5-((4-chlorophenylthio)methyl)-2-phenyl-1H-pyrazol-3(2H)-one | 1227692-45-6

• 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-chlorophenylthio)methyl)-2-phenyl-1H-pyrazol-3(2H)-one
• 英文别名: 3-{[(4-chlorophenyl)thio]methyl}-1-phenyl-1H-pyrazol-5-ol；5-[(4-chlorophenyl)sulfanylmethyl]-2-phenyl-1H-pyrazol-3-one
• CAS: 1227692-45-6
• 化学式: C₁₆H₁₃ClN₂OS
• 分子量: 316.811
• InChiKey: DGOQSGRRVWLWLT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-氯苯硫酚 在 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 5-((4-chlorophenylthio)methyl)-2-phenyl-1H-pyrazol-3(2H)-one
  参考文献：
  名称：

  Arylsulfanyl pyrazolones block mutant SOD1-G93A aggregation. Potential application for the treatment of amyotrophic lateral sclerosis

  摘要：

  Amyotrophic lateral sclerosis (ALS) is an orphan neurodegenerative disease currently without a cure. Mutations in copper/zinc superoxide dismutase 1 (SOD1) have been implicated in the pathophysiology of this disease. Using a high-throughput screening assay expressing mutant G93A SOD1, two bioactive chemical hit compounds (1 and 2), identified as arylsulfanyl pyrazolones, were identified. The structural optimization of this scaffold led to the generation of a more potent analogue (19) with an EC50 of 170 nM. To determine the suitability of this class of compounds for further optimization, 1 was subjected to a battery of pharmacokinetic assays; most of the properties of 1 were good for a screening hit, except it had a relatively rapid clearance and short microsomal half-life stability. Compound 2 was found to be blood-brain barrier penetrating with a brain/plasma ratio = 0.19. The optimization of this class of compounds could produce novel therapeutic candidates for ALS patients. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.10.052

文献信息

• TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS
  申请人：Kirsch Donald R.

  公开号：US20110237907A1

  公开（公告）日：2011-09-29

  The present invention relates to the identification of compounds and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the provided compounds.

  本发明涉及识别用于治疗肌萎缩侧索硬化症（ALS）和其他神经退行性疾病的化合物和药物组合物，还提供了制备所述化合物的方法。
• Treatment of Amyotrophic Lateral Sclerosis
  申请人：Silverman Richard B.

  公开号：US20160016911A1

  公开（公告）日：2016-01-21

  The present invention relates to the identification of compounds and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the provided compounds.

  本发明涉及识别化合物及其制备的药物组合物，用于治疗患有肌萎缩侧索硬化症（ALS）和其他神经退行性疾病的患者。本发明还提供了制备所述化合物的方法。
• Treatment of amyotrophic lateral sclerosis
  申请人：Kirsch Donald R.

  公开号：US10167263B2

  公开（公告）日：2019-01-01

  The present invention relates to the identification of compounds and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the provided compounds.

  本发明涉及用于治疗肌萎缩性脊髓侧索硬化症（ALS）和其他神经退行性疾病的化合物及其药物组合物的鉴定。本发明还提供了制备所提供化合物的方法。
• PYRAZOLONE DERIVATIVES USEFUL IN THE TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS
  申请人：Northwestern University

  公开号：EP2367798B1

  公开（公告）日：2018-02-28
• US9145424B2
  申请人：——

  公开号：US9145424B2

  公开（公告）日：2015-09-29