5-(benzylcarbamoyl)-1-(4-fluorophenyl)-4-isopropyl-1H-pyrazole-3-carboxylic acid | 1005475-61-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(benzylcarbamoyl)-1-(4-fluorophenyl)-4-isopropyl-1H-pyrazole-3-carboxylic acid
• 英文别名: 5-(Benzylcarbamoyl)-1-(4-fluorophenyl)-4-propan-2-ylpyrazole-3-carboxylic acid
• CAS: 1005475-61-5
• 化学式: C₂₁H₂₀FN₃O₃
• 分子量: 381.407
• InChiKey: FKSCSNCAIODVDB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  84.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(benzylcarbamoyl)-1-(4-fluorophenyl)-4-isopropyl-1H-pyrazole-3-carboxylic acid 在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 以35%的产率得到N-benzyl-1-(4-fluorophenyl)-3-(hydroxymethyl)-4-isopropyl-1H-pyrazole-5-carboxamide
  参考文献：
  名称：

  Substituted Pyrazoles as Hepatoselective HMG-CoA Reductase Inhibitors: Discovery of (3R,5R)-7-[2-(4-Fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxyheptanoic Acid (PF-3052334) as a Candidate for the Treatment of Hypercholesterolemia

  摘要：

  In light of accumulating evidence that aggressive LDL-lowering therapy may offer increased protection against coronary heart disease, we undertook the design and synthesis of a novel series of HMG-CoA reductase inhibitors based upon a substituted pyrazole template. Optimizing this series using both structure-based design and molecular property considerations afforded a class of highly efficacious and hepatoselective inhibitors resulting in the identification of (3 R,5 R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2 H-pyrazol-3-yl]-3,5-dihydroxy-heptanoic (PF-3052334) as a candidate for the treatment of hypercholesterolemia.

  DOI：

  10.1021/jm070849r
• 作为产物：
  描述：

  Methyl 5-(benzylcarbamoyl)-1-(4-fluorophenyl)-4-propan-2-ylpyrazole-3-carboxylate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以98%的产率得到5-(benzylcarbamoyl)-1-(4-fluorophenyl)-4-isopropyl-1H-pyrazole-3-carboxylic acid
  参考文献：
  名称：

  Substituted Pyrazoles as Hepatoselective HMG-CoA Reductase Inhibitors: Discovery of (3R,5R)-7-[2-(4-Fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxyheptanoic Acid (PF-3052334) as a Candidate for the Treatment of Hypercholesterolemia

  摘要：

  In light of accumulating evidence that aggressive LDL-lowering therapy may offer increased protection against coronary heart disease, we undertook the design and synthesis of a novel series of HMG-CoA reductase inhibitors based upon a substituted pyrazole template. Optimizing this series using both structure-based design and molecular property considerations afforded a class of highly efficacious and hepatoselective inhibitors resulting in the identification of (3 R,5 R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2 H-pyrazol-3-yl]-3,5-dihydroxy-heptanoic (PF-3052334) as a candidate for the treatment of hypercholesterolemia.

  DOI：

  10.1021/jm070849r