2-(4-fluorophenyl)-3-oxo-3-pyridin-4-ylpropionic acid ethyl ester | 208655-02-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(4-fluorophenyl)-3-oxo-3-pyridin-4-ylpropionic acid ethyl ester
• 英文别名: ethyl 2-(4-fluorophenyl)-3-oxo-3-(4-pyridyl)-propionate；ethyl 2-(4-fluorophenyl)-3-oxo-3-(pyridin-4-yl)-propionate；ethyl 2-(4-fluorophenyl)-3-oxo-3-pyridin-4-ylpropanoate
• CAS: 208655-02-1
• 化学式: C₁₆H₁₄FNO₃
• 分子量: 287.29
• InChiKey: HIMSOLORGBMBAH-UHFFFAOYSA-N

物化性质

• 沸点：
  400.5±35.0 °C(Predicted)
• 密度：
  1.233±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  56.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-fluorophenyl)-3-oxo-3-pyridin-4-ylpropionic acid ethyl ester 在 硫脲 作用下， 以 丙酮 为溶剂， 生成 5-(4-fluorophenyl)-6-pyridin-4-yl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one
  参考文献：
  名称：

  Substituted pyrimidinone and pyridone compounds and methods of use

  摘要：

  所选的新型嘧啶酮和吡啶酮化合物对预防和治疗疾病（如TNF-alpha、IL-1beta、IL-6和/或IL-8介导的疾病）以及其他疾病（如疼痛和糖尿病）具有有效性。该发明涵盖了新型化合物、类似物、前药和其药学上可接受的盐，以及用于预防和治疗涉及炎症、疼痛、糖尿病等疾病和其他疾患或情况的药物组合物和方法。该发明还涉及制备这类化合物的方法，以及在这类方法中有用的中间体。

  公开号：

  US06096753A1
• 作为产物：
  描述：

  异烟酸 、 对氟苯乙酸乙酯 在 N,N'-羰基二咪唑 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以66%的产率得到2-(4-fluorophenyl)-3-oxo-3-pyridin-4-ylpropionic acid ethyl ester
  参考文献：
  名称：

  基于异恶唑酮的p38 MAP激酶抑制剂。

  摘要：

  实现了N-烷基化异恶唑酮的SAR作为p38 MAP激酶抑制剂。本文中的数据显示了将SAR研究和评估从N-1取代的咪唑转移到异恶唑酮的可能性。实现了取代基的优化。

  DOI：

  10.1021/jm701343f

文献信息

• Substituted pyrimidine compounds and methods of use
  申请人：Amgen Inc.

  公开号：US20030069425A1

  公开（公告）日：2003-04-10

  Selected novel substituted pyrimidine compounds are effective for prophylaxis and treatment of diseases, such as TNF-&agr;, IL-1&bgr;, IL-6 and/or IL-8 mediated diseases, and other maladies, such as pain and diabetes. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving inflammation, pain, diabetes and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  选择的新型代替嘧啶类化合物可用于预防和治疗诸如TNF-α、IL-1β、IL-6和/或IL-8介导的疾病，以及其他疾病，如疼痛和糖尿病。该发明涵盖了新型化合物、类似物、前药及其药学上可接受的盐、制药组合物和用于预防和治疗涉及炎症、疼痛、糖尿病等疾病和其他疾病或病况的方法。该发明还涉及制备这种化合物的过程，以及在这些过程中有用的中间体。
• Substituted pyridone compounds and methods of use
  申请人：Amgen Inc.

  公开号：US20030073704A1

  公开（公告）日：2003-04-17

  Selected novel substituted pyrimidinone and pyridone compounds are effective for prophylaxis and treatment of diseases, such as TNF-&agr;, IL-1&bgr;, IL-6 and/or IL-8 mediated diseases, and other maladies, such as pain and diabetes. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving inflammation, pain, diabetes and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  选定的新型嘧啶酮和吡啶酮化合物对于预防和治疗疾病（如TNF-α、IL-1β、IL-6和/或IL-8介导的疾病）以及其他疾病（如疼痛和糖尿病）是有效的。该发明涵盖了新型化合物、类似物、前药和其药学上可接受的盐、制药组合物以及用于预防和治疗涉及炎症、疼痛、糖尿病等疾病和其他疾患或病况的方法。该发明还涉及制造这些化合物的过程以及在这些过程中有用的中间体。
• Substituted pyrimidine compounds and their use
  申请人：AMGEN INC.

  公开号：EP1314731A2

  公开（公告）日：2003-05-28

  Selected novel substituted pyrimidine compounds are effective for prophylaxis and treatment of diseases, such as TNF-α, IL-1β, IL-6 and/or IL-8 mediated diseases, and other maladies, such as pain and diabetes. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving inflammation, pain, diabetes and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  精选的新型取代嘧啶化合物可有效预防和治疗疾病，如TNF-α、IL-1β、IL-6和/或IL-8介导的疾病，以及其他疾病，如疼痛和糖尿病。本发明包括新型化合物、类似物、原药及其药学上可接受的盐、药物组合物以及用于预防和治疗涉及炎症、疼痛、糖尿病等疾病和其他弊病或病症的方法。本发明还涉及制造此类化合物的工艺以及在此类工艺中有用的中间体。
• Pyrroles and other heterocycles as inhibitors of P38 kinase
  作者：Stephen E. de Laszlo、Denise Visco、Lily Agarwal、Linda Chang、Jayne Chin、Gist Croft、Amy Forsyth、Daniel Fletcher、Betsy Frantz、Candice Hacker、William Hanlon、Coral Harper、Matthew Kostura、Bing Li、Sylvie Luell、Malcolm MacCoss、Nathan Mantlo、Edward A. O'Neill、Chad Orevillo、Margaret Pang、Janey Parsons、Anna Rolando、Yousif Sahly、Kelley Sidler、W.Rick Widmer、Stephen J. O'Keefe

  DOI：10.1016/s0960-894x(98)00495-8

  日期：1998.10

  Investigation of furans, pyrroles and pyrazolones identified 3-pyridyl-2,5-diaryl-pyrroles as potent, orally bioavailable inhibitors of p38 kinase. 3-(4-pyridyl-2-(4-fluoro-phenyl)-5-(4-methylsulfinylphenyl)-pyrrole (L-167307) reduces secondary paw swelling in the rat adjuvant arthritis model: ID50 = 7.4 mg/kg/b.i.d. (C) 1998 Elsevier Science Ltd. All rights reserved.
• From Imidazoles to Pyrimidines:  New Inhibitors of Cytokine Release
  作者：Stefan A. Laufer、Gerd K. Wagner

  DOI：10.1021/jm011098a

  日期：2002.6.1

  On the basis of model imidazole inhibitors of cytokine release, a series of novel pyridinyl pyrimidine derivatives was prepared and tested on their ability to inhibit the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-beta) from peripheral blood mononuclear cells (PBMC) and human whole blood. In the pyrimidine series, structure-activity relationships (SARs) similar to those of the imidazole series were found, although generally pyrimidine compounds were less potent. Modification of the substituent at the 2 position of the pyrimidine led to the most active compound 14 which inhibited release of TNF-alpha (IC50 = 3.2 muM) and IL-1beta (IC50 = 2.3 muM) from PBMC as effectively as the model imidazole inhibitor ML 3163 (TNF-alpha, IC50 = 3.7 muM; IL-1beta, IC50 = 0-9 muM). Screening in an isolated enzyme assay revealed both imidazole and pyrimidine compounds as inhibitors of p38 MAP (mitogen-activated protein) kinase.