(E)-(R)-7-[4-(4-Fluoro-phenyl)-2-isopropyl-1-methanesulfonyl-5-methyl-1H-pyrrol-3-yl]-3-hydroxy-5-oxo-hept-6-enoic acid methyl ester | 188557-38-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: (E)-(R)-7-[4-(4-Fluoro-phenyl)-2-isopropyl-1-methanesulfonyl-5-methyl-1H-pyrrol-3-yl]-3-hydroxy-5-oxo-hept-6-enoic acid methyl ester
• CAS: 188557-38-2
• 化学式: C₂₃H₂₈FNO₆S
• 分子量: 465.543
• InChiKey: HIJRFKMXUBTJEB-GNISGLHKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.43
• 重原子数：
  32.0
• 可旋转键数：
  9.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  102.67
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (E)-(R)-7-[4-(4-Fluoro-phenyl)-2-isopropyl-1-methanesulfonyl-5-methyl-1H-pyrrol-3-yl]-3-hydroxy-5-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 1.83h， 以91%的产率得到(3R,5S)-7-[4-(4-fluorophenyl)-2-isopropyl-1-(methanesulfonyl)-5-methyl-1H-pyrrol-3-yl]-3,5-dihydroxy-6-heptenoic acid methyl ester
  参考文献：
  名称：

  Optical Resolution of 3-(Silyloxy)glutaric Acid Half Esters and Their Utilization for Enantioconvergent Synthesis of a HMG-CoA Reductase Inhibitor

  摘要：

  Useful chiral synthons, (3R)- and (3S)-[(tert-butyldimethylsilyl)oxy]penta acid monomethyl ester, (R)-1 and (S)-1, were obtained by optical resolution of a racemic mixture of 1. Sulfoxide 8 has been developed from(S)-1 as a new building block for preparing HMG-CoA reductase inhibitors. Two alternate chiral synthons 2 and 8, synthesized from (R)-1 and(S)-1, respectively, were employed for enantioconvergent synthesis of potent inhibitor 15 containing a pyrrole moiety.

  DOI：

  10.1021/jo9722156
• 作为产物：
  描述：

  [[4-(4-fluorophenyl)-2-isopropyl-5-methyl-1H-pyrrol-3-yl]methyl]dimethylamine 在 氢氟酸 、 potassium tert-butylate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 、 乙腈 、 叔丁醇 为溶剂， 反应 11.25h， 生成 (E)-(R)-7-[4-(4-Fluoro-phenyl)-2-isopropyl-1-methanesulfonyl-5-methyl-1H-pyrrol-3-yl]-3-hydroxy-5-oxo-hept-6-enoic acid methyl ester
  参考文献：
  名称：

  Optical Resolution of 3-(Silyloxy)glutaric Acid Half Esters and Their Utilization for Enantioconvergent Synthesis of a HMG-CoA Reductase Inhibitor

  摘要：

  Useful chiral synthons, (3R)- and (3S)-[(tert-butyldimethylsilyl)oxy]penta acid monomethyl ester, (R)-1 and (S)-1, were obtained by optical resolution of a racemic mixture of 1. Sulfoxide 8 has been developed from(S)-1 as a new building block for preparing HMG-CoA reductase inhibitors. Two alternate chiral synthons 2 and 8, synthesized from (R)-1 and(S)-1, respectively, were employed for enantioconvergent synthesis of potent inhibitor 15 containing a pyrrole moiety.

  DOI：

  10.1021/jo9722156

文献信息

• Synthesis and Biological Activity of Methanesulfonamide Pyrimidine- and N-Methanesulfonyl Pyrrole-Substituted 3,5-Dihydroxy-6-heptenoates, a Novel Series of HMG-CoA Reductase Inhibitors
  作者：Masamichi Watanabe、Haruo Koike、Teruyuki Ishiba、Tetsuo Okada、Shujiro Seo、Kentaro Hirai

  DOI：10.1016/s0968-0896(96)00248-9

  日期：1997.2

  A novel series of methanesulfonamide pyrimidine- and N-methanesulfonyl pyrrole-substituted 3,5-dihydroxy-6-heptenoates were synthesized and evaluated for their ability to inhibit the enzyme HMG-CoA reductase in vitro. Monocalcium bis(+)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulfonylaminopyrimidin)-5-yl]-(3R,5S)-dihydroxy-(E)-6-heptenoate (3a,S-4522) was selected as a candidate for further evaluation. Compound 3a was approximately four times more potent than lovastatin sodium salt (in inhibiting HMG-CoA reductase in vitro (IC50 = 11 nM). Compound 3a was shown to be the most potent cholesterol biosynthesis inhibitor in this series (IC50 = 1.12 nM) in rat isolated hepatocytes; its inhibitory activity was approximately 100 times more potent than pravastatin. (C) 1997, Elsevier Science Ltd.