title: New insight into adenosine receptors selectivity derived from a novel series of [5-substituted-4-phenyl-1,3-thiazol-2-yl] benzamides and furamides.
abstract: A series of [5-substituted-4-phenyl-1,3-thiazol-2-yl] benzamide and furamide analogues were investigated in radioligand binding studies at adenosine receptor subtypes with an aim to obtain potent and selective adenosine receptor ligands. Benzamide and furamide linked to thiazole was found to be crucial for high adenosine receptor affinity. The most potent compound indentified in this study was 5d with low nanomolar affinity for all four adenosine receptor subtypes. Compounds 5a and 5g showed moderate selectivity for A2A adenosine receptors. Molecular docking versus all four human adenosine receptors combined with membrane molecular dynamics studies were performed to rationalise the peculiar selectivity profile of 5d antagonist.
authors.affiliation: Department of Medicinal Chemistry, B.V. Patel Pharmaceutical Education and Research Development, Ahmedabad 380 054, Gujarat, India.
authors.forename: Gajanan S
authors.initials: GS
authors.lastname: Inamdar
authors.forename: Amit N
authors.initials: AN
authors.lastname: Pandya
authors.forename: Hardik M
authors.initials: HM
authors.lastname: Thakar
authors.forename: Vasudevan
authors.initials: V
authors.lastname: Sudarsanam
authors.forename: Sonja
authors.initials: S
authors.lastname: Kachler
authors.forename: Davide
authors.initials: D
authors.lastname: Sabbadin
authors.forename: Stefano
authors.initials: S
authors.lastname: Moro
authors.forename: Karl-Norbert
authors.initials: KN
authors.lastname: Klotz
authors.forename: Kamala K
authors.initials: KK
authors.lastname: Vasu
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D017434:Protein Structure, Tertiary; D058914:Purinergic Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011869:Radioligand Assay; D043705:Receptor, Adenosine A2A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013844:Thiazoles / Q000737:chemistry*; D014162:Transfection
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D000577:Amides; D001549:Benzamides; D005663:Furans; D058914:Purinergic Antagonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D013844:Thiazoles; C004932:diloxanide furoate