4-(4-Fluorophenyl)-3-formyl-2-isopropyl-5-methyl-1-methylsulfonylpyrrole | 139993-90-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 4-(4-Fluorophenyl)-3-formyl-2-isopropyl-5-methyl-1-methylsulfonylpyrrole
• 英文别名: 4-(4-fluorophenyl)-3-formyl-2-isopropyl-5-methyl-1-methylsulfonylpyrrol；4-(4-Fluorophenyl)-5-methyl-1-methylsulfonyl-2-propan-2-ylpyrrole-3-carbaldehyde
• CAS: 139993-90-1
• 化学式: C₁₆H₁₈FNO₃S
• 分子量: 323.388
• InChiKey: SWWHNAQKDONUBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  64.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4-Fluorophenyl)-3-formyl-2-isopropyl-5-methyl-1-methylsulfonylpyrrole 在 sodium tetrahydroborate 、 二乙基甲氧基硼烷 、 氢氟酸 作用下， 以 乙腈 为溶剂， 反应 19.0h， 生成 (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：

  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：

  异丁酰乙酸乙酯 在 四丙基高钌酸铵 、 4 A molecular sieve 、 sodium acetate 、 sodium hydride 、 二异丁基氢化铝 、 溶剂黄146 、 N-甲基吗啉氧化物 作用下， 以 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 9.5h， 生成 4-(4-Fluorophenyl)-3-formyl-2-isopropyl-5-methyl-1-methylsulfonylpyrrole
  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

• Optically active intermediate and method for production thereof
  申请人：Shionogi Seiyaku Kabushiki Kaisha

  公开号：US05354879A1

  公开（公告）日：1994-10-11

  The present invention relates to a synthetic method of optically active starting materials for various medicaments, which are represented by Formula (I): ##STR1## wherein R.sup.1 is hydrogen or hydroxy protecting group; * is an asymmetric carbon; R.sup.2 ' is hydrogen or an optionally substituted lower alkyl; and Q is --CH.dbd.P(Ph).sub.3, --CH.sub.2 P(O)(OMe).sub.2, or --CH.sub.2 S(O)Me, in high optical purity on a large scale. In more detail, the present invention provides intermediates and a method for the production thereof for synthesizing optically active compounds which are able to inhibit activities of HMG-CoA reductase and are, therefore, useful for inhibition of cholesterol biosynthesis.

  本发明涉及一种合成方法，用于合成各种药物的光学活性起始物，该药物由式（I）表示：##STR1## 其中R.sup.1是氢或羟基保护基；*是不对称碳；R.sup.2'是氢或可选择取代的较低烷基；Q是--CH.dbd.P(Ph).sub.3，--CH.sub.2P(O)(OMe).sub.2或--CH.sub.2S(O)Me，以高光学纯度大规模生产。更详细地说，本发明提供了中间体及其生产方法，用于合成能够抑制HMG-CoA还原酶活性的光学活性化合物，因此，对于抑制胆固醇生物合成是有用的。
• Pyrrole derivatives
  申请人：SHIONOGI SEIYAKU KABUSHIKI KAISHA

  公开号：EP0464845A1

  公开（公告）日：1992-01-08

  The compounds of the present invention inhibit the HMG-CoA reductase, and subsequently suppress the synthesis 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。
• OPTICALLY ACTIVE INTERMEDIATE AND PRODUCTION THEREOF
  申请人：SHIONOGI SEIYAKU KABUSHIKI KAISHA

  公开号：EP0554455A1

  公开（公告）日：1993-08-11

  A process for synthesizing an optically active starting material, represented by general formula (I), for various medicines with a high optical purity in a good yield, wherein R¹ represents hydrogen or hydroxyl-protecting group: * represents an asymmetric carbon atom; R2' represents hydrogen or optionally substituted lower alkyl; and Q represents -C=P(Ph)₃, -CH₂P(O)(OMe)₂ or -CN₂S(O)Me. More particularly, an intermediate for the synthesis of an optically active compound useful for inhibiting the activity of HMG-CoA reductase to thereby inhibit the biosynthesis of cholesterol; and a process for producing the intermediate.

  一种用于合成光学纯度高、收率好的各种药物的光学活性起始材料的工艺，由通式(I)表示，其中R¹代表氢或羟基保护基团：* 代表不对称碳原子；R2'代表氢或任选取代的低级烷基；Q 代表-C=P(Ph)₃、-CH₂P(O)(OMe)₂或-CN₂S(O)Me。更具体地说，一种用于合成光学活性化合物的中间体，该化合物可抑制 HMG-CoA 还原酶的活性，从而抑制胆固醇的生物合成；以及一种生产该中间体的工艺。
• Practical Synthesis of Chiral Synthons for the Preparation of HMG-CoA Reductase Inhibitors
  作者：Toshiro Konoike、Yoshitaka Araki

  DOI：10.1021/jo00104a049

  日期：1994.12

  A practical procedure for the enantioselective preparation of optically pure (R)- and (S)-monomethyl esters of 3-[(tert-butyldimethylsilyl)oxy]pentanedioic acid has been developed by diastereoselective ring-opening of 3-[(tert-butyldimethylsilyl)oxy]pentanedioic anhydride 5 by benzyl (R)- and (S)-mandelate, respectively. These half-esters afforded chiral Wittig reagent 2 and Horner-Wadsworth-Emmons (HWE) reagent 1 efficiently which have been proved to be useful in the synthesis of HMG-CoA reductase inhibitors. The method is applied to the synthesis of the (R)-3-methylglutaric acid, monomethyl ester.
• US5128366A
  申请人：——

  公开号：US5128366A

  公开（公告）日：1992-07-07