ω-substituted alkyl carboxylic acids as antidiabetic and lipid-lowering agents

In screening experiments certain ω-substituted alkyl carboxylic acids, were found to produce an increase in insulin-stimulated 14C-acetate incorporation into triglycerides, which may indicate an improvement in the action of insulin. Antidiabetic and lipid-lowering properties in genetically diabetic...

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Hauptverfasser: Meyer, Kirstin (VerfasserIn) , Voss, Edgar (VerfasserIn) , Neidlein, Richard (VerfasserIn) , Kühnle, Hans-Frieder (VerfasserIn) , Pill, Johannes (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 1998
In: European journal of medicinal chemistry
Year: 1998, Jahrgang: 33, Heft: 10, Pages: 775-787
ISSN:1768-3254
DOI:10.1016/S0223-5234(99)80029-4
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/S0223-5234(99)80029-4
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0223523499800294
Volltext
Verfasserangaben:Kirstin Meyer, Edgar Voss, Richard Neidlein, Hans-Frieder Kühnle, Johannes Pill

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520 |a In screening experiments certain ω-substituted alkyl carboxylic acids, were found to produce an increase in insulin-stimulated 14C-acetate incorporation into triglycerides, which may indicate an improvement in the action of insulin. Antidiabetic and lipid-lowering properties in genetically diabetic ob/ob mice demonstrated the in vivo relevance of the insulin-potentiating effects seen in vitro. The chemical structures of the ω-substituted alkyl carboxylic acids with insulin-potentiating effects correspond to the general formula ring-spacer-COOH. A close structure-activity relationship was observed. The most potent compound in ob/ob mice was 3e, which normalized blood glucose as well as hyperinsulinaemia and lowered serum triglycerides and cholesterol by 52% and 37%, respectively. On the basis of these results, ω-substituted alkyl carboxylic acids are interesting as a new class of oral antidiabetic agents with insulin-sensitizing and lipid-lowering activity. 
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