1-(3-aminopropyl)-4-(4-chlorophenyl)piperazine | 79322-93-3

• 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: 1-(3-aminopropyl)-4-(4-chlorophenyl)piperazine
• 英文别名: 4-(4-chlorophenyl)piperazinepropanamine；3-[4-(4-chlorophenyl)piperazin-1-yl]propan-1-amine；1-(4-Chlorphenyl)-4-(3-aminopropyl)-piperazin；3-[4-(4-chloro-phenyl)-piperazin-1-yl]-propylamine；1-Amino-3-[4-(4-chlorophenyl)-1-piperazinyl]propane
• CAS: 79322-93-3
• 化学式: C₁₃H₂₀ClN₃
• mdl: MFCD09836712
• 分子量: 253.775
• InChiKey: HMNCZYNKIDVMGW-UHFFFAOYSA-N

物化性质

• 熔点：
  96-98 °C
• 沸点：
  396.8±42.0 °C(Predicted)
• 密度：
  1.140±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.538
• 拓扑面积：
  32.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3-aminopropyl)-4-(4-chlorophenyl)piperazine 在 盐酸 、 N-羟基丁二酰亚胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 为溶剂， 反应 3.5h， 生成 (S)-Pyrrolidine-2-carboxylic acid {3-[4-(4-chloro-phenyl)-piperazin-1-yl]-propyl}-amide; hydrochloride
  参考文献：
  名称：

  Synthesis of New L-Proline Amides with Anticonvulsive Effect

  摘要：

  一系列杂环L-脯氨酸酰胺是通过BOC-L-脯氨酸和杂环胺（主要是取代哌嗪和吗啉）通过羟基琥珀酰亚胺活化酯制备的。4-(4-氟苯甲酰)哌啶与预期的L-脯氨酸4-(4-氟苯甲酰)哌啶酰胺同时生成L-脯氨酸4-(4-(4-(4-氟苯甲酰)哌啶-1-基)苯甲酰)哌啶（7b）。D-脯氨酸N-(3-(4-(3-氯苯基)哌嗪-1-基)丙基)酰胺（2）是从D-脯氨酸开始制备的。这些酰胺通过生物化学和行为药理学方法进行了测试。

  DOI：

  10.1135/cccc19961085
• 作为产物：
  描述：

  1-(4-chlorophenyl)piperazine dihydrochloride 在 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 21.0h， 生成 1-(3-aminopropyl)-4-(4-chlorophenyl)piperazine
  参考文献：
  名称：

  Benzyl Phenylsemicarbazides: A Chemistry-Driven Approach Leading to G Protein-Biased Dopamine D₄ Receptor Agonists with High Subtype Selectivity

  摘要：

  Many subtype-selective dopamine receptor ligands developed for the D-2-D-4 family incorporate a 1-arylpiperazine-derived primary recognition motif, which is connected to a lipophilic moiety occupying an extended binding pocket (EBP) of the receptor via an aliphatic linker of variable lengths. The evaluation of a novel group of dopamine receptor ligands now showed that highly subtype-selective ligands [up to K-i(D-4.4) = 0.25 nM, D-2L/D-4.4 = 320, D-3/D-4.4 = 710 for APH199 (17)] can be obtained by choosing a relatively large and conformationally flexible 1-benzyl-1-phenylsemicarbazide substructure to fill the EBP. The novel chemotype APH199 (17) was found to act as a full agonist at the D-4 receptor showing significant bias toward G protein activation over beta-arrestin recruitment in comparison to quinpirole.

  DOI：

  10.1021/acs.jmedchem.9b01085

文献信息

• Synthesis, Anticonvulsant and Antinociceptive Activity of New Hybrid Compounds: Derivatives of 3-(3-Methylthiophen-2-yl)-pyrrolidine-2,5-dione
  作者：Małgorzata Góra、Anna Czopek、Anna Rapacz、Anna Dziubina、Monika Głuch-Lutwin、Barbara Mordyl、Jolanta Obniska

  DOI：10.3390/ijms21165750

  日期：——

  The present study aimed to design and synthesize a new series of hybrid compounds with pyrrolidine-2,5-dione and thiophene rings in the structure as potential anticonvulsant and antinociceptive agents. For this purpose, we obtained a series of new compounds and evaluated their anticonvulsant activity in animal models of epilepsy (maximal electroshock (MES), psychomotor (6 Hz), and subcutaneous pentylenetetrazole

  本研究旨在设计和合成一系列新的杂化化合物，其结构中具有吡咯烷-2,5-二酮和噻吩环作为潜在的抗惊厥药和抗伤害感受药。为此，我们获得了一系列新化合物，并在癫痫动物模型（最大电击（MES），精神运动（6 Hz）和皮下戊四氮（scPTZ）癫痫发作试验）中评估了它们的抗惊厥活性。为了确定最具活性的抗惊厥化合物（3、4、6、9）的作用机理，评估了它们对电压门控性钠和钙通道以及GABA转运蛋白（GAT）的影响。最有前途的化合物3-（3-甲基噻吩-2-基）-1-（3-吗啉代丙基）吡咯烷-2,5-二酮盐酸盐（4）具有比参考药物更高的ED50值：丙戊酸（VPA）和乙巯乙酰亚胺（ETX）（MES测试中为62.14 mg / kg与252.7 mg / kg（VPA），75.59 mg / kg与130.6 mg / kg（VPA）和221.7 mg / kg（ETX） ）分别在6 Hz测试中）。此外，化合物4
• An Interactive SAR Approach to Discover Novel Hybrid Thieno Probes as Ligands for D2-Like Receptors with Affinities in the Subnanomolar Range
  作者：Mohamed A. O. Abdel-Fattah、Jochen Lehmann、Ashraf H. Abadi

  DOI：10.1002/cbdv.201300204

  日期：2013.12

  ,3-dione derivatives was synthesized to serve as probes for dopaminergic receptors. Among this series, compound 6a showed the highest affinity towards D4 and D3 receptors with Ki values in the low nanomolar range, and D2/D4- and D2/D3-selectivity indices of 72 and 20, respectively. Optimization rounds were adopted and led to the D4-selective ligand thiophene-2-carboxamide 9a with a Ki (D4) value of

  合成了一系列的[（苯基哌嗪基）烷基]-异吲哚-1,3-二酮衍生物，用作多巴胺能受体的探针。在该系列中，化合物6a对D4和D3受体的亲和力最高，Ki值在低纳摩尔范围内，D2 / D4-和D2 / D3-选择性指数分别为72和20。采用最优化回合，得到Ki（D4）值为0.62 nM的D4选择性配体噻吩-2-羧酰胺9a，其丁基类似物10a的Ki（D4）和Ki（D3）值为0.03和0.26 nM。对接实验揭示了独特的D4残基Arg186在操纵配体D4亚型受体选择性中的重要性。
• Synthesis, anticonvulsant activity and 5-HT1A/5-HT7 receptors affinity of 1-[(4-arylpiperazin-1-yl)-propyl]-succinimides
  作者：Jolanta Obniska、Iwona Chlebek、Krzysztof Kamiński、Andrzej J. Bojarski、Grzegorz Satała

  DOI：10.1016/s1734-1140(12)70772-7

  日期：2012.3

  through which epilepsy can be effectively controlled. Therefore, in the present studies, a series of sixteen new 1-[(4-arylpiperazin-1-yl)-propyl]-3-methyl-3-phenyl- and 3-ethyl-3-methylpyrrolidine-2,5-dione derivatives as potential anticonvulsant agents was synthesized. METHODS Anticonvulsant properties were evaluated in the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and psychomotor

  背景技术癫痫病是最普遍的神经系统疾病，在全世界影响约5000万人。即使癫痫研究取得了重大进展，标准药物治疗仍不足以控制约30％的癫痫发作。因此，人们一直在努力研究可以有效控制癫痫病的新化学药物和机制。因此，在本研究中，一系列十六个新的1-[（（4-芳基哌嗪-1-基）-丙基] -3-甲基-3-苯基-和3-乙基-3-甲基吡咯烷-2,5-二酮合成了作为潜在抗惊厥药的衍生物。方法在小鼠腹膜内注射后，通过最大电击（MES），皮下戊四氮（scPTZ）和精神运动性惊厥（6-Hz）测试评估抗惊厥特性。急性神经毒性在运动障碍转子筛中测定。结果该化合物在小鼠模型中以30 mg / kg（4、8、16）或100 mg / kg（6、9、10、12、17、18）的剂量显示活性。在大鼠中po给药后也评估了四个或四个（8、10、16、17）。在该系列中，活性最高的是1- 3- [4-（3-氯苯基）-哌嗪-1-基]-丙基}
• Quinoline- and isoquinoline-sulfonamide derivatives of LCAP as potent CNS multi-receptor—5-HT1A/5-HT2A/5-HT7 and D2/D3/D4—agents: The synthesis and pharmacological evaluation
  作者：Paweł Zajdel、Krzysztof Marciniec、Andrzej Maślankiewicz、Grzegorz Satała、Beata Duszyńska、Andrzej J. Bojarski、Anna Partyka、Magdalena Jastrzębska-Więsek、Dagmara Wróbel、Anna Wesołowska、Maciej Pawłowski

  DOI：10.1016/j.bmc.2011.12.039

  日期：2012.2

  Two series of arylpiperazinyl-alkyl quinoline-, isoquinoline-, naphthalene-sulfonamides with flexible (13-26) and semi-rigid (33-36) alkylene spacer were synthesized and evaluated for 5-HT1A, 5-HT2A, 5-HT6, 5-HT7 and selected compounds for D-2, D-3, D-4 receptors. The compounds with a mixed 5-HT and D receptors profile 16 (N-4-[4-(3-chlorophenyl)-piperazin-1-yl]-butyl}-3-quinolinesulfonamide) and 36 (4-(4-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-ethyl}-piperidine-1-sulfonyl)-isoquinoline), displaying antagonistic activity at 5-HT7, 5-HT2A, D2 postsynaptic sites, produced antidepressant-like effects in the forced swim test in mice and showed significant anxiolytic activity in the plus-maze test in rats. The lead compound 36, a multi-receptor 5-HT2A/5-HT7/D-2/D-3/D-4 agent, also displayed significant antipsychotic properties in the MK-801-induced hyperlocomotor activity in mice. (C) 2011 Elsevier Ltd. All rights reserved.
• Desai; Samant, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2000, vol. 39, # 6, p. 455 - 457
  作者：Desai、Samant

  DOI：——

  日期：——