Ethyl 4-(4-fluorophenyl)-2-isopropylpyrrole-3-carboxylate | 139993-81-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: Ethyl 4-(4-fluorophenyl)-2-isopropylpyrrole-3-carboxylate
• 英文别名: ethyl 4-(4-fluorophenyl)-2-propan-2-yl-1H-pyrrole-3-carboxylate
• CAS: 139993-81-0
• 化学式: C₁₆H₁₈FNO₂
• 分子量: 275.323
• InChiKey: QBBXIOJFJRDRJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  42.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Ethyl 4-(4-fluorophenyl)-2-isopropylpyrrole-3-carboxylate 在 sodium hydroxide 、 sodium tetrahydroborate 、 四丙基高钌酸铵 、 4 A molecular sieve 、 二乙基甲氧基硼烷 、 氢氟酸 、 sodium hydride 、 二异丁基氢化铝 、 N-甲基吗啉氧化物 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 生成 Sodium; (E)-(3R,5S)-7-[4-(4-fluoro-phenyl)-2-isopropyl-1-methanesulfonyl-1H-pyrrol-3-yl]-3,5-dihydroxy-hept-6-enoate
  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：

  2-氨基-4’-氟苯乙酮盐酸盐 、 异丁酰乙酸乙酯 在 sodium acetate 、 溶剂黄146 作用下， 以 水 为溶剂， 以51.3%的产率得到Ethyl 4-(4-fluorophenyl)-2-isopropylpyrrole-3-carboxylate
  参考文献：
  名称：

  Pyrrole derivatives

  摘要：

  本发明的化合物抑制HMG-CoA还原酶，随后抑制胆固醇的合成。它们在治疗高胆固醇血症、高脂蛋白血症和动脉粥样硬化方面具有用途。这些化合物的化学式为##STR1##其中R.sup.1、R.sup.2和R.sup.3分别独立地为氢、可选择取代的较低烷基或可选择取代的芳基；R.sup.4为较低烷基、芳基烷基、芳基或杂环芳基，每种都可选择取代；X为乙烯或乙烯基；Y为##STR2##其中R.sup.5为氢、较低烷基、芳基、芳基烷基或能形成无毒药用可接受盐的阳离子。

  公开号：

  US05128366A1

文献信息

• Pyrrole derivatives
  申请人：Shinogi & Co., Ltd.

  公开号：US05128366A1

  公开（公告）日：1992-07-07

  The compounds of the present invention inhibit HMG-CoA reductase, and subsequently suppress the synthesis of cholesterol. And they are useful in the treatment of hypercholesterolemia, hyperlipoproteinemia, and atherosclerosis. The compounds have the formula ##STR1## wherein R.sup.1, R.sup.2, and R.sup.3 each is independently hydrogen, optionally substituted lower alkyl, or optionally substituted aryl; R.sup.4 is lower alkyl, aralkyl, aryl, or heteroaryl, each of which is optionally substituted; X is vinylene or ethylene; Y is ##STR2## where R.sup.5 is hydrogen, lower alkyl, aryl, aralkyl, or a cation capable of forming a non-toxic pharmaceutically acceptable salt.

  本发明的化合物抑制HMG-CoA还原酶，随后抑制胆固醇的合成。它们在治疗高胆固醇血症、高脂蛋白血症和动脉粥样硬化方面具有用途。这些化合物的化学式为##STR1##其中R.sup.1、R.sup.2和R.sup.3分别独立地为氢、可选择取代的较低烷基或可选择取代的芳基；R.sup.4为较低烷基、芳基烷基、芳基或杂环芳基，每种都可选择取代；X为乙烯或乙烯基；Y为##STR2##其中R.sup.5为氢、较低烷基、芳基、芳基烷基或能形成无毒药用可接受盐的阳离子。
• US5128366A
  申请人：——

  公开号：US5128366A

  公开（公告）日：1992-07-07
• 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.