Synthesis of novel inhibitors of isoprenoid biosynthesis (ISPF)
Antibacterial and antimalarial IspF inhibitor compounds and compositions are described. Methods include administering described compounds and compositions to treat bacterial or parasitic infections and to inhibit parasite or bacterial growth.
1. A method of treating a bacterial infection in a mammal, the method comprising administering to the mammal a therapeutically effective amount of the compound of Formula I or Formula II
wherein
R 1 is OH or OR 5 , wherein R 5 is lower alkyl, acyl, or CH 2 OCOCH 3 ;
R 2 is alkyl, alkylaryl, arylheteroaryl, or heteroaryl;
R 3 is H or lower alkyl; and
R 4 is H or lower alkyl, or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , further comprising administering at least one other antimicrobial agent.
3. A method of treating a protozoan infection in a mammal, the method comprising administering to the mammal a therapeutically effective amount of the compound of Formula I or Formula II
wherein
R 1 is OH or OR 5 , wherein R 5 is lower alkyl, acyl, or CH 2 OCOCH 3 ;
R 2 is alkyl, alkylaryl, arylheteroaryl, or heteroaryl;
R 3 is H or lower alkyl; and
R 4 is H or lower alkyl, or a pharmaceutically acceptable salt thereof.
4. A method for the treatment of bacterial, protozoan, and parasitic infections, the method comprising:
(a) obtaining a pharmaceutical composition comprising a therapeutically effective amount of the compound of Formula I or Formula II and a pharmaceutically acceptable carrier
wherein
R 1 is OH or OR 5 , wherein R 5 is lower alkyl, acyl, or CH 2 OCOCH 3 ;
R 2 is alkyl, alkylaryl, arylheteroaryl, or heteroaryl;
R 3 is H or lower alkyl; and
R 4 is H or lower alkyl, or a pharmaceutically acceptable salt thereof; and
(b) administering the composition to a mammal in need thereof.