非硫醇法尼基转移酶抑制剂：N-（4-氨酰基氨基-3-苯甲酰基苯基）-3-[5-（4-硝基苯基）-2-呋喃基]丙烯酸酰胺及其抗疟活性。

Non-thiol farnesyltransferase inhibitors: N-(4-aminoacylamino-3-benzoylphenyl)-3-[5-(4-nitrophenyl)-2 furyl]acrylic acid amides and their antimalarial activity.

作者信息

Kettler Katja, Wiesner Jochen, Silber Katrin, Haebel Peter, Ortmann Regina, Sattler Isabel, Dahse Hans-Martin, Jomaa Hassan, Klebe Gerhard, Schlitzer Martin

机构信息

Department für Pharmazie, Zentrum für Pharmaforschung, Ludwig-Maximilians Universität München, Butenandtstrasse 5-13, 81377 München, Germany.

出版信息

Eur J Med Chem. 2005 Jan;40(1):93-101. doi: 10.1016/j.ejmech.2004.09.019.

DOI:10.1016/j.ejmech.2004.09.019

PMID:15642414

Abstract

Water solubility was previously found to be essential for in vivo-antimalarial activity of a novel type of benzophenone-based farnesyltransferase inhibitors. Introduction of a alpha-amino group into the phenylacetic acid substructure provided more soluble compounds with high farnesyltransferase inhibitory activity. The in vitro-antimalarial activity was detrimentally influenced by this structural modification.

摘要

先前发现水溶性对于一种新型的基于二苯甲酮的法尼基转移酶抑制剂的体内抗疟活性至关重要。在苯乙酸亚结构中引入α-氨基可提供具有高法尼基转移酶抑制活性的更易溶的化合物。这种结构修饰对体外抗疟活性产生了不利影响。