Henkel J G, Portoghese P S, Miller J W, Lewis P
J Med Chem. 1976 Jan;19(1):6-10. doi: 10.1021/jm00223a002.
Crystalline perchlorate salts of aziridinium ions derived from phenoxybenzamine and dibenamine were prepared. Both aziridinium ions were tested on the rat vas deferens and found to possess alpha-adrenergic potencies which were nearly identical with those of the parent compounds. The hydrolysis rates of phenoxybenzamine and dibenamine aziridinium ions (2a,b) in physiological medium were found to be 6.0 4 x 10(-4) and 8.35 x 10(-4) sec-1, respectively. The rates of cyclization of the parent amines to 2a and 2b in aqueous medium were 1.9 x 10(-2) and 7.2 x 10(-3) sec-1, respectively. The potencies and kinetic profiles indicate that the aziridinium ion is the only active species in alpha-adrenergic blockade. Moreover, differences in potency between phenoxybenzamine and dibenamine appear to be exclusively to a difference in receptor affinity rather than to a difference in intrinsic alkylating ability.
制备了由苯氧苄胺和双苄胺衍生的氮丙啶离子的结晶高氯酸盐。对这两种氮丙啶离子在大鼠输精管上进行了测试，发现它们具有与母体化合物几乎相同的α-肾上腺素能效力。发现在生理介质中苯氧苄胺和双苄胺氮丙啶离子（2a，b）的水解速率分别为6.04×10⁻⁴和8.35×10⁻⁴秒⁻¹。在水性介质中母体胺环化生成2a和2b的速率分别为1.9×10⁻²和7.2×10⁻³秒⁻¹。效力和动力学特征表明，氮丙啶离子是α-肾上腺素能阻断中唯一的活性物种。此外，苯氧苄胺和双苄胺之间效力的差异似乎完全在于受体亲和力的差异，而不是内在烷基化能力的差异。
