title: Discovery of 7-(Prolinol-N-yl)-2-phenylamino-thiazolo[5,4-d]pyrimidines as Novel Non-Nucleoside Partial Agonists for the A2A Adenosine Receptor: Prediction from Molecular Modeling.
abstract: We describe the identification of 7-(prolinol-N-yl)-2-phenylamino-thiazolo[5,4-d]pyrimidines as a novel chemotype of non-nucleoside partial agonists for the A2A adenosine receptor (A2AAR). Molecular-modeling indicated that the (S)-2-hydroxymethylene-pyrrolidine could mimic the interactions of agonists' ribose, suggesting that this class of compounds could have agonistic properties. This was confirmed by functional assays on the A2AAR, where their efficacy could be associated with the presence of the 2-hydroxymethylene moiety. Additionally, the best compound displays promising affinity, selectivity profile, and physicochemical properties.
authors.forename: Sandip B
authors.initials: SB
authors.lastname: Bharate
authors.forename: Baljinder
authors.initials: B
authors.lastname: Singh
authors.affiliation: Institut für Pharmakologie und Toxikologie, Julius-Maximilians-Universität Würzburg , Versbacher Strasse 9, D-97078 Würzburg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Kachler
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University , Box 596, SE-751 24 Uppsala, Sweden.
authors.forename: Ana
authors.initials: A
authors.lastname: Oliveira
authors.forename: Vikas
authors.initials: V
authors.lastname: Kumar
authors.forename: Sonali S
authors.initials: SS
authors.lastname: Bharate
authors.forename: Ram A
authors.initials: RA
authors.lastname: Vishwakarma
authors.affiliation: Institut für Pharmakologie und Toxikologie, Julius-Maximilians-Universität Würzburg , Versbacher Strasse 9, D-97078 Würzburg, Germany.
authors.forename: Karl-Norbert
authors.initials: KN
authors.lastname: Klotz
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University , Box 596, SE-751 24 Uppsala, Sweden.
authors.forename: Hugo
authors.initials: H
authors.lastname: Gutiérrez de Terán
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000737:chemistry* / Q000494:pharmacology*; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000619663:7-(prolinol-N-yl)-2-phenylamino-thiazolo(5,4-d)pyrimidine; D058908:Adenosine A2 Receptor Agonists; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D013844:Thiazoles