N-(4-(benzo[d]thiazol-2-ylmethyl)phenyl)-6-(1,2,3,4-tetrahydroacridin-9-ylamino)hexanamide | 1446670-65-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-(4-(benzo[d]thiazol-2-ylmethyl)phenyl)-6-(1,2,3,4-tetrahydroacridin-9-ylamino)hexanamide
• 英文别名: N-[4-(1,3-benzothiazol-2-ylmethyl)phenyl]-6-(1,2,3,4-tetrahydroacridin-9-ylamino)hexanamide
• CAS: 1446670-65-0
• 化学式: C₃₃H₃₄N₄OS
• 分子量: 534.725
• InChiKey: RIIDMJYSEKXRHA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  95.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  9-氯-1,2,3,4-四氢吖啶 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 potassium iodide 、 苯酚 作用下， 以 二氯甲烷 为溶剂， 反应 28.0h， 生成 N-(4-(benzo[d]thiazol-2-ylmethyl)phenyl)-6-(1,2,3,4-tetrahydroacridin-9-ylamino)hexanamide
  参考文献：
  名称：

  Design, synthesis and neuroprotective evaluation of novel tacrine–benzothiazole hybrids as multi-targeted compounds against Alzheimer’s disease

  摘要：

  Alzheimer's disease (AD) is a multifactorial disorder with several target proteins contributing to its etiology. In search for multifunctional anti-AD drug candidates, taking into account that the acetylcholinesterase (AChE) and beta-amyloid (A beta) aggregation are particularly important targets for inhibition, the tacrine and benzothiazole (BTA) moieties were conjugated with suitable linkers in a novel series of hybrids. The designed compounds (7a-7e) were synthesized and in vitro as well as in ex vivo evaluated for their capacity for the inhibition of acetylcholinesterase (AChE) and A beta self-induced aggregation, and also for the protection of neuronal cells death (SHSY-5Y cells, AD and MCI cybrids). All the tacrine-BTA hybrids displayed high in vitro activities, namely with IC50 values in the low micromolar to sub-micromolar concentration range towards the inhibition of AChE, and high percentages of inhibition of the self-induced A beta aggregation. Among them, compound 7a, with the shortest linker, presented the best inhibitory activity of AChE (IC50 = 0.34 mu M), while the highest activity as anti-A beta(42) self-aggregation, was evidenced for compound 7b (61.3%, at 50 mu M. The docking studies demonstrated that all compounds are able to interact with both catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. Our results show that compounds 7d and 7e improved cell viability in cells treated with A beta(42) peptide. Overall, these multi-targeted hybrid compounds appear as promising lead compounds for the treatment of Alzheimer's disease. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.028

文献信息

• Design, synthesis and neuroprotective evaluation of novel tacrine–benzothiazole hybrids as multi-targeted compounds against Alzheimer’s disease
  作者：Rangappa S. Keri、Catarina Quintanova、Sérgio M. Marques、A. Raquel Esteves、Sandra M. Cardoso、M. Amélia Santos

  DOI：10.1016/j.bmc.2013.05.028

  日期：2013.8

  Alzheimer's disease (AD) is a multifactorial disorder with several target proteins contributing to its etiology. In search for multifunctional anti-AD drug candidates, taking into account that the acetylcholinesterase (AChE) and beta-amyloid (A beta) aggregation are particularly important targets for inhibition, the tacrine and benzothiazole (BTA) moieties were conjugated with suitable linkers in a novel series of hybrids. The designed compounds (7a-7e) were synthesized and in vitro as well as in ex vivo evaluated for their capacity for the inhibition of acetylcholinesterase (AChE) and A beta self-induced aggregation, and also for the protection of neuronal cells death (SHSY-5Y cells, AD and MCI cybrids). All the tacrine-BTA hybrids displayed high in vitro activities, namely with IC50 values in the low micromolar to sub-micromolar concentration range towards the inhibition of AChE, and high percentages of inhibition of the self-induced A beta aggregation. Among them, compound 7a, with the shortest linker, presented the best inhibitory activity of AChE (IC50 = 0.34 mu M), while the highest activity as anti-A beta(42) self-aggregation, was evidenced for compound 7b (61.3%, at 50 mu M. The docking studies demonstrated that all compounds are able to interact with both catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. Our results show that compounds 7d and 7e improved cell viability in cells treated with A beta(42) peptide. Overall, these multi-targeted hybrid compounds appear as promising lead compounds for the treatment of Alzheimer's disease. (C) 2013 Elsevier Ltd. All rights reserved.