Methods of Treating Zika Virus Infection

1 . A method of treating a Zika virus infection, the method comprising administering to a subject in need thereof, an effective amount of a compound according to Formula I:

wherein:

R 1 is C 1 -C 10 alkyl;

each R 2 is independently H, C 1 -C 6 alkyl, or C 1 -C 6 perfluoroalkyl;

Y is NR 3 R 4 , optionally substituted heterocyclyl, or C(R 3 ) 2 R 5 ;

each R 3 is independently H or C 1 -C 6 alkyl;

R 4 is

m is 0, 1, 2, 3, 4 or 5;

R 5 is —O(C 1 -C 4 alkyl);

R 6 is, independently at each occurrence, NO 2 , N 3 , optionally substituted heteroaryl, optionally substituted heterocyclyl,

—(CH 2 ) p N(R 7 ) 2 ,

I, Br, Cl, or F;

p is 1, 2, or 3;

q is 1, 2, or 3; and

R 7 is, independently at each occurrence, H or C 1 -C 6 alkyl, or, when taken together along with the nitrogen to which they are bound, is the group

or a pharmaceutically acceptable salt thereof.

2 . The method of claim 1 , wherein the compound of Formula I is a compound of Formula II:

3 . The method of claim 2 , wherein R 1 is selected from the group consisting of —CH 2 , —CH 2 CH 2 —, —(CH 2 ) 3 —, —(CH 2 ) 4 —, —(CH 2 ) 5 —, —(CH 2 ) 6 —, —(CH 2 ) 7 —, —(CH 2 ) 8 —, —(CH 2 ) 9 —, and —(CH 2 ) 10 —.

4 . The method of claim 3 , wherein R 1 is —(CH 2 ) 4 —, —(CH 2 ) 6 —, or —(CH 2 ) 8 —.

5 . The method of claim 4 , wherein R 1 is —(CH 2 ) 8 — and Y is C(R 3 ) 2 R 5 .

6 . The method of claim 5 , wherein each R 3 is H and R 5 is —O(C 1 -C 4 alkyl), wherein the C 1 -C 4 alkyl is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, butyl, sec-butyl, and t-butyl

7 . The method of claim 4 , wherein R 1 is —(CH 2 ) 6 — and Y is NR 3 R 4 .

8 . The method of claim 7 , wherein R 3 is H and R 4 is

9 . The method of claim 7 , wherein m is 1, 2, or 3, and R 6 is independently at each occurrence NO 2 , N 3 , optionally substituted heteroaryl, optionally substituted heterocyclyl,

—(CH 2 ) p N(R 7 ) 2 ,

I, Br, Cl, or F.

10 . The method of claim 9 , wherein m is 3 and each R 6 is halogen.

11 . The method of claim 10 , wherein the halogen is fluorine.

12 . The method of claim 9 , wherein m is 2, at least one R 6 is NO 2 , and a second R 6 is N 3 , 2H-1,2,3-triazol-2-yl,

1H-tetrazol-1-yl, 1H-pyrazol-1-yl, optionally substituted heterocyclyl, —(CH 2 ) p N(R 7 ) 2 , or

13 . The method of claim 9 , wherein m is 1 and R 6 is optionally substituted heteroaryl.

14 . The method of claim 9 , where in the optionally substituted heteroaryl is pyrimidin-2-yl or 2H-tetrazol-2-yl.

15 . The method of claim 4 , wherein R 1 is —(CH 2 ) 8 — and Y is optionally substituted heterocyclyl or C(R 3 ) 2 R 5 .

16 . The method of claim 15 , wherein Y is tetrahydrofuran-2-yl.

17 . The method of claim 15 , wherein Y is C(R 3 ) 2 R 5 .

18 . The method of claim 17 , wherein R 3 is independently at each occurrence, H or C 1 -C 6 alkyl.

19 . The method of claim 18 , wherein R 3 is independently at each occurrence, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, or t-butyl.

20 . The method of claim 19 , wherein R 3 is methyl at each occurrence.

21 . The method of claim 20 , wherein R 5 is methoxy.

22 . The method of claim 4 , wherein R 1 is —(CH 2 ) 4 —.

23 . The method of claim 1 , wherein the compound is selected from the group consisting of (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(9-methoxynonyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-1-(6-((4-azido-2-nitrophenyl)amino)hexyl)-2-(hydroxymethyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(8-(tetrahydrofuran-2-yl)octyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(9-methoxy-9-methyldecyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(6-((2-nitro-4-(2H-1,2,3-triazol-2-yl)phenyl)amino)hexyl)piperidine-3,4,5-triol; (E)-N′-hydroxy-3-nitro-4-((6-((2R,3R,4R,5S)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl)hexyl)amino)benzimidamide; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(6-((2-nitro-4-(1H-tetrazol-1-yl)phenyl)amino)hexyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(6-((2-nitro-4-(2H-tetrazol-2-yl)phenyl)amino)hexyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(6-((2-nitro-4-(pyrimidin-2-yl)phenyl)amino)hexyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(6-((4-morpholino-2-nitrophenyl)amino)hexyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(6-((2-nitro-5-(1H-tetrazol-1-yl)phenyl)amino)hexyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(6-((2-nitro-5-(piperazin-1-yl)phenyl)amino)hexyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-1-(6-((4-((dimethylamino)methyl)-2-nitrophenyl)amino)hexyl)-2-(hydroxymethyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-1-(6-((5-azido-2-nitrophenyl)amino)hexyl)-2-(hydroxymethyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(6-((3-nitro-4-(1H-pyrazol-1-yl)phenyl)amino)hexyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(6-((3-nitro-4-(1H-tetrazol-1-yl)phenyl)amino)hexyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(6-((4-((4-methylpiperazin-1-yl)methyl)-2-nitrophenyl)amino)hexyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-1-(6-((5-((dimethylamino)methyl)-2-nitrophenyl)amino)hexyl)-2-(hydroxymethyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-1-(4-((4-azido-2-nitrophenyl)amino)butyl)-2-(hydroxymethyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(6-((2,4,6-trifluorophenyl)amino)hexyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-1-butyl-2-(hydroxymethyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-nonylpiperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(6-propoxyhexyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-1-(6-((4-(2H-tetrazol-2-yl)phenyl)amino)hexyl)-2-(hydroxymethyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-1-(6-((7H-purin-2-yl)amino)hexyl)-2-(hydroxymethyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(6-((4-(isoxazolidin-2-ylmethyl)-2-nitrophenyl)amino)hexyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(6-((2-nitro-4-(pyridin-2-yl)phenyl)amino)hexyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(6-((2-nitro-4-(pyridazin-3-yl)phenyl)amino)hexyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(6-((2-nitro-4-(pyrimidin-4-yl)phenyl)amino)hexyl)piperidine-3,4,5-triol; (2R,3R,4R,5S)-2-(hydroxymethyl)-1-(6-((2-nitro-4-(pyridin-3-yl)phenyl)amino)hexyl)piperidine-3,4,5-triol; and pharmaceutically acceptable salts thereof.

24 . The method of claim 1 , wherein the subject is a human.

25 . The method of claim 24 , wherein the human is a human female.