Long chain N-alkyl compounds and oxa-derivatives thereof
Long chain N-alkyl amino and imino compounds, oxa-substituted derivatives thereof, and pharmaceutical compositions including such compounds are described. The long chain N-alkyl group is a C 8 -C 16 alkyl group. The long chain N-alkyl compounds and oxa-substituted derivatives thereof can be used in the treatment of viral infections, in particular hepatitis B virus or hepatitis C virus, in a cell or an individual. For example, the long chain N-alkyl compounds or oxa-substituted derivatives thereof can be derived from piperidines, pyrrolidines, phenylamines, pyridines, pyrroles, or amino acids.
1. A method of inhibiting morphogenesis of a virus selected from hepatitis C virus (HCV) or bovine viral diarrhea virus (BVDV) comprising administering an effective amount of a nitrogen-containing compound having the formula:
or a physiologically acceptable salt thereof to a cell or an individual infected with said virus, wherein:
R′ is an oxa-substituted derivative of C 8 -C 10 alkyl;
each X, independently, is selected from the group consisting of hydrogen, hydroxy, amino, carboxy, C 1 -C 4 alkylcarboxy, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 hydroxyalkyl, C 1 -C 6 acyloxy, and aroyloxy, and each Y, independently, is selected from the group consisting of hydrogen, hydroxy, amino, carboxy, C 1 -C 4 alkylcarboxy, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 hydroxyalkyl, C 1 -C 6 acyloxy, aroyloxy, and deleted;
R 4 is hydrogen or deleted; and
R′ is selected from the group consisting of hydrogen, hydroxy, amino, substituted amino, carboxy, alkoxycarbonyl, aminocarbonyl, aryl, aralkyl, alkoxy, hydroxyalkyl, acyloxy, and aroyloxy,
wherein said oxa-substituted derivative contains 1 to 5 oxygen atoms.
2. The method of claim 1 , wherein each X is hydroxy and each Y is hydrogen.
3. The method claim 2 , wherein the pound is a deoxynojirimycin derivative.
4. The method of claim 3 , wherein said oxa-substituted derivative contains 1 to 3 oxygen atoms.
5. The method of claim 4 , wherein said oxa-substituted derivative contains 1 to 2 oxygen atoms.
6. The method of claim 3 , wherein R 1 is a C 8 -C 10 oxa-alkyl group.
7. The method of claim 6 , wherein R 1 is (CH 2 ) 6 O(CH 2 ) n CH 3 or (CH 2 ) 2 O(CH 2 ) n+4 CH 3 , n is 1, 2 or 3.
8. The method of claim 7 , wherein R 1 is 3-oxanonyl, 3-oxadecyl, 7-oxanonyl or 7-oxadecyl.
9. The method of claim 8 , wherein said compound is N-7-oxadecyl-DNJ.
10. The method of claim 1 , wherein the compound is a deoxygalactonojirimycin derivative.
11. The method of claim 10 , wherein said oxa-substituted derivative contains 1 to 3 oxygen atoms.
12. The method of claim 11 , wherein said oxa-substituted derivative contains 1 to 2 oxygen atoms.
13. The method of claim 12 , wherein R 1 is a C 8 -C 10 oxa-alkyl group.
14. The method of claim 13 , wherein R 1 is (CH 2 ) 6 O(CH 2 ) n CH 3 or (CH 2 ) 2 O(CH 2 ) n+4 CH 3 , n=1, 2 or 3.
15. The method of claim 14 , wherein R 1 is 3-oxanonyl, 3-oxadecyl, 7-oxanonyl or 7-oxadecyl.
16. The method of claim 15 , wherein the compound is N-7-oxa-nonyl-1,5-dideoxy-1,5-imino-D-galactitol.
17. The method of claim 1 , wherein the virus is bovine viral diarrhea virus (BVDV).
18. The method of claim 1 , wherein the virus is hepatitis C virus (HCV).
19. The method of claim 1 , wherein said administering is administering to a cell infected by the virus.
20. The method of claim 19 , wherein said cell is a mammalian cell.
21. The method of claim 20 , wherein said cell is a human cell.
22. The method of claim 1 , wherein said administering is administering to a mammal.
23. The method of claim 22 , wherein said administering is administering to a human.