Novel, potent, selective, and metabolically stable stearoyl-CoA desaturase (SCD) inhibitors

Autor:	Nevena Mollova, Alexei V. Ivanov, Ian Henderson, Parkhill Eric Q, Jeffrey Chisholm, Kwan Leung, Andrew G. Cole, Sandra A. Brunn, Andrei Glushkov, Dmitry Koltun, Natalya I. Vasilevich, Nathan A. Zautke, Timur Zilbershtein, Jeff Zablocki
Rok vydání:	2009
Předmět:	Clinical Biochemistry Drug Evaluation Preclinical Pharmaceutical Science Biochemistry Chemical synthesis Cell Line Inhibitory Concentration 50 Structure-Activity Relationship chemistry.chemical_compound Microsomes Quinoxalines Drug Discovery Animals Humans Enzyme Inhibitors Molecular Biology IC50 chemistry.chemical_classification Bicyclic molecule Pteridines Organic Chemistry Stearoyl-CoA In vitro Rats Stearoyl-CoA Desaturase Enzyme chemistry Cell culture Molecular Medicine
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 19:2048-2052
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2009.02.019
Popis:	We identified a series of structurally novel SCD (Delta9 desaturase) inhibitors via high-throughput screening and follow-up SAR studies. Modification of the central bicyclic scaffold has proven key to our potency optimization effort. The most potent analog (8g) had IC(50) value of 50 pM in a HEPG2 SCD assay and has been shown to be metabolically stable and selective against Delta5 and Delta6 desaturases.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ae47b61e32bb963232729ec6fd27d146 https://doi.org/10.1016/j.bmcl.2009.02.019 Zobrazit plný text záznamu Full Text from ScienceDirect