ethyl 4-(4-nitrophenylthio)-3-oxobutanoate | 1195396-05-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 4-(4-nitrophenylthio)-3-oxobutanoate
• 英文别名: Ethyl 4-(4-nitrophenyl)sulfanyl-3-oxobutanoate
• CAS: 1195396-05-4
• 化学式: C₁₂H₁₃NO₅S
• 分子量: 283.305
• InChiKey: CDHYPWACYYLVTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  115
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 4-(4-nitrophenylthio)-3-oxobutanoate 在 肼 作用下， 以 乙醇 为溶剂， 以0.4 g的产率得到5-((4-nitrophenylthio)methyl)-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
• 作为产物：
  描述：

  4-氯乙酰乙酸乙酯 、 4-硝基苯硫醇 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以1.56 g的产率得到ethyl 4-(4-nitrophenylthio)-3-oxobutanoate
  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

• Arylsulfanyl pyrazolones block mutant SOD1-G93A aggregation. Potential application for the treatment of amyotrophic lateral sclerosis
  作者：Tian Chen、Radhia Benmohamed、Anthony C. Arvanites、Hantamalala Ralay Ranaivo、Richard I. Morimoto、Robert J. Ferrante、D. Martin Watterson、Donald R. Kirsch、Richard B. Silverman

  DOI：10.1016/j.bmc.2010.10.052

  日期：2011.1

  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.