(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-(8-(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)octanamido)ethoxy]ethoxy)ethoxy)acetate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (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-(8-(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)octanamido)ethoxy]ethoxy)ethoxy)acetate
• 英文别名: [(1S,2S,4S,5'R,6R,7S,8R,9S,12S,13R,16S)-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icos-18-ene-6,2'-oxane]-16-yl] 2-[2-[2-[2-[8-[4-[(2Z,4E)-3-hydroxy-5-(4-hydroxy-3-methoxyphenyl)-2-[(E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoyl]penta-2,4-dienyl]triazol-1-yl]octanoylamino]ethoxy]ethoxy]ethoxy]acetate
• 化学式: C₆₇H₉₂N₄O₁₄
• 分子量: 1177.49
• InChiKey: KKJKWKBSQDWQPI-QUASLUEMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.7
• 重原子数：
  85
• 可旋转键数：
  30
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  229
• 氢给体数：
  4
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  8-溴辛酸 在 4-二甲氨基吡啶 、 sodium azide 、 copper(II) sulfate 、 sodium ascorbate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 (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-(8-(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)octanamido)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

文献信息

• Bivalent ligands incorporating curcumin and diosgenin as multifunctional compounds against Alzheimer’s disease
  作者：Jeremy E. Chojnacki、Kai Liu、John M. Saathoff、Shijun Zhang

  DOI：10.1016/j.bmc.2015.10.032

  日期：2015.11

  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.