Inhibition of lethal factor protease activity from anthrax toxin

1. A therapeutic method to treat anthrax comprising inhibiting lethal factor protease activity of anthrax toxin in a mammal in need of such therapy, by administering an effective inhibitory amount of a compound of formula (I):

wherein R 1 is hydrogen or phenyl, optionally substituted with 1, or 2 substituents independently selected from halo, —NO 2 , —COOH, or —SO 2 NH 2 ;

wherein R 2 is —CH 2 COOH,

or a pharmaceutical acceptable salt thereof;

wherein,

X is O, NH, S or CH 2 ;

Y is N or CH; and

Z is N or CH.

2. The method of claim 1 wherein R 1 is nitrophenyl, halophenyl, dihalophenyl, carboxy-phenyl, or halonitrophenyl.

3. The method of claim 1 wherein R 1 is dichlorophenyl, fluorophenyl, iodophenyl, carboxy-phenyl, chlorocarboxy-phenyl, or halonitrophenyl.

4. A therapeutic method to treat anthrax comprising inhibiting lethal factor protease activity of anthrax toxin in a mammal in need of such therapy, by administering an effective inhibitory amount of at least one compound of formula:

5. A therapeutic method to treat anthrax comprising inhibiting lethal factor protease activity of anthrax toxin in a mammal in need of such therapy by administering an effective inhibitory amount of a compound of formula (II):

wherein

each R 1 is independently alkyl, alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, amino, alkylamino, acylamino, nitro, trifluoromethyl, trifluoromethoxy, carboxy, carboxyalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, COOR 7 , C(O)R 7 , NR 7 R 8 or —X—Y—Z;

each Z is independently hydrogen, aryl, heteroaryl, heterocycle or cycloalkyl; optionally substituted with 1, 2 or 3 alkyl, alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, alkanoyl, alkoxycarbonyl, amino, alkylamino, acylamino, nitro, trifluoromethyl, trifluoromethoxy, carboxy, carboxyalkyl, keto, thioxo, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, COOR 7 , C(O)R 7 , or NR 7 R 8 ;

X is O, CO, NH, S or CH 2 ;

Y is O, CO, NH, S or CH 2 ;

L is O, S or NH;

K is N or CH;

each R 7 and R 8 are independently hydrogen, alkyl or aryl; and

n is 1, 2, 3, 4 or 5;

or a pharmaceutically acceptable salt thereof.

6. A therapeutic method to treat anthrax comprising inhibiting lethal factor protease activity of anthrax toxin in a mammal in need of such therapy, by administering an effective inhibitory amount of a compound of formula (I):

wherein R 1 is hydrogen or phenyl, optionally substituted with 1 or 2 substituents independently selected from halo, —NO 2 , or —SO 2 NH 2 ;

R 2 is —(CH 2 ) 1-3 COOH,

or a pharmaceutically acceptable salt thereof; and

wherein,

X is O, NH, S or CH 2 ;

Y is N or CH; and

Z is N or CH.