Potent antiviral pyrazolopyridine compounds
The present technology provides compounds according to Formulas (I), (II), or (III) useful in inhibiting an enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus in a cell and/or treating subjects suffering from an enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus.
1. A compound according to Formula I:
or a pharmaceutically acceptable salt thereof;
wherein:
R 1 is isopropyl;
R 2 is
or an aryl substituted with one or more trifluoromethyl groups;
R 3 is H;
or —N(R 2 )(R 3 ) is
R 4 is unsubstituted thiophenyl, unsubstituted pyridinyl, unsubstituted oxazolyl, or unsubstituted thiazolyl; and
X 1 is —C(O)—, —C(NH)—, —C(S)—, or —S(O) 2 —.
2. The compound of claim 1 , wherein X 1 is —C(O)—.
3. A composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
4. A pharmaceutical composition for treating an enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus infection, the composition comprising an effective amount of the compound of claim 1 and a pharmaceutically acceptable excipient.
5. A method for inhibiting the replication of an enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus in a cell infected with the enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus, the method comprising contacting the cell with a compound of claim 1 .
6. A method of inhibiting death of a cell infected with an enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus, the method comprising contacting the cell with a compound of claim 1 .
7. A method of treating a patient or animal infected with an enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus, the method comprising administration of an effective amount of a compound of claim 1 to the patient or animal.
8. A compound according to Formula I:
or a pharmaceutically acceptable salt thereof;
wherein:
R 1 is isopropyl;
R 2 is
R 3 is H;
R 4 is cycloalkyl, phenyl, thiophenyl, pyridinyl, oxazolyl, or thiazolyl; and
X′ is —C(O)—, —C(NH)—, —C(S)—, or —S(O) 2 —.
9. A composition comprising a compound of claim 8 and a pharmaceutically acceptable carrier.
10. A pharmaceutical composition for treating an enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus infection, the composition comprising an effective amount of the compound of claim 8 and a pharmaceutically acceptable excipient.
11. A method for inhibiting the replication of an enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus in a cell infected with the enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus, the method comprising contacting the cell with a compound of claim 8 .
12. A method of treating a patient or animal infected with an enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus, the method comprising administration of an effective amount of a compound of claim 8 to the patient or animal.
13. The compound of claim 1 , wherein the compound is
14. The compound of claim 8 , wherein the compound is
15. A pharmaceutical composition for treating an enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus infection, the composition comprising an effective amount of the compound of claim 13 and a pharmaceutically acceptable excipient.
16. A method for inhibiting the replication of an enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus in a cell infected with the enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus, the method comprising contacting the cell with a compound of claim 13 .
17. A method of treating a patient or animal infected with an enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus, the method comprising administration of an effective amount of a compound of claim 13 to the patient or animal.
18. A pharmaceutical composition for treating an enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus infection, the composition comprising an effective amount of the compound of claim 14 and a pharmaceutically acceptable excipient.
19. A method for inhibiting the replication of an enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus in a cell infected with the enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus, the method comprising contacting the cell with a compound of claim 14 .
20. A method of treating a patient or animal infected with an enterovirus, paramyxovirus, respiratory virus, flaviviridae virus, bunyaviridae virus, togaviridae virus, or rabies virus, the method comprising administration of an effective amount of a compound of claim 14 to the patient or animal.