Optimization of 8-oxoadenines with toll-like-receptor 7 and 8 activity.
Bioorg Med Chem Lett
; 30(6): 126984, 2020 03 15.
Article
em En
| MEDLINE
| ID: mdl-32001135
ABSTRACT
Toll-like receptors 7 and 8 (TLR7/8) agonists are potent immunostimulants that are attracting considerable interest as vaccine adjuvants. We recently reported the synthesis of a new series of 2-O-butyl-8-oxoadenines substituted at the 9-position with various linkers and N-heterocycles, and showed that TLR7/8 selectivity, potency and cytokine induction could be modulated by varying the alkyl linker length and the N-heterocyclic ring. In the present study, we further optimized the oxoadenine scaffold by investigating the effect of different substituents at the 2-position of the oxoadenine on TLR7/8 potency/selectivity, cytokine induction and DC maturation in human PBMCs. The results show that introducing a 1-(S)-methylbutoxy group at the 2-position of the oxoadenine significantly increased potency for TLR7/8 activity, cytokine induction and DC maturation.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Adenina
/
Adjuvantes Imunológicos
/
Receptor 7 Toll-Like
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Receptor 8 Toll-Like
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article