Substituted (pyrazolylcarbonyl)imidazolidinones and their use
The present invention relates to novel substituted (pyrazolylcarbonyl)imidazolidinones, methods for their preparation, their use for the treatment and/or prophylaxis of diseases, as well as their use for the manufacture of medicaments for the treatment and/or prophylaxis of diseases, especially of retroviral diseases, in humans and/or animals.
1. A compound of formula
in which
R 1 represents phenyl,
whereby phenyl is substituted with 1 to 3 substituents, whereby the substituents are selected independently of one another from the group consisting of halogen, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, (C 1 -C 4 )-alkyl and (C 1 -C 4 )-alkoxy,
wherein
(C 1 -C 4 )-alkyl and (C 1 -C 4 )-alkoxy in turn may be substituted once to three times, identically or differently, with radicals selected from the series halogen, cyano, hydroxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, (C 3 -C 7 )-cycloalkyl and 4- to 7-membered heterocyclyl,
whereby the last-mentioned cycloalkyl and heterocyclyl radicals in turn may each be substituted up to three times, identically or differently, with halogen, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxy, (C 1 -C 4 )-alkoxy, trifluoromethoxy, oxo, amino, mono-(C 1 -C 4 )-alkylamino and di-(C 1 -C 4 )-alkylamino,
R 2 represents phenyl,
whereby phenyl is substituted with 1 to 3 substituents, whereby the substituents are selected independently of one another from the group consisting of halogen, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, (C 1 -C 4 )-alkyl and (C 1 -C 4 )-alkoxy,
wherein
(C 1 -C 4 )-alkyl and (C 1 -C 4 )-alkoxy in turn may be substituted once to three times, identically or differently, with radicals selected from the series halogen, cyano, hydroxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, (C 3 -C 7 )-cyclo-alkyl and 4- to 7-membered heterocyclyl,
whereby the last-mentioned cycloalkyl and heterocyclyl radicals in turn may each be substituted up to three times, identically or differently, with halogen, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxy, (C 1 -C 4 )-alkoxy, trifluoromethoxy, oxo, amino, mono-(C 1 -C 4 )-alkylamino and di-(C 1 -C 4 )-alkylamino,
or a salt thereof.
2. The compound of claim 1 , whereby
R 1 represents phenyl,
whereby phenyl is substituted with 1 to 2 substituents, whereby the substituents are selected independently of one another from the group consisting of halogen, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, (C 1 -C 4 )-alkyl and (C 1 -C 4 )-alkoxy,
R 2 represents phenyl,
whereby phenyl is substituted with 1 to 2 substituents, whereby the substituents are selected independently of one another from the group consisting of halogen, hydroxy, cyano, nitro, trifluoromethoxy, trifluoromethylthio, (C 1 -C 4 )-alkyl and (C 1 -C 4 )-alkoxy,
wherein
(C 1 -C 4 )-alkoxy in turn may be substituted once to three times, identically or differently, with radicals selected from the series halogen, cyano, hydroxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, (C 3 -C 7 )-cycloalkyl and 4- to 7-membered heterocyclyl,
whereby the last-mentioned cycloalkyl and heterocyclyl radicals in turn may each be substituted up to three times, identically or differently, with halogen, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxy, (C 1 -C 4 )-alkoxy, trifluoromethoxy, oxo, amino, mono-(C 1 -C 4 )-alkylamino and di-(C 1 -C 4 )-alkylamino,
or a salt thereof.
3. The compound of claim 1 , whereby
R 1 represents phenyl,
whereby phenyl is substituted with 1 to 2 substituents, whereby the substituents are selected independently of one another from the group consisting of halogen, cyano, trifluoromethyl and methoxy,
R 2 represents phenyl,
whereby phenyl is substituted with 1 to 2 substituents, whereby the substituents are selected independently of one another from the group consisting of halogen, cyano, trifluoromethoxy, methyl and (C 1 -C 3 )-alkoxy,
wherein
(C 1 -C 3 )-alkoxy in turn may be substituted once to three times, identically or differently, with radicals selected from the series hydroxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 ) -alkylamino, di-(C 1 -C 4 )-alkylamino and 4- to 7-membered heterocyclyl,
whereby the last-mentioned heterocyclyl radicals may in turn each be substituted with (C 1 -C 4 )-alkyl,
or a salt thereof.
4. The compound of claim 1 , whereby
R 1 represents phenyl,
whereby phenyl is substituted with 1 to 2 substituents, whereby the substituents are selected independently of one another from the group consisting of halogen, cyano, trifluoromethyl and methoxy,
R 2 represents phenyl,
whereby phenyl is substituted with 1 to 2 substituents, whereby the substituents are selected independently of one another from the group consisting of halogen, cyano, trifluoromethoxy, methyl and methoxy,
or a salt thereof.
5. The compound of claim 1 , whereby
R 1 represents phenyl,
whereby phenyl is substituted with 1 to 2 substituents, whereby the substituents are selected independently of one another from the group consisting of halogen and cyano,
R 2 represents phenyl,
whereby phenyl is substituted with 1 to 2 substituents, whereby the substituents are selected independently of one another from the group consisting of halogen and cyano,
or a salt thereof.
6. The compound of claim 1 , corresponding to formula
in which
R 3 represents hydrogen, halogen, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-alkoxy,
R 4 represents hydrogen or halogen,
R 5 represents halogen, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-alkoxy,
wherein
(C 1 -C 4 )-alkoxy in turn may be substituted once to three times, identically or differently, with radicals selected from the series halogen, cyano, hydroxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, (C 3 -C 7 )-cycloalkyl and 4- to 7-membered heterocyclyl,
whereby the last-mentioned cycloalkyl and heterocyclyl radicals in turn may each be substituted up to three times, identically or differently, with halogen, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxy, (C 1 -C 4 )-alkoxy, trifluoromethoxy, oxo, amino, mono-(C 1 -C 4 )-alkylamino and di-(C 1 -C 4 )-alkylamino,
R 6 represents hydrogen or halogen,
or a salt thereof.
7. The compound of claim 6 , whereby
R 3 represents halogen, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-alkoxy,
R 4 represents hydrogen or halogen,
R 5 represents halogen, hydroxy, cyano, nitro, trifluoromethoxy, trifluoromethylthio, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-alkoxy,
wherein
(C 1 -C 4 )-alkoxy in turn may be substituted once to three times, identically or differently, with radicals selected from the series halogen, cyano, hydroxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 )-alkylamino, di-(C 1 -C 4 )-alkylamino, (C 3 -C 7 )-cycloalkyl and 4- to 7-membered heterocyclyl,
whereby the last-mentioned cycloalkyl and heterocyclyl radicals in turn may each be substituted up to three times, identically or differently, with halogen, cyano, (C 1 -C 4 )-alkyl, trifluoromethyl, hydroxy, (C 1 -C 4 )-alkoxy, trifluoromethoxy, oxo, amino, mono-(C 1 -C 4 )-alkylamino and di-(C 1 -C 4 )-alkylamino,
R 6 represents hydrogen or halogen,
or a salt thereof.
8. The compound of claim 6 , whereby
R 3 represents halogen, cyano, trifluoromethyl or methoxy,
R 4 represents hydrogen or halogen,
R 5 represents halogen, cyano, trifluoromethoxy, methyl or (C 1 -C 3 )-alkoxy,
wherein
(C 1 -C 3 )-alkoxy in turn may be substituted once to three times, identically or differently, with radicals selected from the series hydroxy, (C 1 -C 4 )-alkoxy, amino, mono-(C 1 -C 4 ) -alkylamino, di-(C 1 -C 4 )-alkylamino and 4- to 7-membered heterocyclyl,
whereby the last-mentioned heterocyclyl radicals in turn may each be substituted with (C 1 -C 4 )-alkyl,
R 6 represents hydrogen or halogen,
or a salt thereof.
9. The compound of claim 6 , whereby
R 3 represents halogen, cyano, trifluoromethyl or methoxy,
R 4 represents hydrogen, chlorine or fluorine,
R 5 represents halogen, cyano, trifluoromethoxy, methyl or methoxy,
R 6 represents hydrogen, chlorine or fluorine,
or a salt thereof.
10. The compound of claim 6 , whereby
R 3 represents halogen or cyano,
R 4 represents hydrogen or fluorine,
R 5 represents halogen or cyano,
R 6 represents hydrogen or fluorine,
or a salt thereof.
11. The compound of claim 6 , whereby
R 3 represents chlorine or cyano,
R 4 represents fluorine,
R 5 represents chlorine or cyano,
R 6 represents fluorine,
or a salt thereof.
12. The compound of claim 6 , whereby
R 3 represents chlorine or cyano,
R 4 represents fluorine,
R 5 represents chlorine or cyano,
R 6 represents hydrogen,
or a salt thereof.
13. The compound of claim 6 , whereby
R 3 represents chlorine or cyano,
R 4 represents hydrogen,
R 5 represents chlorine or cyano,
R 6 represents hydrogen,
or a salt thereof.
14. The compound of claim 6 , whereby
R 3 represents chlorine or cyano,
R 4 represents hydrogen,
R 5 represents chlorine or cyano,
R 6 represents fluorine,
or a salt thereof.
15. The compound of claim 6 , whereby
R 3 represents halogen, cyano, trifluoromethyl or methoxy,
R 4 represents hydrogen or halogen,
R 5 represents trifluoromethyl,
R 6 represents fluorine,
or a salt thereof.
16. The compound of claim 6 , whereby
R 3 represents hydrogen,
R 4 represents fluorine or chlorine,
R 5 represents halogen, cyano, trifluoromethoxy, methyl or methoxy,
R 6 represents hydrogen or halogen,
or a salt thereof.
17. A method for preparing a compound of formula (I) of claim 1 , whereby a compound of formula
in which
R 1 and R 2 have the meaning indicated in claim 1 , is reacted with imidazolidin-4-one or a salt of imidazolidin-4-one.
18. A method for manufacturing a medicament, comprising mixing a compound of claim 1 with at least one inert non-toxic pharmaceutically acceptable excipient.
19. A medicament comprising at least one compound of claim 1 in combination with at least one further active ingredient.
20. A medicament comprising at least one compound of claim 1 in combination with at least one inert, non-toxic, pharmaceutically acceptable excipient.
21. A method for controlling retroviral diseases in humans and animals by administering an antivirally effective amount of at least one compound according to claim 1 to a human or animal in need thereof.
22. The method of claim 21 , whereby the retroviral disease is an infection with the HI virus.
23. A method for controlling retroviral diseases in humans and animals by administering an antivirally effective amount of a medicament according to claim 19 to a human or animal in need thereof.
24. The method of claim 23 , whereby the retroviral disease is an infection with the HI virus.
25. A method for controlling retroviral diseases in humans and animals by administering an antivirally effective amount of a medicament according to claim 20 to a human or animal in need thereof.
26. The method of claim 25 , whereby the retroviral disease is an infection with the HI virus.