New alpha-amino phosphonic acid derivatives of vinblastine: chemistry and antitumor activity
| Autor: | Jean A. Boutin, Corinne Schaeffer, Patrick Hautefaye, Alain Pierré, Claude Cudennec, Gilbert Lavielle |
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| Rok vydání: | 1991 |
| Předmět: |
Chemical Phenomena
Stereochemistry Substituent Organophosphonates Antineoplastic Agents Vinblastine chemistry.chemical_compound Mice Structure-Activity Relationship In vivo Drug Discovery medicine Structure–activity relationship Animals Alkyl Cells Cultured chemistry.chemical_classification Leukemia P388 Biological activity Phosphonate Chemistry chemistry Mice Inbred DBA Molecular Medicine Azide medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 34(7) |
| ISSN: | 0022-2623 |
| Popis: | A series of new amino phosphonic acid derivatives of vinblastine (1, VLB) has been synthesized and tested in vitro and in vivo for antitumor activity. The compounds were obtained from O4-deacetyl-VLB azide. All of the new products studied were capable of inhibiting tubulin polymerization in vitro. The most potent antitumor compounds bore an alkyl substituent on the phosphonate. In these compounds, the anti-tumor activity strongly depended on the stereochemistry of the phosphonate. The phosphonate (1S)-[1-[( O4-deacetyl-3-de(methoxycarbonyl)vincaleukoblastin-3-yl] carbonyl]amino]-2-methylpropyl]phosphonic acid diethyl ester exhibited a remarkable activity against cancer cell lines both in vitro and in vivo. |
| Databáze: | OpenAIRE |
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