Potential antitumor agents. 61. Structure-activity relationships for in vivo colon 38 activity among disubstituted 9-oxo-9H-xanthene-4-acetic acids
| Autor: | Gordon W. Rewcastle, Z A Li, Bruce C. Baguley, William A. Denny, G. J. Atwell |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Xanthene
Flavone acetic acid Molecular Structure Stereochemistry Xanthones Antineoplastic Agents Mice Inbred Strains Hemorrhagic necrosis Mice Structure-Activity Relationship chemistry.chemical_compound Xanthenes chemistry Biochemistry In vivo Vadimezan Colonic Neoplasms Drug Discovery Animals Molecular Medicine Potency Indicators and Reagents ZD6126 |
| Zdroj: | Journal of Medicinal Chemistry. 34:217-222 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00105a034 |
| Popis: | Analogues of 9-oxo-9H-xanthene-4-acetic acid (XAA) bearing small, lipophilic 5-substituents are among the most dose-potent compounds yet reported with the capability of causing hemorrhagic necrosis of implanted colon 38 tumors in mice. To further extend structure-activity relationships among this class of compound, a series of XAA derivatives bearing two small lipophilic groups at various positions have been prepared and evaluated. The 5,6-disubstituted compounds in particular show consistently high levels of both dose potency and activity, suggesting this is the optimal configuration among substituted 9-oxo-9H-xanthene-4-acetic acids. The 5,6- dimethyl and 5-methyl-6-methoxy are the most effective analogues, showing in vivo colon 38 activity comparable to that of FAA at 10-15-fold lower doses and superior activity to FAA at the respective optimal doses, and the former has been selected for detailed evaluation. |
| Databáze: | OpenAIRE |
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