Biphenyl amide p38 kinase inhibitors 2: Optimisation and SAR

Bioorg Med Chem Lett. 2008 Jan 1;18(1):324-8. doi: 10.1016/j.bmcl.2007.10.043. Epub 2007 Oct 17.

Abstract

The biphenyl amides are a novel series of p38 MAP kinase inhibitors. Structure-activity relationships of the series against p38alpha are discussed with reference to the X-ray crystal structure of an example. The series was optimised rapidly to a compound showing oral activity in an in vivo disease model.

MeSH terms

  • Administration, Oral
  • Amides / chemistry
  • Amides / pharmacokinetics
  • Amides / pharmacology*
  • Animals
  • Arthritis, Experimental / drug therapy
  • Arthritis, Experimental / metabolism
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / pharmacokinetics
  • Biphenyl Compounds / pharmacology*
  • Crystallography, X-Ray
  • Models, Molecular
  • Molecular Conformation
  • Oxadiazoles / chemistry
  • Oxadiazoles / pharmacokinetics
  • Oxadiazoles / pharmacology
  • Piperazines / chemistry
  • Piperazines / pharmacokinetics
  • Piperazines / pharmacology
  • Protein Binding
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / pharmacology*
  • Rats
  • Structure-Activity Relationship
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / chemistry
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Amides
  • Biphenyl Compounds
  • Oxadiazoles
  • Piperazines
  • Protein Kinase Inhibitors
  • p38 Mitogen-Activated Protein Kinases