METHODS FOR TREATING VIRAL INFECTIONS
Described herein are methods for treating a viral infection comprising administering to an individual in need thereof a therapeutically effective amount of a compound of Formula I: Formula (I).
1 . A method for treating a viral infection comprising administering to an individual in need thereof a therapeutically effective amount of a compound of Formula (II) having the structure:
wherein:
X is a bond, —CH 2 —, —O—, —S—, —N(R 5 )—, —C(═O)—, —S(═O)—, —S(═O) 2 —, —C(═N—R 5 )—, —C(═N—OR 5 )—, or —C(═N—SR 5 )—;
one of Y and Z is N, and the other is CR 7 ;
J is
or —N(R 5 )(R 6 );
V is —C(H)— or —N—;
W is —O—, —S—, —C(R 6 ) 2 —, —N(R 6 )—, —N(R 6 )C(═O)—, —S(═O)—, or —S(═O) 2 —;
R 1 , R 2 , R 5 , and R 6 are each independently H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 3 is
R 4 is substituted or unsubstituted alkyl;
R 7 is H, —CN, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 8 and R 9 are each independently H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
each R 12 and R 13 are each independently H, halogen, or substituted or unsubstituted alkyl;
n is 0, 1, 2, 3, 4, 5, or 6;
p is 0, 1, 2, 3, 4, 5, or 6; and
q is 1 or 2;
or a pharmaceutically acceptable salt, solvate, or prodrug thereof.
2 . The method of claim 1 , wherein R 2 is H.
3 . The method of claim 1 or claim 2 , wherein J is q
4 . The method of claim 3 , wherein p is 0 and q is 1.
5 . The method of any one of claims 1 - 4 , wherein R 8 is H.
6 . The method of any one of claims 1 - 5 , wherein R 9 is substituted aryl.
7 . The method of any one of claims 1 - 6 , wherein R 9 is
8 . The method of any one of claims 1 - 6 , wherein R 9 is
9 . The method of any one of claims 1 - 6 , wherein R 9 is
10 . The method of any one of claims 1 - 4 , wherein R 8 is H or substituted or unsubstituted alkyl, and R 9 is
wherein R 10 is H, halogen, alkyl, or alkoxy; R 11 is halogen, —CN, —OH, alkyl, aryl, heteroaryl, alkoxy, aryloxy, or heteroaryloxy; and m is 0, 1, 2, 3, or 4.
11 . The method of claim 10 , wherein R 10 is alkyl and m is 0.
12 . The method of claim 11 , wherein R 8 is H.
13 . The method of any one of claims 1 - 12 , wherein X is —O—.
14 . The method of any one of claims 1 - 13 , wherein Y is N; and Z is CR 7 .
15 . The method of any one of claims 1 - 14 wherein R 7 is H.
16 . The method of any one of claims 1 - 15 , wherein V is —N—.
17 . The method of any one of claims 1 - 16 , wherein W is —O—.
18 . The method of any one of claims 1 - 17 , wherein R 1 is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.
19 . The method of any one of claims 1 - 17 , wherein R 1 is substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.
20 . The method of any one of claims 1 - 17 , wherein R 1 is substituted or unsubstituted heteroaryl.
21 . The method of any one of claims 1 - 17 , wherein R 1 is substituted or unsubstituted quinolinyl.
22 . The method of any one of claims 1 - 17 , wherein R 1 is substituted or unsubstituted pyridyl.
23 . The method of any one of claims 1 - 17 , wherein R 1 is
24 . The method of any one of claims 1 - 23 , wherein each R 12 and R 13 are H.
25 . The method of any one of claims 1 - 24 , wherein n is 0, 1, 2, or 3.
26 . The method of any one of claims 1 - 23 , wherein n is 0.
27 . The method of any one of claims 1 - 24 , wherein n is 1.
28 . The method of any one of claims 1 - 24 , wherein n is 2.
29 . The method of any one of claims 1 - 24 , wherein n is 3.
30 . A method for treating a viral infection comprising administering to an individual in need thereof a therapeutically effective amount of a compound of Formula (I) having the structure:
wherein:
X is a bond, —CH 2 —, —O—, —S—, —N(R 5 )—, —C(═O)—, —S(═O)—, —S(═O) 2 —, —C(═N—R 5 )—, —C(═N—OR 5 )—, or —C(═N—SR 5 )—;
one of Y and Z is N, and the other is CR 7 ;
V is —C(H)— or —N—;
W is —O—, —S—, —N(R 6 )—, —N(R 6 )C(═O)—, —S(═O)—, or —S(═O) 2 —;
R 1 , R 2 , R 5 , R 6 , and R 7 are each independently H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 3 is
R 4 is H or alkyl;
R 8 and R 9 are each independently H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and
n is 0, 1, 2, 3, 4, 5, or 6;
or a pharmaceutically acceptable salt, solvate, or prodrug thereof.
31 . The method of claim 30 , wherein R 2 is H.
32 . The method of claim 30 or claim 31 , wherein R 4 is H.
33 . The method of any one of claims 30 - 32 , wherein R 8 is H.
34 . The method of any one of claims 30 - 33 , wherein R 9 is substituted aryl.
35 . The method of any one of claims 30 - 34 , wherein R 9 is
36 . The method of any one of claims 30 - 34 , wherein R 9 is
37 . The method of any one of claims 30 - 34 , wherein R 9 is
38 . The method of any one of claims 30 - 32 , wherein R 8 is H or substituted or unsubstituted alkyl, and R 9 is
wherein R 10 is H, halogen, alkyl, or alkoxy; R 11 is halogen, —CN, —OH, alkyl, aryl, heteroaryl, alkoxy, aryloxy, or heteroaryloxy; and m is 0, 1, 2, 3, or 4.
39 . The method of claim 38 , wherein R 10 is alkyl and m is 0.
40 . The method of claim 39 , wherein R 8 is H.
41 . The method of any one of claims 30 - 40 , wherein X is —O—.
42 . The method of any one of claims 30 - 41 , wherein Y is N; and Z is CR 7 .
43 . The method of claim 42 wherein R 7 is H.
44 . The method of any one of claims 30 - 43 , wherein V is —N—.
45 . The method of any one of claims 30 - 44 , wherein W is —O—.
46 . The method of any one of claims 30 - 45 , wherein R 1 is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.
47 . The method of any one of claims 30 - 45 , wherein R 1 is substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.
48 . The method of any one of claims 30 - 45 , wherein R 1 is substituted or unsubstituted heteroaryl.
49 . The method of any one of claims 30 - 45 , wherein R 1 is substituted or unsubstituted quinolinyl.
50 . The method of any one of claims 30 - 45 , wherein R 1 is substituted or unsubstituted pyridyl.
51 . The method of any one of claims 30 - 45 , wherein R 1 is
52 . The method of any one of claims 30 - 51 , wherein n is 0, 1, 2, or 3.
53 . The method of any one of claims 30 - 51 , wherein n is 0.
54 . The method of any one of claims 30 - 51 , wherein n is 1.
55 . The method of any one of claims 30 - 51 , wherein n is 2, 3, 4, 5, or 6.
56 . The method of any one of claims 30 - 51 , wherein n is 2.
57 . The method of claim 1 or 30 , wherein the compound of Formula (I) or Formula (II) is:
58 . The method of any one of claims 1 - 57 , wherein the viral infection is from an RNA virus.
59 . The method of any one of claims 1 - 58 , wherein the viral infection is from the Ebola virus.
60 . The method of any one of claims 1 - 59 , further comprising administration of a second agent.
61 . The method of claim 60 , further comprising administration of a second agent selected from Ribavirin, Fenretinide, Favipiravir, Brincidofovir, ZMapp, TKM-100802, BCX4430, Interferons, Amiodarone, Atorvostatin, Irbesartan, Clomiphene, FX06, Zmab, Tamoxifen, Albendazole, AC-93253, Toremifene, and T-705.
62 . The method of claim 60 , further comprising administration of a second agent selected from Ribavirin, Fenretinide, Favipiravir, Brincidofovir, ZMapp, TKM-100802, BCX4430, Interferons, Amiodarone, Atorvostatin, Irbesartan, Clomiphene, FX06, Zmab, Tamoxifen, Albendazole, AC-93253, Toremifene, T-705, and GS-5734.
63 . A compound having the structure
or a pharmaceutically acceptable salt, solvate, or prodrug thereof.
64 . A pharmaceutical composition comprising a compound of claim 63 , or a pharmaceutically acceptable salt, solvate, or prodrug thereof, and a pharmaceutically acceptable excipient.