Optimization and SAR research at the piperazine and phenyl rings of JNJ4796 as new anti-influenza A virus agents, part 1.
Eur J Med Chem
; 222: 113591, 2021 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-34126455
ABSTRACT
JNJ4796, a small molecule fuse inhibitor targeting the conserved stem region of hemagglutinin, effectively neutralized a broad spectrum of group 1 influenza A virus (IAV), and protected mice against lethal and sublethal influenza challenge after oral administration. In this study, we reported the modification and structure-activity relationship (SAR) of C (piperazine ring) and E (phenyl ring) rings of JNJ4796. Compound (R)-2c was identified to show excellent in vitro activity against IAV H1N1 and Oseltamivir-resistant IAV H1N1 stains (IC50 0.03-0.06 µM), low cytotoxicity (CC50 > 200 µM), accepted oral PK profiles and low inhibition rate of hERG (13.2%, at 10 µM). Evaluation for the in vivo anti-IAV efficacy of (R)-2c will begin soon.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Piperazinas
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Piridinas
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Tetrazóis
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Vírus da Influenza A Subtipo H1N1
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Piperazina
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2021
Tipo de documento:
Article