3,5-bis(3,4-dihydroxybenz-(E)-ylidene)-4-piperidone hydrochloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 3,5-bis(3,4-dihydroxybenz-(E)-ylidene)-4-piperidone hydrochloride
• 英文别名: (3E,5E)-3,5-bis(3,4-dihydroxybenzylidene)piperidin-4-one hydrochloride；(3E,5E)-3,5-bis[(3,4-dihydroxyphenyl)methylidene]piperidin-4-one;hydrochloride
• 化学式: C₁₉H₁₇NO₅*ClH
• 分子量: 375.809
• InChiKey: PDMLLACYCDASEZ-HGYMEXNASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.87
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  115
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,5-bis(3,4-dihydroxybenz-(E)-ylidene)-4-piperidone hydrochloride 在 1-丙基磷酸酐 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 N-{3-[4-(3-aminopropylamino)butylamino]propyl}-4-[3,5-bis-(3,4-dihydroxybenzylidene)-4-oxopiperidin-1-yl]-4-oxobutanamide tri(trifluoroacetate)
  参考文献：
  名称：

  多胺共轭作为在阿尔茨海默氏病框架内靶向淀粉样蛋白聚集的有前途的策略

  摘要：

  精胺缀合物2 - 6，携带各种装饰3,5- dibenzylidenepiperidin -4-酮作为生物活性动机，被设计成引导antiaggregating属性到线粒体，使用多胺的功能的车辆的工具。研究证实线粒体邻苯二酚衍生物2的进口对Aβ诱导的毒性具有有效的抗聚集活性和神经保护作用。值得注意的是，还没有阐明聚胺基序在Aβ分子识别中的关键功能。在计算机模拟研究的支持下，该实验读数为聚胺的作用提供了重要的新见解。因此，我们提出多胺缀合作为开发神经保护剂导线的有前途的策略，可能有助于破译Aβ毒性的复杂图景。

  DOI：

  10.1021/acsmedchemlett.6b00339
• 作为产物：
  描述：

  4-氧代哌啶酮盐酸盐 、 3,4-二羟基苯甲醛 在 盐酸 、 溶剂黄146 作用下， 反应 48.0h， 以86%的产率得到3,5-bis(3,4-dihydroxybenz-(E)-ylidene)-4-piperidone hydrochloride
  参考文献：
  名称：

  多胺共轭作为在阿尔茨海默氏病框架内靶向淀粉样蛋白聚集的有前途的策略

  摘要：

  精胺缀合物2 - 6，携带各种装饰3,5- dibenzylidenepiperidin -4-酮作为生物活性动机，被设计成引导antiaggregating属性到线粒体，使用多胺的功能的车辆的工具。研究证实线粒体邻苯二酚衍生物2的进口对Aβ诱导的毒性具有有效的抗聚集活性和神经保护作用。值得注意的是，还没有阐明聚胺基序在Aβ分子识别中的关键功能。在计算机模拟研究的支持下，该实验读数为聚胺的作用提供了重要的新见解。因此，我们提出多胺缀合作为开发神经保护剂导线的有前途的策略，可能有助于破译Aβ毒性的复杂图景。

  DOI：

  10.1021/acsmedchemlett.6b00339

文献信息

• Design, synthesis, and antihypertensive activity of curcumin-inspired compounds via ACE inhibition and vasodilation, along with a bioavailability study for possible benefit in cardiovascular diseases
  作者：Li-chun Wang、Xiao-dong Zhuang、Li-zhen Liao、Xiao-bian Dong、Xun Hu、Yue Guo、Zhi-min Du、Xin-xue Liao

  DOI：10.2147/dddt.s96315

  日期：——

  This study describes the synthesis of a novel series of curcumin-inspired compounds via a facile synthetic route. The structures of these derivatives were ascertained using various spectroscopic and analytic techniques. The pharmacological effects of the target analogs were assessed by assaying their inhibition of angiotensin-converting enzyme (ACE). All of the synthesized derivatives exhibited considerable

  这项研究描述了通过简便的合成途径合成一系列新的姜黄素类化合物。使用各种光谱学和分析技术确定这些衍生物的结构。通过测定靶类似物对血管紧张素转化酶（ACE）的抑制作用来评估其药理作用。所有合成的衍生物均显示出对ACE的显着抑制，其最大抑制浓度的一半为1.23至120.32μM。在与睾丸ACE（tACE）的对接分析中，最有前途的抑制剂（4j）被有效地容纳在蛋白腔的深裂中，与Glu162，His353和Ala356的原子间紧密接触，与赖诺普利相当。化合物4i，4j，4k，使用Langendorff技术，进一步选择4l和4l来确定其在离体大鼠心脏上的血管舒张活性（心输出量和中风量）。在实验小鼠中测定化合物4j的生物利用度。
• Curcumin Analogs as Potent Aldose Reductase Inhibitors
  作者：Zhi-Yun Du、Ya-Dan Bao、Zhong Liu、Wei Qiao、Lin Ma、Zhi-Shu Huang、Lian-Quan Gu、Albert S. C. Chan

  DOI：10.1002/ardp.200500205

  日期：2006.3

  study, curcuminoids isolated from curcuma longa were demonstrated to possess inhibitory activities on bovine lens aldose reductase. In order to find more potent aldose reductase inhibitor, curcumin analogs were synthesized and evaluated for their ability to inhibit bovine lens aldose reductase enzyme. The results indicated that the compounds with tetrahydroxyl groups, 2,6‐bis(3,4‐dihydroxybenzylidene)cyclohexanone

  在本研究中，从姜黄中分离的姜黄素被证明对牛晶状体醛糖还原酶具有抑制活性。为了找到更有效的醛糖还原酶抑制剂，合成了姜黄素类似物并评估了它们抑制牛晶状体醛糖还原酶的能力。结果表明，具有四羟基基团的化合物、2,6-双(3,4-二羟基亚苄基)环己酮(A2)、2,5-双(3,4-二羟基亚苄基)环戊酮(B2)、1,5-双( 3,4-二羟基苯基)-1,4-戊二烯-3-一(C2)和3,5-双(3,4-二羟基苯亚甲基)-4-哌啶酮(D2)对醛糖还原酶具有显着的抑制作用，IC50分别为 2.9 μM、2.6 μM、3.4 μM 和 4.9 μM。
• 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.
• α-Glucosidase inhibition of natural curcuminoids and curcumin analogs
  作者：Zhi-yun Du、Rong-rong Liu、Wei-yan Shao、Xue-pu Mao、Lin Ma、Lian-quan Gu、Zhi-shu Huang、Albert S.C. Chan

  DOI：10.1016/j.ejmech.2005.10.012

  日期：2006.2

  Natural curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin (3) isolated from Curcuma longa (turmeric), and synthetic curcumin analogs (A(1-7), B1-7, C1-6 and D1-7) were evaluated in vitro for the a-glucosidase inhibitory activity via UV and circular dichroism (CD) spectroscopy. The results indicated that natural curcuminoid compound 3 showed a remarkable inhibitory effect with IC50 of 23.0 mu M, and the synthetic compounds A(2), B-2, C-2 and D-2 showed potent inhibitory effects with IC50 of 2.8, 2.6, 1.6 and 8.2 mu M, respectively. Kinetic study exhibited that the mechanism of alpha-glucosidase inhibition of both 3 and C-2 was non-competitive. The structure activity relationship revealed that the ortho dihydroxyl groups could form a more tight interaction with a-glucosidase to exert more potential inhibitory activities. (c) 2006 Elsevier SAS. All fights reserved.
• Polyamine Conjugation as a Promising Strategy To Target Amyloid Aggregation in the Framework of Alzheimer’s Disease
  作者：Elena Simoni、Roberta Caporaso、Christian Bergamini、Jessica Fiori、Romana Fato、Przemyslaw Miszta、Sławomir Filipek、Filippo Caraci、Maria Laura Giuffrida、Vincenza Andrisano、Anna Minarini、Manuela Bartolini、Michela Rosini

  DOI：10.1021/acsmedchemlett.6b00339

  日期：2016.12.8

  variously decorated 3,5-dibenzylidenepiperidin-4-one as bioactive motives, were designed to direct antiaggregating properties into mitochondria, using a polyamine functionality as the vehicle tool. The study confirmed mitochondrial import of the catechol derivative 2, which displayed effective antiaggregating activity and neuroprotective effects against Aβ-induced toxicity. Notably, a key functional role for

  精胺缀合物2 - 6，携带各种装饰3,5- dibenzylidenepiperidin -4-酮作为生物活性动机，被设计成引导antiaggregating属性到线粒体，使用多胺的功能的车辆的工具。研究证实线粒体邻苯二酚衍生物2的进口对Aβ诱导的毒性具有有效的抗聚集活性和神经保护作用。值得注意的是，还没有阐明聚胺基序在Aβ分子识别中的关键功能。在计算机模拟研究的支持下，该实验读数为聚胺的作用提供了重要的新见解。因此，我们提出多胺缀合作为开发神经保护剂导线的有前途的策略，可能有助于破译Aβ毒性的复杂图景。