Facile synthesis of tetracyclic azepine and oxazocine derivatives and their potential as MAPKAP-K2 (MK2) inhibitors

Bioorg Med Chem Lett. 2012 Jan 15;22(2):1068-72. doi: 10.1016/j.bmcl.2011.11.113. Epub 2011 Dec 6.

Abstract

Facile synthesis of two new series of tetracyclic azepine and oxazocine analogs is described. These analogs were evaluated for their potential as MAPKAP-K2 (MK2) inhibitors and several were found to be potent at inhibiting MK2 with a non-ATP competitive binding mode.

MeSH terms

  • Azepines / chemical synthesis
  • Azepines / chemistry
  • Azepines / pharmacology*
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Molecular Structure
  • Oxazocines / chemical synthesis
  • Oxazocines / chemistry
  • Oxazocines / pharmacology*
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Azepines
  • Intracellular Signaling Peptides and Proteins
  • Oxazocines
  • Protein Kinase Inhibitors
  • MAP-kinase-activated kinase 2
  • Protein Serine-Threonine Kinases