Nakayama R, Masuoka M, Hiraga K, Miki T
Acta Endocrinol Suppl (Copenh). 1979;229:100-7.
The mechanism of anti-androgenic action of a steroidal compound, TSAA-291, was summarized and discussed in reference to its drug-designing and structure-activity relationship. The target of the drug-design was to obtain a substance which is inactive in androgenic activity and is capable of antagonistically competing with androgen for the receptor. With this intention, the androgen molecule was rendered with a steric hindrance influencing upon the functional 17 beta-hydroxy group. Introduction of a bulky group at the steroidal position-13 or -16 led to anti-androgenic properties. Intense steric hindrance by introducing an enormously bulky group or complete elimination of the 17 beta-hydroxy group rather decreased the anti-androgenic activity. Of these anti-androgens thus synthesized, TSAA-291 proved to be the most active in the anti-androgen assay and also antagonistic against the uptake of [3H]testosterone by the rat ventral prostate.
参照甾体化合物TSAA-291的药物设计及其构效关系，对其抗雄激素作用机制进行了总结和讨论。药物设计的目标是获得一种雄激素活性无活性且能够与雄激素竞争性拮抗受体的物质。基于此目的，在雄激素分子上引入了影响功能性17β-羟基的空间位阻。在甾体13位或16位引入庞大基团可产生抗雄激素特性。通过引入极大的庞大基团或完全消除17β-羟基而产生的强烈空间位阻反而降低了抗雄激素活性。在这些合成的抗雄激素中，TSAA-291在抗雄激素测定中被证明是活性最高的，并且对大鼠前列腺腹侧摄取[3H]睾酮也具有拮抗作用。
