2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S) -2-azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498)--a new and highly effective angiotensin I converting enzyme inhibitor

Abstract

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.