Synthesis and biological evaluation of novel 5,6-dihydrobenzo[h]quinazoline derivatives as FLT3 inhibitors

Chem Biol Drug Des. 2022 Apr;99(4):527-534. doi: 10.1111/cbdd.13992. Epub 2021 Dec 16.

Abstract

Fms-like tyrosine kinase 3 (FLT3) is widely expressed and often mutated in acute myeloid leukemia (AML), which makes it an important target for the treatment of AML. The structure-based synthesis and biological evaluation of 5,6-dihydrobenzo[h]quinazoline derivatives as FLT3 inhibitors have been studied in this paper. III-1a, III-1c, III-2a, III-2c, and III-4a displayed comparable inhibitory potency against FLT3-ITD and showed remarkable antiproliferative activities against MV4-11.

Keywords: 5,6-dihydrobenzo[h]; AML; FLT3 inhibitors; MV4-11; drug synthesis; quinazoline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Mutation
  • Protein Kinase Inhibitors / pharmacology
  • Quinazolines* / pharmacology
  • fms-Like Tyrosine Kinase 3

Substances

  • Protein Kinase Inhibitors
  • Quinazolines
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3