5-(4-acetyl[1,4]diazepan-1-yl)-2-methylpentanoic acid [5-(4-methoxyphenyl)-2H-pyrazol-3-yl]amide | 1040718-72-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(4-acetyl[1,4]diazepan-1-yl)-2-methylpentanoic acid [5-(4-methoxyphenyl)-2H-pyrazol-3-yl]amide
• 英文别名: 5-(4-Acetyl-[1,4]diazepan-1-yl)-2-methyl-pentanoic acid [5-(4-methoxy-phenyl)-2H-pyrazol-3-yl]-amide；5-(4-acetyl-1,4-diazepan-1-yl)-N-[5-(4-methoxyphenyl)-1H-pyrazol-3-yl]-2-methylpentanamide
• CAS: 1040718-72-6
• 化学式: C₂₃H₃₃N₅O₃
• 分子量: 427.547
• InChiKey: KELGFUJORMNBDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  90.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-bromo-2-methylpentanoic acid 在 盐酸 、 草酰氯 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 92.0h， 生成 5-(4-acetyl[1,4]diazepan-1-yl)-2-methylpentanoic 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

• 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。
• Modulators of α7 nicotinic acetylcholine receptors and therapeutic uses thereof
  申请人：Wyeth

  公开号：US08163729B2

  公开（公告）日：2012-04-24

  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、制备方法和使用它们调节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。
• WO2008/87529
  申请人：——

  公开号：——

  公开（公告）日：——
• US8163729B2
  申请人：——

  公开号：US8163729B2

  公开（公告）日：2012-04-24