2-{1-[3-(4-chlorophenyl)-3-oxopropyl]piperidin-4-yl}pyridinium N-oxide | 861966-08-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-{1-[3-(4-chlorophenyl)-3-oxopropyl]piperidin-4-yl}pyridinium N-oxide
• 英文别名: 1-(4-Chlorophenyl)-3-[4-(1-oxidopyridin-1-ium-2-yl)piperidin-1-yl]propan-1-one
• CAS: 861966-08-7
• 化学式: C₁₉H₂₁ClN₂O₂
• 分子量: 344.841
• InChiKey: CLPCTUZGMDLKLB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  45.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-{1-[3-(4-chlorophenyl)-3-oxopropyl]piperidin-4-yl}pyridinium N-oxide 、 甲氧基胺盐酸盐 以 吡啶 为溶剂， 反应 12.0h， 生成 2-{1-[(3E)-3-(4-chlorophenyl)-3-(methoxyimino)propyl]piperidin-4-yl}pyridinium N-oxide 、 2-{1-[(3Z)-3-(4-chlorophenyl)-3-(methoxyimino)propyl]piperidin-4-yl}pyridinium N-oxide
  参考文献：
  名称：

  Oximes and hydrazones that are useful in treating sexual dysfunction

  摘要：

  本发明涉及用于治疗性功能障碍的肟和腙的公式（I）化合物，以及含有用于治疗性功能障碍的公式（I）化合物的组合物。

  公开号：

  US20050176727A1
• 作为产物：
  描述：

  1',2',3',4',5',6'-hexahydro[2,4']bipyridinyl 1-oxide hydrochloride 、 3,4'-二氯苯丙酮 以 甲苯 为溶剂， 生成 2-{1-[3-(4-chlorophenyl)-3-oxopropyl]piperidin-4-yl}pyridinium N-oxide
  参考文献：
  名称：

  1-Aryl-3-(4-pyridine-2-ylpiperazin-1-yl)propan-1-one Oximes as Potent Dopamine D₄ Receptor Agonists for the Treatment of Erectile Dysfunction

  摘要：

  A new series of dopamine D-4 receptor agonists, 1-aryl-3-(4-pyridinepiperazin-1-yl) propanone oximes, was designed through the modification of known dopamine D4 receptor agonist PD 168077. Replacement of the amide group with a methylene-oxime moiety produced compounds with improved stability and efficacy. Structure-activity relationsips (SAR) of the aromatic ring linked to the N-4-piperazine ring confirmed the superiority of 2-pyridine as a core for D4 agonist activity. A two-methylene linker between the oxime group and the N-1-piperazine ring displayed the best profile. New dopamine D4 receptor agonists, exemplified by (E)-1-(4-chlorophenyl)-3-(4-pyridin-2-ylpiperazin-1-yl) propan-1-one O-methyloxime (59a) and (E)-1-(3-chloro- 4-fluorophenyl)-3-(4-pyridin-2-ylpiperazin-1-yl) propan-1-one O-methyloxime (64a), exhibited favorable pharmacokinetic profiles and showed oral bioavailability in rat and dog. Subsequent evaluation of 59a in the rat penile erection model revealed in vivo activity, comparable in efficacy to apomorphine. Our results suggest that the oximes provide a novel structural linker for 4-arylpiperazine-based D4 agonists, possessing leadlike quality and with potential to develop a new class of potent and selective dopamine D4 receptor agonists.

  DOI：

  10.1021/jm060279f

文献信息

• Oximes and hydrazones that are useful in treating sexual dysfunction
  申请人：Kolasa Teodzyj

  公开号：US20050176727A1

  公开（公告）日：2005-08-11

  The present invention relates to oximes and hydrazones of formula (I) for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction.

  本发明涉及用于治疗性功能障碍的肟和腙的公式（I）化合物，以及含有用于治疗性功能障碍的公式（I）化合物的组合物。
• 1-Aryl-3-(4-pyridine-2-ylpiperazin-1-yl)propan-1-one Oximes as Potent Dopamine D₄ Receptor Agonists for the Treatment of Erectile Dysfunction
  作者：Teodozyj Kolasa、Mark A. Matulenko、Ahmed A. Hakeem、Meena V. Patel、Kathleen Mortell、Pramila Bhatia、Rodger Henry、Masaki Nakane、Gin C. Hsieh、Marc A. Terranova、Marie E. Uchic、Loan N. Miller、Renje Chang、Diana L. Donnelly-Roberts、Marian T. Namovic、Peter R. Hollingsworth、Brenda Martino、Odile El Kouhen、Kennan C. Marsh、Jill M. Wetter、Robert B. Moreland、Jorge D. Brioni、Andrew O. Stewart

  DOI：10.1021/jm060279f

  日期：2006.8.1

  A new series of dopamine D-4 receptor agonists, 1-aryl-3-(4-pyridinepiperazin-1-yl) propanone oximes, was designed through the modification of known dopamine D4 receptor agonist PD 168077. Replacement of the amide group with a methylene-oxime moiety produced compounds with improved stability and efficacy. Structure-activity relationsips (SAR) of the aromatic ring linked to the N-4-piperazine ring confirmed the superiority of 2-pyridine as a core for D4 agonist activity. A two-methylene linker between the oxime group and the N-1-piperazine ring displayed the best profile. New dopamine D4 receptor agonists, exemplified by (E)-1-(4-chlorophenyl)-3-(4-pyridin-2-ylpiperazin-1-yl) propan-1-one O-methyloxime (59a) and (E)-1-(3-chloro- 4-fluorophenyl)-3-(4-pyridin-2-ylpiperazin-1-yl) propan-1-one O-methyloxime (64a), exhibited favorable pharmacokinetic profiles and showed oral bioavailability in rat and dog. Subsequent evaluation of 59a in the rat penile erection model revealed in vivo activity, comparable in efficacy to apomorphine. Our results suggest that the oximes provide a novel structural linker for 4-arylpiperazine-based D4 agonists, possessing leadlike quality and with potential to develop a new class of potent and selective dopamine D4 receptor agonists.