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Let's explore drug design and medicinal chemistry by looking at the development of Hepatitis C Virus inhibitors! https://total-synthesis.com/organic-c... 🧑🎓➡️ Free organic chemistry practice problems / totalsynthesis 🚀 Thanks to all channel supporters!!! / totalsynthesis_official 👉 Follow me on Instagram for updates on random research, mechanism quizzes and interesting news! https://total-synthesis.com/hepatitis... If you haven't already, please subscribe and activate notifications to show your support. You don't want to miss out on any videos in the future! 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)