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Updated: Sep 13, 2026

Multi-target Parallel Processing Approach for Gene-to-structure Determination of the Influenza Polymerase PB2 Subunit
Published on: June 28, 2013
Multi-step parallel synthesis enabled optimization of benzofuran derivatives as pan-genotypic non-nucleoside
Dong Xiao1, Xing Dai1, Hong Liu1
1Department of Medicinal Chemistry, Merck & Co., Inc., 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Abstract:
In a lead optimization effort towards NS5B NNI inhibitors, two multi-step parallel libraries were designed and successfully synthesized. Through this effort we discovered compound 9B, which achieved rigorous and delicate balance of inhibition across the common genotypes and mutants with <10 nM potency. In addition, the bicyclic compounds 9B exhibited improved FASSIF solubility over the tetracyclic compound MK-8876. This strategic approach demonstrated that, even within limited reaction scope, multi-step parallel libraries could provide access to more complex chemical space. This expedient access facilitates diverse, purpose-driven optimization of SAR and physicochemical properties.
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