A new class of potent antiproliferative glycolipids.
The synthesis and biological activities of a new class of antiproliferative glycolipids with an unexpected broad spectrum of activity, including a human multidrug resistant cell line, are described. Chemically these compounds are glycolipids derived from N-acetyl-D-glucosamine and glycyrrhetinic acid (beta-aglycone). Peptidation of the glucoacids allyl 3 beta-[[2-acetamido-3-O-[(R)-1-carboxyethyl]- 2-deoxy-4,6-O-isopropylidene-beta-D-glucopyranosyl]oxy]-11-oxo-12- oleanen-30-oate and (R,S)-2-methoxy-3-(octadecyloxy)propyl-2-acetamido-3-O-[(R)-1-carb oxyethyl]- 2-deoxy-4,6-O-isopropylidene-beta-D-glucopyranoside was successfully achieved after activation with O-benzotriazolyl-N,N,N',N' -tetramethyluronium hexafluorophosphate.
Adam
S
S
F. Hoffmann-La Roche AG, Basel, Switzerland.
Kaufmann
F
F
D000117:Acetylglucosamine / Q000031:analogs & derivatives*; D002455:Cell Division / Q000187:drug effects*; D006017:Glycolipids / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives*; D009374:Neoplasms, Experimental / Q000188:drug therapy*
D006017:Glycolipids; D006034:Glycyrrhetinic Acid; D000117:Acetylglucosamine