Isolation, synthesis, and biological activity of five metabolites of danazol.
Metabolites of danazol (17 alpha-pregna-2,4-dien-20-yno[2,3-d]isoxazol-17-ol), an orally effective pituitary gonadotropin inhibitory agent devoid of estrogenic and progestational activites, were isolated from urine of a female subject who had taken danzol orally at a dose of 800 mg/day for 7 days, The metabolites isolated were 17-hydroxy-17alpha-pregn-4-en-20-yn-3-one (11), 17-hydroxy-2alpha-(hydroxymethyl)-17alpha-pregn-4-3n-20-yn-3-one (5), 17-hydroxy-2-(hydroxymethyl)-17alpha-pregna-1,4-dien-20-yn-3-one(7), 6beta,17-dihydroxy-2alpha-(hydroxymethyl)-17alphapregn-4-en-20-yn-3-one(8), and 6beta, 17-dihydroxy-2(hydroxymethyl)-17alphapregna-1,4-dien-20yn-3-one(10). None of these metabolites exhibited pituitary inhibiting activity comparable to danazol.
D000818:Animals; D001173:Arthrobacter / Q000378:metabolism; D003613:Danazol / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D004971:Estrus / Q000187:drug effects; D005260:Female; D005285:Fermentation; D005670:Fusarium / Q000378:metabolism; D005837:Genitalia, Male / Q000187:drug effects; D006065:Gonadotropins, Pituitary / Q000037:antagonists & inhibitors; D000882:Haplorhini; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects; D011245:Pregnadienes / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D012233:Rhizopus / Q000378:metabolism
D006065:Gonadotropins, Pituitary; D011245:Pregnadienes; D003613:Danazol