(R)-N-(6-phenylpyrimidin-4-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octan]-2-amine | 1192807-65-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (R)-N-(6-phenylpyrimidin-4-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octan]-2-amine
• 英文别名: (3R)-N-(6-phenylpyrimidin-4-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-4H-1,3-oxazole]-2'-amine
• CAS: 1192807-65-0
• 化学式: C₁₉H₂₁N₅O
• 分子量: 335.409
• InChiKey: WVNOFRZQUMORMI-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  62.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-Aminomethyl-3-hydroxyquinuclidine-borane 在 盐酸 、 二氧化碳 、 sodium carbonate 、 caesium carbonate 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 4.2h， 生成 (R)-N-(6-phenylpyrimidin-4-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octan]-2-amine
  参考文献：
  名称：

  BMS-933043, a Selective α7 nAChR Partial Agonist for the Treatment of Cognitive Deficits Associated with Schizophrenia

  摘要：

  The therapeutic treatment of negative symptoms and cognitive dysfunction associated with schizophrenia is a significant unmet medical need. Preclinical literature indicates that a? neuronal nicotinic acetylcholine (nACh) receptor agonists may provide an effective approach to treating cognitive dysfunction in schizophrenia. We report herein the discovery and evaluation of 1c (BMS-933043), a novel and potent alpha 7 nACh receptor partial agonist with high selectivity against other nicotinic acetylcholine receptor subtypes (>100-fold) and the 5-HT3A receptor (>300-fold). In vivo activity was demonstrated in a preclinical model of cognitive impairment, mouse novel object recognition. BMS-933043 has completed Phase I clinical trials.

  DOI：

  10.1021/acsmedchemlett.7b00032

文献信息

• [EN] QUINUCLIDINE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS<br/>[FR] COMPOSÉ DE QUINUCLIDINE COMME LIGANDS DU RÉCEPTEUR NICOTINIQUE ALPHA-7 DE L'ACÉTYLCHOLINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2011053292A1

  公开（公告）日：2011-05-05

  The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands for the nicotinic 7 receptor and may be useful for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.

  该披露提供了公式I的化合物，包括它们的盐，以及使用这些化合物的组合物和方法。这些化合物是烟碱7受体的配体，可能对治疗中枢神经系统的各种紊乱，特别是情感和神经退行性疾病有用。
• QUINUCLIDINE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS
  申请人：Cook, II James H.

  公开号：US20090270405A1

  公开（公告）日：2009-10-29

  The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands for the nicotinic α7 receptor and may be useful for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.

  该披露提供了公式I的化合物，包括它们的盐，以及使用这些化合物的组合物和方法。这些化合物是烟碱性α7受体的配体，可能对治疗中枢神经系统的各种疾病，特别是情感和神经退行性疾病，有用。
• Design and synthesis of a novel series of 4-heteroarylamino-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octanes as α7 nicotinic receptor agonists 2. Development of 4-heteroaryl SAR
  作者：Christiana Iwuagwu、Dalton King、Ivar M. McDonald、James Cook、F. Christopher Zusi、Matthew D. Hill、Robert A. Mate、Haiquan Fang、Ronald Knox、Lizbeth Gallagher、Debra Post-Munson Amy Easton、Regina Miller、Yulia Benitex、Judy Siuciak、Nicholas Lodge、Robert Zaczek、Daniel Morgan、Linda Bristow、John E. Macor、Richard E. Olson

  DOI：10.1016/j.bmcl.2017.01.058

  日期：2017.3

  potent partial agonists of the α7 receptor, selective against other nicotinic receptors and the serotinergic 5HT3A receptor. (1'S,3'R,4'S)-N-(6-phenylpyrimidin-4-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octan]-2-amine, a potent and selective α7 nAChR partial agonist, was demonstrated to improve cognition in the mouse novel object recognition (NOR) model of episodic memory.

  如该系列以前的报告所述，含奎尼丁的螺环恶唑啉已证明可作为α7烟碱乙酰胆碱受体（α7nAChR）部分激动剂使用。在这项工作中，该化学型的SAR被扩展为包括一系列的二嗪杂环取代。许多杂环类似物是α7受体的有效部分激动剂，对其他烟碱类受体和血清素5HT3A受体具有选择性。（1'S，3'R，4'S）-N-（6-苯基嘧啶-4-基）-4H-1'-氮杂螺[恶唑-5,3'-双环[2.2.2]正辛] -2-胺，a有效和选择性的α7nAChR部分激动剂，被证明可以改善情节记忆的小鼠新对象识别（NOR）模型中的认知。
• Quinuclidine Compounds as Alpha-7 Nicotinic Acetylcholine Receptor Ligands
  申请人：Cook, II James H.

  公开号：US20100099684A1

  公开（公告）日：2010-04-22

  The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands for the nicotinic α7 receptor and may be useful for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.

  本公开提供公式I的化合物，包括其盐，以及使用这些化合物的组合物和方法。这些化合物是尼古丁α7受体的配体，可能对中枢神经系统的各种疾病，特别是情感和神经退行性疾病的治疗有用。
• Quinuclidine compounds as alpha-7 nicotinic acetylcholine receptor ligands
  申请人：Bristol-Myers Squibb Company

  公开号：EP2271650B1

  公开（公告）日：2015-09-16