5-(4-acetyl[1,4]diazepan-1-yl)pentanoic acid [5-(4-methoxyphenyl)-1H-imidazol-2-yl]amide | 1374979-18-6

• 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)pentanoic acid [5-(4-methoxyphenyl)-1H-imidazol-2-yl]amide
• 英文别名: 5-(4-acetyl-1,4-diazepan-1-yl)-N-[5-(4-methoxyphenyl)-1H-imidazol-2-yl]pentanamide
• CAS: 1374979-18-6
• 化学式: C₂₂H₃₁N₅O₃
• 分子量: 413.52
• InChiKey: JJJIVUQWUUXQLP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  1-乙酰基-1H-1,4-二氮杂庚烷 在 N,N'-羰基二咪唑 、 sodium hydroxide 作用下， 以 水 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 38.0h， 生成 5-(4-acetyl[1,4]diazepan-1-yl)pentanoic acid [5-(4-methoxyphenyl)-1H-imidazol-2-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