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

Abstract

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.

Nano nickel [1,2,4]‐triazole‐3‐thiones complex: Design, sonochemical synthesis, and antimicrobial evaluation

“…The technique of co-crystal formation through solid-state grinding has been recognized for a few times. [11,12] A significant development to solid-state grinding was illustrated recently, the co-crystallization kinetics can be significant enhanced by the addition of a few drops of solvent. Nowadays, we perceive that the "solvent-drop grinding" methodology may afford a fruitful means of controlling the polymorphic outcome of a co-crystallization.…”

Bicyclic 5-6 Systems With One Bridgehead (Ring Junction) Nitrogen Atom: Four Extra Heteroatoms 2:2

“…The cleavage of the C-N bond at N6 position could be also clearly identified. 12 <Scheme 2 near here>.…”

An insight on medicinal attributes of 1,2,4-triazoles

“…Some other 1,2,4-triazole derivatives have been synthesized and screened for anti-inflammatory and analgesic activities [ [236] , [237] , [238] ].…”