The synthesis of 4-thiazolidinone derivatives using 2-(4-R-2-formylphenoxy)-N-(R’-phenyl)acetamides and their anti-inflammatory activity

Abstract

The research is devoted to the rational design of new non-steroidal anti-inflammatory drugs (NSAIDs) using the 4-thiazolidinone “core”. A series of 2-(4-R-2-formylphenoxy)-N-(R’-phenyl)acetamides has been synthesized from salicylic aldehydes for structural modifications of basic heterocycles. The aldehydes obtained are active carbonyl agents and suitable “building blocks” for the focused synthesis of biologically active compounds. Ylidene derivatives of 2-thioxo-4-thiazolidinone and 2-(4-hydroxyphenyl)imino-4-thiazolidone have been synthesized in the Knoevenagel reaction conditions. The one-pot reaction between 3(5)-merkapto-1,2,4-triazoles, chloroacetic acid and the salicylic aldehyde derivatives synthesized have been used for the synthesis of 5-ylidene-thiazolo[3,2-b][1,2,4]triazol-6-one. Parameters of acute toxicity and the anti-exudative activity (carrageenin paw edema test) have been studied for the ylidene derivatives synthesized. It has been found that all compounds synthesized demonstrate the anti-exudative activity, and some “structure – acute toxicity – anti-exudative activity” relationships have been analyzed. Based on the results of in vivo studies the lead compound – 4-{2-[4-chloro-2-(6-oxothiazolo[3,2-b][1,2,4]triazole-5-ylidenemethyl)-phenoxy]- acetylamino}-benzoic acid ethyl ester that demonstrates the anti-exudative activity equivalent to the classic NSAID Diclofenac has been identified, it has a low level of toxicity and can be recommended for the profound study.