Di Salle E, Briatico G, Giudici D, Ornati G, Nesi M, Panzeri A
Farmitalia Carlo Erba, Erbamont Group, Milano, Italy.
J Steroid Biochem Mol Biol. 1992 Mar;41(3-8):765-8. doi: 10.1016/0960-0760(92)90420-n.
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.
以人增生前列腺和大鼠前列腺的微粒体部分作为酶源，对一系列17种β-酰脲-4-氮杂-5α-雄甾烷-3-酮衍生物进行了体外睾酮5α-还原酶抑制剂的测定。活性最高的衍生物是1-[4-甲基-3-氧代-4-氮杂-5α-雄甾烷-17β-羰基]-1,3-二环己基脲（化合物1）和1-[4-甲基-3-氧代-4-氮杂-5α-雄甾烷-17β-羰基]-1,3-二异丙基脲（化合物3），它们对人酶的IC50值分别为41和55 nM，对大鼠酶的IC50值分别为83和53 nM。两种化合物对大鼠前列腺雄激素受体均未显示出任何相关的结合亲和力（IC50约为100和84 μM）。在未成熟去势大鼠中，与皮下注射丙酸睾酮（TP）一起连续口服7天，化合物3（实验室编号FCE 26073），剂量为3 mg/kg/天，可使TP促进腹侧前列腺生长的作用显著降低40-50%，而化合物1在剂量高达10 mg/kg/天时无效。
