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The importance of sulfur-containing motifs in drug design and discovery

ABSTRACT Introduction Sulfur-containing functional groups are privileged motifs that occur in various pharmacologically effective substances and several natural products. Various functionalities are found with a sulfur atom at diverse oxidation states, as illustrated by thioether, sulfoxide, sulfone, sulfonamide, sulfamate, and sulfamide functions. They are valuable scaffolds in the field of medicinal chemistry and are part of a large array of approved drugs and clinical candidates. Area Covered Herein, the authors review the current research on the development of organosulfur-based drug discovery. This article also covers details of their roles in the new lead compounds reported in the literature over the past five years 2017–2021. Expert opinion Given its prominent role in medicinal chemistry and its importance in drug discovery, sulfur has attracted continuing interest and has been used in the design of various valuable compounds that demonstrate a variety of biological and pharmacological feature activities. Overall, sulfur’s role in medicinal chemistry continues to grow. However, many sulfur functionalities remain underused in small-molecule drug discovery and deserve special attention in the armamentarium for treating diverse diseases. Research efforts are also still required for the development of a synthetic methodology for direct access to these functions and late-stage functionalization.