Dibenzodioxocinones--a new class of CETP inhibitors.
Derivatives of the natural product 11-hydroxy-3-[(S)-1-hydroxy-3-methylbutyl]-4-methoxy-9-methyl-5H,7H-dibenzo[b,g][1,5]dioxocin-5-one 1 were studied as novel CETP inhibitors. Compound 2 was identified from HTS as a micromolar inhibitor. The compound suffered from very low stability in plasma. Optimisation by partial synthesis started from 1 and led to low-nanomolar inhibitors with good stability in rat plasma.
Brückner
David
D
Bayer Healthcare Pharma Research, Aprather Weg, 42096 Wuppertal, Germany.
Hafner
Frank-Thorsten
FT
Li
Volkhart
V
Schmeck
Carsten
C
Telser
Joachim
J
Vakalopoulos
Alexandros
A
Wirtz
Gabriele
G
D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D004147:Dioxins / Q000138:chemical synthesis / Q000494:pharmacology; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000097:blood; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D004147:Dioxins; D006023:Glycoproteins; D006575:Heterocyclic Compounds, 3-Ring; D000960:Hypolipidemic Agents