Novel selective inhibitors of neutral endopeptidase: discovery by screening and hit-to-lead optimisation?

摘要

A diverse library of carboxylic acids was synthesized on solid-support. The screening on hNEP identified a low molecular weight hit. Structure-activity relationships around the hit highlighted the critical role of configuration for both chiral centers. The path, that involves a side reaction, to the potent and selective NEP optimised inhibitor is presented.