(2R)-N-(6-(1H-imidazol-1-yl)-4-pyrimidinyl)-4'H-spiro[4-azabicyclo[2.2.2]octane-2,5'-[1,3]oxazol]-2'-amine 4-oxide | 1346215-60-8

• 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: (2R)-N-(6-(1H-imidazol-1-yl)-4-pyrimidinyl)-4'H-spiro[4-azabicyclo[2.2.2]octane-2,5'-[1,3]oxazol]-2'-amine 4-oxide
• 英文别名: (3S)-N-(6-imidazol-1-ylpyrimidin-4-yl)-1-oxidospiro[1-azoniabicyclo[2.2.2]octane-3,5'-4H-1,3-oxazole]-2'-amine
• CAS: 1346215-60-8
• 化学式: C₁₆H₁₉N₇O₂
• 分子量: 341.373
• InChiKey: NOQNGSRYXXBJGH-YPTUBRHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  95.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 盐酸 、 caesium carbonate 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 反应 0.78h， 生成 (2R)-N-(6-(1H-imidazol-1-yl)-4-pyrimidinyl)-4'H-spiro[4-azabicyclo[2.2.2]octane-2,5'-[1,3]oxazol]-2'-amine 4-oxide
  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] AZA-BICYCLIC AMINE N-OXIDE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGAND PRO-DRUGS<br/>[FR] COMPOSÉS N-OXYDE D'AMINE AZA-BICYLIQUE EN TANT QUE PROMÉDICAMENTS DE LIGANDS DE RÉCEPTEURS NICOTINIQUES D'ACÉTYLCHOLINE ALPHA-7
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2011137313A1

  公开（公告）日：2011-11-03

  The disclosure generally relates to compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are prodrugs for ligands, agonists, and partial agonists 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.

  该披露通常涉及到公式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。这些化合物是尼古丁α7受体的配体、激动剂和部分激动剂的前体药物，可能对中枢神经系统的各种障碍，特别是情感和神经退行性障碍的治疗有用。
• Aza-Bicyclic Amine N-Oxide Compounds as Alpha-7 Nicotinic Acetylcholine Receptor Ligand Pro-Drugs
  申请人：Lentz Kimberley A.

  公开号：US20120108596A1

  公开（公告）日：2012-05-03

  The disclosure generally relates to compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are prodrugs for ligands, agonists, and partial agonists 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.

  本公开涉及式I的化合物，包括其盐，以及使用该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、激动剂和部分激动剂的前药，可用于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。
• Aza-bicyclic amine N-oxide compounds as alpha-7 nicotinic acetylcholine receptor ligand pro-drugs
  申请人：Lentz Kimberley A.

  公开号：US08481555B2

  公开（公告）日：2013-07-09

  The disclosure generally relates to compounds of the following formula, including their salts, as well as compositions and methods of using the compounds. The compounds are prodrugs for ligands, agonists, and partial agonists 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.

  本公开涉及以下式子的化合物，包括它们的盐，以及使用这些化合物的组合物和方法。这些化合物是尼古丁α7受体的配体、激动剂和部分激动剂的前药，可能对中枢神经系统的各种障碍，特别是情感和神经退行性障碍的治疗有用。
• AZA-BICYCLIC AMINE N-OXIDE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGAND PRO-DRUGS
  申请人：Bristol-Myers Squibb Company

  公开号：EP2563796B1

  公开（公告）日：2015-03-18
• US8481555B2
  申请人：——

  公开号：US8481555B2

  公开（公告）日：2013-07-09