The anti-tubercular activity of 6-chloro-2-ethyl-N-(4-(4-(4-(trifluoromethoxy)phenyl)piperidin-1-yl)benzyl)imidazo [1,2-a]pyridine-3-carboxamide (Q203) is modified by varying its side chain. In this study, we synthesized Q203 analogues with different side chains and studied their effects on anti-tubercular activity. Many analogues showed good potency against M. tuberculosis replicating in liquid broth culture medium (extracellular activity) regardless of chain length and conformational changes. However, a polar character in the side chain region was unfavorable for anti-tubercular activity. The analogues, 25, 28, 35, and 36, displayed excellent activity against M. tuberculosis replicating inside macrophages (intracellular activity) and promising pharmacokinetic (PK) properties with high drug exposure level and long half-life.