A series of forty Mannich bases of glutarimides with sulfonamides and secondary amines were synthesized and evaluated in vitro against six pathogenic Gram-positive and Gram-negative bacteria. The synthesized Mannich bases were characterized by elemental and spectral analysis. The modeling anti-bacterial activities of these newly synthesized Mannich bases against six bacteria was attempted employing ¹H NMR chemical shift, physicochemical properties and topological indices as the correlating parameters. Our results, based on Quantitative Structure-Activity Relationships (QSARs), have indicated that statistically significant models are obtained for modeling the anti-bacterial activities The results are discussed critically using a variety of statistical parameters.