[4-[(4-Chlorophenyl)methoxy]phenyl]methanamine | 771572-76-0

• 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: [4-[(4-Chlorophenyl)methoxy]phenyl]methanamine
• CAS: 771572-76-0
• 化学式: C₁₄H₁₄ClNO
• 分子量: 247.724
• InChiKey: LEDAXZNXGSKTID-UHFFFAOYSA-N

物化性质

• 沸点：
  386.1±27.0 °C(Predicted)
• 密度：
  1.202±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  [4-[(4-Chlorophenyl)methoxy]phenyl]methanamine 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 0.5h， 以1.74 g的产率得到4-(4'-chlorobenzyloxy)benzylammonium chloride
  参考文献：
  名称：

  Benzyloxybenzylammonium chlorides: Simple amine salts that display anticonvulsant activity

  摘要：

  Several antiepileptic drugs exert their activities by inhibiting Na+ currents. Recent studies demonstrated that compounds containing a biaryl-linked motif (Ar-X-Ar') modulate Na+ currents. We, and others, have reported that compounds with an embedded benzyloxyphenyl unit (ArOCH2Ar', OCH2 = X) exhibit potent anticonvulsant activities. Here, we show that benzyloxybenzylammonium chlorides (+H3NCH2C6H4OCH2 Ar' Cl-) displayed notable activities in animal seizure models. Electrophysiological studies of 4-(2'-trifluoromethoxybenzyloxy)benzylammonium chloride (9) using embryonic cortical neurons demonstrated that 9 promoted both fast and slow inactivation of Na+ channels. These findings suggest that the potent anticonvulsant activities of the earlier compounds were due, in part, to the benzyloxyphenyl motif and provide support for the use of the biaryl-linked pharmacophore in future drug design efforts. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.10.031
• 作为产物：
  描述：

  4-羟基苯甲腈 在 lithium aluminium tetrahydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 32.0h， 生成 [4-[(4-Chlorophenyl)methoxy]phenyl]methanamine
  参考文献：
  名称：

  N-(4-(苄氧基)苄基)-4-氨基喹啉的合成及抗分枝杆菌评价

  摘要：

  结核病仍然是一个影响全球数百万人的全球健康问题。尽管最近在药物开发方面做出了努力，但仍需要新的替代品。在此，合成了一系列 27 N- (4-(苄氧基)苄基)-4-氨基喹啉，并评估了它们抑制结核分枝杆菌的能力H37Rv 菌株。其中两种化合物表现出与一线药物异烟肼相似的最低抑菌浓度 (MIC)。此外，这些命中化合物对芽孢杆菌具有选择性，而 Vero 和 HepG2 细胞的活力没有显着变化。最后，还评估了化学稳定性、渗透性和代谢稳定性。获得的数据表明，针对结核病治疗候选药物的开发，可以优化分子命中。

  DOI：

  10.3390/molecules27082556

文献信息

• SUBSTITUTED PHENYLPROPIONIC ACID DERIVATIVES AS AGONISTS TO HUMAN PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR ALPHA(PPAR)
  申请人：KYORIN PHARMACEUTICAL CO., LTD.

  公开号：EP1184366B1

  公开（公告）日：2005-02-09
• Hitting on the move: Targeting intrinsically disordered protein states of the MDM2-p53 interaction
  作者：Constantinos G. Neochoritis、Jack Atmaj、Aleksandra Twarda-Clapa、Ewa Surmiak、Lukasz Skalniak、Lisa-Maria Köhler、Damian Muszak、Katarzyna Kurpiewska、Justyna Kalinowska-Tłuścik、Barbara Beck、Tad A. Holak、Alexander Dömling

  DOI：10.1016/j.ejmech.2019.111588

  日期：2019.11

  Intrinsically disordered proteins are an emerging class of proteins without a folded structure and currently disorder-based drug targeting remains a challenge. p53 is the principal regulator of cell division and growth whereas MDM2 consists its main negative regulator. The MDM2-p53 recognition is a dynamic and multistage process that amongst other, employs the dissociation of a transient alpha-helical N-terminal "lid" segment of MDM2 from the proximity of the p53-complementary interface. Several small molecule inhibitors have been reported to inhibit the formation of the p53-MDM2 complex with the vast majority mimicking the p53 residues Phe19, Trp23 and Leu26. Recently, we have described the transit from the 3-point to 4-point pharmacophore model stabilizing this intrinsically disordered N-terminus by increasing the binding affinity by a factor of 3. Therefore, we performed a thorough SAR analysis, including chiral separation of key compound which was evaluated by FP and 2D NMR. Finally, p53-specific anti-cancer activity towards p53-wild-type cancer cells was observed for several representative compounds. (C) 2019 Elsevier Masson SAS. All rights reserved.
• Transient Protein States in Designing Inhibitors of the MDM2-p53 Interaction
  作者：Michal Bista、Siglinde Wolf、Kareem Khoury、Kaja Kowalska、Yijun Huang、Ewa Wrona、Marcelino Arciniega、Grzegorz M. Popowicz、Tad A. Holak、Alexander Dömling

  DOI：10.1016/j.str.2013.09.006

  日期：2013.12

  Reactivation of p53 by release of the functional protein from its inhibition by MDM2 provides an efficient, nongenotoxic approach to a wide variety of cancers. We present the cocrystal structures of two complexes of MDM2 with inhibitors based on 6-chloroindole scaffolds. Both molecules bound to a distinct conformational state of MDM2 with nM-μM affinities. In contrast to other structurally characterized antagonists, which mimic three amino acids of p53 (Phe19, Trp23, and Leu26), the compounds induced an additional hydrophobic pocket on the MDM2 surface and unveiled a four-point binding mode. The enlarged interaction interface of the inhibitors resulted in extension of small molecules binding toward the "lid" segment of MDM2 (residues 19-23)--a nascent element that interferes with p53 binding. As supported by protein engineering and molecular dynamics studies, employing these unstable elements of MDM2 provides an efficient and yet unexplored alternative in development of MDM2-p53 association inhibitors.
• Benzyloxybenzylammonium chlorides: Simple amine salts that display anticonvulsant activity
  作者：Hyosung Lee、Alexander S. Gold、Xiao-Fang Yang、Rajesh Khanna、Harold Kohn

  DOI：10.1016/j.bmc.2013.10.031

  日期：2013.12

  Several antiepileptic drugs exert their activities by inhibiting Na+ currents. Recent studies demonstrated that compounds containing a biaryl-linked motif (Ar-X-Ar') modulate Na+ currents. We, and others, have reported that compounds with an embedded benzyloxyphenyl unit (ArOCH2Ar', OCH2 = X) exhibit potent anticonvulsant activities. Here, we show that benzyloxybenzylammonium chlorides (+H3NCH2C6H4OCH2 Ar' Cl-) displayed notable activities in animal seizure models. Electrophysiological studies of 4-(2'-trifluoromethoxybenzyloxy)benzylammonium chloride (9) using embryonic cortical neurons demonstrated that 9 promoted both fast and slow inactivation of Na+ channels. These findings suggest that the potent anticonvulsant activities of the earlier compounds were due, in part, to the benzyloxyphenyl motif and provide support for the use of the biaryl-linked pharmacophore in future drug design efforts. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis and Antimycobacterial Evaluation of N-(4-(Benzyloxy)benzyl)-4-aminoquinolines
  作者：Estevão Silveira Grams、Alessandro Silva Ramos、Mauro Neves Muniz、Raoní S. Rambo、Marcia Alberton Perelló、Nathalia Sperotto、Laura Calle González、Lovaine Silva Duarte、Luiza Galina、Adilio Silva Dadda、Guilherme Arraché Gonçalves、Cristiano Valim Bizarro、Luiz Augusto Basso、Pablo Machado

  DOI：10.3390/molecules27082556

  日期：——

  millions of people around the world. Despite recent efforts in drug development, new alternatives are required. Herein, a series of 27 N-(4-(benzyloxy)benzyl)-4-aminoquinolines were synthesized and evaluated for their ability to inhibit the M. tuberculosis H37Rv strain. Two of these compounds exhibited minimal inhibitory concentrations (MICs) similar to the first-line drug isoniazid. In addition, these

  结核病仍然是一个影响全球数百万人的全球健康问题。尽管最近在药物开发方面做出了努力，但仍需要新的替代品。在此，合成了一系列 27 N- (4-(苄氧基)苄基)-4-氨基喹啉，并评估了它们抑制结核分枝杆菌的能力H37Rv 菌株。其中两种化合物表现出与一线药物异烟肼相似的最低抑菌浓度 (MIC)。此外，这些命中化合物对芽孢杆菌具有选择性，而 Vero 和 HepG2 细胞的活力没有显着变化。最后，还评估了化学稳定性、渗透性和代谢稳定性。获得的数据表明，针对结核病治疗候选药物的开发，可以优化分子命中。