Synthesis, molecular docking with COX 1 and II enzyme, ADMET screening and in vivo anti-inflammatory activity of oxadiazole, thiadiazole and triazole analogs of felbinac

Abstract EN

Based on the core structure of Felbinac drug, three series (4a–d, 5a–d and 6a–n) of five membered heterocyclic derivatives containing three heteroatoms were designed and synthesized starting from Felbinac.

In the rational design of the target molecules, the biphenyl ring along with the methylene bridge of felbinac was retained while the carboxyl group was substituted with biologically active substituents like 1,2,4-triazole, 1,3,4-thiadiazole and 1,3,4-oxadiazole, with an intent to obtain novel, better and safer anti-inflammatory agents with improved efficacy.

The prepared molecules were then investigated for their anti-inflammatory, ulcerogenicity and analgesic activity in experimental animals.

The tested compounds exhibited varying degrees of inflammatory activity (25.21–72.87%), analgesic activity (27.50–65.24%) and severity index on gastric mucosa in the range of 0.20–0.80 in comparison to positive control felbinac (62.44%, 68.70% and 1.5, respectively).

Among all the prepared compounds, 2-(biphenyl-4-ylmethyl)-5-(4-chlorophenyl)-1,3,4-oxa diazole (6c) emerged as the most potent NSAID compound exhibiting the highest antiinflammatory activity (72.87% inhibition) and analgesic activity (65.24%) along with the least