5-(3-oxopiperazin-1-yl)pentanoic acid [5-(4-methoxyphenyl)-2H-pyrazol-3-yl]amide | 1374979-05-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 5-(3-oxopiperazin-1-yl)pentanoic acid [5-(4-methoxyphenyl)-2H-pyrazol-3-yl]amide
• 英文别名: N-[5-(4-methoxyphenyl)-1H-pyrazol-3-yl]-5-(3-oxopiperazin-1-yl)pentanamide
• CAS: 1374979-05-1
• 化学式: C₁₉H₂₅N₅O₃
• 分子量: 371.439
• InChiKey: XJQFQLWVHXSRMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  99.4
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-溴戊酰氯 在 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.5h， 生成 5-(3-oxopiperazin-1-yl)pentanoic acid [5-(4-methoxyphenyl)-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

• 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).