| 1240264-92-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• CAS: 1240264-92-9
• 化学式: C₁₄H₂₇N₅O₂
• 分子量: 297.401
• InChiKey: KZPATYQRGQDDTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.67
• 重原子数：
  21.0
• 可旋转键数：
  13.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  106.96
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  、 5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4-propargyloxyphenyl)hepta-1,4,6-trien-3-one 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 N-butyl-N'-[6-[4-[[4-[3-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-5-oxohepta-1,3,6-trienyl]-2-methoxyphenoxy]methyl]triazol-1-yl]hexyl]butanediamide
  参考文献：
  名称：

  “Clicked” Bivalent Ligands Containing Curcumin and Cholesterol As Multifunctional Aβ Oligomerization Inhibitors: Design, Synthesis, and Biological Characterization

  摘要：

  In our effort to develop multifunctional compounds that cotarget beta-amyloid oligomers (A beta Os), cell membrane/lipid rafts (CM/LR), and oxidative stress, a series of bivalent multifunctional A beta oligomerization inhibitors (BMAOIs) containing cholesterol and curcumin were designed, synthesized, and biologically characterized as potential treatments for Alzheimer's disease (AD). The in vitro assay results established that the length of spacer that links cholesterol and curcumin and the attaching position of the spacer on curcumin are important structural determinants for their biological activities. Among the BMAOIs tested, 14 with a 21-atom-spacer was identified to localize to the CM/LR of human neuroblastoma MC65 cells, to inhibit the formation of A beta Os in MC65 cells, to protect cells from A beta Os-induced cytotoxicity, and to retain antioxidant properties of curcumin. Furthermore, 14 was confirmed to have the potential to cross the blood-brain barrier (BBB) as demonstrated in a Caco-2 cell model. Collectively, these results strongly encourage further optimization of 14 as a new hit to develop more potent BMAOIs.

  DOI：

  10.1021/jm100601q

文献信息

• [EN] BIVALENT MULTIFUNCTIONAL LIGANDS TARGETING Aß OLIGOMERS AS TREATMENT FOR ALZHEIMER'S DISEASE<br/>[FR] LIGANDS MULTIFONCTIONNELS BIVALENTS CIBLANT DES OLIGOMÈRES A? COMME TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：UNIV VIRGINIA COMMONWEALTH

  公开号：WO2012012257A2

  公开（公告）日：2012-01-26

  Bivalent multifunctional Αβ 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 Αβ plaques in brain tissue. The BMAOIs comprise i) an Αβ 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) and ii) together.