Inhibitors and methods of inhibiting bacterial and viral pathogens
View Patent ↗Compounds, pharmaceutical compositions and methods for treating viral and bacterial infections, by administering certain thiourea compounds, specifically acylthiourea, carboximidoylthiourea and S-alkyl isothiourea derivatives and analogs, in therapeutically effective amounts are disclosed.
1. A method for the treatment of a viral or bacterial infection or disease associated therewith wherein the viral infection is caused by a virus family selected from the group consisting of: Bunyaviridae, Poxviridae, Arenaviridae, Picornaviridae, Togaviridae, Flaviviridae, Filoviridae, Paramyxoviridae, Orthomyxoviridae and Retroviridae, comprising administering in a therapeutically effective amount to a mammal in need thereof, a compound of Formula II below or a pharmaceutically acceptable salt thereof:
wherein X is selected from the group consisting of oxygen and NH;
Y is selected from the group consisting of: —CH 2 —, —C(═O)—, —C(═S)— and —C(═NH)—;
A is selected from the group consisting of: N and CR 5 ;
B is selected from the group consisting of: N and CR 6 ;
R 1 is selected from the group consisting of: hydrogen and ethyl;
R 2 is selected from the group consisting of: hydrogen and chloro;
R 3 is selected from the group consisting of: hydrogen, methoxy, amino and hydroxyl;
R 4 is selected from the group consisting of: hydrogen, chloro and amino;
R 5 is selected from the group consisting of hydrogen and aminomethyl; and
R 6 is selected from the group consisting of hydrogen, amino and aminomethyl.
2. The method of claim 1 , wherein X is oxygen.
3. The method of claim 1 , wherein Y is —CH 2 —.
4. The method of claim 1 , wherein Y is —C(═O)—.
5. The method of claim 1 , wherein A is C—H.
6. The method of claim 1 , wherein B is C—H.
7. The method of claim 1 , wherein R 1 is hydrogen.
8. The method of claim 1 , wherein R 2 is hydrogen.
9. The method of claim 1 , wherein R 3 is methoxy.
10. The method of claim 1 , wherein R 4 is chloro.
11. The method of claim 1 , wherein each of R 5 and R 6 is hydrogen.
12. The method of claim 1 , wherein the compound of Formula II is selected from the group consisting of: N-[4-[(4-tert-butylbenzoyl)-carbamothioylamino]-2-hydroxy-phenyl]-2-chloro-benzamide; 4-tert-butyl-N-[[4-[(2-chlorophenyl)-methylamino]-3-methoxy-phenyl]-carbamothioyl]-benzamide; N-[2-amino-4-[(4-tert-butylbenzoyl)-carbamothioylamino]-phenyl]-2-chloro-benzamide hydrochloride; N-[(4-benzamido-2-chloro-phenyl)carbamothioyl]-4-tert-butyl-benzamide; 4-tert-butyl-N-[[4-[(2-chlorobenzene-carbothioyl)amino]-3-methoxy-phenyl]-carbamothioyl]benzamide; 4-(aminomethyl)-N-[4-[(4-tert-butylbenzoyl)-carbamothioylamino]-2-methoxy-phenyl]benzamide hydrochloride; N-[4-[(4-tert-butylbenzene-carboximidoyl) -carbamothioylamino]-2-methoxy-phenyl]-2-chloro-benzamide; 4-tert-butyl-N-[[4-[(2-chlorobenzene-carboximidoyl)amino]-3-methoxy-phenyl]-carbamothioyl]benzamide; 3-(aminomethyl)-N-[4-[(4-tert-butylbenzoyl)-carbamothioylamino]-2-methoxy-phenyl]benzamide hydrochloride; 2-amino-N-[4-[(4-tert-butylbenzoyl)-carbamothioylamino]-2-methoxy-phenyl]benzamide; N-[4-[(4-tert-butylbenzoyl)-carbamothioylamino]-2-methoxy-phenyl]pyridine-3-carboxamide; N-[4-[(4-tert-butylbenzoyl)-carbamothioylamino]-2-methoxy-phenyl]pyridine-4-carboxamide; N-[[4-[(4-aminobenzoyl)amino]-3-methoxy-phenyl]-carbamothioyl]-4-tert-butyl-benzamide hydrochloride; N-[4-[(4-tert-butylbenzoyl) -carbamothioyl-ethyl-amino]-2-methoxy-phenyl]-2-chloro-benzamide; N-[4-[(4-tert -butylbenzoyl)-carbamothioylamino]-2-methoxy-phenyl]-2-chloro-benzamide; and N-[(4-benzamidophenyl)-carbamothioyl]-4-tert-butyl-benzamide.
13. The method of claim 12 , wherein the compound of Formula II is N-[2-amino-4-[(4-tert-butylbenzoyl)-carbamothioylamino]-phenyl]-2-chloro-benzamide hydrochloride.
14. The method of claim 1 , wherein the mammal is a human.
15. The method of claim 1 , wherein said Bunyaviridae is selected from the group consisting of Rift Valley fever virus, La Crosse virus and Andes virus.
16. The method of claim 1 , wherein said Poxviridae is selected from the vaccinia virus and monkeypox virus.
17. The method of claim 1 , wherein said Arenaviridae is selected from the group consisting of Tacaribe virus and lymphocytic choriomeningitis virus.
18. The method of claim 1 , wherein said Picornaviridae is Encephalomyocarditis virus.
19. The method of claim 1 , wherein said Togaviridae is Sindbis virus.
20. The method of claim 1 , wherein said Flaviviridae is Dengue virus.
21. The method of claim 1 , wherein the viral infection is caused by a Filoviridae and said Filoviridae is Ebola virus.
22. The method of claim 1 , wherein said Orthomyxoviridae is an influenza virus.
23. The method of claim 22 , wherein said influenza virus is H1N1 virus.
24. The method of claim 1 , wherein said Retroviridae is a Human Immunodeficiency virus.
25. The method of claim 1 , which further comprises co-administration of at least one agent selected from the group consisting of antiviral agent, vaccine, and interferon.
26. The method of claim 25 , wherein said antiviral agent is Ribavirin.
27. The method of claim 25 , wherein said antiviral agent is cidofovir.
28. The method of claim 25 , wherein said interferon is pegylated.
29. The method of claim 1 , wherein said bacterial infection is caused by a bacteria family selected from the group consisting of Chlamydiaceae and Coxiellaceae.
30. The method of claim 29 , wherein said Chlamydiaceae is selected from the group consisting of Chlamydophila caviae and Chlamydophila muridarum .
31. The method of claim 29 , wherein said Coxiellaceae is Coxiella burnetti.
32. The method of claim 1 , wherein the compound of Formula II is N-[4-[(4-tert -butylbenzoyl)-carbamothioylamino]-2-methoxy-phenyl]-2-chloro-benzamide.
33. The method of claim 32 , wherein the viral infection is Ebola virus.