Design and Synthesis of 1,2,4 ‐Triazolo[3,2‐b]‐1,3,5‐thiadiazine Derivatives as a Novel Template for Analgesic/Anti‐Inflammatory Activity

Previously, we demonstrated that certain heterocyclic compounds derived from 3‐substituted‐1,2,4‐triazole‐5‐thiones had promising analgesic/anti‐inflammatory activities together with low ulcerogenic properties. Therefore, we sought to design and synthesize new derivatives of triazol‐5‐thiones‐fused heterocycles. In the present study, a series of novel bis‐Mannich bases, namely 2,6‐disubstituted‐6,7‐dihydro‐5H‐1,2,4‐triazolo[3,2‐b]‐1,3,5‐thiadiazines (1a–d, 2a–c, and 3a–d), were synthesized and characterized to assess their possible anti‐inflammatory/analgesic properties. Additionally, their ability to induce gastric toxicity was also evaluated. Several of the condensed compounds produced a degree of analgesic activity comparable to reference drugs in both the hot plate and tail‐flick tests. A strong anti‐inflammatory effect was observed for the derivatives carrying a benzyl group at the second position (2a–c). The majority of the prepared compounds caused comparatively less gastrointestinal (GI) side effects than the reference drugs naproxen and indomethacin did. These results showed that 1,2,4‐triazolo[3,2‐b]‐1,3,5‐thiadiazine derivatives might afford a safer alternative to currently available analgesic/anti‐inflammatory agents for the treatment and management of inflammatory disease and pain. Several of the new compounds derived from 1,2,4‐triazolo[3,2‐b]‐1,3,5‐thiadiazine had marked analgesic activity w...
Source: Archiv der Pharmazie - Category: Drugs & Pharmacology Authors: Tags: Full Paper Source Type: research