Identification of a pharmacophore for thrombopoietic activity of small, non-peptidyl molecules. 1. Discovery and optimization of salicylaldehyde thiosemicarbazone thrombopoietin mimics

J Med Chem. 2002 Aug 15;45(17):3573-5. doi: 10.1021/jm025535c.

Abstract

High-throughput screening has resulted in the discovery of thiosemicarbazone thrombopoietin mimics. A shared pharmacophore hypothesis between this series and a previously identified class, the pyrazol-4-ylidenehydrazines, led to the rapid optimization of both potency and efficacy of the thiosemicarbazones. The application of high-throughput chemistry and purification techniques allowed for the rapid elucidation of structure-activity relationships.

MeSH terms

  • Aldehydes / chemical synthesis*
  • Aldehydes / chemistry
  • Aldehydes / pharmacology
  • Cell Division / drug effects
  • Cell Line
  • Combinatorial Chemistry Techniques
  • Humans
  • Models, Molecular
  • Molecular Mimicry
  • Phosphorylation
  • Recombinant Proteins / pharmacology
  • Structure-Activity Relationship
  • Thiosemicarbazones / chemical synthesis*
  • Thiosemicarbazones / chemistry
  • Thiosemicarbazones / pharmacology
  • Thrombopoietin / chemistry*
  • Thrombopoietin / pharmacology

Substances

  • Aldehydes
  • Recombinant Proteins
  • Thiosemicarbazones
  • salicylaldehyde thiosemicarbazone
  • Thrombopoietin