2-[4-[[6-[2-(6-Chloro-1,2,3,4-tetrahydroacridin-9-yl)hydrazinyl]-6-oxohexyl]carbamoyl]phenoxy]ethyl-triethylazanium;bromide;hydrochloride | 959682-27-0

• 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: 2-[4-[[6-[2-(6-Chloro-1,2,3,4-tetrahydroacridin-9-yl)hydrazinyl]-6-oxohexyl]carbamoyl]phenoxy]ethyl-triethylazanium;bromide;hydrochloride
• CAS: 959682-27-0
• 化学式: Br*C₃₄H₄₇ClN₅O₃*ClH
• 分子量: 725.597
• InChiKey: MVJUVLGKCKECMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.88
• 重原子数：
  45
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  92.4
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N,N,N-triethyl-2-(4-(((6-hydrazino-6-oxohexyl)amino)carbonyl)phenoxy)ethanammonium bromide 、 6,9-二氯-1,2,3,4-四氢吖啶 以 乙醇 为溶剂， 反应 24.0h， 以94%的产率得到2-[4-[[6-[2-(6-Chloro-1,2,3,4-tetrahydroacridin-9-yl)hydrazinyl]-6-oxohexyl]carbamoyl]phenoxy]ethyl-triethylazanium;bromide;hydrochloride
  参考文献：
  名称：

  First Gallamine−Tacrine Hybrid:  Design and Characterization at Cholinesterases and the M₂ Muscarinic Receptor

  摘要：

  Gallamine and tacrine are allosteric antagonists at muscarinic M-2 acetylcholine receptors and inhibitors of acetylcholinesterase. At both acetylcholine-binding proteins, gallamine and tacrine are known to occupy two different binding sites: in M-2 receptors within the allosteric binding area and in acetylcholinesterase at its catalytic and its peripheral site. To find new ligands of both targets, we designed a gallamine-tacrine dimer and several derived hybrid compounds to address the two binding sites. Their M-2 receptor allosteric and acetylcholinesterase inhibitory potential was determined. The hybrid compounds revealed an allosteric potency in the low nanomolar range exceeding the allosteric potency of gallamine and tacrine by factors of 100 and 4800, respectively. Cholinesterase inhibition was augmented by hybrid formation, and all compounds exhibited IC50 values in the lower nanomolar range. Thus, gallamine-tacrine hybrid formation is a valuable approach toward high affinity ligands concurrently targeting these acetylcholine-binding proteins.

  DOI：

  10.1021/jm070859s

文献信息

• First Gallamine−Tacrine Hybrid:  Design and Characterization at Cholinesterases and the M₂ Muscarinic Receptor
  作者：Paul W. Elsinghorst、Julia S. Cieslik、Klaus Mohr、Christian Tränkle、Michael Gütschow

  DOI：10.1021/jm070859s

  日期：2007.11.1

  Gallamine and tacrine are allosteric antagonists at muscarinic M-2 acetylcholine receptors and inhibitors of acetylcholinesterase. At both acetylcholine-binding proteins, gallamine and tacrine are known to occupy two different binding sites: in M-2 receptors within the allosteric binding area and in acetylcholinesterase at its catalytic and its peripheral site. To find new ligands of both targets, we designed a gallamine-tacrine dimer and several derived hybrid compounds to address the two binding sites. Their M-2 receptor allosteric and acetylcholinesterase inhibitory potential was determined. The hybrid compounds revealed an allosteric potency in the low nanomolar range exceeding the allosteric potency of gallamine and tacrine by factors of 100 and 4800, respectively. Cholinesterase inhibition was augmented by hybrid formation, and all compounds exhibited IC50 values in the lower nanomolar range. Thus, gallamine-tacrine hybrid formation is a valuable approach toward high affinity ligands concurrently targeting these acetylcholine-binding proteins.