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 A1 and A2A receptors

Synthesis of a New Series of 1H‐Imidazol‐1‐yl Substituted 8‐Phenylxanthines as Adenosine Receptor Ligands

“…The observed affinities of various newly synthesized 8-phenylxanthine derivatives in radioligand-binding assays at human A 1 and A 2A receptors are compiled in the Table. The three series, i.e., vanillin-, isovanillin-, and 3-hydroxybenzaldehyde-based xanthine derivatives displayed varying degrees of affinity and selectivity towards A 1 and A 2A receptor subtypes despite a common substitution of chloro/(imidazolyl)alkoxy group on 8-phenyl ring in accordance with our earlier report [6]. This is attributed to the varied positioning of the phenyl substituent.…”

“…As a part of our ongoing research program directed towards the search for new 8-phenyl-substituted xanthine-based highly effective ligands for the adenosine receptors [6] [7], here we report a new series of 8-{[(imidazolyl)alkoxy]phenyl}xanthines along with variable substitutions at 1-, 3-, and 7-positions of the 8-phenylxanthine scaffold. The substitution pattern of the 8-phenyl substituent was also changed to study its effects on the affinity for adenosine A 1 and A 2A receptors.…”

“…8-Phenyltheophylline is the parent member of a variety of potent adenosine receptor antagonists. It has been established that appropriate substituents on the phenyl ring at C(8) affects the potency and selectivity towards adenosine receptors and thus their pharmacological effects [4] [6].…”

Synthesis of 8-(cyclopentyloxy)phenyl substituted xanthine derivatives as adenosine A2A ligands

“…The yellowcolored precipitateo btained wasfiltered off,washed withi ce-cold water,dried and crystallized from ethertoo btain 4d (0.67 g,M .p.80-84°C). 1 …”

“…Recentlyw eh avereported astudyon the effects of the substitution patterno fp henylsubstituents on the affinity foradenosine receptors in anews eriesof 8-(substituted-phenyl)xanthines( 1 ) [1] (Fig. 1).…”