title: Synthesis of novel 7-imino-2-thioxo-3,7-dihydro-2H-thiazolo [4,5-d] pyrimidine derivatives as adenosine A2A receptor antagonists.
abstract: Novel bicyclic thiazolopyrimidine compounds (15-26) were synthesized to develop adenosine A(2A) receptor (A(2A)R) antagonist for the treatment of Parkinson's disease (PD). The binding affinity of the compounds (15-26) with A(2A)R was evaluated using radioligand binding assay on isolated membranes from stably transfected HEK293 cells. Selectivity of the compounds towards A(2A)R was assessed by comparing their binding affinities with A(1) receptors (A(1)R). cAMP concentrations were measured from HEK293 cells treated with compounds (15-26) as compared to NECA (A(2A)R agonist). The compound (16) possessed strongest A(2A)R binding affinity (K(i) value=0.0038 nM) and selectivity (737-fold) versus A(1)R. Decrease in A(2A)R-coupled release of endogenous cAMP from HEK293 cells treated with compounds (15-26) is evocative of their potential as A(2A)R antagonist.
authors.affiliation: Medicinal Chemistry Division, Dr BR Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110 007, India. pmluthra@acbr.du.ac.in
authors.forename: Pratibha Mehta
authors.initials: PM
authors.lastname: Luthra
authors.forename: Chandra Bhushan
authors.initials: CB
authors.lastname: Mishra
authors.forename: Pawan Kumar
authors.initials: PK
authors.lastname: Jha
authors.forename: Sandeep Kumar
authors.initials: SK
authors.lastname: Barodia
mesh_terms: D058917:Adenosine A2 Receptor Antagonists; D002460:Cell Line; D006801:Humans; D011485:Protein Binding; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D013844:Thiazoles