Liang T, Rasmusson G H, Brooks J R
J Steroid Biochem. 1983 Jul;19(1A):385-90. doi: 10.1016/s0022-4731(83)80051-x.
A series of 4-aza-3-oxosteroids were found to be good inhibitors of steroid 5 alpha-reductase. Two of these compounds. 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA) and 4-methyl-4-aza-5 alpha-pregnan-3-one-20(s)-carboxylate, inhibit 5 alpha-reductase competitively with testosterone (T) with Ki values of 5 and 1.7 nM, respectively. These 5 alpha-reductase inhibitors also have an affinity to the androgen receptor which is orders of magnitude lower than that of 5 alpha-dihydrotestosterone (DHT), spironolactone and cyproterone acetate. 4-MA decreases the prostatic concentration of DHT and increases that of T in intact male rats and in castrates given T or its propionate derivative. 4-MA is a better inhibitor of T-induced growth than of DHT-induced growth of the prostate and seminal vesicles in castrated rats. It decreases the weight of the prostate and seminal vesicles in intact rats and that of the prostate in dogs. It has no significant antifertility activity in rats. In pregnant rats, 4-MA reduces the ano-genital distance of male fetuses. 4-MA has no significant androgenic, estrogenic, progestational, antiprogestational or antigonadotrophic activity.
发现一系列4-氮杂-3-氧代甾体是甾体5α-还原酶的良好抑制剂。其中两种化合物，17β-N，N-二乙基氨基甲酰基-4-甲基-4-氮杂-5α-雄甾烷-3-酮（4-MA）和4-甲基-4-氮杂-5α-孕甾烷-3-酮-20（s）-羧酸盐，分别以5和1.7 nM的Ki值与睾酮（T）竞争性抑制5α-还原酶。这些5α-还原酶抑制剂对雄激素受体也有亲和力，但其亲和力比5α-二氢睾酮（DHT）、螺内酯和醋酸环丙孕酮低几个数量级。在完整雄性大鼠和给予T或其丙酸酯衍生物的去势大鼠中，4-MA降低了DHT的前列腺浓度并增加了T的浓度。在去势大鼠中，4-MA对T诱导的前列腺和精囊生长的抑制作用比对DHT诱导的生长的抑制作用更好。它降低了完整大鼠前列腺和精囊的重量以及犬前列腺的重量。它在大鼠中没有明显的抗生育活性。在怀孕大鼠中，4-MA缩短了雄性胎儿的肛门与生殖器之间的距离。4-MA没有明显的雄激素、雌激素、孕激素、抗孕激素或抗促性腺激素活性。
