(2E,6E)-2,6-bis(3,4-dihydroxybenzylidene)cyclohexanone

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: (2E,6E)-2,6-bis(3,4-dihydroxybenzylidene)cyclohexanone
• 英文别名: 2,6-bis((E)-3,4-dihydroxybenzylidene)cyclohexane-1-one；2,6-bis((E)-3,4-dihydroxybenzylidene)cyclohexan-1-one；2,6-bis(3,4-dihydroxybenz-(E)-ylidene)cyclohexanone；2,6-Bis(3,4-dihydroxybenzylidene)cyclohexanone；(2E,6E)-2,6-bis[(3,4-dihydroxyphenyl)methylidene]cyclohexan-1-one
• 化学式: C₂₀H₁₈O₅
• 分子量: 338.36
• InChiKey: JZODVJPLOFJTJZ-VOMDNODZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  98
• 氢给体数：
  4
• 氢受体数：
  5

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 22.0h， 生成 (2E,6E)-2,6-bis(3,4-dihydroxybenzylidene)cyclohexanone
  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

• Dynamic covalent assembly and disassembly of nanoparticle aggregates
  作者：Stefan Borsley、Euan R. Kay

  DOI：10.1039/c6cc00135a

  日期：——

  A new type of dynamic covalent nanoparticle (NP) building block is reported, exhibiting rapid constitutional adaptation in a NP-bound monolayer of boronate esters, and formation of covalently linked NP assemblies, which despite being connected by covalent bonds, can be fully disassembled on application of a chemical stimulus.

  报道了一种新型的动态共价纳米粒子（NP）构建块，它在NP结合的硼酸酯单层中表现出快速的结构适应性，并形成共价连接的NP组装体，尽管它们通过共价键连接，但仍可在其上完全分解化学刺激的应用。
• 一种双取代芳基类化合物及其应用
  申请人：中国人民解放军第二军医大学

  公开号：CN106800547B

  公开（公告）日：2019-07-23

  本发明涉及一种双取代芳基类化合物及其应用，所述的双取代芳基类化合物结构如式I、II或III所示，通过实验验证发现该类双取代芳基类化合物可以与唑类抗真菌药物共同使用，可提高耐药菌对唑类药物的敏感性，实现逆转耐药，因此本发明为临床耐药真菌的治疗提供了一种新途径。
• 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。
• Cinnamoyl Compounds as Simple Molecules that Inhibit p300 Histone Acetyltransferase
  作者：Roberta Costi、Roberto Di Santo、Marino Artico、Gaetano Miele、Paola Valentini、Ettore Novellino、Anna Cereseto

  DOI：10.1021/jm060943s

  日期：2007.4.1

  vitro tested as p300 inhibitors. At different degrees, all tested compounds were proven to inactivate p300, particularly, derivative 2c was the most active inhibitor, also showing high specificity for p300 as compared to other histone acetyltransferases. Most notably, 2c showed anti-acetylase activity in mammalian cells. These compounds represent a new class of synthetic inhibitors of p300, characterized

  设计，合成肉桂醛化合物1a-c和2a-d作为p300抑制剂并进行体外测试。在不同程度上，所有被测试的化合物均被证明能使p300失活，特别是衍生物2c是活性最高的抑制剂，与其他组蛋白乙酰转移酶相比，p300也显示出高特异性。最值得注意的是，2c在哺乳动物细胞中显示出抗乙酰酶活性。这些化合物代表了一类新的p300合成抑制剂，其化学结构简单。
• Phosphonate Analogs Of Hiv Integrase Inhibitor Compounds
  申请人：Cai R. Zhenhong

  公开号：US20080076738A1

  公开（公告）日：2008-03-27

  Novel HIV integrase inhibitor compounds having at least one phosphonate group, protected intermediates thereof, and methods for inhibition of HIV-integrase are disclosed.

  本发明公开了至少具有一个膦酸酯基团的新型HIV整合酶抑制剂化合物、其受保护的中间体以及用于抑制HIV整合酶的方法。