2-{4-[3-(4-chloro-2-fluorophenyl)-4-pyrimidin-4-yl-1H-pyrazol-5-yl]piperidin-1-yl}-2-oxoethanol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-{4-[3-(4-chloro-2-fluorophenyl)-4-pyrimidin-4-yl-1H-pyrazol-5-yl]piperidin-1-yl}-2-oxoethanol
• 英文别名: N-(2-hydroxyacetyl)-5-(4-piperidyl)-3-(phenyl)pyrazole；p38 MAPK-IN-2；1-[4-[3-(4-chloro-2-fluorophenyl)-4-pyrimidin-4-yl-1H-pyrazol-5-yl]piperidin-1-yl]-2-hydroxyethanone
• 化学式: C₂₀H₁₉ClFN₅O₂
• 分子量: 415.855
• InChiKey: IGGNAIYXGIUMQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  95
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-oxo-2-(4-(3-phenyl-1H-pyrazole-5-yl)piperidin-1-yl)ethyl acetate 在 甲醇 、 sodium hydroxide 、 水 、 盐酸 作用下， 以 水 为溶剂， 生成 2-{4-[3-(4-chloro-2-fluorophenyl)-4-pyrimidin-4-yl-1H-pyrazol-5-yl]piperidin-1-yl}-2-oxoethanol
  参考文献：
  名称：

  [EN] PROCESS FOR MAKING SUBSTITUTED PYRAZOLES
  [FR] PROCEDE DE FABRICATION DE PYRAZOLES SUBSTITUES

  摘要：

  这项发明通常涉及一种制备取代吡唑的方法，所述取代吡唑在结构上对应于式9：其中Q、R4、R3A、R3B、R3C、R3D和R3E如规范中所定义。

  公开号：

  WO2005061485A1

文献信息

• [EN] PROCESS FOR MAKING SUBSTITUTED PYRAZOLES<br/>[FR] PROCEDE DE FABRICATION DE PYRAZOLES SUBSTITUES
  申请人：PHARMACIA CORP

  公开号：WO2005061485A1

  公开（公告）日：2005-07-07

  This invention is directed generally to a process for making substituted pyrazoles, The substituted pyrazole corresponds in structure to formula 9 : wherein Q, R4,R3A, R3B, R3C, R3D, and R3E are as defined in the specification.

  这项发明通常涉及一种制备取代吡唑的方法，所述取代吡唑在结构上对应于式9：其中Q、R4、R3A、R3B、R3C、R3D和R3E如规范中所定义。
• [EN] PYRAZOLE-DERIVATIVES AS P38 KINASE INHIBITORS<br/>[FR] DERIVES DE PYRAZOLS UTILISES COMME INHIBITEURS DE LA P38 KINASE
  申请人：PHARMACIA CORP

  公开号：WO2003104223A1

  公开（公告）日：2003-12-18

  This invention is directed generally to pyrazoles that, inter alia, inhibit p38 kinase, TNF, and/or cyclooxygenase-2 activity. Such pyrazoles include compounds generally corresponding in structure to the following formula (I), wherein L1, L2,Xl, X2, X3, X4, X5, X6, Rl, R3A, R3b,R3C, R4, and R5 are as defined in this specification. The pyrazoles further include tautomers of such compounds, as well as salts of such compounds and tautomers. This invention also is directed to compositions of such pyrazoles, intermediates for the syntheses of such pyrazoles, methods for making such pyrazoles, and methods for treating (including preventing) conditions (particularly pathological conditions) associated with p38 kinase, TNF, and/or cyclooxygenase-2 activity.

  该发明通常涉及对吡唑酮的研究，其可以抑制p38激酶、TNF和/或环氧合酶-2的活性。这些吡唑酮包括通常对应于以下结构式(I)的化合物，其中L1、L2、X1、X2、X3、X4、X5、X6、R1、R3A、R3b、R3C、R4和R5的定义如本说明书所述。这些吡唑酮还包括这些化合物的互变异构体，以及这些化合物和互变异构体的盐。该发明还涉及这些吡唑酮的组合物，合成这些吡唑酮的中间体，制备这些吡唑酮的方法，以及治疗（包括预防）与p38激酶、TNF和/或环氧合酶-2活性相关的病症（特别是病理病症）的方法。
• Combination therapies utilizing benzamide inhibitors of the P2X7 receptor
  申请人：Chung B. James

  公开号：US20060018904A1

  公开（公告）日：2006-01-26

  This invention provides methods of treatment of IL-1 mediated diseases comprising administering a pharmaceutically effective amount of a pharmaceutical agent selected from the group of sulfasalazine, a statin, a glucocorticoid agent, an inhibitor of p38 kinase, an anti-IL-6-receptor antibody, anakinra, an IL-1 monoclonal antibody, an inhibitor of JAK3 protein tyrosine kinase, a M-CSF monoclonal antibody or a humanized anti-CD20 monoclonal antibody and a benzamide inhibitor of the P2X 7 receptor of the formula: wherein R 1 -R 3 are as defined herein. The methods of the invention are useful in the treatment of IL-1 mediated disorders, including, without limitation, inflammatory diseases such as osteoarthritis and rheumatoid arthritis; allergies, asthma, COPD, cancer, reperfusion or ischemia in stroke or heart attack, autoimmune diseases and other disorders.

  本发明提供了治疗IL-1介导疾病的方法，包括给予从磺胺嘧啶、他汀、糖皮质激素、p38激酶抑制剂、抗IL-6受体抗体、阿那西单抗、IL-1单克隆抗体、JAK3蛋白酪氨酸激酶抑制剂、M-CSF单克隆抗体或人源化的抗CD20单克隆抗体和P2X7受体苯甲酰胺抑制剂中选择的药物剂量。本发明的方法对于治疗IL-1介导的疾病非常有用，包括但不限于炎症性疾病如骨关节炎和类风湿性关节炎；过敏、哮喘、COPD、癌症、中风或心脏病的再灌注或缺血、自身免疫性疾病和其他疾病。
• [EN] CRYSTALLINE FORMS OF 3-[5-CHLORO-4-[(2,4-DIFLUOROBENZYL) OXY]-6-OXOPYRIMIDIN-1(6H)-YL]-N-(2-HYDROXYETHYL)-4-METHYLBENZAMIDE<br/>[FR] FORMES CRISTALLINES DE 3-[5-CHLORO-4-[(2,4-DIFLUOROBENZYL) OXY]-6-OXOPYRIMIDIN-1(6H)-YL]-N-(2-HYDROXYETHYL)-4-METHYLBENZAMIDE
  申请人：PHARMACIA & UPJOHN CO LLC

  公开号：WO2006040649A1

  公开（公告）日：2006-04-20

  Crystalline forms of the p38 kinase inhibitor 3-[5-chloro-4-[(2,4­difluorobenzyl) oxy]-6-oxopyrimidin-1(6H)-yl]-N-(2-hydroxyethyl)-4-methylbenzamide is provided. Also provided are combinations and pharmaceutical compositions comprising the crystalline forms and methods for the prophylaxis and/or treatment of a p38 kinase-mediated condition comprising administering to a subject a therapeutically effective amount of the crystalline forms.

  本发明提供了p38激酶抑制剂3-[5-氯-4-[(2,4-二氟苯甲基)氧基]-6-氧代嘧啶-1(6H)-基]-N-(2-羟乙基)-4-甲基苯甲酰晶体形式。此外，本发明还提供了包含上述晶体形式的组合物和药物组合物，以及用于预防和/或治疗p38激酶介导的疾病的方法，包括向受体内投与治疗有效量的晶体形式。
• Novel pyrazoles and their use as p38 kinase inhibitors
  申请人：——

  公开号：US20040082551A1

  公开（公告）日：2004-04-29

  This invention is directed generally to pyrazoles that, inter alia, inhibit p38 kinase, TNF, and/or cyclooxygenase-2 activity. Such pyrazoles include compounds generally corresponding in structure to the following formula: 1 wherein L 1 , L 2 , X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , R 1 , R 3A , R 3B , R 3C , R 4 , and R 5 are as defined in this specification. The pyrazoles further include tautomers of such compounds, as well as salts of such compounds and tautomers. This invention also is directed to compositions of such pyrazoles, intermediates for the syntheses of such pyrazoles, methods for making such pyrazoles, and methods for treating (including preventing) conditions (particularly pathological conditions) associated with p38 kinase, TNF, and/or cyclooxygenase-2 activity.

  本发明通常涉及对吡唑烷的研究，其中包括抑制p38激酶、TNF和/或环氧合酶-2活性的化合物。这些吡唑烷包括通常对应于以下结构式的化合物：1其中L1、L2、X1、X2、X3、X4、X5、X6、R1、R3A、R3B、R3C、R4和R5如本说明书所定义。这些吡唑烷还包括这些化合物的互变异构体，以及这些化合物和互变异构体的盐。本发明还涉及这些吡唑烷的组合物、合成这些吡唑烷的中间体、制备这些吡唑烷的方法，以及用于治疗（包括预防）与p38激酶、TNF和/或环氧合酶-2活性相关的病理条件的方法。