Additional interest in saturated sultams has rised from their advantageous physicochemical properties. Unlike azetidines, pyrrolidines, piperidines, etc., sultams demonstrate lower basicity, increased aqueous solubility, easy modification via N-alkylation, non-planar threedimensional structure, as well as resistance to proteasecatalyzed cleavage. Notably, γ-sultams closely resemble pyrrolidines in conformation, rather than their direct isosteric analogs -γ-lactams (pyrrolidones) with a flat amide moiety, therefore providing higher three-dimensionality. Theoretical studies and experimental data have demonstrated distinct conformational properties between amide and sulfonamide groups. Amide fragments typically adopt a planar configuration (torsion angle of the amide bond at 0° or 180°), while sulfonamides mainly exist in synclinal or anticlinal conformations (with corresponding torsion angles of ±60° and ±100°). Furthermore, the sulfonamide nitrogen atom exhibits non-planarity, characterized by significant pyramidization. Therefore, sultams can be considered bioisosteres of lactams, accounting for a certain degree of conformational divergence (Figure ). For instance, β-keto-γ-sultams are widely regarded as bioisosteres of tetramic acid 21. The corresponding ketosultam derivatives demonstrate efficacy in treating inflammation and autoimmune diseases due to their potent inhibitory effect on the adhesion of immunoglobulin LFA-1 (integrin αLβ2) to its ligand ICAM-1 (molecule of intercellular adhesion 1, also known as CD54). Other functionalyzed derivatives with amino-and alkoxy carbonyl groups attached to the sultam skeleton has also been enlightened (Figure ). Notably, compound 22, bearing an ester residue at the C-3 position exhibits notable antimycobacterial activity, particularly against Mycobacterium tuberculosis and M. kansasii.