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Multi-step parallel synthesis enabled optimization of benzofuran derivatives as pan-genotypic non-nucleoside inhibitors of HCV NS5B.

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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Xiao D,Dai X,Liu H,He S,Shi ZC,Ludmerer SW,Li F,Nargund R,Palani A

doi

10.1016/j.bmcl.2020.127004

subject

Has Abstract

pub_date

2020-04-01 00:00:00

pages

127004

issue

7

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(20)30068-8

journal_volume

30

pub_type

杂志文章

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