Design, Synthesis, and Biological Evaluation of Novel Quinazoline Clubbed Thiazoline Derivatives

Arch Pharm (Weinheim). 2017 Feb;350(2). doi: 10.1002/ardp.201600298. Epub 2017 Jan 17.

Abstract

A novel series of quinazoline clubbed thiazoline derivatives was rationally designed and synthesized. The newly synthesized compounds were evaluated for in vitro dipeptidyl peptidase IV (DPP-4) inhibitory activity. Compounds that showed good to moderate activity were compared using linagliptin as standard. Compound 4x (IC50 = 1.12 nM) exhibited the most promising results. The special chemical feature of compound 4x also imparts good inhibition selectivity for DPP-4 over DPP-8/9. Moreover, docking of compound 4x into the active site of DPP-4 illustrates its possible binding interactions.

Keywords: Antidiabetic; DPP-4 inhibitors; Molecular docking; Quinazoline; Thiazoline.

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Dipeptidyl-Peptidase IV Inhibitors / chemical synthesis*
  • Dipeptidyl-Peptidase IV Inhibitors / chemistry
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / antagonists & inhibitors*
  • Drug Design*
  • Linagliptin / pharmacology
  • Molecular Docking Simulation
  • Quinazolines / chemical synthesis*
  • Quinazolines / chemistry
  • Quinazolines / pharmacology*
  • Rats
  • Structure-Activity Relationship

Substances

  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Quinazolines
  • Linagliptin
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases