N3-cyclopropyl-5-fluoro-6-methyl-N4'-(2-hydroxy-2-methylpropyl)-3,4'-biphenyldicarboxamide | 1191988-27-8

• 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: N3-cyclopropyl-5-fluoro-6-methyl-N4'-(2-hydroxy-2-methylpropyl)-3,4'-biphenyldicarboxamide
• 英文别名: N-cyclopropyl-3-fluoro-5-[4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl]-4-methylbenzamide
• CAS: 1191988-27-8
• 化学式: C₂₂H₂₅FN₂O₃
• 分子量: 384.451
• InChiKey: OLVRNGODZLMUKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  78.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5'-[(cyclopropylamino)carbonyl]-3'-fluoro-2'-methyl-4-biphenylcarboxylic acid 、 1-氨基-2-甲基-2-丙醇 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 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以57%的产率得到N3-cyclopropyl-5-fluoro-6-methyl-N4'-(2-hydroxy-2-methylpropyl)-3,4'-biphenyldicarboxamide
  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

• Benzamide derivative
  申请人：CSPC ZHONGQI PHARMACEUTICAL TECHNOLOGY (SHIJIAZHUANG) CO., LTD.

  公开号：US10550073B2

  公开（公告）日：2020-02-04

  The present invention relates to a benzamide derivative of general formula I, a drug composition containing same and a use thereof as a drug, wherein the definitions of R1, Z and Q are as described in the description.

  本发明涉及通式 I 的苯甲酰胺衍生物、含有该衍生物的药物组合物及其作为药物的用途，其中 R1、Z 和 Q 的定义如说明书所述。
• 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.