3-(2-methoxy-4-hydroxybenzylidene)anabaseine | 248270-40-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 3-(2-methoxy-4-hydroxybenzylidene)anabaseine
• 英文别名: 3-(4-hydroxy-2-methoxybenzylidene)anabaseine；GTS-21；3-methoxy-4-[(6-pyridin-3-yl-3,4-dihydro-2H-pyridin-5-ylidene)methyl]phenol
• CAS: 248270-40-8
• 化学式: C₁₈H₁₈N₂O₂
• 分子量: 294.353
• InChiKey: KXAAIPFSUGPVMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  54.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(2-methoxy-4-hydroxybenzylidene)anabaseine 、 乙酰溴-Alpha-D-葡萄糖酮酸甲基酯 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  A computational study of the binding of 3-(arylidene) anabaseines to two major brain nicotinic acetylcholine receptors and to the acetylcholine binding protein

  摘要：

  Nicotinic acetylcholine receptors (nAChRs) have become targets for drug development in recent years. 3-(2,4-dimethoxybenzylidene)-anabaseine (DMXBA), which selectively stimulates the alpha 7 nAChR, has been shown to alleviate some cognitive deficits associated with schizophrenia. In this paper we report an analysis of the interactions between 47 arylidene-anabaseines (including 45 benzylidene-anabaseines) and rat brain alpha 7 and alpha 4 beta 2 nicotinic acetylcholine receptors, using three different modeling techniques, namely 2D-QSAR, 3D-QSAR and molecular docking to the Aplysia californica acetylcholine binding protein (AChBP), a water soluble, homomeric nAChR surrogate receptor with a known crystal structure. Our investigation indicates the importance of; (1) the nitrogen atom of the tetrahydropyridyl (THP) ring for hydrogen bond formation; (2) pi-pi interactions between the aromatic rings of the ligands and the nAChBP binding site; (3) molecular surface recognition expressed in terms of steric complimentarity. On the basis of the 3D-QSAR results, bulky substituents at positions 2 (and due to the rotational freedom also at position 6) and 4 of the benzylidene moiety, with highly electronegative atoms projecting approximately 3-3.5 angstrom away from the benzylidene ring at position 4 seem optimal for enhancing binding affinity to the alpha 7 nAChR.

  DOI：

  10.1016/j.ejmech.2010.02.027

文献信息

• A computational study of the binding of 3-(arylidene) anabaseines to two major brain nicotinic acetylcholine receptors and to the acetylcholine binding protein
  作者：Svetoslav H. Slavov、Maksim Radzvilovits、Susan LeFrancois、Iva B. Stoyanova-Slavova、Ferenc Soti、William R. Kem、Alan R. Katritzky

  DOI：10.1016/j.ejmech.2010.02.027

  日期：2010.6

  Nicotinic acetylcholine receptors (nAChRs) have become targets for drug development in recent years. 3-(2,4-dimethoxybenzylidene)-anabaseine (DMXBA), which selectively stimulates the alpha 7 nAChR, has been shown to alleviate some cognitive deficits associated with schizophrenia. In this paper we report an analysis of the interactions between 47 arylidene-anabaseines (including 45 benzylidene-anabaseines) and rat brain alpha 7 and alpha 4 beta 2 nicotinic acetylcholine receptors, using three different modeling techniques, namely 2D-QSAR, 3D-QSAR and molecular docking to the Aplysia californica acetylcholine binding protein (AChBP), a water soluble, homomeric nAChR surrogate receptor with a known crystal structure. Our investigation indicates the importance of; (1) the nitrogen atom of the tetrahydropyridyl (THP) ring for hydrogen bond formation; (2) pi-pi interactions between the aromatic rings of the ligands and the nAChBP binding site; (3) molecular surface recognition expressed in terms of steric complimentarity. On the basis of the 3D-QSAR results, bulky substituents at positions 2 (and due to the rotational freedom also at position 6) and 4 of the benzylidene moiety, with highly electronegative atoms projecting approximately 3-3.5 angstrom away from the benzylidene ring at position 4 seem optimal for enhancing binding affinity to the alpha 7 nAChR.