Design and Synthesis of 3‐Substituted‐thiazolyl‐2‐iminothiazolidin‐4‐ones as a New Class of Anticonvulsants

Abstract

A new series of 3-substituted-thiazolyl-2-iminothiazolidin-4-ones were synthesized by nucleophilic substitution of p-substituted-thiazol-2-yl-chloroacetamides with potassium thiocyanide by cyclization. The starting material p-substituted-thiazol-2-yl-chloroacetamides were synthesized from p-substituted-thiazol-2-yl-amines with chloroacetyl chloride, which in turn was prepared from one pot reaction of substituted aryl acetophenone and amino group of thiourea. The title compounds were investigated for their anticonvulsant activity. Among the tested compounds, compound 3-(4-(4-fluorophenyl)thiazol-2-yl)-2-iminothiazolidin-4-one (16) emerged as the most active compound of the series, and it is moderately more potent than the reference standard diazepam.

Thiazole-Bearing 4-Thiazolidinones as New Anticonvulsant Agents

“…Among different thiazolidinone subtypes, 5-substituted 2-amino(imino)-4-thiazolidinones [27] and 2-R-substituted-4-thiazolidinones are the most discussed compounds with confirmed anticonvulsant activity [28][29][30][31]. One of the efficient approaches for the design of new anticonvulsants is the combination of different heterocyclic cores, especially (thi)azoles in one molecule within a hybrid pharmacophore approach [19,21,[31][32][33][34][35][36].…”

“…Among different thiazolidinone subtypes, 5-substituted 2-amino(imino)-4-thiazolidinones [27] and 2-R-substituted-4-thiazolidinones are the most discussed compounds with confirmed anticonvulsant activity [28][29][30][31]. One of the efficient approaches for the design of new anticonvulsants is the combination of different heterocyclic cores, especially (thi)azoles in one molecule within a hybrid pharmacophore approach [19,21,[31][32][33][34][35][36]. Highly active compounds with anticonvulsant activity have been identified among compounds combining thiazolidinone and quinazoline-4(3H)-one [37], thiobarbituric acid, triazole [27], benzodiazepine [19], coumarin [18], thiazole [31], thiadiazole [21], indole [30] fragments, etc.…”

“…Moreover, thiazolidinone derivatives correspond to the structural requirements to new anticonvulsant structure: i) Contain cyclic imide or N-CO-CN fragments [20]; ii) involve the combination of two aromatic rings as hydrophobic domain; iii) contain N=C-NH moiety as hydrogen bonding domain; iv) contain carbonyl group as the electron donor group [21][22][23][24][25][26] (Figure 1). Among different thiazolidinone subtypes, 5-substituted 2-amino(imino)-4-thiazolidinones [27] and 2-R-substituted-4-thiazolidinones are the most discussed compounds with confirmed anticonvulsant activity [28][29][30][31]. One of the efficient approaches for the design of new anticonvulsants is the combination of different heterocyclic cores, especially (thi)azoles in one molecule within a hybrid pharmacophore approach [19,21,[31][32][33][34][35][36].…”

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“…Aminothiazole analogs have also been reported as ligands at adenosine receptors, 8 Anticonvulsants 9 and Thiazoles are also showed to exhibit numerous pharmacological activities 10 . This heterocyclic core is also reported in many natural products and pharmaceuticals.…”