吡唑-3-卡巴肼,4-溴-1-甲基- | 400878-08-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 吡唑-3-卡巴肼,4-溴-1-甲基-
• 英文名称: 4-bromo-1-methyl-1H-pyrazole-3-carboxylic acid hydrazide
• 英文别名: 4-Bromo-1-methyl-1H-pyrazole-3-carbohydrazide；4-bromo-1-methylpyrazole-3-carbohydrazide
• CAS: 400878-08-2
• 化学式: C₅H₇BrN₄O
• mdl: MFCD02253808
• 分子量: 219.041
• InChiKey: JINYGSMERXPQMD-UHFFFAOYSA-N

物化性质

• 密度：
  1.98±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  72.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  吡唑-3-卡巴肼,4-溴-1-甲基- 、 2-(三氟乙酰基)环己酮 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 0.5h， 以56%的产率得到(4-bromo-1-methyl-1H-pyrazol-3-yl)-(3-hydroxy-3-trifluoromethyl-3,3a,4,5,6,7-hexahydroindazol-2-yl)methanone
  参考文献：
  名称：

  Fused 3-Hydroxy-3-trifluoromethylpyrazoles Inhibit Mutant Huntingtin Toxicity

  摘要：

  Here, we describe the selection and optimization of a chemical series active in both a full-length and a fragment-based Huntington's disease (HD) assay. Twenty-four thousand small molecules were screened in a phenotypic HD assay, identifying a series of compounds bearing a 3-hydroxy-3-trifluoromethylpyrazole moiety as able to revert the toxicity induced by full-length mutant Htt by up to 50%. A chemical exploration around the series led to the identification of compound 4f, which demonstrated to be active in a Htt171-82Qrat primary striatal neuron assay and a PC12-Exon-1 based assay. This compound was selected for testing in R6/2 mice, in which it was well-tolerated and showed a positive effect on body weight and a positive trend in preventing ventricular volume enlargment. These studies provide strong rationale for further testing the potential benefits of 3-hydroxy-3-trifluoromethylpyrazoles in treating HD.

  DOI：

  10.1021/ml400251g
• 作为产物：
  描述：

  1-甲基-4-硝基-3-吡唑羧酸甲酯 在 亚硝酸特丁酯 、 palladium 10% on activated carbon 、 氢气 、 一水合肼 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 20.0~60.0 ℃ 、2.0 MPa 条件下， 反应 10.75h， 生成 吡唑-3-卡巴肼,4-溴-1-甲基-
  参考文献：
  名称：

  Fused 3-Hydroxy-3-trifluoromethylpyrazoles Inhibit Mutant Huntingtin Toxicity

  摘要：

  Here, we describe the selection and optimization of a chemical series active in both a full-length and a fragment-based Huntington's disease (HD) assay. Twenty-four thousand small molecules were screened in a phenotypic HD assay, identifying a series of compounds bearing a 3-hydroxy-3-trifluoromethylpyrazole moiety as able to revert the toxicity induced by full-length mutant Htt by up to 50%. A chemical exploration around the series led to the identification of compound 4f, which demonstrated to be active in a Htt171-82Qrat primary striatal neuron assay and a PC12-Exon-1 based assay. This compound was selected for testing in R6/2 mice, in which it was well-tolerated and showed a positive effect on body weight and a positive trend in preventing ventricular volume enlargment. These studies provide strong rationale for further testing the potential benefits of 3-hydroxy-3-trifluoromethylpyrazoles in treating HD.

  DOI：

  10.1021/ml400251g

文献信息

• Fused 3-Hydroxy-3-trifluoromethylpyrazoles Inhibit Mutant Huntingtin Toxicity
  作者：Salvatore La Rosa、Tiziana Benicchi、Laura Bettinetti、Ilaria Ceccarelli、Enrica Diodato、Cesare Federico、Pasquale Fiengo、Davide Franceschini、Ozgun Gokce、Freddy Heitz、Giulia Lazzeroni、Ruth Luthi-Carter、Letizia Magnoni、Vincenzo Miragliotta、Carla Scali、Michela Valacchi

  DOI：10.1021/ml400251g

  日期：2013.10.10

  Here, we describe the selection and optimization of a chemical series active in both a full-length and a fragment-based Huntington's disease (HD) assay. Twenty-four thousand small molecules were screened in a phenotypic HD assay, identifying a series of compounds bearing a 3-hydroxy-3-trifluoromethylpyrazole moiety as able to revert the toxicity induced by full-length mutant Htt by up to 50%. A chemical exploration around the series led to the identification of compound 4f, which demonstrated to be active in a Htt171-82Qrat primary striatal neuron assay and a PC12-Exon-1 based assay. This compound was selected for testing in R6/2 mice, in which it was well-tolerated and showed a positive effect on body weight and a positive trend in preventing ventricular volume enlargment. These studies provide strong rationale for further testing the potential benefits of 3-hydroxy-3-trifluoromethylpyrazoles in treating HD.