Development of dihydropyridone indazole amides as selective Rho-kinase inhibitors.
J Med Chem
; 50(1): 6-9, 2007 Jan 11.
Article
de En
| MEDLINE
| ID: mdl-17201405
ABSTRACT
Rho kinase (ROCK1) mediates vascular smooth muscle contraction and is a potential target for the treatment of hypertension and related disorders. Indazole amide 3 was identified as a potent and selective ROCK1 inhibitor but possessed poor oral bioavailability. Optimization of this lead resulted in the discovery of a series of dihydropyridones, exemplified by 13, with improved pharmacokinetic parameters relative to the initial lead. Indazole substitution played a critical role in decreasing clearance and improving oral bioavailability.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Pyridones
/
Protein-Serine-Threonine Kinases
/
Protéines et peptides de signalisation intracellulaire
/
Amides
/
Indazoles
/
Antihypertenseurs
Limites:
Animals
Langue:
En
Journal:
J Med Chem
Sujet du journal:
QUIMICA
Année:
2007
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique