1-(4-chlorophenyl)-4-piperidin-1-yl-1,5-dihydropyrrol-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: 1-(4-chlorophenyl)-4-piperidin-1-yl-1,5-dihydropyrrol-2-one
• 英文别名: 1-(4-chlorophenyl)-3-piperidin-1-yl-2H-pyrrol-5-one
• 化学式: C₁₅H₁₇ClN₂O
• 分子量: 276.766
• InChiKey: LWDCLBDXJCPUNW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  对氯苯胺 在 disodium hydrogenphosphate 、 溶剂黄146 、 sodium iodide 作用下， 以 乙腈 为溶剂， 反应 26.0h， 生成 1-(4-chlorophenyl)-4-piperidin-1-yl-1,5-dihydropyrrol-2-one
  参考文献：
  名称：

  Synthesis, Pharmacology, and Structure−Activity Relationships of Novel Imidazolones and Pyrrolones as Modulators of GABA_A Receptors

  摘要：

  New series of imidazolones and pyrrolones were synthesized. The compounds were tested regarding their anxiolytic properties due to modulation of the GABA(A) receptor response. Several derivatives exhibit considerable pharmacological activity while lacking the typical side effects of benzodiazepine receptor agonists. 1-(4-chlorophenyl)-4-morpholin-1-yl-1,5-dihydro-imidazol-2-one (2) and 1-(4-chlorophenyl)-4-piperidin-1-yl-1,5-dihydro-imidazol-2-one (3) were protective in the pentylenetetrazole test in rats with oral ED50 of 27.4 and 12.8 mg/kg and TD50 (rotarod) of > 500 and 265 mg/kg, respectively. The minimum effective dose in the Vogel conflict test was 3 mg/kg for both compounds. Common structure-activity relationship and comparative molecular field analysis models of the various series of derivatives could be established which are in accordance with a GABAA mediated pharmacological action. The findings fit well into an established pharmacophore model. This model is refined by an additional steric restriction feature.

  DOI：

  10.1021/jm0509400

文献信息

• ANTIKONVULSIV UND ANXIOLYTISCH WIRKENDE 4-AMINO-1-ARYL-1,5-DIHYDRO-PYRROL-2-ONE UND VERFAHREN ZU DEREN DARSTELLUNG
  申请人：Arzneimittelwerk Dresden GmbH

  公开号：EP1212297A1

  公开（公告）日：2002-06-12
• US6500821B1
  申请人：——

  公开号：US6500821B1

  公开（公告）日：2002-12-31
• [DE] ANTIKONVULSIV UND ANXIOLYTISCH WIRKENDE 4-AMINO-1-ARYL-1,5-DIHYDRO-PYRROL-2-ONE UND VERFAHREN ZU DEREN DARSTELLUNG<br/>[EN] 4-AMINO-1-ARYL-1,5-DIHYDRO-PYRROLE-2-ONE WITH ANTI-CONVULSIVE AND ANXIOLYTIC PROPERTIES AND A METHOD FOR PRODUCING THE SAME<br/>[FR] 4-AMINO-1-ARYL-1,5-DIHYDROPYRROLE-2-ONE A EFFET ANTICONVULSIF ET ANXIOLYTIQUE ET SON PROCEDE DE FABRICATION
  申请人：DRESDEN ARZNEIMITTEL

  公开号：WO2001019793A1

  公开（公告）日：2001-03-22

  Die Erfindung betrifft 1,5-Dihydro-pyrrol-2-one der allgemeinen Formel (1), die in 1-Stellung einen Aryl-Rest und in 4-Stellung einen sekundären Aminrest enthalten, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel insbesondere zur Behandlung von Epilepsien verschiedener Formen und zur Behandlung von Angst- und Spannungszuständen.
• Synthesis, Pharmacology, and Structure−Activity Relationships of Novel Imidazolones and Pyrrolones as Modulators of GABA_A Receptors
  作者：Christian Grunwald、Chris Rundfeldt、Hans-Joachim Lankau、Thomas Arnold、Norbert Höfgen、Rita Dost、Ute Egerland、Hans-Jörg Hofmann、Klaus Unverferth

  DOI：10.1021/jm0509400

  日期：2006.3.1

  New series of imidazolones and pyrrolones were synthesized. The compounds were tested regarding their anxiolytic properties due to modulation of the GABA(A) receptor response. Several derivatives exhibit considerable pharmacological activity while lacking the typical side effects of benzodiazepine receptor agonists. 1-(4-chlorophenyl)-4-morpholin-1-yl-1,5-dihydro-imidazol-2-one (2) and 1-(4-chlorophenyl)-4-piperidin-1-yl-1,5-dihydro-imidazol-2-one (3) were protective in the pentylenetetrazole test in rats with oral ED50 of 27.4 and 12.8 mg/kg and TD50 (rotarod) of > 500 and 265 mg/kg, respectively. The minimum effective dose in the Vogel conflict test was 3 mg/kg for both compounds. Common structure-activity relationship and comparative molecular field analysis models of the various series of derivatives could be established which are in accordance with a GABAA mediated pharmacological action. The findings fit well into an established pharmacophore model. This model is refined by an additional steric restriction feature.