5-piperidin-1-yl-pentanoic acid (5-pyridin-4-yl-2H-pyrazol-3-yl)amide | 1040718-99-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 5-piperidin-1-yl-pentanoic acid (5-pyridin-4-yl-2H-pyrazol-3-yl)amide
• 英文别名: 5-piperidin-1-yl-N-(5-pyridin-4-yl-1H-pyrazol-3-yl)pentanamide
• CAS: 1040718-99-7
• 化学式: C₁₈H₂₅N₅O
• 分子量: 327.429
• InChiKey: DWJPLBZSCNLIAR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  73.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  异烟酸甲酯 在 正丁基锂 、 一水合肼 、 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 乙醇 、 正己烷 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 21.16h， 生成 5-piperidin-1-yl-pentanoic acid (5-pyridin-4-yl-2H-pyrazol-3-yl)amide
  参考文献：
  名称：

  Discovery of a Novel Alpha-7 Nicotinic Acetylcholine Receptor Agonist Series and Characterization of the Potent, Selective, and Orally Efficacious Agonist 5-(4-Acetyl[1,4]diazepan-1-yl)pentanoic Acid [5-(4-Methoxyphenyl)-1H-pyrazol-3-yl] Amide (SEN15924, WAY-361789)

  摘要：

  Alpha-7 nicotinic acetylcholine receptors (alpha 7 nAChR) are implicated in the modulation of many cognitive functions such as attention, working memory, and episodic memory. For this reason, alpha 7 nAChR agonists represent promising therapeutic candidates for the treatment of cognitive impairment associated with Alzheimer's disease (AD) and schizophrenia. A medicinal chemistry effort, around our previously reported chemical series, permitted the discovery of a novel class of alpha 7 nAChR agonists with improved selectivity, in particular against the alpha 3 receptor subtype and better ADME profile. The exploration of this series led to the identification of 5-(4-acetyl[1,4]diazepan-1-yl)pentanoic acid [5-(4-methoxyphenyl)-1H-pyrazol-3-yl] amide (25, SEN15924, WAY-361789), a novel, full agonist of the alpha 7 nAChR that was evaluated in vitro and in vivo. Compound 25 proved to be potent and selective, and it demonstrated a fair pharmacokinetic profile accompanied by efficacy in rodent behavioral cognition models (novel object recognition and auditory sensory gating).

  DOI：

  10.1021/jm300247y

文献信息

• MODULATORS OF ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS AND THERAPEUTIC USES THEREOF
  申请人：Ghiron Chiara

  公开号：US20100029606A1

  公开（公告）日：2010-02-04

  The present invention provides compounds of formula (I) and compositions thereof, methods of making them, and methods of using them to modulate alpha7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can affect, among other things, neurological, psychiatric and/or inflammatory system.

  本发明提供了式(I)的化合物及其组合物，制备它们的方法，以及使用它们调节α7尼古丁乙酰胆碱受体和/或治疗各种疾病、疾病和病症的方法。提供的化合物可以影响神经、精神和/或炎症系统等方面。
• ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR INHIBITORS
  申请人：Bothmann Hendrick

  公开号：US20100130474A1

  公开（公告）日：2010-05-27

  The present invention provides compounds and compositions, methods of making them, and methods of using them to modulate α7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can affect, among other things, neurological, psychiatric and/or inflammatory systems.

  本发明提供了化合物和组合物，制备它们的方法以及使用它们调节α7尼古丁乙酰胆碱受体和/或治疗各种疾病、疾病和情况的方法。所提供的化合物可以影响神经系统、精神病和/或炎症系统等方面。
• US8163729B2
  申请人：——

  公开号：US8163729B2

  公开（公告）日：2012-04-24
• Discovery of a Novel Alpha-7 Nicotinic Acetylcholine Receptor Agonist Series and Characterization of the Potent, Selective, and Orally Efficacious Agonist 5-(4-Acetyl[1,4]diazepan-1-yl)pentanoic Acid [5-(4-Methoxyphenyl)-1H-pyrazol-3-yl] Amide (SEN15924, WAY-361789)
  作者：Riccardo Zanaletti、Laura Bettinetti、Cristiana Castaldo、Giuseppe Cocconcelli、Thomas Comery、John Dunlop、Giovanni Gaviraghi、Chiara Ghiron、Simon N. Haydar、Flora Jow、Laura Maccari、Iolanda Micco、Arianna Nencini、Carla Scali、Elisa Turlizzi、Michela Valacchi

  DOI：10.1021/jm300247y

  日期：2012.5.24

  Alpha-7 nicotinic acetylcholine receptors (alpha 7 nAChR) are implicated in the modulation of many cognitive functions such as attention, working memory, and episodic memory. For this reason, alpha 7 nAChR agonists represent promising therapeutic candidates for the treatment of cognitive impairment associated with Alzheimer's disease (AD) and schizophrenia. A medicinal chemistry effort, around our previously reported chemical series, permitted the discovery of a novel class of alpha 7 nAChR agonists with improved selectivity, in particular against the alpha 3 receptor subtype and better ADME profile. The exploration of this series led to the identification of 5-(4-acetyl[1,4]diazepan-1-yl)pentanoic acid [5-(4-methoxyphenyl)-1H-pyrazol-3-yl] amide (25, SEN15924, WAY-361789), a novel, full agonist of the alpha 7 nAChR that was evaluated in vitro and in vivo. Compound 25 proved to be potent and selective, and it demonstrated a fair pharmacokinetic profile accompanied by efficacy in rodent behavioral cognition models (novel object recognition and auditory sensory gating).