Paclitaxel C-10 carbamates: potential candidates for the treatment of neurodegenerative tauopathies.

Abstract

A series of paclitaxel C-10 carbamates was synthesized and evaluated in a bi-directional permeability assay in comparison with paclitaxel and the blood-brain barrier-permeable C-10 ester derivative, TX-67. A number of the carbamates were found not to be substrates for Pgp. Moreover, when tested for Pgp-inhibitory potential, representative compounds proved to be devoid of Pgp interactions. Side-by-side comparison between TX-67 and the corresponding C-10 carbamate, CNDR-3, revealed a significantly longer half-life for CNDR-3 in both mouse and human plasma, suggesting that this class of derivatives is appropriate for further in vivo evaluation.

• Authors: Carlo Ballatore, Edward Hyde, Robert F Deiches, Virginia M-Y Lee, John Q Trojanowski, Donna Huryn, Amos B Smith 3rd
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 17 Issue 13 Pg. 3642-6 (Jul 01 2007) ISSN: 0960-894X [Print] England
• PMID: 17485207 (Publication Type: Journal Article)

Chemical References

• 10-O-deacetylpaclitaxel 10-monosuccinyl ester
• Carbamates
• Paclitaxel

Topics

• Animals
• Blood-Brain Barrier (drug effects)
• Brain (drug effects)
• Carbamates (chemical synthesis, chemistry)
• Chemistry, Pharmaceutical (methods)
• Drug Design
• Humans
• Mice
• Models, Chemical
• Neurodegenerative Diseases (drug therapy)
• Paclitaxel (analogs & derivatives, pharmacology)
• Permeability
• Tauopathies (drug therapy)
• Time Factors