ethyl(1-azabicyclo[2.2.2]octan-3-ylidene)cyanoacetate | 141593-49-9

• 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-ylidene)cyanoacetate
• 英文别名: Ethyl (1-azabicyclo[2.2.2]octan-3-ylidene)cyanoacetate；ethyl 2-(1-azabicyclo[2.2.2]octan-3-ylidene)-2-cyanoacetate
• CAS: 141593-49-9
• 化学式: C₁₂H₁₆N₂O₂
• 分子量: 220.271
• InChiKey: WRCZZMYKSMOYBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 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-ylidene)cyanoacetate 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 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
• 作为产物：
  描述：

  3-奎宁环酮盐酸盐 、 氰乙酸乙酯 在 三乙胺 作用下， 反应 2.0h， 生成 ethyl(1-azabicyclo[2.2.2]octan-3-ylidene)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 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.

  这项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。
• Central Cholinergic Agents. III. Synthesis of 2-Alkoxy-2,8-diazaspiro(4.5)decane-1,3-diones as Muscarinic Agonists.
  作者：Yuji ISHIHARA、Hidehumi YUKIMASA、Masaomi MIYAMOTO、Giichi GOTO

  DOI：10.1248/cpb.40.1177

  日期：——

  and tested for muscarinic receptor binding affinity using [3H]pirenzepine and [3H]oxotremorine M as ligands. They were also evaluated for agonistic activities in the guinea pig ileum assay. 2-Methoxy- 2,8-diazaspiro[4.5]decane-1,3-dione (1i) was found to be a relatively M1 selective agonist. It reversed CO2-induced impairment of passive avoidance response with long duration of action, but also displayed

  合成了一系列的2-烷氧基-2,8-二氮杂螺[4.5]癸烷-1,3-二酮和相关化合物，并以[3H]哌仑西平和[3H]氧代苯甲酸M作为配体测试了毒蕈碱受体的结合亲和力。还通过豚鼠回肠试验评估了它们的激动活性。发现2-甲氧基-2,8-二氮杂螺[4.5]癸烷-1,3-二酮（1i）是相对M1选择性的激动剂。它以较长的作用时间逆转了CO2引起的被动回避反应的损害，但在低剂量时也表现出外周效应。为了最小化这些副作用，我们提出了将1i与毒蕈碱拮抗剂结合的想法。因此，检查了1i的氨基甲酸酯连接的共轭物（1u）与甲基阿托品。
• Heterocyclic compounds and their preparation and use
  申请人：Novo Nordisk A.S

  公开号：US05641791A1

  公开（公告）日：1997-06-24

  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氮化合物、其制备方法以及包含该化合物的制药组合物。这些新型化合物可用作哺乳动物前脑和海马的认知功能的刺激剂，特别适用于治疗阿尔茨海默病、严重疼痛症和青光眼。
• 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。
• 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.

  本发明涉及有治疗活性的吡啶化合物，其制备方法以及包含这些化合物的制药组合物。这些新型化合物可用作哺乳动物的前脑和海马的认知功能的刺激剂，特别是用于治疗阿尔茨海默病、严重疼痛和青光眼。