5-methyl-4-(2-(2-methyl-5-((8-((1,2,3,4-tetrahydroacridin-9-yl)amino)octyl)carbamoyl)thiophen-3-yl)cyclopent-1-en-1-yl)thiophene-2-carboxylic acid | 1581280-13-8

• 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: 5-methyl-4-(2-(2-methyl-5-((8-((1,2,3,4-tetrahydroacridin-9-yl)amino)octyl)carbamoyl)thiophen-3-yl)cyclopent-1-en-1-yl)thiophene-2-carboxylic acid
• CAS: 1581280-13-8
• 化学式: C₃₈H₄₅N₃O₃S₂
• 分子量: 655.926
• InChiKey: KUUMWNOJOUDWOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.83
• 重原子数：
  46.0
• 可旋转键数：
  14.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  91.32
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  5-methyl-4-(2-(2-methyl-5-((8-((1,2,3,4-tetrahydroacridin-9-yl)amino)octyl)carbamoyl)thiophen-3-yl)cyclopent-1-en-1-yl)thiophene-2-carboxylic acid 以 乙醇 为溶剂， 生成
  参考文献：
  名称：

  Acetylcholinesterase Inhibitors with Photoswitchable Inhibition of β-Amyloid Aggregation

  摘要：

  Photochromic cholinesterase inhibitors were obtained from cis-1,2-a-dithienylethene-based compounds by incorporating one or two aminopolymethylene tacrine groups. All target compounds are potent acetyl- (AChE) and butyrylcholinesterase (BChE) inhibitors in the nanomolar concentration range. Compound Jib bearing an octylene linker exhibited interactions with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Yet upon irradiation with light, the mechanism of interaction varied from one photochromic form to another, which was investigated by kinetic studies and proved "photoswitchable". The AChE-induced fl-amyloid (Afl) aggregation assay gave further experimental support to this finding: Afil aggregation catalyzed by the PAS of AChE might be inhibited by compound Jib in a concentration-dependent manner and seems to occur only with one photochromic form. Computational docking studies provided potential binding modes of the compound. Docking studies and molecular dynamics (MD) simulations for the ringopen and -closed form indicate a difference in binding. Although both forms can interact with the PAS, more stable interactions are observed for the ring-open form based upon stabilization of a water molecule network within the enzyme, whereas the ringclosed form lacks the required conformational flexibility for an analogous binding mode. The photoswitchable inhibitor identified might serve as valuable molecular tool to investigate the different biological properties of AChE as well as its role in pathogenesis of AD in in vitro assays.

  DOI：

  10.1021/cn500016p
• 作为产物：
  描述：

  1,5-bis(5-chloro-2-methylthien-3-yl)pentane-1,5-dione 在 正丁基锂 、 四氯化钛 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 锌 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 5-methyl-4-(2-(2-methyl-5-((8-((1,2,3,4-tetrahydroacridin-9-yl)amino)octyl)carbamoyl)thiophen-3-yl)cyclopent-1-en-1-yl)thiophene-2-carboxylic acid
  参考文献：
  名称：

  Acetylcholinesterase Inhibitors with Photoswitchable Inhibition of β-Amyloid Aggregation

  摘要：

  Photochromic cholinesterase inhibitors were obtained from cis-1,2-a-dithienylethene-based compounds by incorporating one or two aminopolymethylene tacrine groups. All target compounds are potent acetyl- (AChE) and butyrylcholinesterase (BChE) inhibitors in the nanomolar concentration range. Compound Jib bearing an octylene linker exhibited interactions with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Yet upon irradiation with light, the mechanism of interaction varied from one photochromic form to another, which was investigated by kinetic studies and proved "photoswitchable". The AChE-induced fl-amyloid (Afl) aggregation assay gave further experimental support to this finding: Afil aggregation catalyzed by the PAS of AChE might be inhibited by compound Jib in a concentration-dependent manner and seems to occur only with one photochromic form. Computational docking studies provided potential binding modes of the compound. Docking studies and molecular dynamics (MD) simulations for the ringopen and -closed form indicate a difference in binding. Although both forms can interact with the PAS, more stable interactions are observed for the ring-open form based upon stabilization of a water molecule network within the enzyme, whereas the ringclosed form lacks the required conformational flexibility for an analogous binding mode. The photoswitchable inhibitor identified might serve as valuable molecular tool to investigate the different biological properties of AChE as well as its role in pathogenesis of AD in in vitro assays.

  DOI：

  10.1021/cn500016p