Renin-Inhibitoren – Von 'transition-state' Analogen und Peptidmimetika zu blutdrucksenkenden Wirkstoffen

During the last 10 years, a great worldwide effort was devoted towards the discovery of orally active renin inhibitors as blood-pressure-lowering drugs. Design principles and synthesis of successive generations of renin inhibitors are discussed using selected examples. The progression from the concept of the 'transition-state' inhibitor, through compounds stable towards protease cleavage and hence towards orally active 'non-peptide' inhibitors is described. All this experience in design, molecular modelling, and synthesis – although not too successful for renin itself – has been applied to the search for inhibitors of other proteolytic enzymes. Thus, the extremely rapid progress made in identifying HIV-protease inhibitors was possible largely through the 'know how' obtained during the search for renin inhibitors.