5-(溴甲基)异噁唑-3(2H)-酮 | 83014-80-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 5-(溴甲基)异噁唑-3(2H)-酮
• 英文名称: 5-(bromomethyl)isoxazol-3-one
• 英文别名: 5-(Bromomethyl)isoxazol-3(2H)-one；5-(bromomethyl)-1,2-oxazol-3-one
• CAS: 83014-80-6
• 化学式: C₄H₄BrNO₂
• 分子量: 177.985
• InChiKey: KNAQMJBBBONHOY-UHFFFAOYSA-N

物化性质

• 密度：
  1.819±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,5-二氯苯酚 、 5-(溴甲基)异噁唑-3(2H)-酮 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 0.17h， 以28 mg的产率得到5-((3,5-dichlorophenoxy)methyl)isoxazol-3(2H)-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
• 作为产物：
  描述：

  ethyl 4-bromobut-2-ynoate 在 羟胺 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 0.25h， 以98 mg的产率得到5-(溴甲基)异噁唑-3(2H)-酮
  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