A new series of 3,3'-spirocyclic-2-oxo-indoline derivatives was synthesized and evaluated against respiratory syncytial virus (RSV) in a cell-based assay and animal model. Extensive structure-activity relationship study led to a lead compound , which exhibited excellent potency with an EC value of 0.8 nM and demonstrated 71% oral bioavailability in mice. In a mouse challenge model of RVS infection, demonstrated superior efficacy with a 3.9log RSV virus load reduction in the lung following an oral dose of 50 mg/kg.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807868 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.7b00418 | DOI Listing |
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