tert-butyl 4-(3,5-dichlorobenzoyl)piperazine-1-carboxylate | 501908-50-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl 4-(3,5-dichlorobenzoyl)piperazine-1-carboxylate
• CAS: 501908-50-5
• 化学式: C₁₆H₂₀Cl₂N₂O₃
• 分子量: 359.252
• InChiKey: PVTUZLMIUBPHAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(3,5-dichlorobenzoyl)piperazine-1-carboxylate 在 三乙酰氧基硼氢化钠 、 potassium carbonate 、 一水合肼 、 三氟乙酸 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 39.0h， 生成 (3,5-dichlorophenyl)(4-(2-((3-isopropylisoxazol-5-ylmethyl)amino)ethyl)piperazin-1-yl)methanone
  参考文献：
  名称：

  4-Aminoethylpiperazinyl aryl ketones with 5-HT1A/5-HT7 selectivity

  摘要：

  The well-known 5-HT1A/5-HT7 selectivity issue was tackled by a new series of 4-aminoethylpiperazinyl aryl ketones (1a-1l) specifically designed to distinguish the two hydrophobic sites centered at the anchoring salt bridge. The 4-aminoethylpiperazinyl aryl ketones showed a wide spectrum of activity and selectivity for the 5-HT receptors depending on the type of the hydrophobic groups attached at the aryl piperazinyl ketone scaffold. Docking study of the most active compounds against 5-HT7R and 5-HT1AR revealed that both receptors have two hydrophobic pockets around the anchoring salt bridge. These two binding sites are perpendicular to each other in 5-HT7R but parallel in 5-HT1AR, and this observation is well matched with the previous report which claimed that 5-HT7R affinity arises from bent conformation of the bound ligand whereas an extended one is best suited for 5-HT1AR selectivity. Also, as these pockets have different size and shape, inhibitory activity as well as selectivity of the 4-aminoethylpiperazinyl aryl ketones against 5-HT7R and 5-HT1AR seemed to be determined by combination of two hydrophobic substituents attached at both ends of the title compounds. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.005
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 吡啶 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 40.0h， 生成 tert-butyl 4-(3,5-dichlorobenzoyl)piperazine-1-carboxylate
  参考文献：
  名称：

  哌嗪基嘧啶类似物的设计、合成和先导优化，作为针对基孔肯雅病毒病毒加帽机制的有效小分子

  摘要：

  基孔肯雅病毒 (CHIKV) 在全球范围内重新出现、与之相关的高发病率以及可用疫苗或抗病毒治疗的缺乏，使得开发一种有效的 CHIKV 抑制剂非常迫切。因此，基于之前报道的 CHVB 化合物1b进行了广泛的先导化合物优化，并对报道的合成路线进行了优化——在显着更短的合成和后处理时间内提高了总产率。设计、合成了数百种类似物，并研究了它们的抗病毒活性、生理化学和毒理学特征。进行了广泛的构效关系研究 (SAR)，主要关注支架变化的组合，并揭示了有效抗 CHIKV 抑制的关键化学特征。此外，对这些化合物进行了彻底的 ADMET 研究：筛选了这些化合物的水溶性、亲脂性、在 CaCo-2 细胞中的毒性以及可能的 hERG 通道相互作用。此外，还评估了 55 种类似物在人肝微粒体 (HLM) 中的代谢稳定性，从而开展了结构-代谢关系研究 (SMR)。这些化合物表现出优异的安全性、良好的理化特性和所需的代谢稳定性。交叉耐药性研究证实病毒加帽机制

  DOI：

  10.1016/j.ejmech.2023.116010

文献信息

• Novel 2-phenyl-4H-chromen derivatives: synthesis and anti-inflammatory activity evaluation <i>in vitro</i> and <i>in vivo</i>
  作者：Yun Xiao、Yaoyao Yan、Juncheng Du、Xiaoxiao Feng、Famin Zhang、Xu Han、Yong Hu、Xinhua Liu

  DOI：10.1080/14756366.2022.2124983

  日期：2022.12.31

  Abstract It is significant to design, synthesise and optimise flavonoid derivatives with better anti-inflammatory activity. This study aims to design and synthesise a series of novel 2-phenyl-4H-chromen-4-one compounds with anti-inflammatory; among them, compound 8 was discovered as the best one. And then, the effects of compound 8 on the TLR4/MAPK signalling pathway was carried out in vivo, the results

  摘要 设计、合成和优化具有更好抗炎活性的黄酮衍生物具有重要意义。本研究旨在设计合成一系列具有抗炎作用的新型2-苯基-4H-chromen-4-one化合物；其中，化合物8被认为是最好的化合物。然后，在体内研究了化合物8对TLR4/MAPK信号通路的影响，结果表明化合物8可以下调NO、IL-6和TNF-α的表达，并通过抑制LPS诱导的炎症反应来抑制LPS诱导的炎症反应。 TLR4/MAPK 通路。此外，化合物8通过 LPS 诱导的体内炎症疾病小鼠模型减轻炎症. 结果表明，化合物8通过调节 TLR4/MAPK 途径具有抗炎症的潜力，可以进一步评估药物开发。
• 4-Aminoethylpiperazinyl aryl ketones with 5-HT1A/5-HT7 selectivity
  作者：Mi Kyoung Kim、Hyo Seon Lee、Sora Kim、Suh Young Cho、Bryan L. Roth、Youhoon Chong、Hyunah Choo

  DOI：10.1016/j.bmc.2011.11.005

  日期：2012.1

  The well-known 5-HT1A/5-HT7 selectivity issue was tackled by a new series of 4-aminoethylpiperazinyl aryl ketones (1a-1l) specifically designed to distinguish the two hydrophobic sites centered at the anchoring salt bridge. The 4-aminoethylpiperazinyl aryl ketones showed a wide spectrum of activity and selectivity for the 5-HT receptors depending on the type of the hydrophobic groups attached at the aryl piperazinyl ketone scaffold. Docking study of the most active compounds against 5-HT7R and 5-HT1AR revealed that both receptors have two hydrophobic pockets around the anchoring salt bridge. These two binding sites are perpendicular to each other in 5-HT7R but parallel in 5-HT1AR, and this observation is well matched with the previous report which claimed that 5-HT7R affinity arises from bent conformation of the bound ligand whereas an extended one is best suited for 5-HT1AR selectivity. Also, as these pockets have different size and shape, inhibitory activity as well as selectivity of the 4-aminoethylpiperazinyl aryl ketones against 5-HT7R and 5-HT1AR seemed to be determined by combination of two hydrophobic substituents attached at both ends of the title compounds. (C) 2011 Elsevier Ltd. All rights reserved.
• Design, synthesis, and lead optimization of piperazinyl-pyrimidine analogues as potent small molecules targeting the viral capping machinery of Chikungunya virus
  作者：Verena Battisti、Julia Moesslacher、Rana Abdelnabi、Pieter Leyssen、Ana Lucia Rosales Rosas、Lana Langendries、Mohammed Aufy、Christian Studenik、Jadel M. Kratz、Judith M. Rollinger、Gerhard Puerstinger、Johan Neyts、Leen Delang、Ernst Urban、Thierry Langer

  DOI：10.1016/j.ejmech.2023.116010

  日期：2024.1

  structure-metabolism relationship study (SMR). The compounds showed an excellent safety profile, favourable physicochemical characteristics, and the required metabolic stability. A cross-resistance study confirmed the viral capping machinery (nsP1) to be the viral target of these compounds. This study identified 31b and 34 as potent, safe, and stable lead compounds for further development as selective

  基孔肯雅病毒 (CHIKV) 在全球范围内重新出现、与之相关的高发病率以及可用疫苗或抗病毒治疗的缺乏，使得开发一种有效的 CHIKV 抑制剂非常迫切。因此，基于之前报道的 CHVB 化合物1b进行了广泛的先导化合物优化，并对报道的合成路线进行了优化——在显着更短的合成和后处理时间内提高了总产率。设计、合成了数百种类似物，并研究了它们的抗病毒活性、生理化学和毒理学特征。进行了广泛的构效关系研究 (SAR)，主要关注支架变化的组合，并揭示了有效抗 CHIKV 抑制的关键化学特征。此外，对这些化合物进行了彻底的 ADMET 研究：筛选了这些化合物的水溶性、亲脂性、在 CaCo-2 细胞中的毒性以及可能的 hERG 通道相互作用。此外，还评估了 55 种类似物在人肝微粒体 (HLM) 中的代谢稳定性，从而开展了结构-代谢关系研究 (SMR)。这些化合物表现出优异的安全性、良好的理化特性和所需的代谢稳定性。交叉耐药性研究证实病毒加帽机制