3-Phenyl-1H-5-pyrazolylamine-based derivatives as potent and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3)

Bioorg Med Chem Lett. 2012 Jul 15;22(14):4654-9. doi: 10.1016/j.bmcl.2012.05.116. Epub 2012 Jun 7.

Abstract

A new class of FLT3 inhibitors has been identified based on the 3-phenyl-1H-5-pyrazolylamine scaffold. The structure-activity relationships led to the discovery of two carbamate series, and some potent compounds within these two series exhibited better growth inhibition of FLT3-mutated MOLM-13 cells than FLT3 inhibitors sorafenib (2) and ABT-869 (3). In particular, compound 8d exhibited the ability to regress tumors in mouse xenograft model using MOLM-13 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry*
  • Amines / pharmacology
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Humans
  • Mice
  • Molecular Structure
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Pyrazoles / chemistry*
  • Structure-Activity Relationship
  • Xenograft Model Antitumor Assays
  • fms-Like Tyrosine Kinase 3 / antagonists & inhibitors*

Substances

  • Amines
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyrazoles
  • pyrazole
  • fms-Like Tyrosine Kinase 3