4-(5-methyl-6-nitrooxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane | 887470-23-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶唑并吡啶类
• 英文名称: 4-(5-methyl-6-nitrooxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane
• 英文别名: 4-(5-methyl-6-nitro-oxazolo[4,5-b]pyridin-2-yl)-1,4-diaza-bicyclo[3.2.2]nonane；2-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-5-methyl-6-nitro-[1,3]oxazolo[4,5-b]pyridine
• CAS: 887470-23-7
• 化学式: C₁₄H₁₇N₅O₃
• 分子量: 303.321
• InChiKey: LOSLOYVAKKGGPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  91.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(5-methyl-6-nitrooxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane 在 钯 氢气 作用下， 以 乙醇甲醇混合物 为溶剂， 反应 2.0h， 以to give 2-(1,4-Diaza-bicyclo[3.2.2]non-4-yl)-5-methyl-oxazolo[4,5-b]pyridin-6-ylamine的产率得到2-(1,4-diazabicyclo[3.2.2]non-4-yl)-5-methyloxazolo[4,5-b]pyridin-6-ylamine
  参考文献：
  名称：

  Azabenzoxazoles for the treatment of CNS disorders

  摘要：

  本发明涉及如下式所述的α7烟碱受体激动剂，以及通过向哺乳动物施用本文所示的α7烟碱受体激动剂来治疗中枢神经系统（CNS）疾病，如精神分裂症中的认知缺陷的方法。

  公开号：

  US20060166974A1
• 作为产物：
  描述：

  4-(5-Methyl-oxazolo[4,5-b]pyridin-2-yl)-1,4-diaza-bicyclo[3.2.2]nonane 在 硫酸 、 硝酸 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 16.0h， 以33%的产率得到4-(5-methyl-6-nitrooxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane
  参考文献：
  名称：

  WO2006/51407

  摘要：

  公开号：

文献信息

• Methods of modulating the activities of alpha-7 nicotinic acetylcholine receptor
  申请人：Hurst S. Raymond

  公开号：US20060142349A1

  公开（公告）日：2006-06-29

  The present invention provides methods for identifying compounds useful in modulating α7 nicotinic acetylcholine receptors. The invention also provides compounds that prevent, suppress or inhibit desensitization of an α7 nicotinic acetylcholine receptor, and which resensitize such receptors. Pharmaceutical compositions, and methods of treatment, particularly in regard of neurological diseases are also described.

  本发明提供了鉴定有助于调节α7烟碱乙酰胆碱受体的化合物的方法。本发明还提供了防止、抑制或抑制α7烟碱乙酰胆碱受体脱敏以及使这种受体重新敏化的化合物。本发明还描述了药物组合物和治疗方法，特别是治疗神经系统疾病的方法。
• Discovery of 4-(5-Methyloxazolo[4,5-<i>b</i>]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (CP-810,123), a Novel α7 Nicotinic Acetylcholine Receptor Agonist for the Treatment of Cognitive Disorders in Schizophrenia: Synthesis, SAR Development, and in Vivo Efficacy in Cognition Models
  作者：Christopher J. O’Donnell、Bruce N. Rogers、Brian S. Bronk、Dianne K. Bryce、Jotham W. Coe、Karen K. Cook、Allen J. Duplantier、Edelweiss Evrard、Mihaly Hajós、William E. Hoffmann、Raymond S. Hurst、Noha Maklad、Robert J. Mather、Stafford McLean、Frank M. Nedza、Brian T. O’Neill、Langu Peng、Weimin Qian、Melinda M. Rottas、Steven B. Sands、Anne W. Schmidt、Alka V. Shrikhande、Douglas K. Spracklin、Diane F. Wong、Andy Zhang、Lei Zhang

  DOI：10.1021/jm9015075

  日期：2010.2.11

  A novel alpha 7 nAChR agonist, 4-(5-methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (24, CP-810,123), has been identified as a potential treatment for cognitive deficits associated with psychiatric or neurological conditions including schizophrenia and Alzheimer's disease. Compound 24 is a potent and selective Compound with excellent pharmaceutical properties. In rodent, the compound displays high oral bioavailability and excellent brain penetration affording high levels of receptor occupancy and in vivo efficacy in auditory sensory gating and novel object recognition. The structural diversity of this compound and its preclinical in vitro and in vivo package support the hypothesis that alpha 7 nAChR agonists may have potential as a pharmacotherapy for the treatment of cognitive deficits in schizophrenia.
• AZABENZOXAZOLES FOR THE TREATMENT OF CNS DISORDERS
  申请人：Pfizer Products Incorporated

  公开号：EP1814887A1

  公开（公告）日：2007-08-08
• METHODS OF MODULATING THE ACTIVITIES OF ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR
  申请人：Pfizer Products Inc.

  公开号：EP1831683A1

  公开（公告）日：2007-09-12
• [EN] AZABENZOXAZOLES FOR THE TREATMENT OF CNS DISORDERS<br/>[FR] AZABENZOXAZOLES POUR LE TRAITEMENT DES TROUBLES DU SYSTEME NERVEUX CENTRAL
  申请人：PFIZER PROD INC

  公开号：WO2006051407A1

  公开（公告）日：2006-05-18

  [EN] The present invention relates to a7 nicotinic receptor agonists of formula I as described herein and to a method for treating disorders of the Central Nervous System (CNS) and other disorders in a mammal, including a human, by administering to the mammal an a7 nicotinic receptor agonist of formula I as shown herein. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier and a CNS-penetrant a7 nicotinic receptor agonist of formula I.
  [FR] Cette invention concerne des agonistes du récepteur a7-nicotinique représentés par la formule (I), tels que décrits dans les pièces descriptives de la demande, ainsi qu'un procédé pour traiter les troubles du système nerveux central et d'autres troubles chez un mammifère, notamment l'homme, en administrant à ce mammifère un agoniste du récepteur a7-nicotinique de formule (I). Cette invention concerne également des compositions pharmaceutiques contenant un véhicule pharmaceutiquement acceptable et un agoniste du récepteur a7-nicotinique de formule (I), pénétrant dans le système nerveux central .