Pyrimidinyl-piperazines useful as D
The present invention relates to new dopamine D 3 and D 2 ligands of formula (I): wherein R1, R2 and Q are as described herein, and/or geometric isomers and/or stereoisomers and/or diastereomers and/or salts and/or hydrates and/or solvates and/or polymorphs thereof. The invention also relates to processes for preparing the same, to compositions containing the same and to their use in the treatment and/or prevention of conditions which requires modulation of dopamine receptors.
1. A method of treating a condition selected from the group consisting of psychoses, drug abuse, cognitive impairment accompanying schizophrenia, mild-to-moderate cognitive deficits, dementia, attention deficit disorders, hyperactivity disorders, mania, bipolar disorder, paranoid and delusional disorders, Parkinson's disease, neuroleptic-induced parkinsonism, depression and depressive states, and autism, which comprises administering to a subject in need thereof an effective amount of a compound of formula (I)
wherein
Q represents C 1-4 alkyl, —NR 3 R 4 , phenyl, optionally substituted phenyl, 1-pyrrolidinyl, 1-piperidinyl, 4-R 5 -piperazin-1-yl or 4-morpholinyl group,
R 1 represents hydrogen or C 1-4 alkyl group,
R 2 represents hydrogen or C 1-4 alkyl group,
R 3 represents hydrogen, C 1-4 alkyl group, phenyl or optionally substituted phenyl,
R 4 represents hydrogen, C 1-4 alkyl group, phenyl or optionally substituted phenyl,
R 5 represents hydrogen or C 1-4 alkyl group,
and/or geometric isomers and/or stereoisomers and/or diastereomers and/or salts thereof.
2. The method according to claim 1 , wherein the condition is responds to modulation of a dopamine receptor, wherein the dopamine receptor is a dopamine D3 and/or D2 receptor.
3. The method according to claim 1 , wherein the drug abuse is alcohol abuse, cocaine abuse, nicotine abuse, or opioid abuse.
4. The method according to claim 1 , wherein the condition is selected from Parkinson's disease and neuroleptic induced parkinsonism.
5. The method according to claim 1 , wherein the psychoses are selected from the group consisting of schizophrenia and schizo-affective disorders.
6. The method according to claim 1 , wherein
Q represents C 1-4 alkyl, —NR 3 R 4 or 4-morpholinyl group;
R 1 represents hydrogen atom or C 1-4 alkyl group;
R 2 represents hydrogen atom or C 1-4 alkyl group;
R 3 represents hydrogen atom or C 1-4 alkyl group; and
R 4 represents hydrogen atom or C 1-4 alkyl group.
7. The method according to claim 1 , wherein the compound of Formula (I) is selected from the group consisting of:
trans-N-(4-{2-[4-(5,6-dichloro-2-methylamino-pyrimidin-4-yl)-piperazin-1-yl]-ethyl]-cyclohexyl}-acetamide,
trans-(4-{2-[4-(5,6-dichloro-2-methylamino-pyrimidin-4-yl)-piperazin-1-yl]-ethyl}-cyclohexyl)-urea,
trans-morpholine-4-carboxylic acid (4-{2-[4-(5,6-dichloro-2-ethylamino-pyrimidin-4-yl)-piperazin-1-yl]-ethyl}-cyclohexyl)-amide,
trans-(4-{2-[4-(5,6-dichloro-2-ethylamino-pyrimidin-4-yl)-piperazin-1-yl]-ethyl}-cyclohexyl)-urea,
trans-N-(4-{2-[4-(5,6-dichloro-2-dimethylamino-pyrimidin-4-yl)-piperazin-1-yl]-ethyl}-cyclohexyl)-acetamide,
trans-N-(4-{2-[4-(5,6-dichloro-2-ethylamino-pyrimidin-4-yl)-piperazin-1-yl]-ethyl}-cyclohexyl)-acetamide,
trans-morpholine-4-carboxylic acid (4-{2-[4-(5,6-dichloro-2-methylamino-pyrimidin-4-yl)-piperazin-1-yl]-ethyl}-cyclohexyl)-amide,
trans-3-(4-{2-[4-(5,6-dichloro-2-methylamino-pyrimidin-4-yl)-piperazin-1-yl]-ethyl}-cyclohexyl-1,1-dimethyl-urea,
trans-3-(4-{2-[4-(5,6-dichloro-2-ethyl-amino-pyrimidin-4-yl)-piperazin-1-yl]-ethyl}-cyclohexyl}-1,1-dimethyl-urea,
trans-1-(4-{2-[4-(5,6-dichloro-2-methylamino-pyrimidin-4-yl)-piperazin-1-yl]-ethyl}-cyclohexyl)-3-ethyl-urea,
trans-N-(4-{2-[4-(5,6-dichloro-2-methylamino-pyrimidin-4-yl)-piperazin-1-yl]-ethyl}-cyclohexyl-propionamide,
trans-N-(4-{2-[4-(2-amino-5,6-dichloro-pyrimidin-4-yl)-piperazin-1-yl]-ethyl}-cyclohexyl)-acetamide,
trans-1-(4-{2-[4-(5,6-dichloro-2-methylamino-pyrimidin-4-yl)-piperazin-1-yl]-ethyl}-cyclohexyl)-3-methyl-urea,
trans-N-(4-{2-[4-(5,6-dichloro-2-methylamino-pyrimidin-4-yl)-piperazin-1-yl]-ethyl}-cyclohexyl)-benzamide,
trans-3-bromo-N-(4-{2-[4-(5,6-dichloro-2-methylamino-pyrimidin-4-yl)-piperazin-1-yl]-ethyl}-cyclohexyl)-benzamide,
and/or geometric isomers and/or stereoisomers and/or diastereomers and/or salts thereof.