Discovery and biological evaluation of benzo[a]carbazole-based small molecule agonists of the thrombopoietin (Tpo) receptor

Bioorg Med Chem Lett. 2008 Oct 1;18(19):5255-8. doi: 10.1016/j.bmcl.2008.08.068. Epub 2008 Aug 22.

Abstract

A novel series of benzo[a]carbazole-based small molecule agonists of the thrombopoietin (Tpo) receptor is reported. Starting from a 3.4 microM high throughput screen hit, members of this series have been identified which are full agonists with functional potency <50 nM and oral bioavailability in mice.

MeSH terms

  • Administration, Oral
  • Animals
  • Benzene Derivatives / chemical synthesis*
  • Benzene Derivatives / chemistry
  • Benzene Derivatives / pharmacology*
  • Carbazoles / chemical synthesis*
  • Carbazoles / chemistry
  • Carbazoles / pharmacology*
  • Combinatorial Chemistry Techniques
  • Drug Design
  • Humans
  • Mice
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Receptors, Thrombopoietin / agonists*
  • Receptors, Thrombopoietin / chemistry
  • Structure-Activity Relationship
  • Thrombopoietin* / chemistry
  • Thrombopoietin* / metabolism

Substances

  • Benzene Derivatives
  • Carbazoles
  • Receptors, Thrombopoietin
  • Thrombopoietin