1-[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-4-methylpiperazine | 960126-38-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-4-methylpiperazine
• 英文别名: 1-[5-(4-chlorophenyl)-4-pyridin-4-yl-1H-pyrazol-3-yl]-4-methylpiperazine
• CAS: 960126-38-9
• 化学式: C₁₉H₂₀ClN₅
• 分子量: 353.854
• InChiKey: BKQFXMIFPQJYMZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  48
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-[3-(4-chlorophenyl)-3-oxo-2-(4-pyridinyl)-1-thiopropyl]-4-methylpiperazine 在 肼 作用下， 以 四氢呋喃 为溶剂， 以60%的产率得到1-[5-(4-chlorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-4-methylpiperazine
  参考文献：
  名称：

  Substituted pyrazoles as p38 kinase inhibitors

  摘要：

  描述了一类吡唑衍生物，用于治疗p38激酶介导的疾病。特别感兴趣的化合物由下式IA定义： 其中R1、R2、R3和R4如规范中所述。

  公开号：

  US06514977B1

文献信息

• Process for making substituted pyrazoles
  申请人：G.D. Searle & Company

  公开号：US06342608B1

  公开（公告）日：2002-01-29

  This invention relates to a novel process of preparing selected 5-substituted pyrazoles useful as p38 kinase and COX-2 inhibitors.

  这项发明涉及一种新颖的工艺，用于制备作为p38激酶和COX-2抑制剂有用的选定的5-取代吡唑。
• [EN] SUBSTITUTED PYRAZOLES AS p38 KINASE INHIBITORS<br/>[FR] PYRAZOLES SUBSTITUES UTILISES COMME INHIBITEURS DE LA KINASE p38
  申请人：SEARLE & CO

  公开号：WO2000031063A1

  公开（公告）日：2000-06-02

  A class of pyrazole derivatives is described for use in treating p38 kinase mediated disorders. Compounds of particular interest are defined by Formula (IA), wherein R?1, R2, R3 and R4¿ are as described in the specification.

  本文描述了一类吡唑衍生物，用于治疗p38激酶介导的疾病。 特别感兴趣的化合物由公式（IA）定义，其中R?1，R2，R3和R4¿如规范中所述。
• Substituted pyrazoles as P38 kinase inhibitors
  申请人：G.D. Searle LLC

  公开号：EP1500657A1

  公开（公告）日：2005-01-26

  A class of pyrazole derivatives is described for use in treating p38 kinase mediated disorders. Compounds of particular interest are defined by Formula (IA), wherein R1, R2, R3 and R4 are as described in the specification.

  描述了一类吡唑衍生物用于治疗 p38 激酶介导的疾病。特别感兴趣的化合物由式（IA）定义、 其中 R1、R2、R3 和 R4 如说明书所述。
• [EN] SUBSTITUTED PYRAZOLES AS p38 KINASE INHIBITORS<br/>[FR] PYRAZOLES SUBSTITUES UTILISES COMME INHIBITEURS DE p38 KINASE
  申请人：G.D. SEARLE AND CO.

  公开号：WO1998052940A1

  公开（公告）日：1998-11-26

  (EN) A class of pyrazole derivatives is described for use in treating p38 kinase mediated disorders. Compounds of particular interest are defined by Formula (I) wherein R1, R2, R3 and R4 are as described in the specification.(FR) L'invention concerne une classe de dérivés de pyrazoles, utile pour traiter des troubles associés à la p38 kinase. Des composés particulièrement intéressants sont définis par la formule (I), dans laquelle R1, R2, R3 et R4 sont tels que décrits dans la description.

  本发明涉及一类吡唑衍生物，可用于治疗与p38激酶相关的疾病。特别感兴趣的化合物由式(I)表示，其中R1、R2、R3和R4的定义如说明书所述。
• Synthesis, Crystal Structure, and Activity of Pyrazole-Based Inhibitors of p38 Kinase
  作者：Matthew J. Graneto、Ravi G. Kurumbail、Michael L. Vazquez、Huey-Sheng Shieh、Jennifer L. Pawlitz、Jennifer M. Williams、William C. Stallings、Lifeng Geng、Ashok S. Naraian、Francis J. Koszyk、Michael A. Stealey、Xiangdong D. Xu、Richard M. Weier、Gunnar J. Hanson、Robert J. Mourey、Robert P. Compton、Stephen J. Mnich、Gary D. Anderson、Joseph B. Monahan、Rajesh Devraj

  DOI：10.1021/jm0611915

  日期：2007.11.1

  A series of pyrazole inhibitors of p38 mitogen-activated protein (MAP) kinase were designed using a binding model based on the crystal structure of 1 (SC-102) bound to p38 enzyme. New chemistry using dithietanes was developed to assemble nitrogen-linked substituents at the 5-position of pyrazoles. Calculated log D was used in tandem with structure-based design to guide medicinal chemistry strategy and improve the in vivo activity of a series of molecules. The crystal structure of an optimized inhibitor, 4 (SC-806), in complex with p38 enzyme was obtained to confirm the hypothesis that the addition of a basic nitrogen to the molecule induces an interaction with Asp112 of p38 alpha. A compound identified from this series was efficacious in an animal model of rheumatic disease.