methyl-7,7'-dimethoxy-5'-(4-(1,2,3,4-tetrahydroacridin-9-ylamino)butylcarbamoyl)-4,4'-bibenzo[d][1,3]dioxole-5-carboxylate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 单宁
• 英文名称: methyl-7,7'-dimethoxy-5'-(4-(1,2,3,4-tetrahydroacridin-9-ylamino)butylcarbamoyl)-4,4'-bibenzo[d][1,3]dioxole-5-carboxylate
• 英文别名: Methyl 7-methoxy-4-[7-methoxy-5-[4-(1,2,3,4-tetrahydroacridin-9-ylamino)butylcarbamoyl]-1,3-benzodioxol-4-yl]-1,3-benzodioxole-5-carboxylate；methyl 7-methoxy-4-[7-methoxy-5-[4-(1,2,3,4-tetrahydroacridin-9-ylamino)butylcarbamoyl]-1,3-benzodioxol-4-yl]-1,3-benzodioxole-5-carboxylate
• 化学式: C₃₆H₃₇N₃O₉
• 分子量: 655.704
• InChiKey: ZPXHUZUXFHUXKW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  48
• 可旋转键数：
  12
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  联苯双酯 在 氯化亚砜 、 水 、 乙酸酐 、 三乙胺 、 N,N-二甲基甲酰胺 、 potassium hydroxide 作用下， 以 1,4-二氧六环 、 氯仿 为溶剂， 反应 53.0h， 生成 methyl-7,7'-dimethoxy-5'-(4-(1,2,3,4-tetrahydroacridin-9-ylamino)butylcarbamoyl)-4,4'-bibenzo[d][1,3]dioxole-5-carboxylate
  参考文献：
  名称：

  Development of tacrine-bifendate conjugates with improved cholinesterase inhibitory and pro-cognitive efficacy and reduced hepatotoxicity

  摘要：

  A novel series of tacrine-bifendate (THA-DDB) conjugates (7a-e) were synthesized and evaluated as potential anti-Alzheimer's agents. These compounds showed potent cholinesterase and self-induced beta-amyloid (A beta) aggregation inhibitory activities. A Lineweaver-Burk plot and molecular modeling study showed that these compounds can target both catalytic active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase (AChE). The cytotoxicity of the conjugate 7d against PC12 and HepG2 cells and hepatotoxicity against human hepatocyte cell line (HL-7702) were found to be considerably less compared to THA. Moreover, treatment with 7d did not exhibit significant hepatotoxicity in mice. Finally, in vivo studies confirmed that 7d significantly ameliorates the cognitive performances of scopolamine treated ICR mice. Therefore, 7d has high potential for the treatment of Alzheimer's disease and warrants further investigation. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.12.005

文献信息

• 他克林-联苯双酯杂合物、其制备方法及应用
  申请人：河南大学

  公开号：CN105111195B

  公开（公告）日：2018-06-19

  他克林‑联苯双酯杂合物、其制备方法及应用，属于医药与化工领域，所述杂合物具有下述式（I）或式（II）的通式结构：其中，R1=H或Cl，R2=H或Cl；Y=CH2，NCH3，NH，羰基，乙二酰基，1,3‑丙二酰基，对环己烷基，或OCH2CH2O；m=0~4，n=0~4；且m、n均为整数，式（II）的‑CH2‑NH‑的碳端在苯环的3‑位或4‑位。由上述结构式（I）和（II）表示的化合物显示优越的乙酰胆碱酯酶抑制作用。因此本发明另一方面涉及它们以及以它们为活性成分的药物组合物，在治疗、改善或预防乙酰胆碱酯酶介导的相关疾病的药物的用途。
• Development of tacrine-bifendate conjugates with improved cholinesterase inhibitory and pro-cognitive efficacy and reduced hepatotoxicity
  作者：Juan Cen、Huiyan Guo、Chen Hong、Jianwu Lv、Yacheng Yang、Ting Wang、Dong Fang、Wen Luo、Chaojie Wang

  DOI：10.1016/j.ejmech.2017.12.005

  日期：2018.1

  A novel series of tacrine-bifendate (THA-DDB) conjugates (7a-e) were synthesized and evaluated as potential anti-Alzheimer's agents. These compounds showed potent cholinesterase and self-induced beta-amyloid (A beta) aggregation inhibitory activities. A Lineweaver-Burk plot and molecular modeling study showed that these compounds can target both catalytic active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase (AChE). The cytotoxicity of the conjugate 7d against PC12 and HepG2 cells and hepatotoxicity against human hepatocyte cell line (HL-7702) were found to be considerably less compared to THA. Moreover, treatment with 7d did not exhibit significant hepatotoxicity in mice. Finally, in vivo studies confirmed that 7d significantly ameliorates the cognitive performances of scopolamine treated ICR mice. Therefore, 7d has high potential for the treatment of Alzheimer's disease and warrants further investigation. (C) 2017 Elsevier Masson SAS. All rights reserved.