Substituted hexahydropyrrolo[1,2-a]pyrazines, octahydropyrido[1,2-a]-pyrazines and decahydropyrazino[1,2-a]azepines
View Patent ↗Novel substituted hexahydropyrrolo[1,2-a]pyrazines, octahydropyrido[1,2-a]-pyrazines and decahydropyrazino[1,2-a]azepines, use of these compounds as pharmaceutical compositions, pharmaceutical compositions comprising the compounds, and a method of treatment employing these compounds and compositions. The compounds show a high and selective binding affinity to the histamine H3 receptor indicating histamine H3 receptor antagonistic, inverse agonistic or agonistic activity. As a result, the compounds are useful for the treatment of diseases and disorders related to the histamine H3 receptor.
1. A compound selected from the following group:
1-(3,4-Dimethoxyphenyl)-4-((S)-hexahydropyrrolo[1,2-a]pyrazin-2-yl)butane-1,4-dione,
1-(4-Chlorophenyl)-4-((S)-hexahydropyrrolo[1,2-a]pyrazin-2-yl)butane-1,4-dione,
1-(4-Chlorophenyl)-4-(octahydropyrido[1,2-a]pyrazin-2-yl)butane-1,4-dione,
1-(3-Fluoro-4-methoxyphenyl)-4-(octahydropyrido[1,2-a]pyrazin-2-yl)butane-1,4-dione,
1-(3,4-Dimethoxyphenyl)-4-(octahydropyrido[1,2-a]pyrazin-2-yl)butane-1,4-dione,
1-(3-Fluoro-4-methoxyphenyl)-4-((S)-octahydropyrido[1,2-a]pyrazin-2-yl)butane-1,4-dione,
1-(3-Fluoro-4-methoxyphenyl)-4-((R)-octahydropyrido[1,2-a]pyrazin-2-yl)butane-1,4-dione;
(S)-Octahydropyrido[1,2-a]pyrazine-2-carboxylic acid 2-(4-methoxyphenyl)ethyl ester,
(R)-Octahydropyrido[1,2-a]pyrazine-2-carboxylic acid 2-(3-(trifluoromethyl)phenyl)ethyl ester,
[3,5-Difluoro-4-((R)-octahydropyrido[1,2-a]pyrazin-2-yl)phenyl]-[phenyl]methanone,
(4-Fluorophenyl)-[4-((R)-octahydropyrido[1,2-a]pyrazin-2-yl)phenyl]methanone,
{[4-((R)-Octahydropyrido[1,2-a]pyrazin-2-yl)phenyl]}-{phenyl}methanone, and
(R)-2-[6-(4-Trifluoromethyl-phenyl)-pyridazin-3-yl]-octahydro-pyrido[1,2-a]pyrazine,
as well as any diastereomer or enantiomer or tautomeric form thereof or mixtures of these or a pharmaceutically acceptable salt thereof.
2. A pharmaceutical composition comprising, as an active ingredient, at least one compound according to claim 1 together with one or more pharmaceutically acceptable carriers or excipients.
3. A pharmaceutical composition according to claim 2 in unit dosage form, comprising from about 0.05 mg to about 1000 mg of the compound.
4. A pharmaceudcal composition according to claim 2 in unit dosage form,
comprising from about 0.1 mg to about 500 mg of the compound.
5. A pharmaceutical composition according to claim 2 in unit dosage form,
comprising from about 0.5 mg to about 200 mg of the compound.