N-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)isonicotinamide | 184951-38-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)isonicotinamide
• 英文别名: N-{2-[4-(2-Methoxy-phenyl)-piperazin-1-yl]-ethyl}-isonicotinamide；N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]pyridine-4-carboxamide
• CAS: 184951-38-0
• 化学式: C₁₉H₂₄N₄O₂
• 分子量: 340.425
• InChiKey: IQYRBWJVVBVMOS-UHFFFAOYSA-N

物化性质

• 沸点：
  586.1±50.0 °C(Predicted)
• 密度：
  1.164±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  57.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(2-甲氧苯基)哌嗪 在 potassium carbonate 、 一水合肼 、 三乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 生成 N-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)isonicotinamide
  参考文献：
  名称：

  Pharmacophore-based design, synthesis, biological evaluation, and 3D-QSAR studies of aryl-piperazines as α1-adrenoceptor antagonists

  摘要：

  Phenyl-piperazines were designed and synthesized based on pharmacophore for uro-selective alpha(1)-adrenoceptor antagonists and 3D chemical database searching. Within this series, three compounds, 2, 3, and 13, showed similar or better alpha(1)-AR antagonistic activity compared with prazosin. The 3D-QSAR study of these compounds may provide useful information for the development of novel aryl-piperazines as uro-selective alpha(1)-adrenoceptor antagonists, which can be used for the treatment of BPH with fewer side effects. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.003

文献信息

• Synthesis, in vitro and in vivo pharmacological evaluation of serotoninergic ligands containing an isonicotinic nucleus
  作者：Ferdinando Fiorino、Antonio Ciano、Elisa Magli、Beatrice Severino、Angela Corvino、Elisa Perissutti、Francesco Frecentese、Paola Di Vaio、Angelo A. Izzo、Raffaele Capasso、Paola Massarelli、Cristina Nencini、Ilaria Rossi、Ewa Kędzierska、Jolanta Orzelska-Gòrka、Anna Bielenica、Vincenzo Santagada、Giuseppe Caliendo

  DOI：10.1016/j.ejmech.2016.01.021

  日期：2016.3

  prepared and their affinity to 5-HT1A, 5-HT2A and 5-HT2C receptors were evaluated. The combination of structural elements (heterocyclic nucleus, alkyl chain and 4-substituted piperazine) known to play critical roles in affinity for serotoninergic receptors and the proper selection of substituents led to compounds with high specificity and affinity towards serotoninergic receptors. In binding studies, several

  制备了与芳基哌嗪部分连接的异烟酰胺衍生物，并评估了它们对5-HT 1A，5-HT 2A和5-HT 2C受体的亲和力。已知在对血清素受体，并导致以高特异性和亲和力向血清素受体的化合物的取代基的合适选择亲和力中起关键作用的结构元件（杂环核，烷基链和4-取代的哌嗪）的组合。在结合研究中，几个分子在5-HT 1A，5-HT 2A和5-HT 2C受体的纳摩尔和亚纳摩尔范围内显示出高亲和力，而对其他相关受体（D 1，D 2，α 1和α 2）。N-（3-（4-（双（4-（4-氟苯基）甲基）哌嗪-1-基）丙基）异烟酰胺（4s），Ki = 0.130 nM，是5-HT 1A受体相比活性最高，选择性最高的衍生物对其他5-羟色胺能，多巴胺能和肾上腺素能受体。相反，化合物4o在亚摩尔范围内显示5-HT 2A亲和力值。此外，选择对5-HT 1A和5-HT 2A受体具有更好的亲和力和选择性结合特性的化合物，以便通过体
• 5-HT_1A- versus D₂-Receptor Selectivity of Flesinoxan and Analogous <i>N</i> ⁴-Substituted <i>N</i> ¹-Arylpiperazines
  作者：Wilma Kuipers、Chris G. Kruse、Ineke van Wijngaarden、Piet J. Standaar、Martin Th. M. Tulp、Nora Veldman、Anthony L. Spek、Adriaan P. IJzerman

  DOI：10.1021/jm960496o

  日期：1997.1.1

  We investigated the structural requirements for high 5-HT1A affinity of the agonist flesinoxan and its selectivity versus D-2 receptors. For this purpose a series of arylpiperazine congeners of flesinoxan were synthesized and evaluated for their ability to displace [H-3]-8-OH-DPAT and [H-3]spiperone from their specific binding sites in rat frontal cortex homogenates and rat striatum, respectively. Variations were made in the N-4-substituent and the arylpiperazine region. Effects of N-4-substitution in the investigated compounds appeared to be quite similar for 5-HT1A- and D-2-receptor affinity. Lipophilicity at a distance of four carbon atoms from the piperazine N-4 atom seems to be the main contributing factor to affinity for both receptors. Our data show that the amide group in the flesinoxan N-4-substituent is unlikely to interact with the 5-HT1A receptor but, instead, acts as a spacer. In contrast to the structure-affinity relationships (SARs) of the N-4-substituents, selectivity for 5-HT1A versus D-2 receptors was gained by the arylpiperazine substitution pattern of flesinoxan. Restriction of flexibility of the N-4-(benzoylamino)ethyl substituent and its effect on 5-HT1A-receptor affinity and activity were also studied. Our data show that in the bioactive conformation, the N-4-[(p-fluorobenzoyl)amino]ethyl substituent is probably directed anti-periplanar relative to the H-N4 atom. These results were used to dock flesinoxan (1) and two of its congeners (27 and 33) into a model of the 5-HT1A receptor that we previously reported. Amino acid residues surrounding the N-4-[(p-fluorobenzoyl)amino]ethyl substituent of flesinoxan and its congeners are also present in D-2 receptors. In contrast, several residues that contact the benzodioxane moiety differ from those in D-2 receptors. These observations from the 3D model agree with the 5-HT1A SAR data and probably account for the selectivity of flesinoxan versus D-2 receptors.