Synthesis and antitumor activity of tropolone derivatives. 3

• Published in: Journal of medicinal chemistry Vol. 29; no. 7; pp. 1202 - 1205
• Main Authors: Yamato, Masatoshi, Hashigaki, Kuniko, Kokubu, Nobuhiko, Tashiro, Tazuko, Tsuruo, Takashi
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.07.1986; Amer Chemical Soc
• Subjects: Animals; Antineoplastic Agents; Chemistry, Medicinal; Cycloheptanes - chemical synthesis; Drug Evaluation, Preclinical; Humans; Indicators and Reagents; KB Cells; Leukemia P388 - drug therapy; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Mass Spectrometry; Mice; Pharmacology & Pharmacy; Science & Technology; Structure-Activity Relationship; Tropolone - analogs & derivatives; Tropolone - chemical synthesis; Tropolone - therapeutic use
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00157a014

As part of a study on the antitumor activities of tropolone derivatives prepared from hinokitiol (1), which naturally occurs in the plants of Chamaecyparis species, effects of aromatic substituents of .alpha.,.alpha.-bis(7-hydroxy-5-isopropyltropon-2-yl)toluenes (4) 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 structure analysis of highly potent 4-methoxy analogue 4b was undertaken.