The success of paclitaxel and docetaxel as anticancer agents stimulated the search of innovative analogs endowed with more favorable pharmacol. profile. Ortataxel, lead of the class of 14-hydroxy taxoids, represents a milestone in such a research. Although the 14-substitution plays an important role in the biol. of Taxanes, an extensive SAR for this position was believed not possible due the lacking of natural occurring 14-substituted taxoids and of chem. methodologies for the modification of position 14. During our studies to solve the supply of 14-hydroxytaxoids we have developed the chem. of the enolate of 13-oxo-7-protected baccatin. Such a chem. gave us a powerful tool for modifying position 14, opening new perspectives in the Taxane chem. By quenching the enolate with different electrophiles, we have generated a wide no. of 14-functionalized taxoids. In vitro and in vivo data confirmed the importance of 14-substitution and permitted the selection of new candidates.

SAR of 14-substituted taxanes / G. Fontana, A. Battaglia, M.L. Gelmi, E. Baldelli, G. Carenzi, E. Bombardelli, C. Manzotti, R.J. Bernacki. - In: ABSTRACTS OF PAPERS - AMERICAN CHEMICAL SOCIETY. - ISSN 0065-7727. - 228:(2004), pp. MEDI-099-MEDI-099. ((Intervento presentato al 228. convegno ACS National Meeting tenutosi a Philadelphia nel 2004.

SAR of 14-substituted taxanes

M.L. Gelmi;
2004

Abstract

The success of paclitaxel and docetaxel as anticancer agents stimulated the search of innovative analogs endowed with more favorable pharmacol. profile. Ortataxel, lead of the class of 14-hydroxy taxoids, represents a milestone in such a research. Although the 14-substitution plays an important role in the biol. of Taxanes, an extensive SAR for this position was believed not possible due the lacking of natural occurring 14-substituted taxoids and of chem. methodologies for the modification of position 14. During our studies to solve the supply of 14-hydroxytaxoids we have developed the chem. of the enolate of 13-oxo-7-protected baccatin. Such a chem. gave us a powerful tool for modifying position 14, opening new perspectives in the Taxane chem. By quenching the enolate with different electrophiles, we have generated a wide no. of 14-functionalized taxoids. In vitro and in vivo data confirmed the importance of 14-substitution and permitted the selection of new candidates.
Settore CHIM/06 - Chimica Organica
http://oasys2.confex.com/acs/228nm/techprogram/
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/145399
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