Synthesis of 3,6-disubstituted 7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines as novel analgesic/anti-inflammatory compounds

• Published in: European journal of medicinal chemistry Vol. 44; no. 11; pp. 4528 - 4538
• Main Authors: Aytac, S. Peri, Tozkoparan, Birsen, Kaynak, F. Betuel, Aktay, Goeknur, Goektas, Oezguer, Uenuevar, Songuel
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier 01.11.2009
• Subjects: Analgesics; Analgesics - adverse effects; Analgesics - chemical synthesis; Analgesics - chemistry; Analgesics - therapeutic use; Animals; Anti-Inflammatory Agents - adverse effects; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - therapeutic use; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - therapeutic use; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Carrageenan; Chemistry, Medicinal; Edema - chemically induced; Edema - drug therapy; Female; Life Sciences & Biomedicine; Male; Medical sciences; Mice; Mice, Inbred BALB C; Models, Molecular; Molecular Structure; Neuropharmacology; Pain Measurement - drug effects; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Thiadiazines - adverse effects; Thiadiazines - chemical synthesis; Thiadiazines - chemistry; Thiadiazines - therapeutic use; Triazoles - adverse effects; Triazoles - chemical synthesis; Triazoles - chemistry; Triazoles - therapeutic use; Ulcer - etiology; Triazolothiadiazines; Aminomercaptotriazoles; IBUPROFEN; Analgesic/anti-inflammatory activity; DERIVATIVES; Antioxidant activity; Edema; Toxicity; Rodentia; Antiinflammatory agent; Oral administration; Antioxidant; Biological activity; Dose activity relation; Vertebrata; Gastroduodenal; Mammalia; Analgesic; Mouse; Animal; Chlorine Organic compounds; Ulcer; Chemical synthesis
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2009.06.026

In this study, a new class of 4-amino-3-substituted-1,2,4-triazole-5-thiones (1-4) and their corresponding condensed derivatives 3,6-disubstituted 7H-1,2,4-triazolo[3,4-bi-1,3,4-thiadiazines (1a-4c) were synthesized and evaluated for their analgesic/anti-inflammatory activities. All synthesized compounds were also tested for their gastric toxicity and antioxidant activity on acute administration. Most of the compounds showed significant activity in both carrageenan-induced oedema and acetic acid-induced writhing tests besides negligible gastrointestinal toxicity. The compounds showing less ulcerogenic effect also showed less lipid peroxidation (LPO) level. Most promising results were obtained with the compounds that placed a fluoro or a chloride on the phenyl ring at the sixth position of the fused ring. (C) 2009 Elsevier Masson SAS. All rights reserved.