Synthesis and antitumor activity of novel 4-demethoxyanthracyclines
| Autor: | Hans R. Hartmann, Michael J. Broadhurst, Alan R. Stratton, Elizabeth Keech, David J. Bushnell, Colin C. F. Blake, Nigel Adams, Gareth John Thomas, Cedric H. Hassall |
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| Rok vydání: | 1990 |
| Předmět: |
Chemical Phenomena
Stereochemistry Daunorubicin Mice Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Animals Structure–activity relationship Doxorubicin Hydroxymethyl Silver trifluoromethanesulfonate Leukemia L1210 Antibiotics Antineoplastic Leukemia P388 Chemistry Biological activity Quinone Daunosamine Molecular Medicine Female Idarubicin medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 33:2375-2379 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | A versatile and efficient synthetic route to 4-demethoxyanthracyclinones has been utilized in the preparation of a number of aglycons having 9-alkyl, 9-(hydroxylalkyl), or 9-carbamoyl substituents. Silver trifluoromethanesulfonate catalyzed coupling of these aglycons with various daunosamine derivatives has yielded a series of novel anthracyclines which have been evaluated as antitumor agents. 9-Alkylanthracyclines 22, 23, 33, and 34 have higher efficacy vs L-1210 leukemia than the parent 4-demethoxydaunorubicin (21), or the natural anthracyclines daunorubicin (1) and doxorubicin (2). 9-(Hydroxyalkyl) derivatives have in most cases high efficacy but are slightly less potent than 21. 9-Methyl analogue 22 has higher efficacy vs P388 leukemia than other anthracyclines tested, while 9-(hydroxymethyl) derivative 37 retains similar efficacy to anthracyclines 1, 2, and 21 but is considerably more potent. The N-substituted 9-carbamoylanthracyclines are devoid of antitumor activity. |
| Databáze: | OpenAIRE |
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