1-methyl-1H-imidazole-4-sulfonyl hydrazide | 890522-69-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-methyl-1H-imidazole-4-sulfonyl hydrazide
• 英文别名: 1-Methylimidazole-4-sulfonohydrazide
• CAS: 890522-69-7
• 化学式: C₄H₈N₄O₂S
• 分子量: 176.199
• InChiKey: ZFKSVHFSNZELRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  98.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-methyl-1H-imidazole-4-sulfonyl hydrazide 、 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16%的产率得到2-(1-methyl-1H-imidazole-4-sulfonyl)-3-trifluoromethyl-3,3a,4,5,6,7-hexahydro-2H-indazol-3-ol
  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-1H-咪唑-4-磺酰氯 在 一水合肼 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 1-methyl-1H-imidazole-4-sulfonyl hydrazide
  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

• Quinazolinedione sulfonamides: A novel class of competitive AMPA receptor antagonists with oral activity
  作者：Manuel Koller、Kurt Lingenhoehl、Markus Schmutz、Ivan-Toma Vranesic、Joerg Kallen、Yves P. Auberson、David A. Carcache、Henri Mattes、Silvio Ofner、David Orain、Stephan Urwyler

  DOI：10.1016/j.bmcl.2011.04.017

  日期：2011.6

  Quinazoline-2,4-diones with a sulfonamide group attached to the N(3) ring atom constitute a novel class of competitive AMPA receptor antagonists. One of the synthesized compounds, 28, shows nanomolar receptor affinity, whereas other examples of the series display oral anticonvulsant activity in animal models.

  带有与N（3）环原子相连的磺酰胺基的喹唑啉2,4-二酮构成一类新的竞争性AMPA受体拮抗剂。一种合成的化合物28显示出纳摩尔受体亲和力，而该系列的其他实例在动物模型中显示出口服抗惊厥活性。
• 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.