1.
Bioorg Med Chem Lett
; 13(6): 1067-70, 2003 Mar 24.
Artículo
en Inglés
| MEDLINE
| ID: mdl-12643913
RESUMEN
Modification of the pyrimidone 5-substituent in clinical candidate SB-435495 has given a series of inhibitors of recombinant lipoprotein-associated phospholipase A(2) with sub-nanomolar potency. Cyclopentyl fused derivative 21, SB-480848, showed an enhanced in vitro and in vivo profile versus SB-435495 and has been selected for progression to man.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Fosfolipasas A/antagonistas & inhibidores , Pirimidinonas/farmacología , 1-Alquil-2-acetilglicerofosfocolina Esterasa , Animales , Inhibidores del Citocromo P-450 CYP2D6 , Inhibidores Enzimáticos/química , Humanos , Técnicas In Vitro , Cinética , Fosfolipasas A/sangre , Fosfolipasas A2 , Pirimidinonas/química , Conejos , Proteínas Recombinantes/antagonistas & inhibidores
2.
Bioorg Med Chem Lett
; 12(18): 2603-6, 2002 Sep 16.
Artículo
en Inglés
| MEDLINE
| ID: mdl-12182870
RESUMEN
The introduction of a functionalised amido substituent into a series of 1-(biphenylmethylacetamido)-pyrimidones has given a series of inhibitors of recombinant lipoprotein-associated phospholipase A(2) with sub-nanomolar potency and very encouraging developability properties. Diethylaminoethyl derivative 32, SB-435495, was selected for progression to man.
