环戊基(吩噻嗪-10-基)甲酮 | 828266-39-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 中文名称: 环戊基(吩噻嗪-10-基)甲酮
• 英文名称: N-(cyclopentylcarbonyl)phenothiazine
• 英文别名: Cyclopentyl(10H-phenothiazin-10-yl)methanone；cyclopentyl(phenothiazin-10-yl)methanone
• CAS: 828266-39-3
• 化学式: C₁₈H₁₇NOS
• 分子量: 295.405
• InChiKey: JPXLUBKKYWSLLR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  45.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  环戊基甲酰氯 、 吩噻嗪 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以65.5%的产率得到环戊基(吩噻嗪-10-基)甲酮
  参考文献：
  名称：

  Structure–activity relationships for inhibition of human cholinesterases by alkyl amide phenothiazine derivatives

  摘要：

  Several lines of evidence indicate that inhibition of butyrylcholinesterase (BuChE) is important in the treatment of certain dementias. Further testing of this concept requires inhibitors that are both BuChE-selective and robust.N-alkyl derivatives (2, 3, 4) of phenothiazine (1) have previously been found to inhibit only BuChE in a mechanism involving pi-pi interaction between the phenothiazine tricyclic ring system and aromatic residues in the active site gorge. To explore features of phenothiazines that affect the selectivity and potency of BuChE inhibition, a series of N-carbonyl derivatives (5-25) was synthesized and examined for the ability to inhibit cholinesterases.Some of the synthesized derivatives also inhibited AChE through a different mechanism involving carbonyl interaction within the active site gorge. Binding of these derivatives takes place within the gorge, since this inhibition disappears when the molecular volume of the derivative exceeds the estimated active site gorge volume of this enzyme. In contrast, BuChE, with a much larger active site gorge, exhibited inhibition that increased directly with the molecular volumes of the derivatives. This study describes two distinct mechanisms for binding phenothiazine amide derivatives to BuChE and AChE. Molecular volume was found to be an important parameter for BuChE-specific inhibition. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.09.059

文献信息

• Structure–activity relationships for inhibition of human cholinesterases by alkyl amide phenothiazine derivatives
  作者：Sultan Darvesh、Robert S. McDonald、Andrea Penwell、Sarah Conrad、Katherine V. Darvesh、Diane Mataija、Geraldine Gomez、Angela Caines、Ryan Walsh、Earl Martin

  DOI：10.1016/j.bmc.2004.09.059

  日期：2005.1

  Several lines of evidence indicate that inhibition of butyrylcholinesterase (BuChE) is important in the treatment of certain dementias. Further testing of this concept requires inhibitors that are both BuChE-selective and robust.N-alkyl derivatives (2, 3, 4) of phenothiazine (1) have previously been found to inhibit only BuChE in a mechanism involving pi-pi interaction between the phenothiazine tricyclic ring system and aromatic residues in the active site gorge. To explore features of phenothiazines that affect the selectivity and potency of BuChE inhibition, a series of N-carbonyl derivatives (5-25) was synthesized and examined for the ability to inhibit cholinesterases.Some of the synthesized derivatives also inhibited AChE through a different mechanism involving carbonyl interaction within the active site gorge. Binding of these derivatives takes place within the gorge, since this inhibition disappears when the molecular volume of the derivative exceeds the estimated active site gorge volume of this enzyme. In contrast, BuChE, with a much larger active site gorge, exhibited inhibition that increased directly with the molecular volumes of the derivatives. This study describes two distinct mechanisms for binding phenothiazine amide derivatives to BuChE and AChE. Molecular volume was found to be an important parameter for BuChE-specific inhibition. (C) 2004 Elsevier Ltd. All rights reserved.