Substituted (thiophenyl-carbonyl)imidazolidinones, and use thereof
The present invention relates to novel substituted (thiophenyl-carbonyl)imidazolidinones, methods for their production, their use for the treatment and/or prevention of diseases, as well as their use for the production of medicaments for the treatment and/or prophylaxis of diseases, especially 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 one to three times identically or differently with radicals selected from the group consisting of 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 substituents selected from the group consisting of 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, and
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 one to three times identically or differently with radicals selected from the group consisting of 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 substituents selected from the group consisting of 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 one of the salts 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, and
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, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, (C 1 -C 4 )-alkyl and (C 1 -C 4 )-alkoxy,
wherein
(C 1 -C 4 )-alkoxy in turn may be substituted one or three times identically or differently with radicals selected from the group consisting of 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, or di-(C 1 -C 4 )-alkylamino,
or one of the salts 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, methyl 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, trifluoromethyl, trifluoromethoxy, methyl and (C 1 -C 3 )-alkoxy,
or one of the salts thereof.
4. The compound of claim 1 , corresponding to formula
in which
R 3 represents halogen or cyano,
R 4 represents hydrogen or halogen,
R 5 represents halogen, cyano or trifluoromethyl, and
R 6 represents hydrogen or halogen,
or one of the salts thereof.
5. The compound of claim 4 , whereby
R 3 represents fluorine, chlorine or cyano,
R 4 represents hydrogen, chlorine or fluorine,
R 5 represents fluorine, chlorine or cyano, and
R 6 represents hydrogen, chlorine or fluorine,
or one of the salts thereof.
6. The compound of claim 4 , whereby
R 3 represents chlorine or cyano,
R 4 represents hydrogen or fluorine,
R 5 represents chlorine or cyano, and
R 6 represents hydrogen or fluorine,
or one of the salts thereof.
7. A method for preparing a compound of formula (I) of claim 1 , comprising reacting a compound of formula
in which
R 1 and R 2 have the meaning given in claim 1 ,
with imidazolidin-4-one or with a salt of imidazolidin-4-one.
8. A method for preparing a compound of formula (I) of claim 1 , comprising reacting a compound of formula
in which
R 2 has the meaning given in claim 1 ,
under Suzuki coupling conditions with a compound of formula
R 1 -Q (V),
in which
R 1 has the meaning given in claim 1 and
Q represents —B(OH) 2 , a boronic acid ester, boronic acid pinacol ester, or —BF 3 − K + .
9. A method for preparing a compound of formula (I) of claim 1 , comprising reacting a compound of formula
in which
R 1 has the meaning given in claim 1 ,
under Suzuki coupling conditions with a compound of formula
R 2 -Q (VII),
in which
R 2 has the meaning given in claim 1 and
Q represents —B(OH) 2 , a boronic acid ester, boronic acid pinacol ester, or —BF 3 − K + .
10. A method for the manufacture of a medicament for the treatment of retroviral diseases comprising mixing a compound of claim 1 with an inert, non-toxic, pharmaceutically acceptable excipient.
11. A medicament comprising a therapeutically effective amount of at least one compound of claim 1 in combination with at least one inert, non-toxic, pharmaceutically acceptable excipient.
12. A method for controlling HIV-1 infections in humans and animals by administering an antivirally effective amount of at least one compound of claim 1 or a medicament of claim 11 to a human or animal in need thereof.