How scientists discover new drugs against viruses: Medicinal Chemistry & Drug Design (Hepatitis C)

Let's explore drug design and medicinal chemistry by looking at GSK's development of Hepatitis C Virus inhibitors!

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Correction: Before the nerds call me out 🤓 - some visuals are missing the N-methyl group on the amide and aryl fluoride on the inhibitor

00:00 Drug discovery is not easy
02:30 What is Hepatitis C and why do we care
07:14 How to inhibit a virus
08:57 Chemical optimization & structure-activity relationship
13:22 UNEXPECTED turn of events in clinical development
18:44 Implications of new design on DMPK and clinical success

Key references:
- Design of N-Benzoxaborole Benzofuran GSK8175—Optimization of Human Pharmacokinetics Inspired by Metabolites of a Failed Clinical HCV Inhibitor: J. Med. Chem. 2019, 62, 7, 3254
- Discovery of a Potent Boronic Acid Derived Inhibitor of the HCV RNA-Dependent RNA Polymerase: J. Med. Chem. 2014, 57, 5, 1902
- HCV796: A Selective Nonstructural Protein 5B Polymerase Inhibitor with Potent Anti-Hepatitis C Virus Activity In Vitro, in Mice with Chimeric Human Livers,and in Humans Infected with Hepatitis C Virus: Hepatology 2009, 49, 3, 745

Some recommended books on organic synthesis:
- Clayden, Greeves, Warren; Organic Chemistry (basic organic chemistry knowledge)
- Wyatt, Warren; Organic Synthesis: The Disconnection Approach (excellent introduction to retrosynthesis)
- Kurti, Czako; Strategic Applications of Named Reactions in Organic Synthesis (extensive toolkit of functional group reactions and applications thereof with common conditions)
- Nicolaou et al; Classics in Total Synthesis 1-3 (the ultimate total synthesis trilogy)
- Nicolaou; Molecules That Changed the World (the world's most important molecules and their impact on everyday life)
- Carreira, Kvaerno; Classics in Stereoselective Synthesis (compilation of the groundbreaking methods of stereoselective synthesis and application to synthesis of stereochemically complex structures)