5-ethoxycarbonyl-6-(4'-fluorophenyl)-4-isopropyl-2-methoxypyrimidine | 147118-33-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-ethoxycarbonyl-6-(4'-fluorophenyl)-4-isopropyl-2-methoxypyrimidine
• 英文别名: Ethyl 4-(4-fluorophenyl)-2-methoxy-6-propan-2-ylpyrimidine-5-carboxylate
• CAS: 147118-33-0
• 化学式: C₁₇H₁₉FN₂O₃
• 分子量: 318.348
• InChiKey: GTSRSPNPVQEOAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  61.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-ethoxycarbonyl-6-(4'-fluorophenyl)-4-isopropyl-2-methoxypyrimidine 在 四丙基高钌酸铵 、 4 A molecular sieve 、 二异丁基氢化铝 、 N-甲基吗啉氧化物 作用下， 以 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 17.0h， 生成 (E)-(R)-3-(tert-Butyl-dimethyl-silanyloxy)-7-[4-(4-fluoro-phenyl)-6-isopropyl-2-methoxy-pyrimidin-5-yl]-5-oxo-hept-6-enoic acid methyl ester
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(96)00248-9
• 作为产物：
  描述：

  ethyl 2-(4-fluorobenzylidene)-4-methyl-3-oxopentanoate 在 六甲基磷酰三胺 、 间氯过氧苯甲酸 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 氯仿 为溶剂， 反应 22.5h， 生成 5-ethoxycarbonyl-6-(4'-fluorophenyl)-4-isopropyl-2-methoxypyrimidine
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(96)00248-9

文献信息

• Pyrimidine derivatives as HMG-CoA reductase inhibitors
  申请人：SHIONOGI SEIYAKU KABUSHIKI KAISHA

  公开号：EP0521471A1

  公开（公告）日：1993-01-07

  The compounds of the present invention inhibit the HMG-CoA reductase, and subsequently suppress the biosynthesis of cholesterol. And they are useful in the treatment of hypercholesterolemia, hyperlipoproteinemia, and atherosclerosis.

  本发明的化合物可抑制 HMG-CoA 还原酶，从而抑制胆固醇的生物合成。它们可用于治疗高胆固醇血症、高脂蛋白血症和动脉粥样硬化。
• Oxidative Dehydrogenation of Dihydropyrimidinones and Dihydropyrimidines
  作者：Kana Yamamoto、Ye Grace Chen、Frédéric G. Buono

  DOI：10.1021/ol051879w

  日期：2005.10.1

  A mild, practical procedure for oxidative dehydrogenation with catalytic amounts of a Cu salt, K2CO3, and tert-butylhydroperoxide (TBHP) as a terminal oxidant has been developed. This oxidation procedure is generally applicable to dihydropyrimidinones and most dihydropyrimidines.
• US5260440A
  申请人：——

  公开号：US5260440A

  公开（公告）日：1993-11-09
• USRE37314E1
  申请人：——

  公开号：USRE37314E1

  公开（公告）日：2001-08-07
• 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.