3-hydroxy-2-methylene-1-azabicyclo<2.2.2>octane | 135757-79-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 英文名称: 3-hydroxy-2-methylene-1-azabicyclo<2.2.2>octane
• 英文别名: 3-hydroxy-2-methylene-1-azabicyclo[2.2.2]octane；2-Methylene-3-hydroxyquinuclidine；2-methylidene-1-azabicyclo[2.2.2]octan-3-ol
• CAS: 135757-79-8
• 化学式: C₈H₁₃NO
• 分子量: 139.197
• InChiKey: YMFATMJNFMYHIW-UHFFFAOYSA-N

物化性质

• 熔点：
  90-92 °C
• 沸点：
  259.8±19.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-hydroxy-2-methylene-1-azabicyclo<2.2.2>octane 在 N-甲基吗啉 、 氯化亚砜 、 氨 、 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 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 34.0h， 生成 N-((1-aza-bicyclo[2.2.2]oct-2-en-2-yl)methyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide
  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
• 作为产物：
  描述：

  2-亚甲基奎宁环-3-酮 在 potassium carbonate 、 sodium tetrahydroborate 作用下， 以 二氯甲烷 、 水 、 甲醇 为溶剂， 反应 72.5h， 以51%的产率得到3-hydroxy-2-methylene-1-azabicyclo<2.2.2>octane
  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

文献信息

• Kinetically-controlled displacement by azide on an allylic chloride: Synthesis of a highly potent serotonin-3 receptor ligand prototype
  作者：Terry Rosen、Karen J. Guarino

  DOI：10.1016/s0040-4020(01)80973-x

  日期：1991.7

  The discovery and selective synthesis of a novel and highly potent serotonin-3 receptor ligand, 4-amino-5-chloro-2-methoxy-N-(1-azabicyclo[2.2.2]-oct-2-enyl-2-methyl) benzamide (4) are described. The key step in the preparation of 4 involves an unusual example of a kinetically controlled displacement to provide a thermodynamically disfavored allylic azide isomer. This azide is a precursor to 2-aminomethyl-1-azabicylo[2.2.2]oct-2-ene (5), a convergent intermediate for the synthesis of analogs related to 4.
• ROSEN, TERRY;GUARINO, KAREN J., TETRAHEDRON, 47,(1991) N9, C. 5391-5400
  作者：ROSEN, TERRY、GUARINO, KAREN J.

  DOI：——

  日期：——
• Azabicyclo amides and esters as 5-HT3 receptor antagonists
  申请人：PFIZER INC.

  公开号：EP0434202B1

  公开（公告）日：1994-06-08
• COMPOSITIONS AND METHODS FOR THE TREATMENT OR PREVENTION OF DISORDERS RELATING TO OXIDATIVE STRESS
  申请人：Biswal Shyam

  公开号：US20110250300A1

  公开（公告）日：2011-10-13

  The present invention features methods for treating or preventing conditions, diseases, or disorders related to oxidative stress. In one embodiment, the method increases Nrf2 biological activity or expression. In particular, the invention provides for the treatment or prevention of diseases relating to oxidative stress including emphysema, sepsis, septic shock, ischemic injury, cerebral ischemia and neurodegenerative disorders, meningitis, encephalitis, hemorrhage, cerebral ischemia, heart ischemia, cognitive deficits and neurodegenerative disorders.
• COMPOSITIONS AND METHODS FOR TREATING OR PREVENTING RADIATION INJURY
  申请人：Biswal Shyam

  公开号：US20120029071A1

  公开（公告）日：2012-02-02

  The invention provides compositions and methods featuring Nrf2 activators for treating or preventing radiation-associated tissue damage.