达那唑五种代谢物的分离、合成及生物活性

Isolation, synthesis, and biological activity of five metabolites of danazol.

作者信息

Rosi D, Neumann H C, Christiansen R G, Schane H P, Potts G O

出版信息

J Med Chem. 1977 Mar;20(3):349-52. doi: 10.1021/jm00213a007.

Abstract

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.

摘要

达那唑（17α-孕甾-2,4-二烯-20-炔诺[2,3-d]异恶唑-17-醇）是一种口服有效的垂体促性腺激素抑制剂，无雌激素和孕激素活性。从一名女性受试者的尿液中分离出其代谢产物，该受试者口服达那唑，剂量为800mg/天，共7天。分离出的代谢产物有17-羟基-17α-孕甾-4-烯-20-炔-3-酮（11）、17-羟基-2α-（羟甲基）-17α-孕甾-4-烯-20-炔-3-酮（5）、17-羟基-2-（羟甲基）-17α-孕甾-1,4-二烯-20-炔-3-酮（7）、6β,17-二羟基-2α-（羟甲基）-17α-孕甾-4-烯-20-炔-3-酮（8）和6β,17-二羟基-2-（羟甲基）-17α-孕甾-1,4-二烯-20-炔-3-酮（10）。这些代谢产物均未表现出与达那唑相当的垂体抑制活性。