title: Synthesis of a series of 8-(substituted-phenyl)xanthines and a study on the effects of substitution pattern of phenyl substituents on affinity for adenosine A(1) and A(2A) receptors.
abstract: A new series of 8-(substituted-phenyl)xanthines have been synthesized and compounds were evaluated for their affinity for A(1) and A(2) adenosine receptors (AR) using radioligand binding assays. The effects of varying the positions of 8-phenyl substituents on affinity and selectivity at A(1) and A(2A) adenosine receptors have been studied. Isovanilloid 1,3-dimethyl-8-[4-methoxy-3-(2-morpholin-4-ylethoxy)phenylxanthine (9d) displayed the highest affinity and selectivity towards A(2A) AR subtypes with K(i)=100nM over A(1) receptors (Ki>100mM). It has been observed that substitution pattern on 8-phenyl group greatly affects the affinity and selectivity at adenosine receptors, with A(2A) tolerating bulkier substituents than did A(1) receptors.
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: Ranju
authors.initials: R
authors.lastname: Bansal
authors.forename: Gulshan
authors.initials: G
authors.lastname: Kumar
authors.forename: Deepika
authors.initials: D
authors.lastname: Gandhi
authors.forename: Louise C
authors.initials: LC
authors.lastname: Young
authors.forename: Alan L
authors.initials: AL
authors.lastname: Harvey
mesh_terms: D000818:Animals; D006801:Humans; D011485:Protein Binding; D011869:Radioligand Assay; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D014970:Xanthines