Z-Gly-L-Gln-[N¹-methyl-N⁴-(5-(2-acetamide)-1,2,3,4-tetrahydroacridin-9-yl)-N¹-(3-(1,2,3,4-tetrahydroacridin-9-yl)propyl)butane-1,4-diamine]-L-Phe-OBn

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Z-Gly-L-Gln-[N¹-methyl-N⁴-(5-(2-acetamide)-1,2,3,4-tetrahydroacridin-9-yl)-N¹-(3-(1,2,3,4-tetrahydroacridin-9-yl)propyl)butane-1,4-diamine]-L-Phe-OBn
• 英文别名: benzyl (2S)-2-[[(2S)-5-[[2-[[9-[4-[methyl-[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]amino]butylamino]-5,6,7,8-tetrahydroacridin-4-yl]amino]-2-oxoethyl]amino]-5-oxo-2-[[2-(phenylmethoxycarbonylamino)acetyl]amino]pentanoyl]amino]-3-phenylpropanoate
• 化学式: C₆₇H₇₈N₁₀O₈
• 分子量: 1151.42
• InChiKey: IPFFEMHJNMAEKB-YQOHNZFASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.8
• 重原子数：
  85
• 可旋转键数：
  31
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  234
• 氢给体数：
  7
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  3-苯基-L-丙氨酸苄酯 在 甲酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 二乙胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 43.0h， 生成 Z-Gly-L-Gln-[N¹-methyl-N⁴-(5-(2-acetamide)-1,2,3,4-tetrahydroacridin-9-yl)-N¹-(3-(1,2,3,4-tetrahydroacridin-9-yl)propyl)butane-1,4-diamine]-L-Phe-OBn
  参考文献：
  名称：

  Multifunctional Cholinesterase and Amyloid Beta Fibrillization Modulators. Synthesis and Biological Investigation

  摘要：

  In order to identify novel Alzheimer's modifying pharmacological tools, we developed bis-tacrines bearing a peptide moiety for specific interference with surface sites of human acetylcholinesterase (hAChE) binding amyloid-beta (A beta). Accordingly, compounds 2a-c proved to be inhibitors of hAChE catalytic and noncatalytic functions, binding the catalytic and peripheral sites, interfering with A beta aggregation and with the A beta self-oligomerization process (2a). Compounds 2a-c in complex with TcAChE span the gorge with the bis-tacrine system, and the peptide moieties bulge outside the gorge in proximity of the peripheral site These moieties are likely responsible for the observed reduction of hAChE-induced A beta aggregation since they physically hamper A beta binding to the enzyme surface. Moreover, 2a was able to significantly interfere with A beta self-oligornerization, while 2b,c showed improved inhibition of hAChE-induced A beta aggregation.

  DOI：

  10.1021/ml4002908

文献信息

• Multifunctional Cholinesterase and Amyloid Beta Fibrillization Modulators. Synthesis and Biological Investigation
  作者：Stefania Butini、Margherita Brindisi、Simone Brogi、Samuele Maramai、Egeria Guarino、Alessandro Panico、Ashima Saxena、Ved Chauhan、Raffaella Colombo、Laura Verga、Ersilia De Lorenzi、Manuela Bartolini、Vincenza Andrisano、Ettore Novellino、Giuseppe Campiani、Sandra Gemma

  DOI：10.1021/ml4002908

  日期：2013.12.12

  In order to identify novel Alzheimer's modifying pharmacological tools, we developed bis-tacrines bearing a peptide moiety for specific interference with surface sites of human acetylcholinesterase (hAChE) binding amyloid-beta (A beta). Accordingly, compounds 2a-c proved to be inhibitors of hAChE catalytic and noncatalytic functions, binding the catalytic and peripheral sites, interfering with A beta aggregation and with the A beta self-oligomerization process (2a). Compounds 2a-c in complex with TcAChE span the gorge with the bis-tacrine system, and the peptide moieties bulge outside the gorge in proximity of the peripheral site These moieties are likely responsible for the observed reduction of hAChE-induced A beta aggregation since they physically hamper A beta binding to the enzyme surface. Moreover, 2a was able to significantly interfere with A beta self-oligornerization, while 2b,c showed improved inhibition of hAChE-induced A beta aggregation.