17 beta-acylurea derivatives of 4-azasteroids as inhibitors of testosterone 5 alpha-reductase.
J Steroid Biochem Mol Biol
; 41(3-8): 765-8, 1992 Mar.
Article
en En
| MEDLINE
| ID: mdl-1373305
ABSTRACT
A series of 17 beta-acylurea-4-aza-5 alpha-androstan-3-one derivatives has been assayed in vitro as inhibitors of testosterone 5 alpha-reductase, using the particulate fraction of human hyperplastic prostate and rat prostate as enzyme sources. The most active derivatives were 1-[4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carbonyl]- 1,3-dicyclohexylurea (compound 1) and 1-[4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carbonyl]- 1,3-diisopropylurea (compound 3) which demonstrated IC50 values of 41 and 55 nM for the human enzyme and of 83 and 53 nM for the rat enzyme, respectively. Neither compound showed any relevant binding affinity to the rat prostate androgen receptor (IC50 of approximately 100 and 84 microM). When given orally in immature castrated rats together with subcutaneous testosterone propionate (TP) for 7 consecutive days, compound 3 (laboratory code FCE 26073), at 3 mg/kg/day, significantly decreased the ventral prostate growth promoting effect of TP by 40-50%, whereas compound 1 was ineffective up to the dose of 10 mg/kg/day.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Próstata
/
Hiperplasia Prostática
/
Compuestos Aza
/
Urea
/
Receptores Androgénicos
/
Inhibidores de 5-alfa-Reductasa
/
Androstanos
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Steroid Biochem Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
1992
Tipo del documento:
Article
País de afiliación:
Italia