According to the IUPAC recommendations in 1998, ‘Medicinal Chemistry’ is defined as: “Medicinal Chemistry is a chemistry-based discipline, also involving aspects of biological, medical, and pharmaceutical sciences. It is concerned with the invention, discovery, design, identification, and preparation of biologically active compounds, the study of their metabolism, the interpretation of their mode of action at the molecular level, and the construction of structure-activity relationships.” In this course all aspects of Medicinal Chemistry will be discussed (during lectures and work-sessions), although with a strong emphasis on drug design and synthesis, inspired by the most significant molecules now used in modern medicine, like: cyclosporine, maraviroc, oseltamivir, imatinib, epothilone, enalapril, and paroxetine.
The course starts with a short recapitulation of the most important items as learned in the Organic Chemistry 2 course, followed by the introduction of retrosynthetic analysis, one-group C-X disconnections, functional group interconversions (FGI), and 1,2- respectively 1,3-disconnections for the synthesis of C-X and C-C bonds. Then, protecting group strategy is discussed and applied for the synthesis of peptides (including amide bond formation), either in solution or on the solid support. Based on solid phase organic synthesis, combinatorial chemistry, parallel synthesis, and library design is discussed, and some approaches to achieve high chemical diversity (multicomponent reactions, diverted total synthesis) will be used as important examples for lead finding and optimization. Important carbon-carbon formation reactions, Pd-catalyzed cross-coupling reactions, and Ru-based ring-closing metathesis will be exemplified and discussed. Finally, reaction optimization of initial laboratory routes toward large-scale industrial processes will be the last topic of this course.

Examination
Written exam (60%); Drug Monograph: ‘The birth and life of a first-in-class drug’; a written report (30%) followed by a short oral presentation (10%) to discuss the results with the teacher and students.