Iminosugars and methods of treating bunyaviral and togaviral diseases
Provided are novel methods of treating and/or preventing a disease or condition caused by or associated with a virus belonging to the Bunyaviridae or Togaviridae family using iminosugars, such as DNJ derivatives.
1. A method of treating a disease or condition caused by or associated with a virus belonging to the Bunyaviridae family, the method comprising
administering to a subject in need thereof a compound of the formula,
or a pharmaceutically acceptable salt thereof, wherein R is either selected from substituted or unsubstituted alkyl groups, substituted or unsubstituted cycloalkyl groups, substituted or unsubstituted aryl groups, or substituted or unsubstituted oxaalkyl groups; or wherein R is
R 1 is a substituted or unsubstituted alkyl group;
X 1-5 are independently selected from H, NO 2 , N 3 , or NH 2 ;
Y is absent or is a substituted or unsubstituted C 1 -alkyl group, other than carbonyl; and
Z is selected from a bond or NH; provided that when Z is a bond, Y is absent, and provided that when Z is NH, Y is a substituted or unsubstituted C 1 -alkyl group, other than carbonyl; and
wherein W 1-4 are independently selected from hydrogen, substituted or unsubstituted alkyl groups, substituted or unsubstituted haloalkyl groups, substituted or unsubstituted alkanoyl groups, substituted or unsubstituted aroyl groups, or substituted or unsubstituted haloalkanoyl groups.
2. The method of claim 1 , wherein R is a C8-C16 alkyl group.
3. The method of claim 2 , wherein each of W 1-4 is hydrogen.
4. The method of claim 3 , wherein the compound is N-nonyl-deoxynojirimycin or a pharmaceutically acceptable salt thereof.
5. The method of claim 1 , wherein R is
6. The method of claim 5 , wherein each of W 1-4 is hydrogen.
7. The method of claim 5 , wherein X 1 is NO 2 and X 3 is N 3 .
8. The method of claim 5 , wherein each of X 2 , X 4 and X 5 is hydrogen.
9. The method of claim 5 , wherein the compound is N—(N-{4′-azido-2′-nitrophenyl}-6-aminohexyl)deoxynojirimycin or a pharmaceutically acceptable salt thereof.
10. The method of claim 1 , wherein the subject is a mammal.
11. The method of claim 1 , wherein the subject is a human being.
12. The method of claim 1 , wherein the virus is selected from Andes virus; Hantaan virus; Puumala virus; Seoul virus; Sin Nimbre virus; Dugbe virus; Crimean-Congo hemorrhagic fever virus; La Crosse virus and Raft Valley Fever virus.
13. The method of claim 1 , wherein the virus belongs to Genus Phlebovirus.
14. The method of claim 1 , wherein the virus is Rift Valley fever virus.
15. The method of claim 1 , wherein the disease or condition is selected from hemorrhagic fever with renal syndrome; Hantavirus cardiopulmonary syndrome;
Nephropathia epidemica; hemorrhagic fever caused by Seoul virus; Sweating sickness; Crimean-Congo hemorrhagic fever; La Crosse encephalitis; Phlebotomus fever; and Rift Valley fever.
16. The method of claim 1 , wherein the disease or condition is Rift Valley fever.
17. A method of treating a disease or condition caused by or associated with a virus belonging to the Togaviridae family, the method comprising administering to a subject in need thereof a compound of the formula,
or a pharmaceutically acceptable salt thereof, wherein R is either selected from substituted or unsubstituted alkyl groups, substituted or unsubstituted cycloalkyl groups, substituted or unsubstituted aryl groups, or substituted or unsubstituted oxaalkyl groups; or wherein R is
R 1 is a substituted or unsubstituted alkyl group;
X 1-5 are independently selected from H, NO 2 , N 3 , or NH 2 ;
Y is absent or is a substituted or unsubstituted C 1 -alkyl group, other than carbonyl; and
Z is selected from a bond or NH; provided that when Z is a bond, Y is absent, and provided that when Z is NH, Y is a substituted or unsubstituted C 1 -alkyl group, other than carbonyl; and
wherein W 1-4 are independently selected from hydrogen, substituted or unsubstituted alkyl groups, substituted or unsubstituted haloalkyl groups, substituted or unsubstituted alkanoyl groups, substituted or unsubstituted aroyl groups, or substituted or unsubstituted haloalkanoyl groups.
18. The method of claim 17 , wherein R is a C8-C16 alkyl group.
19. The method of claim 18 , wherein each of W 1-4 is hydrogen.
20. The method of claim 19 , wherein the compound is N-nonyl-deoxynojirimycin or a pharmaceutically acceptable salt thereof.
21. The method of claim 17 , wherein R is
22. The method of claim 21 , wherein each of W 1-4 is hydrogen.
23. The method of claim 21 , wherein X 1 is NO 2 and X 3 is N 3 .
24. The method of claim 21 , wherein each of X 2 , X 4 and X 5 is hydrogen.
25. The method of claim 21 , wherein the compound is N—(N-{4′-azido-2′-nitrophenyl}-6-aminohexyl)deoxynojirimycin or a pharmaceutically acceptable salt thereof.
26. The method of claim 17 , wherein the subject is a mammal.
27. The method of claim 17 , wherein the subject is a human being.
28. The method of claim 17 , wherein the virus is selected from Sindbis virus; Semliki Forest virus; O′nyong'nyong virus; Chikungunya virus; Mayaro virus; Ross River virus; Barmah Forest virus; Eastern equine encephalitis virus; Western equine encephalitis virus; Venezuelan equine encephalitis virus and Rubella virus.
29. The method of claim 17 , wherein the virus belongs to Genus Alphavirus.
30. The method of claim 17 , wherein the virus is Chikungunya virus.
31. The method of claim 17 , wherein the virus is Venezuelan equine encephalitis virus.
32. The method of claim 17 , wherein the disease or condition is selected from sindbis fever; O′nyong'nyong fever; Chikungunya disease; Ross River fever; Barmah Forest virus infection; Eastern equine encephalitis; Western equine encephalitis; Venezuelan equine encephalitis and Rubella.
33. The method of claim 17 , wherein the disease or condition is Chikungunya disease.
34. The method of claim 17 , wherein the disease or condition is equine encephalitis.
35. The method of claim 17 , wherein the disease or condition is Venezuelan equine encephalitis.