title: Analgesic activity of new 8-methoxy-1,3-dimethyl-2,6-dioxo-purin-7-yl derivatives with carboxylic, ester or amide moieties.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University, Medical College, Kraków, Poland. Electronic address: malgorzata.zygmunt@uj.edu.pl.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zygmunt
authors.affiliation: Department of Medicinal Chemistry, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Grażyna
authors.initials: G
authors.lastname: Chłoń-Rzepa
authors.affiliation: Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Sapa
authors.affiliation: Department of Medicinal Chemistry, Jagiellonian University, Medical College, Kraków, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Pawłowski
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde; D007202:Indicators and Reagents; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D018712:Analgesics, Non-Narcotic; D007202:Indicators and Reagents; D010726:Phosphodiesterase Inhibitors; D011687:Purines; D005557:Formaldehyde; D010727:Phosphoric Diester Hydrolases
keywords: 8-Methoxy-2,6-dioxo-purin-7-yl derivatives; Analgesic; Anti-inflammatory activities