3-(3-hydroxy-3-trifluoromethyl-3,3a,4,5,6,7-hexahydroindazole-2-sulfonyl)-1H-pyrazole-4-carboxylic acid ethyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(3-hydroxy-3-trifluoromethyl-3,3a,4,5,6,7-hexahydroindazole-2-sulfonyl)-1H-pyrazole-4-carboxylic acid ethyl ester
• 英文别名: ethyl 5-[[(3R,3aS)-3-hydroxy-3-(trifluoromethyl)-4,5,6,7-tetrahydro-3aH-indazol-2-yl]sulfonyl]-1H-pyrazole-4-carboxylate
• 化学式: C₁₄H₁₇F₃N₄O₅S
• 分子量: 410.374
• InChiKey: YVWIMSPARQWAJQ-TVQRCGJNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  133
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2-氰基-3-乙氧基丙烯酸乙酯 在 哌啶 、 盐酸 、 一水合肼 作用下， 以 四氢呋喃 、 乙醇 、 水 、 甲苯 为溶剂， 反应 4.17h， 生成 3-(3-hydroxy-3-trifluoromethyl-3,3a,4,5,6,7-hexahydroindazole-2-sulfonyl)-1H-pyrazole-4-carboxylic acid ethyl ester
  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