(3E,5E)-3,5-bis(3,4-dihydroxybenzylidene)dihydro-2H-pyran-4(3H)-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (3E,5E)-3,5-bis(3,4-dihydroxybenzylidene)dihydro-2H-pyran-4(3H)-one
• 英文别名: (3E,5E)-3,5-bis(3,4-dihydroxybenzylidene)-tetrahydropyran-4-one；3,5-Bis((3,4-dihydroxyphenyl)methylene)oxan-4-one；(3E,5E)-3,5-bis[(3,4-dihydroxyphenyl)methylidene]oxan-4-one
• 化学式: C₁₉H₁₆O₆
• 分子量: 340.332
• InChiKey: WJXMHIODWHBGHP-ACFHMISVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  25
• 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：
  107
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3,4-二(四氢吡喃-2-氧基)苯甲醛 在 barium hydroxide octahydrate 、 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 反应 18.5h， 生成 (3E,5E)-3,5-bis(3,4-dihydroxybenzylidene)dihydro-2H-pyran-4(3H)-one
  参考文献：
  名称：

  Geometrically and Conformationally Restrained Cinnamoyl Compounds as Inhibitors of HIV-1 Integrase:  Synthesis, Biological Evaluation, and Molecular Modeling

  摘要：

  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.

  DOI：

  10.1021/jm9707232

文献信息

• Design, synthesis, and evaluation of NDGA analogues as potential anti-ischemic stroke agents
  作者：Lili Huang、Jiabing Wang、Liping Chen、Min Zhu、Shoubiao Wu、Shenghui Chu、Yuantie Zheng、Ziliang Fan、Jiafeng Zhang、Wulan Li、Dahui Chen、Xiufei Yang、Sicen Wang、Peihong Qiu、Jianzhang Wu

  DOI：10.1016/j.ejmech.2017.09.028

  日期：2018.1

  supplementation of antioxidants with ROS scavenging activity would be a potential therapy to cerebral ischemia-reperfusion injury in stroke. In the present study, a series of NDGA analogues with attenuation oxidative stress by directly scavenging ROS and indirectly through keap1/Nrf2/ARE pathway activation were designed and synthesized. All analogues were found to effectively remove ROS directly by DPPH radical

  外源补充具有清除ROS活性的抗氧化剂可能是中风脑缺血再灌注损伤的一种潜在疗法。在本研究中，设计和合成了一系列通过直接清除ROS以及通过keap1 / Nrf2 / ARE途径间接激活而具有降低氧化应激作用的NDGA类似物。发现所有类似物均可通过DPPH自由基清除法直接有效去除ROS，化合物3a通过促进Nrf2易位进入细胞核并增加血红素加氧酶-1（HO-1）的表达，有效保护PC12细胞免受氧化损伤。间接强烈降低细胞内ROS水平。更重要的是3a显着减少了短暂性脑中动脉闭塞（MCAO）大鼠的脑缺血再灌注损伤后的脑梗塞。总体而言，我们的发现表明化合物3a可以作为治疗中风的有前途的化合物。
• New MD2 inhibitors derived from curcumin with improved anti-inflammatory activity
  作者：Yali Zhang、Zhiguo Liu、Jianzhang Wu、Bin Bai、Hongjin Chen、Zhongxiang Xiao、Lingfeng Chen、Yunjie Zhao、Hazel Lum、Yi Wang、Hong Zhang、Guang Liang

  DOI：10.1016/j.ejmech.2018.02.008

  日期：2018.3

  An overactive Toll-like receptor (TLR) signaling complex is a significant pathogenic factor of acute and chronic inflammatory diseases. The natural product curcumin is reported to inhibit the TLR4 co-receptor, MD2 (myeloid differentiation protein 2), but its low in vivo bioavailability limits its therapeutic potential. We developed new curcumin analogs (MACs) with removal of the beta-diketone moiety and substituted residues in benzene rings, and identify these as potential MD2 inhibitors with improved inhibition potency and stability over that of curcumin. Specifically, MAC 17 and 28 showed the highest anti-inflammatory activity, with >90% inhibition of LPS-stimulated cytokine secretion from macrophages, and protected against LPS-induced acute lung injury and sepsis. The MACs inhibited the TLR4-MD2 signaling complex through competition with LPS for binding on MD2, likely at Arg(90). Our findings indicated that MAC 17 and 28 are promising candidates for future development as therapeutic drugs for inflammatory diseases with an endotoxin etiology. (C) 2018 Elsevier Masson SAS. All rights reserved.
• METHODS TO PREPARE PENTA-1,4-DIEN-3-ONES AND SUBSTITUTED CYCLOHEXANONES AND DERIVATIVES WITH ANTITUMORAL AND ANTIPARASITIC PROPERTIES, THE COMPOUNDS AND THEIR USES
  申请人：Uniban - Universidade Bandeirante De São Paulo

  公开号：EP2054365A2

  公开（公告）日：2009-05-06
• US8859625B2
  申请人：——

  公开号：US8859625B2

  公开（公告）日：2014-10-14
• [EN] METHODS TO PREPARE PENTA-1,4-DIEN-3-ONES AND SUBSTITUTED CYCLOHEXANONES AND DERIVATIVES WITH ANTITUMORAL AND ANTIPARASITIC PROPERTIES, THE COMPOUNDS AND THEIR USES<br/>[FR] PROCÉDÉS DE PRÉPARATION DE PENTA-1,4-DIÈN-3-ONES ET DE CYCLOHEXANONES SUBSTITUÉS, DÉRIVÉS PRÉSENTANT DES PROPRIÉTÉS ANTITUMORALES ET ANTIPARASITIQUES, ET COMPOSÉS ET LEURS UTILISATIONS
  申请人：UNIBAN UNIVERSIDADE BANDEIRANT

  公开号：WO2008003155A2

  公开（公告）日：2008-01-10

  [EN] The present invention refers to new derivatives of the penta-1,4-dien-3-ones, as well as their processes of preparation. These compounds present strong antitumoral activity and promising antiparasitic action, behaving as almost atoxic by laboratory assays and also by hystopathologic studies. The present invention refers also to a pharmaceutical composition consisting of the referred compounds, method of treatment for cancer and parasitic diseases.
  [FR] La présente invention concerne de nouveaux dérivés de penta-1,4-dièn-3-ones, ainsi que leurs procédés de préparation. Ces composés présentent une forte activité antitumorale et une action antiparasitique prometteuse, se comportant presque de manière atoxique lors des essais en laboratoire, ainsi que lors d'études hystopathologiques. La présente invention concerne également une composition pharmaceutique comprenant lesdits composés, un procédé de traitement du cancer et des maladies parasitiques.