Metzger H, Maier R, Sitter C, Stern H O
Arzneimittelforschung. 1984;34(10B):1402-6.
2-[N-[(S)-1-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl] - (1S,3S,5S) -2-azabicyclo [3.3.0] octane-3-carboxylic acid (Hoe 498) is a new, very effective and long lasting, nonsulfhydryl angiotensin I converting enzyme inhibitor. Using hip-his-leu as substrate, the IC50-values for Hoe 498 and its diacid derivative were 26 or 4.2 nmol/l, respectively. Hoe 498 acts as a prodrug. It is hydrolyzed by an esterase into its active diacid derivative. Sera contain high esterase activities. In comparison to sera from man, dog and rabbit, rat sera have the highest esterase activity. Hoe 498 or its diacid derivative do not modulate the membrane bound adenylatecyclase system of tissues under investigation. The results are discussed in respect of the regulation of the angiotensin II-synthesis and to the regulation of Ca2+-channels in membranes.
2-[N-[(S)-1-乙氧羰基-3-苯基丙基]-L-丙氨酰基]-(1S,3S,5S)-2-氮杂双环[3.3.0]辛烷-3-羧酸（Hoe 498）是一种新型、高效且长效的非巯基血管紧张素I转换酶抑制剂。以髋组氨酸亮氨酸为底物时，Hoe 498及其二酸衍生物的IC50值分别为26或4.2纳摩尔/升。Hoe 498起前药的作用。它被酯酶水解成其活性二酸衍生物。血清含有高酯酶活性。与来自人、狗和兔子的血清相比，大鼠血清具有最高的酯酶活性。Hoe 498或其二酸衍生物不调节所研究组织的膜结合腺苷酸环化酶系统。就血管紧张素II合成的调节和膜中Ca2+通道的调节对结果进行了讨论。
