Topliss approach to the synthesis of biologically active substituted N-benzoyl taxol analogues

A series of compounds, directed by the Topliss Operational Scheme, were synthesized and evaluated to investigate structure activity relationships of the N-benzoyl moiety of taxol. Evaluation of the newly prepared derivatives in the microtubule assembly assay and for cytotoxicity revealed that they p...

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Published inBioorganic & medicinal chemistry letters Vol. 4; no. 15; pp. 1825 - 1830
Main Authors Georg, Gunda I., Boge, Thomas C., Cheruvallath, Zacharia S., Harriman, Geraldine C.B., Hepperle, Michael, Park, Haeil, Himes, Richard H.
Format Journal Article
LanguageEnglish
Published Elsevier Ltd 11.08.1994
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Summary:A series of compounds, directed by the Topliss Operational Scheme, were synthesized and evaluated to investigate structure activity relationships of the N-benzoyl moiety of taxol. Evaluation of the newly prepared derivatives in the microtubule assembly assay and for cytotoxicity revealed that they possessed biological properties similar to taxol. Nine novel substituted N-benzoyl analogues of taxol were prepared, using the Topliss approach to drug design. The taxanes were prepared from N-acyl-3-hydroxy-4-phenyl-2-azetidinones and baccatin III or by acylation of N-debenzoyltaxol. In vitro biological evaluation revealed that these analogues had activity similar to taxol.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(01)80378-4