4-[3-(4-fluorophenyl)-5-phenylisoxazol-4-yl]pyridine

• 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-[3-(4-fluorophenyl)-5-phenylisoxazol-4-yl]pyridine
• 英文别名: 3-(4-Fluorophenyl)-5-phenyl-4-pyridin-4-yl-1,2-oxazole
• 化学式: C₂₀H₁₃FN₂O
• 分子量: 316.334
• InChiKey: LNPXPKXFNXASDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  38.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(4-氟苯基)-2-(4-吡啶基)乙酮 在 盐酸羟胺 、 sodium acetate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 13.5h， 生成 4-[3-(4-fluorophenyl)-5-phenylisoxazol-4-yl]pyridine
  参考文献：
  名称：

  From Five- to Six-Membered Rings:  3,4-Diarylquinolinone as Lead for Novel p38MAP Kinase Inhibitors

  摘要：

  In this study we describe the design, synthesis, and biological evaluation of 3-(4-fluorophenyl)-4-pyridin-4-ylquinoline-2(1H)-one (5) as a new inhibitor of MAPK with a p38 alpha MAPK IC50 of 1.8 mu M. By keeping the common vicinal pyridine/4-F-phenyl pharmacophore, such as in prototypical imidazole 20 or isoxazole 13 but in 5 connected to the six-membered quinoline core, we were particularly interested in comparing biological activity, details of molecular geometry, and different binding modes of these compounds. Compounds 20 and 13 were active both in the p38 alpha- and JNK3-assay, whereas 5 was selective for p38 alpha, with no JNK3 inhibition. By comparing the X-ray structures of the compounds, we found a significantly larger distance between the pyridine and the 4-F-phenyl moiety in five-membered core structures relevant for ligand-protein interactions. Molecular modeling studies support the results based on differences in the ATP pockets of p38 alpha and JNK3. Because most five-membered core based p38 alpha inhibitors show also activity for JNK3, compound 5 is an interesting lead for selective p38 alpha inhibitors.

  DOI：

  10.1021/jm061097o

文献信息

• Substituted isoxazole derivatives and their use in pharmaceutics
  申请人：Laufer Stefan

  公开号：US20060128759A1

  公开（公告）日：2006-06-15

  The invention relates to substituted isoxazole derivatives of formula (I), wherein the radicals R 1 , R 2 and R 3 have the meanings as cited in the description. The inventive compounds comprise an immunomodulatory action and/or an action that inhibits the release of cytokines and are thus suited for treating diseases associated with a disorder of the immune system, particularly immunologically mediated inflammatory diseases

  本发明涉及式(I)的取代异噁唑衍生物，其中基团R1、R2和R3的含义如描述中所述。本发明化合物具有免疫调节作用和/或抑制细胞因子释放作用，因此适用于治疗与免疫系统紊乱有关的疾病，特别是免疫介导的炎症性疾病。
• SUBSTITUIERTE ISOXAZOLDERIVATE UND IHRE VERWENDUNG IN DER PHARMAZIE
  申请人：MERCKLE GMBH

  公开号：EP1530468A1

  公开（公告）日：2005-05-18
• [DE] SUBSTITUIERTE ISOXAZOLDERIVATE UND IHRE VERWENDUNG IN DER PHARMAZIE<br/>[EN] SUBSTITUTED ISOXAZOLE DERIVATIVES AND THEIR USE IN PHARMACEUTICS<br/>[FR] DERIVES D'ISOXAZOLE SUBSTITUES ET LEUR UTILISATION EN PHARMACIE
  申请人：MERCKLE GMBH

  公开号：WO2004017968A1

  公开（公告）日：2004-03-04

  Die Erfindung betrifft substituierte Isoxazolderivate der Formel (I) worin die Reste R1, R2 und R3 die in der Beschreibung angegebene Bedeutung besitzen. Die erfindungsgemässen Verbindungen besitzen eine immunmodulierende und/oder die Cytokinfreisetzung hemmende Wirkung und sind daher geeignet zur Behandlung von Erkrankungen, die mit einer Störung des Immunsystems im Zusammenhang stehen, insbesondere immunologisch vermittelte entzündliche Erkrankungen.
• From Five- to Six-Membered Rings:  3,4-Diarylquinolinone as Lead for Novel p38MAP Kinase Inhibitors
  作者：Christian Peifer、Katrin Kinkel、Mohammed Abadleh、Dieter Schollmeyer、Stefan Laufer

  DOI：10.1021/jm061097o

  日期：2007.3.1

  In this study we describe the design, synthesis, and biological evaluation of 3-(4-fluorophenyl)-4-pyridin-4-ylquinoline-2(1H)-one (5) as a new inhibitor of MAPK with a p38 alpha MAPK IC50 of 1.8 mu M. By keeping the common vicinal pyridine/4-F-phenyl pharmacophore, such as in prototypical imidazole 20 or isoxazole 13 but in 5 connected to the six-membered quinoline core, we were particularly interested in comparing biological activity, details of molecular geometry, and different binding modes of these compounds. Compounds 20 and 13 were active both in the p38 alpha- and JNK3-assay, whereas 5 was selective for p38 alpha, with no JNK3 inhibition. By comparing the X-ray structures of the compounds, we found a significantly larger distance between the pyridine and the 4-F-phenyl moiety in five-membered core structures relevant for ligand-protein interactions. Molecular modeling studies support the results based on differences in the ATP pockets of p38 alpha and JNK3. Because most five-membered core based p38 alpha inhibitors show also activity for JNK3, compound 5 is an interesting lead for selective p38 alpha inhibitors.