2-Amino-7-substituted benzoxazole analogs as potent RSK2 inhibitors

Bioorg Med Chem Lett. 2014 Mar 15;24(6):1592-6. doi: 10.1016/j.bmcl.2014.01.058. Epub 2014 Jan 30.

Abstract

2-Amino-7-substituted benzoxazole analogs were identified by HTS as inhibitors of RSK2. Molecular modeling and medicinal chemistry techniques were employed to explore the SAR for this series with a focus of improving in vitro and target modulation potency and physicochemical properties.

Keywords: Benzoxazole; HTS; Heterocycle; Kinase; RSK.

MeSH terms

  • Benzoxazoles / chemical synthesis
  • Benzoxazoles / chemistry*
  • Benzoxazoles / metabolism
  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • Molecular Dynamics Simulation
  • Protein Binding
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Structure, Tertiary
  • Ribosomal Protein S6 Kinases, 90-kDa / antagonists & inhibitors*
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism
  • Structure-Activity Relationship

Substances

  • Benzoxazoles
  • Protein Kinase Inhibitors
  • Ribosomal Protein S6 Kinases, 90-kDa
  • ribosomal protein S6 kinase, 90kDa, polypeptide 3