Synthesis and Antiinflammatory Activity of 3‐Substituted 4‐(4′‐Thiazolyl)‐Sydnones

Abstract

Sydnone derivatives with various substituents at C-4 of the phenyl ring and at C-2 of the thiazolyl ring were synthesised and tested for antiinflammatory activity. Five compounds have shown promising results. Synthese und entziindungshemmende Wirkung 3-subslituierter 4-(4'-Thiazolyl)-SydnoneSydnonderivate mit verschiedenen Substituenten in 4-Position des Phenyl-und 2-Position des Thiazolylringes wurden synthetisiert und auf entziindungshemmende Wirkung getestet. Fiinf der untersuchten Verbindungen zeigen vielversprechende Ergebnisse.Varied types of biological activities have been claimed for the mesoionic compounds. Sydnones, in particular have been studied for antibacterial, antitumour, antifungal, antimalarial, antiparasitic, analgesic, antiinflammantory, coccidiostatic, diuretic, hepatotoxic, and insecticidal activities').Various disubstituted 3-phenylsydnones2), sydnone 4-sulphonamides3), and 3-pyrazolyl phenyl sydnones4), have been synthesised in this laboratory and are shown t o possess considerable activity. Encouraged by these reports, it was planned t o introduce a thiazolyl moiety in 4-position of the 3-phenyl sydnone and t o subject these thiazolyl sydnones for biological evaluation.It may b e pointed out here that only two sydnones with thiazolyl moiety in 4-position have been reported5). However they have not been subjected for biological evaluation.Various 4-thiazolyl-3-phenyl sydnones with substitution in both, thiazolyl and phenyl ring have been synthesised and subjected for biological evaluation.T h e sydnones have been prepared (Table 1) by the literature methods as shown in the scheme. Acylation has been carried o u t with acetic acid and phoshorous pentoxide in benzene, following the method of Greco et a1.6). T h e ketones are then broniinated and further condensed with t h i o u r e a 8 to yield the desired compounds.Somc selected sydnones have been subjected t o antiinflammatory studies. They have been studied f o r acute toxicity test and were found t o b e non-toxic even at a dose of 400 mg/kg. T h e method used for screening o f these compounds is that according t o Winter e t al.7).

Mesoionic Sydnone: A Review in Their Chemical and Biological Properties

“…It was found that 3-substituted-4-(thiazol-4-yl) sydnone had a weak to moderate activity [51]. On the other hand, the presence of 5-arylpyrazole at C4 of the sydnone ring resulted in a favourable antiinflammatory activity as an anti-arthritis, anti-edema, and analgesic with less ulcerogenic side effects.…”

Novel sydnone derivatives carrying azidomethyl-1,2, 4-oxadiazole unit and their 1,3-dipolar cycloadditions

“…For example, muscarinic agonists, histamine H3 antagonists, antitumoral, anti-inflammatory, and antimycobacterium tuberculosis agents containing a 1,2,4-oxadiazole ring are among them. [7][8][9][10][11][12] On the other hand, triazole rings have also attracted remarkable attention due to their biological activities such as antifungal, anti-convulsant agents and especially popular in designing anticancer agents. [13][14][15][16][17] 1,3-Dipolar cycloaddition route is a valuable process to assemble molecules having fragments in biologically active agents of five-membered nitrogen heterocycles.…”

Synthesis and biological evaluation of 3-[p-(heterocyclocarbonyl)]phenylsydnones from the versatile precursor, 3-[p-(hydrazinocarbonyl)]phenylsydnone

“…Various pharmacologically active heterocycles such as thiazoles [5], imidathiazoles [6], pyrazoles [7,8], 8-hydroxy quinolines, coumarins [9,10], benzimidazoles [11], triazinoindoles [12], indazoles, and other such rings have been incorporated at the position 4 of the 3-arylsydnones. Very few heterocycles on the 3-phenyl ring of 3-phenylsydnone have been reported so far [13] despite the fact that many of these compounds have exhibited considerable analgesic, anti-inflammatory, and antimicrobial properties in preliminary screening.…”