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

作者：Zygmunt Malgorzata^*; Chlon Rzepa Grazyna; Sapa Jacek; Pawlowski Maciej

来源：Pharmacological Reports, 2015, 67(1): 9-16.

DOI：10.1016/j.pharep.2014.07.018

• 8-Methoxy-2,6-dioxo-purin-7-yl derivatives
• Analgesic
• Anti-inflammatory activities

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.

• 出版日期2015-2