1-(chloroacetyl)-4-(3-trifluoromethylphenyl)piperazine | 87358-98-3

• 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-(chloroacetyl)-4-(3-trifluoromethylphenyl)piperazine
• 英文别名: 2-chloro-1-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethanone；2-chloro-1-[4-(3-trifluoromethylphenyl)-1-piperazinyl]ethan-1-one；2-Chloro-1-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]ethanone
• CAS: 87358-98-3
• 化学式: C₁₃H₁₄ClF₃N₂O
• 分子量: 306.715
• InChiKey: ZBHZRRFNIURTET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(chloroacetyl)-4-(3-trifluoromethylphenyl)piperazine 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 0.5h， 以60%的产率得到1-(2-氯乙基)-4-[3-(三氟甲基)苯基]哌嗪二盐酸盐
  参考文献：
  名称：

  2-[(3-Methoxyphenylethyl)phenoxy]-Based ABCB1 Inhibitors: Effect of Different Basic Side-Chains on Their Biological Properties

  摘要：

  Recently, 2-[(3-methoxyphenylethyl)phenoxy]-moiety has been selected for the design and synthesis of new small ABCB1 inhibitors. In the present paper, this moiety has been linked through a spacer of 2-5 carbon atoms to the nitrogen of three different basic nuclei such as: (i) N-4-arylpiperazine, (ii) N-4-methylpiperazine, and (iii) 6,7-dimethoxytctrahydroisoquinoline. The results demonstrated that all the selected basic nuclei were well tolerated and that, globally, the best inhibitory activity for each series was obtained when the spacer between the 2-[(3-methoxyphenylethyl)phenoxy]moiety and the basic nucleus consisted of a four-carbon chain. Among the synthesized compounds, N-4-methylpiperazine- 10C (IC50 = 0.15 W) and tetrahydroisoquinoline-derivatives 11c (IC50 = 0.08 W) with the spacer n = 4 for both series, displayed the best potency to inhibit ABCB1 activity. Moreover, for each compound, the ABCB1 interacting mechanism has been evaluated by three combined biological assays. N-4-methylpiperazine- (10a-d) and tetrahydroisoquinoline-(11a-d) derivatives were Cyclosporin A-like ABCB1 nontransported substrates.

  DOI：

  10.1021/jm800928j
• 作为产物：
  描述：

  氯乙酰氯 、 1-(3-三氟甲基苯基)哌嗪 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以45%的产率得到1-(chloroacetyl)-4-(3-trifluoromethylphenyl)piperazine
  参考文献：
  名称：

  A 2B腺苷受体拮抗剂：新型黄嘌呤衍生物的设计，合成和生物学评估

  摘要：

  甲2BA Dor是低亲和力腺苷受体，通过GS功能介导的cAMP的升高和随后的下游信号传导。该受体与肺炎性疾病如COPD和哮喘有关。在文献中已经报道了几种有效的和选择性的A 2B AdoR拮抗剂，但是大多数化合物的药代动力学特性较差。因此，为了鉴定具有改善的药代动力学特性的新颖，有效和选择性的A 2B AdoR拮抗剂，我们首先探索了更受约束的MRS-1754形式（4）。为了改善代谢稳定性，尝试了几种接头修饰，以取代黄嘌呤头基的C8位和末端苯环之间的酰胺接头以及不同的苯基或其他杂芳基。SAR优化导致鉴定了两种新型A 2B AdoR拮抗剂，即8- {1- [5-Oxo-1-（4-三氟甲基-苯基）-吡咯烷-3-基甲基] -1H-吡唑-4-基} -1 ，3-二丙基-黄嘌呤（31）和8-（1- {2-氧代-2- [4-（3-三氟甲基-苯基）-哌嗪-1-基]-乙基} -1H-吡唑-4-基）-1,3-二丙

  DOI：

  10.1016/j.ejmech.2016.11.007

文献信息

• New N-Substituted-1,2,4-triazole Derivatives of Pyrrolo[3,4-d]pyridazinone with Significant Anti-Inflammatory Activity—Design, Synthesis and Complementary In Vitro, Computational and Spectroscopic Studies
  作者：Łukasz Szczukowski、Edward Krzyżak、Benita Wiatrak、Paulina Jawień、Aleksandra Marciniak、Aleksandra Kotynia、Piotr Świątek

  DOI：10.3390/ijms222011235

  日期：——

  there is still a current need to search for and develop new, safe and effective anti‑inflammatory agents. As a continuation of our previous work, we designed and synthesized a series of 18 novel N‑substituted-1,2,4-triazole-based derivatives of pyrrolo[3,4‑d]pyridazinone 4a-c-9a-c. The target compounds were afforded via a convenient way of synthesis, with good yields. The executed cell viability assay

  鉴于常用的非甾体抗炎药（NSAIDs）的长期使用往往受到其不良反应的限制，目前仍需要寻找和开发新的、安全有效的抗炎药。作为我们之前工作的延续，我们设计并合成了一系列 18 种新型N-取代-1,2,4-三唑基吡咯并[3,4- d ]哒嗪酮4a - c - 9a - c衍生物。目标化合物通过简便的合成方式得到，收率良好。执行的细胞活力测定显示分子4a - 7a , 9a , 4b- 7b , 4c - 7c不发挥细胞毒性作用，有资格进行进一步研究。根据进行的体外试验，化合物4a - 7a、9a、4b、7b、4c显示出显着的环氧合酶-2 (COX-2) 抑制活性和有希望的 COX-2/COX-1 选择性比。这些发现得到了分子对接研究的支持，该研究表明新衍生物在 COX-2 的活性位点中占据一席之地，与美洛昔康非常相似. 此外，在细胞内进行的体外评估中，标题分子增加了与促炎脂多糖预孵育的细胞的活力，并降低了诱导氧化应激中活性氧和氮物质
• A New N-Substituted 1H-Isoindole-1,3(2H)-Dione Derivative—Synthesis, Structure and Affinity for Cyclooxygenase Based on In Vitro Studies and Molecular Docking
  作者：Dominika Szkatuła、Edward Krzyżak、Paulina Stanowska、Magdalena Duda、Benita Wiatrak

  DOI：10.3390/ijms22147678

  日期：——

  Isoindoline-1,3-dione derivatives constitute an important group of medicinal substances. In this study, nine new 1H-isoindole-1,3(2H)-dione derivatives and five potential pharmacophores were obtained in good yield (47.24–92.91%). The structure of the new imides was confirmed by the methods of elemental and spectral analysis: FT–IR, H NMR, and MS. Based on the obtained results of ESI–MS the probable

  Isoindoline-1,3-dione 衍生物构成了一组重要的药用物质。在这项研究中，九个新的 1 H -isoindole-1,3(2 H)-二酮衍生物和五种潜在的药效团以良好的产率 (47.24–92.91%) 获得。新酰亚胺的结构通过元素和光谱分析的方法得到证实：FT-IR、H NMR和MS。基于获得的 ESI-MS 结果，已经提出了分子衰变的可能路径和产生的假分子离子的假设结构。新邻苯二甲酰亚胺的理化性质是根据​​利平斯基法则确定的。生物学特性是根据它们的环氧合酶 (COX) 抑制活性来确定的。三种化合物对 COX-2 的抑制作用更强，三种化合物对 COX-1 的抑制作用比参考化合物美洛昔康更强。由所得结果计算亲和比COX-2/COX-1。两种化合物的值大于美洛昔康的值。所有测试的化合物都显示出氧化或亚硝基应激（ROS 和 RNS）清除活性。在与所有测试化合物一起温育后，细胞核
• Design, synthesis, and evaluation of phenylpiperazine-phenylacetate derivatives as rapid recovery hypnotic agents
  作者：Zhaoyang Qi、Ziying Li、Mo Zhu、Xiaohua Zhang、Guisen Zhang、Tao Zhuang、Yin Chen、Ling Huang

  DOI：10.1016/j.bmcl.2021.128497

  日期：2022.2
• Synthesis of isonicotinic acid N′-arylidene-N-[2-oxo-2-(4-aryl-piperazin-1-yl)-ethyl]-hydrazides as antituberculosis agents
  作者：Neelima Sinha、Sanjay Jain、Ajay Tilekar、Ram Shankar Upadhayaya、Nawal Kishore、Gour Hari Jana、Sudershan K. Arora

  DOI：10.1016/j.bmcl.2005.01.073

  日期：2005.3

  A new series of antituberculosis agents 6-9 was designed, synthesized and evaluated for antituberculosis activity against Mycobacterium tuberculosis H(37)Rv and clinical isolates in an agar dilution method. Compound 9h showed comparable in vitro activity (MIC) to isoniazid against M. tuberculosis H(37)Rv and clinical isolates (sensitive strains) and superior activity against resistant strains of M. tuberculosis. (c) 2005 Elsevier Ltd. All rights reserved.