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Structure‐Based Design, Synthesis, and in vitro Evaluation of Nonpeptidic Neprilysin Inhibitors
Author(s) -
Sahli Stefan,
Stump Bernhard,
Welti Tobias,
BlumKaelin Denise,
Aebi Johannes D.,
Oefner Christian,
Böhm HansJoachim,
Diederich François
Publication year - 2004
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200400005
Subject(s) - benzimidazole , chemistry , neprilysin , imidazole , combinatorial chemistry , endopeptidase , stereochemistry , in vitro , binding affinities , ic50 , peptide , biochemistry , enzyme , receptor , organic chemistry
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 (IC 50 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.