3-(3-Methoxyphenyl)-1H-pyrazol-5-amine hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(3-Methoxyphenyl)-1H-pyrazol-5-amine hydrochloride
• 英文别名: 5-(3-methoxyphenyl)-1H-pyrazol-3-amine;hydrochloride
• 化学式: C₁₀H₁₁N₃O*(x)ClH
• 分子量: 225.67
• InChiKey: IXRIPOUUDUXBOP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.09
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  63.9
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(3-Methoxyphenyl)-1H-pyrazol-5-amine hydrochloride 在 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 1.0h， 生成 N-[5-(3-methoxyphenyl)-1H-pyrazol-3-yl]-4-piperidin-1-ylbutanamide
  参考文献：
  名称：

  N-[5-(5-Fluoropyridin-3-yl)-1H-pyrazol-3-yl]-4-piperidin-1-ylbutyramide (SEN78702, WYE-308775): A Medicinal Chemistry Effort toward an α7 Nicotinic Acetylcholine Receptor Agonist Preclinical Candidate

  摘要：

  alpha 7 nicotinic acetylcholine receptors (alpha 7 nAChR) represent promising therapeutic candidates for the treatment of cognitive impairment, associated with Alzheimer's disease (AD) and schizophrenia. A medicinal chemistry effort around previously reported compound 1 (SEN15924, WAY 361789) led to the identification of 12 (SEN78702, WYE-308775) a potent and selective full agonist of the alpha 7 nAChR that demonstrated improved plasma stability, brain levels, and efficacy in behavioral cognition models.

  DOI：

  10.1021/jm3013568

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).