3-chloromethyl-N,N-diethyl-4-phenylquinoline-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3-chloromethyl-N,N-diethyl-4-phenylquinoline-2-carboxamide
• 英文别名: 3-(chloromethyl)-N,N-diethyl-4-phenylquinoline-2-carboxamide
• 化学式: C₂₁H₂₁ClN₂O
• 分子量: 352.864
• InChiKey: OQFASRYWJAOITQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-chloromethyl-N,N-diethyl-4-phenylquinoline-2-carboxamide 在 potassium [¹⁸F]fluoride 、 potassium carbonate 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 作用下， 以 乙腈 为溶剂， 反应 0.2h， 生成 N,N-diethyl-3-((18F)fluoranylmethyl)-4-phenylquinoline-2-carboxamide
  参考文献：
  名称：

  A novel ¹⁸F-labelled high affinity agent for PET imaging of the translocator protein

  摘要：

  一种新型的¹⁸F标记的喹啉-2-甲酰胺已被确定为一种新型的PET成像剂，用于转运蛋白。

  DOI：

  10.1039/c5sc01647a
• 作为产物：
  描述：

  9-phenylfuro[3,4-b]quinolin-1(3H)-one 在 lithium aluminium tetrahydride 、 氯化亚砜 、 三甲基铝 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 61.0h， 生成 3-chloromethyl-N,N-diethyl-4-phenylquinoline-2-carboxamide
  参考文献：
  名称：

  A novel ¹⁸F-labelled high affinity agent for PET imaging of the translocator protein

  摘要：

  一种新型的¹⁸F标记的喹啉-2-甲酰胺已被确定为一种新型的PET成像剂，用于转运蛋白。

  DOI：

  10.1039/c5sc01647a

文献信息

• Mapping and Fitting the Peripheral Benzodiazepine Receptor Binding Site by Carboxamide Derivatives. Comparison of Different Approaches to Quantitative Ligand−Receptor Interaction Modeling
  作者：Maurizio Anzini、Andrea Cappelli、Salvatore Vomero、Michele Seeber、Maria Cristina Menziani、Thierry Langer、Bertram Hagen、Cristina Manzoni、Jean-Jacques Bourguignon

  DOI：10.1021/jm0009742

  日期：2001.4.1

  electrostatic contribution to the interaction (CoMFA, CoMSIA, and surface approaches) perform well, but they do not improve the quantitative models. Moreover, useful hints for the identification of the antagonist binding site in the three-dimensional modeling of the receptor (direct approach) were provided by the receptor hypothesis derived by the pharmacophoric approach. The ligand-receptor complexes

  研究与1-（2-氯苯基）-N-甲基-N-（1-甲基丙基）-3-异喹啉羧酰胺相关的外围苯并二氮杂receptor受体（PBR）配体结合位点的合成计算方法（PK11195，1）它们的受体中的内切酶（Cappelli等人，J.Med.Chem.1997，40，2910-2921）已被扩展。设计了一系列具有不同取代的平面芳族或杂芳族体系的羧酰胺衍生物，其目的是获得有关羰基和芳族部分与PBR结合位点相互作用的拓扑学要求的进一步信息。这些化合物中的大多数的合成涉及适当内酯的Weinreb酰胺化作为关键步骤。在新合成的化合物中，最有效的化合物是 图1显示了与1所示相似的纳摩尔PBR亲和力，并且在喹啉核的3位上存在碱性N-乙基-N-苄基氨基甲基。因此，可以认为它是一类新的1类水溶性衍生物的第一个例子。几种计算方法被用来提供分离的配体的描述子（间接方法），这些配体能够合理化扩大序列的结合亲和力的变化。化合物
• Kinetic modelling and quantification bias in small animal PET studies with [18F]AB5186, a novel 18 kDa translocator protein radiotracer
  作者：Mark G. MacAskill、Tashfeen Walton、Lewis Williams、Timaeus E. F. Morgan、Carlos José Alcaide-Corral、Marc R. Dweck、Gillian A. Gray、David E. Newby、Christophe Lucatelli、Andrew Sutherland、Sally L. Pimlott、Adriana A. S. Tavares

  DOI：10.1371/journal.pone.0217515

  日期：——

  Introduction Positron Emission Tomography (PET) imaging with selective 18 kDa translocator protein (TSPO) radiotracers has contributed to our understanding on the role of inflammation in disease development and progression. With an increasing number of rodent models of human disease and expansion of the preclinical PET imaging base worldwide, accurate quantification of longitudinal rodent TSPO PET datasets is necessary. This is particularly relevant as TSPO PET quantification relies on invasive blood sampling due to lack of a suitable tissue reference region. Here we investigate the kinetics and quantification bias of a novel TSPO radiotracer [18F]AB5186 in rats using automatic, manual and image derived input functions. Methods [18F]AB5186 was administered intravenously and dynamic PET imaging was acquired over 2 hours. Arterial blood was collected manually to derive a population based input function or using an automatic blood sampler to derive a plasma input function. Manually sampled blood was also used to analyze the [18F]AB5186 radiometabolite profile in plasma and applied to all groups as a population based dataset. Kinetic models were used to estimate distribution volumes (VT) and [18F]AB5186 outcome measure bias was determined. Results [18F]AB5186 distribution in rats was consistent with TSPO expression and at 2 h post-injection 50% of parent compound was still present in plasma. Population based manual sampling methods and image derived input function (IDIF) underestimated VT by ~50% and 88% compared with automatic blood sampling, respectively. The VT variability was lower when using IDIF versus arterial blood sampling methods and analysis of the Bland-Altman plots showed a good agreement between methods of analysis. Conclusion Quantification of TSPO PET rodent data using image-derived methods, which are more amenable for longitudinal scanning of small animals, yields outcome measures with reduced variability and good agreement, albeit biased, compared with invasive blood sampling methods.

  引言 选择性18 kDa转运蛋白（TSPO）放射性示踪剂正电子发射断层扫描（PET）成像有助于我们了解炎症在疾病发展和进展中的作用。随着人类疾病啮齿动物模型数量的增加以及全球临床前PET成像基础的扩大，对啮齿动物纵向TSPO PET数据集进行精确量化是必要的。由于缺乏合适的组织参考区域，TSPO PET量化依赖于侵入性血液采样，因此这一点尤为重要。本文使用自动、手动和图像衍生输入函数，研究了新型TSPO放射性示踪剂[18F]AB5186在大鼠体内的动力学和量化偏差。方法 [18F]AB5186静脉注射，并在2小时内进行动态PET成像。手动采集动脉血以获得基于人群的输入函数，或使用自动采血器获得血浆输入函数。手动采血还用于分析血浆中[18F]
• New iodinated quinoline-2-carboxamides for SPECT imaging of the translocator protein
  作者：Louise Stevenson、Adriana A.S. Tavares、Aurélie Brunet、Fiona I. McGonagle、Deborah Dewar、Sally L. Pimlott、Andrew Sutherland

  DOI：10.1016/j.bmcl.2009.12.061

  日期：2010.2

  With the aim of developing new SPECT imaging agents for the translocator protein (TSPO), a small library of iodinated quinoline-2-carboxamides have been prepared and tested for binding affinity with TSPO. N,N-Diethyl-3-iodomethyl-4-phenylquinoline-2-carboxamide was found to have excellent affinity (K-i 12.0 nM), comparable to that of the widely used TSPO imaging agent PK11195. (c) 2009 Elsevier Ltd. All rights reserved.