Methods for treating Filoviridae virus infections

1. A method of treating a Filoviridae infection in a human in need thereof comprising administering to the human a therapeutically effective amount of a compound of Formula IV:

or a pharmaceutically acceptable salt or ester, thereof;

wherein,

R 7 is selected from the group consisting of

a) H, —C(═O)R 11 , —C(═O)OR 11 , —C(═O)NR 11 R 12 , —C(═O)SR 11 , —S(O)R 11 , —S(O) 2 R 11 , —S(O)(OR 11 ), —S(O) 2 (OR 11 ), and —SO 2 NR 11 R 12 ;

b)

and

c)

wherein:

R c is selected from the group consisting of phenyl, 1-naphthyl, 2-naphthyl,

R d is selected from the group consisting of H and CH 3 ;

R e1 and R e2 are each independently selected from the group consisting of H, (C 1 -C 6 )alkyl and benzyl;

R f is selected from the group consisting of H, (C 1 -C 8 )alkyl, benzyl, (C 3 -C 6 )cycloalkyl, and —CH 2 —(C 3 -C 6 )cycloalkyl;

R g is selected from selected from the group consisting of (C 1 -C 8 )alkyl, —O—(C 1 -C 8 )alkyl, benzyl, —O-benzyl, —CH 2 —(C 3 -C 6 )cycloalkyl, —O—CH 2 —(C 3 -C 6 )cycloalkyl, and CF 3 ; and

n′ is an integer selected from the group consisting of 1, 2, 3, and 4;

wherein

each R 11 and R 12 is independently H, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, (C 4 -C 8 )carbocyclylalkyl, (C 6 -C 20 )optionally substituted aryl, optionally substituted heteroaryl, —C(═O)(C 1 -C 8 )alkyl, —S(O) n (C 1 -C 8 )alkyl or (C 6 -C 20 )aryl(C 1 -C 8 )alkyl; or R 11 and R 12 taken together with a nitrogen to which they are both attached form a 3 to 7 membered heterocyclic ring wherein any one carbon atom of said heterocyclic ring can optionally be replaced with —O—, —S— or —NR a —;

each R a is independently selected from the group consisting of H, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, (C 6 -C 20 )aryl(C 1 -C 8 )alkyl, (C 4 -C 8 )carbocyclylalkyl, —C(═O)R, —C(═O)OR, —C(═O)NR 2 , —C(═O)SR, —S(O)R, —S(O) 2 R, —S(O)(OR), —S(O) 2 (OR), and —SO 2 NR 2 ; wherein

each R is independently selected from the group consisting of H, (C 1 -C 8 ) alkyl, (C 1 -C 8 ) substituted alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 ) substituted alkenyl, (C 2 -C 8 ) alkynyl, (C 2 -C 8 ) substituted alkynyl, (C 6 -C 20 )aryl, (C 6 -C 20 )substituted aryl, (C 2 -C 20 )heterocyclyl, (C 2 -C 20 )substituted heterocyclyl, (C 6 -C 20 )aryl(C 1 -C 8 )alkyl and substituted (C 6 -C 20 )aryl(C 1 -C 8 )alkyl;

each n is an integer independently selected from the group consisting of 0, 1, or 2; and

wherein each (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl and (C 6 -C 20 )aryl(C 1 -C 8 )alkyl of each R 11 and R 12 is, independently, optionally substituted with one or more substituents selected from the group consisting of halo, hydroxy, CN, N 3 , N(R a ) 2 and OR a ; and wherein one or more of the non-terminal carbon atoms of each said (C 1 -C 8 )alkyl is optionally replaced with —O—, —S— or —NR a —.

2. The method of claim 1 wherein

R e1 is H, C 1 -C 6 alkyl or benzyl; and

R e2 is H or C 1 -C 6 alkyl.

3. The method of claim 1 wherein R 7 is

4. The method of claim 1 wherein R 7 is

5. The method of claim 1 wherein the compound of Formula IV is:

6. The method of claim 1 further comprising administering a pharmaceutically acceptable carrier or excipient.

7. The method of claim 1 further comprising administering a therapeutically effective amount of at least one other therapeutic agent or composition thereof selected from the group consisting of a corticosteroid, an anti-inflammatory signal transduction modulator, a β2-adrenoreceptor agonist bronchodilator, an anticholinergic, a mucolytic agent, hypertonic saline and other drugs for treating Filoviridae virus infections; and mixtures thereof.

8. The method of claim 1 wherein the Filoviridae infection is caused by a Filoviridae virus.

9. The method of claim 1 wherein the Filoviridae infection is caused by an ebolavirus.

10. The method of claim 1 wherein the Filoviridae infection is caused by Bundibugyo ebolavirus, Reston ebolavirus, Sudan ebolavirus, Tai Forest ebolavirus, or Zaire ebolavirus.

11. The method of claim 1 wherein the Filoviridae infection is caused by a Marburg virus.

12. The method of claim 1 wherein a Filoviridae polymerase is inhibited.

13. A method of treating a Filoviridae infection in a human in need thereof comprising administering to the human a therapeutically effective amount of a compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

14. The method of claim 13 , wherein the Filoviridae infection is caused by a Filoviridae virus.

15. The method of claim 13 , wherein the Filoviridae infection is caused by an ebolavirus.

16. The method of claim 13 , wherein the Filoviridae infection is caused by a Marburg virus.