Antiviral 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 method for the treatment of a Arenavirus infection, comprising administering in a therapeutically effective amount to a mammal in need thereof, a compound of Formula I below:
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 substituted or unsubstituted.
2. The method of claim 1 , wherein R 1 is hydrogen.
3. The method of claim 1 , wherein R 2 is hydrogen.
4. The method of claim 1 , wherein R 3 is hydrogen.
5. The method of claim 1 , wherein R 3 is —S(O) 2 -substituted aryl.
6. The method of claim 5 , wherein R 3 is —S(O) 2 -substituted phenyl.
7. The method of claim 6 , wherein R 3 is —S(O) 2 -alkoxyphenyl.
8. The method of claim 7 , wherein R 3 is —S(O) 2 -methoxyphenyl.
9. The method of claim 7 , wherein R 3 is —S(O) 2 -p-methoxyphenyl.
10. The method of claim 1 , wherein Ar 1 is unsubstituted aryl.
11. The method of claim 10 , wherein Ar 1 is unsubstituted phenyl.
12. The method of claim 1 , wherein Ar 1 is mono-substituted aryl.
13. The method of claim 12 , wherein Ar 1 is mono-substituted phenyl.
14. The method of claim 13 , wherein Ar 1 is alkoxyphenyl.
15. The method of claim 14 , wherein Ar 1 is methoxyphenyl.
16. The method of claim 15 , wherein Ar 1 is o-methoxyphenyl.
17. The method of claim 15 , wherein Ar 1 is p-methoxyphenyl.
18. The method of claim 1 , wherein Ar 2 is substituted aryl.
19. The method of claim 18 , wherein Ar 2 is substituted phenyl.
20. The method of claim 19 , wherein Ar 2 is mono-substituted phenyl.
21. The method of claim 20 , wherein Ar 2 is alkoxyphenyl.
22. The method of claim 21 , wherein Ar 2 is methoxyphenyl.
23. The method of claim 22 , wherein Ar 2 is o-methoxyphenyl.
24. The method of claim 22 , wherein Ar 2 is m-methoxyphenyl.
25. The method of claim 22 , wherein Ar 2 is p-methoxyphenyl.
26. The method of claim 21 , wherein Ar 2 is ethoxyphenyl.
27. The method of claim 26 , wherein Ar 2 is p-ethoxyphenyl.
28. The method of claim 20 , wherein Ar 2 is alkylphenyl.
29. The method of claim 28 , wherein Ar 2 is methylphenyl.
30. The method of claim 29 , wherein Ar 2 is p-methylphenyl.
31. The method of claim 20 , wherein Ar 2 is propylphenyl.
32. The method of claim 31 , wherein Ar 2 is p-propylphenyl.
33. The method of claim 32 , wherein Ar 2 is p-isopropylphenyl.
34. The method of claim 13 , wherein Ar 2 is halo-substituted phenyl.
35. The method of claim 34 , wherein Ar 2 is p-halo-substituted phenyl.
36. The method of claim 35 , wherein Ar 2 is p-bromophenyl.
37. The method of claim 36 , wherein Ar 2 is p-chlorophenyl.
38. The method of claim 13 , wherein Ar 2 is hydroxyphenyl.
39. The method of claim 38 , wherein Ar 2 is o-hydroxyphenyl.
40. The method of claim 13 , wherein Ar 2 is dimethylaminophenyl.
41. The method of claim 40 , wherein Ar 2 is p-dimethylaminophenyl.
42. The method of claim 12 , wherein Ar 2 is —S(O) 2 -substituted aryl.
43. The method of claim 42 , wherein Ar 2 is —S(O) 2 -substituted phenyl.
44. The method of claim 43 , wherein Ar 2 is —S(O) 2 -alkoxyphenyl.
45. The method of claim 44 , wherein Ar 2 is —S(O) 2 -methoxyphenyl.
46. The method of claim 45 , wherein Ar 2 is —S(O) 2 -p-methoxyphenyl.
47. The method of claim 20 , wherein Ar 2 is diphenyl.
48. The method 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-l-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)-1 H-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. A method of claim 1 , wherein the mammal is a human.
50. A method of claim 1 , wherein the Arenavirus is selected from the group consisting of Tacaribe, Guanarito, Machupo, and Pichinde.
51. A method for the treatment of a Arenavirus infection, comprising administering in a therapeutically effective amount to a mammal in need thereof, a compound of Formula I below:
52. The method of claim 51 , wherein the mammal is a human.
53. A method of claim 51 , wherein the Arenavirus is selected from the group consisting of Lassa, Tacaribe, Guanarito, Machupo, and Pichinde.
54. A method of claim 51 , which further comprises co-administering ribavirin.