Regioselectivity of thiouracil alkylation: Application to optimization of Darapladib synthesis.
Bioorg Med Chem Lett
; 28(4): 787-792, 2018 02 15.
Article
en 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oximas
/
Tiouracilo
/
Benzaldehídos
/
Inhibidores de Fosfolipasa A2
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Francia