2-(4-(2-氯乙酰基)哌嗪-1-基)苯甲腈 | 177488-98-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 2-(4-(2-氯乙酰基)哌嗪-1-基)苯甲腈
• 英文名称: 2-(4-(2-chloroacetyl)piperazin-1-yl)benzonitrile
• 英文别名: 2-Chloro-1-[4-(2-cyanophenyl)piperazin-1-yl]ethanone；2-[4-(2-chloroacetyl)piperazin-1-yl]benzonitrile
• CAS: 177488-98-1
• 化学式: C₁₃H₁₄ClN₃O
• 分子量: 263.727
• InChiKey: UPIARRWEWDORGB-UHFFFAOYSA-N

物化性质

• 沸点：
  478.0±45.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  47.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-(2-氯乙酰基)哌嗪-1-基)苯甲腈 在 镍 吡啶 、 ammonium hydroxide 、 氢气 、 potassium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 、 丁酮 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 53.0h， 生成 tert-butyl N-[2-[5-[2-[4-[2-(methanesulfonamidomethyl)phenyl]piperazin-1-yl]-2-oxoethoxy]-1H-indol-3-yl]ethyl]carbamate
  参考文献：
  名称：

  血清素的芳基哌嗪衍生物的合成和血清素能活性：5-HT1D受体的强效激动剂。

  摘要：

  已经制备了一系列新的5-羟色胺的芳基哌嗪衍生物，并将其评估为5-HT1D受体激动剂。在克隆的人5-HT1Dα，5-HT1Dβ和5-HT1A受体上进行的结合实验表明，所有化合物都是5-HT1D受体亚型的强效和选择性配体。功能活性研究（新西兰大白兔大隐静脉的收缩）表明，大多数衍生物表现为完全激动剂。其中，芳基磺酰胺衍生物5q（舒马普坦的pD2 = 8.33，舒马曲坦为5.75）也被认为是抑制与5-HT1Dβ受体偶联的毛喉素介导的环化酶的非常有效的激动剂（EC50 = 0.52nM）。

  DOI：

  10.1021/jm00018a020
• 作为产物：
  描述：

  氯乙酰氯 、 1-(2-苯甲腈)哌嗪 在 calcium carbonate 作用下， 以 丁酮 为溶剂， 生成 2-(4-(2-氯乙酰基)哌嗪-1-基)苯甲腈
  参考文献：
  名称：

  血清素的芳基哌嗪衍生物的合成和血清素能活性：5-HT1D受体的强效激动剂。

  摘要：

  已经制备了一系列新的5-羟色胺的芳基哌嗪衍生物，并将其评估为5-HT1D受体激动剂。在克隆的人5-HT1Dα，5-HT1Dβ和5-HT1A受体上进行的结合实验表明，所有化合物都是5-HT1D受体亚型的强效和选择性配体。功能活性研究（新西兰大白兔大隐静脉的收缩）表明，大多数衍生物表现为完全激动剂。其中，芳基磺酰胺衍生物5q（舒马普坦的pD2 = 8.33，舒马曲坦为5.75）也被认为是抑制与5-HT1Dβ受体偶联的毛喉素介导的环化酶的非常有效的激动剂（EC50 = 0.52nM）。

  DOI：

  10.1021/jm00018a020

文献信息

• 5-HT_1B Receptor Antagonist Properties of Novel Arylpiperazide Derivatives of 1-Naphthylpiperazine
  作者：Catherine Jorand-Lebrun、Petrus J. Pauwels、Christiane Palmier、Chantal Moret、Philippe Chopin、Michel Perez、Marc Marien、Serge Halazy

  DOI：10.1021/jm9703552

  日期：1997.11.1

  A new series of arylpiperazide derivatives of 1-naphthylpiperazine of general formula 4 has been prepared and evaluated as 5-HT1B antagonists. Binding experiments at cloned human 5-HT1A, 5-HT1B, and 5-HT1D receptors show that these derivatives are potent and selective ligands for 5-HT1B/1D subtypes with increased binding selectivity versus the 5-HT1A receptor when compared to 1-naphthylpiperazine (1-NP)

  已经制备了一系列新的通式4的1-萘基哌嗪的芳基哌嗪衍生物，并将其评估为5-HT1B拮抗剂。在克隆的人5-HT1A，5-HT1B和5-HT1D受体上进行的结合实验表明，与1-萘基哌嗪相比，这些衍生物是5-HT1B / 1D亚型的有效和选择性配体，与5-HT1A受体相比具有更高的结合选择性（1-NP）。关于抑制人5-HT1B受体介导的毛喉素刺激的cAMP形成的研究表明，芳基哌嗪取代基的性质调节了这些1-NP衍生物的内在活性。他们之中，2-[[[8-（4-甲基哌嗪-1-基）萘-2-基]氧基] -1-（4-邻甲苯基哌嗪-1-基）乙酮（4a）被鉴定为有效的中性5-HT1B能拮抗豚鼠下丘脑片中5-CT（5-氨基甲酰基色胺）诱导的5-HT释放抑制作用的拮抗剂。此外，在豚鼠口服给药后（ED50 ＝ 0.13mg / kg），发现4a在体内有效拮抗由选择性5-HT1B / 1D激动剂引起的体内低温。
• Piperazides derived from arylpiperazine, processes for their
  申请人：Pierre Fabre Medicament

  公开号：US05789412A1

  公开（公告）日：1998-08-04

  Novel 5HT receptor antagonists of general formula (I) ##STR1## in which Ar.sub.1 and Ar.sub.2 are aromatic residues, X is O, NH, CH.sub.2 O, or CH.sub.2 NH, and R.sub.1 is hydrogen or linear or branched alkyl comprising 1-6 carbon atoms, as well as their salts, hydrates, solvates, and physiologically-acceptable bioprecursors for their therapeutic use, their geometric and optical isomers, and their mixtures in all proportions and in racemic form, methods for the preparation of these novel antagonists, and their use in the treatment of a living animal and pharmaceutical compositions comprising them.

  通式（I）的新型5HT受体拮抗剂 ##STR1## 其中Ar.sub.1和Ar.sub.2是芳香基团，X是O，NH，CH.sub.2 O或CH.sub.2 NH，R.sub.1是氢或由1-6个碳原子组成的线性或支链烷基，以及它们的盐，水合物，溶剂物和生理上可接受的生物前体，它们的几何和光学异构体，以及它们在所有比例和外消旋形式的混合物中的治疗用途，制备这些新型拮抗剂的方法，以及包含它们的制药组合物用于治疗活体动物。
• 3-Nitrotriazole-based piperazides as potent antitrypanosomal agents
  作者：Maria V. Papadopoulou、William D. Bloomer、Howard S. Rosenzweig、Ivan P. O'Shea、Shane R. Wilkinson、Marcel Kaiser

  DOI：10.1016/j.ejmech.2015.08.042

  日期：2015.10

  Novel linear 3-nitro-1H-1,2,4-triazole-based piperazides were synthesized and evaluated as anti-trypanosomal agents. In addition, some bisarylpiperazine-ethanones which were formed as by-products were also screened for antiparasitic activity. Most 3-nitrotriazole-based derivatives were potent and selective against Trypanosoma cruzi parasites, but only one displayed these desired properties against Trypanosoma brucei rhodesiense. Moreover, two 3-nitrotriazole-based chlorophenylpiperazides were moderately and selectively active against Leishmania donovani. Although the bisarylpiperazineethanones were active or moderately active against I cruzi, none of them demonstrated an acceptable selectivity. In general, 3-nitrotriazole-based piperazides were less toxic to host L6 cells than the previously evaluated 3-nitrotriazole-based piperazines and seven of 13 were 1.54- to 31.2-fold more potent antichagasic agents than the reference drug benznidazole. Selected compounds showed good ADMET characteristics. One potent in vitro antichagasic compound (3) was tested in an acute murine model and demonstrated antichagasic activity after a 10-day treatment of 15 mg/kg/day. However, neither compound 3 nor benznidazole showed a statistically significant P value compared to control due to high variability in parasite burden among the untreated animals. Working as prodrugs, 3-nitrotriazole-based piperazides were excellent substrates of trypanosomal type I nitroreductases and constitute a novel class of potentially effective and more affordable antitrypanosomal agents. (C) 2015 Elsevier Masson SAS. All rights reserved.