title: Design and synthesis of (4E)-4-(4-substitutedbenzylideneamino)-3-substituted-2,3-dihydro-2-thioxothiazole-5-carbonitrile as novel A2A receptor antagonists.
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.
authors: Neuropharmaceutical Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, Mall Road, Delhi 110 007, India.
authors: Chandra Bhushan
authors: CB
authors: Mishra
authors: Dimpy
authors: D
authors: Sharma
authors: Amresh
authors: A
authors: Prakash
authors: Namrata
authors: N
authors: Kumari
authors: Nitin
authors: N
authors: Kumar
authors: Pratibha Mehta
authors: PM
authors: Luthra
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D015195:Drug Design; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008954:Models, Biological; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology; D043705:Receptor, Adenosine A2A / Q000737:chemistry; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology
chemical_list: C471060:4-thioxothiazolidin-2-one; C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058917:Adenosine A2 Receptor Antagonists; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D013844:Thiazoles; D014230:Triazoles
keywords: 2-Thioxothiazole; A(2A)R antagonist; Haloperidol; Radioligand-binding assay; cAMP assay