2-[5-[(4aS,6R,8aS)-4a,5,9,10-tetrahydro-6-hydroxy-3-methoxy-6H-benzofuro[3a,3,2-ef][2]benzazepin-11(12H)-yl]hexyl]-1,2-benzoisothiazol-3(2H)-one 1,1-dioxide | 365570-22-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 石蒜科生物碱
• 英文名称: 2-[5-[(4aS,6R,8aS)-4a,5,9,10-tetrahydro-6-hydroxy-3-methoxy-6H-benzofuro[3a,3,2-ef][2]benzazepin-11(12H)-yl]hexyl]-1,2-benzoisothiazol-3(2H)-one 1,1-dioxide
• 英文别名: 2-[6-[(4aS,6R,8aS)-4a,5,9,10-tetrahydro-6-hydroxy-3-methoxy-6H-benzofuro[3a,3,2-ef][2]benzazepin-11(12H)-yl]hexyl]-1,2-benzoisothiazol-3(2H)-one 1,1-dioxide；N-saccharinohexyl-galanthamine；2-{6-[(4aS,6R,8aS)-6-hydroxy-3-methoxy-5,6,9,10-tetrahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-11(12H)-yl]hexyl}-1,2-benzisothiazol-3(2H)-one 1,1-dioxide；2-[6-[(1S,12S,14R)-14-hydroxy-9-methoxy-11-oxa-4-azatetracyclo[8.6.1.01,12.06,17]heptadeca-6(17),7,9,15-tetraen-4-yl]hexyl]-1,1-dioxo-1,2-benzothiazol-3-one
• CAS: 365570-22-5
• 化学式: C₂₉H₃₄N₂O₆S
• 分子量: 538.665
• InChiKey: VAEMEXGGRSPJEF-LOMAHXHCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-[5-[(4aS,6R,8aS)-4a,5,9,10-tetrahydro-6-hydroxy-3-methoxy-6H-benzofuro[3a,3,2-ef][2]benzazepin-11(12H)-yl]hexyl]-1,2-benzoisothiazol-3(2H)-one 1,1-dioxide 、 富马酸 以 乙醇 为溶剂， 以76%的产率得到2-[5-[(4aS,6R,8aS)-4a,5,9,10-tetrahydro-6-hydroxy-3-methoxy-6H-benzofuro[3a,3,2-ef][2]benzazepin-11(12H)-yl]hexyl]-1,2-benzoisothiazol-3(2H)-one 1,1-dioxide monofumarate
  参考文献：
  名称：

  Probing Torpedo californica Acetylcholinesterase Catalytic Gorge with Two Novel Bis-functional Galanthamine Derivatives

  摘要：

  N-Piperidinopropyl-galanthamine (2) and N-saccharinohexyl-galanthamine (3) were used to investigate interaction sites along the active site gorge of Torpedo californica actyleholinesterase (TcAChE). The crystal structure of TcAChE-2 solved at 2.3 angstrom showed that the N-piperidinopropyl group in 2 is not stretched along the gorge but is folded over the galanthamine moiety. This result was unexpected because the three carbon alkyl chain is just long enough For the bulky piperidine group to be placed above the bottleneck (Tyr121, Phe330) midway down the gorge. The crystal structure of TcAChE-3 at 2.2 angstrom confirmed that it dual interaction with the sites at the bottom, and at the entrance of the gorge, enhances inhibitory activity: it chain of six carbon atoms has, in this class of derivatives, the correct length for optimal interactions with the peripheral anionic site (PAS).

  DOI：

  10.1021/jm901296p
• 作为产物：
  描述：

  2-(6-bromohexyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide 、 N-去甲基加兰它敏氢溴酸盐 在 N,N-二异丙基乙胺 作用下， 以 氯仿 为溶剂， 反应 24.0h， 以71.4%的产率得到2-[5-[(4aS,6R,8aS)-4a,5,9,10-tetrahydro-6-hydroxy-3-methoxy-6H-benzofuro[3a,3,2-ef][2]benzazepin-11(12H)-yl]hexyl]-1,2-benzoisothiazol-3(2H)-one 1,1-dioxide
  参考文献：
  名称：

  Probing Torpedo californica Acetylcholinesterase Catalytic Gorge with Two Novel Bis-functional Galanthamine Derivatives

  摘要：

  N-Piperidinopropyl-galanthamine (2) and N-saccharinohexyl-galanthamine (3) were used to investigate interaction sites along the active site gorge of Torpedo californica actyleholinesterase (TcAChE). The crystal structure of TcAChE-2 solved at 2.3 angstrom showed that the N-piperidinopropyl group in 2 is not stretched along the gorge but is folded over the galanthamine moiety. This result was unexpected because the three carbon alkyl chain is just long enough For the bulky piperidine group to be placed above the bottleneck (Tyr121, Phe330) midway down the gorge. The crystal structure of TcAChE-3 at 2.2 angstrom confirmed that it dual interaction with the sites at the bottom, and at the entrance of the gorge, enhances inhibitory activity: it chain of six carbon atoms has, in this class of derivatives, the correct length for optimal interactions with the peripheral anionic site (PAS).

  DOI：

  10.1021/jm901296p

文献信息

• US7166588B2
  申请人：——

  公开号：US7166588B2

  公开（公告）日：2007-01-23
• Probing <i>Torpedo californica</i> Acetylcholinesterase Catalytic Gorge with Two Novel Bis-functional Galanthamine Derivatives
  作者：Cecilia Bartolucci、Lars A. Haller、Ulrich Jordis、Gregor Fels、Doriano Lamba

  DOI：10.1021/jm901296p

  日期：2010.1.28

  N-Piperidinopropyl-galanthamine (2) and N-saccharinohexyl-galanthamine (3) were used to investigate interaction sites along the active site gorge of Torpedo californica actyleholinesterase (TcAChE). The crystal structure of TcAChE-2 solved at 2.3 angstrom showed that the N-piperidinopropyl group in 2 is not stretched along the gorge but is folded over the galanthamine moiety. This result was unexpected because the three carbon alkyl chain is just long enough For the bulky piperidine group to be placed above the bottleneck (Tyr121, Phe330) midway down the gorge. The crystal structure of TcAChE-3 at 2.2 angstrom confirmed that it dual interaction with the sites at the bottom, and at the entrance of the gorge, enhances inhibitory activity: it chain of six carbon atoms has, in this class of derivatives, the correct length for optimal interactions with the peripheral anionic site (PAS).