Small Molecules and a Pharmacophore Model for Inhibition of Anthrax Lethal Factor.

摘要

Disclosed herein is a pharmacophore model for inhibiting anthrax lethal factor protease activity which comprises a first aromatic center A, a second aromatic center B, a first polar center C, a second polar center D, a third polar center E, and a neutral linker F. In some embodiments, the distance between the first aromatic center A and the neutral linker F is about 4.7 to about 6.7 .ANG., preferably about 5.7 .ANG.. In some embodiments, the distance between the neutral linker F and the second aromatic center B is about 3.4 to about 4.4 .ANG., preferably about 3.9 .ANG.. In some embodiments, the distance between first aromatic center A and the first polar center C is about 5.5 to about 7.5 .ANG., preferably about 6.5 .ANG.. In some embodiments, the distance between the first aromatic center A and the second polar center D is about 4.6 to about 6.6 .ANG., preferably about 5.6 .ANG.. In some embodiments, the distance between the second aromatic center B and the second polar center D is about 3.6 to about 4.6 .ANG., preferably about 4.1 .ANG.. In some embodiments, the distance between the second aromatic center B and the third polar center E is about 2.6 to about 3.6 .ANG., preferably about 3.1 .ANG.. In some embodiments, the distance between the first polar center C and the third polar center E is about 15.6 to about 19.6 .ANG., preferably about 17.6 .ANG.. Also disclosed are small molecules fitting the pharmacophore model and compositions and methods of using thereof.