(5R)-1-azabicyclo[3.2.1]octane-6-one | 162184-58-9

• 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: (5R)-1-azabicyclo[3.2.1]octane-6-one
• 英文别名: (1S,5R)-1-Azabicyclo[3.2.1]octan-6-one；(5R)-1-azabicyclo[3.2.1]octan-6-one
• CAS: 162184-58-9
• 化学式: C₇H₁₁NO
• 分子量: 125.17
• InChiKey: WFYPDOYHAZFTIR-ZCFIWIBFSA-N

物化性质

• 沸点：
  204.9±23.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (5R)-1-azabicyclo[3.2.1]octane-6-one 在 palladium on activated charcoal TEA 、 氢气 、 sodium ethanolate 、 亚硝酸异戊酯 作用下， 以 甲醇 、 乙醇 为溶剂， 生成 (5R,6S)-1-Aza-bicyclo[3.2.1]oct-6-yl-[(Z)-hydroxyimino]-acetonitrile
  参考文献：
  名称：

  具有抗精神病样活性的毒蕈碱激动剂：1,2,5-噻二唑类似物与功能性多巴胺拮抗剂活性的结构-活性关系。

  摘要：

  在两种指示临床抗精神病活性的模型中测试了毒蕈碱激动剂：大鼠的条件回避反应（CAR）和小鼠中的阿扑吗啡诱导的爬升抑制。标准毒蕈碱激动剂oxotremorine和毛果芸香碱在这些测试中均很活跃，但在功效和胆碱能副作用之间几乎没有分离。显示了烷硫基1,2,5-噻二唑氮杂环型毒蕈碱部分激动剂的结构-活性关系，揭示了exo-6-（3-丙基/丁基硫代1,2,5-噻二唑-4-基）-1 -氮杂双环[3.2.1]辛烷类似物（4a，b和9a，b）是最有效的抗精神病药，在疗效和胆碱能副作用之间有较大的分隔。对映异构体选择性的缺乏表明药效团元素在化合物的镜平面中。提供了一个解释紧密相关化合物功效差异的模型。数据表明毒蕈碱激动剂起功能性多巴胺拮抗剂的作用，它们可能成为精神病患者的新型治疗方法。

  DOI：

  10.1021/jm981048e
• 作为产物：
  描述：

  1-氮杂双环[3.2.1]辛烷-6-酮 生成 (5R)-1-azabicyclo[3.2.1]octane-6-one
  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

• Design and Synthesis of a New Series of 4-Heteroarylamino-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octanes as α7 Nicotinic Receptor Agonists. 1. Development of Pharmacophore and Early Structure–Activity Relationship
  作者：James Cook、F. Christopher Zusi、Ivar M. McDonald、Dalton King、Matthew D. Hill、Christiana Iwuagwu、Robert A. Mate、Haiquan Fang、Rulin Zhao、Bei Wang、Jingfang Cutrone、Baoqing Ma、Qi Gao、Ronald J. Knox、Michele Matchett、Lizbeth Gallagher、Meredith Ferrante、Debra Post-Munson、Thaddeus Molski、Amy Easton、Regina Miller、Kelli Jones、Siva Digavalli、Francine Healy、Kimberley Lentz、Yulia Benitex、Wendy Clarke、Joanne Natale、Judith A. Siuciak、Nicholas Lodge、Robert Zaczek、Rex Denton、Daniel Morgan、Linda J. Bristow、John E. Macor、Richard E. Olson

  DOI：10.1021/acs.jmedchem.6b01506

  日期：2016.12.22

  The design and synthesis of a series of quinuclidine-containing spirooxazolidines (“spiroimidates”) and their utility as α7 nicotinic acetylcholine receptor partial agonists are described. Selected members of the series demonstrated excellent selectivity for α7 over the highly homologous 5-HT3A receptor. Modification of the N-spiroimidate heterocycle substituent led to (1S,2R,4S)-N-isoquinolin-3-y

  描述了一系列含喹核苷的螺杂恶唑烷（“螺酰胺化物”）的设计和合成及其作为α7烟碱型乙酰胆碱受体部分激动剂的用途。该系列的选定成员对α7的选择性优于高度同源的5-HT 3A受体。所述的修饰Ñ导致（1 -spiroimidate杂环取代基小号，2 - [R，4小号- ）ñ -异喹啉-3-基）-4' ħ -4-氮杂螺[二环[2.2.2]辛烷-2,5-'恶唑] -2'-胺（BMS-902483），一种有效的α7部分激动剂，可改善临床前啮齿动物模型的认知度。
• A METHOD OF TREATING GASTROINTESTINAL MOTILITY DISORDERS
  申请人：NOVO NORDISK A/S

  公开号：EP0735869A1

  公开（公告）日：1996-10-09
• A METHOD OF TREATING URINARY BLADDER DYSFUNCTIONS
  申请人：NOVO NORDISK A/S

  公开号：EP0790995A1

  公开（公告）日：1997-08-27
• US5612351A
  申请人：——

  公开号：US5612351A

  公开（公告）日：1997-03-18
• US6271229B1
  申请人：——

  公开号：US6271229B1

  公开（公告）日：2001-08-07