Substituted imidazolidines, process for their preparation, and their use as a medicament or diagnostic, and medicament comprising them
View Patent ↗The invention relates to novel compounds of the type of the imidazolidines of the formula I in which R1 to R7 are as defined in the claims. They are used for preparing a medicament for the treatment or prophylaxis of the central nervous system, of lipid metabolism, of infection by ectoparasites, of disorders of gall function and for improving the respiratory drive and are therefore used for treating respiratory distress. Additionally, the compounds increase the muscle tone of the upper respiratory tract, thus suppressing snoring.
1. An imidazlidine of the formula
in which
R1 and R2
independently of one another are —CN, —(C 2 –C 5 )-alkyl, —(C 2 –C 5 )-alkenyl, —(C 2 –C 5 )-alkynyl, —(C 3 –C 6 )-cycloalkyl or —(C 4 –C 6 )-cycloalkenyl
where the carbon chains and carbon rings, independently of one another, are unsubstituted or substituted by 1–11 fluorine atoms or by up to two radicals selected from the group consisting of —OH; —NH 2 , —NHCH 3 , —N(CH 3 ) 2 and —OCH 3 ;
or
R1 and R2
together with the two carbon atoms to which they are attached arc a five-to eight-membered, non-aromatic, saturated or unsaturated carbon ring, where the ring is unsubstituted or substituted by 1–12 fluorine atoms or by up to two radicals selecled from the group consisting of —CH 3 and —OCH 3 , with the proviso that there is no double bond between the two carbon atoms to which R1 and R2 are attached;
R3 is F, Cl, Br, I, —(C 1 –C 4 )-alkYl, —(C 2 –C 4 )-alkenyl, —(C 3 –C 6 )-cycloalkenyl, —OH, —(C 1 –C 4 )-alkoxy, —O-phenyl, —CN, —NO 2 or —NH 2 ;
where the phenyl is unsubstituted or substituted by up to two radicals selected from the group consisting of —CH 3 , F, Cl, Br, I, —OH and —OCH 3 ; and
where the carbon chains or carbon rings, independently of one another, are unsubstituted or substituted by 1–11 fluorine atoms;
R4 to R6
independently of one another are H, F, Cl, Br, I, —(C 2 –C 4 )-alkyl, —(C 2 –C 4 )-alkenyl, —(C 3 –C 6 )-cycloalkyl, —OH, —(C 1 –C 4 )-alkoxy, —CN, —NO 2 , —NH 2 , —(C 1 –C 4 )-alkylamino or —(C 1 –C 4 )-dialkylamino;
where the carbon chains or carbon rings, independently of one another, are unsubstituted or substituted by 1–11 fluorine atoms;
R7 is H, F, Cl, Br, I, —(C 1 –C 4 )-alkyl, —(C 2 –C 4 )-alkenyl, —(C 3 –C 6 )-cycloalkyl, —OH, —(C 1 –C 4 )-alkoxy, —CN, —NO 2 or NH 2 ;
where the carbon chains or carbon rings independently of one another, are unsubstituted or substituted by 1–11 fluorine atoms;
or a pharmaceutically acceptable, salt thereof, or a trifluoroacetic acid salt thereof, in any stereoisomeric form, or a mixture of any such compounds in any ratio.
2. The compound as claimed in claim 1 , in which
R1 and R2
independently of one another are —(C 1 –C 5 )-alkyl, —(C 2 –C 5 )-alkenyl, —(C 2 –C 5 )-alkynyl, —(C 3 –C 6 )-cycloalkyl or —(C 4 –C 6 )-cycloalkeyl,
where the carbon chains and carbon rings, independently of one another, are unsubstituted or substituted by 1–11 fluorine atoms or by up to two radicals selected from the group consisting of —NHCH 3 , —N(CH 3 ) 2 and —OCH 3 ;
or
R1 and R2
together with the two carbon atoms to which they are attached are a five-to eight-membered, non-aromatic, saturated or unsaturated carbon ring, where the ring is unsubstituted or substituted by 1–12 fluorine atoms or by up to two radicals selected from the group consisting of —CH 3 and —OCH 5 ;
with the proviso that there is no double bond between the two carbon atoms to which R1 and R2 are attached;
R3 is F, Cl, Br, I, —(C 1 –C 4 )-alkyl, —(C 2 –C 4 )-alkenyl, —(C 3 –C 6 )-cycloalkyl, —OH, —(C1.C4)-alkoxy, —O-phenyl, —CN, —NO 2 or —NH 2 ;
where the phenyl is unsubstituted or substituted by up to two radicals selected from the group consisting of —CH 3 , F, Cl, BR, —OH and —OCH 3 ; and
where the carbon chains or carbon rings independently of one another, are unsubstituted or substituted by 1–11 fluorine atoms;
R4 to R6
independently of one another are H, F, Cl, Br, —CH 3 , —OH, —OCH 3 , —CN, —NO 2 , —NH 2 , —NHCH 3 , or —N(CH 3 ) 2 ;
where the methyl group, independently of one another, are unsubstituted or substituted by 1–3 fluorine atoms;
R7 is H, F, Cl, Br, I, —(C 1 –C 4 )-alkyl, —(C 2 –C 4 )-alkenyl, —(C 3 –C 6 )-cycloalkyl, —OH, —(C 1 –C 4 )-alkoxy, —CN, —NO 2 or —NH 2 ;
where the carbon chains or carbon rings, independently of one another, are unsubstituted or substituted by 1–11 fluorine atoms;
or a pharmaceutically acceptable salt thereof, or a trifluoroacetic acid salt thereof, in any stereoisomeric form, or a mixture of any such compounds in any ratio.
3. The compound as claimed in claim 1 , chosen from:
trans-(2-chloro-6-trifluoromethylphenyl)-(octahydrobenzimidazol-2-ylidene)amine hydrochloride,
(S,S)-(2,6-dichlorophenyl)-(octahydrobenzimidazol-2-ylidene)amine trifluoroacetic acid salt,
cis-(2,6-dichlorophenyl)-(octahydrobenzimidazol-2-ylidene)amine trifluoroacetic acid salt,
(R,R)-(2,6-dichlorophenyl)-(octahydrobenzimidazol-2-ylidene)amine trifluoroacetic acid salt,
trans-(octahydrobenzimidazol-2-ylidene)-(2-phenoxyphenyl)amine hydrochloride,
trans-(2,6-dichlorophenyl)-(4,5-diisopropylimidazolidin-2-ylidene)amine hydrochloride,
trans-(2,6-dichlorophenyl)-(4,5-dicyclopropylimidazolidin-2-ylidene)amine trifluoroacetic acid salt,
cis-(2,6-dichlorophenyl)-(4,5-dicyclopropylimidazolidin-2-ylidene)amine hydrochloride,
trans-(2,6-dichlorophenyl)-(4,5-diethylimidazolidin-2-ylidene)amine hydrochloride,
(2,6-dichlorophenyl)-(4,5-diimethylimidazolidin-2-ylidene)amine nitric acid salt, and
trans-(2,6-dichlorophenyl)-(hexahydrocyclopentaimidazol-2-ylidene)amine trifluoroacetic acid salt.
4. The compound as claims in claim 1 , chosen from:
(S,S)-(2,6-dichlorophenyl)-(octahydrobenzimidazol-2-ylidene)amine trifluoroacetic acid salt,
cis-(2,6-dichlorophenyl)-(octahydrobenzimidazol-2-ylidene)amine trifluoroacetic acid salt,
(R,R)-(2,6-dichlorophenyl)-(octahydrobenzimidazol-2-ylidene)amine trifluoroacetic acid salt,
trans-(2,6-dichlorophenyl)-(4,5-diisopropylimidazolidin-2-ylidene)amine hydrochloride,
trans-(2,6-dichlorophenyl)-(4,5-dicyclopropylimidazolidin-2-ylidene)amine trifluoroacetic acid salt,
cis-(2,6-dichlorophenyl)-(4,5-dicyclopropylimidazolidin-2-ylidene)amine hydrochloride,
trans-(2,6-dichlorophenyl)-(4,5-diethylimidazolidin-2-ylidene)amine hydrochloride,
(2,6-dichlorophenyl)-(4,5-dimethylimidazolidin-2-ylidene)amine nitric acid salt, and
trans-(2,6-dichlorophenyl)-(hexahydrocyclopentaimidazol-2-ylidene)amine trifluoroacetic acid salt.
5. A pharmaceutical comprising at least one compound as claimed in claim 1 and at least one pharmaceutical carrier, with the proviso that said compound is not a trifluoroacetic acid salt.