title: New pyrrolopyrimidin-6-yl benzenesulfonamides: potent A2B adenosine receptor antagonists.
abstract: A new series of 4-(1,3-dialkyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulfonamides has been identified as potent A2B adenosine receptor antagonists. The products have been evaluated for their binding affinities for the human A2B, A1 and A3 adenosine receptors. 6-(4-{[4-(4-Bromobenzyl)piperazin-1-yl]sulfonyl}phenyl)-1,3-dimethyl-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione (16) showed a high affinity for the A2B adenosine receptor (IC50=1 nM) and selectivity (A1: 183x; A3: 12660x). Synthesis and SAR of this novel class of compounds showing improved absorption properties is presented herein.
authors.affiliation: Medicinal Chemistry Department, Almirall, Treball 2-4, E-08960 St. Just Desvern, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Esteve
authors.forename: Arsenio
authors.initials: A
authors.lastname: Nueda
authors.forename: José Luis
authors.initials: JL
authors.lastname: Díaz
authors.forename: Jorge
authors.initials: J
authors.lastname: Beleta
authors.forename: Alvaro
authors.initials: A
authors.lastname: Cárdenas
authors.forename: Estrella
authors.initials: E
authors.lastname: Lozoya
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Cadavid
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Loza
authors.forename: Hamish
authors.initials: H
authors.lastname: Ryder
authors.forename: Bernat
authors.initials: B
authors.lastname: Vidal
mesh_terms: D058917:Adenosine A2 Receptor Antagonists; D001667:Binding, Competitive; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D011744:Pyrimidinones; D013449:Sulfonamides