Regioselectivity of thiouracil alkylation: Application to optimization of Darapladib synthesis.
Bioorg Med Chem Lett
; 28(4): 787-792, 2018 02 15.
Article
em En
| MEDLINE
| ID: mdl-29336874
ABSTRACT
Darapladib is one of the most potent Lp-PLA2 (Lipoprotein-associated phospholipase A2) inhibitor with an IC50 of 0.25â¯nM. We demonstrate that a crucial step of Darapladib synthesis was not correctly described in the literature, leading to the production of wrong regioisomers. Moreover we show that the inhibitory activity is directly linked to the position on N1 since compounds bearing alkylation on different sites have potentially less interaction within the active site of Lp-PLA2.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oximas
/
Tiouracila
/
Benzaldeídos
/
Inibidores de Fosfolipase A2
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
França