Inhibitors of filovirus entry into host cells
Organic compounds showing the ability to inhibit viral glycoprotein (GP)-mediated entry of a filovirus into a host cell are disclosed. The disclosed filovirus entry inhibitor compounds are useful for treating, preventing, or reducing the spread of infections by filovirus including the type species Marburg virus (MARV) and Ebola virus (EBOV). Preferred inhibitors of the invention provide therapeutic agents for combating the Ivory Coast, Sudan, Zaire, Bundibugyo, and Reston Ebola virus strains.
1. A method for treating an individual infected with or exposed to a filovirus comprising administering to said individual, as an active ingredient, a compound of the formula J-1:
wherein
n is 0, 1, or 2;
R 1 is at the meta-, ortho-, or para- position and is independently selected from C 1-2 alkyl, C 1-2 alkoxy, chloro, fluoro, and phenyl;
R 2 is at the meta-, ortho-, or para- position and is selected from hydrogen, C 1-2 alkyl, C 1-2 alkoxy, chloro, and fluoro; and
R 3 is at the meta-, ortho-, or para- position and is selected from hydrogen, C 1-2 alkyl, and C 1-2 alkoxy.
2. The method according to claim 1 , wherein said individual is human.
3. The method according to claim 1 , wherein said filovirus is Marburg virus or Ebola virus.
4. The method according to claim 3 , wherein said filovirus is Ebola virus.
5. The method according to claim 4 , wherein said Ebola virus is a strain selected from the Ivory Coast, Sudan, Zaire, Bundibugyo and Reston species.
6. The method according to claims 1 , further comprising administering an additional active ingredient in conjunction with said filovirus entry inhibitor compound, said additional active ingredient being selected from the group consisting of an antibiotic, an antibody, an antiviral agent, an anticancer agent, an analgesic, an immunostimulatory agent, a natural, synthetic or semi-synthetic hormone, a central nervous system stimulant, an antiemetic agent, an anti-histamine, an erythropoietin, a complement stimulating agent, a sedative, a muscle relaxant agent, an anesthetic agent, an anticonvulsive agent, an antidepressant, an antipsychotic agent, and combinations thereof.