4-[(1,3-Benzodioxol-5-yl)methyl]-1,2-dihydro-5-(trifluoromethyl)-3H-pyrazol-3-one | 148135-16-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 4-[(1,3-Benzodioxol-5-yl)methyl]-1,2-dihydro-5-(trifluoromethyl)-3H-pyrazol-3-one
• 英文别名: 4-(1,3-benzodioxol-5-ylmethyl)-5-(trifluoromethyl)-1,2-dihydropyrazol-3-one
• CAS: 148135-16-4
• 化学式: C₁₂H₉F₃N₂O₃
• 分子量: 286.21
• InChiKey: UIIBRGPUSXPFQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  59.6
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-Benzo[1,3]dioxol-5-ylmethyl-4,4,4-trifluoro-3-oxo-butyric acid ethyl ester 在 肼 作用下， 以 乙二醇二甲醚 为溶剂， 以59%的产率得到4-[(1,3-Benzodioxol-5-yl)methyl]-1,2-dihydro-5-(trifluoromethyl)-3H-pyrazol-3-one
  参考文献：
  名称：

  Studies on New Acidic Azoles as Glucose-Lowering Agents in Obese, Diabetic db/db Mice

  摘要：

  Bioisosteric substitution was used as a tool to generate several new structural alternatives to the thiazolidine-2,4-dione and tetrazole heterocycles as potential antidiabetic agents. Among the initial leads that emerged from this strategy, a family of acidic azoles isoxazol-3- and -5-ones and a pyrazol-3-one, showed significant plasma glucose-lowering activity (17-42% reduction) in genetically obese, diabetic db/db mice at a dose of 100 mg/kg/day x 4. Structure-activity relationship studies determined that 5-alkyl-4-(arylmethyl)pyrazol-3-ones, which exist in solution as aromatic enol/iminol tautomers, were the most promising new class of potential antidiabetic agent (32-45% reduction at 20 mg/kg/d x 4). Included in this work are convenient syntheses for several types of acidic azoles that may find use as new acidic bioisosteres in medicinal chemistry such as the antidiabetic lead 5-(trifluoromethyl)pyrazol-3-one (hydroxy tautomer) and aza homologs of the pyrazolones, 1,2,3-triazol-5-ones (hydroxy tautomer) and 1,2,3,4-tetrazol-5-one heterocycles. log P and pK(a) data for 15 potential acidic bioisosteres, all appended to a 2-naphthalenylmethyl residue so as to maintain a similar distance between the acidic hydrogen and arene nucleus, are presented. This new data set allows comparison of a wide variety of potential acid mimetics (pK(a) 3.78-10.66; log P -0.21 to 2.76) for future drug design.

  DOI：

  10.1021/jm00004a008

文献信息

• US5194435A
  申请人：——

  公开号：US5194435A

  公开（公告）日：1993-03-16
• US5183825A
  申请人：——

  公开号：US5183825A

  公开（公告）日：1993-02-02