N-[4-[(4-氟苯基)乙酰基]-2-吡啶基]乙酰胺 | 452056-81-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: N-[4-[(4-氟苯基)乙酰基]-2-吡啶基]乙酰胺
• 中文别名: N-{4-[2-(4-氟苯基)-乙酰基]-吡啶-2-基}-乙酰胺
• 英文名称: N-(4-(2-(4-fluorophenyl)acetyl)pyridin-2-yl)acetamide
• 英文别名: N-{4-[2-(4-fluorophenyl)acetyl]pyridin-2-yl}acetamide；2-(4-fluorophenyl)-1-(2-acetamido-4-pyridyl)ethanone；N-[4-[2-(4-fluorophenyl)acetyl]pyridin-2-yl]acetamide
• CAS: 452056-81-4
• 化学式: C₁₅H₁₃FN₂O₂
• 分子量: 272.279
• InChiKey: IBIRZTPHSLNZFC-UHFFFAOYSA-N

物化性质

• 熔点：
  140.9℃
• 沸点：
  515.0±45.0 °C(Predicted)
• 密度：
  1.283±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  59.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[4-[(4-氟苯基)乙酰基]-2-吡啶基]乙酰胺 在 盐酸 、 2,2,4,4-四甲基-1,3-环丁烷二硫酮 、 sodium methylate 、 potassium carbonate 、 亚硝酸异戊酯 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 44.0h， 生成 4-(4-(4-fluorophenyl)-1-methyl-2-(methylthio)-1H-imidazol-5-yl)pyridin-2-amine
  参考文献：
  名称：

  Identification of Regioisomers in a Series of N-Substituted Pyridin-4-yl Imidazole Derivatives by Regiospecific Synthesis, GC/MS, and ¹H NMR

  摘要：

  The regiospecific synthesis of 2a (Scheme 3), a novel and potent pyridinyl imidazole inhibitor of p38 MAP (mitogen-activated protein) kinase, and the regioselective preparation of its regioisomer 2b (Scheme 4) are described. Chromatographic and spectroscopic data are presented, which in this class of compounds allow the unambiguous identification of regioisomers prepared by a nonregiospecific synthetic strategy. Biological data demonstrating the importance of the correct regiochemistry for inhibition of p38 are given.

  DOI：

  10.1021/jo026619w
• 作为产物：
  描述：

  2-(乙酰氨基)-4-甲基吡啶 在 potassium permanganate 、 氢溴酸 、 N,N'-羰基二咪唑 作用下， 以 水 为溶剂， 生成 N-[4-[(4-氟苯基)乙酰基]-2-吡啶基]乙酰胺
  参考文献：
  名称：

  Discovery of N-{4-[5-(4-Fluorophenyl)-3-methyl-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-acetamide (CBS-3595), a Dual p38α MAPK/PDE-4 Inhibitor with Activity against TNFα-Related Diseases

  摘要：

  The anti-inflammatory potential of p38 mitogen-activated protein kinase (MAPK) inhibitors was coincidentally expanded to a dual inhibition of p38 alpha MAPK and phosphodiesterase 4 (PDE4), and the potential benefits arising from the blockage of both inflammation-related enzymes were thoroughly investigated. The most promising compound, CBS-3595 (1), was successively evaluated in in vitro experiments as well as in ex vivo and in vivo preclinical studies after administration of 1 to rodents, dogs, and monkeys. The resulting data clearly indicated a potent suppression of tumor necrosis factor alpha release. For reconfirming the findings of the animal studies when administering 1 to healthy human volunteers, a phase I clinical trial was conducted. Apart from further information regarding the pharmacokinetic and pharmacodynamic characteristics of 1, it was demonstrated that dual inhibition of p38 alpha MAPK and PDE4 is able to synergistically attenuate the excessive anti-inflammatory response.

  DOI：

  10.1021/acs.jmedchem.6b01647
• 作为试剂：
  描述：

  乙酸酐 、 1-(2-氨基吡啶-4-基)-2-(4-氟苯基)-乙酮 在 4-二甲氨基吡啶 乙酸酐 、 N-[4-[(4-氟苯基)乙酰基]-2-吡啶基]乙酰胺 、 四磷十氧化物 作用下， 反应 5.0h， 生成 N-[4-[(4-氟苯基)乙酰基]-2-吡啶基]乙酰胺
  参考文献：
  名称：

  2-thio-substituted imidazole derivatives and the use thereof in the pharmaceutical industry

  摘要：

  本发明涉及公式I中的2-硫代取代咪唑衍生物，其中基团R1、R2、R3和R4如描述中所定义。根据本发明的化合物具有免疫调节和/或细胞因子释放抑制作用，因此适用于治疗与免疫系统紊乱相关的疾病。

  公开号：

  US07253191B2

文献信息

• Pyridinylimidazoles as GSK3β Inhibitors: The Impact of Tautomerism on Compound Activity via Water Networks
  作者：Fabian Heider、Tatu Pantsar、Mark Kudolo、Francesco Ansideri、Angela De Simone、Letizia Pruccoli、Taiane Schneider、Marcia Inês Goettert、Andrea Tarozzi、Vincenza Andrisano、Stefan A. Laufer、Pierre Koch

  DOI：10.1021/acsmedchemlett.9b00177

  日期：2019.10.10

  GSK3β/p38α mitogen-activated protein kinase inhibitors and identified N-(4-(4-(4-fluorophenyl)-2-methyl-1H-imidazol-5-yl)pyridin-2-yl)cyclopropanecarboxamide (1) as a potent dual inhibitor of both target kinases. In this study, we aimed to design selective GSK3β inhibitors based on our pyridinylimidazole scaffold. Our efforts resulted in several novel and potent GSK3β inhibitors with IC50 values in the

  糖原合酶激酶3β（GSK3β）参与许多病理状况，代表了有吸引力的药物靶标。我们先前曾报道过两种GSK3β/p38α丝裂原活化蛋白激酶抑制剂，并鉴定出N-（4-（4-（4-氟苯基）-2-甲基-1 H-咪唑-5-基）吡啶-2-基）环丙烷甲酰胺（1）作为两种靶激酶的有效双重抑制剂。在这项研究中，我们旨在基于我们的吡啶基咪唑骨架设计选择性GSK3β抑制剂。我们的努力导致了几种新颖且有效的GSK3β抑制剂，其IC 50值在低纳摩尔范围内。5-（2-（环丙烷甲酰胺基）吡啶-4-基）-4-环丙基-1 H-咪唑-2-羧酰胺（6g）在神经元SH-SY5Y细胞中表现出非常好的激酶选择性以及代谢稳定性，并抑制了GSK3β活性。有趣的是，我们观察到了2-甲基咪唑的互变异构状态对于化合物活性的重要性。最后，我们揭示了咪唑-2-羧酰胺如何克服这种关键的互变异构效应，无论它们的互变异构状态如何，咪唑-2-羧酰胺都能通过增强的水网络相互作用来稳定结合。
• Imidazole compounds having an antiinflammatory effect
  申请人：MERCKLE GMBH

  公开号：EP1894925A1

  公开（公告）日：2008-03-05

  The invention relates to 2-sulfinyl- or 2-sulfonyl-substituted imidazole derivatives of the formula I in which the radicals R1, R2, R3 and R4 have the meaning indicated in the description. The compounds of the invention have an immunomodulating and/or cytokine release-inhibiting effect and are therefore suitable for the treatment of disorders associated with an impairment of the immune system.

  这项发明涉及公式I的2-磺酰基或2-磺酰基取代的咪唑衍生物， 其中基团R1、R2、R3和R4具有描述中指示的含义。该发明的化合物具有免疫调节和/或细胞因子释放抑制作用，因此适用于治疗与免疫系统功能障碍相关的疾病。
• IMIDAZOLE COMPOUNDS HAVING AN ANTIINFLAMMATORY EFFECT
  申请人：Albrecht Wolfgang

  公开号：US20100069436A1

  公开（公告）日：2010-03-18

  The invention relates to imidazole derivatives of the Formula (I) in which the radicals R 1 , R 2 , R 3 , R 4 and R 5 have the meanings indicated in the description. The compounds of the invention have an immunomodulating and/or cytokine release-inhibiting effect and are therefore suitable for the treatment of disorders associated with an impairment of the immune system.

  本发明涉及式（I）的咪唑衍生物，其中基团R1、R2、R3、R4和R5具有说明书中指示的含义。该发明的化合物具有免疫调节和/或细胞因子释放抑制作用，因此适用于治疗与免疫系统受损有关的疾病。
• Tri- and tetrasubstituted imidazoles as p38α mitogen-activated protein kinase inhibitors
  作者：Stefan Laufer、Dominik Hauser、Thomas Stegmiller、Claudia Bracht、Kathrin Ruff、Verena Schattel、Wolfgang Albrecht、Pierre Koch

  DOI：10.1016/j.bmcl.2010.09.012

  日期：2010.11

  The synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles as potent p38 alpha mitogen-activated protein kinase inhibitors is described. The trisubstituted imidazole series was found to be more potent than the tetrasubstituted imidazole series. Many of these compounds show low-nanomolar activities in the isolated p38 alpha MAP kinase inhibition assay. The structure-activity relationships between these two series are different and not comparable. (C) 2010 Elsevier Ltd. All rights reserved.
• WO2006/89798
  申请人：——

  公开号：——

  公开（公告）日：——