哌嗪,1-(3-溴丙基)-4-(3-氯苯基)- | 142944-48-7

• 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: 哌嗪,1-(3-溴丙基)-4-(3-氯苯基)-
• 英文名称: 1-(3-bromopropyl)-4-(3-chlorophenyl)-piperazine
• 英文别名: 1-(3-bromopropyl)-4-(3-chlorophenyl)piperazine；4-(3-bromopropyl)-1-(3-chlorophenyl)piperazine
• CAS: 142944-48-7
• 化学式: C₁₃H₁₈BrClN₂
• 分子量: 317.656
• InChiKey: GKCRZVPPCINNAW-UHFFFAOYSA-N

物化性质

• 沸点：
  407.7±45.0 °C(Predicted)
• 密度：
  1.369±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  哌嗪,1-(3-溴丙基)-4-(3-氯苯基)- 在 ammonium formate 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 5-acetyl-4-amino-2-{3-[4-(3-chlorophenyl)piperazin-1-yl]propyl}-6-methylpyridazin-3(2H)-one
  参考文献：
  名称：

  [(3-Chlorophenyl)piperazinylpropyl]pyridazinones and Analogues as Potent Antinociceptive Agents

  摘要：

  A number of [(3-chlorophenyl)piperazinylpropyl]pyridazinones and the corresponding isoxazolo-pyridazinones, showing the arylpiperazinyl substructure present in very potent antinociceptive agents reported in the literature, were synthesized and tested for their analgesic activity. The investigated compounds showed antinociceptive properties in the mouse hot-plate test (thermal nociceptive stimulus) after systemic administration with an efficacy similar to that exerted by morphine. The increase of the pain threshold induced by the compounds labeled 5a, 7, 8, and 11 was prevented by reserpine, suggesting the involvement of the noradrenergic and/or serotoninergic system in their mechanism of action. Among them, 7 and 11 showed the highest analgesic potency and efficacy together with a good ratio (133 and 200, respectively) of the minimal nontoxic dose (MNTD) to the minimal analgesic dose (MAD). Furthermore, they were also active after icv administration and in the presence of a chemical, painful stimulus (abdominal constriction test).

  DOI：

  10.1021/jm021057u
• 作为产物：
  描述：

  1-氯-3-碘苯 在 potassium phosphate 、 sodium hydride 、 三氟乙酸 、 copper(I) bromide 、 S-1,1'-联-2-萘酚 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 46.0h， 生成 哌嗪,1-(3-溴丙基)-4-(3-氯苯基)-
  参考文献：
  名称：

  1-Boc-哌嗪与芳基碘的高效铜催化交叉偶联及其在曲唑酮合成中的应用

  摘要：

  提出了一种方便实用的策略，以CuBr / 1,1'-bi-2-萘酚为催化剂，K 3 PO 4为碱，将N - Boc保护的哌嗪与芳基碘交叉偶联。该协议在优化条件下以中等到良好的产率提供了N-芳基哌嗪产品。使用市场上可买到的底物也成功地证明了该催化体系在合成曲唑酮中的应用。

  DOI：

  10.1016/j.tetlet.2013.07.104

文献信息

• Arylpiperazinylalkylpyridazinones and Analogues as Potent and Orally Active Antinociceptive Agents:  Synthesis and Studies on Mechanism of Action
  作者：Nicoletta Cesari、Claudio Biancalani、Claudia Vergelli、Vittorio Dal Piaz、Alessia Graziano、Pierfrancesco Biagini、Carla Ghelardini、Nicoletta Galeotti、Maria Paola Giovannoni

  DOI：10.1021/jm060743g

  日期：2006.12.1

  arylpiperazinylalkylpyridazinones structurally related to the previously described lead A (5-[4-(3-chlorophenyl)piperazin-1-yl]-propyl}-3-methyl-7-phenylisossazolo[4,5-d] pyridazin-4-(5H)-one) were synthesized and tested for their analgesic activity. Many of the tested molecules, at the dose of 20 mg kg-1 p.o., showed high antinociceptive activity, in particular, compounds 5a, 11c, 15a, 21 and 22, which were

  在结构上与先前描述的铅A（5-[4-（3-氯苯基）哌嗪-1-基]-丙基} -3-甲基-7-苯基异s唑并[4,5-d]哒嗪-合成4-（5H）-一）并测试其镇痛活性。许多受试分子的剂量为20 mg kg-1 po，表现出很高的抗伤害感受活性，尤其是化合物5a，11c，15a，21和22，能够将腹部收缩的数量减少50多种％在扭体测试中。铅A的药理研究使我们阐明了该化合物的作用机理，表明它通过抑制去甲肾上腺素的再摄取而发挥了镇痛作用。用α2-拮抗剂育亨宾预处理可以完全防止某些最有趣的新分子的抗伤害感受，
• Structure-Activity Relationship Studies of CNS Agents, Part 22: A Search for New Trazodone-Like Antidepressants: Synthesis and Preliminary Receptor Binding Studies
  作者：Jerzy L. Mokrosz、Beata Duszynska、Maria H. Paluchowska、S. Charakchieva-Minol、Maria J. Mokrosz

  DOI：10.1002/ardp.19953280711

  日期：——

  New 1‐phenyl‐ and 1‐(3‐chlorophenyl)piperazines containing a 4‐[3‐(heterocyclic)propyl] fragment were synthesized. It was found that of all the investigated compounds 11b (Ki = 13 ± 2 nM) and 8b (Ki = 38 ± 2 nM) were the most active 5‐HT1A and 5‐HT2A ligands, respectively. Several derivatives (3a, 4a, 8b, 11b, 12b, 13a, and 13b) were selected as good candidates for new, potential antidepressants on

  合成了含有 4-[3-（杂环）丙基] 片段的新 1-苯基-和 1-（3-氯苯基）哌嗪。发现在所有研究的化合物中，11b (Ki = 13 ± 2 nM) 和 8b (Ki = 38 ± 2 nM) 分别是最活跃的 5-HT1A 和 5-HT2A 配体。几种衍生物（3a、4a、8b、11b、12b、13a 和 13b）根据其 5-HT1A/5-HT2A 受体结合特征被选为新型潜在抗抑郁药的良好候选者。
• 1-{8 3-(4-metrachlorophenyl-1-piperazinyl)-propyl{9 -3,4-diethyl-{66 {11 -1,2,4-triazolin-5-one
  申请人：AZIENDE CHIMICHE RIUNITE ANGELINI FRANCESCO A.C.R.

  公开号：US03857845A1

  公开（公告）日：1974-12-31

  The novel compound 1-[;3-(4-metachlorophenyl-1-piperazinyl)-propyl];-3,4-diethyl- DELTA 2-1,2,4-triazolin-5-one having hypotensive and analgesic activity is disclosed.

  本发明揭示了具有降压和镇痛活性的新化合物1-[;3-(4-甲基氯苯基-1-哌嗪基)-丙基];-3,4-二乙基- DELTA 2-1,2,4-三唑啉-5-酮。
• Synthesis of new piperazine–pyridazinone derivatives and their binding affinity toward α1-, α2-adrenergic and 5-HT1A serotoninergic receptors
  作者：Laura Betti、Marco Zanelli、Gino Giannaccini、Fabrizio Manetti、Silvia Schenone、Giovannella Strappaghetti

  DOI：10.1016/j.bmc.2005.12.009

  日期：2006.4

  We report the design and synthesis of a new class of piperazine-pyridazinone analogues. The arylpiperazine moiety, the length of the spacer, and the terminal molecular fragment were varied to evaluate their influence in determining the affinity of the new compounds toward the alpha(1)-adrenergic receptor (alpha(1)-AR), alpha(2)-adrenergic receptor (alpha(2)-AR), and the 5-HT1A serotoninergic receptor (5-HT1AR). Biological data showed that most of the compounds have an alpha(1)-AR affinity in the nanomolar or subnanomolar range, while affinity toward the other two receptors was lower in most cases. However, several of the tested compounds also showed very good (in the nanomolar range) or moderate affinity toward the 5-HT1AR subtype. (c) 2005 Elsevier Ltd. All rights reserved.
• Further Studies on Arylpiperazinyl Alkyl Pyridazinones: Discovery of an Exceptionally Potent, Orally Active, Antinociceptive Agent in Thermally Induced Pain
  作者：Claudio Biancalani、Maria Paola Giovannoni、Stefano Pieretti、Nicoletta Cesari、Alessia Graziano、Claudia Vergelli、Agostino Cilibrizzi、Amalia Di Gianuario、Mariantonella Colucci、Giorgina Mangano、Beatrice Garrone、Lorenzo Polenzani、Vittorio Dal Piaz

  DOI：10.1021/jm900458r

  日期：2009.12.10

  A number of pyridazinone derivatives bearing all arylpiperazinylalkyl chain were synthesized and tested icv in it model of acute nociception induced by thermal stimuli in mice (tail flick). The most interesting and potent compound in this series was 6a, which showed an ED50 = 3.5 mu g, a value about 3-fold higher with respect to morphine by the same route of administration. When administered per os, 6a was 4-fold more potent than morphine in the same test, suggesting it significant bioavailability. The same compound also showed high potency in the hot plate test. The antinociceptive effect of 6a was completely reversed by pretreatment with yohimbine both in the hot plate test and in the tail flick test. This demonstrated the involvement of the adrenergic system, which was confirmed by in vitro radioligand binding studies.