18d-Glycyrrhetic acid (lb) was converted in good yield to the 3-oxo-4,4-bis(nor-18J-olean-4-ene) derivative 11a in 25% overall yield. Derivatives of lb substituted in the A, B, C, and E ring were also prepared. Several 11-deoxoglycyrrhetic acid derivatives exhibited anti-DCA activity. In particular, when administered subcutaneously, 3-oxo-18/3-olean-12-en-30-oic acid (2d) had about 75% the activity of spironolactone administered subcutaneously. Several compounds also exhibited weak antiviral and antiinflammatory properties.
Derivatives of 3-hydroxy-3-methylglutaric acid (HMG), a portion of the substrate for HMG CoA reductase, were prepared and tested for their inhibitory action against rat liver HMG CoA reductase and for their hypocholesterolemic activity. Structure-dependent competitive inhibition was observed. Optimal structures had a free dicarboxylic acid with an alkyl group of 13-16 carbons at position 3. 3-n-Pentadecyl-3-hydroxyglutaric acid (3j) (IC50 = 50 microM) reduced serum cholesterol in the Triton-treated rat and HMG CoA reductase activity in the 20,25-diazacholesterol-treated rat.
Aus 18ß‐Glycyrrhetinsäure (I) werden verschiedene Derivate nach den üblichen Verfahren der Steroidchemie hergestellt und ihre pharmakologische Aktivität diskutiert.
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