N-(3-(benzo[d][1,3]dioxol-5-yl)-4,5-dimethoxyphenethyl)acetamide | 1241833-91-9

• 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: N-(3-(benzo[d][1,3]dioxol-5-yl)-4,5-dimethoxyphenethyl)acetamide
• CAS: 1241833-91-9
• 化学式: C₁₉H₂₁NO₅
• 分子量: 343.379
• InChiKey: SWUYEBJKPKXOST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.78
• 重原子数：
  25.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  66.02
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-(3-(benzo[d][1,3]dioxol-5-yl)-4,5-dimethoxyphenethyl)acetamide 在 sodium tetrahydroborate 、 三乙酰氧基硼氢化钠 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 36.0h， 生成 8-(benzo[d][1,3]dioxol-5-yl)-6,7-dimethoxy-1,2-dimethyl-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Nantenine as an acetylcholinesterase inhibitor: SAR, enzyme kinetics and molecular modeling investigations

  摘要：

  Nantenine, as well as a number of flexible analogs, were evaluated for acetylcholinesterase (AChE) inhibitory activity in microplate spectrophotometric assays based on Ellman''s method. It was found that the rigid aporphine core of nantenine is an important structural requirement for its anticholinesterase activity. Nantenine showed mixed inhibition kinetics in enzyme assays. Molecular docking experiments suggest that nantenine binds preferentially to the catalytic site of AChE but is also capable of interacting with the peripheral anionic site (PAS) of the enzyme, thus accounting for its mixed inhibition profile. The aporphine core of nantenine may thus be a useful template for the design of novel PAS or dual-site AChE inhibitors. Inhibiting the PAS is desirable for prevention of aggregation of the amyloid peptide A beta beta, a major causative factor in the progression of Alzheimer''s disease (AD).

  DOI：

  10.3109/14756361003671078
• 作为产物：
  描述：

  3-溴-4,5-二甲氧基苯甲醛 在 锂硼氢 、 四(三苯基膦)钯 、 三甲基氯硅烷 、 ammonium acetate 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 28.25h， 生成 N-(3-(benzo[d][1,3]dioxol-5-yl)-4,5-dimethoxyphenethyl)acetamide
  参考文献：
  名称：

  Nantenine as an acetylcholinesterase inhibitor: SAR, enzyme kinetics and molecular modeling investigations

  摘要：

  Nantenine, as well as a number of flexible analogs, were evaluated for acetylcholinesterase (AChE) inhibitory activity in microplate spectrophotometric assays based on Ellman''s method. It was found that the rigid aporphine core of nantenine is an important structural requirement for its anticholinesterase activity. Nantenine showed mixed inhibition kinetics in enzyme assays. Molecular docking experiments suggest that nantenine binds preferentially to the catalytic site of AChE but is also capable of interacting with the peripheral anionic site (PAS) of the enzyme, thus accounting for its mixed inhibition profile. The aporphine core of nantenine may thus be a useful template for the design of novel PAS or dual-site AChE inhibitors. Inhibiting the PAS is desirable for prevention of aggregation of the amyloid peptide A beta beta, a major causative factor in the progression of Alzheimer''s disease (AD).

  DOI：

  10.3109/14756361003671078

文献信息

• Affinity of aporphines for the human 5-HT2A receptor: Insights from homology modeling and molecular docking studies
  作者：Stevan Pecic、Pooja Makkar、Sandeep Chaudhary、Boojala V. Reddy、Hernan A. Navarro、Wayne W. Harding

  DOI：10.1016/j.bmc.2010.06.043

  日期：2010.8

  Analogs of nantenine were docked into a modeled structure of the human 5-HT2A receptor using ICM Pro, GLIDE, and GOLD docking methods. The resultant docking scores were used to correlate with observed in vitro apparent affinity (K-e) data. The GOLD docking algorithm when used with a homology model of 5-HT2A, based on a bovine rhodopsin template and built by the program MODELLER, gives results which are most in agreement with the in vitro results. Further analysis of the docking poses among members of a C1 alkyl series of nantenine analogs, indicate that they bind to the receptor in a similar orientation, but differently than nantenine. Besides an important interaction between the protonated nitrogen of the C1 alkyl analogs and residue Asp155, we identified Ser242, Phe234, and Gly238 as key residues responsible for the affinity of these compounds for the 5-HT2A receptor. Specifically, the ability of some of these analogs to establish a H-bond with Ser242 and hydrophobic interactions with Phe234 and Gly238 appears to explain their enhanced affinity as compared to nantenine. Published by Elsevier Ltd.