Steroidal androgen biosynthesis inhibitors
| Autor: | T. Jefopoulus, L. H. Peterson, R. L. Bugianesi, Frederick A. Kuehl, N. G. Brink, G. E. Arth, E. A. Ham, Arthur A. Patchett |
|---|---|
| Rok vydání: | 1971 |
| Předmět: |
Male
medicine.medical_specialty Carbamate Chromatography Gas Chemical Phenomena medicine.medical_treatment Lyases Structure-Activity Relationship chemistry.chemical_compound Corticosterone Microsomes Internal medicine Testis Drug Discovery Hydroxyprogesterones medicine Animals Testosterone Androstenols Carbon Isotopes Chemistry Cholesterol Ketones Lyase Rats Endocrinology Depression Chemical Androgens Urea Microsome Pregnenolone Molecular Medicine Chromatography Thin Layer Androstanes medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 14:675-679 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00290a003 |
| Popis: | 23,17beta-acylaminoandrost-4-en-3-ones and 3 previously known nonsteroids were synthesized and screened as inhibitors of 17,20-lyase, a step in androgen synthesis from progesterone or OH-progesterone. The screening involved measuring side chain cleavage (carbon-14-acetate release) from 21-carbon-14-17alpha-OH-progesterone by rat testis microsomes. The amide, urea, guanidino and carbamate derivatives were also tested by conversion of cholesterol to pregnenolone by a bovine corpora lutea acetone powder, by conversion of corticosterone to 18-OH-corticosterone by crude adrenal mitochondria, and by feeding to male rats to check effect on adrenal weight and testis testosterone level. More than 80% inhibition was achieved with androst-4-en-3-ones having the C-17beta carbamate, formamido, acetamido and ureido groups. These compounds did not inhibit OH-corticosterone synthesis. 6-alpha methylation inhibited the lyase 50-70%. 1 compound 17-beta-ureidoandrost-1,4-dien-3-one was fed to male rats for 6 weeks at 500 mg per kg; it reduced testis testosterone but not adrenal weight. Selective inhibition of androgen synthesis would be useful for treating benign prostate hypertrophy, hirsutism, acne and androgen dependent tumors. |
| Databáze: | OpenAIRE |
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