Heteroalicyclic carboxamidines as inhibitors of inducible nitric oxide synthase; the identification of (2R)-2-pyrrolidinecarboxamidine as a potent and selective haem-co-ordinating inhibitor

Autor:	James Michael Woolven, Simon Teanby Hodgson, Miriam Crowe, Linda J. Russell, Wendy Karen Alderton, John Dawson, C. Lynn Chambers, Christopher Charles Frederick Hamlett, Richard G. Knowles, Richard Stocker, Robert J. Young, Paul John Beswick, David W. Brown, Anthony D R Angell, Savvas Kleanthous
Rok vydání:	2011
Předmět:	Models Molecular Proline Stereochemistry Clinical Biochemistry Amidines Nitric Oxide Synthase Type II Pharmaceutical Science Heme Biochemistry Chemical synthesis Nitric oxide Inhibitory Concentration 50 chemistry.chemical_compound Heterocyclic Compounds Enos Drug Discovery medicine Humans Enzyme Inhibitors Molecular Biology chemistry.chemical_classification Molecular Structure biology Organic Chemistry Glutamate receptor biology.organism_classification Enzyme Activation Nitric oxide synthase Enzyme Mechanism of action chemistry Enzyme inhibitor biology.protein Molecular Medicine medicine.symptom
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 21:3037-3040
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2011.03.038
Popis:	Heteroalicyclic carboxamidines were synthesised and evaluated as inhibitors of nitric oxide synthases. (2R)-2-Pyrrolidinecarboxamidine, in particular, was shown to be a highly potent in vitro (IC50 = 0.12 μM) and selective iNOS inhibitor (>100-fold vs both eNOS and nNOS), with probable binding to the key anchoring glutamate residue and co-ordination to the haem iron.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::773439dbec64b955efa494d151e9cf88 https://doi.org/10.1016/j.bmcl.2011.03.038 Zobrazit plný text záznamu Full Text from ScienceDirect