Synthesis and biological evaluation of 2-anilino-4-substituted-7H-pyrrolopyrimidines as PDK1 inhibitors

Bioorg Med Chem. 2014 Aug 1;22(15):3879-86. doi: 10.1016/j.bmc.2014.06.018. Epub 2014 Jun 18.

Abstract

PDK1, a biological target that has attracted a large amount of attention recently, is responsible for the positive regulation of the PI3K/Akt pathway that is often activated in a large number of human cancers. A series of second-generation 2-anilino-4-substituted-7H-pyrrolopyrimidines were synthesised by installation of various functions at the 4-position of the 7H-pyrrolopyrimidine scaffold. All compounds were screened against the isolated PDK1 enzyme and dose response analysis was obtained on the best compounds of the series.

Keywords: 2-Anilino-4-substituted-pyrrolopyrimidines; 3-Phosphoinositide-dependent kinase 1 (PDK1); Buchwald–Hartwig cross-coupling; Inhibitor; Suzuki cross-coupling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Protein Binding
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / metabolism
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / metabolism
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / metabolism
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry*
  • Pyrroles / metabolism
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Structure-Activity Relationship

Substances

  • PDK1 protein, human
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Pyrroles
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • pyrrolopyrimidine
  • Protein Serine-Threonine Kinases