(2R,3S)-(+)- and (2S,3R)-(-)-Halofuginone lactate:: Synthesis, absolute configuration, and activity against Cryptosporidium parvum

被引：28
|
作者：
Linder, Michael R.
Heckeroth, Anja R.
Najdrowski, Michael
Daugschies, Arwid
Schollmeyer, Dieter
Miculka, Christian
机构：
[1] Intervet Innovat GmbH, D-55270 Schwabenheim, Germany
[2] Univ Leipzig, Fac Med Vet, Inst Parasitol, D-04103 Leipzig, Germany
[3] Univ Mainz, Inst Organ Chem, D-55099 Mainz, Germany
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 15期
关键词：
anti-protozoal; halofuginone; Cryptosporidium parvum; chiral switch;
D O I：
10.1016/j.bmcl.2007.05.053
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The trans-enantiomers of the commercially important anti-protozoal compound Halofuginone have been prepared and characterized, and the absolute configuration was assigned by X-ray crystallography. The activity of both enantiomers against Cryptosporidium parvum was determined in vitro and related to acute toxicity in vivo. It was shown that both the activity and the toxicity are properties of the (2R,3S)-enantiomer. We conclude that with respect to broadening the therapeutic window there is no advantage in application of one enantiomer over the application of the racemic mixture in the treatment of C parvum infections. (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4140 / 4143
页数：4
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