(2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-1-morpholinopenta-2,4-dien-1-one | 26163-80-4

• 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-(benzo[d][1,3]dioxol-5-yl)-1-morpholinopenta-2,4-dien-1-one
• 英文别名: 4-(5-(1,3-Benzodioxol-5-yl)-1-oxo-2,4-pentadienyl)morpholine；(2E,4E)-5-(1,3-benzodioxol-5-yl)-1-morpholin-4-ylpenta-2,4-dien-1-one
• CAS: 26163-80-4
• 化学式: C₁₆H₁₇NO₄
• 分子量: 287.315
• InChiKey: BVFLEPVRTQXJQL-ZPUQHVIOSA-N

物化性质

• 沸点：
  519.1±49.0 °C(Predicted)
• 密度：
  1.268±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  胡椒碱 在 氯化亚砜 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-1-morpholinopenta-2,4-dien-1-one
  参考文献：
  名称：

  Wahab, Aneela; Sultana, Amina; Khan, Khalid Mohammed, Journal of the Chemical Society of Pakistan, 2015, vol. 37, # 5, p. 1008 - 1014

  摘要：

  DOI：

文献信息

• The development of novel cytochrome P450 2J2 (CYP2J2) inhibitor and the underlying interaction between inhibitor and CYP2J2
  作者：Xiangge Tian、Meirong Zhou、Jing Ning、Xiaopeng Deng、Lei Feng、Huilian Huang、Dahong Yao、Xiaochi Ma

  DOI：10.1080/14756366.2021.1896500

  日期：2021.1.1

  identified a novel natural inhibitor (Piperine, 9a) with IC50 value of 0.44 μM from 108 common herbal medicines. Next, a series of its derivatives were designed and synthesised based on the underlying interactions of Piperine with CYP2J2. As expected, the much stronger inhibitors 9k and 9l were developed and their inhibition activities increased about 10 folds than Piperine with the IC50 values of 40

  摘要 人细胞色素P450 2J2（CYP2J2）作为一种重要的代谢酶，在多不饱和脂肪酸（PUFA）的代谢中起着至关重要的作用。CYP2J2水平升高与各种类型的癌症有关，因此它可能成为潜在的药物靶标。在本文中，我们基于CYP2J2的酶活性使用高通量筛选方法，从108种常见草药中快速有效地鉴定了IC 50值为0.44μM的新型天然抑制剂（Piperine，9a）。接下来，根据胡椒碱与CYP2J2的潜在相互作用，设计并合成了一系列衍生物。不出所料，更强的抑制剂9k和9l研发了它们，其抑制活性比Piperine增加了约10倍，IC 50值分别为40和50 nM。此外，抑制动力学说明9k和9l对CYP2J2的竞争抑制类型，K i的计算分别为0.11和0.074μM。此外，通过对接和分子动力学阐明了与CYP2J2相互作用的详细机理，我们的研究结果表明，CYP2J2的残基Thr114和Thr 315是关
• 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.
• Disruption of redox homeostasis with synchronized activation of apoptosis highlights the antifilarial efficacy of novel piperine derivatives: An in vitro mechanistic approach
  作者：Nikhilesh Joardar、Pradip Shit、Satyajit Halder、Utsab Debnath、Sudipto Saha、Anup Kumar Misra、Kuladip Jana、Santi P. Sinha Babu

  DOI：10.1016/j.freeradbiomed.2021.04.026

  日期：2021.6
• 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.
• Toxic effects of natural piperine and its derivatives on epimastigotes and amastigotes of Trypanosoma cruzi
  作者：Tatiana Santana Ribeiro、Leonardo Freire-de-Lima、José Osvaldo Previato、Lucia Mendonça-Previato、Norton Heise、Marco Edilson Freire de Lima

  DOI：10.1016/j.bmcl.2004.04.019

  日期：2004.7

  We describe herein an evaluation of trypanocidal effects of the natural alkaloid piperine and twelve synthetic derivatives against epimastigote and amastigote forms of the protozoan parasite Trypanosoma cruzi, the causative agent of the incurable human disease, Chagas' disease. The results obtained point to piperine as a suitable template for the development of new drugs with trypanocidal activity. (C) 2004 Elsevier Ltd. All rights reserved.