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17 beta-acylurea derivatives of 4-azasteroids as inhibitors of testosterone 5 alpha-reductase.

Authors
  • Di Salle, E
  • Briatico, G
  • Giudici, D
  • Ornati, G
  • Nesi, M
  • Panzeri, A
Type
Published Article
Journal
The Journal of Steroid Biochemistry and Molecular Biology
Publisher
Elsevier
Publication Date
Mar 01, 1992
Volume
41
Issue
3-8
Pages
765–768
Identifiers
PMID: 1373305
Source
Medline
License
Unknown

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.

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