure-activity relationship of synthetic analogues. In general, most of the inhibitory potential of the parent molecule is lost with modification in either of the three components of piperine. Saturation of the side chain resulted in significantly enhanced inhibition of CYP while modifications in the phenyl and basic moieties in few analogues offered maximal selectivity in inhibiting either constitutive or inducible CYP activities. Thus Few novel analogues as CYP inactivators have been synthesized which may have important consequences in pharmacokinetics and bioavailability of drugs. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Piperine analogs as potent Staphylococcus aureus NorA efflux pump inhibitors
  作者：Payare L. Sangwan、Jawahir L. Koul、Surrinder Koul、Mallepally V. Reddy、Niranjan Thota、Inshad A. Khan、Ashwani Kumar、Nitin P. Kalia、Ghulam N. Qazi

  DOI：10.1016/j.bmc.2008.09.042

  日期：2008.11

  Based on our recent findings that piperine is a potent Staphylococcus aureus NorA efflux pump inhibitor (EPI), 38 piperine analogs were synthesized and bioevaluated for their EPI activity. Twenty-five of them were found active with potentiating activity equivalent or more than known EPIs like reserpine, carsonic acid and verapamil. The inhibitory mechanism of the compounds was confirmed by efflux inhibition assay using ethidium bromide as NorA substrate. The present communication describes the synthesis, bioevaluation and structure related activity of these efflux pump inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.
• Effects of piperine analogues on stimulation of melanocyte proliferation and melanocyte differentiation
  作者：Radhakrishnan Venkatasamy、Laura Faas、Antony R Young、Amala Raman、Robert C Hider

  DOI：10.1016/j.bmc.2004.01.036

  日期：2004.4

  A wide range of piperine analogues has been synthesised in order to undertake a structure-activity study of their ability to stimulate melanocyte proliferation. Results demonstrate that an aromatic ring containing at least one ether function and a carbonyl group containing side chain is essential for this activity. A number of highly active piperine analogues have been identified, for instance 1-(3,4-methylenedioxyphenyl)-penta-2E,4E-dienoic acid methyl ester (3a), 1-E,E-piperinoyl-isobutylamine (4f) and 1-(3,4-methylenedioxyphenyl)-pentanoic acid cyclohexyl amide (20). A selection of analogues has also been evaluated for their effect on melanocyte morphology and melanogenesis. The piperine analogues altered cell morphology by increasing dendrite formation leading to bi-, tri- and quadripolar cells. These same analogues were found to increase total melanin in cell cultures, although melanin content per cell was not significantly altered from control in the presence of these compounds. (C) 2004 Elsevier Ltd. All rights reserved.
• Synthesis and insecticidal activity of new amide derivatives of piperine
  作者：Vanderlúcia F de Paula、Luiz C de A Barbosa、Antônio J Demuner、Dorila Piló-Veloso、Marcelo C Picanço

  DOI：10.1002/(sici)1526-4998(200002)56:2<168::aid-ps110>3.0.co;2-h

  日期：2000.2