ethyl 4-(3-chlorophenylthio)-3-oxobutanoate | 1263406-20-7

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: ethyl 4-(3-chlorophenylthio)-3-oxobutanoate
• 英文别名: Ethyl 4-(3-chlorophenyl)sulfanyl-3-oxobutanoate
• CAS: 1263406-20-7
• 化学式: C₁₂H₁₃ClO₃S
• 分子量: 272.752
• InChiKey: GAHURMAWWDGPHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 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：
  68.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-(3-chlorophenylthio)-3-oxobutanoate 在 ammonium acetate 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 6.0h， 以45%的产率得到(Z)-ethyl 4-(3-chlorophenylthio)-3-aminobut-2-enoate
  参考文献：
  名称：

  Exploring the role of chloro and methyl substitutions in 2-phenylthiomethyl-benzoindole derivatives for 5-LOX enzyme inhibition

  摘要：

  Following the results we previously reported on a series of ethyl 2-phenylthiomethyl 5-hydroxyindole-3-carboxylate derivatives as 5-lipoxygenase (5-LOX) inhibitors, in order to obtain a more selective compound with respect to the previous generation of derivatives, we decided to modify the structure of the core ligand.The first level of structural modification involved the annelation of benzene to the indole, yielding corresponding benzo[g]indole derivatives, systematic optimization of methyl or chlorine groups in meta, ortho- and ortho/para-position of 2-phenylthiomethyl moiety were applied. The reported results show that extension of the aromatic core led to a great enhancement of activity, especially in cell-free assay, and the accurate structure-based design provided compounds 6f, 6g and 61 that block 5-LOX activity in cell-free assays with IC50 ranging from 0.17 to 0.22 mu M, and suppress 5-LOX product synthesis in polymorphonuclear leukocytes with IC50 ranging from 0.19 to 0.37 mu M. Moreover we have identified 6f and 61 as dual 5-lipoxygenase (5-LO) and microsomal prostaglandin E-2 synthase-1 (mPGES-1) inhibitors and compound 61 significantly reduces inflammatory reactions in the carrageenan-induced mouse paw oedema. The reported in vivo analysis, together with the accessible synthetic procedure, stimulate for the generation of further potent antinflammatory benzoindoles-based agents. (C) 2015 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.11.048
• 作为产物：
  描述：

  4-氯乙酰乙酸乙酯 、 3-氯苯硫酚 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以81%的产率得到ethyl 4-(3-chlorophenylthio)-3-oxobutanoate
  参考文献：
  名称：

  Exploring the role of chloro and methyl substitutions in 2-phenylthiomethyl-benzoindole derivatives for 5-LOX enzyme inhibition

  摘要：

  Following the results we previously reported on a series of ethyl 2-phenylthiomethyl 5-hydroxyindole-3-carboxylate derivatives as 5-lipoxygenase (5-LOX) inhibitors, in order to obtain a more selective compound with respect to the previous generation of derivatives, we decided to modify the structure of the core ligand.The first level of structural modification involved the annelation of benzene to the indole, yielding corresponding benzo[g]indole derivatives, systematic optimization of methyl or chlorine groups in meta, ortho- and ortho/para-position of 2-phenylthiomethyl moiety were applied. The reported results show that extension of the aromatic core led to a great enhancement of activity, especially in cell-free assay, and the accurate structure-based design provided compounds 6f, 6g and 61 that block 5-LOX activity in cell-free assays with IC50 ranging from 0.17 to 0.22 mu M, and suppress 5-LOX product synthesis in polymorphonuclear leukocytes with IC50 ranging from 0.19 to 0.37 mu M. Moreover we have identified 6f and 61 as dual 5-lipoxygenase (5-LO) and microsomal prostaglandin E-2 synthase-1 (mPGES-1) inhibitors and compound 61 significantly reduces inflammatory reactions in the carrageenan-induced mouse paw oedema. The reported in vivo analysis, together with the accessible synthetic procedure, stimulate for the generation of further potent antinflammatory benzoindoles-based agents. (C) 2015 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.11.048

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.
• Exploring the role of chloro and methyl substitutions in 2-phenylthiomethyl-benzoindole derivatives for 5-LOX enzyme inhibition
  作者：Antonella Peduto、Verena Krauth、Selene Collarile、Fiederike Dehm、Marika Ambruosi、Carmela Belardo、Francesca Guida、Antonio Massa、Veronica Esposito、Sabatino Maione、Mario de Rosa、Oliver Werz、Rosanna Filosa

  DOI：10.1016/j.ejmech.2015.11.048

  日期：2016.1

  Following the results we previously reported on a series of ethyl 2-phenylthiomethyl 5-hydroxyindole-3-carboxylate derivatives as 5-lipoxygenase (5-LOX) inhibitors, in order to obtain a more selective compound with respect to the previous generation of derivatives, we decided to modify the structure of the core ligand.The first level of structural modification involved the annelation of benzene to the indole, yielding corresponding benzo[g]indole derivatives, systematic optimization of methyl or chlorine groups in meta, ortho- and ortho/para-position of 2-phenylthiomethyl moiety were applied. The reported results show that extension of the aromatic core led to a great enhancement of activity, especially in cell-free assay, and the accurate structure-based design provided compounds 6f, 6g and 61 that block 5-LOX activity in cell-free assays with IC50 ranging from 0.17 to 0.22 mu M, and suppress 5-LOX product synthesis in polymorphonuclear leukocytes with IC50 ranging from 0.19 to 0.37 mu M. Moreover we have identified 6f and 61 as dual 5-lipoxygenase (5-LO) and microsomal prostaglandin E-2 synthase-1 (mPGES-1) inhibitors and compound 61 significantly reduces inflammatory reactions in the carrageenan-induced mouse paw oedema. The reported in vivo analysis, together with the accessible synthetic procedure, stimulate for the generation of further potent antinflammatory benzoindoles-based agents. (C) 2015 Published by Elsevier Masson SAS.