New pyrrolopyrimidin-6-yl benzenesulfonamides: potent A2B adenosine receptor antagonists.
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.
Esteve
Cristina
C
Medicinal Chemistry Department, Almirall, Treball 2-4, E-08960 St. Just Desvern, Barcelona, Spain.
Nueda
Arsenio
A
Díaz
José Luis
JL
Beleta
Jorge
J
Cárdenas
Alvaro
A
Lozoya
Estrella
E
Cadavid
Maria Isabel
MI
Loza
Maria Isabel
MI
Ryder
Hamish
H
Vidal
Bernat
B
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*
D058917:Adenosine A2 Receptor Antagonists; D011744:Pyrimidinones; D013449:Sulfonamides