((R)-hexahydro-1H-pyrrolo[1,2-a][1,4]diazepin-2(3H)-yl)(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanone trifluoroacetate | 1378379-27-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: ((R)-hexahydro-1H-pyrrolo[1,2-a][1,4]diazepin-2(3H)-yl)(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanone trifluoroacetate
• CAS: 1378379-27-1
• 化学式: C₂HF₃O₂*C₁₇H₂₂N₂O₃
• 分子量: 416.397
• InChiKey: ATVLGAMZACSZBW-PFEQFJNWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  29.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  79.31
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  2,3-二氢-1,4-苯并二噁烷-6-羧酸 、 (R)-octahydro-1H-pyrrolo[1,2-a][1,4]diazepine 、 三氟乙酸 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 14.0h， 以37%的产率得到((R)-hexahydro-1H-pyrrolo[1,2-a][1,4]diazepin-2(3H)-yl)(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanone trifluoroacetate
  参考文献：
  名称：

  Synthesis and Nicotinic Receptor Activity of Chemical Space Analogues of N-(3R)-1-Azabicyclo[2.2.2]oct-3-yl-4-chlorobenzamide (PNU-282,987) and 1,4-Diazabicyclo[3.2.2]nonane-4-carboxylic Acid 4-Bromophenyl Ester (SSR180711)

  摘要：

  The Chemical Universe Generated Databases up to 11 atoms of CNOF (GDB-11) and up to 13 atoms of CNOClS (GDB-13) were used to enumerate analogues of the diamine part of two known alpha 7 nicotinic receptor agonists and construct libraries of virtual analogues of these drugs. The libraries were scored using structure-based (docking to the nicotine binding site of the acetylcholine binding protein 1uw6.pdb) or ligand-based (similarity to the parent drugs) methods, and the top-scoring virtual ligands were inspected for easily accessible synthetic targets. In total, 21 diamines were prepared and acylated with aromatic carboxylic or oxycarbonic acids to produce 85 analogues of the parent drugs. The compounds were profiled by electrophysiology in Xenopus oocytes expressing human nicotinic acetylcholine receptor (nAChR) subtypes alpha 7, alpha 3 beta 2, alpha 4 beta 2, alpha 3 beta 4, or alpha 4 beta 4. Characterization of selected compounds revealed eight inhibitors of the alpha 7 nicotinic receptor and three positive allosteric modulators of the alpha 3 beta 2 nAChR.

  DOI：

  10.1021/jm300030r