5-[(3,5-dichlorophenoxy)methyl]-2-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-3-one | 1412895-99-8

• 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-[(3,5-dichlorophenoxy)methyl]-2-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-3-one
• CAS: 1412895-99-8
• 化学式: C₁₇H₉Cl₄F₃N₂O₂
• 分子量: 472.078
• InChiKey: YWOXJGNOGKTIJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-(3,5-dichlorophenoxy)-N-methoxy-N-methylacetamide 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 7.0h， 生成 5-[(3,5-dichlorophenoxy)methyl]-2-[2,6-dichloro-4-(trifluoromethyl)phenyl]-1H-pyrazol-3-one
  参考文献：
  名称：

  Substituted pyrazolones require N2 hydrogen bond donating ability to protect against cytotoxicity from protein aggregation of mutant superoxide dismutase 1

  摘要：

  Amyotrophic lateral sclerosis (ALS) is a debilitating and fatal neurodegenerative disease. Although the cause remains unknown, misfolded protein aggregates are seen in neurons of sporadic ALS patients, and familial ALS mutations, including mutations in superoxide dismutase 1 (SOD1), produce proteins with an increased propensity to misfold and aggregate. A structure activity relationship of a lead scaffold exhibiting neuroprotective activity in a G93A-SOD1 mouse model for ALS has been further investigated in a model PC12 cellular assay. Synthesis of biotinylated probes at the N-1 nitrogen of the pyrazolone ring gave compounds (5d-e) that retained activity within 10-fold of the proton-bearing lead compound (5a) and were equipotent with a sterically less cumbersome N-1-methyl substituted analogue (5b). However, when methyl substitution was introduced at N-1 and N-2 of the pyrazolone ring, the compound was inactive (5c). These data led us to investigate further the pharmacophoric nature of the pyrazolone unit. A range of N-1 substitutions were tolerated, leading to the identification of an N-1-benzyl substituted pyrazolone (5m), equipotent with 5a. Substitution at N-2 or excision of N-2, however, removed all activity. Therefore, the hydrogen bond donating ability of the N-2-H of the pyrazolone ring appears to be a critical part of the structure, which will influence further analogue synthesis. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.114