1,3-Dipropyl-8-(1-phenylacetamide-1H-pyrazol-3-yl)-xanthine derivatives as highly potent and selective human A(2B) adenosine receptor antagonists.
A new series of 1,3-dipropyl-8-(1-phenylacetamide-1H-pyrazol-3-yl)-xanthine derivatives has been identified as potent A(2B) adenosine receptor antagonists. The products have been evaluated for their binding affinities for the human A(2B), A(1), A(2A), and A(3) adenosine receptors. N-(4-chloro-phenyl)-2-[3-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-5-methyl-pyrazol-1-yl] (11c) showed a high affinity for the human A(2B) adenosine receptor K(i)=7nM and good selectivity (A(1), A(2A), A(3)/A(2B)>140). Synthesis and SAR of this novel class of compounds is presented herein.
Tabrizi
Mojgan Aghazadeh
MA
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Via Fossato di Mortara 17-19, 44100 Ferrara, Italy.
Baraldi
Pier Giovanni
PG
Preti
Delia
D
Romagnoli
Romeo
R
Saponaro
Giulia
G
Baraldi
Stefania
S
Moorman
Allan R
AR
Zaid
Abdel Naser
AN
Varani
Katia
K
Borea
Pier Andrea
PA
D058917:Adenosine A2 Receptor Antagonists; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D043704:Receptor, Adenosine A2B / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
C528615:1,3-dipropyl-8-(1-phenylacetamide-1H-pyrazol-3-yl)-xanthine; D058917:Adenosine A2 Receptor Antagonists; D011720:Pyrazoles; D043704:Receptor, Adenosine A2B; D014970:Xanthines