5'-[(cyclopropylamino)carbonyl]-3'-fluoro-2'-methyl-4-biphenylcarboxylic acid

• 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: 5'-[(cyclopropylamino)carbonyl]-3'-fluoro-2'-methyl-4-biphenylcarboxylic acid
• 英文别名: 4-[5-(Cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]benzoic acid
• 化学式: C₁₈H₁₆FNO₃
• 分子量: 313.328
• InChiKey: WWYZEESJNUPOQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  杂氮环丁烷 、 5'-[(cyclopropylamino)carbonyl]-3'-fluoro-2'-methyl-4-biphenylcarboxylic acid 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 16.08h， 生成 4'-(azetidin-1-ylcarbonyl)-N-cyclopropyl-5-fluoro-6-methyl-1,1'-biphenyl-3-carboxamide
  参考文献：
  名称：

  [EN] BIPHENYLCARBOXYLIC AMIDE DERIVATIVES AS P38 KINEASE INHIBITORS
  [FR] DERIVES D'AMIDE BIPHENYLCARBOXYLIQUE UTILISES EN TANT QU'INHIBITEURS DE LA KINASE P38

  摘要：

  化合物的公式（I）或其药学上可接受的衍生物，并将其用作药物，特别是作为p38激酶抑制剂。

  公开号：

  WO2004089876A1
• 作为产物：
  描述：

  在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以0.28 g的产率得到5'-[(cyclopropylamino)carbonyl]-3'-fluoro-2'-methyl-4-biphenylcarboxylic acid
  参考文献：
  名称：

  p38α Mitogen-Activated Protein Kinase Inhibitors: Optimization of a Series of Biphenylamides to Give a Molecule Suitable for Clinical Progression

  摘要：

  p38 alpha MAP kinase is a key anti-inflammatory target for rheumatoid arthritis, influencing biosynthesis of pro-inflammatory cytokines TNF alpha and IL-1 beta at a translational and transcriptional level. In this paper, we describe how we have optimized a series of novel p38 alpha/beta inhibitors using crystal structures of our inhibitors bound to p38 alpha, classical medicinal chemistry, and modeling of virtual libraries to derive a molecule suitable for progression into clinical development.

  DOI：

  10.1021/jm9004779

文献信息

• p38α Mitogen-Activated Protein Kinase Inhibitors: Optimization of a Series of Biphenylamides to Give a Molecule Suitable for Clinical Progression
  作者：Nicola M. Aston、Paul Bamborough、Jacqueline B. Buckton、Christopher D. Edwards、Duncan S. Holmes、Katherine L. Jones、Vipulkumar K. Patel、Penny A. Smee、Donald O. Somers、Giovanni Vitulli、Ann L. Walker

  DOI：10.1021/jm9004779

  日期：2009.10.22

  p38 alpha MAP kinase is a key anti-inflammatory target for rheumatoid arthritis, influencing biosynthesis of pro-inflammatory cytokines TNF alpha and IL-1 beta at a translational and transcriptional level. In this paper, we describe how we have optimized a series of novel p38 alpha/beta inhibitors using crystal structures of our inhibitors bound to p38 alpha, classical medicinal chemistry, and modeling of virtual libraries to derive a molecule suitable for progression into clinical development.
• [EN] BIPHENYLCARBOXYLIC AMIDE DERIVATIVES AS P38 KINEASE INHIBITORS<br/>[FR] DERIVES D'AMIDE BIPHENYLCARBOXYLIQUE UTILISES EN TANT QU'INHIBITEURS DE LA KINASE P38
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004089876A1

  公开（公告）日：2004-10-21

  Compounds of formula (I) or pharmaceutically acceptable derivatives thereof, and their use as pharmaceuticals, particularly as p38 kinase inhibitors.

  化合物的公式（I）或其药学上可接受的衍生物，并将其用作药物，特别是作为p38激酶抑制剂。