1.
Bioorg Med Chem Lett
; 21(21): 6348-52, 2011 Nov 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-21955943
RESUMO
We describe the design, synthesis and profiling of a novel series of PDE5 inhibitors. We take advantage of an alternate projection into the solvent region to identify compounds with excellent potency, selectivity and pharmacokinetic profiles.
Assuntos
Inibidores da Fosfodiesterase 5/farmacologia , Pirazinas/farmacologia , Cristalografia por Raios X , Concentração Inibidora 50 , Modelos Moleculares , Inibidores da Fosfodiesterase 5/química , Inibidores da Fosfodiesterase 5/farmacocinética , Pirazinas/química , Pirazinas/farmacocinética , Solventes/química
2.
Bioorg Med Chem Lett
; 19(15): 4088-91, 2009 Aug 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-19540112
RESUMO
A new class of potent and selective PDE5 inhibitors is disclosed. Guided by X-ray crystallographic data, optimization of an HTS lead led to the discovery of a series of 2-aryl, (N8)-alkyl substituted-6-aminosubstituted pyrido[3,2b]pyrazinones which show potent inhibition of the PDE5 enzyme. Synthetic details and some structure-activity relationships are also presented.