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

Bioorganic & Medicinal Chemistry Letters
2007.0

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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