N-(4-fluorophenylacetyl)-1,2-ethanediamine

• 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: N-(4-fluorophenylacetyl)-1,2-ethanediamine
• 英文别名: N-(2-aminoethyl)-2-(4-fluorophenyl)acetamide
• 化学式: C₁₀H₁₃FN₂O
• mdl: MFCD09740632
• 分子量: 196.224
• InChiKey: YPAHAZXFULVNQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-fluorophenylacetyl)-1,2-ethanediamine 在 哌啶 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.5h， 生成 1-benzyl-N-[2-[[2-(4-fluorophenyl)acetyl]amino]ethyl]-4-(thiophene-2-carbonylamino)piperidine-4-carboxamide
  参考文献：
  名称：

  Exploration of N-(2-aminoethyl)piperidine-4-carboxamide as a potential scaffold for development of VEGFR-2, ERK-2 and Abl-1 multikinase inhibitor

  摘要：

  VEGFR, ERK and Abl had been respectively identified as good drug targets, and their crosstalk also had been well elaborated. Multitarget drugs were more advantageous for cancer treatment, however, no inhibitors simultaneously acting on the three proteins were developed due to their structural diversities. Herein, N-(4-((2-(2-(naphthaen-1-yl)acetamido)ethyl)carbamoyl)piperidin-4-yl)-6-(trifluoromethyl)nicotinamide (NEPT, 6a) was discovered as an active scaffold against VEGFR-2, ERK-2 and Abl-1 kinases through the combination of support vector machine, similarity searching and molecular docking. NEPT and its derivatives were synthesized by convenient routine, their in vitro anti-proliferative abilities against human liver cancer cell line HepG2 were preliminarily evaluated. A representative compound 6b showed an IC50 value of 11.3 mu M and induced significant HepG2 cells apoptosis. Besides, these compounds displayed better anti-proliferative abilities against 1(562 cells (a cell line with typical hyperactivity of the above multikinases), for example compound 6b exhibited an IC50 value of 4.5 mu M. Based on hepatotoxicity case reports of Abl inhibitors, cytotoxicity of synthetic compounds against normal liver cell lines (QSG7701 and HL7702) was studied, 6b had a similar toxic effect with positive control imatinib, and most compounds showed less than 35% inhibition activities at 100 mu M. Molecular docking study disclosed interactions of 6b with VEGFR-2, ERK-2 and Abl-1 kinases, respectively. Our data suggested the biological activities of 6b may derived from collaborative effects of VEGFR-2, ERK-2 and Abl-1 inhibition. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.07.026
• 作为产物：
  描述：

  对氟苯乙酰氯 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 N-(4-fluorophenylacetyl)-1,2-ethanediamine
  参考文献：
  名称：

  Synthesis and Cardiac Imaging of ¹⁸F-Ligands Selective for β₁-Adrenoreceptors

  摘要：

  A series of potent and selective beta(1)-adrenoreceptor ligands were identified (IC50 range, 0.04-0.25 nM; beta(1)/beta(2) selectivity range, 65-450-fold), labeled with the PET radioisotope fluorine-18 and evaluated in normal Sprague-Dawley rats. Tissue distribution studies demonstrated uptake of each radiotracers from the blood pool into the myocardium (0.48-0.62% ID/g), lung (0.63-0.97% ID/g), and liver (1.03-1.14% ID/g). Dynamic mu PET imaging confirmed the in vivo dissection studies.

  DOI：

  10.1021/ml1002458

文献信息

• Design, Synthesis, and Biological Evaluation of Novel Non-Piperazine Analogues of 1-[2-(Diphenylmethoxy)ethyl]- and 1-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazines as Dopamine Transporter Inhibitors
  作者：Sung-Woon Choi、David R. Elmaleh、Robert N. Hanson、Alan J. Fischman

  DOI：10.1021/jm990161h

  日期：1999.9.1

  A series of novel diamine, amine-amide, and piperazinone analogues of N-[2-(bisarylmethoxy)ethyl]-N'-(phenylpropyl)piperazines, GBR 12909 and 12935, were synthesized and evaluated as inhibitors of presynaptic monoamine neurotransmitter transporters. The primary objective of the study was to determine the structural requirements for selectivity of ligand binding and potency for neurotransmitter reuptake

  合成了一系列新型的N- [2-（双芳基甲氧基）乙基] -N'-（苯丙基）哌嗪二胺，胺-酰胺和哌嗪酮类似物GBR 12909和12935，并将其评估为突触前单胺神经递质转运蛋白的抑制剂。该研究的主要目的是确定配体结合的选择性和抑制神经递质再摄取的能力的结构要求。通常，目标化合物保留了转运蛋白的亲和力。然而，结构变化对再摄取抑制和转运蛋白选择性产生了显着影响。例如，通过用N，N'-二甲基丙基二胺部分代替GBR结构中的哌嗪环而制备的类似物在去甲肾上腺素（NE）转运蛋白位点（例如4和5）显示出增强的结合和再摄取抑制选择性。其中酰胺氮原子连接到GBR分子的芳烷基部分的同类物显示出中等的亲和力（K（i）= 51-61 nM）和对多巴胺转运蛋白（DAT）位点的选择性。相反，与哌嗪环的任一氮原子（例如25和27）相邻的羰基的引入不能很好地耐受。从制备的化合物中，选择类似物16用于进一步评估。使用该同类物，可卡因以20
• [EN] LIGANDS FOR CARDIAC BETA1 ADRENOCEPTOR FOR IMAGING CONGESTIVE HEART FAILURE<br/>[FR] LIGANDS POUR L'ADRÉNORÉCEPTEUR BÊTA1 CARDIAQUE, DESTINÉS À DES APPLICATIONS D'IMAGERIE DE L'INSUFFISANCE CARDIAQUE CONGESTIVE
  申请人：BRISTOL MYERS SQUIBB PHARMA CO

  公开号：WO2008083054A2

  公开（公告）日：2008-07-10

  [EN] Novel ß₁ adrenoreceptor ligands that find use as imaging agents within nuclear medicine applications (e.g., PET imaging and SPECT imaging) are provided. Methods of imaging, including methods of imaging congestive heart failure, are also provided. The novel compounds may exhibit high affinity and selectivity, minimal metabolism, minimal non-specific binding and have a favorable log P value (< 0). In some instances, ß₁-AR selective ligands are conjugated to an imaging moiety in such a way that it does not impact the antagonist affinity and their use. In other instances, the conjugation may be directly to the antagonist at several sites that will not impact affinity. In further instances, the conjugation may be by means of a linking group, which can be used to alter the pharmacokinetics and clearance of the complex.
  [FR] L'invention concerne de nouveaux ligands d'adrénorécepteurs ß₁ utilisés comme agents d'imagerie dans des applications de médecine nucléaire (en imagerie TEP et en imagerie TEM, par exemple). L'invention concerne également des procédés d'imagerie, y compris des procédés d'imagerie de l'insuffisance cardiaque congestive. Les nouveaux composés peuvent présenter une affinité et une sélectivité élevées, un métabolisme minimal, une fixation non spécifique minimale et posséder une valeur log P favorable (<0). Dans certains cas, des ligands sélectifs des récepteurs adrénergiques bêta 1 sont conjugués avec un groupe fonctionnel d'imagerie de façon à ne pas avoir d'effet sur l'affinité de l'antagoniste et leur utilisation. Dans d'autres cas, les ligands sont conjugués directement avec l'antagoniste au niveau de différents sites qui n'ont aucun effet sur l'affinité. Dans d'autres cas, les ligands peuvent être conjugués à l'aide d'un groupe de liaison, pour modifier la pharmacocinétique et la clairance du complexe.
• Exploration of N-(2-aminoethyl)piperidine-4-carboxamide as a potential scaffold for development of VEGFR-2, ERK-2 and Abl-1 multikinase inhibitor
  作者：Feng Jin、Dan Gao、Qin Wu、Feng Liu、Yuzong Chen、Chunyan Tan、Yuyang Jiang

  DOI：10.1016/j.bmc.2013.07.026

  日期：2013.9

  VEGFR, ERK and Abl had been respectively identified as good drug targets, and their crosstalk also had been well elaborated. Multitarget drugs were more advantageous for cancer treatment, however, no inhibitors simultaneously acting on the three proteins were developed due to their structural diversities. Herein, N-(4-((2-(2-(naphthaen-1-yl)acetamido)ethyl)carbamoyl)piperidin-4-yl)-6-(trifluoromethyl)nicotinamide (NEPT, 6a) was discovered as an active scaffold against VEGFR-2, ERK-2 and Abl-1 kinases through the combination of support vector machine, similarity searching and molecular docking. NEPT and its derivatives were synthesized by convenient routine, their in vitro anti-proliferative abilities against human liver cancer cell line HepG2 were preliminarily evaluated. A representative compound 6b showed an IC50 value of 11.3 mu M and induced significant HepG2 cells apoptosis. Besides, these compounds displayed better anti-proliferative abilities against 1(562 cells (a cell line with typical hyperactivity of the above multikinases), for example compound 6b exhibited an IC50 value of 4.5 mu M. Based on hepatotoxicity case reports of Abl inhibitors, cytotoxicity of synthetic compounds against normal liver cell lines (QSG7701 and HL7702) was studied, 6b had a similar toxic effect with positive control imatinib, and most compounds showed less than 35% inhibition activities at 100 mu M. Molecular docking study disclosed interactions of 6b with VEGFR-2, ERK-2 and Abl-1 kinases, respectively. Our data suggested the biological activities of 6b may derived from collaborative effects of VEGFR-2, ERK-2 and Abl-1 inhibition. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis and Cardiac Imaging of ¹⁸F-Ligands Selective for β₁-Adrenoreceptors
  作者：Heike S. Radeke、Ajay Purohit、Thomas D. Harris、Kelley Hanson、Reinaldo Jones、Carol Hu、Padmaja Yalamanchili、Megan Hayes、Ming Yu、Mary Guaraldi、Mikhail Kagan、Michael Azure、Michael Cdebaca、Simon Robinson、David Casebier

  DOI：10.1021/ml1002458

  日期：2011.9.8

  A series of potent and selective beta(1)-adrenoreceptor ligands were identified (IC50 range, 0.04-0.25 nM; beta(1)/beta(2) selectivity range, 65-450-fold), labeled with the PET radioisotope fluorine-18 and evaluated in normal Sprague-Dawley rats. Tissue distribution studies demonstrated uptake of each radiotracers from the blood pool into the myocardium (0.48-0.62% ID/g), lung (0.63-0.97% ID/g), and liver (1.03-1.14% ID/g). Dynamic mu PET imaging confirmed the in vivo dissection studies.