7-{2-(4-fluorophenyl)-4-isopropyl-5-[methyl-(2-methylbenzyl)carbamoyl]-2H-pyrazol-3-yl}-5-hydroxy-3-oxo-hept-6-enoic acid methyl ester | 1005475-76-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 7-{2-(4-fluorophenyl)-4-isopropyl-5-[methyl-(2-methylbenzyl)carbamoyl]-2H-pyrazol-3-yl}-5-hydroxy-3-oxo-hept-6-enoic acid methyl ester
• 英文别名: methyl (E,3R)-7-[2-(4-fluorophenyl)-5-[methyl-[(2-methylphenyl)methyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3-hydroxy-5-oxohept-6-enoate
• CAS: 1005475-76-2
• 化学式: C₃₀H₃₄FN₃O₅
• 分子量: 535.615
• InChiKey: KYRRHTGTULGVOG-LECGRMGRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  7-{2-(4-fluorophenyl)-4-isopropyl-5-[methyl-(2-methylbenzyl)carbamoyl]-2H-pyrazol-3-yl}-5-hydroxy-3-oxo-hept-6-enoic acid methyl ester 在 二乙基甲氧基硼烷 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 以81.1%的产率得到7-{2-(4-fluorophenyl)-4-isopropyl-5-[methyl-(2-methylbenzyl)carbamoyl]-2H-pyrazol-3-yl}-3,5-dihydroxy-hept-6-enoic acid methyl ester
  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：

  C₃₆H₄₈FN₃O₅Si 在 氢氟酸 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以98%的产率得到7-{2-(4-fluorophenyl)-4-isopropyl-5-[methyl-(2-methylbenzyl)carbamoyl]-2H-pyrazol-3-yl}-5-hydroxy-3-oxo-hept-6-enoic acid methyl ester
  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