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...

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Published in:Bioorganic & medicinal chemistry 2008-03, Vol.16 (5), p.2419-2430
Main Authors: Tabrizi, Mojgan Aghazadeh, Baraldi, Pier Giovanni, Preti, Delia, Romagnoli, Romeo, Saponaro, Giulia, Baraldi, Stefania, Moorman, Allan R, Zaid, Abdel Naser, Varani, Katia, Borea, Pier Andrea
Format: Article
Language:English
Subjects:
Adenosine A2 Receptor Antagonists
Humans
Magnetic Resonance Spectroscopy
Molecular Structure
Pyrazoles - chemical synthesis
Pyrazoles - chemistry
Pyrazoles - pharmacology
Receptor, Adenosine A2B - metabolism
Structure-Activity Relationship
Xanthines - chemical synthesis
Xanthines - chemistry
Xanthines - pharmacology
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Summary: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.
ISSN:1464-3391
DOI:10.1016/j.bmc.2007.11.058