Daclatasvir discovery

A triumph of the decade (2010 – 2019) is the suite of Hepatitis C small molecule drugs treatments. These took a previously fatal disease to a 97% cure rate in 6 to 12 weeks of treatment. The second half of the decade saw the medicinal chemists involved presenting their work at major conferences. One of the most impressive of these talks, and it is reflected in the publication, was the discovery of Daclatasvir. By phenotypic screening a relatively unattractive hit was found and the SAR explored. The breakthrough came when the instability of the compound was examined and a dimerization process discovered. An almost complete rework occurred and the diligence of the chemists yielded a candidate drug with exquisite potency and high bio-availability. A remarkable piece of work.

Discovery of Daclatasvir, a Pan-Genotypic Hepatitis C Virus NS5A Replication Complex Inhibitor with Potent Clinical Effect

J. Med. Chem. 2014, 57, 12, 5057–5071

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