Synthesis and antitumor activity of tropolone derivatives. 3.
As part of a study on the antitumor activities of tropolone derivatives prepared from hinokitiol, which naturally occurs in the plants of Chamaecyparis species, effects of aromatic substituents of alpha,alpha-bis(7-hydroxy-5-isopropyltropon-2-yl)toluenes on the activity were examined. Several of the compounds showed high potency in the P388 leukemia assay. 4-Hydroxy analogue 4d showed the most potent activity (T/C = 195%) at a 5 mg/kg dose. The introduction of large-size substituents, of which the steric influence prevents coplanarity of the substituted aromatic function, resulted in a remarkable decrease in the potency. X-ray structural analysis of highly potent 4-methoxy analogue 4b was undertaken.
D000818:Animals; D000970:Antineoplastic Agents; D003508:Cycloheptanes / Q000138:chemical synthesis*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007202:Indicators and Reagents; D007624:KB Cells; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D013329:Structure-Activity Relationship; D014334:Tropolone / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D003508:Cycloheptanes; D007202:Indicators and Reagents; D014334:Tropolone