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

Background: the 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.methods: the 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.results: majority 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.conclusion: the 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. © 2014 institute of pharmacology,polish academy of sciences.