In situ blood-brain barrier permeability of a C-10 paclitaxel carbamate

被引：9

作者：

Ballatore, Carlo ^{[1
]}

Zhang, Bin ^{[1
]}

Trojanowski, John Q. ^{[1
]}

Lee, Virginia M. -Y. ^{[1
]}

Smith, Amos B., III ^{[2
]}

机构：

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

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 23期

关键词：

Taxane; Paclitaxel C-10 carbamate; Blood-brain barrier; Mouse brain perfusion; Neurodegenerative diseases;

D O I：

10.1016/j.bmcl.2008.10.024

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report the synthesis and blood-brain barrier (BBB)-permeability of (14)C-CNDR-29, a paclitaxel C-10 carbamate derivative shown to be devoid of P-glycoprotein (Pgp)-interactions, in an in situ mouse brain perfusion model, in comparison with (14)C-paclitaxel. The results presented reveal a 3- to 4-fold higher BBB-permeability for the C-10 modified taxane compared to paclitaxel. These results support the notion that circumvention of Pgp-mediated efflux can lead to higher BBB-permeability. Further studies however are needed to evaluate the therapeutic potential of the C-10 carbamates paclitaxel derivatives for the treatment of CNS diseases. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：6119 / 6121

页数：3

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