Sulfonic acid salts of heterocyclylamide-substituted imidazoles
The invention relates to sulfonic acid salts of heterocyclylamide-substituted imidazoles, and to solvates and hydrates thereof, to the use thereof for treating and/or preventing diseases, and to use thereof for producing drugs for treating and/or preventing diseases, in particular for use as antiviral agents, in particular against cytomegaloviruses.
1. A salt of a compound of formula (I)
in which
R 1 stands for methyl, ethyl, butyl, or cyclopropylmethyl,
R 2 stands for phenyl, which phenyl is substituted with a substituent that is selected from the group consisting of trifluoromethoxy and difluoromethoxy, and
R 3 stands for hydrogen, methyl, chlorine, methoxy, or trifluoromethyl,
with methanesulfonic acid
or a hydrate thereof.
2. A salt according to claim 1 , which is a dimesylate salt.
3. A salt according to claim 1 , which is of the following formula:
4. Crystalline N-(1-methyl-2-{[4-(5-methylpyridin-2-yl)piperazin-1-yl]-carbonyl}-1H-imidazol-4-yl)-N′-[4-trifluoromethoxyphenyl]urea dimesylate, which has a powder-XRD diffractogram with characteristic peaks at approximately 6.37, 11.77, 12.56, 17.17, 18.81, 20.34, 21.47, 23.04, and 35.46 degrees 2theta.
5. Crystalline N-(1-methyl-2-{[4-(5-methylpyridin-2-yl)piperazin-1-yl]-carbonyl}-1H-imidazol-4-yl)-N′-[4-trifluoromethoxyphenyl]urea dimesylate, which has a powder-XRD diffractogram as essentially depicted in FIG. 1 .
6. A method for preparing a salt according to claim 1 , comprising reacting a compound of Formula (I) or an acid salt of a compound of formula (I), which is not a salt of methanesulfonic acid, with methanesulfonic acid or a source of methanesulfonate ions in a solvent.
7. A pharmaceutical composition comprising a salt according to claim 1 in combination with at least one inert, non-toxic, pharmaceutically suitable adjuvant.
8. A pharmaceutical composition according to claim 7 , comprising
5 to 12.5 mg/ml of a salt according to claim 1 ,
50 to 150 mg/ml of hydroxypropyl-β-cyclodextrin,
0.5 to 2.0 mg/ml of sodium acetate
as well as water and
optionally other pharmaceutically acceptable adjuvants.
9. A salt of a compound of formula (I) according to claim 1 with methanesulfonic acid.
10. A hydrate of a salt of a compound of formula (I) according to claim 1 with methanesulfonic acid.
11. A method for treating or preventing a viral infection by a member of Herpesviridae, comprising administering to a subject in need thereof an effective amount of a salt according to claim 1 .
12. A method according to claim 11 , which is for treating a viral infection by a member of Herpesviridae.
13. A method according to claim 11 , which is for preventing a viral infection by a member of Herpesviridae.
14. A method according to claim 11 , which is for treating a viral infection by a cytomegalovirus.
15. A method according to claim 11 , which is for preventing a viral infection by a cytomegalovirus.
16. A method according to claim 11 , which is for treating a viral infection by human cytomegalovirus.
17. A method according to claim 11 , which is for preventing a viral infection by human cytomegalovirus.
18. A method for treating or preventing a viral infection by a member of Herpesviridae, comprising administering to a subject in need thereof an effective amount of a salt according to claim 3 .
19. A method for treating or preventing a viral infection by a member of Herpesviridae, comprising administering to a subject in need thereof an effective amount of a salt according to claim 9 .
20. A method for treating or preventing a viral infection by a member of Herpesviridae, comprising administering to a subject in need thereof an effective amount of a hydrate of a salt according to claim 10 .