@article{3062304,
    title = "Lipid-lowering (hetero)aromatic tetrahydro-1,4-oxazine derivatives with antioxidant and squalene synthase inhibitory activity",
    author = "Kourounakis, A.P. and Charitos, C. and Rekka, E.A. and Kourounakis, P.N.",
    journal = "Journal of Medicinal Chemistry",
    year = "2008",
    volume = "51",
    number = "18",
    pages = "5861-5865",
    issn = "0022-2623, 1520-4804",
    doi = "10.1021/jm800663w",
    keywords = "2 [4 (2 fluorophenyl)phenyl] 4 methylmorpholinyl 2 ol;  2 [4 (4 chlorophenyl)phenyl] 4 methylmorpholinyl 2 ol;  2 [4 (4 fluorophenyl)phenyl] 4 methyloctahydro 1,4 benzoxazin 2 ol;  3 [4 (4 fluorophenyl)phenyl]octahydro 1,4 pyrido[2,1 c]oxazin 3 ol;  antilipemic agent;  aromatic compound;  biphenyl derivative;  cholesterol;  low density lipoprotein cholesterol;  morpholine derivative;  oxazine derivative;  squalene synthase;  squalene synthase inhibitor;  triacylglycerol;  unclassified drug, animal experiment;  animal model;  animal tissue;  antioxidant activity;  article;  controlled study;  drug design;  drug potency;  drug synthesis;  enzyme inhibition;  hyperlipidemia;  IC 50;  in vivo study;  lipid peroxidation;  nonhuman;  rat;  structure activity relation, Animals;  Antilipemic Agents;  Antioxidants;  Cholesterol;  Enzyme Inhibitors;  Farnesyl-Diphosphate Farnesyltransferase;  Magnetic Resonance Spectroscopy;  Microsomes, Liver;  Morpholines;  Rats;  Triglycerides",
    abstract = "A number of newly synthesized 2-[4-(hetero)aromatic]phenyl-2-hydroxy- tetrahydro-1,4-oxazine derivatives were found to inhibit lipid peroxidation (IC50 of the most potent was 20 μM) as well as rat squalene synthase (IC50 for most between 1-10 μM). Antidyslipidemic action was demonstrated in vivo: the most active compound decreased triglycerides, total cholesterol, and LDL-cholesterol of hyperlipidemic rats by 64, 67, and 82%, respectively, at 56 μmol/kg (ip). Most of the novel compounds are more active than the structurally related and reference biphenyl-morpholine, pointing to useful structural approaches for the design of antiatherosclerotic agents. © 2008 American Chemical Society."
}