4-(3-hydroxy-4-methoxyphenyl)-pyrrolidin-2-one | 57724-60-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 4-(3-hydroxy-4-methoxyphenyl)-pyrrolidin-2-one
• 英文别名: 4-(4-methoxy-3-hydroxyphenyl)pyrrolidin-2-one；4-(3-hydroxy-4-methoxyphenyl)-2-pyrrolidone；4-(3-Hydroxy-4-methoxyphenyl)-2-pyrrolidon；4-(3-hydroxy-4-methoxyphenyl)pyrrolidin-2-one
• CAS: 57724-60-4
• 化学式: C₁₁H₁₃NO₃
• 分子量: 207.229
• InChiKey: PAIFAXUSHBVXHY-UHFFFAOYSA-N

物化性质

• 沸点：
  452.9±45.0 °C(Predicted)
• 密度：
  1.234±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(3-hydroxy-4-methoxyphenyl)-pyrrolidin-2-one 在 sodium hydroxide 、 potassium carbonate 、 三乙胺 、 potassium iodide 、 氯甲酸异丁酯 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 12.75h， 生成 4-[3-({[(N-n-Butyl)carbonyl]propyl}oxy)-4-methoxyphenyl]-2-pyrrolidinone
  参考文献：
  名称：

  Inhibition of cyclic adenosine-3',5'-monophosphate phosphodiesterase from vascular smooth muscle by rolipram analogs

  摘要：

  Rolipram [(R,S)-4-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidone] has been shown to inhibit selectively the cAMP phosphodiesterase (PDE) of vascular smooth muscle. In order to further explore the structural requirements for selective PDE inhibition, we synthesized a series of rolipram derivatives differently substituted either at the pyrrolidinone or at the aromatic ring. Among these compounds, rolipram was the most active compound. Semirigid analogues were prepared and used for an evaluation of the active conformation of rolipram. Structural comparison with two other potent and chemically different smooth muscle cAMP-PDE inhibitors, trequinsin and Ro 20-1724, allows us to propose a first topological model of the smooth muscle cAMP-PDE pharmacophore.

  DOI：

  10.1021/jm00127a009
• 作为产物：
  描述：

  Ethyl 3-cyano-3-<3-(benzyloxy)-4-methoxyphenyl>propionate 在 palladium on activated charcoal 盐酸 、 高氯酸 、 氢气 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 甲苯 为溶剂， 反应 12.0h， 生成 4-(3-hydroxy-4-methoxyphenyl)-pyrrolidin-2-one
  参考文献：
  名称：

  Inhibition of cyclic adenosine-3',5'-monophosphate phosphodiesterase from vascular smooth muscle by rolipram analogs

  摘要：

  Rolipram [(R,S)-4-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidone] has been shown to inhibit selectively the cAMP phosphodiesterase (PDE) of vascular smooth muscle. In order to further explore the structural requirements for selective PDE inhibition, we synthesized a series of rolipram derivatives differently substituted either at the pyrrolidinone or at the aromatic ring. Among these compounds, rolipram was the most active compound. Semirigid analogues were prepared and used for an evaluation of the active conformation of rolipram. Structural comparison with two other potent and chemically different smooth muscle cAMP-PDE inhibitors, trequinsin and Ro 20-1724, allows us to propose a first topological model of the smooth muscle cAMP-PDE pharmacophore.

  DOI：

  10.1021/jm00127a009

文献信息

• Synthesis of diarylic compounds by palladium catalyzed reaction of aromatic triflates with boronic acids
  作者：Andreas Huth、Ilse Beetz、Ingrid Schumann

  DOI：10.1016/s0040-4020(01)89138-9

  日期：1989.1

  The known triflates 3c-5c react with the boronic acid 2j to produce the known biarylic compounds 3j-Sj. An extension of this new procedure by reacting the novel triflate 1c with the arylboronic acids 2f-j affords the new correspondingly arylated compounds 1f-j.

  已知的三氟甲磺酸酯3c-5c与硼酸2j反应以产生已知的二元化合物3j-Sj。通过使新的三氟甲磺酸盐1c与芳基硼酸2f-j反应来扩展该新方法，得到了新的相应的芳基化化合物1f-j。
• Phosphodiesterase 4 inhibitors
  申请人：MEMORY PHARMACEUTICALS CORP.

  公开号：US20030139406A1

  公开（公告）日：2003-07-24

  Selective PDE4 inhibition is achieved by 4-(substituted-phenyl)-2-pyrrolidinone compounds. The compounds exhibit improved PDE4 inhibition as compared to compounds like rolipram and show selectivity with regard to inhibition of other classes of PDEs. The compounds of the present invention are of formula I: 1 wherein R 1 , R 2 , and R 3 are as defined herein.

  选择性PDE4抑制是通过4-(取代苯基)-2-吡咯烷酮化合物实现的。与类似于洛利普兰（rolipram）的化合物相比，这些化合物表现出改善的PDE4抑制作用，并且在抑制其他类别的PDE方面表现出选择性。本发明的化合物具有以下式I的结构： 1 其中R 1 ，R 2 和R 3 如本文所定义。
• 3,4-disubstituted phenyl heterocycles and their use
  申请人：Schering Aktiengesellschaft

  公开号：US05064854A1

  公开（公告）日：1991-11-12

  Compounds of general Formula I are disclosed ##STR1## wherein R.sup.1 is C.sub.1-4 -alkyl, R.sup.3 is hydrogen, C.sub.1-4 -alkyl, acyl, aryl, R.sup.5 is hydrogen, C.sub.1-4 -alkyl, X is oxygen, CH.sub.2 or NR.sup.4 with R.sup.4 =hydrogen, C.sub.1-4 -alkyl and Y is an aromatic or nonaromatic ring system which can optionally contain one to two hetero atoms and can be substituted, and the stereoisomers and their mixtures, as well as their preparation and use as medicinal agents.

  通用式I的化合物被披露，其中R.sup.1是C.sub.1-4-烷基，R.sup.3是氢，C.sub.1-4-烷基，酰基，芳基，R.sup.5是氢，C.sub.1-4-烷基，X是氧，CH.sub.2或NR.sup.4，其中R.sup.4=氢，C.sub.1-4-烷基，Y是一个含有一到两个杂原子的芳香或非芳香环系统，可以选择性地含有取代基，以及其立体异构体及其混合物，以及它们的制备和用途作为药用剂。
• Aminoalkoxyphenylpyrrolidone antihypertonic agents and use thereof
  申请人：Schering Aktiengesellschaft

  公开号：US04219551A1

  公开（公告）日：1980-08-26

  Novel aminoalkoxyphenylpyrrolidones of the following formula show antihypertonic activity: ##STR1## wherein R.sub.1 is H or OCH.sub.3 ; R.sub.2 and R.sub.3 are each, independently, H, C.sub.1-4 alkyl, OH, C.sub.1-6 acyloxy, or C.sub.1-3 alkoxy; m and n are each, independently, integers of from 0 to 3; and A is >O, >S >N--R.sub.5, or >CH--R.sub.5 ; R.sub.5 is H, ##STR2## X is H, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, halogen, CF.sub.3, or OCF.sub.3 ; and Y is O, S or NH; and pharmaceutically acceptable salts thereof.

  以下公式的新型氨基烷氧基苯基吡咯烷酮显示抗高血压活性：##STR1##其中R.sub.1为H或OCH.sub.3；R.sub.2和R.sub.3分别独立地为H，C.sub.1-4烷基，OH，C.sub.1-6酰氧基或C.sub.1-3烷氧基；m和n分别独立地为0至3的整数；A为>O，>S，>N--R.sub.5或>CH--R.sub.5；R.sub.5为H，##STR2##X为H，C.sub.1-4烷基，C.sub.1-4烷氧基，卤素，CF.sub.3或OCF.sub.3；Y为O，S或NH；以及其药学上可接受的盐。
• Syntheses of the phosphodiesterase-4 inhibitors [11C]Ro 20-1724, R-, R/S- and S-[11C]rolipram
  作者：Jean N. DaSilva、Celia M. Lourenco、Alan A. Wilson、Sylvain Houle

  DOI：10.1002/jlcr.465

  日期：2001.4

  The high affinity and selective cAMP-specific phosphodiesterase-4 inhibitors Ro 20-1724, R-, R/S- and S-rolipram were labeled with 11C by O-[11C]methylation of their respective phenolic precursors using [11C]methyl iodide. The desmethyl precursor of Ro 20-1724 was prepared by selective dealkylation with iodotrimethylsilane, whereas, dealkylation of racemic rolipram was not selective and yielded several products. Enantiomeric separation of R- and S-desmethylrolipram was carried out by chiral semi-preparative high performance liquid chromatography. The final 11C-labeled products were prepared in high radiochemical purity (>99%), yields (45-75%, decay-corrected) and specific activities [18.5-92.5 GBq/µmol], within 30 min from end-of-bombardment. Copyright © 2001 John Wiley & Sons, Ltd.

  利用[11C]甲基碘对各自的酚类前体进行 O-[11C]甲基化，用 11C 标记了高亲和力和选择性 cAMP 特异性磷酸二酯酶-4 抑制剂 Ro 20-1724、R-、R/S- 和 S-罗利普仑。Ro 20-1724 的脱甲基前体是通过碘三甲基硅烷选择性脱烷基制备的，而外消旋罗利普仑的脱烷基反应则没有选择性，会产生多种产物。采用手性半制备高效液相色谱法对 R-和 S-脱甲基罗利普仑的对映体进行了分离。最终制备出的 11C 标记产品具有较高的放射化学纯度（>99%）、收率（45-75%，衰变校正）和比活度[18.5-92.5 GBq/µmol]，且均在轰炸结束后 30 分钟内完成。Copyright © 2001 John Wiley & Sons, Ltd. All Rights Reserved.