Discovery of N-[5-(6-Chloro-3-cyano-1-methyl-1H-indol-2-yl)-pyridin-3-ylmethyl]-ethanesulfonamide, a Cortisol-Sparing CYP11B2 Inhibitor that Lowers Aldosterone in Human Subjects.
J Med Chem
; 58(23): 9382-94, 2015 Dec 10.
Article
em En
| MEDLINE
| ID: mdl-26540564
ABSTRACT
Human clinical studies conducted with LCI699 established aldosterone synthase (CYP11B2) inhibition as a promising novel mechanism to lower arterial blood pressure. However, LCI699's low CYP11B1/CYP11B2 selectivity resulted in blunting of adrenocorticotropic hormone-stimulated cortisol secretion. This property of LCI699 prompted its development in Cushing's disease, but limited more extensive clinical studies in hypertensive populations, and provided an impetus for the search for cortisol-sparing CYP11B2 inhibitors. This paper summarizes the discovery, pharmacokinetics, and pharmacodynamic data in preclinical species and human subjects of the selective CYP11B2 inhibitor 8.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Piridinas
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Sulfonamidas
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Citocromo P-450 CYP11B2
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Antagonistas de Receptores de Mineralocorticoides
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Inibidores Enzimáticos
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Indóis
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2015
Tipo de documento:
Article