SCT-63

• 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: SCT-63
• 英文别名: 1-((2E,4E)-5-(1,3-benzodioxol-5-yl)-2,4-pentadien-1-yl)-piperidine；N-(5-(3,4-methylenedioxyphenyl)penta-2,4-dienyl)piperidine；1,3-Pentadiene, 1-(3,4-methylenedioxybenzyl)-5-(piperidine-1-yl)-；1-[(2E,4E)-5-(1,3-benzodioxol-5-yl)penta-2,4-dienyl]piperidine
• 化学式: C₁₇H₂₁NO₂
• 分子量: 271.359
• InChiKey: WSPMSRHCKZFXOA-YYPVUZKKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  胡椒碱 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 72.0h， 以34%的产率得到SCT-63
  参考文献：
  名称：

  Efficient Modulation of γ-Aminobutyric Acid Type A Receptors by Piperine Derivatives

  摘要：

  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.

  DOI：

  10.1021/jm5002277

文献信息

• 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.
• 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 inhibitory effect of piperine derivates on monoamine oxidase
  作者：Li-Hua Mu、Bo Wang、Hao-Yang Ren、Ping Liu、Dai-Hong Guo、Fu-Meng Wang、Lin Bai、Yan-Shen Guo

  DOI：10.1016/j.bmcl.2012.02.090

  日期：2012.5

  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.
• Is a Nitrogen Atom an Important Pharmacophoric Element in Sigma Ligand Binding?
  作者：Seth Y Ablordeppey、James B Fischer、Richard A Glennon

  DOI：10.1016/s0968-0896(00)00148-6

  日期：2000.8

  A lingering question in sigma receptor ligand development is whether a nitrogen atom serves as an important pharmacophoric clement in binding affinity. To address this question, we have synthesized several phenylalkylpiperidines and phenylalkylpiperazines and demonstrated that removal of the N atom from a typical phenylalkylpiperidine led to little or no binding to sigma receptors. Tn addition, where two N atoms occur in a compound, such as with phenylalkylpiperazines, the N atom on the longer alkyl chain appears to be more important. Thus, based on this study, the N atom is an important pharmacophoric element in the binding of phenylalkyllpiperidines and phenylalkylpiperazines to sigma receptors. (C) 2000 Elsevier Science Ltd. All rights reserved.
• SIGMA RECEPTOR LIGANDS AND THE USE THEREOF
  申请人：VIRGINIA COMMONWEALTH UNIVERSITY

  公开号：EP0591426A1

  公开（公告）日：1994-04-13