Synthesis of 3,6-disubstituted 7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines as novel analgesic/anti-inflammatory compounds.
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-b]-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.
Aytaç
S Peri
SP
Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 06100 Sihhiye, Ankara, Turkey.
Tozkoparan
Birsen
B
Kaynak
F Betül
FB
Aktay
Göknur
G
Göktaş
Ozgür
O
Unüvar
Songül
S
D000700:Analgesics / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D015394:Molecular Structure; D010147:Pain Measurement / Q000187:drug effects; D013829:Thiadiazines / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D014230:Triazoles / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D014456:Ulcer / Q000209:etiology
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D013829:Thiadiazines; D014230:Triazoles; C045575:1,2,4-triazole; D002351:Carrageenan