Synthesis and Structure−Activity Relationship for a Novel Class of Potent and Selective Carbamate-Based Inhibitors of Hormone Selective Lipase with Acute In Vivo Antilipolytic Effects.
In: Journal of Medicinal Chemistry, Jg. 50 (2007-11-01), Heft 22, S. 5449-5456
academicJournal
Zugriff:
Hormone-sensitive lipase (HSL) is an intracellular enzyme that has a central role in the regulation of fatty acid metabolism. The enzyme, therefore, is a potentially interesting pharmacological target for the treatment of insulin resistance and dyslipidemic disorders. Based on a high throughput screening, a carbamate based HSL inhibitor was identified and optimized into the selective HSL inhibitors 4-hydroxymethyl-piperidine-1-carboxylic acid 4-(5-trifluoromethylpyridin-2-yloxy)-phenyl ester (13f) and 4-hydroxy-piperidine-1-carboxylic acid 4-(5-trifluoromethylpyridin-2-yloxy)-phenyl ester (13g), with IC50values of 110 and 500 nM, respectively. Both inhibitors were active in acute antilipolytic experiments in vivo and none of the inhibitors inhibited the cytochrome P450 (CYP) isoforms 2D6, 3A4, and 1A2. [ABSTRACT FROM AUTHOR]
Titel: |
Synthesis and Structure−Activity Relationship for a Novel Class of Potent and Selective Carbamate-Based Inhibitors of Hormone Selective Lipase with Acute In Vivo Antilipolytic Effects.
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Autor/in / Beteiligte Person: | Ebdrup, Søren ; Hanne Hoffmann Frølund Refsgaard ; Fledelius, Christian ; Jacobsen, Poul |
Zeitschrift: | Journal of Medicinal Chemistry, Jg. 50 (2007-11-01), Heft 22, S. 5449-5456 |
Veröffentlichung: | 2007 |
Medientyp: | academicJournal |
ISSN: | 0022-2623 (print) |
DOI: | 10.1021/jm0607653 |
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