Advanced Synthesis of Pharmaceutical Substances 1200-2CHMMO1W3
This lecture will outline the contemporary medicinal chemistry of low-molecular-weight antiviral active substances, with particular emphasis on nucleoside and oligopeptide drugs. The lecture will discuss methods for the design, synthesis, and optimization of nucleoside antivirals such as remdesivir, molnupiravir, favipiravir, and galidesivir, as well as selected peptide compounds, including lufotrelvir and its structural evolution leading to nirmatrelvir. The highly effective enzymatic reaction cascade strategy leading to the production of an antiviral substance with exceptionally high yield and purity will be explained. Principles for studying the biological activity of antiviral substances and strategies for optimizing their chemical structure will be presented. Particular emphasis will be placed on elucidating the mechanisms of action of these compounds at the molecular level. Nobel Prize-winning diffraction and spectroscopic methods used in structural studies of antiviral substances and their interactions with macromolecular targets will also be discussed. The lecture also includes a presentation of the PROTIDE nucleotide prodrug concept. The multi-level rationale for the repositioning strategy for antiviral substances will be discussed, based on the molecular biology of viruses, with particular emphasis on viral genome replication by RNA-dependent RNA polymerase. It will be explained how this repositioning strategy enables the strategic goal of creating libraries of antiviral substances for further structural optimization and rapid deployment in the event of future epidemics. The lecture is illustrated with materials from leading research centers published in major open access journals (no textbooks). The teaching material is presented in the form of slides and short videos, and is subsequently made available for each lecture.
Estimated student workload during the semester – 38 hours, including:
participation in classes – 15 hours
individual study after each lecture – 5 hours
exam preparation – 13 hours
consultations with the instructor – 5 hours
Type of course
Mode
Course coordinators
Learning outcomes
Understanding modern methods of advanced medical chemistry on the example of designing and obtaining active substances of drugs against the SARS-CoV-2 virus. Acquiring the ability to perform retrosynthetic analysis and design a general scheme for the synthesis of antiviral nucleosides. Understanding the mechanisms of action of antiviral drugs at the molecular level.
Knowledge: the graduate knows and understands:
K_W04 – contemporary methods for the synthesis of complex organic compounds, including those with therapeutic effects, utilizing both classical and the latest achievements in organic synthesis.
Skills: the graduate is able to:
K_U24 – plan the synthesis of complex organic compounds, including those with therapeutic effects.
Social competences: the graduate is ready to:
K_K05 – assess the scope of their own knowledge and skills and to continuously improve their professional and personal competences.
Assessment criteria
Final written exam, covering lecture material only. Answering 15 questions in 1.5 hours, either descriptively or graphically (structural formulas or synthesis diagrams), in handwritten or electronic format.
Bibliography
Open Access 2-3 publications from the leading scientific journals presented at each lecture.
Additional information
Additional information (registration calendar, class conductors, localization and schedules of classes), might be available in the USOSweb system: