Synthesis, antimicrobial and anti‐tubercular activity study of N‐(substituted‐benzyl)‐4‐(trifluoromethyl)thiazole‐2‐sulfonamide and 2‐(N‐(substituted‐benzyl)sulfamoyl)thiazole‐4‐carboxylic acid

Abstract

A series of novel N‐(substituted‐benzyl)‐4‐(trifluoromethyl)thiazole‐2‐sulfonamide (4a‐4i) and 2‐(N‐[2‐chlorobenzyl]sulfamoyl)thiazole‐4‐carboxylic acid (7a‐7i) derivatives were synthesized from readily available 4‐(trifluoromethyl)thiazol‐2‐amine (1) and ethyl 2‐aminothiazole‐4‐carboxylate (5), respectively. Eighteen novel thiazole‐2‐sulfonamide derivatives were synthesized. The targets were synthesized through a series of reactions involving diazotization and sulfonamide coupling reactions. All the synthesized compounds were characterized by 1H NMR, 19F, 13C NMR, HRMS, and HPLC analytical techniques. All the synthetic derivatives were evaluated for their antimicrobial activity (minimum inhibitory concentration) against a series of strains of Bacillus subtillis, Staphylococcus aureus, and Escherichia coli for antibacterial activity and against the strains of Candida albicans, Aspergillus flavus, and Aspergillus niger for antifungal activity. Also synthetic derivatives were tested for their in vitro anti‐tubercular (Mycobacterium tuberculosis: H37 Rv, MDR, and XDR strains) activities. Most of compounds showed moderate to good activity for antimicrobial and anti‐tubercular strains. The compounds 4b (MIC = 12.5 μg/ml and 3.125 μM), 4c (MIC = 1.562 μM), 4d (MIC = 12.5 μg/ml), 7b (MIC = 12.5 μg/ml), 7c (MIC = 26 μg/ml and 1.562 μM), and 7i (MIC = 26 μg/ml and 6.25 μM) showed good antimicrobial and anti‐tubercular activity in the range of (MIC = 12.5–26 μg/ml) and (MIC = 1.562–6.25 μM) against tested strains, while some derivatives show moderate inhibitions through the series.

Synthesis of 2-trifluoromethyl thiazoles via [3 + 2] cycloaddition of pyridinium 1,4-zwitterionic thiolates with CF3CN

“…DMSO = dimethyl sulfoxide, DMF = N,N-dimethylformamide, DMAC = dimethylacetamide, and NMP = N-methylpyrrolidone. b The yield was determined by 19 F NMR spectroscopy with PhOCF 3 as the internal standard.…”

“…[6][7][8] Particularly, trifluoromethylated thiazoles have gained more attention in recent years. [9][10][11][12][13][14][15][16][17][18][19] This is probably because the biological activity of thiazoles can be modified by the incorporation of trifluoromethyl into their structure. [20][21][22] For example, 2-trifluoromethylthiazole-5-carboxamides GPS488 and GPS491 (Fig.…”

“…), 2a derivative (0.10 mmol), NMP (1.0 mL), N 2 . b The yield was determined by19 F NMR spectroscopy with PhOCF 3 as the internal standard.…”

Thiazole Heterocycle: An Incredible and Potential Scaffold in Drug Discovery and Development of Antitubercular Agents

“…H 37 Rv showed excellent inhibition with a MIC value in a range between 1.562-3.125 μg/mL (Figure 15). [92] 4.13. Miscellaneous thiazole-based scaffolds…”