1-(3-trifluoromethylphenyl)piperazine hydrochloride | 16015-69-3

• 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-trifluoromethylphenyl)piperazine hydrochloride
• 英文别名: 1-[3-(trifluoromethyl)phenyl]piperazine;hydrochloride
• CAS: 16015-69-3
• 化学式: C₁₁H₁₃F₃N₂*(x)ClH
• 分子量: 266.69
• InChiKey: DGNLGWJZZZOYPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.42
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  19.8
• 氢给体数：
  1
• 氢受体数：
  5

制备方法与用途

制备方法用于合成氟丁洛芬、安拉非宁、洛匹普拉唑、拖西普拉辛、氟哌乙脲等原料药。

用途简介暂无具体内容。

用途同样用于合成氟丁洛芬、安拉非宁、洛匹普拉唑、拖西普拉辛、氟哌乙脲等原料药。

反应信息

• 作为反应物：
  描述：

  1-(3-trifluoromethylphenyl)piperazine hydrochloride 在 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 potassium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 N-(benzimidazol-2-yl)-5-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)pentanamide
  参考文献：
  名称：

  Synthesis and evaluation of arylpiperazine-reverse amides as biased dopamine D3 receptor ligands

  摘要：

  The dopamine D3 receptor (D3R) preferential ligands have been universally adopted as a strategy for the treatment of drug addiction and other neuropsychiatric disorders due to fewer side effects. However, the high sequence homology between D3R and the D2 receptor (D2R) challenges the development of D3R-biased compounds. Herein, we design and synthesize a novel series of reverse amide-piperazine hybrid ligands and evaluate their biological affinities in vitro. Compound 4d was found to be the most potent D3R-selective ligand among these hybrid derivatives. Molecular modeling revealed that extracellular loop 1 (EL1) and loop 2 (EL2) of D3R together likely contribute to D3R selectivity over D2R. In particular, Gly94 in EL1 of D3R may act as a molecular determinant for D3R specificity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.07.072
• 作为产物：
  描述：

  二(2-氯乙基)胺盐酸盐 、 间氨基三氟甲苯 在 potassium carbonate 作用下， 以 正丁醇 为溶剂， 反应 0.5h， 生成 1-(3-trifluoromethylphenyl)piperazine hydrochloride
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 1-Aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as novel microtubule destabilizers

  摘要：

  A series of 1-aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as microtubule destabilizers were designed, synthesised and evaluated for anticancer activity. Based on bioisosterism, we introduced the tetrazole moiety containing the hydrogen-bond acceptors as B-ring of XRP44X analogues. The key intermediates ethyl 1-aryl-1H-tetrazole-5-carboxylates 10 can be simply and efficiently prepared via a microwave-assisted continuous operation process. Among the compounds synthesised, compound 6-31 showed noteworthy potency against SGC-7901, A549 and HeLa cell lines. In mechanism studies, compound 6-31 inhibited tubulin polymerisation and disorganised microtubule in SGC-7901 cells by binding to tubulin. Moreover, compound 6-31 arrested SGC-7901cells in G2/M phase. This study provided a new perspective for development of antitumor agents that target tubulin.

  DOI：

  10.1080/14756366.2020.1759582

文献信息

• Design, synthesis, and evaluation of bitopic arylpiperazine-phthalimides as selective dopamine D₃ receptor agonists
  作者：Yongkai Cao、Ningning Sun、Jiumei Zhang、Zhiguo Liu、Yi-zhe Tang、Zhengzhi Wu、Kyeong-Man Kim、Seung Hoon Cheon

  DOI：10.1039/c8md00237a

  日期：——

  docking demonstrated that the orientation of Leu2.64 and Phe7.39 and the packing at the junction of helices may affect the specificity for D3R over D2R. Functional evaluation revealed that D3R-selective ligand 9i displayed a subpicomolar agonist activity at D3R with a 199-fold increase in potency compared to quinpirole. These results may be useful for the fragment-based design of bitopic compounds as selective

  多巴胺D 3受体（D 3 R）是公认的治疗神经系统疾病和神经精神疾病的治疗靶标。特别地，已经验证了可以消除与多巴胺D 2受体（D 2 R）治疗剂相关的副作用的D 3 R选择性配体。但是，信号通路的高度同源性以及D 2 R和D 3 R之间的序列相似性使D 3 R选择性配体的开发具有挑战性。在本文中，我们基于片段和分子对接启发设计，设计并合成了一系列哌嗪-邻苯二甲酰亚胺双位配体。化合物9i在这些双位配体中，被鉴定为最有选择性的D 3 R配体。与参考化合物1和2相比，其选择性分别提高了9倍和2倍，并且比化合物2的效价高21倍。分子对接表明亮氨酸的取向2.64和Phe 7.39和在螺旋的结填料可能影响d特异性3 R经由d 2 R.功能评价揭示，d 3 R-选择性配体9i中在显示亚皮摩尔激动剂活性d 3与喹吡罗相比，R的效价提高了199倍。这些结果可能对双主题化合物作为选择性D 3 R配体的基于片段的设计有用。
• Design, synthesis and anticancer activity of 5-aryl-4-(4-arylpiperazine-1-carbonyl)-1,2,3-thiadiazoles as microtubule-destabilizing agents
  作者：Chao Wang、Zeyu Wang、Minghuan Gao、Yuelin Li、Yujing Zhang、Kai Bao、Yingliang Wu、Qi Guan、Daiying Zuo、Weige Zhang

  DOI：10.1016/j.bioorg.2020.104199

  日期：2021.1

  Hereby, we report our efforts on discovery and optimization of a new series of 5-aryl-4-(4-arylpiperazine-1-carbonyl)-1,2,3-thiadiazoles as new microtubule-destabilizing agents along our previous study. Guided by docking model analysis, we introduced the 1,2,3-thiadiazole moiety containing the hydrogen-bond acceptors as B-ring of XRP44X analogues. Extensive structure modifications were performed to

  在此，我们报告了我们在之前的研究中发现和优化一系列新的 5-芳基-4-(4-芳基哌嗪-1-羰基)-1,2,3-噻二唑作为新的微管不稳定剂的努力。在对接模型分析的指导下，我们引入了含有氢键受体的 1,2,3-噻二唑部分作为 XRP44X 类似物的 B 环。进行了广泛的结构修改以研究详细的结构和活性关系 (SAR)。一些化合物对三种人类癌细胞系（SGC-7901、A549 和 HeLa）表现出有效的抗增殖活性。化合物5m对三种癌细胞系表现出最高的效力。微管蛋白聚合实验表明化合物5m有效地抑制了微管蛋白聚合，免疫染色分析显示它显着破坏了微管动力学。此外，细胞周期研究表明，化合物5m在 G2/M 期显着阻止细胞周期进程。
• Spiroalkene carboxamide derivatives and their use as chemokine receptor modulators
  申请人：Ares Trading SA

  公开号：EP2508526A1

  公开（公告）日：2012-10-10

  The present invention is directed to compounds of Formula (I) below, which are antagonists to the chemoattractant cytokine receptor 2 (CCR2), and/or 5 (CCR5), pharmaceutical compositions, and methods for use thereof.

  本发明涉及以下式（I）的化合物，这些化合物是趋化因子细胞因子受体2（CCR2）和/或5（CCR5）的拮抗剂，以及其药物组合物和使用方法。
• Exploration of substituted arylpiperazine–tetrazoles as promising dual norepinephrine and dopamine reuptake inhibitors
  作者：Suresh Paudel、Srijan Acharya、Goo Yoon、Kyeong-Man Kim、Seung Hoon Cheon

  DOI：10.1016/j.bmc.2016.09.005

  日期：2016.11

  In the search for potent dual norepinephrine and dopamine reuptake inhibitors, several substituted arylpiperazine–tetrazoles were designed, synthesized and evaluated for their neurotransmitter reuptake inhibitory activities. Various derivatives exhibited selective and strong neurotransmitter reuptake inhibitory activity. In particular, compounds with a three-carbon linker displayed selective and stronger

  在寻找有效的去甲肾上腺素和多巴胺双重再摄取抑制剂时，设计，合成了几种取代的芳基哌嗪-四唑并评估了它们对神经递质再摄取的抑制活性。各种衍生物表现出选择性和强大的神经递质再摄取抑制活性。特别地，具有三碳连接基的化合物比具有二碳和四碳连接基的化合物显示出选择性和更强的效力。有趣的是，六个化合物9b，9c，9d，9o，9q和9u显示出比标准药物安非他酮更有效的活性。所提供的SAR数据和有效的生物活性可以为设计去甲肾上腺素和多巴胺再摄取抑制剂作为治疗几种中枢神经系统疾病的有效治疗剂提供有用的指导。
• HETEROCYCLIC DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
  申请人：Isabel Elise

  公开号：US20110301143A1

  公开（公告）日：2011-12-08

  Heterocyclic compounds of structural formula (I), or a pharmaceutically acceptable salt thereof, wherein W is a R 1 — substituted heteroaryl, R 1 is an heteroaryl ring substituted with an ester or carboxylic acid containing radical, X-T is N—CR 5 R 6 , C═CR 5 or CR 13 —CR 5 R 6 , Y is a bond or —C(O)—, a and b represent an integer selected from 1 to 4, and Ar is an optionally substituted phenyl or naphtyl, are inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD) The heterocyclic compounds are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, atherosclerosis, obesity, diabetes, neurological disease, Metabolic Syndrome, insulin resistance, cancer, liver steatosis, and non-alcoholic steatohepatitis.

  结构式（I）的杂环化合物，或其药学上可接受的盐，其中W是R1-取代的杂芳基，R1是取代有酯基或羧基的杂芳基环，X-T是N—CR5R6，C═CR5或CR13—CR5R6，Y是键或—C(O)—，a和b代表选自1到4的整数，Ar是可选择取代的苯基或萘基，是硬脂酰辅酶A 9-脱饱和酶（SCD）的抑制剂。这些杂环化合物对于预防和治疗与异常脂质合成和代谢有关的疾病非常有用，包括心血管疾病、动脉粥样硬化、肥胖症、糖尿病、神经系统疾病、代谢综合征、胰岛素抵抗、癌症、肝脂肪变性和非酒精性脂肪肝。