Discovery of gem-Dimethyl-hydroxymethylpyridine Derivatives as Potent Non-nucleoside RSV Polymerase Inhibitors
Neonatal Medicine
Discovery of gem-Dimethyl-hydroxymethylpyridine Derivatives as Potent Non-nucleoside RSV Polymerase Inhibitors
Neonatal Medicine

Discovery of gem-Dimethyl-hydroxymethylpyridine Derivatives as Potent Non-nucleoside RSV Polymerase Inhibitors

J Med Chem. 2024 Aug 6. doi: 10.1021/acs.jmedchem.4c00525. Online ahead of print.

ABSTRACT

Respiratory syncytial virus (RSV) is an RNA virus infecting the upper and lower respiratory tract and is recognized as a major respiratory health threat, particularly to older adults, immunocompromised individuals, and young children. Around 64 million children and adults are infected every year worldwide. Despite two vaccines and a new generation monoclonal antibody recently approved, no effective antiviral treatment is available. In this manuscript, we present the medicinal chemistry efforts resulting in the identification of compound 28 (JNJ-8003), a novel RSV non-nucleoside inhibitor displaying subnanomolar activity in vitro as well as prominent efficacy in mice and a neonatal lamb models.

PMID:39105710 | DOI:10.1021/acs.jmedchem.4c00525