Kaminski J M, Nuzzo N A, Bauer L, Waller D P, Zaneveld L J
Contraception. 1985 Aug;32(2):183-9. doi: 10.1016/0010-7824(85)90106-4.
Nine aryl 4-guanidinobenzoates were synthesized as inhibitors of the sperm enzyme acrosin. These esters were prepared from 4-guanidinobenzoic acid and a number of phenols which had been approved by the FDA for clinical use. The vaginal contraceptive activity of the inhibitors was evaluated in the rabbit at nonspermicidal concentrations (0.1 mg/ml). All the inhibitors except the 2'-carboxamidophenyl and the 2'-isopropyl-5'-methylphenyl 4-guanidinobenzoates caused significant reductions in fertilization compared to the controls. Several of the aryl 4-guanidinobenzoates appeared to be particularly effective. Nonoxynol-9, under the same conditions but at 10- and 100-fold higher concentrations, also showed an antifertility effect. However, even at these increased dose levels, the contraceptive efficacy of nonoxynol-9 was no higher than that of most of the inhibitors and was less consistent than that of the most active aryl 4-guanidinobenzoates. The relatively high in vivo antifertility activity exhibited by several of the aryl 4-guanidinobenzoates encourages their further evaluation as vaginal contraceptive agents.
合成了9种芳基4-胍基苯甲酸酯作为精子顶体酶的抑制剂。这些酯是由4-胍基苯甲酸与一些已获美国食品药品监督管理局批准可用于临床的酚类化合物制备而成。在非杀精浓度（0.1毫克/毫升）下，对家兔的阴道避孕活性进行了评估。与对照组相比，除2'-羧基酰胺基苯基4-胍基苯甲酸酯和2'-异丙基-5'-甲基苯基4-胍基苯甲酸酯外，所有抑制剂均导致受精率显著降低。几种芳基4-胍基苯甲酸酯似乎特别有效。壬苯醇醚-9在相同条件下，但浓度高10倍和100倍时，也显示出抗生育作用。然而，即使在这些增加的剂量水平下，壬苯醇醚-9的避孕效果也不高于大多数抑制剂，且不如最具活性的芳基4-胍基苯甲酸酯稳定。几种芳基4-胍基苯甲酸酯在体内表现出的相对较高的抗生育活性，促使人们进一步将它们作为阴道避孕剂进行评估。
