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

被引：17

作者：

Ballatore, Carlo

Hyde, Edward

Deiches, Robert F.

Lee, Virginia M. -Y.

Trojanowski, John Q.

Huryn, Donna

Smith, Amos B., III

机构：

[1] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA

[2] Univ Penn, Inst Aging, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 13期

关键词：

D O I：

10.1016/j.bmcl.2007.04.058

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 G 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. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：3642 / 3646

页数：5

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