Kinesin spindle protein (KSP) inhibitors. Part 3: synthesis and evaluation of phenolic 2,4-diaryl-2,5-dihydropyrroles with reduced hERG binding and employment of a phosphate prodrug strategy for aqueous solubility.
Bioorg Med Chem Lett
; 16(7): 1780-3, 2006 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-16439122
ABSTRACT
2,4-Diaryl-2,5-dihydropyrroles have been discovered to be novel, potent and water-soluble inhibitors of KSP, an emerging therapeutic target for the treatment of cancer. A potential concern for these basic KSP inhibitors (1 and 2) was hERG binding that can be minimized by incorporation of a potency-enhancing C2 phenol combined with neutral N1 side chains. Aqueous solubility was restored to these, and other, non-basic inhibitors, through a phosphate prodrug strategy.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirróis
/
Pró-Fármacos
/
Cinesinas
/
Canais de Potássio Éter-A-Go-Go
Tipo de estudo:
Prognostic_studies
Aspecto:
Determinantes_sociais_saude
Limite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos