3-[(5R,6R)-1-azabicyclo[3.2.1]octan-6-yl]-4-butylsulfonyl-1,2,5-thiadiazole | 162183-57-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环庚烷
• 英文名称: 3-[(5R,6R)-1-azabicyclo[3.2.1]octan-6-yl]-4-butylsulfonyl-1,2,5-thiadiazole
• CAS: 162183-57-5
• 化学式: C₁₃H₂₁N₃O₂S₂
• 分子量: 315.461
• InChiKey: LQGUSKJCEFYQRO-QWRGUYRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  99.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-[(5R,6R)-1-azabicyclo[3.2.1]octan-6-yl]-4-butylsulfonyl-1,2,5-thiadiazole 在 sodium sulfide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成
  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：

  ethyl (1-azabicyclo[3.2.1]octan-6-yl)cyanoacetate 在 palladium on activated charcoal 盐酸 、 二氯化二硫 、 Oxone 、 sodium hydrogensulfide 、 氢气 、 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 ℃ 、137.9 kPa 条件下， 反应 6.0h， 生成 3-[(5R,6R)-1-azabicyclo[3.2.1]octan-6-yl]-4-butylsulfonyl-1,2,5-thiadiazole
  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

• Muscarinic Analgesics with Potent and Selective Effects on the Gastrointestinal Tract:  Potential Application for the Treatment of Irritable Bowel Syndrome
  作者：Charles H. Mitch、Thomas J. Brown、Frank P. Bymaster、David O. Calligaro、Donna Dieckman、Leander Merrit、Steven C. Peters、Steven J. Quimby、Harlan E. Shannon、Lisa A. Shipley、John S. Ward、Kristian Hansen、Preben H. Olesen、Per Sauerberg、Malcolm J. Sheardown、Michael D. B. Swedberg、Peter Suzdak、Beverley Greenwood

  DOI：10.1021/jm9602470

  日期：1997.2.1

  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.