Russeau G G, Quivy J I
Steroids. 1981 Apr;37(4):383-92. doi: 10.1016/0039-128x(81)90040-4.
The equilibrium affinity constant for rat prostate androgen receptor and epididymal androgen binding protein (ABP) has been determined for thirty-four potential progestogens. Three A-nor-, four A,19-dinor-, and one A-homo-5 alpha-androstane derivative bind to the androgen receptor (KD less than 0.5 muM). Five of these compounds also bind to ABP with an affinity of the same order of magnitude. "Anordrin" (compound 24) and "Dinordrins" (compounds 10, 14, 15, 16, 17), which are potential female contraceptives, do not bind with high affinity to the androgen receptor or to ABP. The following modifications in A-nor derivatives favour binding to the receptor as compared to ABP: 19-nor substitution (compound 1), C-18 methyl homologation (compound 5), 2 alpha-ethinylation (compound 22). One 2 alpha-allenyl A-nor derivative (compound 25) and one A-homo derivative (compound 34) bind almost exclusively to ABP. The interaction with either binding protein is decreased by oxidation or esterification of the hydroxyl group at C-17, and by addition of a 17 alpha-ethinyl group. The latter modifications are likely to increase the specificity of androstane derivatives for receptors other than androgen binding proteins, such as the progesterone receptor.
已测定了34种潜在孕激素与大鼠前列腺雄激素受体及附睾雄激素结合蛋白（ABP）的平衡亲和常数。3种A-去甲、4种A,19-二去甲和1种A-高-5α-雄烷衍生物可与雄激素受体结合（解离常数KD小于0.5μM）。其中5种化合物也以相同数量级的亲和力与ABP结合。作为潜在女性避孕药的“双炔失碳酯”（化合物24）和“双炔诺酮”（化合物10、14、15、16、17）与雄激素受体或ABP的结合亲和力不高。与ABP相比，A-去甲衍生物中的以下修饰有利于与受体结合：19-去甲取代（化合物1）、C-18甲基同系化（化合物5）、2α-乙炔基化（化合物22）。一种2α-亚丙基A-去甲衍生物（化合物25）和一种A-高衍生物（化合物34）几乎只与ABP结合。C-17位羟基的氧化或酯化以及添加17α-乙炔基会降低与任何一种结合蛋白的相互作用。后一种修饰可能会增加雄烷衍生物对除雄激素结合蛋白以外的其他受体（如孕激素受体）的特异性。
