Synthesis and evaluation of heteroarylalanine diacids as potent and selective neutral endopeptidase inhibitors

Autor:	Dack Kevin Neil, Fox David Nathan Abraham, Strang Ross Sinclair, Dafydd R. Owen, Keith A. Reeves, Melanie S. Glossop, Graeme Arthur Macdonald, Christopher Phillips, Christine Anne Louise Watson, Mark Mills, Richard Bazin, Tracy J. Ringer
Rok vydání:	2011
Předmět:	Models Molecular Stereochemistry Clinical Biochemistry Pharmaceutical Science Matrix metalloproteinase Crystallography X-Ray Biochemistry Chemical synthesis Inhibitory Concentration 50 chemistry.chemical_compound Drug Discovery Hydrolase Humans Protease Inhibitors Oxazoles Molecular Biology Neprilysin Oxazole chemistry.chemical_classification Alanine Molecular Structure Chemistry fungi Organic Chemistry Biological activity Enzyme Activation Enzyme Molecular Medicine Selectivity Acids
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 21:3404-3406
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2011.03.109
Popis:	Heteroarylalanine derivatives 4 were designed as potential inhibitors of neutral endopeptidase (NEP EC 3.4.24.11). Selectivity over other zinc metalloproteinases was explored through occupation of the S2′ subsite within NEP. Structural optimisation led to the identification of 5-phenyl oxazole 4f, a potent and selective NEP inhibitor. A crystal structure of the inhibitor bound complex is reported.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5699785823bf7067227ef1f304784fa6 https://doi.org/10.1016/j.bmcl.2011.03.109 Zobrazit plný text záznamu Full Text from ScienceDirect