Structure-Based Design, Synthesis, and in vitro Evaluation of Nonpeptidic Neprilysin Inhibitors

Using X‐ray structure‐based de novo design, a new class of inhibitors of the zinc‐dependent endopeptidase Neprilysin has been developed that feature binding affinities (IC50 values) in the upper nanomolar range. The imidazole moieties of the central benzimidazole or imidazo[4,5‐c]pyridine (see pictu...

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Veröffentlicht in:	Chembiochem : a European journal of chemical biology 2004-07, Vol.5 (7), p.996-1000
Hauptverfasser:	Sahli, Stefan, Stump, Bernhard, Welti, Tobias, Blum-Kaelin, Denise, Aebi, Johannes D, Oefner, Christian, Böhm, Hans-Joachim, Diederich, François
Format:	Artikel
Sprache:	eng
Schlagworte:	Drug Design Drug Evaluation endopeptidases Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Imidazoles - chemistry In Vitro Techniques inhibitors medicinal chemistry Models, Molecular neprilysin Neprilysin - antagonists & inhibitors Structure-Activity Relationship structure-based design
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Beschreibung
Zusammenfassung:	Using X‐ray structure‐based de novo design, a new class of inhibitors of the zinc‐dependent endopeptidase Neprilysin has been developed that feature binding affinities (IC50 values) in the upper nanomolar range. The imidazole moieties of the central benzimidazole or imidazo[4,5‐c]pyridine (see picture) scaffolds act as efficient peptide‐bond isosters.
ISSN:	1439-4227 1439-7633
DOI:	10.1002/cbic.200400005