2 ‐Benzamido‐4‐methylthiazole‐5‐carboxylic Acid Derivatives as Potential Xanthine Oxidase Inhibitors and Free Radical Scavengers

The new chemical entities febuxostat and topiroxostat have been approved by the US Food and Drug Administration, opening new avenues for exploiting different heterocycles other than purines as xanthine oxidase (XO) inhibitors. A different series of substituted 2‐benzamido‐4‐methylthiazole‐5‐carboxylic acid derivatives (5a–r) was synthesized and characterized by the collective use of IR, 1H and 13C NMR, and mass spectroscopy, for the treatment of gout and hyperuricemia. In vitro studies of the synthesized derivatives revealed that the presence of a fluoro group at the para position in 5b (IC50 = 0.57 μm) and a chloro group in 5c (IC50 = 0.91 μm) signifies excellent XO inhibitory activity among the series, along with their DPPH free radial scavenging activity. In vivo serum uric acid inhibition studies established that 5b and 5c displayed 62 and 53% uric acid inhibition, respectively. Studies on enzyme kinetics indicated that 5b acts as a mixed type inhibitor. In silico prediction by various softwares also helped in the recognition of potent XO inhibitors. A series of 2‐benzamido‐4‐methylthiazole‐5‐carboxylic acid derivatives as structural analogs of febuxostat was synthesized and their xanthine oxidase inhibitory activities were established by in vitro and in vivo methods. Compound 5b exhibited significant uric acid inhibition activity along with DPPH free radical scavenging activity.
Source: Archiv der Pharmazie - Category: Drugs & Pharmacology Authors: Tags: Full Paper Source Type: research