Synthesis and antitumor activity of tropolone derivatives. 4.
Modifications of monotropolone 2 having poor potency against P388 in mice were studied. The alpha-ethoxy group of 2, prepared from hinokitiol and benzaldehyde diethyl acetal, was replaced with a phenolic or heteroaromatic compound by heating 2 with the appropriate nucleophile. Structure-activity relationships indicated that an acidic hydroxyl and a proton-accepting group situated in the neighboring position, which permits the formation of a chelate with a metal ion, contributed to enhanced activity. Among the compounds studied, the 8-hydroxyquinoline analogue 10f was the most favorable compound.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D003508:Cycloheptanes / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D007941:Leukemia P388 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D013329:Structure-Activity Relationship; D014334:Tropolone / Q000031:analogs & derivatives / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D003508:Cycloheptanes; D014334:Tropolone