Screen for inhibitors of filovirus and uses therefor

1. A method to inhibit or treat filovirus infection in a mammal, comprising administering to the mammal an effective amount of a compound of formula (IX) or (X), wherein formula (IX) is:

wherein

Ar is a furan;

X is —O;

a dashed line represents either the presence or absence of a bond;

R 1 and R 2 taken together form an epoxide ring, aziridine ring, cyclopropyl ring, or a bond of a carbon-carbon double bond;

R 3 is hydrogen; methyl; ethyl; or propyl;

R 4 is hydrogen; methyl; ethyl; or propyl;

R 5 is hydrogen; methyl; ethyl; or propyl;

R 6 is hydrogen; hydroxy; oxo (═O); acetyl protected hydroxyl; methyl; ethyl; or propyl;

R 7 is hydrogen; hydroxy; methyl; ethyl; or propyl;

R 8 is hydrogen; hydroxy; methyl; ethyl; or propyl;

R 9 is hydrogen; hydroxy; oxo (═O); acetyl protected hydroxyl; methyl; ethyl; or propyl;

R 10 is hydrogen; hydoxy; oxo (═O); acetyl protected hydroxyl; methyl; ethyl; propyl; or epoxy;

R 11 is hydrogen, halo, hydroxy, or a carbonyl;

or a pharmaceutically acceptable salt, stereoisomer, or tautomer; and

wherein formula (X) is:

wherein

R 6 is hydrogen; hydroxy; oxo (═O); or acetyl-protected hydroxyl; and

R 9 is hydrogen; hydroxy; oxo (═O); or acetyl-protected hydroxyl, or a pharmaceutically acceptable salt, stereoisomer, or tautomer.

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

3. A method to inhibit or treat filovirus infection in a mammal, comprising administering to the mammal an effective amount of 7-deacetoxy-3-deacetyl-7-oxokhivorin, 1,2alpha-epoxy-7-deacetoxy-7-oxodihxdrogedunin, epoxygedunin, 1,3-dideacetyl-7-deacetoxy-7-oxokhivorin, gedunin, gedunol, dihydrogedunin, 3beta-acetoxydeoxodihydrogedunin, 3alpha-hydroxydeoxodihydrogedunin, deacetoxy-7-oxogedunin, 3beta-hydroxydeoxodihydrogedunin, 1,2alpha-epoxydeacetoxydihydrogedunin, 3beta-hydroxydeoxydesacetoxy-7-oxogedunin, tridesacetoxykhivorin, 1,3-dideacetylkhivorin, heudelottin C, deacetylgedunin, deacetoxy-7-oxisogedunin, 1,7-dideacetoxy-1,7-dioxokhivorin, isogedunin, or 6-acetoxyangolensic acid methyl ester, or any combination thereof.

4. The method of claim 1 wherein the agent is orally administered.

5. The method of claim 1 wherein the agent is intravenously administered.

6. The method of claim 1 wherein the agent is subcutaneously administered.

7. The method of claim 3 wherein the mammal is a human.

8. The method of claim 3 wherein the agent is orally administered.

9. The method of claim 3 wherein the effective amount is intravenously administered.

10. The method of claim 3 wherein the effective amount is subcutaneously administered.

11. The method of claim 1 wherein R 3 , R 4 , R 5 , R 7 , or R 8 independently is hydrogen or methyl.

12. The method of claim 3 wherein 7-deacetoxy-3-deacetyl-7-oxokhivorin, 1,2alpha-epoxy-7-deacetoxy-7-oxodihxdrogedunin, epoxygedunin, 1,3-dideacetyl-7-deacetoxy-7-oxokhivorin, gedunin, gedunol, dihydrogedunin, 3beta-acetoxydeoxodihydrogedunin, 3alpha-hydroxydeoxodihydrogedunin, deacetoxy-7-oxogedunin, 3beta-hydroxydeoxodihydrogedunin, 1,2alpha-epoxydeacetoxydihydrogedunin, 3beta-hydroxydeoxydesacetoxy-7-oxogedunin, tridesacetoxykhivorin, 1,3-dideacetylkhivorin, or heudelottin C is administered.

13. The method of claim 3 wherein epoxygedunin, 1,3-dideacetyl-7-deacetoxy-7-oxokhivorin, gedunin, gedunol, dihydrogedunin, 3beta-acetoxydeoxodihydrogedunin, 3alpha-hydroxydeoxodihydrogedunin, deacetoxy-7-oxogedunin, 3beta-hydroxydeoxodihydrogedunin, 1,2alpha-epoxydeacetoxydihydrogedunin, 3beta-hydroxydeoxydesacetoxy-7-oxogedunin, 1,3-dideacetylkhivorin, or heudelottin is administered.

14. The method of claim 3 wherein epoxygedunin, 1,3-dideacetyl-7-deacetoxy-7-oxokhivorin, gedunin, or 7-deacetoxy-3-deacetyl-7-oxokhivorin is administered.

15. The method of claim 1 wherein R 6 or R 9 independently is hydrogen, hydroxyl, oxo (═O), or acetyl-protected hydroxyl.

16. The method of claim 1 wherein R 10 is hydrogen, hydroxyl or acetyl.