Synthesis of some 1,2,4-triazolo[3,2-b]-1,3-thiazine-7-ones with potential analgesic and antiinflammatory activities.
Starting from 3-substituted-1,2,4-triazole-5-thiones (la-h), eight new 5-carbomethoxy-2-substituted-7H-1,2,4-triazolo[3,2-b]-1,3-thiazine-7-ones (2a-h) were synthesized and characterized by spectral and elementary analysis. The obtained compounds were submitted to preliminary pharmacological assay to evaluate their antiinflammatory and analgesic activities as well as gastrointestinal irritation liability and acute toxicity. Among the compounds studied, compounds 2c, 2d, 2e and 2h showed most remarkable antiinflammatory activity in the carrageenan and serotonin induced edema and in the inhibition of castor oil-induced diarrhea tests. The analgesic activity of these active compounds correlated with their antiinflammatory activities in the inhibition of acetic acid-induced writhing test. In gastric ulceration studies, the compounds were found safety at low dose levels (10 and 20 mg/kg).
Tozkoparan
Birsen
B
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Sihhiye, Turkey. tbirsen@hacettepe.edu.tr
Aktay
Göknur
G
Yeşilada
Erdem
E
D019342:Acetic Acid / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D002351:Carrageenan / Q000494:pharmacology; D002368:Castor Oil / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005528:Foot / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D012701:Serotonin / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D014456:Ulcer / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013843:Thiazines; D012701:Serotonin; D002368:Castor Oil; D002351:Carrageenan; D019342:Acetic Acid