1-phenyl-3-(4-pyrimidin-2-ylpiperazin-1-yl)propan-1-one | 93726-14-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-phenyl-3-(4-pyrimidin-2-ylpiperazin-1-yl)propan-1-one
• 英文别名: 1-Phenyl-3-(4-(pyrimidin-2-yl)piperazin-1-yl)propan-1-one
• CAS: 93726-14-8
• 化学式: C₁₇H₂₀N₄O
• 分子量: 296.372
• InChiKey: PEUZJVQWTJDZOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  49.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-phenyl-3-(4-pyrimidin-2-ylpiperazin-1-yl)propan-1-one 在 sodium tetrahydroborate 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基乙酰胺 为溶剂， 反应 6.0h， 生成 2-{4-[3-Phenyl-3-(4-trifluoromethyl-phenoxy)-propyl]-piperazin-1-yl}-pyrimidine
  参考文献：
  名称：

  新的1-芳基-3-（4-芳基哌嗪-1-基）丙烷衍生物对5-HT1A血清素受体和血清素转运蛋白具有双重作用，是一类新型的抗抑郁药。

  摘要：

  为了寻求新的有效的抗抑郁药，设计，合成了1-芳基-3-（4-芳基哌嗪-1-基）丙烷衍生物，并对5-HT再摄取抑制和5-HT1A受体拮抗作用进行了评估。原则上，这种双重药理学特征应导致5-羟色胺能神经传递的快速而明显的增强，从而导致抑郁症的更有效治疗。该设计基于与抑制5-羟色胺再摄取有关的结构部分，例如γ-苯氧基丙胺，与典型的5-HT1A配体芳基哌嗪偶联。在结合研究中，几种化合物对5-HT转运蛋白和5-HT1A受体表现出亲和力。在两个结合研究中，最初在强迫游泳试验中使用Ki <200 nM的那些化合物测定了抗抑郁样活性。通过测量对小鼠直肠温度的内在作用以及对8-OH-DPAT诱导的体温过低的拮抗作用，进行功能表征。进一步研究了最有效的化合物（12f，23gE，28a和28b）在表达5-HT1A受体的细胞系中拮抗8-OH-DPAT诱导的福斯科林刺激的cAMP形成的抑制作用。此外，还在后天研究中

  DOI：

  10.1021/jm001059j
• 作为产物：
  描述：

  1-(2-嘧啶基)哌嗪 、 3-氯代苯丙酮 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 1-phenyl-3-(4-pyrimidin-2-ylpiperazin-1-yl)propan-1-one
  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。
• New 1-Aryl-3-(4-arylpiperazin-1-yl)propane Derivatives, with Dual Action at 5-HT_1A Serotonin Receptors and Serotonin Transporter, as a New Class of Antidepressants
  作者：Javier Martínez-Esparza、Ana-M. Oficialdegui、Silvia Pérez-Silanes、Begoña Heras、Lara Orús、Juan-A. Palop、Berta Lasheras、Joan Roca、Marisa Mourelle、Ana Bosch、Juan-C. Del Castillo、Rosa Tordera、Joaquín Del Río、Antonio Monge

  DOI：10.1021/jm001059j

  日期：2001.2.1

  In a search toward new and efficient antidepressants, 1-aryl-3-(4-arylpiperazin-1-yl)propane derivatives were designed, synthesized, and evaluated for 5-HT reuptake inhibition and 5-HT1A receptor antagonism. This dual pharmacological profile should lead, in principle, to a rapid and pronounced enhancement in serotoninergic neurotransmission and consequently to a more efficacious treatment of depression

  为了寻求新的有效的抗抑郁药，设计，合成了1-芳基-3-（4-芳基哌嗪-1-基）丙烷衍生物，并对5-HT再摄取抑制和5-HT1A受体拮抗作用进行了评估。原则上，这种双重药理学特征应导致5-羟色胺能神经传递的快速而明显的增强，从而导致抑郁症的更有效治疗。该设计基于与抑制5-羟色胺再摄取有关的结构部分，例如γ-苯氧基丙胺，与典型的5-HT1A配体芳基哌嗪偶联。在结合研究中，几种化合物对5-HT转运蛋白和5-HT1A受体表现出亲和力。在两个结合研究中，最初在强迫游泳试验中使用Ki <200 nM的那些化合物测定了抗抑郁样活性。通过测量对小鼠直肠温度的内在作用以及对8-OH-DPAT诱导的体温过低的拮抗作用，进行功能表征。进一步研究了最有效的化合物（12f，23gE，28a和28b）在表达5-HT1A受体的细胞系中拮抗8-OH-DPAT诱导的福斯科林刺激的cAMP形成的抑制作用。此外，还在后天研究中
• 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.
• Synthesis of benzenepropanamine analogues as non-detergent spermicides with antitrichomonas and anticandida activities
  作者：S.T.V.S. Kiran Kumar、Vishnu Lal Sharma、Manish Kumar、Praveen Kumar Shukla、Pratibha Tiwari、Rajeev Kumar Jain、Jagdamba Prasad Maikhuri、Divya Singh、Gopal Gupta、Man Mohan Singh

  DOI：10.1016/j.bmc.2006.06.003

  日期：2006.10

  Fifteen analogues of benzenepropanamine were synthesized and evaluated for their spermicidal as well as microbicidal activities against Trichomonas vaginalis and Candida spp. Several compounds showed appreciable dual activities. Compound 12 exhibited good spermicidal (MEC = 0.1%) along with substantial anticandidal (MIC = 0.05%) activities, while compounds 3 and 6 showed significant microbicidal activities with moderate spermicidal effect. The SAR of these structures is being discussed here in this communication. It is concluded that suitable structural modifications in this class of compounds at 3-amino position may lead to a potent spermicide with associated microbicidal activity. (c) 2006 Elsevier Ltd. All rights reserved.