Synthesis and anti-coronavirus activity of a series of 1-thia-4-azaspiro[4.5]decan-3-one derivatives.
Arch Pharm (Weinheim)
; 352(6): e1800330, 2019 Jun.
Article
en En
| MEDLINE
| ID: mdl-31073993
ABSTRACT
A series of 1-thia-4-azaspiro[4.5]decan-3-ones bearing an amide group at C-4 and various substitutions at C-2 and C-8 were synthesized and evaluated against human coronavirus and influenza virus. Compounds 7m, 7n, 8k, 8l, 8m, 8n, and 8p were found to inhibit human coronavirus 229E replication. The most active compound was N-(2-methyl-8-tert-butyl-3-oxo-1-thia-4-azaspiro[4.5]decan-4-yl)-3-phenylpropanamide (8n), with an EC50 value of 5.5 µM, comparable to the known coronavirus inhibitor, (Z)-N-[3-[4-(4-bromophenyl)-4-hydroxypiperidin-1-yl]-3-oxo-1-phenylprop-1-en-2-yl]benzamide (K22). Compound 8n and structural analogs were devoid of anti-influenza virus activity, although their scaffold is shared with a previously discovered class of H3 hemagglutinin-specific influenza virus fusion inhibitors. These findings point to the 1-thia-4-azaspiro[4.5]decan-3-one scaffold as a versatile chemical structure with high relevance for antiviral drug development.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Antivirales
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Compuestos de Espiro
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Compuestos Aza
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Diseño de Fármacos
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Coronavirus
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Año:
2019
Tipo del documento:
Article