Antiviral drugs for treatment of arenavirus infection

1. A method for the treatment or prophylaxis of a viral infection or disease associated therewith, comprising administering in a therapeutically effective amount to a mammal in need thereof, a compound of Formula I below or a pharmaceutically acceptable salt thereof:

wherein B, D, and E are independently N or C—R′ and G is N;

R′ is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, arylalkyl, aryl, heteroaryl, hydroxy, alkyloxy, aryloxy, heteroaryloxy, acyloxy, arylacyloxy, heteroarylacyloxy, alkylsulfonyloxy, arylsulfonyloxy, thio, alkylthio, arylthio, amino, alkylamino, dialkylamino, cycloalkylamino, heterocycloalkylamino, arylamino, heteroarylamino, acylamino, arylacylamino, heteroarylacylamino, alkylsulfonylamino, arylsulfonylamino, acyl, arylacyl, heteroarylacyl, alkylsulfinyl, arylsulfinyl, heteroarylsulfinyl, hydroxysulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aminosulfonyl, substituted aminosulfonyl, carboxy, alkoxycarbonyl, cycloalkyloxycarbonyl, aryloxycarbonyl, carbamoyl, substituted carbamoyl, halogen, cyano, isocyano and nitro;

R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, arylalkyl, aryl, heteroaryl, acyl, arylacyl, heteroarylacyl, alkylsulfinyl, arylsulfinyl, heteroarylsulfinyl, hydroxysulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aminosulfonyl, substituted aminosulfonyl, alkoxycarbonyl, cycloalkyloxycarbonyl, aryloxycarbonyl, carbamoyl and substituted carbamoyl;

R 1 and R 2 are selected from the group consisting of:

(a) independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, arylalkyl, aryl, heteroaryl, acyl, aryl acyl, heteroarylacyl, alkylsulfinyl, arylsulfinyl, heteroarylsulfinyl, hydroxysulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aminosulfonyl, substituted aminosulfonyl, alkoxycarbonyl, cycloalkyloxycarbonyl, aryloxycarbonyl, carbamoyl and substituted carbamoyl;

(b) R 1 and R 2 together with the carbon atom they are attached to form a substituted or unsubstituted ring, which optionally include one or more heteroatoms in the ring;

(c) R 1 or R 2 together with the carbon atom it is attached to, the nitrogen next to this carbon, the carbon between this nitrogen and E or D, and the R′ of E or D when E or D is C—R′, form a substituted or unsubstituted ring, which optionally include one or more heteroatoms in the ring; and

(d) R 1 or R 2 together with the carbon atom it is attached to, and at least some of the carbons of Ar 2 , form a substituted or unsubstituted ring, which optionally include one or more heteroatoms in the ring; and

Ar 1 and Ar 2 are independently (un)substituted aryl or heteroaryl.

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 Ar 1 is mono-substituted phenyl.

5. The method of claim 1 , wherein Ar 2 is mono-substituted phenyl.

6. The method of claim 5 , wherein said mono-substituted phenyl is ethyl-phenyl.

7. The method of claim 1 , wherein the compound of Formula I is selected from the group consisting of [3-(4-Ethoxy-phenyl)-3H-imidazo[4,5-b]pyridin-6-yl]-(4-ethyl-benzyl)-amine; [3-(6-Ethoxy-pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-6-yl]-(4-ethyl-benzyl)-amine; [3-(4-Ethoxy-phenyl)-3H-imidazo[4,5-b]pyridin-6-yl]-(5-methyl-pyridin-2-ylmethyl)-amine; [1-(4-Ethoxy-phenyl)-1H-imidazo[4,5-b]pyridin-5-yl]-(4-ethyl-benzyl)-amine; N-[3-(4-Ethoxy-phenyl)-3H-imidazo[4,5-b]pyridin-6-yl]-N-(4-ethyl-benzyl)-acetamide; N-[3-(4-Ethoxy-phenyl)-3H-imidazo[4,5-b]pyridin-6-yl]-N-(4-ethyl-benzyl)-benzamide; 2-Dimethylamino-N-[3-(4-ethoxy-phenyl)-3H-imidazo[4,5-b]pyridin-6-yl]-N-(4-ethyl-benzyl)-acetamide hydrochloride; N-[3-(4-Ethoxy-phenyl)-3H-imidazo[4,5-b]pyridin-6-yl]-N-(4-ethyl-benzyl)-succinamic acid; N-[3-(4-Ethoxy-phenyl)-3H-imidazo[4,5-b]pyridin-6-yl]-N-(4-ethyl-benzyl)-methanesulfonamide; N-[3-(4-Ethoxy-phenyl)-3H-imidazo[4,5-b]pyridin-6-yl]-N-(4-ethyl-benzyl)-benzenesulfonamide; and [3-(4-Ethoxy-phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-6-yl]-(4-ethyl-benzyl)-amine.

8. The method of claim 1 , wherein the compound of Formula I is [3-(4-Ethoxy-phenyl)-3H-imidazo[4,5-b]pyridin-6-yl]-(4-ethyl-benzyl)-amine.

9. The method of claim 1 , wherein the compound of Formula I is [3-(4-Ethoxy-phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridine-6-yl]-(4-ethyl-benzyl)-amine.

10. The method of claim 1 , wherein the mammal is a human.

11. The method of claim 1 , wherein the viral infection is an Arenavirus infection.

12. The method of claim 11 , wherein the Arenavirus is selected from the group consisting of Lassa, Junín, Machupo, Guanarito, Sabia, Whitewater Arroyo, Chapare, LCMV, and LCMV-like viruses.

13. The method of claim 12 , wherein said LCMV-like viruses are selected from the group consisting of Dandenong, Tacaribe, and Pichinde.

14. The method of claim 1 , wherein said viral infection is associated with a condition selected from the group consisting of Lassa fever, Argentine hemorrhagic fever, Bolivian hemorrhagic fever, and Venezuelan hemorrhagic fever.

15. The method of claim 14 , wherein said viral infection is associated with Lassa fever.

16. 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.

17. The method of claim 16 , wherein said antiviral agent is Ribavirin.

18. The method of claim 16 , wherein said interferon is pegylated.