A simple synthetic methodology was employed for synthesis of series of 5-methylpyrazine-2-carbohydrazide derivatives (PM series). In vitro anti-tubercular activity was evaluated against Mycobacterium tuberculosis (H37Rv) in Middle brook 7H-9 broth medium. Amongst synthesized compounds, seven compounds showed remarkable anti-tubercular activity. The 2-D QSAR illustrates the design PM series of compounds as potential anti-tubercular scaffolds that can be further optimized to improve the activity.