New Urea and Thiourea Derivatives of Piperazine Doped with Febuxostat: Synthesis and Evaluation of Anti-TMV and Antimicrobial Activities

Abstract

A series of new 4-(5-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-2-carbonyl)-N-(substituted phenyl)piperazine-1-carboxamides8(a–e)/carbothioamides8(f–j)were accomplished for biological interest by the simple addition of active functionalized arylisocyanates7(a–e)/arylisothiocyanates7(f–j)with 2-isobutoxy-5-(4-methyl-2-(piperazine-1-carbonyl)thiazol-5-yl)benzonitrile(4). Compound4was synthesized in high yields (94%) by the condensation reaction of febuxostat (1) with piperazine using a selective reagent such as propylphosphonic anhydride (T3P). Antiviral activity againstTobacco mosaic virus(TMV) and antimicrobial activity of the synthesized compounds were evaluated. Biological data revealed that 4-nitrophenyl substituted urea8d, and 3-bromophenyl substituted thiourea8fexhibited promising antiviral activities. Moreover, 4-fluorophenyl substituted urea8a, 4-nitrophenyl substituted urea8d, 3-bromophenyl substituted thiourea8f, and 2,4-dichlorophenyl substituted thiourea8jexhibited potent antimicrobial activity.