Design and synthesis of novel 2-phenylaminopyrimidine (PAP) derivatives and their antiproliferative effects in human chronic myeloid leukemia cells

Molecules. 2009 Oct 19;14(10):4166-79. doi: 10.3390/molecules14104166.

Abstract

A series of novel 2-phenylaminopyrimidine (PAP) derivatives structurally related to STI-571 were designed and synthesized. The abilities of these compounds to inhibit proliferation were tested in human chronic myeloid leukemia K562 cells. (E)-3-(2-bromophenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acrylamide(12d) was the most effective cell growth inhibitor and was 3-fold more potent than STI-571.

MeSH terms

  • Acrylamides / chemical synthesis
  • Acrylamides / chemistry*
  • Acrylamides / pharmacology
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Benzamides
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Drug Design*
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Fusion Proteins, bcr-abl / metabolism
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Piperazines / chemical synthesis
  • Piperazines / chemistry*
  • Piperazines / pharmacology
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology

Substances

  • (E)-3-(2-bromophenyl)-N-(4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl)acrylamide
  • Acrylamides
  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl