title: (6-methyl-2-methylsulfanyl-4-oxo-3,4-dihydro-3-pyrimidinyl)acetic acid and related compounds exhibiting anti-inflammatory activity.
abstract: Base-promoted hydrolysis of methyl or ethyl esters 1a-c gave the (6-methyl-2-methylsulfanyl-4-oxo-3,4-dihydro-3-pyrimidinyl)- and (5-ethyl-6-methyl-2-methylsulfanyl-4-oxo-3,4-dihydro-3-pyrimidinyl)acetic acids 2a, b. Under the reaction of ester 1a or acid 2a with nucleophilic reagents a series of derivatives 3-7 of acid 2a were synthesized and evaluated for their anti-inflammatory activity. Most of them were found to be more active than acetylsalicylic acid, and compounds 2a, 6a, b, 7a, f were significantly more active than ibuprofen. The compounds exhibiting the best anti-inflammatory activity showed negative inotropic effect.
mesh_terms: D000085:Acetates / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009200:Myocardial Contraction; D010210:Papillary Muscles / Q000187:drug effects; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
chemical_list: C467238:(6-methyl-2-methylsulfanyl-4-oxo-3,4-dihydro-3-pyrimidinyl)acetic acid; D000085:Acetates; D000889:Anti-Arrhythmia Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007202:Indicators and Reagents; D011743:Pyrimidines; D002351:Carrageenan