Rooney F R, Jackson H
Chem Biol Interact. 1980 Oct;32(1-2):233-41. doi: 10.1016/0009-2797(80)90080-0.
Due to the drawbacks in the potential use of alpha-chlorohydrin itself as a male oral contraceptive, two novel crystalline derivatives, alpha-chlorohydrin-bis-m-nitrobenzoate and alpha-chlorohyrdin-mono-p-acetamidobenzoate, were synthesized and tested for antifertility activity in male rats. In addition, the nephrotoxic effects of alpha-chlorohydrin itself and of the two aromatic esters were investigated by the use of diuretic experiments, plasma biochemical analyses and kidney histology. Both esters were found to be of comparable molar potency to alpha-chlorohydrin in inducing temporary infertility following daily oral administration. The nephrotoxic effects following high oral doses of alpha-chlorohydrin were largely eliminated by the use of either ester. These derivatives have several advantages over alpha-chlorohydrin, being crystalline compounds of definable purity. Although potency was retained, acute oral toxicity was greatly reduced, due to a combination of factors - the esters were poorly absorbed in high dosage whilst relatively slow breakdown permitted effective levels to be attained on epididymal spermatozoa.
由于α-氯甘油本身作为男性口服避孕药在潜在应用方面存在缺陷，合成了两种新型结晶衍生物，α-氯甘油双间硝基苯甲酸酯和α-氯甘油单对乙酰氨基苯甲酸酯，并在雄性大鼠中测试了它们的抗生育活性。此外，通过利尿实验、血浆生化分析和肾脏组织学研究了α-氯甘油本身以及这两种芳香酯的肾毒性作用。发现两种酯在每日口服给药后诱导暂时不育方面的摩尔效力与α-氯甘油相当。使用任何一种酯都可在很大程度上消除高剂量口服α-氯甘油后的肾毒性作用。这些衍生物相对于α-氯甘油具有几个优点，它们是具有可定义纯度的结晶化合物。尽管保留了效力，但由于多种因素的综合作用，急性口服毒性大大降低——酯在高剂量下吸收不良，而相对缓慢的分解使得能够在附睾精子上达到有效水平。
