ethyl (1-azabicyclo[2.2.2]octan-3-yl)cyanoacetate | 141593-50-2

• 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: ethyl (1-azabicyclo[2.2.2]octan-3-yl)cyanoacetate
• 英文别名: ethyl 2-(1-azabicyclo[2.2.2]octan-3-yl)-2-cyanoacetate
• CAS: 141593-50-2
• 化学式: C₁₂H₁₈N₂O₂
• 分子量: 222.287
• InChiKey: LZNORTUAWKRVHP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  53.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl (1-azabicyclo[2.2.2]octan-3-yl)cyanoacetate 在 5% Pd on active carbon 二氯化二硫 、 sodium hydrogensulfide 、 氢气 、 sodium methylate 、 sodium ethanolate 、 potassium carbonate 、 亚硝酸异戊酯 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 2.0h， 生成 4-(1-Aza-bicyclo[2.2.2]oct-3-yl)-[1,2,5]thiadiazole-3-thiol
  参考文献：
  名称：

  Muscarinic Analgesics with Potent and Selective Effects on the Gastrointestinal Tract:  Potential Application for the Treatment of Irritable Bowel Syndrome

  摘要：

  Irritable bowel syndrome (IBS) is a pathopysiolocal condition characterized by abnormal bowel habits that are frequently accompanied by abdominal pain. Current therapy based on reducing high-amplitude GI contractions with nonselective muscarinic antagonists is limited in efficacy due to typical muscarinic side effects and provides no pain relief. We have previously found potent antinociceptive agents acting through muscarinic receptors. In the present work, new 1,2,5-thiadiazole-based structures with muscarinic activity have been evaluated both for activity as analgesics in the mouse withing assay and for activity in normalizing spontaneous cluster contractions in ferret jejunum as a model of IBS in humans. (5R,6R)-exo-6-[4-[(4,4,4-Trifluorobutyl)thio]-1,2,5-thiadiazol-3-yl]-1-azabicyclo[3.2.1]octane (35, LY316108/NNC11-2192) was found to offer an exceptional profile combining analgesic potency in mouse writhing (ED(50) = 0.1 mg/kg) along with potency for normalization of GI motility (ED(50) = 0.17 mg/kg). This combination of GI and analgesic potency suggests 35 as an excellent candidate for evaluation as a potential treatment of IBS.

  DOI：

  10.1021/jm9602470
• 作为产物：
  描述：

  3-奎宁环酮盐酸盐 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 乙醇 为溶剂， 25.0~80.0 ℃ 、101.33 kPa 条件下， 反应 2.0h， 生成 ethyl (1-azabicyclo[2.2.2]octan-3-yl)cyanoacetate
  参考文献：
  名称：

  Muscarinic Analgesics with Potent and Selective Effects on the Gastrointestinal Tract:  Potential Application for the Treatment of Irritable Bowel Syndrome

  摘要：

  Irritable bowel syndrome (IBS) is a pathopysiolocal condition characterized by abnormal bowel habits that are frequently accompanied by abdominal pain. Current therapy based on reducing high-amplitude GI contractions with nonselective muscarinic antagonists is limited in efficacy due to typical muscarinic side effects and provides no pain relief. We have previously found potent antinociceptive agents acting through muscarinic receptors. In the present work, new 1,2,5-thiadiazole-based structures with muscarinic activity have been evaluated both for activity as analgesics in the mouse withing assay and for activity in normalizing spontaneous cluster contractions in ferret jejunum as a model of IBS in humans. (5R,6R)-exo-6-[4-[(4,4,4-Trifluorobutyl)thio]-1,2,5-thiadiazol-3-yl]-1-azabicyclo[3.2.1]octane (35, LY316108/NNC11-2192) was found to offer an exceptional profile combining analgesic potency in mouse writhing (ED(50) = 0.1 mg/kg) along with potency for normalization of GI motility (ED(50) = 0.17 mg/kg). This combination of GI and analgesic potency suggests 35 as an excellent candidate for evaluation as a potential treatment of IBS.

  DOI：

  10.1021/jm9602470

文献信息

• Method of treating gastrointestinal motility disorders
  申请人：Novo Nordisk A/S

  公开号：US06265419B1

  公开（公告）日：2001-07-24

  The present invention relates to a novel method for treating a mammal suffering from gastrointestinal motility disorders.

  这项发明涉及一种治疗患有胃肠动力障碍的哺乳动物的新方法。
• Certain 3-(1,2,5-oxa- or thiadiazol-4-yl)-1-azabicyclo [2.2.2]octanes
  申请人：Novo Nordisk A/S

  公开号：US05260314A1

  公开（公告）日：1993-11-09

  The present invention relates to therapeutically active piperidine compounds, a method of preparing the same and to pharmaceutical compositions comprising the compounds. The novel compounds are useful as stimulants of the cognitive function of the forebrain and hippocampus of mammals and especially in the treatment of Alzheimer's disease, severe painful conditions and glaucoma.

  本发明涉及治疗活性吡啶化合物，一种制备该化合物的方法以及包含该化合物的药物组合物。这些新颖的化合物可用作刺激哺乳动物前脑和海马的认知功能的兴奋剂，特别适用于治疗阿尔茨海默病、严重疼痛症状和青光眼。
• Heterocyclic compounds and their preparation and use
  申请人：Novo Nordisk A/S

  公开号：US05527813A1

  公开（公告）日：1996-06-18

  The present invention relates to therapeutically active azabicyclic compounds, a method of preparing the same and to pharmaceutical compositions comprising the compounds. The novel compounds are useful as stimulants of the cognitive function of the forebrain and hippocampus of mammals and especially in the treatment of Alzheimer's disease, severe painful conditions and glaucoma.

  本发明涉及治疗活性的杂环化合物，一种制备该化合物的方法以及包含该化合物的药物组合物。这些新颖的化合物可用作哺乳动物前脑和海马的认知功能刺激剂，特别适用于治疗阿尔茨海默病、严重疼痛症状和青光眼。
• Method of treating urinary bladder dysfunctions
  申请人：Novo Nordisk A/S

  公开号：US05612351A1

  公开（公告）日：1997-03-18

  The present invention relates to a novel method for treating a mammal suffering from urinary bladder dysfunctions.

  本发明涉及一种治疗患有尿道膀胱功能障碍的哺乳动物的新方法。
• Antipsychotic method
  申请人：——

  公开号：US05663182A1

  公开（公告）日：1997-09-02

  The present invention relates to a novel method for treating a mammal suffering from or susceptible to schizophrenia and schizophreniform diseases.

  本发明涉及一种治疗患有或易患精神分裂症和分裂样疾病哺乳动物的新方法。