Synthesis and Anti-Tuberculosis Activity of Novel 3-(1-(4-(benzoyl)benzyl)-1H-indol-5-yl)-1,2,4-oxadiazol-5(4H)-one Derivatives

A novel class of 3-(1-(4-(benzoyl)benzyl)-1H-indol-5-yl)-1,2,4-oxadiazol-5(4H)-one derivatives has been synthesized. Structure–activity relationship studies revealed that attaching N-(4-methoxyphenyl)-4-methylbenzamide group to the 1H-indol-5-yl-1,2,4-oxadiazol-5(4H)-one ring significantly improved antituberculosis activity. Furthermore substitution of electron withdrawing groups such as chloro, fluoro, or cyano substitutions on 4- and 6-positions of the N-(4-methoxyphenyl)-4-methylbenzamide significantly improved metabolic stability. Some of the synthesized compounds showed improved in vitro activity compared to most of the current standard antituberculosis drugs such as rifampicin and isoniazid. Thus, substituted 3-(1-(4-(benzoyl)benzyl)-1H-indol-5-yl)-1,2,4-oxadiazol-5(4H)-one derivatives may serve as promising new class of antituberculosis agents.