Synthesis of 8-(cyclopentyloxy)phenyl substituted xanthine derivatives as adenosine A2A ligands.
The present paper describes the synthesis of a series of 8-(cyclopentyloxy)phenyl-xanthines and their evaluation for affinity for A1 and A2 adenosine receptors using radioligand binding assays. The effects of moving the cyclopentyloxy substituent with or without an ortho methoxy group on the various positions of the 8-phenyl ring have been studied. The vanilloid based xanthines 8-[4-(cyclopentyloxy)-3-methoxyphenyl]-1,3-dimethylxanthine (6a) (K(i)= 100 nM) and 8-[(4-cyclopentyloxy)-3-methoxyphenyl] -3-methyl-1-propylxanthine (12) (K(i) = 150 nM) displayed the highest affinity at A2A receptors as well as over 1000 fold selectivity over the A1 adenosine receptor subtype.
Bansal
Ranju
R
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India. ranju29in@yahoo.co.in
Kumar
Gulshan
G
Gandhi
Deepika
D
Yadav
Rakesh
R
Young
Louise C
LC
Harvey
Alan L
AL
D018927:Anti-Asthmatic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D011869:Radioligand Assay; D043682:Receptor, Adenosine A1 / Q000187:drug effects / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000187:drug effects* / Q000378:metabolism; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D019820:Xanthine / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*
D018927:Anti-Asthmatic Agents; D007202:Indicators and Reagents; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D019820:Xanthine