An in situ oxidation strategy towards overcoming hERG affinity.
Bioorg Med Chem Lett
; 20(22): 6400-4, 2010 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-20934332
ABSTRACT
In an effort to overcome hERG affinity with a lead compound, several S-oxide and N-oxide analogues were synthesised with a much improved hERG profile but low in vivo absorption. This led to the implementation of an in situ oxidation strategy wherein a sulfide was dosed orally and systemic levels of the corresponding sulfoxide and sulfone were monitored. SAR and pharmacokinetic data to support this as a possible strategy are presented, although ultimately the approach was shown not to be suitable due to very low levels of active circulating metabolites.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Sulfuros
/
Canales de Potasio Éter-A-Go-Go
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Reino Unido