Anti-viral drugs for treatment of arenavirus infection
View Patent ↗Compounds, methods and pharmaceutical compositions for treating viral infections, by administering certain novel compounds in therapeutically effective amounts are disclosed. Methods for preparing the compounds and methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment and prophylaxis of viral infections such as caused by hemorrhagic fever viruses is disclosed, i.e., including but not limited to, Arenaviridae (Junin, Machupo, Guanarito, Sabia, Lassa, Tacaribe, Pichinde, and LCMV), Filoviridae (Ebola and Marburg viruses), Flaviviridae (yellow fever, Omsk hemorrhagic fever and Kyasanur Forest disease viruses), and Bunyaviridae (Rift Valley fever).
1. A composition comprising a compound of Formula I
wherein R l and R 2 are independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, arylalkyl, aryl, acyl, arylacyl, hydroxy, alkyloxy, alkylthio, amino, alkylamino, acetamido, halogen, cyano or nitro;
R 3 is hydrogen, acyl, arylacyl or sulfonyl; and
Ar 1 and Ar 2 are independently (un)substituted aryl and a pharmaceutically acceptable carrier therefore.
2. The composition of claim 1 , wherein R 1 is hydrogen.
3. The composition of claim 1 , wherein R 2 is hydrogen.
4. The composition of claim 1 , wherein R 3 is hydrogen.
5. The composition of claim 1 , wherein R 3 is —S(O) 2 -substituted aryl.
6. The composition of claim 5 , wherein R 3 is —S(O) 2 -substituted phenyl.
7. The composition of claim 6 , wherein R 3 is —S(O) 2 -alkoxyphenyl.
8. The composition of claim 7 , wherein R 3 is —S(O) 2 -methoxyphenyl.
9. The composition of claim 8 , wherein R 3 is —S(O) 2 -p-methoxyphenyl.
10. The composition of claim 1 , wherein Ar 1 is unsubstituted aryl.
11. The composition of claim 10 , wherein Ar 1 is unsubstituted phenyl.
12. The composition of claim 1 , wherein Ar 1 is mono-substituted aryl.
13. The composition of claim 1 , wherein Ar 1 is mono-substituted phenyl.
14. The composition of claim 13 wherein Ar 1 is alkoxyphenyl.
15. The composition of claim 14 wherein Ar 1 is methoxyphenyl.
16. The composition of claim 15 , wherein Ar 1 is o-methoxyphenyl.
17. The composition of claim 15 , wherein Ar 1 is p-methoxyphenyl.
18. The composition of claim 1 , wherein Ar 2 is substituted aryl.
19. The composition of claim 18 , wherein Ar 2 is substituted phenyl.
20. The composition of claim 19 , wherein Ar 2 is mono-substituted phenyl.
21. The composition of claim 20 , wherein Ar 2 is alkoxyphenyl.
22. The composition of claim 21 , wherein Ar 2 is methoxyphenyl.
23. The composition of claim 22 , wherein Ar 2 is o-methoxyphenyl.
24. The composition of claim 22 , wherein Ar 2 is m-methoxyphenyl.
25. The composition of claim 22 , wherein Ar 2 is p-methoxyphenyl.
26. The composition of claim 21 , wherein Ar 2 is ethoxyphenyl.
27. The composition of claim 26 , wherein Ar 2 is p-ethoxyphenyl.
28. The composition of claim 19 , wherein Ar 2 is alkylphenyl.
29. The composition of claim 28 , wherein Ar 2 is methylphenyl.
30. The composition of claim 29 , wherein Ar 2 is p-methylphenyl.
31. The composition of claim 28 , wherein Ar 2 is propylphenyl.
32. The composition of claim 31 , wherein Ar 2 is p-propylphenyl.
33. The composition of claim 32 , wherein Ar 2 is p-isopropylphenyl.
34. The composition of claim 1 , wherein Ar 2 is halo-substituted phenyl.
35. The composition of claim 28 , wherein Ar 2 is p-halo-substituted phenyl.
36. The composition of claim 35 , wherein Ar 2 is p-bromophenyl.
37. The composition of claim 36 , wherein Ar 2 is p-chlorophenyl.
38. The composition of claim 20 , wherein Ar 2 is hydroxyphenyl.
39. The composition of claim 38 , wherein Ar 2 is o-hydroxyphenyl.
40. The composition of claim 20 , wherein Ar 2 is dimethylaminophenyl.
41. The composition of claim 40 , wherein Ar 2 is p-dimethylaminophenyl.
42. The composition of claim 20 , wherein Ar 2 is —S(O) 2 -substituted aryl.
43. The composition of claim 42 , wherein Ar 2 is —S(O) 2 -substituted phenyl.
44. The composition of claim 43 , wherein Ar 2 is —S(O) 2 -alkoxyphenyl.
45. The composition of claim 38 , wherein Ar 2 is —S(O) 2 -methoxyphenyl.
46. The composition of claim 45 , wherein Ar 2 is —S(O) 2 -p-methoxyphenyl.
47. The composition of claim 19 , wherein Ar 2 is diphenyl.
48. The composition of claim 1 , wherein compound of Formula I is selected from the group consisting of (4-Methoxy-benzyl)-[1-(4-methoxy-phenyl)-1H-benzimidazol-5-yl]-amine, (4-Dimethylamino-benzyl)-[1-(2-methoxy-phenyl)-1H-benzimidazol-5-yl]-amine, (4-Dimethylamino-benzyl)-(1-phenyl-1H-benzimidazol-5-yl)-amine, (4-Dimethylamino-benzyl)-(1-phenyl-1H-benzimidazol-5-yl)-amine, (4-Bromo-benzyl)-[1-(4-methoxy-phenyl)-1H-benzimidazol-5-yl]-amine, (2-Methoxy-benzyl)-[1-(4-methoxy-phenyl)-1H-benzimidazol-5-yl]-amine, (4-Ethoxy-benzyl)-[1-(4-methoxy-phenyl)-1H-benzimidazol-5-yl]-amine, (2-Methoxy-benzyl)-[1-(2-methoxy-phenyl)-1H-benzimidazol-5-yl]-amine, [1-(4-Methoxy-phenyl)-1H-benzimidazol-5-yl]- naphthalen-1-ylmethyl-amine, (4-Methoxy-benzyl)-(1-p-tolyl-1H-benzimidazol-5-yl)-amine, (4-Chloro-benzyl)-[1-(4-methoxy-phenyl)-1H-benzimidazol-5-yl]-amine, (3,4-Dimethoxy-benzyl)-[1-(4-methoxy-phenyl)-1H-benzimidazol-5-yl]-amine, (4-Bromo-benzyl)-(1-phenyl-1H-benzimidazol-5-yl)-amine, N-(4-Ethoxy-benzyl)-N-[1-(2-methoxy-phenyl)-1H-benzimidazol-5-yl]-4-methylbenzenesulfonamide, [1-(4-Methoxy-phenyl)-1H-benzimidazol-5-yl]-(4-methyl-benzyl)-amine, (2,3-Dimethoxy-benzyl)-[1-(4-methoxy-phenyl)-1H-benzimidazol-5-yl]-amine, (4-Methoxy-benzyl)-[1-(2-methoxy-phenyl)-1H-benzimidazol-5-yl]-amine, (3-Methoxy-benzyl)-[1-(4-methoxy-phenyl)-1H-benzimidazol-5-yl]-amine, (2,3-Dimethoxy-benzyl)-[1-(2-methoxy-phenyl)-1H-benzimidazol-5-yl]-amine, (4-Isopropyl-benzyl)-[1-(4-methoxy-phenyl)-1H-benzimidazol-5-yl]-amine, (4-Methoxy-benzyl)-(1-phenyl-1H-benzimidazol-5-yl)-amine, N-(4-Isopropyl-benzyl)-N-[1-(4-methoxy-phenyl)-1H-benzimidazol-5-yl]-acetamide, and N-(4-Isopropyl-benzyl)-N-[1-(4-methoxy-phenyl)-1H-benzimidazol-5-yl]-4-methylbenzenesulfonamide.
49. The composition of claim 1 , wherein the compound of Formula I is (4-isopropyl-benzyl)-[1-(4-methoxy-phenyl)-1H-benzimidazol-5-yl]-amine.