Synthesis, antimycobacterial activity, and acid dissociation constants of polyfunctionalized 3-[2-(pyrrolidin-1-yl)thiazole-5-carbonyl]-2 H-chromen-2-one derivatives

摘要

This study reports on synthesis and determination of antimycobacterial activity and acid dissociation constants of polyfunctionalized 3-[2-(pyrrolidin-1-yl)thiazole-5-carbonyl]-2 H -chromen-2-one derivatives, containing thiazole, coumarin, and pyrrolidine octahydropyrrolo[3,4- c ]pyrrole moieties. The products were synthesized by a cyclization reaction of 5,5-diphenylpyrrolidine N -aroylthioureas or methyl 5-substituted 4,6-dioxo-3,3-diphenyloctahydropyrrolo[3,4- c ]pyrrole-1-carboxylate N -aroylthioureas and 3-(bromoacetyl)coumarin with good to excellent yield (81–97%). The compounds exhibited antimycobacterial activity against the M. tuberculosis H37Rv strain with minimum inhibitory concentration values in the range of 31.25–125?μg/cm_(3). Acid dissociation constants of the compounds were determined using data which were obtained using a potentiometric titration method in 50% (v/v) dimethyl sulfoxide–water hydroorganic solvent at 25?±?0.1?°C, at an ionic background of 0.1?mol/dm_(3)of NaCl. Acid dissociation constants were calculated using the HYPERQUAD computer program. The acid dissociation constants obtained might be associated with SH, OH, and two NH groups, which were formed by the protonation of thiazole and pyrrolidine rings. Graphical abstract.