Pyrazolo[1,5-a]pyrimidine based Trk inhibitors: Design, synthesis, biological activity evaluation

Bioorg Med Chem Lett. 2021 Jan 1:31:127712. doi: 10.1016/j.bmcl.2020.127712. Epub 2020 Nov 25.

Abstract

Tropomyosin receptor kinases (Trks), a transmembrane receptor tyrosine kinases, have attracted more and more attention as a drug target. Here we reported the structure-based synthesis and biological evaluation of novel pyrazolo[1,5-a]pyrimidine derivatives as Trk inhibitors, which exhibited potent Trk inhibitory activities. Particularly, compounds 8a, 8f, 9a, 9b and 9f (IC50 < 5 nM) showed significant inhibitory potency against Trk.

Keywords: Anticancer; Design and synthesis; Molecular docking; Tropomyosin receptor kinases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Drug Design*
  • Humans
  • Molecular Docking Simulation
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / metabolism*
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • pyrazolo(1,5-a)pyrimidine
  • Protein Kinases
  • tropomyosin kinase