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This lecture introduces the fundamentals of medicinal chemistry, focusing on the interrogation of Structure-Activity Relationships (SAR) in drug design. Topics include the multidisciplinary nature of medicinal chemistry, the limited synthetic toolbox available to med chemists, the importance of high-throughput screening (HTS) in lead discovery, and key milestones to reduce late-stage attrition of drug candidates. The lecture also covers the concepts of reversible vs. irreversible binders, compound selectivity in SAR evaluations, and the considerations for setting up small-molecule HTS. Practical examples and case studies are used to illustrate these concepts.