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

Bioorg Med Chem Lett. 2007 Jul 1;17(13):3642-6. doi: 10.1016/j.bmcl.2007.04.058.

Carlo Ballatore ¹, Edward Hyde, Robert F Deiches, Virginia M-Y Lee, John Q Trojanowski, Donna Huryn, Amos B Smith 3rd

Affiliations

Affiliation

1 Department of Chemistry, University of Pennsylvania, 231 South 34th St., Philadelphia, PA 19104-6323, USA. [email protected]

PMID: 17485207 DOI: 10.1016/j.bmcl.2007.04.058

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.

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