Analgesic activity of new 8-methoxy-1,3-dimethyl-2,6-dioxo-purin-7-yl derivatives with carboxylic, ester or amide moieties

BackgroundThe previous studies in a group of 4-arylpiperazinylalkyl derivatives of purine-2,6-dione and several other heterocyclic systems revealed their analgesic properties. In an effort to establish new analgesic agents we designed and synthesized a series of new 8-methoxy-1,3-dimethyl-2,6-dioxo-purin-7-yl derivatives with terminal carboxylic, ester or amide moieties.MethodsThe obtained compounds were evaluated pharmacologically in two in vivo models: the writhing syndrome and the formalin tests. The influence of the investigated compounds on the phosphodiesterase (PDE) activity was also determined.ResultsMajority of the tested compounds showed significant analgesic activity. The strongest analgesic and anti-inflammatory effect were observed for benzylamide (10) and 4-phenylpiperazinamide (11–14) derivatives which were more active than acetylic acid used as a reference drug (up to 23 and 36 fold increase in activity in writhing and formalin test, respectively). Several active compounds stronger than theophylline inhibited the phosphodiesterase activity.ConclusionThe present study revealed that the presented compounds are new class of analgesic and anti-inflammatory agents and are worthy of the further evaluation regarding to their pharmacological properties.