Discovery of spirocyclic-diamine inhibitors of mammalian acetyl CoA-carboxylase

Autor:	Kathrine Loomis, Kristin L. Rockwell, Meihua Tu, Paul A. Amor, Kirk McPherson, William P. Esler, Tereece Banks, Aaron C. Smith, Shawn Cabral, James J. Valentine, Susan Tapley, Kristen Ford, Colin R. Rose, Mark Niosi, Felix Vajdos, Carmen N. Garcia-Irizarry, Shawn D. Doran, James A. Southers, Scott W. Bagley, Margaret S. Landis, Alan M. Mathiowetz, Daniel W. Kung, David A. Griffith
Rok vydání:	2015
Předmět:	Gene isoform Stereochemistry Clinical Biochemistry Pharmaceutical Science Biochemistry Models Biological Small Molecule Libraries chemistry.chemical_compound Enzyme activator Inhibitory Concentration 50 Acetyl Coenzyme A Diamine Drug Discovery Animals Humans Spiro Compounds Enzyme Inhibitors Molecular Biology Molecular Structure Drug discovery Organic Chemistry Acetyl-CoA carboxylase Pyruvate carboxylase Rats Enzyme Activation chemistry Lipogenesis Hepatocytes Molecular Medicine Lead compound Acetyl-CoA Carboxylase
Zdroj:	Bioorganicmedicinal chemistry letters. 25(22)
ISSN:	1464-3405
Popis:	A novel series of spirocyclic-diamine based, isoform non-selective inhibitors of acetyl-CoA carboxylase (ACC) is described. These spirodiamine derivatives were discovered by design of a library to mimic the structural rigidity and hydrogen-bonding pattern observed in the co-crystal structure of spirochromanone inhibitor I. The lead compound 3.5.1 inhibited de novo lipogenesis in rat hepatocytes, with an IC50 of 0.30 μM.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d97747d7f1eb5d78c33f023f1c9e7174 https://pubmed.ncbi.nlm.nih.gov/26411795 Zobrazit plný text záznamu Full Text from ScienceDirect