(1E,4Z,6E)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4-(prop-2-yn-1-yloxy)phenyl)hepta-1,4,6-trien-3-one | 1240264-79-2

• 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-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4-(prop-2-yn-1-yloxy)phenyl)hepta-1,4,6-trien-3-one
• 英文别名: (1E,4Z,6E)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4-prop-2-ynoxyphenyl)hepta-1,4,6-trien-3-one
• CAS: 1240264-79-2
• 化学式: C₂₄H₂₂O₆
• 分子量: 406.435
• InChiKey: MSOHANQKDJYWED-PHDHLXRDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1E,4Z,6E)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4-(prop-2-yn-1-yloxy)phenyl)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 2-(2-(2-(2-(10-azidodecanamido)ethoxy)ethoxy)ethoxy)acetate 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 24.0h， 以85%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[10.8.0.0^2,9.0^4,8.0^13,18]icosan]-18'-en-16'-yl 2-[2-(2-(2-[10-(4-(4-[(1E,3Z,6E)-3-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-5-oxohepta-1,3,6-trien-1-yl]-2-methoxyphenoxymethyl)-1H-1,2,3-triazol-1-yl)decanamido]ethoxy)ethoxy)ethoxy]acetate
  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 在 氧化硼 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 50.0h， 生成 (1E,4Z,6E)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4-(prop-2-yn-1-yloxy)phenyl)hepta-1,4,6-trien-3-one
  参考文献：
  名称：

  [EN] PROBE DIRECTED TO ENZYME ALDH1A3 AND USE THEREOF IN THE DIAGNOSIS OF GLIOBLASTOMA
  [FR] SONDE DIRIGÉE CONTRE L'ENZYME ALDH1A3 ET SON UTILISATION DANS LE DIAGNOSTIC DU GLIOBLASTOME

  摘要：

  The present invention relates to compounds of formula (I), wherein X is –OH, -N(CH3)2, (II) or (III) or (IV); Y is CH or N; and Z is (V), (VI), (VII), (VIII) or (IX) and salts, solvates and solvates of the salts thereof.

  公开号：

  WO2022214995A1

文献信息

• 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.
• US9260473B2
  申请人：——

  公开号：US9260473B2

  公开（公告）日：2016-02-16