Pyrazino[1,2-a]indole compounds, their preparation and use in medicaments

1. A compound selected from the group consisting of:

2-(2-(4-methylpiperazin-1-yl)propyl)-1,2,3,4-tetrahydropyrazino[1,2-a]indole,

2-(2-(azepan-1-yl)ethyl)-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole,

2-(2-(azepan-1-yl)ethyl)-1,2,3,4-tetrahydropyrazino[1,2-a]indole hydrochloride,

2-(2-(4-benzylpiperidin-1-yl)ethyl)-1,2,3,4-tetrahydropyrazino[1,2-a]indole hydrochloride,

2-(2-(4-methylpiperazin-1-yl)ethyl)-1,2,3,4-tetrahydropyrazino[1,2-a]indole hydrochloride,

2-(2-(4-benzylpiperidin-1-yl)propyl)-1,2,3,4 tetrahydropyrazino[1,2-a]indole maleate,

2-(2-(azepan-1-yl)ethyl)-10-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indole,

2-(2-(azepan-1-yl)ethyl)-8-fluoro-1,2,3,4-tetrahydropyrazino[1,2-a]indole,

2-(2-(azepan-1-yl)propyl)-8-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indole,

2-(2-(4-benzylpiperidin-1-yl)ethyl)-10-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indole,

8-fluoro-2-(4-(piperidin-1-yl)butyl)-1,2,3,4-tetrahydropyrazino[1,2-a]indole,

2-(3-(azepan-1-yl)propyl)-1,2,3,4-tetrahydropyrazino[1,2-a]indole,

2-(4-(piperidin-1-yl)butyl)-1,2,3,4-tetrahydropyrazino[1,2-a]indole,

2-(4-(azepan-1-yl)butyl)-8-fluoro-1,2,3,4-tetrahydropyrazino[1,2-a]indole,

2-(4-(4-methylpiperazin-1-yl)butyl)-1,2,3,4-tetrahydropyrazino[1,2-a]indole,

2-(2-(4-cyclohexylpiperazin-1-ylpropyl)-1,2,3,4-tetrahydropyrazino[1,2-a]indole,

8-fluoro-2-(2-(4-methylpiperazin-1-yl)propyl)-1,2,3,4-tetrahydropyrazino[1,2-a]indole,

N,N-dimethyl-4-(3,4,10,10a-tetrahydropyrazino[1,2-a]indol-2(1H)-yl)butan-1-amine,

and pharmaceutically acceptable salts, enantiomers, diastereomers, racemates and/or solvates thereof.

2. A process for the preparation of the compound according to claim 1 , or a pharmaceutically acceptable salt, enantiomer, diastereomer, racemate or solvate thereof, the process being selected from:

a) a process comprising the reduction of a compound of general formula (II)

wherein m is selected from the group consisting of 0, 1 and 2,

is a single or a double bond,

R 1 is selected from the group consisting of hydrogen, methyl and fluoro,

R 2 and R 3 are hydrogen,

R 4 and R 5 are methyl or together with the bridging nitrogen form a heterocyclic radical selected from the group consisting of 4-methylpiperazin-1-yl, 4-cyclohexylpiperazin-1-yl, azepan-1-yl, piperidin-1-yl and 4-benzylpyperidin-1-yl,

R 6 is selected from the group consisting of hydrogen and methyl, and p is 0; or

b) a process comprising the reaction a compound of general formula (V)

wherein is a single or a double bond,

R 1 is selected from the group consisting of hydrogen, methyl and fluoro, and

R 6 is selected from the group consisting of hydrogen and methyl with a compound of general formula (VIII)

wherein the sum of m and n is 1, 2, or 3,

R 2 and R 3 are hydrogen,

R 4 and R 5 are methyl or together with the bridging nitrogen form a heterocyclic radical selected from the group consisting of 4-methylpiperazin-1-yl, 4-cyclohexylpiperazin-1-yl, azepan-1-yl, piperidin-1-yl and 4-benzylpyperidin-1-yl, and X is a suitable leaving group.

3. A pharmaceutical composition comprising at least one compound according to claim 1 , or a pharmaceutically acceptable salt, enantiomer, diastereomer, racemate or solvate thereof and a pharmaceutically acceptable excipient.

4. A method for the treatment and/or prophylaxis of a sigma receptor-mediated disease or condition, the method comprising administering to a subject in need of such a treatment or prophylaxis a therapeutically effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt, enantiomer, diastereomer, racemate or solvate thereof.

5. The method according to claim 4 , wherein the sigma receptor-mediated disease or condition is selected from pain; diarrhoea; lipoprotein disorders; hyperlipidemia; hypertriglyceridemia; hypercholesterolemia; obesity; migraine; arthritis; hypertension; arrhythmia; ulcer; glaucoma; learning, memory and attention deficits; cognition disorders; neurodegenerative diseases; demyelinating diseases; addiction to drugs and chemical substances; tardive dyskinesia; stroke; epilepsy; stress; cancer, psychotic conditions; inflammation and autoimmune diseases.

6. The method according to claim 5 , wherein the pain is selected from neuropathic pain, inflammatory pain or other pain conditions involving allodynia and/or hyperalgesia.

7. The method according to claim 5 , wherein the addiction to drugs and chemical substances is selected from cocaine, amphetamine, ethanol and nicotine.

8. The method according to claim 5 , wherein the stroke is ischemic stroke.

9. The method according to claim 5 , wherein psychotic conditions are selected from depression, anxiety or schizophrenia.