Diversity oriented synthesis and IKK inhibition of aminobenzimidazole tethered quinazoline-2,4-diones, thioxoquinazolin-4-ones, benzodiazepine-2,3,5-triones, isoxazoles and isoxazolines

Bioorg Med Chem Lett. 2015 Feb 1;25(3):685-9. doi: 10.1016/j.bmcl.2014.11.078. Epub 2014 Dec 8.

Abstract

The derivatization of resin-bound aminobenzimidazole toward the parallel solid-phase synthesis of aminobenzimidazole tethered pharmacologically important heterocycles such as quinazoline-2,4-diones, thioxoquinazolin-4-ones, benzodiazepine-2,3,5-triones, isoxazoles and isoxazolines is reported. All the compounds were tested for IKK inhibition. Only one compound elicited significant inhibition of IKKε, TBK-1 and IKK2.

Keywords: 1,3-Dipolar cycloaddition; Aminobenzimidazoles; Benzodiazepinetriones; Heterocycles; Intramolecular cyclization; Isoxazoles; Isoxazolines; Quinazolinediones; Solid-phase synthesis; Thioxoquina-zolinones.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry*
  • Benzimidazoles / metabolism
  • Benzodiazepinones / chemistry*
  • I-kappa B Kinase / antagonists & inhibitors*
  • I-kappa B Kinase / metabolism
  • Isoxazoles / chemistry*
  • Kinetics
  • Protein Binding
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / metabolism
  • Quinazolinones / chemistry*
  • Solid-Phase Synthesis Techniques

Substances

  • Benzimidazoles
  • Benzodiazepinones
  • Isoxazoles
  • Protein Kinase Inhibitors
  • Quinazolinones
  • benzimidazole
  • I-kappa B Kinase