4-Amino-6-piperazin-1-yl-pyrimidine-5-carbaldehyde oximes as potent FLT-3 inhibitors

Bioorg Med Chem Lett. 2007 Sep 1;17(17):4861-5. doi: 10.1016/j.bmcl.2007.06.046. Epub 2007 Jun 14.

Abstract

A series of 4-amino-6-piperazin-1-yl-pyrimidine-5-carbaldehyde oximes has been discovered and developed as potent FLT3 tyrosine kinase inhibitors. The series exhibited potent antiproliferative activity against both an FLT3 ITD-mutated human leukemic cell line as well as a wild-type FLT3 BaF(3) expressed cell line. The structure-activity relationship of this class of compounds is described.

MeSH terms

  • Aldehydes / chemistry*
  • Cell Line, Tumor
  • Cell Proliferation
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Humans
  • Inhibitory Concentration 50
  • Models, Chemical
  • Mutation
  • Oximes / chemical synthesis*
  • Oximes / chemistry
  • Oximes / therapeutic use*
  • Structure-Activity Relationship
  • fms-Like Tyrosine Kinase 3 / antagonists & inhibitors*

Substances

  • Aldehydes
  • Oximes
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3