Design and synthesis of (4E)-4-(4-substitutedbenzylideneamino)-3-substituted-2,3-dihydro-2-thioxothiazole-5-carbonitrile as novel A2A receptor antagonists

Bioorg Med Chem. 2013 Oct 1;21(19):6077-83. doi: 10.1016/j.bmc.2013.07.005. Epub 2013 Jul 13.

Abstract

Novel 2-thioxothiazole derivatives (6-19) as potential adenosine A2A receptor (A2AR) antagonists were synthesized. The strong interaction of the compounds (6-19) with A2AR in docking study was confirmed by high binding affinity with human A2AR expressed in HEK293T cells using radioligand-binding assay. The compound 19 demonstrated very high selectivity for A2AR as compared to standard A2AR antagonist SCH58261. Decrease in A2AR-coupled release of endogenous cAMP in treated HEK293T cells demonstrated in vitro A2AR antagonist potential of the compound 19. Attenuation in haloperidol-induced impairment (catalepsy) in Swiss albino male mice pre-treated with compound 19 is evocative to explore its prospective in therapy of PD.

Keywords: 2-Thioxothiazole; A(2A)R antagonist; Haloperidol; Radioligand-binding assay; cAMP assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine A2 Receptor Antagonists / chemical synthesis*
  • Adenosine A2 Receptor Antagonists / chemistry
  • Adenosine A2 Receptor Antagonists / pharmacology
  • Animals
  • Drug Design*
  • HEK293 Cells
  • Humans
  • Male
  • Mice
  • Models, Biological
  • Molecular Structure
  • Protein Binding / drug effects
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology
  • Receptor, Adenosine A2A* / chemistry
  • Thiazoles / chemical synthesis*
  • Thiazoles / chemistry
  • Thiazoles / pharmacology
  • Triazoles / chemistry
  • Triazoles / pharmacology

Substances

  • 4-thioxothiazolidin-2-one
  • 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
  • Adenosine A2 Receptor Antagonists
  • Pyrimidines
  • Receptor, Adenosine A2A
  • Thiazoles
  • Triazoles