2,5-Bis-[4-(tetrahydro-pyran-2-yloxy)-benzylidene]-cyclopentanone | 946161-26-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2,5-Bis-[4-(tetrahydro-pyran-2-yloxy)-benzylidene]-cyclopentanone
• 英文别名: 2,5-bis[[4-(oxan-2-yloxy)phenyl]methylidene]cyclopentan-1-one
• CAS: 946161-26-8
• 化学式: C₂₉H₃₂O₅
• 分子量: 460.57
• InChiKey: KAMOVQGOLIORTQ-UHFFFAOYSA-N

物化性质

• 沸点：
  683.6±55.0 °C(Predicted)
• 密度：
  1.225±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,5-Bis-[4-(tetrahydro-pyran-2-yloxy)-benzylidene]-cyclopentanone 在 对甲苯磺酸 作用下， 以 乙醇 为溶剂， 反应 10.0h， 生成 2,5-bis(4-hydroxybenzylidene)-cyclopentanone
  参考文献：
  名称：

  Synthesis, crystal structure and anti-inflammatory properties of curcumin analogues

  摘要：

  Curcuminoids have been reported to possess multifunctional bioactivities, especially the ability to inhibit proinflammatory induction. Since it has been suggested that the seven-carbon beta-diketone linker in curcumin is responsible for its instability, nine mono-carbonyl five-carbon linker containing analogues were designed and synthesized. Their bioactivity against lipopolysaccharide-induced TNF-alpha amd IL-6 secretion was evaluated by using mouse J774.1 macrophages. The results showed that the 3'-methoxyl plays an important role in bioactivity and cyclohexanone containing analogues exhibited stronger inflammatory inhibition than acetone and cyclopentanone analogues. Subsequently the most active analogue 3c was determined using single-crystal X-ray diffraction. X-ray analysis and comparison with curcumin reveals that the presence of cyclohexanone in 3c, which remotely resembles the 6-membered ring in the enol tautomer in curcumin, may play an important role in the bioactivity. It is suggested that five-carbon linker analogues containing a cyclohexane ring which are synthetically assessable may be pharmacologically important. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.01.031
• 作为产物：
  描述：

  对羟基苯甲醛 在 4-甲基苯磺酸吡啶 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 7.0h， 生成 2,5-Bis-[4-(tetrahydro-pyran-2-yloxy)-benzylidene]-cyclopentanone
  参考文献：
  名称：

  Functionalized curcumin analogs as potent modulators of the Wnt/β-catenin signaling pathway

  摘要：

  Osteosarcoma is a primary bone malignancy with aggressive metastatic potential and poor prognosis rates. In our earlier work we have investigated the therapeutic potential of curcumin as an anti-invasive agent in osteosarcoma by its ability to regulate the Wnt/beta-catenin signaling pathway. However, the clinical use of curcumin is limited owing to its low potency and poor pharmacokinetic profile. In this study, an attempt was made to achieve more potent Wnt inhibitory activity in osteosarcoma cells by carrying out synthetic chemical modifications of curcumin. We synthesized a total of five series consisting of 43 curcumin analogs and screened in HEK293T cells for inhibition of beta-catenin transcriptional activity. Six promising analogs, which were 6.5- to 60-fold more potent than curcumin in inhibiting Wnt activity, were further assessed for their anti-invasive activity and Wnt inhibitory mechanisms. Western blot analysis showed disruption of beta-catenin protein nuclear translocation following treatment with analogs 2f, 3c and 4f. Using transwell assays, we also found that these compounds were more potent than la (curcumin) in impeding the invasion of osteosarcoma cells, possibly through suppressing MMP-9 activity. Structure-activity-relationship studies revealed that Wnt inhibitory effects could be enhanced by shortening and restraining the flexibility of the 7-carbon linker moiety connecting the terminal aromatic rings of curcumin and substituting both rings with appropriate substituents. Our results demonstrate that the synthesized curcumin analogs are more potent Wnt inhibitors in osteosarcoma cell lines as compared to parental curcumin and are good lead compounds for further development. Future in vivo tests with these compounds will define their therapeutic potentials as promising drug candidates for clinical treatment of osteosarcoma. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.10.073

文献信息

• Cycloalkanone derivatives
  申请人：MERCK KGAA

  公开号：US20030080321A1

  公开（公告）日：2003-05-01

  The invention relates to compounds of formula I 1 wherein M 1 , M 2 and M 3 have the meanings of claim 1, to liquid crystalline mixtures and polymers containing them, and to the use of the compounds of formula I, the liquid crystalline mixtures and the polymers containing them in optical and electrooptical devices like liquid crystal displays or projection systems, patterned films and optical elements like polarizers, retardation films, compensators, colour filters, holographic elements or polarization beam splitters, for photoswitching, in anisotropic membranes for the permeation of gases or fluids, adhesives, synthetic resins with anisotropic mechanical properties, cosmetic or pharmaceutical compositions, UV absorbers and sunscreens, diagnostics or liquid crystal pigments, for decorative and security applications, in nonlinear optics, optical information storage or as dopants.

  本发明涉及式I1的化合物，其中M1、M2和M3具有权利要求1中的含义，液晶混合物和含有它们的聚合物，以及在光学和电光设备中使用式I的化合物、液晶混合物和含有它们的聚合物，如液晶显示器或投影系统、图案膜和光学元件，如偏振器、延迟膜、补偿器、彩色滤光片、全息元件或偏振分束器，用于光开关、各向异性膜用于气体或流体渗透、粘合剂、具有各向异性机械性能的合成树脂、化妆品或药物组合物、UV吸收剂和防晒霜、诊断或液晶颜料，用于装饰和安全应用，非线性光学、光学信息存储或作为掺杂剂。
• Cycloalkanone Derivates
  申请人：Merck Patent GmbH

  公开号：EP1247797B1

  公开（公告）日：2007-07-04
• Functionalized curcumin analogs as potent modulators of the Wnt/β-catenin signaling pathway
  作者：Pay-Chin Leow、Priti Bahety、Choon Pei Boon、Chong Yew Lee、Kheng Lin Tan、Tianming Yang、Pui-Lai Rachel Ee

  DOI：10.1016/j.ejmech.2013.10.073

  日期：2014.1

  Osteosarcoma is a primary bone malignancy with aggressive metastatic potential and poor prognosis rates. In our earlier work we have investigated the therapeutic potential of curcumin as an anti-invasive agent in osteosarcoma by its ability to regulate the Wnt/beta-catenin signaling pathway. However, the clinical use of curcumin is limited owing to its low potency and poor pharmacokinetic profile. In this study, an attempt was made to achieve more potent Wnt inhibitory activity in osteosarcoma cells by carrying out synthetic chemical modifications of curcumin. We synthesized a total of five series consisting of 43 curcumin analogs and screened in HEK293T cells for inhibition of beta-catenin transcriptional activity. Six promising analogs, which were 6.5- to 60-fold more potent than curcumin in inhibiting Wnt activity, were further assessed for their anti-invasive activity and Wnt inhibitory mechanisms. Western blot analysis showed disruption of beta-catenin protein nuclear translocation following treatment with analogs 2f, 3c and 4f. Using transwell assays, we also found that these compounds were more potent than la (curcumin) in impeding the invasion of osteosarcoma cells, possibly through suppressing MMP-9 activity. Structure-activity-relationship studies revealed that Wnt inhibitory effects could be enhanced by shortening and restraining the flexibility of the 7-carbon linker moiety connecting the terminal aromatic rings of curcumin and substituting both rings with appropriate substituents. Our results demonstrate that the synthesized curcumin analogs are more potent Wnt inhibitors in osteosarcoma cell lines as compared to parental curcumin and are good lead compounds for further development. Future in vivo tests with these compounds will define their therapeutic potentials as promising drug candidates for clinical treatment of osteosarcoma. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Synthesis, crystal structure and anti-inflammatory properties of curcumin analogues
  作者：Guang Liang、Shulin Yang、Huiping Zhou、Lili Shao、Kexin Huang、Jian Xiao、Zhifeng Huang、Xiaokun Li

  DOI：10.1016/j.ejmech.2008.01.031

  日期：2009.2

  Curcuminoids have been reported to possess multifunctional bioactivities, especially the ability to inhibit proinflammatory induction. Since it has been suggested that the seven-carbon beta-diketone linker in curcumin is responsible for its instability, nine mono-carbonyl five-carbon linker containing analogues were designed and synthesized. Their bioactivity against lipopolysaccharide-induced TNF-alpha amd IL-6 secretion was evaluated by using mouse J774.1 macrophages. The results showed that the 3'-methoxyl plays an important role in bioactivity and cyclohexanone containing analogues exhibited stronger inflammatory inhibition than acetone and cyclopentanone analogues. Subsequently the most active analogue 3c was determined using single-crystal X-ray diffraction. X-ray analysis and comparison with curcumin reveals that the presence of cyclohexanone in 3c, which remotely resembles the 6-membered ring in the enol tautomer in curcumin, may play an important role in the bioactivity. It is suggested that five-carbon linker analogues containing a cyclohexane ring which are synthetically assessable may be pharmacologically important. (C) 2008 Elsevier Masson SAS. All rights reserved.