(1E,4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-4-(prop-2-ynyl)hepta-1,4,6-trien-3-one | 1240264-80-5

• 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: (1E,4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-4-(prop-2-ynyl)hepta-1,4,6-trien-3-one
• 英文别名: (1E,4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-4-(prop-2-yn-1-yl)hepta-1,4,6-trien-3-one；(1E,4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-4-prop-2-ynylhepta-1,4,6-trien-3-one
• CAS: 1240264-80-5
• 化学式: C₂₄H₂₂O₆
• 分子量: 406.435
• InChiKey: MLSFNAALQBYSHY-YMASAERZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  96.2
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1E,4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-4-(prop-2-ynyl)hepta-1,4,6-trien-3-one 、 (1'S,2R,2'S,4'S,5R,7'S,8'R,9'S,12'S,13'R,16'S)-5,7',9',13'-tetramethyl-5'-oxaspiro[oxane-2,6'-pentacyclo[10.8.0.0^2,9.0^4,8.0^13,18]icosan]-18'-en-16'-yl 3-(2-[2-(2-azidoethoxy)ethoxy]ethylcarbamoyl)propanoate 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 24.0h， 以40%的产率得到(1'S,2R,2'S,4'S,5R,7'S,8'R,9'S,12'S,13'R,16'S)-5,7',9',13'-tetramethyl-5'-oxaspiro[oxane-2,6'-pentacyclo[10.8.0.0²,⁹.0⁴,⁸.0¹³,¹⁸]icosan]-18'-en-16'-yl 3-(2-[2-(2-(4-[(2Z,4E)-2-[(2E)-1-hydroxy-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-ylidene]-5-(4-hydroxy-3-methoxyphenyl)-3-oxopent-4-en-1-yl]-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy]ethylcarbamoyl)propanoate
  参考文献：
  名称：

  Bivalent ligands incorporating curcumin and diosgenin as multifunctional compounds against Alzheimer’s disease

  摘要：

  In an effort to combat the multifaceted nature of Alzheimer's disease (AD) progression, a series of multifunctional, bivalent compounds containing curcumin and diosgenin were designed, synthesized, and biologically characterized. Screening results in MC65 neuroblastoma cells established that compound 38 with a spacer length of 17 atoms exhibited the highest protective potency with an EC50 of 111.7 +/- 9.0 nM. A reduction in protective activity was observed as spacer length was increased up to 28 atoms and there is a clear structural preference for attachment to the methylene carbon between the two carbonyl moieties of curcumin. Further study suggested that antioxidative ability and inhibitory effects on amyloid-b oligomer (A beta O) formation may contribute to the neuroprotective outcomes. Additionally, compound 38 was found to bind directly to A beta, similar to curcumin, but did not form complexes with the common biometals Cu, Fe, and Zn. Altogether, these results give strong evidence to support the bivalent design strategy in developing novel compounds with multifunctional ability for the treatment of AD. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.10.032
• 作为产物：
  描述：

  香草醛 、 3-溴丙炔 、 乙酰丙酮 在 potassium carbonate 、 氧化硼 作用下， 以 丙酮 、 甲苯 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 (1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-4-(prop-2-yn-1-yl)hepta-1,6-diene-3,5-dione 、 (1E,4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-4-(prop-2-ynyl)hepta-1,4,6-trien-3-one
  参考文献：
  名称：

  用于靶向癌症细胞凋亡机制的姜黄素-1,2,3-三唑偶联物

  摘要：

  肿瘤疾病的负担被广泛认为是导致死亡的一个严重原因。大多数抗癌疗法在临床上的不足迫切促使人们进行大量的药物发现工作，以鉴定具有有效和安全抗肿瘤特性的新化学实体。在这种情况下，靶向癌细胞凋亡机制已成为一种相关策略，可用于解决耐药性的出现。在此基础上，通过点击化学方法将“特权”合成子（如姜黄素支架和 1,2,3-三唑结构单元）组合在一起，获得了一个小型的受自然启发的杂化分子库。带有对氟苯基部分的化合物 1 显示出对 T 急性淋巴细胞白血病细胞生长的低微摩尔效力。更深入的生物学研究表明，对于这种类似物，细胞死亡诱导特性与其同时激活受体和线粒体凋亡级联的能力有关。这种特殊的行为为实现扩大的抗癌作用提供了希望，即强烈的细胞毒性反应以及降低的化学抗性暴动的倾向。总而言之，该研究允许将化合物 1 鉴定为值得作为抗癌药物候选物进行的先导化合物。

  DOI：

  10.3390/molecules25133066

文献信息

• [EN] NEW METAL CARBONYL COMPLEXES OF CURCUMIN DERIVATIVES, THEIR SYNTHESIS AND THEIR USES IN THERAPEUTIC APPLICATION<br/>[FR] NOUVEAUX COMPLEXES MÉTAL CARBONYLE DE DÉRIVÉS DE CURCUMINE, LEUR SYNTHÈSE ET LEURS APPLICATIONS DANS LE CHAMP THÉRAPEUTIQUE
  申请人：UNIV PARIS CURIE

  公开号：WO2012076696A1

  公开（公告）日：2012-06-14

  The present invention relates to new metal carbonyl complexes of curcumin derivatives, their synthesis and their uses in therapeutic application.

  本发明涉及姜黄素衍生物新金属羰基配合物、它们的合成以及它们在治疗应用中的用途。
• BIVALENT MULTIFUNCTIONAL LIGANDS TARGETING A[BETA] OLIGOMERS AS TREATMENT FOR ALZHEIMER'S DISEASE
  申请人：Zhang Shujin

  公开号：US20130156705A1

  公开（公告）日：2013-06-20

  Bivalent multifunctional Aβ oligomerization inhibitors (BMAOIs) that target multiple risk factors involved in Alzheimer's disease are provided. The BMAOIs are useful for the treatment and/or prevention of Alzheimer's disease, as well as for diagnostic imaging of Aβ plaques in brain tissue. The BMAOIs comprise i) an Aβ oligomer (ApO)-inhibitor moiety which may have antioxidant activity (e.g. curcumin, curcumin derivatives, curcumin hybrids, resveratrol, etc.); ii) a cell membrane/lipid raft (CM/LR) anchoring moiety (e.g. cholesterol, cholesterylamine, a steroid, etc.); and iii) a spacer or linker moiety that stably links i)

  提供了针对多个阿尔茨海默病风险因素的二价多功能Aβ寡聚体化抑制剂（BMAOI）。BMAOI对于阿尔茨海默病的治疗和/或预防以及Aβ斑块在脑组织中的诊断成像具有用途。BMAOI包括：i）Aβ寡聚体（ApO）抑制剂基团，可能具有抗氧化活性（例如姜黄素，姜黄素衍生物，姜黄素杂合物，白藜芦醇等）；ii）细胞膜/脂 rafts（CM / LR）锚定基团（例如胆固醇，胆固醇胺，类固醇等）；和iii）稳定连接i）和ii）的间隔或连接基团。
• Bivalent Ligands Targeting Multiple Pathological Factors Involved in Alzheimer's Disease
  作者：Kai Liu、Ronak Gandhi、Jiangmin Chen、Shijun Zhang

  DOI：10.1021/ml300229y

  日期：2012.11.8

  In a continuing effort to develop multifunctional compounds as potential treatment agents for Alzheimer's disease (AD), a series of bivalent ligands containing curcumin and cholesterylamine were designed, synthesized, and biologically characterized. Biological characterization supported earlier results that the spacer length and its attachment position on curcumin are essential structural determinants for biological activity in this class. Compounds with a spacer length of 17-21 atoms exhibited optimal neuro-protection in human neuroblastoma MC65 cells with submicromolar potency. These compounds inhibited the formation of amyloid-beta oligomers (A beta Os) and exhibited antioxidative activities in MC65 cells. Bivalent ligand 8, with its spacer (length of 17 atoms) connected at the methylene carbon between the two carbonyls of the curcumin moiety, is the most potent with an EC50 of 0.083 +/- 0.017 mu M. In addition, 8 formed a complex with biometals, such as Cu, Fe, and Zn. Collectively, the results strongly support our assertion that these compounds are designed bivalent ligands with potential as multifunctional and neuroprotective agents.
• Insights into the Impact of a Membrane-Anchoring Moiety on the Biological Activities of Bivalent Compounds As Potential Neuroprotectants for Alzheimer’s Disease
  作者：Liu He、Yuqi Jiang、Kai Liu、Victoria Gomez-Murcia、Xiaopin Ma、Alejandro Torrecillas、Qun Chen、Xiongwei Zhu、Edward Lesnefsky、Juan C. Gomez-Fernandez、Bin Xu、Shijun Zhang

  DOI：10.1021/acs.jmedchem.7b01284

  日期：2018.2.8

  Bivalent compounds anchoring in different manners to the membrane were designed and biologically characterized to understand the contribution of the anchor moiety to their biological activity as neuroprotectants for Alzheimer's disease. Our results established that the anchor moiety is essential, and we identified a preference for diosgenin, as evidenced by 17MD. Studies in primary neurons and mouse brain mitochondria also identified 17MD as exhibiting activity on neuritic outgrowth and the state 3 oxidative rate of glutamate while preserving the coupling capacity Of the mitochondria. Significantly, our studies demonstrated that the integrated bivalent structure is essential to the observed biological activities. Further studies employing bivalent compounds as, probes in a model membrane also revealed the influence of the anchor moiety on how they interact with the membrane. Collectively, our results suggest diosgenin to be an optimal anchor moiety, providing bivalent compounds with promising pharmacology that have potential applications for Alzheimer's disease.
• US9260473B2
  申请人：——

  公开号：US9260473B2

  公开（公告）日：2016-02-16