MX2007008044A - Aryl piperazine derivatives for the treatment of neuropsychiatric disorders - Google Patents

Abstract

This invention provides novel aryl piperazine derivatives having medical utility, in particular as modulators of dopamine and serotonin receptors, preferably the D3, D2-like and 5-HT2receptor subtypes, and in particular useful for the treatment of neuropsychiatric disorders incl. schizophrenia. Formula (I) an enantiomer thereof or a mixture of its enantiomers, or a pharmaceutically acceptable salt thereof, or an N-oxide thereof.

Description

NEW DERIVATIVES OF ARILPHIPERAZINE WITH MEDICAL UTILITY FIELD OF THE INVENTION This invention relates to new derivatives of arylpiperazine which have medical utility, in particular as modulators of the dopamine and serotonin receptors, preferably the subtypes of the receptor similar to D3, D2 and 5-HT2, and in particular useful for the treatment of neuropsychiatric disorders, including schizophrenia.

BACKGROUND OF THE INVENTION Dopamine is involved in several important functions, excitatory and inhibitory, through the dopaminergic receptors in the central and peripheral nervous system. The dopamine receptors were originally classified into two main groups: Di and D2. The five dopamine receptors currently cloned fall into these classes. In this way, receivers similar to Di include? and D5, while D2-like receptors include D2, D3 and D4. Dopamine receptors, and in particular D2-like receptors, are recognized as potential therapeutic targets for different neurological and psychiatric disorders, in particular psychotic disorders, including schizophrenia. Other indications REF. : 182358 Therapeutics associated with dopamine receptors include depression, Parkinson's disease, Huntington's disease, movement disorders, such as dystonia, anxiety, restless legs syndrome, obsessive compulsive disorders, mania, geriatric disorders, dementia, sexual dysfunction, symptoms of musculoskeletal pain, for example, pain associated with fibromyalgia, substance abuse (abuse and addiction to cocaine), withdrawal symptoms in drug addicts and sleep disorders. Finally, selective receptor ligands find use as diagnostic tools in diagnostic methods, and in particular for in vivo imaging (neuroimaging). Selective ligands of the dopamine receptor have been associated in, for example, WO 2004024878, and by i. to. Leopoldo et al. (J. Med. Chem. 2002 45 5727-5733), Campiani et al. (J. Med. Chem. 2003 46 3822-3839). and Hackling et al. (J. Med. Chem. 2003 46 3883-3899).

BRIEF DESCRIPTION OF THE INVENTION According to the present invention it has been found that some arylpiperazine derivatives show superior activity as modulators of the dopamine and serotonin receptors, preferably the receptor subtypes similar to D3, D2 and 5-HT2 / and , in this way, they are particularly useful as antipsychotic agents. Therefore, in its first aspect, the invention provides novel arylpiperazine derivatives represented by Formula I: an enantiomer thereof or a mixture of its enantiomers, or a pharmaceutically acceptable salt thereof or an N-oxide thereof, wherein, R1, R2 and R3, independently of each other, represent hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro, cyano and / or carboxy; - represents an optional double bond; if it represents a simple bond, then A represents CH or N; if - represents a double bond, then A represents C; --B-- may be absent or present; --B-- is absent; and Z represents CH or N; or --B-- is present and represents a methylene bridge (-CH2-), an ethylene bridge (-CH = CH-), or a -NH- bridge, linked as indicated in the figure; and Z represents C (carbon); W represents CH, N or CR4, wherein R4 represents hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro or cyano; m and n, independently of each other, is 0, 1 or 2; and X may be absent or present; X is present and represents 0, S, NR ', CO, S02, CH2, CH2-0, 0-CH2, CH2-S, S-CH2, CH2-NR', CH2-C0, CH2-S02, NR'- CO, CO-NR ', NR'-S02, S02-NR', CH2-CH2, 0-CO, CO-0, 0-CH = CH, S-CH = CH, NR'-CH = CH, CO- CH = CH, S02-CH = CH, CH2-0-CH = CH, CH2-S-CH = CH, CH2-NR '-CH = CH, CH2-C0-CH = CH, CONHCH2CH2 or CH2-S02-CH = CH, where R 'represents hydrogen or alkyl; and Y represents phenyl or a monocyclic or polycyclic aromatic heterocyclic group, such phenyl or heterocyclic group can be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo , haloalkyl, haloalkoxy, amino, nitro and cyano; or Y represents a hydrogenated heterocyclic group, such a hydrogenated heterocyclic group can be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino , nitro and cyano; or Y represents a group of formula III wherein R7 represents hydrogen, alkyl, alkoxy, haloalkyl; or X is absent; and Y represents a diazacyclic group of the formula where, or is 1, 2 or 3; D represents alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano; and E represents alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano; or D and E together with the diazacyclic group form a fused ring system, this fused ring system can be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano; or Y represents a group of formula IV: where A 'represents CH or N; and R8 represents hydrogen, alkyl, alkoxy, halo or haloalkyl. In another aspect, the invention relates to the use of the arylpiperazine derivative of the invention, or a pharmaceutically acceptable salt thereof, or a prodrug thereof for the manufacture of a pharmaceutical composition. The use of the arylpiperazine derivative of the invention, or a pharmaceutically acceptable salt thereof, or a prodrug thereof, for the manufacture of a pharmaceutical composition for the treatment, prevention or alleviation of a disease or disease is visualized in another aspect of the invention. a disorder or condition of a mammal, including a human, such a disease, disorder or condition is sensitive to the modulation of the dopamine and serotonin receptors. In a final aspect, the invention provides a method of diagnosis, treatment, prevention or alleviation of a disease or disorder or condition of a living animal body, including a human, such disorder, disease or condition is sensitive to the modulation of the dopamine and serotonin receptors, in particular the receptor subtypes similar to D3, D2 and 5-HT2, preferably the subtype of the dopamine D3 receptor and / or the D3 / 5-HTiA or D3 / 5-HT2A receptor subtypes , which method comprises the step of administering to such a living animal body in need thereof, a therapeutically effective amount of the arylpiperazine derivative of the invention, or a pharmaceutically acceptable salt thereof or a prodrug thereof. Other objects of the invention will be apparent to the person skilled in the art from the following detailed description and examples.

DETAILED DESCRIPTION OF THE INVENTION In accordance with the present invention, it has now been found that a particular group of arylpiperazine derivatives show a superior biological profile as modulators of the dopamine and serotonin receptors. Therefore, in its first aspect, the invention provides novel arylpiperazine derivatives represented by Formula I: an enantiomer thereof or a mixture of its enantiomers, or a pharmaceutically acceptable salt thereof or an N-oxide thereof, wherein: R1, R2 and R3, independently of each other, represent hydrogen, alkyl, cycloalkyl, cycloalkyl -alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro, cyano and / or carboxy; ~ represents an optional double bond; if ~ represents a simple bond, then A represents CH or N; if ^ represents a double bond, then A represents C; --B-- may be absent or present; --B-- is absent; and Z represents CH or N; or --B-- is present and represents a methylene bridge (-CH2-), an ethylene bridge (-CH = CH-), or a -NH- bridge, linked as indicated in the figure; and Z represents C (carbon); W represents CH, N or CR4, wherein R4 represents hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro or cyano; m and n, independently of each other, is 0, 1 or 2; and X may be absent or present; X is present and represents 0, S, NR ', CO, S02, CH2, CH2-0, 0-CH2, CH2-S, S-CH2, CH2-NR', CH2-CO, CH2-S02 / NR'- CO, CO-NR ', NR'-S02, S02-NR', CH2-CH2, 0-CO, CO-0, 0-CH = CH, S-CH = CH, NR'-CH = CH, C0- CH = CH, S02-CH = CH, CH2-0-CH = CH, CH2-S-CH = CH, CH2-NR '-CH = CH, CH2-C0-CH = CH, CONHCH2CH2 or CH2-S02-CH = CH, where R 'represents hydrogen or alkyl; and Y represents phenyl or a monocyclic or polycyclic aromatic heterocyclic group, such phenyl or heterocyclic group can be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo , haloalkyl, haloalkoxy, amino, nitro and cyano; or Y represents a hydrogenated heterocyclic group, such a hydrogenated heterocyclic group may be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino , nitro and cyano; or Y represents a group of the formula III wherein R7 represents hydrogen, alkyl, alkoxy, halo or haloalkyl; or X is absent; and Y represents a diazacyclic group of the formula II, where, or is 1, 2 or 3; D represents alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano; and E represents alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano; or D and E together with the diazacyclic group form a fused ring system, this fused ring system can be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano; or Y represents a group of formula IV: where A 'represents CH or N; and R8 represents hydrogen, alkyl, alkoxy, halo or haloalkyl. In a preferred embodiment the arylpiperazine derivative of the invention is a compound of Formula I, wherein: R1, R2 and R3, independently of each other, represent hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy , halo, haloalkyl, haloalkoxy, amino, nitro and / or cyano, carboxy; represents an optional double bond; if - represents a simple bond, then A represents CH or N; if ~ represents a double bond, then A represents C (carbon); --B-- may be absent or present; --B-- is absent; and Z represents CH or N; or --B-- is present and represents a methylene bridge (-CH2-), an ethylene bridge (-CH = CH-), or a -NH- bridge, linked as indicated in the figure; and Z represents C (carbon); W represents CH, N or CR4, wherein R4 represents hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro or cyano; m and n, independently of each other, is 0, 1 or 2; and X may be absent or present; X is present and represents 0, S, NR ', CO, S02, CH2, CH2-0, 0-CH2, CH2-S, S-CH2, CH2-NR ', CH2-C0, CH2-S02, NR'-CO, CO-NR', NR'-S02, S02-NR ', CH2 -CH2, 0-CO, CO-0, 0-CH = CH, S-CH = CH, NR'-CH = CH, C0-CH = CH, S02-CH = CH, CH2-0-CH = CH, CH2-S-CH = CH, CH2-NR '-CH = CH, CH2-C0-CH = CH, CONHCH2CH2 or CH2-S02-CH = CH, where R' represents hydrogen or alkyl; and Y represents phenyl or a monocyclic or polycyclic aromatic heterocyclic group, such phenyl or heterocyclic group can be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo , haloalkyl, haloalkoxy, amino, nitro and cyano; or Y represents a hydrogenated heterocyclic group, such a hydrogenated heterocyclic group may be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino , nitro and cyano; or X is absent; and Y represents a diazacyclic group of the formula II, where, or is 1, 2 or 3; D represents alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano; and E represents alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano; or D and E together with the diazacyclic group form a fused ring system, this fused ring system can be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano. In another preferred embodiment the arylpiperazine derivative of the invention is a compound of Formula I, wherein - represents a single bond, and A represents CH or N. In a most preferred embodiment - represents a single bond, and A represents N.

In a more preferred embodiment it represents a double bond, and A represents C (carbon). In a third preferred modality, the arylpiperazine derivative of the invention is a compound of Formula I, wherein W represents CH, or CR4, wherein R4 represents hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl , haloalkoxy, amino, nitro or cyano. In a preferred embodiment W represents CR 4, wherein R 4 represents hydrogen, alkyl, in particular methyl, alkoxy, in particular methoxy or halo, in particular chlorine. In an even more preferred embodiment, W represents CR 4, wherein R 4 represents hydrogen, methyl, ethyl, methoxy, fluorine or chlorine. In a more preferred embodiment, W represents CH or N. In a fourth preferred embodiment, the arylpiperazine derivative of the invention is a compound of Formula I, wherein -B-- is absent and Z represents CH or N. In a more preferred embodiment, --B-- is present and represents a methylene bridge (-CH2-), an ethylene bridge (_-CH = CH-) or a bridge -NH-, linked as indicated in the figure; and Z represents C (carbon). In an even more preferred embodiment, -B-- is present and represents a methylene bridge (-CH2-), and Z represents C (carbon); and W represents CR 4, wherein R 4 represents hydrogen, alkyl, in particular methyl, alkoxy, in particular methoxy, halo, in particular chlorine, haloalkyl, haloalkoxy, amino, nitro or cyano. In a fourth preferred embodiment, the arylpiperazine derivative of the invention is a compound of Formula I, wherein W represents CR 4, wherein R 4 represents hydrogen, alkyl, in particular methyl, alkoxy, in particular methoxy, halo, in particular chlorine . In a more preferred embodiment W represents CR4, wherein R4 represents hydrogen, methyl, ethyl, methoxy, fluorine or chlorine. In an even more preferred embodiment, W represents CR 4, wherein R 4 represents hydrogen, alkyl or alkoxy [methoxy]. In a fifth preferred embodiment, the arylpiperazine derivative of the invention is a compound of Formula I, wherein m and n, independently of each other, is 0, 1 or 2. In a preferred embodiment m is 1 or 2; and n is 0 or 2. In an even more preferred embodiment, m is 1; and n is 0. In another preferred embodiment, m is 1; and n is 1. In a third preferred embodiment, m is 1; and n is 2. In an even more preferred mode, m is 2; and n is 0. In a sixth preferred embodiment, the arylpiperazine derivative of the invention is a compound of Formula I, wherein R 1, R 2 and R 3, independently of one another, represent hydrogen, alkyl, in particular methyl, ethyl or propyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, in particular methoxy or ethoxy, cycloalkoxy, halo, in particular fluorine, chlorine or bromine, haloalkyl, in particular trifluoromethyl, haloalkoxy, amino, nitro, cyano and / or carboxy; In a more preferred embodiment R1, R2 and R3 represent hydrogen. In an even more preferred embodiment R 1 represents alkyl, in particular methyl, ethyl or propyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, in particular methoxy or ethoxy, cycloalkoxy, halo, in particular fluorine, chlorine or bromine, haloalkyl, in particular trifluoromethyl, haloalkoxy, amino, nitro, cyano or carboxy; and R2 and R3 represent hydrogen. In an even more preferred embodiment R 1 represents alkyl, in particular methyl, ethyl or propyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, in particular methoxy or ethoxy, cycloalkoxy, halo, in particular fluorine, chlorine or bromine, haloalkyl, in particular trifluoromethyl, haloalkoxy, amino, nitro or cyano; and R2 and R3 represent hydrogen. In an even more preferred embodiment R 1 represents alkyl, in particular methyl, ethyl or propyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, in particular methoxy or ethoxy, cycloalkoxy, halo, in particular fluorine, chlorine or bromine, haloalkyl, in particular trifluoromethyl, haloalkoxy, amino, nitro or cyano. In a further preferred embodiment R1 represents alkyl, in particular methyl, ethyl or propyl, alkoxy, in particular methoxy or ethoxy, halo, in particular fluorine, chlorine or bromine, haloalkyl, in particular trifluoromethyl, haloalkoxy, amino, nitro or cyano. In a further preferred embodiment, R1 represents methyl, ethyl, methoxy, chloro, trifluoromethyl, trifluoromethoxy or cyano. In a further preferred embodiment, R1 represents methyl, ethyl, methoxy, chloro, trifluoromethyl, trifluoromethoxy, cyano or carboxy. In a preferred embodiment, R 2 represents alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, in particular chloro, haloalkyl, haloalkoxy, amino, nitro or cyano; and R1 and R3 represent hydrogen. In a more preferred embodiment R2 represents alkyl, cycloalkyl, alkoxy, halo, trifluoromethyl, trifluoromethoxy, amino, nitro or cyano. In an even more preferred embodiment R2 represents methyl, ethyl, methoxy, chloro, trifluoromethyl, trifluoromethoxy or cyano. In a seventh preferred embodiment, the arylpiperazine derivative of the invention is a compound of Formula I, wherein X is present and represents 0, S, NR ', C0, S02, CH2 / CH2-0, 0-CH2, CH2-S, S-CH2, CH2-NR', CH2-C0, CH2-S02 / NR'-CO, CO-NR ' , CH2-CH2 0-CO, CO-0, CH-CH = CH, S-CH = CH, NR'-CH = CH, C0-CH = CH, S02-CH = CH, CH2-0-CH = CH , CH2-S-CH = CH, CH2-NR '-CH = CH, CH2-C0-CH = CH, CONHCH2CH2 or CH2-S02-CH = CH, where R' represents hydrogen or alkyl. In a more preferred embodiment, X represents 0, CH2-0, 0-CH2, CH2-S, S-CH2, CH2-NR ', CH2-C0, CH2-S02, NR'-CO, CO-NR', NR '-S02, S02-NR', 0-CO or CH2-0-CH = CH, where R 'represents hydrogen or alkyl. In an even more preferred embodiment, X represents O, CH2-0, 0-CH2, CH2-S, S-CH2, CH2-NR ', CH2-C0, CH2-S02, NR'-CO, CO-NR', 0-CO or CH2-0-CH = CH; wherein R 'represents hydrogen or alkyl. In an even more preferred embodiment, X represents O, CH2-0, NR'-CO, CO-NR ', NR'-S02 or 0-C0; wherein R 'represents hydrogen or alkyl. In an even more preferred embodiment, X represents 0, CH2-0, NR'-CO, CO-NR 'or 0-CO; wherein R 'represents hydrogen or alkyl. In an even more preferred embodiment, X represents 0, CH2-0, NH-C0, C0-NH or 0-CO. In an eighth preferred embodiment, the arylpiperazine derivative of the invention is a compound of Formula I, wherein Y represents phenyl or a monocyclic or polycyclic aromatic heterocyclic group, in particular pyridyl, benzo [b] furanyl, indolyl, quinolinyl or isoquinolinyl , this phenyl or heterocyclic group can be optionally substituted one or more times with substituents selected from the group consisting of alkyl, in particular methyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, in particular chlorine, haloalkyl, haloalkoxy , amino, nitro and cyano; or Y represents a hydrogenated heterocyclic group, in particular tetrahydroquinolinyl, this hydrogenated heterocyclic group can be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl , haloalkoxy, amino, nitro and cyano. In a more preferred embodiment, Y represents phenyl, such phenyl group can be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, in particular chloro, haloalkyl, haloalkoxy, amino, nitro and cyano. In an even more preferred embodiment, Y represents phenyl, optionally substituted one or more times with alkyl, alkoxy, chloro, trifluoromethyl and / or trifluoromethoxy. In an even more preferred embodiment Y represents phenyl.

In a ninth preferred embodiment, the arylpiperazine derivative of the invention is a compound of Formula I, wherein Y represents an aromatic monocyclic heterocyclic group selected from furanyl, thienyl, pyrrolyl, oxazolyl, imidazolyl, pyridyl, pyridazinyl and pyrimidinyl, such group Amino monocyclic aromatic heterocyclic may be optionally substituted one or more times with substituents selected from the group consisting of alkyl, in particular methyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano. In a more preferred embodiment, Y represents furanyl, thienyl or pyridyl, this monocyclic aromatic heterocyclic group can be optionally substituted once or twice with substituents selected from the group consisting of alkyl, in particular methyl, alkoxy, chloro, trifluoromethyl and trifluoromethoxy. In a more preferred embodiment, Y represents pyridyl, optionally substituted by methyl, ethyl, methoxy, chloro or trifluoromethyl. In a tenth preferred embodiment, the arylpiperazine derivative of the invention is a compound of Formula I, wherein Y represents an aromatic bicyclic heterocyclic group selected from indolyl, isoindolyl, benzo [b] furanyl, benzo [b] thienyl, benzimidazolyl, benzthiazolyl, quinolinyl and isoquinolinyl, such aromatic bicyclic heterocyclic group can be optionally substituted once or twice with substituents selected from the group consisting of alkyl, in particular methyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, in particular chlorine, haloalkyl, haloalkoxy, amino, nitro and cyano. In a more preferred embodiment, Y represents indolyl, in particular indol-2-yl or indol-3-yl; benzo [b] furanyl, in particular, benzo [b] furan-2-yl or benzo [b] furan-3-yl; benzo [b] thienyl, in particular benzo [b] thien-2-yl or benzo [b] thien-3-yl; quinolinyl, in particular quinolin-2-yl, quinolin-3-yl or quinolin-4-yl; or isoquinolinyl, in particular isoquinolin-1-yl, isoquinolin-3-yl or isoquinolin-4-yl; such an aromatic bicyclic heterocyclic group can be optionally substituted once or twice with substituents selected from alkyl, in particular methyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, in particular chloro, haloalkyl, haloalkoxy, amino, nitro and cyano. In an even more preferred embodiment, Y represents indolyl, in particular indol-2-yl or indol-3-yl; benzo [b] furanyl, in particular benzo [b] furan-2-yl or benzo [b] furan-3-yl; quinolinyl, in particular quinolin-2-yl, quinolin-3-yl or quinolin-4-yl; or isoquinolinyl, in particular isoquinolin-1-yl, isoquinolin-3-yl or isoquinolin-4-yl; wherein the benzo [b] furanyl or isoquinolinyl can be optionally substituted once or twice with substituents selected from alkyl, in particular methyl, hydroxy, alkoxy, chloro, trifluoromethyl, trifluoromethoxy, amino, nitro and cyano. In an even more preferred embodiment, Y represents indol-2-yl, benzo [b] furan-2-yl or isoquinolin-3-yl; wherein the benzo [b] furanyl or isoquinolinyl can be optionally substituted once or twice with substituents selected from alkyl, in particular methyl, hydroxy, alkoxy, chloro, trifluoromethyl, amino, nitro and cyano. In an even more preferred embodiment, Y represents indol-2-yl, benzo [b] furan-2-yl or isoquinolin-3-yl; wherein the benzo [b] furanyl or isoquinolinyl can be optionally substituted with alkyl, in particular methyl, halo, in particular chloro or trifluoromethyl. In a further preferred embodiment, Y represents indol-2-yl, benzo [b] furan-2-yl or isoquinolin-3-yl; wherein the benzo [b] furanyl or isoquinolinyl can be optionally substituted with methyl, ethyl, fluorine, chlorine or trifluoromethyl. In a more preferred embodiment, Y represents indolyl, benzo [b] furanyl or isoquinolinyl. In an eleventh preferred embodiment, the arylpiperazine derivative of the invention is a compound of Formula I, wherein Y represents a hydrogenated heterocyclic group, in particular tetrahydroquinolinyl, such a hydrogenated heterocyclic group can be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo , haloalkyl, haloalkoxy, amino, nitro and cyano. In a more preferred embodiment Y represents tetrahydroquinolinyl or tetrahydroisoquinolinyl, such heterocyclic group can be optionally substituted once or twice with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy , amino, nitro and cyano. In a more preferred embodiment, Y represents tetrahydroquinolinyl or tetrahydroisoquinolinyl. In another preferred embodiment, X represents 0, CH2-0, NH-CO, CO-NH, NR'-S02 or CO-0; and Y represents phenyl, methyl-phenyl, pyridyl, indolyl, methyl-indolyl, benzo [b] furanyl, tetrahydroquinolinyl, isoquinolinyl or tetrahydroisoquinolinyl. In a more preferred embodiment, X represents CH2-0, NH-CO, CO-NH or CO-O; and Y represents indolyl, benzo [b] furanyl, tetrahydroquinolinyl, isoquinolinyl or tetrahydroisoquinolinyl. In an even more preferred embodiment, X represents 0, CH2-0, NH-CO, CO-NH, NR'-S02 or CO-0; Y represents phenyl, methyl-phenyl, pyridyl, methyl-pyridyl, indolyl, methyl-indolyl, benzo [b] furanyl, tetrahydroquinolinyl, isoquinolinyl or tetrahydroisoquinolinyl; R 'represents alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro or cyano; and R2 and R3 represent hydrogen. In an even more preferred embodiment, X represents CH2-0, NH-CO, CO-NH or CO-0; Y represents indolyl, benzo [b] furanyl, tetrahydroquinolinyl, isoquinolinyl or tetrahydroisoquinolinyl; R 'represents alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro or cyano; and R2 and R3 represent hydrogen. In a more preferred embodiment, the aryl derivative of the invention is: N- [4- [4- (3-Trifluoromethylphenyl) piperazin-1-yl] butyl] indole-2-carboxamide; N- [2- (1H-indol-3-yl) ethyl] -3- (4-m-tolyl-piperazin-1-yl) propanamide; N- [2- (1H-indol-3-yl) ethyl] -3- [4- (3-methoxyphenyl) piperazin-1-y1] propanamide; . { 4- [4- (3-methoxy-phenyl) -piperazin-1-yl] -butyl} benzo [b] furan-2-carboxylic acid amide; N- [4- [4- (3-Cyanophenyl) piperazin-l-yl] butyl] benzo [b] furan-2-carboxamide; . { 4- [4- (3-chloro-pheny1) -piperazin-1-yl] -butyl} -amide; of benzo [b] furan-2-carboxylic acid; . { 4- [4- (3-carboxy-phenyl) -piperazin-1-yl] -butyl} benzo [b] furan-2-carboxylic acid amide; N- [4- [4- (m-Tolyl) piperazin-1-yl] butyl] benzo [b] furan-2-carboxamide; . { 4- [4- (3-cyano-phenyl) -piperazin-1-yl] -butyl} isoquinoline-3-carboxylic acid amide; N- [4- [4- (3-Chlorophenyl) piperazin-1-yl] butyl] isoquinoline-3-carboxamide; N- [4- [4- (m-Tolyl) piperazin-1-yl] butyl] isoquinoline-3-carboxamide; N- [4- [4- (3-Methoxyphenyl) piperazin-1-yl] butyl] isoquinoline-3-carboxamide; 3- [5- [4- (3-Chlorophenyl) piperazin-1-yl] pentyloxy] isoquinoline; 3-. { 5- [4- (3-Methoxy-phenyl) -piperazin-1-yl] -pentyloxy} -isoquinoline; 3- [5- (4-m-Tolylpiperazin-1-yl) pentyloxy] isoquinoline; 3- . { 5- [4- (3-Cyano-phenyl) -piperazin-1-yl] -pentyloxy} -isoquinoline; N- [4- (1,2,3,4-Tetrahydro-5-methoxy-p-carbolin-2-yl) butyl] isoquinoline-3-carboxamide; N- [4- (3,4-Dihydro-6-methoxypyrazino [1,2-a] indol-2 (1 H) -yl) butyl] isoquinoline-3-carboxamide; N- [4- [4- (Pyridin-2-yl) piperazin-1-yl] butyl] isoquinoline-3-carboxamide; 1,2,3,4-Tetrahydro-quinoline-2-carboxylic acid [4- (4-phenyl-piperazin-1-yl) -butyl] -amide; (S) - (-) - N- [4- [4- (m-Tolyl) piperazin-1-yl] butyl] -1,2,4,4-tetrahydroisoquinoline-2-carboxamide; (R) - (+) - N - [4- [4- (m-Tolyl.} Piperazin-1-yl] butyl] -1,2,4,4-tetrahydroisoquinoline-2-carboxamide; [1- (2, 4-dichloro-phenyl) -piperazin-1-yl] -butyl} -amide of lH-indole-2-carboxylic acid; {. 4- [4- (2, 4- 5-Chloro-1H-indole-2-carboxylic acid dichloro-phenyl) -piperazin-1-yl] -butyl} -amide;. {4- [4- (2, 3-dichloro-phenyl) - piperazin-1-yl] -butyl} -amide of isoquinoline-3-carboxylic acid; 3- {4- [4- (2, 3-dichloro-phenyl} -piperazin-1-yl] - butoxy.}. -isoquinoline; 3- {5- [4- (2,3-dichloro-phenyl) -piperazin-1-yl} -pentyloxy} -isoquinoline; 1H-indole-2-carboxylate; - [4- (2,3-dichlorophenyl) piperazin-1-yl] butyl; N- (4- (4- (phenylpiperazin-1-yl) butyl-benzo [b] furan-2-carboxamide; . { Benzo [b] furan-2-carboxylic acid 4- [2, 3-dimethyl-phenyl] -piperazin-1-yl] -butyl} -amide; N- (4- (4- (3-methoxyphenyl) piperazin-1-yl) butyl) benzo [b] furan-2-carboxamide; N- (4- (4- (6-methylpyridin-2-yl) piperazin-1-yl) butyl) isoquinoline- 3-carboxamide; N- (4- (4-phenylpiperazin-1-yl) butyl) isoquinoline-3-carboxamide; N- (4- (4- (6-methylpyridin-2-yl) piperazin-1-yl) butyl benzo [b] furan-2-carboxamide; N- (4- (4-phenylpiperazin-1-yl) butyl) quinoline-2-ca boxamide; N- (4- (4-m-tolyl-piperazin-1-yl) butyl) quinoline-2-carboxamide; N- (4- (4- (3-methoxyphenyl) piperazin-1-yl) butyl) -1-methyl-lH-indo-1-carboxamide; N- (4- (4- ( 3-methoxyphenyl) piperazin-1-yl) butyl) -lH-indole-3-carboxamide; (S) -1, 2, 3, 4-tetrahydro-N- (4- (4-phenylpiperazin-1-yl) butyl) quinoline-2-carboxamide; N- (4- (4-m-tolylpiperazin-1-yl) butyl) picolinamide; N- (4- (4- (quinolin-3-pi) piperazin-1-yl) butyl) isoquinoline 3-carboxamide; N- (4- (4- (3-methoxyphenyl) piperazine-1- il) butyl) -6-methylpyridin-2-carboxamide; N- (4- (4- (3-inetoxyphenyl) piperazin-1-yl) butyl) quinoline-3-carboxamide; N- (4- (4- (pierain-2-yl) piperazin-1-yl) butyl) o ^ iinoline-3-carboxamide; N- (4- (4-phenylpiperazin-1-yl) butyl) picolinarnide; N- (4- (4- (3-iretoxyphenyl) piperazin-1-yl) butyl) picolinate; N- (4- (4- (3-methoxyphenyl) piperazin-1-yl) butyl) benzamide; N- (4- (4-m-tolyl-piperazin-1-yl) butyl) -benzamide; N- (4- (4-phenylpiperazin-1-yl) butyl) nicotinamide; N- (4- (4- (6-methylpyridin-2-yl) piperazin-1-yl) butyl) benzamide; N- (4- (4- (6-methoxypyridin-2-yl) piperazin-1-yl) butyl) benzamide; N- (4- (4- (6-methoxypyridin-2-yl) piperazin-1-yl) butyl) picolinamide; or N- (4- (4- (6-methylpyridin-2-yl) piperazin-1-yl) butyl) picolinamide; or a pharmaceutically acceptable salt thereof. In a twelfth preferred embodiment, the arylpiperazine derivative of the invention is a compound of Formula I, wherein Y represents a group of formula III: where : R represents hydrogen, alkyl, alkoxy, halo or haloalkyl. In a more preferred embodiment, the arylpiperazine derivative of the invention is: 7- [4- [4- (2,3-dichloro-phenyl) -piperazin-1-yl] -butoxy] -pyrrolo [1, 2-a] ] quinoxalin-4 (5H) -one; 7- (5- (4-phenylpiperazin-1-yl) pentyloxy) pyrrolo [1, 2- a] quinoxalin-4 (5H) -one; or 7- (4- (4-phenylpiperazin-1-yl) butoxy) pyrrolo [1, 2-a] uinoxalin- (5H) -one; or a pharmaceutically acceptable salt thereof. In a thirteenth embodiment, the arylpiperazine derivative of the invention is a compound of Formula I, wherein X is absent; and Y represents a diazacyclic group of Formula II, where, or is 1, 2 or 3; D represents alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano; and E represents alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, halcalkoxy, amino, nitro and cyano; or D and E together with the diazacyclic group form a fused ring system, this fused ring system can optionally be substituted one or more with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo , haloalkyl, haloalkoxy, amino, nitro and cyano. In a more preferred embodiment Y represents a bicyclic heterocyclic group (i.e., a fused ring system) selected from the following group: wherein R5 and R6, independently of each other, represent hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and / or cyano. In an even more preferred embodiment Y represents a bicyclic heterocyclic group selected from: wherein R5 and R6, independently of each other, represent hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and / or cyano. In an even more preferred embodiment, Y represents: wherein R 5 represents hydrogen, alkyl, halo, trifluoromethyl or trifluoromethoxy. In an even more preferred embodiment, the arylpiperazine derivative of the invention is: 2-. { 4- [4- (3-cyano-phenyl) -piperazin-1-yl] -butyl} -3,4-dihydro-2H-pyrazino f 1, 2-a] indol-1-one; 2- [4- [4- (3-chlorophenyl) piperazin-1-yl] -butyl] -3,4-dihydropyrazino [1,2-a] indole-1 (2H) -one; 2-. { 4- [4- (3-methoxy-phenyl) -piperazin-1-yl] -butyl} -3,4-dihydro-2H-pyrazino [1,2-a] indol-1-one; 2- [4- (4-M-tolyl) piperazin-1-yl] -butyl] -3,4-dihydropyrazino [1,2-a] indole-1 (2H) -one; 3,4-dihydro-2- [4- (3,4-dihydro-6-methoxypyrazino [1,2-a] indol-2 (1H) -yl) butyl] pyrazino [1,2-a] indole-1 (2H) -one; 2-. { 4- [4- (2-methoxy-phenyl) -piperazin-1-yl] -butyl} -3,4-dihydro-2H-pyrazino [1,2-a] indol-1-one; or 2-. { 4- [4- (2,3-dichloro-phenyl) -piperazin-1-yl] -butyl} -3,4-dihydro-2H-pyrazino [1,2-a] indol-1-one; or a pharmaceutically acceptable salt thereof. In a fourteen preferred embodiment, the arylpiperazine derivative of the invention is a compound of Formula I, wherein X is absent; and Y represents a group of Formula IV: where A 'represents CH or N; and R represents hydrogen, alkyl, in particular methyl, alkoxy, in particular methoxy, halo, in particular chlorine or haloalkyl.

In a more preferred embodiment, the arylpiperazine derivative of the invention is: 1,6-bis (4- (3-chlorophenyl) piperazin-1-yl) hexane; 1, 6-bis (4- (3-methoxyphenyl) piperazin-1-yl) hexane; 1,6-bis (4-phenylpiperazin-1-yl) hexane; 1- (3-chlorophenyl) -4- (6- (4- (3-methoxyphenyl) piperazin-1-y1) hexy1) iperazine; 1-phenyl-4- (6- (4- (pyridin-2-yl) piperazin-1-yl) hexyl) piperazine; 1- (6-methylpyridin-2-yl) -4- (6- (4-m-tolyl-piperazin-1-yl) hexyl) -perazine; 1- (6-methylpyridin-2-yl) -4- (6- (4-phenylpiperazin-1-yl) hexyl) piperazine; l-Phenyl-4- (6- (4-m-tolyl-piperazin-1-yl) hexyl) piperazine 4- (4- (6- (4-phenylpiperazin-1-yl) hexyl) piperazin-1-yl) quinoline; 1, 6-Bis (4- (pyridin-2-yl) iperazin-1-yl) hexane; 4- (4- (6- (4-m-tolyl-piperazin-1-yl) hexyl) piperazin-1-yl) quinoline; 1,6-bis (4-m-tolylpiperazin-1-yl) hexane; 1- (pyridin-2-yl) -4- (6- (4-m-tolyl-piperazin-1-yl) hexyl) piperazine; or 1- (3-methoxyphenyl) -4- (6- (4-m-tolyl-piperazin-1-yl) hexyl) piperazine; or a pharmaceutically acceptable salt thereof.

Any combination of two or more of the embodiments described herein is considered within the scope of the present invention.

DEFINITION OF SUBSTITUENTS In the context of this invention, halo represents fluorine, chlorine, bromine or iodine. In the context of this invention an alkyl group designates a saturated, linear or branched univalent hydrocarbon chain. The hydrocarbon chain preferably contains from one to eighteen carbon atoms (Ci-18 alkyl), more preferably from one to six carbon atoms (Ci_6 lower alkyl), which includes pentyl, isopentyl, neopentyl, tertiary pentyl, hexyl and isohexyl. In a preferred embodiment, alkyl represents a Ci_4 alkyl group, which includes butyl, isobutyl, secondary butyl and tertiary butyl. In another preferred embodiment of this invention, alkyl represents a Ci_3 alkyl group, which may be in particular methyl, ethyl or isopropyl. In the context of this invention a haloalkyl group designates an alkyl group as defined herein, such alkyl group is replaced one or more times with halo. Preferred haloalkyl groups of the invention include trihalomethyl, preferably -CF3. In the context of this invention, an alkoxy group designates an "alkyl-O-" group, wherein alkyl is as defined above. Examples of the preferred alkoxy groups of the invention include methoxy and ethoxy. In the context of this invention a haloalkoxy group designates an alkoxy group as defined herein, such an alkoxy group is substituted one or more times with halo. Preferred haloalkoxy groups of the invention include trihalomethoxy, preferably -OCF3. In the context of this invention, a cycloalkyl group designates a cyclic alkyl group, preferably containing from three to seven carbon atoms (C3-7 cycloalkyl), which includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. In the context of this invention, a cycloalkyl-alkyl group designates a cycloalkyl group as defined above, such a cycloalkyl group is substituted in an alkyl group also as defined above. Examples of the preferred cycloalkyl-alkyl groups of the invention include cyclopropylmethyl and cyclopropylethyl. In the context of this invention, a cycloalkoxy group designates a "cycloalkyl-O-" group, wherein cycloalkyl is as defined above. Examples of the preferred cycloalkoxy groups of the invention include cyclopropylmethoxy and cyclopropylethoxy. In the context of this invention, a monocyclic or polycyclic aromatic heterocyclic group is a mono- or polycyclic compound, which maintains one or more heteroatoms in its ring structure. The term "poly-heterocyclic groups" includes benzo-fused five- and six-membered heterocyclic rings containing one or more heteroatoms. Preferred heteroatoms include nitrogen (N), oxygen (0) and sulfur (S).

PHARMACEUTICALLY ACCEPTABLE SALTS The arylpiperazine derivatives of the invention can be provided in any form suitable for the intended administration. Appropriate forms include the pharmaceutically acceptable salts (i.e., physiologically) and the pre- and prodrug forms of the arylpiperazine derivatives of the invention. Examples of pharmaceutically acceptable salts include, without limitation, salts of non-toxic inorganic and organic acids, such as hydrochloride, hydrobromide, nitrate, perchlorate, phosphate, sulfate, formate, acetate, aconate, ascorbate, benzenesulfonate, benzoate, cinnamate, citrate, embonate, enanthate, fumarate, glutamate, glycolate, lactate, maleate, malonate, mandelate, methanesulfonate, naphthalene-2-sulfonate derivative, phthalate, salicylate, sorbate, stearate, succinate, tartrate, toluene-p-sulfonate and the like. These salts can be formed by methods well known and described in the art.

STERIUM ISOMERS Some of the arylpiperazine derivatives of the present invention may exist in the (+) and (-) forms, as well as in the racemic forms (±). The racemates of these isomers and the individual isomers thereof are within the scope of the present invention. The racemic forms can be resolved in the optical antipodes by known methods and techniques. One way to separate the diastereomeric salts is by the use of an optically active acid, and by releasing the optically active amine compound by treatment with a base. Another method to solve the racemates in the optical antipodes is based on chromatography in an optical active matrix. A synthetic stereoselective method can be followed. In this manner, the racemic compounds of the present invention can be resolved in their optical antipodes, for example, by fractional crystallization of the D- or L- salts (tartrates, mandelates or camphorsulfonates). The initiator materials and / or the intermediate compounds used to produce the chemical compounds of the present invention can also be resolved by the formation of the diastereomeric amides by the reaction of the arylpiperazine derivative of the present invention with an optically active carboxylic acid, such as derivative of (+) or (-) phenylalanine, (+) or (-) phenylglycine, (+) or (-) canfánico acid or by the formation of diastereomeric carbamates by the reaction of the initiator material or intermediate compound for the use according to with the present invention with an optically active chloroformate or the like. Additional methods for resolution of optical isomers are known in the art. These methods include those described by Jaques J, Collet A, &; Wilen S in "Enantiomers, Racemates, and Resolutions", John Wiley and Sons, New York (1981). The active optical compounds can also be prepared from the active optical initiator materials.

Methods of preparation The arylpiperazine derivatives of the invention can be prepared by conventional methods for chemical synthesis, for example, those described in the working examples. In general, the amides can be prepared by the transformation of the acids or acid chlorides into the corresponding hydroxyamides by a standard procedure. The esters can be obtained by reacting the acid starter materials with 1,4-dihydroxybutane.

After replacement of the terminal hydroxy group with bromine, hydroxylamides, it can be treated with the arylpiperazine in the presence of a base to give the desired terminal product. Compounds based on an ether ether can be synthesized starting with the appropriate phenol, which is then condensed with 1,4-dihydroxybutane or 1,5-dihydroxypentane, followed by transformation into the final products as described above. The intermediates of the invention can be resolved by the formation of diastereomeric amides by reaction with an activated, optically active carboxylic acid such as the derivative of (+) or (-) phenylalanine, (+) or (-) phenylglycine, (+) or (-) canphanic acid or by the formation of diastereomeric carbamates by the reaction of the intermediate compound with an optically active chloroformate or the like.

Biological activity The arylpiperazine derivatives of the invention were found to possess selectivity for the dopamine and serotonin receptors, in particular the receptor subtypes similar to D3, D2 and 5-HT2. Therefore, in a preferred embodiment, the invention relates to the use of the arylpiperazine derivatives of the invention for the treatment, prevention or alleviation of a disease or disorder or condition of a mammal, including a human, wherein the disease, disorder or condition is sensitive to the modulation of the dopamine and serotonin receptors, in particular the receptor subtypes similar to D3, D2 and 5-HT2, preferably the subtype of the dopamine D3 receptor and / or the subtypes of the D3 / 5-HTiA or D3 / 5-HT2A receptor. In a more preferred embodiment, the disease, disorder or condition is a neurological or psychiatric disorder, in particular psychotic disorders, including schizophrenia, depression, Parkinson's disease, Huntington's disease, movement disorders, in particular dystonia, anxiety, leg syndrome. restless, obsessive-compulsive disorders, mania, geriatric disorders, dementia, sexual dysfunction, musculoskeletal pain symptoms, in particular, pain associated with fibromyalgia, sleep disorders, substance abuse or addiction and withdrawal symptoms in drug addicts, abuse or addition of cocaine. In an even more preferred embodiment, the disease, disorder or condition is a neurological or psychiatric disorder, in particular a psychotic disorder, preferably schizophrenia. In another preferred embodiment, the disease, disorder or condition contemplated according to the invention is schizophrenia or Parkinson's disease. In yet another preferred embodiment, the arylpiperazine derivatives of the invention are used as diagnostic tools in diagnostic methods, and in particular for in vivo receptor imaging (neuroimaging).

Pharmaceutical compositions In another aspect, the invention provides novel pharmaceutical compositions comprising a therapeutically effective amount of the arylpiperazine derivative of the invention While an arylpiperazine derivative of the invention for use in therapy can be administered in the form of the crude chemical compound, it prefers to introduce the active ingredient, optionally in the form of a physiologically acceptable salt, into a pharmaceutical composition together with one or more customary adjuvants, excipients, vehicles, buffers, diluents and / or other pharmaceutical auxiliaries. In a preferred embodiment, the invention provides pharmaceutical compositions comprising the arylpiperazine derivative of the invention, or a pharmaceutically acceptable salt or derivative thereof, together with one or more pharmaceutically acceptable carriers, and, optionally, other therapeutic and / or prophylactic ingredients, known and used in the art. The vehicle or vehicles must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not damaging the recipient thereof. The pharmaceutical composition of the invention can be administered by any convenient route, which is convenient for the desired therapy. Preferred routes of administration include oral administration, in particular in tablets, in capsules, in dragees, in powders, or in liquid form, and parenteral administration, in particular cutaneous, subcutaneous, intramuscular or intravenous injection. The pharmaceutical composition of the invention can be prepared by any person skilled in the art, by the use of standard methods and conventional techniques, appropriate for the desired formulation. When desired, compositions adapted to give a prolonged release of the active ingredient may be employed. Additional details regarding the techniques for formulation and administration can be found in the most recent edition of Remington's Pharmaceutical Sciences (Maack Publishing Co., Easton, PA). The actual dosage depends on the nature and severity of the disease being treated, and is within the discretion of the physician and can be varied by titration of the dosage to the particular circumstances of this invention to produce the desired therapeutic effect. However, it is now contemplated that pharmaceutical compositions containing from about 0.1 to about 500 mg of the active ingredient per individual dose, preferably from about 1 to about 100 mg, more preferably from about 1 to about 10 mg, are suitable for therapeutic treatments. The active ingredient can be administered in one or several doses per day. A satisfactory result, in some circumstances, can be obtained at a dosage as low as 0.1 pg / kg i.v. and 1 pg / kg p.o. The upper limit of the dosage range is currently considered to be approximately 10 mg / kg i.v. and 100 mg / kg p.o. Preferred ranges are from about 0.1 pg / kg to about 10 mg / kg / day i.v. and from about 1 pg / kg to about 100 mg / kg / day p.o.

Methods of therapy In another aspect, the invention provides a method for diagnosis, treatment, prevention or alleviation of a disease or disorder or condition of a living animal body, including a human, such a disease, disorder or condition is sensitive to the modulation of the dopamine and serotonin receptors, and the method comprises administering to such a living animal body, including a human, in need thereof, an effective amount of an arylpiperazine derivative of the invention. In the context of this invention, the term "treatment" covers treatment, prevention, prophylaxis or relief and the term "disease" covers discomforts, diseases, disorders and conditions related to the disease in question. The preferred indications contemplated according to the invention are those set forth above. It is contemplated herein that an appropriate dosage of the active pharmaceutical ingredient (API) is within the range of about 0.1 to about 1000 mg API per day, more preferably about 10 to about 500 mg API per day, more preferred from about 30 to about 100 mg API per day, depending, however, on the exact mode of administration, the manner in which it is administered, the indication considered, the patient and, in particular, the body weight of the patient involved, and also the preference and experience of the doctor or veterinarian in charge.

EXAMPLES The invention is further illustrated with reference to the following examples, which are not intended to limit in any way the scope of the invention as claimed.

Example 1 Preparation example This example describes the synthesis of the compounds presented in Table 1. The compounds can be visualized by having the following generic structure: HEAD - E LAZADOR - COLA Table 1 Compounds of the invention General description of the synthesis Reaction Schemes 1-11 represent the synthesis route followed in this example. Table 2 specifies the variables indicated in the reaction schemes.

REACTION SCHEME 1 REACTION SCHEME 1-2 t, R = H 3i.R = H 2, R = Boc ¼. », R = Boc If R = Boc: TFA REACTION SCHEME 2 REACTION SCHEME 2-2 Table 2 Specification of variables REACTION SCHEME 3 REACTION SCHEME 4 REACTION SCHEME 5 REACTION SCHEME 6 REACTION SCHEME 7 arylpiperazine, TEA, CHjCN 1l .1s .1M REACTION SCHEME 8 REACTION SCHEME 9 , 4-amlnobutanol, DCC, HOBt, CHjC¾ (fl) -30 (fl) 2 (S) -33 (fl) -33 REACTION SCHEME 10 twenty REACTION SCHEME The melting points were determined using an Electrothermal 8103 apparatus. The IR spectra were taken with Perkin-Elmer 398 and FT 1600 spectrophotometers. The 1 H NMR spectra were recorded on a Bruker 200 MHz spectrometer with TMS as an internal standard; the value of the chemical changes (d) is taken in ppm and the coupling constants (J) in Hertz (Hz). All reactions were carried out in an argon atmosphere. GC-MS were performed on a GC-MS Saturn 3 (Varian) or Saturn 2000 (Varian) system using a Chrompack DB5 capillary column (30 m x 0.25 mm internal diameter, film thickness 0.25 μp \). The mass spectra were recorded using a VG 70-250S spectrometer. The spectra of ESI-MS and APCI-MS were taken by an LCQDeca-Thermofinnigan spectrometer. Optical rotations were recorded on a Perkin-Elmer Model 343 polarimeter on the D sodium line at 20 ° C. The elemental analyzes were made on a Perkin-Elmer 240C elemental analyzer and the results were within 0.4% of the theoretical values, unless otherwise stated. The yields refer to the purified products and are not optimized. For the test, the claimed compounds were transformed into the corresponding hydrochloride salts by a standard procedure.

N- [4- [4- (3-cyanophenyl) piperazin-1-yl] butyl] benzo [b] furan-2-carboxamide (Compound 1-1 / la) 1- (3-cyanophenyl) piperazine (3). A mixture of 3-bromobenzonitrile (0.50 g, 2.74 mmol), piperazine (0.71 g, 8.24 mmol), sodium tert-butoxide (0.37 g, 3.8 mmol), tris (dibenzylidene ketone) dipalladium- (0) (6.27 mg, 0.0068 mmol) and rac-2, 2'-bis (diphenylphosphino) -1,1-biphenyl (BINAP) in dry toluene (8.0 mL) was heated at 80 ° C under argon. After stirring for 2 h, the mixture was allowed to cool to room temperature, placed in ethyl ether (30.0 mL), filtered and concentrated. The crude product was then purified by flash chromatography (10% methanol in chloroform) to give 0.32 g (63% yield) of 3 as a yellow oil: XH NMR (CDC13) d 1.87 (br s, 1H), 3.03 (t, 4H, J = 4.4 Hz), 3.17 (t, 4H, J = 4.3 Hz), 7.08 (m, 3H), 7.31 (m, 1H); IR (CHC13) Vmax 2230 was "1. Anal. (CnHi3N3) C, H, N.

N- [4- (l-hydroxy) butyl] benzo [b] furan-2-carboxamide (5a).

To a solution of 2-benzofurancarboxylic acid 4a (0.50 g, 3.08 mmol) in dry dichloromethane (10.0 mL), 1-hydroxybenzotriazole hydrate (HOBT) (0.46 g, 3.40 mmol) and 1,3-dicyclohexylcarbodiimide (0.70 g, 3.40 mmol ) were added at 0 ° C under argon; the suspension was warmed to room temperature and stirred for 1 h. Then, 4-amino-1-butanol (0.28 mL, 3.08 mmol) was added and the mixture was stirred overnight at room temperature. The resulting suspension was filtered through Celite®, washed with chloroform (3 x 10 mL) and the filtrate was evaporated. The crude product was purified by flash chromatography (10% methanol in chloroform) to give 0.70 g (97%) of 5a as a white solid: mp (methanol) 95-96 ° C; H NMR (CDC13) d 1.67 (m, 4H), 2.14 (br s, 1H), 3.53 (m, 2H), 3.73 (m, 2H), 6.89 (br s, 1H), 7.25-7.48 (m, 4H ), 7.63 (d, 1H, J = 7.7 Hz). Anal. (Ci3Hi5N03) C, H, N.

N- [4- (1-Bromo) butyl] benzo [b] furan-2-carboxamide (6a). To a vigorously stirred solution of 5a (0.50 g, 2.14 mmol) in dry acetonitrile (25 or mL), triphenylphosphine (0.86 g, 3.22 mmol) and carbon tetrabromide (1.06 g, 3.22 mmol) were added at room temperature. After 2 h, the mixture was quenched with 15% NaOH and the heterogeneous mixture was extracted with ethyl acetate (EtOAc) (3 x 25 mL). The organic layers were dried and evaporated. The residue was chromatographed (20% n-hexane in ethyl acetate) to give 0.58 g (91% yield) of 6a as a white solid: mp (EtOAc) 65-66 ° C; X H NMR (CDC13) d 1.67 (m, 4 H), 3.37 (m, 4 H), 7.36 (m, 4 H), 7.63 (d, 1 H, J = 7.7 Hz); GC-MS m / z 297 [M + H] \ 216 (100), 202, 188, 174, 161, 145, 118.89. Anal. (Ci3H14BrN02) C, H, N.

N- [4- [4- (3-cyanophenyl) piperazn-l-yl] butyl] benzo [b] furan-2-carboxamide (1-1 / la). To a stirred solution of 6a (50.0 mg, 0.17 mmol) in dry acetonitrile (3.0 mL) under argon, 1- (3-cyanophenyl) piperazine 3 (31.7 mg, 0.17 mmol) and triethylamine (38.2 ih, 0.27 mmol) were added.; the solution was refluxed overnight under agitation. The solvent was removed under reduced pressure, water was added and the mixture was extracted with dichloromethane (3 x 10 mL). The organic layers were dried and concentrated and the crude product was subjected to chromatography (10% methanol in chloroform) to give 60.0 mg of the (90% yield) as a colorless oil. XH RM (CDC13) d 1.72 (m, 4H), 2.46 (t, 2H, J = 6.7 Hz), 2.61 (t, 4H, J = 4.9 Hz), 3.24 (t, 4, J = 5.0 Hz), 3.52 (q, 2H, J = 6.1 Hz), 6.89 (br s, 1H), 7.09 (m, 3H), 7.47-7.25 (m, 5H), 7.66 (d, 1H, J = 7.5); FAB-MS m / z 403 [M + H] \ 147. Anal. (C24H26 4O2) C, H, N. 3, 4-Dihydro-2- [4- (3,4-dihydro-6-methoxypyrazino [1,2- a] indol-2 (1H) -yl) butyl] pyrazino [1,2-a] indole-1 (2H) -one (Compound 2 / lb) 1b ethyl 3- (3-methoxy-2-nitrophenyl) -2-oxopropanoate (8). To a suspension of potassium tert-butoxide (2.0 g, 18.0 mmol) in dry diethyl ether (50.0 mL), diethyl oxalate (3.16 mL, 23.3 mmol) was added dropwise at room temperature and the mixture was stirred for 15 minutes. min. Then 3-methoxy-2-nitrotoluene 7 (3.0 g) was added, 18.0 mmol) and the mixture was stirred for 30 minutes and left for 12 h without stirring. The solvent was removed in vacuo and water and ammonium chloride were added to the residue. The aqueous mixture was extracted with ethyl acetate (3 x 25 mL) and the collected organic layer was dried over anhydrous sodium sulfate (Na2SO4) and the solvent was evaporated. The crude product was chromatographed (30% EtOAc in n-hexane) to give 4.2 g of pure 8 as a yellow oil, 88% yield; 1 H RM (CDC13) d 1.27 (m, 3 H), 2.18 (s, 3 H), 3.75 (m, 2 H), 4.25 (m, 2 H), 6.78 (m, 2 H), 7.20 (m, 1 H); GG-MS m / z 267 [M + H] + 194, 166 (100), 135, 121; ES-MS m / z 268 [M + H] +. Anal. (Ci2H13N06) C, H, N.

Ethyl 7-methoxy-lH-indole-2-carboxylate (9). To a solution of 8 (4.8 g, 18.0 mmol) in absolute ethanol (120.0 mL) previously degassed under N2, 5% catalytic Pd / C was added and the mixture was left under a hydrogen atmosphere at room temperature for 24 h. The mixture was filtered over Celite® by washing with ethanol and the filtrate was evaporated under reduced pressure. The crude product was purified by flash chromatography (20% EtOAc in n-hexane) to provide 9 as a yellow solid (79%): mp 69-72 ° C; XH NMR (CDC13) d 1.42 (t, 3H, J = 6.94 Hz), 3.96 (8, 3H), 4.41 (q, 2H, J = 7.2 Hz), 6.72 (d, 1 H, J = 7.5 Hz), 7.07 (t, 1 H, J = 7.9 Hz), 7.25 (m, 2H), 9.18 (br s, 1H). ESI-MS m / z 220 [M + H] +, ES-MS / MS from [M + H] + 192, 176, 174 (100), 176, 148. Anal. (Ci2Hi3N03) C, H, N. 1- (Cyanomethyl) -7-methoxy-1H-indole-2-carboxylic acid ethyl ester (10). A mixture of sodium hydride (60% dispersion in mineral oil, 509.6 mg, 21.23 mmol) and ethyl 7-methoxyindole-2-carboxylate 9 (3.1 g, 14.15 mmol) in dry N, N-dimethylformamide (DMF) ( 15.0 mL), was stirred at room temperature for 30 minutes and to this was added bromoacetonitrile (2.0 mL, 28.3 mmol) in dry DMF (2.0 mL). The reaction mixture was then kept at 60-65 ° C for 30 minutes, and it was stirred for 6 h more at room temperature, left overnight and decomposed with ice. The separated solid was filtered and purified by flash chromatography (33% n-hexane in dichloromethane) to give 10 (30% yield) as a white solid: mp (ethanol) 99-101 ° C; XH RM (CDC13) d 1.41 (t, 3H J = 7.2 Hz), 3.99 (s, 3H), 4.40 (q, 2H, J = 7.1 Hz), 5.96 (s, 2H), 6.80 (d, 1H, J = 7.7 Hz), 7.10 (t, 1H, J = 7.9 Hz), 7.25 m, 1H), 7.33 (s, 1H). GC-MS m / z 258 (100) [M] +, 232, 213, 201, 187, 172, 144, 130, 114, 89. Anal. (Ci4Hi4N203) C, H, N. 1, 2,3,4-Tetrahydro-6-methoxypyrazino [1,2-a] indole (11).

A suspension of 10 (0.50 g, 1.93 mmol) in dry diethyl ether (Et20) (20.0 mL) was added slowly to a well-stirred suspension of lithium aluminum hydride (LiAlH4) (293.4 mg, 7.72 mmol) in dry Et20 (10.0 mL). mL). The reaction mixture was poured into an ice-water bath and 1N NaOH (10.0 mL) was added. The aqueous phase was extracted with EtOAc (3 x 30 mL) and the collected organic layers were dried and evaporated. The crude product was subjected to chromatography (10% ethanol in chloroform) to provide 11 as a yellow solid (40% yield): mp 120-122 ° C; 1H RN (CDC13) d 7.14 (d, 1 H, J = 7.8 Hz), 6.97 (t, 1 H, J = 7.7 Hz), 6.58 (d, 1 H, J = 7.7 Hz), 6.14 (s, 1H ), 4.47 (t, 2H, J = 5.8 Hz), 4.17 (s, 2H), 3.90 (s, 3H), 3.26 (t, 2H, J = 5.7 Hz); ES-MS m / z 405 [2M + H] +, 203 (100) [M + H] +. Anal. (d2HiN20) C, H, N. 1- (Cyanomethyl) -lH-indol-2-carboxylic acid ethyl ester (13). A mixture of sodium hydride (60% dispersion in mineral oil, 190.0 mg, 7.94 mmol) in ethyl indole-2-carboxylate 12 (1.0 g, 5.29 mmol) in dry DMF (4.6 mL), was stirred at room temperature for 30 minutes and to this was added bromoacetonitrile (0.74 mL, 10.60 mmol) in dry DMF (1.0 mL). The reaction mixture was then kept at 65 ° C for 30 minutes, and it was stirred for a further 6 hours at room temperature, left overnight and decomposed with ice. The separated solid was re-crystallized from ethanol to give 13 (90% yield) as a white solid: mp (ethanol) 83-84 ° C; ¾ NMR (CDCI3) d 1.42 (t, 3H, J = 7.3 Hz), 4.41 (q, 2H, J = 14.2, 7.2 Hz), 5.60 (s, 2H), 7.37 (m, 4H), 7.71 ( d, 1 H; J = 7.9 Hz); GG-MS m / z 228 [M] + (100), 199, 182, 154, 128, 115, 101, 89, 77. Anal. (Ci3Hi2N202) C, H, N. 1, 2, 3, -Tetrahydropyrazino. { 2H) -l-one [l, 2-a] indole (14). To a hot (60 ° C) solution of 13 (200.0 mg, 0.87 mmol) in dry methanol (8.0 mL) under argon, cobalt boride prepared in fresh form (450.0, 3.50 mmol), was added under stirring. Sodium borohydride (166.0 mg, 4.38 mmol) was added portion by portion and the mixture was refluxed for 3 h. The mixture was cooled, and the solvent was removed under reduced pressure then added and the mixture was extracted with EtOAc (3 x 25 mL). The organic layers were dried, evaporated and the crude product was purified by flash chromatography (10% methanol in chloroform) to give 14 (68% yield) as a white solid: mp (methanol) 261-265 ° C (dec); JH R N (CDC13) d 3.82 (m, 2H), 4.27 (m, 2H), 6.65 (br s, 1H), 7.23 (m, 4H), 7.72 (d, 1 H, J = 8.0 Hz); APCI-MS m / z 187 [M + H] +; APCI-MS / MS of [M + H] + 159 (100), 144. Anal. (CnHi0N2O) C, H, N.

N- [1-. { 4-Bromo) butyl] -1,2, 3, 4-tetrahydropyrazino (2H, -1-one [1,2-a] indole (15). To a suspension of 14 (130.0 mg, 0.69) dry DMF was added. (1.0 mL) sodium hydride, 60% in mineral oil, (20.0 mg, 0.83 mmol) After stirring for 1 h at 60 ° C under argon, a solution of 1,4-dibromobutane (0.41 mL) was added dropwise. 3.47 mmol) in dry DMF (0.50 mL) The mixture was refluxed under argon at 110 ° C for 3 h, then the solvent was evaporated under reduced pressure, and the residue was re-suspended in water and extracted with water. dichloromethane (3 x 10 mL) The combined organic layers were dried, evaporated and the residue was subjected to chromatography (30% EtOAc in n-hexane) to give 15 as a yellow solid (41% yield): mp ( EtOAc) 101-102 ° C; XH RM (CDC13) dd 1.85 (m, 4H), 3.67 (m, 4H), 3.81 (m, 2H), 4.29 (m, 2H), 7.20 (m, 4H), 7.70 (d, 1H; J = 8.0 Hz); APCI-MS m / z 321 [M + H] \ 241, 227, 199 (100), 187, 159, 144, 117. Anal. (Ci5Hi7BrN20) C, H, N. 3, 4-Dihydro-2- [4-. { 3, 4-dihydro-6-methoxypyrazino [1,2-a] indole-2. { lH) -il) b til] pyrazino [1,2-a] indole-1. { 2H) -one (Ib). To a suspension of 1, 2, 3, 4- tetrahydro-6-metoxipirazino [1, 2-a] indole 11 (30.0 mg, 0.15 mmol) and K2C03 (71.6 mg, 0.52 mol) in dry acetonitrile (5.0 mL) derivative of bromine 15 (47.7 mg, 0.15 mmol) and a catalytic amount of sodium iodide (Nal) were added and the resulting mixture was heated to reflux for 18 h. The mixture was then filtered and the filtrate was evaporated to dryness under reduced pressure. The residue was suspended in water (10.0 mL) and extracted with Et20 (2 x 25 mL). The combined ether extract was evaporated under reduced pressure and the crude product was purified by flash chromatography (5% methanol in chloroform) to give Ib as a yellow oil (62% yield); H NMR (CDC13) d 1.69 (m, 4H), 2.58 (t, 2H, J = 6.6 Hz), 2.88 (t, 2H, J = 5.5 Hz), 3.66 (t, 2H, J = 6.7 Hz), 3.77 (m, 4H), 3.88 (s, 3H), 4.24 (t, 2H, J = 5.8 Hz), 4.45 (t, 2H, J = 5.6 Hz), 6.10 (s, 1H), 6.54 (d, 1 H) , J = 7.6 Hz), 6.93 (t, 1 H, J = 7.8 Hz), 7.13 (m, 3H), 7.29 (m, 2H), 7.70 (d, 1H, J = 7.9 Hz); ES-MS m / z 907 [2M + Na] +, 884 [2M + H] 443 (100) [+ H] +; 13C NMR (CDC13) d 24.3, 25.3, 29.6, 40.2, 45.5, 45.9, 46.1, 51.2, 51.7, 55.3, 57.2, 97.1, 101.8, 106.0, 109.5, 112.9, 120.6, 122.6, 124.3, 125.9, 127.5, 129.4, 130.3, 134.5, 136.3, 147.7, 159.9. Anal. (C27H3o 402) C, H, N.

N- [4- [4- (3-Chlorophenyl) piperazin-l-yl] butyl] isoquinoline-3-carboxamide (Compound 1-3 / lc) N- [1- (4-Hydroxy.) Butyl] isoquinoline-3-carboxamide (5b) The title compound was prepared by starting from 3-isoquinolinecarboxylic acid 4b (100.0 mg, 0.57 mmol) and following the procedure as it was described to obtain 5a The derivative 5b was obtained as a white solid (96% yield): mp (methanol) 126-127 ° C; XH NMR (CDC13) d 1.74 (m, 4H), 3.57 (q, 2H J = 6.3 Hz), 3.73 (t, 2H, J = 5.9 Hz), 7.40 (m, 2H), 7.75 (m, 2H), 8.39 (br s, 1H), 8.57 (s, 1H), 9.14 ( s, 1 H); ES-MS m / z 510 [2M + Na +], 267 (100) [M + Na] 245 [M + H] + ES-MS / MS of [M + H] + 227, 174 Anal. (C14Hi6N202) C, H, N.

N- [1- (4-Bromo) butyl] isoquinoline-3-carboxamide (6b). To a solution of 5b (140.0 mg, 0.57 mmol) in dry acetonitrile (10.0 ml) were added triphenylphosphine (225.0 mg, 0.86 mmol) and carbon tetrabromide (285.0 mg, 0.86 mmol) under vigorous stirring at room temperature. After 2 h, the mixture was quenched with 15% NaOH and extracted with EtOAc (3 x 10 mL). The organic layers were dried and evaporated. The residue was chromatographed (30% n-hexane in EtOAc) to give 130.0 mg of 6b (75% yield) as a yellow solid: mp (EtOAc) 72-73 ° C; ½ NMR (CDCl 3) 6 2.06 (m, 4H), 3.48 (m, 4H), 7.66 (m, 2H), 7.93 (m, 2H), 8.36 (br s, 1H), 8.55 (s, 1H), 9.08 (s, 1H); ES-MS m / z 329 [M + Na] +, 308 (100) [M + Na] +. Anal. (Ci4H1BBrN20) C, H, N.

N- [4- [4- (3-Chlorophenyl) piperazin-l-yl] butyl] isoquinoline-3-carboxamide (le). To a stirred solution of 6b (190.0 mg, 0.62 mmol) in dry acetonitrile (20.0 ml) under argon, 1- (3-chlorophenyl) piperazine (144.0 mg, 0.62 mmol) and triethylamine (141.0 uL, 1.0 mmol was added ); the solution was refluxed overnight under agitation. The solvent was removed under reduced pressure, water was added and the mixture was extracted with dichloromethane (3 x 10 mL). The organic layers were dried and concentrated and the crude product was chromatographed (10% methanol in chloroform) to give 130.0 mg of le (50% yield) as a white solid: mp (methanol) 156-157 ° C; H RM (CDC13) d 1.65 (m, 4H), 2.46 (t, 2H, J = 6.7 Hz), 2.60 (t, 4H, J = 4.9 Hz), 3.21 (t, 4H, J = 5.0 Hz), 3.57 (q, 2H, J = 6.5 Hz), 6.78 (m, 2H), 6.86 (d, 1H, J = 1.6 Hz), 7.14 (t, 1H, J = 8.0 Hz), 7.72 (m, 2H), 8.00 (t, 2H, J = 8.2 Hz), 8.33 (br s, 1H), 8.61 (s, 1H), 9.14 (s, 1H); ES-MS m / z 445 (100) [M + Na] +, 423 [M + H] +, ES-MS / MS from [M + H] + 251, 227 (100); 13C NMR (CDC13) d 24.4, 27.8, 29.8, 39.5, 48.7, 53.1, 58.2, 114.0, 115.9, 119.4, 120.4, 127.8, 128.3, 128.9, 129.8, 130.2, 131.2, 135.1, 136.2, 144.0, 151.2, 152.5, 165.0. Anal. (C24H27C1N40) C, H, N.

N- [4- (1, 2, 3, 4-Tetrahydro-5-methoxy-p-carbolin-2-yl) butyl] isoquinoline-3-carboxamide (Compound 1-4 / ld) 1d 4- ethoxy-lH-indol-3-carbaldehyde (17). N-Chlorosuccinimide (2.72 g, 20.41 mmol) was added portion by portion to a solution of triphenylphosphine (5.35 g, 20.41 mmol) in tetrahydrofuran (100.0 mL) and stirred at room temperature for 30 minutes. DMF (1.54 mL, 40.8 mmol) was added to the suspension, and the mixture was heated to reflux for 1 h. Then 4-methoxy-1H-indole 16 (1.0 g, 6.80 mmol) was added and the mixture was heated to reflux for 1 h. After cooling, tetrahydrofuran was evaporated, added (80.0 mL), and the mixture was heated to reflux for 1 h and then basified with 10% NaOH. Then, the aqueous phase was extracted with EtOAc (3 x 50 mL) and the collected organic layers were dried and evaporated. The crude product was purified by flash chromatography (50% n-hexane in EtOAc) to give 17 as an orange solid in quantitative yield: mp (EtOAc) 154-156 ° C; XH NMR (CDC13) d 4.00 (s, 3H), 6.72 (m, 1H), 7.07 (d, 1H, J = 8.1 Hz), 7.19 (d, 1H, J = 8.1 Hz), 7.92 (d, 1H, J = 2.9 Hz), 9.05 (br s, 1H), 10.50 (s.h.H); FAB-MS m / z 175 (100) [M] +, 160, 144, 129, 116, 104, 89, 77. Anal. (Ci0H9NO2) C, H, N. 4- ethoxy-3- (2-nitrovinyl) -lH-indole (18). Ammonium acetate (168.0 mg, 2.19 mmol), was added to 4-methoxy-lH-indole-3-carbaldehyde 17 (1.20 g, 7.27 mmol) in nitromethane (12.0 mL) and the mixture was stirred vigorously while heating to reflux for 1 h. The resulting solution was concentrated under reduced pressure and the crude product was purified by flash chromatography (50% n-hexane in EtOAc) to give 0.95 g of 18 as a bright yellow solid (64% yield): mp (EtOAc 179-181 ° C dec.; X H NMR (DMSO-d 6) d 3.95 (s, 3 H), 6.73 (d, 1 H, J = 7.3 Hz), 1.13 (m, 2 H), 8.08 (d, 1 H, J = 13.4 Hz), 8.24 (s, 1H), 8.55 (d, 1H, J = 13.0 Hz), 12.20 (br s, 1 H). Anal. (CiiHioN203) C, H, N. 4-Methoxytryptamine (19). A solution of 18 (0.90 g, 4. 33 mmol) in dry tetrahydrofuran (40.0 mL) was added dropwise to a suspension of LiAlH4 (1.73 g, 45.22 mmol) in dry tetrahydrofuran (17.0 mL) and heated to reflux for 1 h with stirring. The excess LiAlH4 was quenched by the addition of methanol with caution under cooling in an ice bath. Then water and sodium-potassium tartrate s.s. were added. and the mixture was extracted with a dichloromethane-methanol solution (95: 5 v / v). The organic layers were washed with brine, dried over Na 2 SO, and evaporated under reduced pressure. The crude product was purified by flash chromatography (CHCl3-MeOH-NH0H 20: 5: 1 v / v) to give 0.60 g of 19 as a white solid (77% yield: pf (methanol) 139-140 ° C; 1 H NMR (CDC13) d 2.00 (br s, 2 H), 3.00 (m, 4 H), 3.89 (s, 3 H), 6.46 (d, 1 H, J = 7.6 Hz), 6.80 (s, 1 H), 6.92 ( d, 1H, J = 8.1 Hz), 7.06 (t, 1H, J = 7.9 Hz), 8.85 (br s, 1H) Anal. (C11H14N2O) C, H, N. 1, 2, 3, 4-tetrahydro-5-methoxy-p-carboline (20). 4-Methoxytryptamine 19 (375.0 mg, 1.97 mmol) was pre-transformed into the corresponding hydrochloride salt by a standard procedure. To a solution of 4-methoxytryptamine hydrochloride (445.0 mg, 1.97 mmol) in water (50.0 mL) was added glyoxylic acid monohydrate (181.2 mg, 1.97 mmol) and the mixture was stirred at reflux for 1 h. After cooling to room temperature, a 20% NaOH solution was added and the mixture was extracted with EtOAc (3 x 30 mL) and the organic layers were dried and evaporated. The crude product was chromatographed (CHCl3-MeOH-NH4OH 20: 5: 0.5 v / v) to give 20 as an amorphous solid (63% yield); ½ RM (CDCI3) d 1.67 (br s, 2H), 2.96 (m, 2H), 3.13 (m, 2H), 3.88 (s, 3H), 3.98 (s, 2H), 6.47 (d, 1H, J = 7.6 Hz), 6.89 (d, 1H, J = 8.1 Hz), 7.01 (t, 1H, J = 7.9 Hz), 7.75 (br s, 1H). Anal. (Ci2H14N20) C, H, N.

N- [4- (1,2,3,4-Tetrahydro-5-methoxy-p-carbolin-2-yl) butyl] isoquinoline-3-carboxamide (Id). To a suspension of 1, 2, 3, 4-tetrahydro-5-methoxy-carboline 20 (94.0 mg, 0.55 mmol) and K2C03 (218.6 mg, 1.57 mol) in dry acetonitrile (10.0 mL) were added with bromine derivative 6b (137.0 mg, 0.45 mmol) and a catalytic amount of Nal and the resulting mixture was heated to reflux for 18 h. Then, the mixture was filtered and the filtrate was evaporated to dryness under reduced pressure. The residue was suspended in water (10.0 mL) and extracted with Et20 (2 x 25 mL) and dichloromethane (1 x 25 mL). The combined organic layers were evaporated under reduced pressure and the crude product was purified by flash chromatography (0.5% methanol in chloroform) providing Id as a yellow oil (30% yield); 1 H NMR (CDCl 3) d 1.74 (m, 4 H), 2.64 (m, 2 H), 2.82 (m, 2 H), 3.03 (m, 2 H), 3.57 (m, 4 H), 3.86 (s, 3 H), 6.44 ( d, 1H, J = 7.5 Hz), 6.92 (m, 2H), 7.72 (m, 2H), 7.97 (m, 2H), 8.39 (br s, 1H), 8.59 (s, 1H), 9.07 (s, 1 HOUR); ES-MS m / z 429 (100) [M + H] +, 256, 227. Anal. (C26H28N402) C, H, N.

N- [4- (3,4-Dihydro-6-methoxypyrazino [1,2-a] indol-2 (1 H) -yl) butyl] isoquinoline-3-carboxamide (Compound 1-5 / le) 1e N- [4- (3,4-Dihydro-6-methoxypyrazino [1,2- a] indol-2 (1 H) -yl) butyl] isoquinoline-3-carboxamide (le). The title compound was prepared using the bromo derivative 6b (98.0 mg, 0.32 mmol) and the amino derivative 11 (0.32 mmol) and following the procedure described to obtain Ib. The compound was obtained as a colorless oil (55% yield); 1H RM (CDC13) d 1.75 (m, 4H), 2.60 (m, 2H), 2.89 (t, 2H, J = 5.5 Hz), 3.57 (q, 2H, J = 6.1 Hz), 3.79 (s, 2H) , 3.86 (s, 3H), 4.49 (t, 2H, J = 5.6 Hz), 6.12 (s, 1H), 6.53 (d, 1H, J = 7.6 Hz), 6.93 (t, 1H, J = 7.7 Hz) , 7.10 (d, 1H, J = 7.9 Hz), 7.70 (m, 2H), 7.97 (m, 2H), 8.39 (br s, 1H), 8.59 (s, 1H), 9.05 (s, 1H); ES-MS m / z 879 [2M + Na] +, 451 [M + Na] +, 429 (100) [M + H] +. Anal. (C26H28N4O2) C, H, N. 3- [5- [4- (3-Chlorophenyl) piperazin-1-yl] pentyloxy] isoquinoline (Compound 1-6 / lf) 1f 3- (5-Bromopentyloxy) isoquinoline (22). To a solution of isoquinolin-3-ol 21 (200.0 mg, 1.37 mmol) in dry DMF (5.0 mL) was added 1,5-dibromopentane (204.0 μ, 1.50 mmol) was added and the mixture was stirred at room temperature for 10 minutes. Then cesium carbonate (538.0 mg, 1.64 mmol) was added and the mixture was heated at 65 ° C for 12 h. After cooling to room temperature, methyl tert-butyl ether (MTBE) (20.0 mL) and water (15.0 mL) were added and the mixture was extracted with MTBE (3 x 25 mL). The organic layers collected were dried over Na2SC > 4, filtered and evaporated. The residue was subjected to chromatography (dichloromethane) to provide 197.0 mg of pure 22 as a yellow oil (49% yield). H NMR (CDC13) d 1.64 (m, 2H), 1.89 (m, 4H), 3.43 (t, 2H, J = 6.5 Hz), 4.34 (t, 2H, J = 6.3 Hz), 6.97 (s, 1H) , 7.33 (m, 1H), 7.54 (t, 1H, J = 7.2 Hz), 7.66 (d, 1H, J = 8.3 Hz), 7.85 (d, 1H, J = 8.2 Hz), 8.92 (s, 1H); ES-MS m / z 296 (100) [M + H] +, 146. Anal. (Ci4Hi6BrNO) C, H, N. 3- [5- [4- (3-Chlorophenyl) piperazin-1-yl] pentyloxy] isoquinoline (lf). To a stirred solution of 22 (430.0 mg, 1.46 mmol) in dry acetonitrile (30.0 mL) under argon, l- (3-chlorophenyl) piperazine hydrochloride (338.7 mg, 1.46 mmol) and triethylamine (329.0 uL, 2.36 mmol) were added. ) and the solution was refluxed for 4 h under agitation. The solvent was removed under reduced pressure, water was added and the mixture was extracted with dichloromethane (3 x 10 mL). The organic layers were dried and concentrated and the crude product was chromatographed (50% n-hexane in EtOAc) to give 320.0 mg of lf (78.2% yield) as a white solid: mp (EtOAc) 88-89 °. C; 1 H NMR (CDC13) d 1.52-1.76 (m, 4H), 1.88 (q, 2H, J = 6.6 Hz), 2.42 (t, 2H, J = 7.2 Hz), 2.57 (m, 4H), 3.18 (m, 4H), 4.35 (t, 2H, J = 6.4 Hz), 6.73-6.85 (m, 3H), 6.97 (s, 1H), 7.13 (t, 1H, J = 8.0 Hz), 7.34 (dd, 1H, J = 8.3, 6.4 Hz), 7.54 (dd, 1H, J = 7.9, 6.4 Hz), 7.66 (d, 1H, J = 8.1 Hz), 7.85 (d, 1H, J = 8.2 Hz), 8.93 (s, 1H ); ES-M S m / z 410 (100) [M + H] +, 265. Anal. (C24H28C I 3O) C, H, N.

N- [4- [4- (m-Tolyl) piperazin-1-yl] butyl] benzo [b] furan-2-carboxamide (Compound 1-7 / lg) 19 N- [4- [4- (m-Tolyl) piperazin-1-yl] butyl] benzo [b] furan-2-carboxamide (1 g). To a stirred solution of 6a (0.62 g, 2.09 mmol) in dry acetonitrile (30.0 mL) under argon, 1- (m-tolyl) piperazine dihydrochloride (0.52 g, 2.09 mmol) and triethylamine (0.62 mL, 4.60 mmol) were added. ) and the solution was refluxed overnight under agitation. The solvent was removed under reduced pressure, water was added and the mixture was extracted with dichloromethane (3 x 30 mL). The organic layers were dried and concentrated and the crude product was chromatographed (6% methanol in chloroform) to give 0.42 g of 19 (52% yield) as a white solid: mp 119-120 ° C; XH NMR (CDC13) d 1.70 (m, 4H), 2.31 (s, 3H), 2.46 (t, 2H, J = 6.6 Hz), 2.62 (t, 4H, J = 4.9 Hz), 3.23 (t, 4H, J = 4.9 Hz), 3.52 (q, 2H, J = 6.1 Hz), 6.70 (m, 3H), 7.00 (br s, 1H), 7.13 (t, I 1H, J = 4.4 Hz), 7.18-7.48 ( m, 4H), 7.66 (d, 1H, J = 7.7 Hz); ES-MS m / z 805 (100) [2 + Na] +, 414 [M + Na]? 392 [M + H] +; 13 C RM (CDCl 3) d 22.0, 24.5, 27.7, 39.4, 49.4, 49.3, 53.5, 58.1, 110.5, 111.9, 113.4, 117.1, 120.9, 122.9, 123.9, 127.0, 127.9, 129.2, 139.0, 149.2, 151.5, 154.9, 159.1. Anal. (C24H29N3O2) C, H, N. lH-indole-2-carboxylate of 4- [4-. { 2, 3-dichlorophenyl) piperazin-1-yl] butyl (Compound 1-8 / lh) 1 hour 4-hydroxybutyl H-indole-2-carboxylate (5c). To a solution of butan-1,4-diol (0.46 mL, 5.21 mmol), dimethylaminopyridine (DMAP) (68.41 mg, 0.56 mmol), and lH-indole-2-carboxylic acid 4c (1.0 g, 6.20 mmol) in dry dichloromethane (20.0 mL) at 0 ° C was added dropwise over 45 minutes, a solution of DCC (1.4 g, 6.76 mmol) in dry dichloromethane (10.0 mL). The resulting suspension was stirred for an additional 1 h at 0 ° C, the cooling bath was removed, and the mixture was stirred for an additional 12 h. The mixture was filtered through Celite® and evaporated to dryness under reduced pressure. The product was purified by flash chromatography (7.5% methanol in chloroform) to give 5c as a white amorphous solid (45% yield). XH NMR (CDC13) d 1.81 (m, 4H), 2.08 (br s, 1H), 3.73 (t, 2H, J = 6.0 Hz), 4.39 (t, 2H, J = 6.2 Hz), 7.14 (t, 1H , J = 7.4 Hz), 7.27 (m, 3H), 7.42 (d, 1H, J = 8.2 Hz), 7.68 (d, 1H, J = 8.0 Hz), 9.39 (br s, 1H); ES-MS m / z 232 (100) [M-H] ~ 160, 116. Anal. (C13Hi5N03) C, H, N. 4-bromobutyl lH-indole-2-carboxylate (6c). The title compound was prepared starting from 5c (0.45 g, 1.93 mmol) and following the procedure described to obtain 6a. Compound 6c was obtained as a white solid (91% yield): mp (ethyl acetate) 85-85 ° C; ½ NMR (CDC13) dd 1.93 (m, 4H), 3.44 (t, 2H, J = 6.2 Hz), 4.37 (t, 2H, J = 6.0 Hz), 7.15 (t, 1H, J = 7.3 Hz), 7.30 (m, 2H), 7.45 (d, 1H, J = 8.2 Hz), 7.69 (d, 1H, J = 8.0 Hz), 9.81 (br s, 1 H). Anal. (Ci3H14BrN02) C, H, N. lH-indole-2-carboxylate of 4- [4- (2,3-dichlorophenyl) piperazin-1-yl] butyl (lh). To a stirred solution of 6c (220.0 mg, 0.74 mmol) in dry acetonitrile (20.0 mL) under argon, l- (2,3-dichloro) piperazine hydrochloride (198.0 mg, 0.74 iranol) and triethylamine were added. (167.0 VLL, 1.20 mmol) and the solution was refluxed overnight under stirring. The solvent was removed under reduced pressure, water was added and the mixture was extracted with dichloromethane (3 x 30 mL). The organic layers were dried and concentrated and the crude product was chromatographed (5% methanol in chloroform) to give lh (60% yield) as a white solid: mp (methanol) 136-137 ° C; XH RM (CDC13) d 1.79 (m, 4H), 2.50 (t, 2H, J = 6.7 Hz), 2.66 (m, 4H), 3.07 (m, 4H), 4.40 (t, 2H, J = 5.9 Hz) , 6.93 (m, 1H), 7.08-7.35 (m, 5H), 7.43 (d, 1 H, J = 8.1 Hz), 7.69 (d, 1H, J = 7.9 Hz), 9.16 (br, 1H); ES-MS m / z 468 [H + N] +. 446 (100) [M + Na] +. Anal. (C23H25Cl2N3O2) C. H. N. 2- [4- [4- (3-Chlorophenyl) piperazin-1-yl] butyl] -3,4-dihydropyrazino [1,2-a] indole-1 (2H) -one (Compound 1-9 / li) 2- [4- [4- (3-Chlorophenyl) piperazin-1-yl] butyl] -3,4-dihydropyrazino [1,2-a] indole-1 (2H) -one (li). The title compound was prepared starting from 15 (410.0 mg, 1 mmol) and following the procedure described to obtain it. The compound li was obtained as a white solid (68% yield): mp (EtOAc) 180-181 ° C; ?? NMR (CDC13) d 1.64 (m, 4H), 2.43 (t, 2H, J = 7.1 Hz), 2.56 (t, 4H, J = 4.9 Hz), 3.17 (t 4H, J = 4.9 Hz), 3.62 (t. t, 2H, J = 6.8 Hz), 3.75 (t, 2H, J = 5.9 Hz), 4.22 (m, 3H). 6.76 (m, 3H). 6.84 (d.sub.1 H, J = 2.0 Hz). 7.14 (m, 2H), 7.30 (m, 2H). 7.69 (d, 1H, J = 7.9 Hz); ES-MS m / z 437 [M + H] +; 13c NMR (CDC13) d 24.0, 25.5, 40.2. 46.0, 46.2, 48.5, 53.0, 58.0, 106.0, 109.4, 113.7. 115.6. 119.1, 120.5, 122.6. 124.3, 127.5, 129.4, 129.9, 134.9. 136.3, 152.3, 159.8. Anal. (C25H29C IN4O) C, H, N.

N- [4- [4- (Pyridin-2-yl) iperazin-1-yl] butyl] isoquinoline-3-carboxamide (Compound 1-10 / L) N- [4- [4- (Pyridin-2-yl) piperazin-1-yl] butyl] -isoquinoline-3-carboxamide (lj). To a stirred solution of 6b (190.0 mg, 0.62 mmol) in dry acetonitrile (20.0 mL) under argon, 1- (2-pyridin-2-yl) piperazine hydrochloride (101.0 mg, 0.62 mmol) and triethylamine (141.0) were added. uL, 1.0 mmol) and the solution was refluxed overnight with stirring. The solvent was removed and the crude product was chromatographed (10% methanol in chloroform) to give 225.0 mg of lj (93.4% yield) as a white solid: mp (methanol) 108-109 ° C; lH NMR (CDC13) d 1.62 (m, .4H), 2.38 (m, 2H), 2.49 (m, 4H), 3.52 (m, 6H), 6.54 (m, 2H), 7.40 (m, 1H), 7.65 (m, 2H), 7.91 (t, 2H, J = 8.6 Hz), 8.11 (d, 1H, J = 4.7 Hz), 8.32 (br s, 1H), 8.54 (s, 1H), 9.06 (s, 1H) ); ES-MS m / z 412 (100) [M + Na +], 390 [M + H +], 242. Anal. (C23H27N5O) C, H, N. 2- [4- (4-m-Tolyl) piperazin-1-yl] butyl] -3,4-dihydropyrazino [1,2-a] indole-1 (2H) -one (Compound 1-11 / lk) 2- [4- (4-m-Tolyl) piperazin-1-yl] butyl] -3,4-dihydropyrazino [1,2-a] indole-1 (2H) -one (lk). Starting from 15 (127.0 mg, 0.40 mmol) and 1- (m-tolyl) piperazine dihydrochloride (0.40 mmol), the title compound was prepared following the procedure described for 19. The product lk was obtained as a white solid (40.0% yield): mp (methanol) 155-156 ° C; ¾ NMR (CDC13) d 1.68 (m, 4H), 2.36 (s, 3H), 2.49 (m, 2H), 2.60 (t, 4H, J = 5.0 Hz), 3.18 (t, 4H, J = 4.9 Hz) , 3.66 (m, 2H), 3.78 (t, 2H, J = 3.0 Hz), 4.25 (m, 2H), 6.70 (m, 4H), 7.14 (m, 2H), 7.31 (m, 2H), 7.70 ( d, 1H, J = 8.2 Hz); ES-MS m / z 416 [M + H] +. Anal. (C26H32N4O) C, H, N. 3- [5- (4-m-Tolylpiperazin-1-yl) pentyloxy] isoquinoline (Compound 1-12 / 11) II 3- [5- (4-M-Tolylpiperazin-1-yl) pentyloxy] isoquinoline (11). Beginning from 22 (101.0 mg, 0.34 mmol) and 1- (m-tolyl) piperazine dihydrochloride (0.34 mmol), the title compound was prepared following the procedure described for lf. The product 11 was obtained as a white solid (65.0% yield): mp (methanol) 94-95 ° C; ½ NMR (CDCl 3) d 1.72 (m, 4H), 1.92 (m, 2H), 2.30 (s, 3H), 2.42 (t, 2H, J = 6.8 Hz), 2.60 (m, 4H), 3.19 (m, 4H), 4.34 (t, 2H, J = 6.5 Hz), 6.70 (m, 3H), 6.97 (s, 1H), 7.13 (t, 1H, J = 8.1 Hz), 7.55 (t, 1H, J = 7.2 Hz), 7.67 (d, 1H, J = 8.1 Hz), 7.86 (d, 1H, J = 8.2 Hz), 8.93 (s, 1H). Anal. (C25H31N3O) C, H, N.

N- [4- [4- (m-Tolyl) piperazin-l-yl] butyl] isoquinoline-3-carboxamide (Compound 1-13 / lm) N- [4- [4- (m-Tolyl) piperazin-1-yl] butyl] isoquinoline-3-carboxamide (lm). Beginning from 6b (1.0 g, 3.26 mmol) and 1- (m-tolyl) piperazine dihydrochloride (3.26 mmol), the title compound was prepared following the procedure described for 1 g. The product lm was obtained as a yellowish solid (48.0% yield): mp (methanol) 152-153 ° C; XH NMR (CDC13) d 1.68 (m, 4H), 2.30 (s, 3H), 2.46 (t, 2H, J = 6.8 Hz), 2.60 (t, 4H, J = 5.0 Hz), 3.20 (t, 4H, J = 4.9 Hz), 3.58 (q, 2H, J = 6.4 Hz), 6.70 (m, 3H), 7.14 (t, 1H, J = 8.1 Hz), 7.72 (m, 2H), 8.00 (t, 2H, J = 8.0 Hz), 8.33 (br s, 1H), 8.61 (s, 1H), 9.14 (s, 1H); ES-MS m / z 403 [M + H] +; 13 C NMR (DMSO-d6) 21.3, 22.0, 27.1, 39.1, 46.2, 51.1, 55.7, 114.1, 117.5, 121.1, 121.9, 128.7, 129.0, 129.7, 130.2, 133.0, 136.5, 139.0, 143.0, 150.0, 151.7, 164.1 170.0 Anal. (C25H30N4O) C, H, N. 7- [4- [4- (2, 3-Dichlorophenyl) piperazin-1-yl] butoxy] pyrrolo [1,2-a] quinoxalin-4 (5H) -one (Compound 1-14 / ln) 1n 7-Hydroxypyrrolo [1,2-a] quinoxalin-4 (5H) -one (24). A solution of 23 (100.0 mg, 0.35 mmol) in THF (70.0 mL) was hydrogenated at atmospheric pressure over 10% Pd-C (1.62 mg) for 16 h. The catalyst was removed by filtration, the solvent was evaporated, and the residue was purified by flash chromatography (15% methanol in chloroform) to provide compound 24 in a quantitative yield as an amorphous solid. XK R (???? - a½) d 6.57 (m, 2H), 6.69 (m, 1H), 6.90 (m, 1H), 7.80 (d, 1H, J = 8.8 Hz), 7.98 (s, 1H) , 9.62 (s, 1H), 11.03 (s, 1H). Anal. (CiiH8N202) C, H, N. 7- (4-Bromobutoxy.) Pyrrolo [1,2-a] uinoxalin-4 (5H) -one (25). To a solution of compound 24 (50.0 mg, 0.25 mmol) in dry DMF (5.0 mL) was added. added 1,4-dibromobutane (64.0 ih, 0.29 mmol) and the mixture was stirred at room temperature for 10 min.Casium carbonate (98.0 mg, 0.30 mmol) was added and the mixture was heated at 65 ° C for 12 h. After cooling to room temperature, methyl tert-butyl ether (MTBE) (10.0 mL) and water (5.0 mL) were added and the mixture was extracted with MTBE (3 x 25 mL) .The organic layers collected were dried over Na2SO4, filtered and evaporated The residue was subjected to chromatography (15% n-hexane in EtOAc) to give pure 25 as a yellow oil (22.5% yield) H-NMR (CD3OD) d 1.64 (m, 2H), 1.96 (m, 4H), 3.52 (m, 2H), 3.99 (m, 2H), 6.62 (m, 1H), 6.77 (m, 2H), 7.10 (d, 1H, J = 3.5 Hz), 7.73 (m , 1H), 7.83 (d, 1H, J = 1.5 Hz) Anal. (Ci5Hi5BrN202) C, H, N. 7- [4- [4- (2, 3-Dichlorophenyl) piperazin-1-yl] butoxy] irrolo [1, 2-a] guinoxalin-4 (5H) -one (ln). Beginning from 25 (100.0 mg, 0.50 mmol) and (2,3-dichloro) phenylpiperazine dihydrochloride (0.50 mmol), the title compound was prepared following the procedure described for lf. The product ln was obtained as an amorphous solid (81.0% yield). 1 H NMR (DMSO-d 6) d 1.67 (m, 4 H), 2.44 (m, 6 H), 2.95 (m, 4 H), 3.99 (t, 2 H, J = 5.9 Hz), 6.77 (m, 2 H), 6.94 ( m, 1H), 7.08 (m, 1H), 7.25 (m, 2H), 7.92 (d, 1H, J = 8.6 Hz), 8.04 (s, 1H), 11.03 (s, 1H). Anal. (C25H26Cl2 402) C, H, N.

N- [4- [4-. { 3-Methoxyphenyl) piperazin-l-yl] butyl] isoquinoline-3-carboxamide (Compound I-15 / lo) 1o N- [4- [4- (3-ethoxyphenyl) piperazin-1-yl] butyl] isoquinoline-3-carboxamide (lo). Beginning from 6b (1.0 g, 2.39 mmol) and (3-methoxy) phenylpiperazine (458.9 mg, 2.39 mmol), the title compound was prepared following the procedure described for Ig. The product was obtained as a colorless oil (54.0% yield). XH NMR (CDC13) d 1.66 (m, 4H), 2.44 (t, 2H, J = 6.8 Hz), 2.59 (t, 4H, J = 4.9 Hz), 3.19 (t, 4H, J = 4.9 Hz), 3.56 (q, 2H, J = 6.3 Hz), 3.77 (s, 3H), 6.47 (m, 3H), 7.14 (t, 1H, J = 8.1 Hz), 7.73 (m, 2H), 7.99 (t, 2H, J = 8.2 Hz), 8.32 (br s, 1H), 8.60 (s, 1H), 9.12 (s, 1H); ES-MS m / z 441 [M + Na] +, 419 [M + H] +. Anal. (C25H30N4O2) C, H, N.

N- [4- [4- (3-Trifluoromethylphenyl) piperazin-1-yl] butyl] indole-2-carboxamide (Compound 1-16 / lp) 1p N- [1- (4-Hydroxy) butyl] indole-2-carboxamide (5d). To a solution of 2-indolecarboxylic acid 4c (150.0 mg, 0.93 mmol) in dry dichloromethane (20.0 mL), hydrated 1-hydroxybenzotriazole (460.0 mg, 1.03 mmol) and 1,3-dicyclohexylcarbodiimide (210.0 mg, 1.03 mmol) were added. ° C under argon; the suspension was warmed to room temperature and stirred for 1 h. Then, 4-amino-1-butanol (93.6 pL, 1.03 mmol) was added and the mixture was stirred at room temperature for 16 h. The resulting suspension was filtered through Celite, washed with chloroform and the filtrate was evaporated. The crude product was purified by flash chromatography (10% methanol in chloroform) to give 5d as colorless prisms (93% yield): mp (methanol) 108-109 ° C; ?? RJN (CDC13) d 1.67 (m, 4H), 3.52 (q, 2H, J) 11.5, 5.6) 3.72 (t, 2H, J) 5.8 Hz), 6.65 (br s, 1H), 6.82 (s, 1H) , 7.11 (d, 1H, J) 8.0 Hz), 7.29 (m, 1H), 7.39 (d, 1H, J) 7.7 Hz), 7.59 (d, 1H, J) 7.8 Hz), 9.25 (br s, 1H ). Anal. (Ci3H16N202) C, H, N. N- [1- (4-Bromo) bu il] indole-2-carboxamide (6d). To a stirred solution of 5d (170.0 mg, 0.73 mmol) in acetonitrile (25.0 mL), triphenylphosphine (0.86 g, 3.22 mmol) and carbon tetrabromide (1.06 g, 3.22 mmol) were added at room temperature. After 2 h, the mixture was quenched with 15% NaOH and extracted with ethyl acetate. The organic layers were dried and evaporated. The residue was purified by flash chromatography (20% n-hexane in ethyl acetate) to provide 6b as colorless prisms (84% yield): mp (ethyl acetate) 133-134 ° C; X H NMR (CDC13) d 1.96 (m, 4 H), 3.56 (m, 4 H), 7.28 (m, 5 H), 7.60 (d, 1 H, J) 7.6 Hz), 9.80 (br s, 1 H). Anal. (Ci3Hi5BrN20) C. H. N.

N- [4- [4- (3-Trifluoromethylphenyl) piperazin-1-yl] butyl] indole-2-carboxamide (lp). Starting at 6d (35.0 mg, 0.12 mmol) and (3-trifluoromethyl) phenylpiperazine (27.3 mg, 0.12 mmol), the title compound was prepared following the procedure described for lg and was obtained as a yellow oil (56.0% yield). ). 1 H NMR (CDC13) d 1.82 (m, 4 H), 2.43 (m, 2 H), 2.57 (m, 4 H), 3.21 (m, 4 H), 3.54 (m, 2 H), 6.58 (m, 1 H), 6.83 (m s, 1H), 7.11 (m, 3H), 7.31 (m, 2H), 7.45 (d, 1H, J = 8.0 Hz), 7.61 (d, 1H, J = 7.9 Hz). 10.08 (br s, 1H); ES-MS m / z 445 [M + H] +. Anal. (C24H27F3N4O) C, H, N.

N- [2- (lH-indol-3-yl) ethyl] -3- (4-m-tolyl-piperazin-1-yl) propanamide (Compound 1-17 / lq) N- [2- (lH-indol-3-yl) ethyl] -3-bromopropanamide (27). To a solution of tryptamine (1.0 g, 6.24 mmol) in dry dichloromethane (10.0 mL), 3-bromopropanoyl chloride (691.0 μ ?, 6.86 mmol) and triethylamine (870.0 μ ?, 6.24 mmol) were added and the solution was stirred in a microwave oven for 1 minute at 200 W. After the solvent was evaporated, water was added to the residue and extracted with EtOAc (3 x 20 mL). The crude product was purified by flash chromatography (10% methanol in chloroform) to give 27 as a white solid (22.0% yield): mp (EtOAc) = 106-107 ° C. XH NMR (CDC13) d 2.64 (t, 2H, J = 6.4 Hz), 2.98 (t, 2H, J = 6.6 Hz), 3.56 (m, 4H), 5.61 (br s, 1H), 7.06 (m, 1H ), 7.18 (m, 2H), 7.36 (d, 1H, J = 7.9 Hz), 7.60 (d, 1H, J = 7.6 Hz), 8.10 (br s, 1H); ES-MS m / z 319 [M + Na] +, 295 [M + H] +. Anal. Anal. (Ci3Hi5BrN20) C, H, N.

N- [2- (lH-indol-3-yl) ethyl] -3- (4-m-tolylpiperazin-1-yl) propanamide (lq). To a stirred solution of 27 (200.0 mg, 0.68 mmol) in dry acetonitrile (20.0 mL) under argon, 1- (m-tolyl) piperazine dihydrochloride (0.68 mmol) and triethylamine (141.0 μ ?, 1.0 mmol) were added; the solution was refluxed overnight while stirring. The solvent was removed under reduced pressure, water was added and the mixture was extracted with dichloromethane (3 x 10 mL). The organic layers were dried and concentrated and the crude product was chromatographed (10% methanol in chloroform) to give lq (50% yield) as a white amorphous solid. 1 H NMR (CDC13) d 2.23-2.41 (m, 9H), 2.51 (m, 2H), 2.74 (m, 4H), 2.96 (t, 2H, J = 6.5 Hz), 3.64 (q, 2H, J = 6.3 j Hz), 6.60 (m, 2H), 6.69 (m, 1H), 6.98-7.28 (m (5H), 7.58 (m, 1H), 8.09 (br s, 1H), 8.20 (br s, 1H); ES-MS m / z 413 [M + Na] +, 391 [M + H] + Anal. (C24H3ON4O) C, H, N.

N- [2- (1H-indol-3-yl) ethyl] -3- [4- (3-methoxyphenyl) piperazin-1-yl] propanamide (Compound 1-18 / Ir) N- [2- (1H-indol-3-yl) ethyl] -3- [4- (3-methoxyphenyl) piperazin-1-yl] propanamide (Ir). Beginning from 27 (100.0 mg, 0.34 mmol) and (3-methoxy) phenylpiperazine (0.34 mmol), the title compound was prepared following the procedure described for lq and was obtained as a white amorphous solid (47.0% yield). XK NMR (CDC13) d 2.33 (m, 6H), 2.46 (m, 2H), 2.73 (m, 4H), 2.95 (m, 2H), 3.62 (m, 2H), 3.79 (s, 3H), 6.38 ( m, 3H), 6.97 (s, 1H), 7.03-7.27 (m, 4H), 7.57 (d, 1H, J = 7.4 Hz), 8.24 (br s, 1H), 8.48 (br s, 1H). Anal. (C24H30N4O2) C, H, N.

(S) - (-) - N- [4- [4- (m-Tolyl) piperazin-1-yl] butyl] -1,2,4,4-tetrahydroisoquinoline-2-carboxamide (Compound 1-19 / ls ) (S) - (-) -1- (benzyloxycarbonyl) -1,2,3,4-tetrahydroquinoline-2-carboxylic acid 2-methyl ((S) -30). To a solution of amino ester (8) -28 (160.0 mg, 0.84 mmol) in aqueous NaHCO 3 (2M), benzyl chloroformate (158.2 mg, 0.92 mmol) was added dropwise in 30 min. The mixture was stirred for 1.5 h at room temperature then evaporated. The residue was extracted with EtOAc (3 x 20 mL) and the organic layers were dried and evaporated. The crude product was purified by flash chromatography (20% acetone in n-hexane) to give the compound (S) -30 as a colorless oil (80% yield). [a] 20 D = -50.0 ° (c = 0.94, MeOH); TH R (CDC13) d 1.81 (m, 1H), 2.31-2.43 (m, 1H), 2.43-2.69 (m, 2H), 3.61 (s, 3H), 4.96 (t, 1H, J = 7.6 Hz), 5.24 (s, 2H), 6.97-7.08 (m, 2H), 7.16-7.23 (m, 1H), 7.24-7.35 (m, 5H), 7.81 (d, 1H, J = 7.4 Hz); ESI-MS m / z 325 [M +], 281, 266, 222, 190, 130, 91. Anal. (C19H19NO4) C, H, N.

(S) - (-) -1- (Benzyloxycarbonyl) -1,2,4,4,4-tetrahydroquinoline-2-carboxylic acid [(S) -31]. To a solution of (S) -30 (218.5 mg, 0.67 mmol) in methanol and water (3: 2) was added NaOH (27.0 mg, 0.67 mmol) and the mixture was heated to reflux for 2 h. After the solvents were evaporated, water was added to the residue and the mixture was acidified with 1 N HC1. The aqueous layer was extracted with chloroform (3 x 15 mL) and the collected organic layers were dried and evaporated. The crude product was purified by flash chromatography (CHCl3 / MeOH / CH3COOH 9: 1: 0.1) to give (S) -31 as an amorphous solid and in quantitative yield. XH RM (CDC13) d 1.81-1.99 (m, 1H), 2.31-2.43 (m, 1H), 2.46-2.69 (m, 2H), 3.61 (s, 3H), 4.96 (t, 1H, J = 7.6 Hz ), 5.24 (s, 2H), 6.97-7.08 (m, 2H), 7.16-7.23 (m, 1H), 7.24-7.35 (m, 5H), 7.81 (d, 1H, J = 7.4 Hz); ESI-MS m / z 310 [M] + (100), 266, 202. Anal. (Ci8H17N04) C, H, N. [] 20D-50 ° (c = 0.98, MeOH).

(S) - (-) - N - [4- (1-Hydroxy) butyl] -1- (benzyloxycarbonyl) -1,2,4,4-tetrahydroisoquinoline-2-carboxamide [(S) -32]. To an acid in solution (S) -31 (980.5 mg, 3.15 mmol) in dry dichloromethane (20.0 mL), 1-hydroxybenzotriazole hydrate (HOBT) (920.0 mg, 6.80 mmol) and 1,3-dicyclohexylcarbodiimide (1.40 g, 6.80 mmol) were added at 0 ° C under argon; the suspension was warmed to room temperature and stirred for 1 h. Then 4-amino-1-butanol (0.56 mL, 6.16 mmol) was added and the mixture was stirred overnight at room temperature. The resulting suspension was filtered through Celite®, washed with chloroform (3 x 25 mL) and the filtrate was evaporated. The crude product was purified by flash chromatography (10% methanol in chloroform) to give (S) -32 as a colorless oil (84% yield). XH NMR (CDC13) d 1.17-1.40 (m, 4H), 2.03-2.32 (m, 2H), 2.50-2.74 (m, 2H), 3.11 (m; 2H), 3.36-3.43 (m, 2H), 4.92 (t, 1H, J = 6.8 Hz), 5.12-5.27 (m, 2H), 6.43 (br s, 1H), 6.96-7.17 (m, 3H), 7.31 (m, 5H), 7.63 (d, 1H, J = 8.10 Hz); ESI-MS m / z 405 [M + Na] + (100); MS / MS (405) m / z 361, 270. [] 20D 41.9 ° (c = 1.56, CHCl3). Anal. (C22H26N2O4) C, H, N.

(S) - (-) - N- [4- (1-Bromo) butyl] -1- (benzyloxycarbonyl) -1,2,4,4-tetrahydroisoquinoline-2-carboxamide [(S) -33]. ? a vigorously stirred solution of (S) -32 (1.0 g, 2.62 mmol) in dry acetonitrile (50.0 mL), triphenylphosphine (0.86 g, 3.22 mmol) and carbon tetrabromide (1.06 g, 3.22 mmol) were added at room temperature. After 2 h, the mixture was quenched with 15% NaOH and the heterogeneous mixture was extracted with ethyl acetate (EtOAc) (3 x 25 mL). The organic layers were dried and evaporated. The residue was chromatographed (20% n-hexane in ethyl acetate) to give 0.58 g (91% yield) of (S) -33 as a yellow oil (33% yield). 1 H NMR (CDC13) d 1.34-1.61 (m, 4H), 2.15-2.26 (m, 2H), 2.57-2.78 (m, 2H), 3.02-3.30 (m, 4H), 5.00 (t, 1H, J = 6.70 Hz), 5.14-5.30 (m, 2H), 6.07 (br s, 1H), 6.99-7.21 (m, 3H), 7.33 (m, 5H), 7.61 (d, 1H, J = 8.02 Hz); ESI-MS m / z 467 [M + Na] +. [] 20D -50.9 ° (e = 0.53, CHCI3) · Anal. (C22H25BrN203) C, H, N.

(S) - (-) - N- [4- [4- (m-Tolyl) piperazin-1-yl] butyl] -2- (benzyloxycarbonyl) -1,2,3,4-tetrahydroisoquinoline-2-carboxamide [ (S.) -34a] To a stirred solution of (S) -33 (180.4 mg, 0.40 mmol) in dry acetonitrile (10.0 mL) under argon, 1- (m-tolyl) iperazine dihydrochloride (150.9) was added. mg, 0.40 mmol) and triethylamine (62.0 μl, 0.46 mmol) and the solution was refluxed overnight with stirring, the solvent was removed under reduced pressure, water was added and the mixture was extracted with dichloromethane (3 x 30 mL) The organic layers were dried and concentrated and the crude product was chromatographed (6% methanol in chloroform) to give (S) -34a as a yellow oil (40% yield) XH NMR (CDC13) d 1.25-1.37 (m, 4H), 2.15-2.33 (m, 7H), 2.47-2.57 (m, 4H), 2.62-2.79 (m, 2H), 3.12-3.27 (m, 6H), 4.97 (t, 1H, J = 6.65 Hz), 5.16-5.31 (m, 2H), 6.12 (br s, 1H), 6.65-6.73 (m, 3H), 7.03-7.24 (m, 3H), 7.34 (m, 5H), 7.64 (d, 1H, J = 8.10 Hz). [a] 20D = -34.3 ° (c = 1.75, CHC13). Anal. (C33H4o 403) C, H, N.

(S) - (-) - N- [4- [4- (m-Tolyl) piperazin-1-yl] butyl] -1,2,3,4-tetrahydroisoquinoline-2-carboxamide (ls). To a solution of (S.) - 34a (50.0 mg, 0.15 mmol) in methanol and EtOAc (1: 1), catalytic Pd was added on 5% carbon under argon and the suspension was hydrogenated at 60 psi (4.13 bar). ) for 8 h The mixture was then filtered through Celite® and the filtrate was evaporated The crude product was subjected to chromatography (10% methanol in chloroform) to give ls as a colorless oil (90% yield). XH RM (CDC13) d 1.20-1.58 (m, 4H), 1.86-1.95 (m, 4H), 2.19-1.37 (m, 3H), 2.39-2.46 (m, 2H), 2.57-2.77 (m, 4H) , 3.22-3.33 (m, 6H), 3.64-3.84 (m, 1H), 6.63-6.73 (m, 3H), 6.96-7.03 (m, 2H), 7.07-7.18 (m,); ESI-MS m / z 407 [M] + (100); MS / MS (407) m / z 300, 276, 258, 248, 231, 189, 177, 161, 132. [a] 20D = -42.1 ° (c = 1.26, MeOH) Anal. (C25H34N4O) C, H, N.

(R) - (+) - N- [4- [4- (m-Tolyl) piperazin-1-yl] butyl] -1,2,3,4-tetrahydroisoquinoline-2-carboxamide (Compound 1-20 / lt ) (R) - (+) -1- (Benzyloxycarbonyl) -1,2, 3,4-tetrahydropylin-2-carboxylic acid [(R.) .31] The title compound was prepared starting from (R ) -29 (1.30 g, 7.34 mmol) and following the procedure described to obtain (S) -31 Compound (R) -29 was obtained as a colorless oil (81% yield) XH NMR (CDC13) d 1.85 -1.99 (m, 1H), 2.35-2.50 (m, 1H), 2.58-2.79 (m, 2H), 4.99 (t, 1H, J = 7.74 Hz), 5.19-5.34 (m, 2H), 6.99-7.10 (m, 2H), 7.18-7.25 (m, 1H), 7.32-7.38 (m, 5H), 7.78 (d, 1H, J = 7.92 Hz), 9.94 (br s, 1 H). [a] 20D + 44.6 ° (c = 0.74, MeOH) Anal. (Ci8H17N04) C, H, N (R) - (+) - N - [4- (l-Hydroxy) butyl] -1- (benzyloxycarbonyl) -1,2,4,4-tetrahydroisoquinoline-2-carboxamide [(R) -32]. The title compound was prepared starting from (R) -31 (418.2 mg, 1.34 mmol) and following the procedure described to obtain (S) -32. Compound (R) -32 was obtained as a colorless oil (72% yield). H NMR (CDCl 3) d 1.21-1.40 (m, 4H), 2.01-2.10 (m, 1H), 2.14-2.28 (m, 1H), 2.56-2.74 (m, 2H), 2.82 (br s, 1H), 3.10-3.13 (m, 2H), 3.40-3.45 (m, 2H), 4.87-4.94 (m, 1H), 5.11-5.26 (m, 2H), 6.51 (br s, 1H), 6.95-7.17 (m, 3H), 7.30 (m, 5H), 7.64 (d, 1H, J = 8.14 Hz); ESI-MS m / z 405 [M + Na] + (100), 267. [a] 20 D + 50 ° (c = 1.94, CHCl 3). Anal. (C22H26 2O4) C, H, N.

(R) - (+) - N - [4- (1-Bromo) butyl] -1- (benzyloxycarbonyl) -1,2,4,4-tetrahydroisoquinoline-2-carboxamide [(R) -33]. The title compound was prepared starting from (R) -32 (368.9 mg, 0.97 mmol) and following the procedure described to obtain (S) -33. The compound (R) -33 was obtained as a colorless oil (33% yield). XH NMR (CDCl 3) d 1.40-1.64 (m, 4H), 2.20-2.31 (m, 2H), 2.62-2.80 (m, 2H), 3.07-3.28 (m, 4H), 4.99 (t, 1H, J = 6.67 Hz), 5.16-5.31 (m, 2H), 6.07 (br s, 1H), 7.04-7.21 (m, 3H), 7.34 (m, 5H), 7.62 (d, 1H, J = 8. 06 Hz); [a] 20D + 50.9 ° (c = 0.15, CHCl3). Anal. (C22H25BrN203) C, H, N.

(R) - (+) - N - [4- [4- (m-Tolyl) piperazin-1-yl] butyl] -2- (benzyloxycarbonyl) -1, 2, 3, 4-tetrahydroisoguinoline-2-carboxamide [ (R) -34a]. The title compound was prepared starting from (R) -33 (70.0 mg, 0.16 mmol) and (m-tolyl) piperazine dihydrochloride (39 mg, 0.16 mmol) following the procedure described to obtain (S) -34a. The compound (R) -34a was obtained as a colorless oil (40% yield). XH NMR (CDC13) d 1.25-1.46 (m, 4H), 2.16-2.28 (m, 4H), 2.31 (s, 3H), 2.48-2.58 (m, 4H), 2.64-2.80 (m, 2H), 3.12 -3.25 (m, 6H), 4.95-5.01 (m, 1H), 5.16-5.32 (m, 2H), 6.05 (br s, 1H), 6.66-6.73 (m, 3H), 7.04-7.21 (m, 3H) ), 7.25 (s, 1H), 7.35 (m, 5H), 7.63 (d, 1H, J = 8.11 Hz). [a] 20D = + 34.3 ° (c = 0.19, CHCI3). Anal. (C33H40N4O3) C, H, N.

(R) - (+) - N - [4- [4- (m-Tolyl) piperazin-1-yl] butyl] -1,2,4,4-tetrahydroisoquinoline-2-carboxamide (lt). The title compound was prepared starting from (R) -34a (50.0 mg, 0.15 mmol) following the procedure described to obtain ls. Compound lt was obtained as a colorless oil (85% yield). XH NMR (CDC13) d 1.20-1.58 (m, 4H), 1.86-1.95 (m, 4H), 2.19-1.37 (m, 3H), 2.39-2.46 (m, 2H), 2.57-2.77 (m, 4H) , 3.22-3.33 (m, 6H), 3.64-3.84 (m, 1H), 6.63-6.73 (m, 3H), 6.96-7.03 (m, 2H), 7.07-7.18 (m,); ESI-MS m / z 407 [M +] (100); MS / MS (407) m / z 300, 276, 258, 248, 231, 189, 177, 161, 132. [a] 20 D = + 42.1 ° (c = 1.26, MeOH). Anal. (C25H34N40) C, H, N.

(R) - (+) - N - [4- (4-phenylpiperazin-1-yl) butyl] -1,2,4,4-tetrahydroisoquinoline-2-carboxamide (Compound 1-21 / lu) () - (+) - N- [4- [4- (3-Chloro) phenylpiperazin-1-yl] butyl] -2- (benzyloxycarbonyl) -1,2,4,4-tetrahydroisoquinoline-2-carboxamide [( R) -34b]. The title compound was prepared starting from (R) -33 (140.0 mg, 0.31 mmol) and (3-chloro) phenylpiperazine hydrochloride (73.4 mg, 0.31 mmol) following the procedure described to obtain (S) -34a. The compound (R) -34b was obtained as a colorless oil (40% yield). XH RM (CDC13) d 1.25-1.36 (m, 4H), 2.20-2.45 (m, 4H), 2.48-2.59 (m, 4H), 2.64-2.80 (m, 2H), 3.12-3.21 (m, 6H), 4.98 (t, 1H, J = 6.65 Hz), 5.16-5.31 (m , 2H), 6.02 (br s, 1H), 6.74-6.85 (m, 3H), 7.04-7.21 (m, 3H), 7.25 (s, 1H), 7.34 (m, 5H), 7.63 (d, 1H, J = 7.97 Hz); ESI-MS m / z 584 [M + Na +], 561 [M + H +] (100), 508. Anal. (C32H3-7N4O3) C, H, N. [] 20D + 31 ° (c = 0.19, CHCI3). Anal. (C32H37C1N403) C, H, N.

(R) - (+) - N - [4- (4-Phenylpiperazin-1-yl) butyl] -1,2,3,4-tetrahydroisoquinoline-2-carboxamide (1). The title compound was prepared starting from (R) -34b (50.0 mg, 0.15 mmol) following the procedure described to obtain ls. The compound lu was obtained as a colorless oil (92% yield). XH NMR (CDC13) d 1.49-1.53 (m, 4H), 1.79-1.95 (m, 2H), 2.24-2.46 (m, 2H), 2.48-2.61 (m, 5H), 2.65-2.78 (m, 1H) , 3.13-3.18 (m, 4H), 3.24-3.33 (m, 2H), 3.93-4.00 (m, 1H), 6.59-6.74 (m, 2H), 6.80-7.06 (m, 5H), 7.20-7.28 ( m, 2H). ESI-MS m / z 393 [M +] (100), 132. Anal (C 24 H 32 N 4 O) C, H, N. [a] 20 D = + 41.66 ° (c = 0.24, CHCl 3). Anal. (C23H30N4O) C, H, N.

N- (4- (4- (Phenylpiperazin-1-yl) butyl) benzo [b] furan-2-carboxamide (Compound 1-22) Starting from ?? and 1-phenylpiperazine, the title compound was prepared following the procedure described to obtain 17. Compound 122 was obtained as a white solid (70% yield): mp (methanol) 149-150 ° C; XH RM, 300 MHz, (CDC13) d 1.71 (m, 4H), 2.47 (m, 2H), 2.64 (m, 4H), 3.24 (m, 4H), 3.53 (m, 2H), 6.89 (m, 3H) ), 7.02 (br s, 1H), 7.28 (m, 3H), 7.39 (m, 1H), 7.46 (m, 2H), 7.66 (m, 1H). ESI-MS m / z 400 [M + Na +], 377 [M + H +] (100). Anal. (C23H27N302) C, H, N.N- (4- (4- (2,3-Dimethylphenyl) piperazin-1-yl) butyl) benzo [b] furan-2-carboxamide (Compound 1-23) Starting from 1 \ and 4- (2,3-dimethylphenyl) piperazine, the title compound was prepared following the procedure described to obtain 17. Compound 123 was obtained as a white solid (73% yield): mp ( methanol) 151-152 ° C. X H NMR, 200 MHz, (CDC13) d 1.73 (m, 4 H), 2.21 (s, 3 H), 2.25 (s, 3 H), 2.47 (m, 2 H), 2.62 (m, 4 H), 2.93 (m, 4 H) ), 3.52 (m, 2H), 6.87 (m, 2H), 7.05 (m, 2H), 7.35 (m, 3H), 7.64 (m, 1 H). ESI-MS m / z 428 [M + Na +], 406 [M + H +] (100). Anal. (C25H31N3O2) C, H, N.

N- (4- (4- (3-Methoxyphenyl) piperazin-1-yl) butyl) benzo [b] furan-2-carboxamide (Compound 1-24) Starting from T1 and 4- (3-methoxyphenyl) piperazine, the title compound was prepared following the procedure described to obtain 17. Compound 124 was obtained as a white solid (70% yield): mp (methanol) 104 -105 ° C. 1 H NMR, 200 MHz, (CDC13) d 1-62 (m, 4 H), 2.40 (m, 2 H), 2.56 (m, 4 H), 3.19 (m, 4 H), 3.49 (m, 2 H), 3.74 (s) , 3H), 6.44 (m, 3H), 7.25 (m, 5H), 7.61 (m, 1H). ESI-MS m / z 430 [M + Na +], 408 [M + H +] (100). Anal. (C24H29N3O3) C H, N.

Experimental procedure for compound 1-25 125NF862 Ter-butyl-4- (6-methylpyridin-2-yl) piperazine-l-carboxylate (32) In a sealed tube, 2-bromo-6-methylpyridine (461 mg, 2.68 mmol) Pd2 (dba) 2 (2%), BINAP (4%), and sodium t-butoxide (386.4 mg, 4.02 mmol) were added. to N-Boc-piperazine (500 mg, 2.68 mmol) and the solids were dissolved in dry toluene (5 mL). The mixture was stirred at 70 ° C for 90 min., Filtered over Celite®, washing with ethyl acetate and the organic layer was evaporated under reduced pressure. The crude was purified by flash chromatography (40% ethyl acetate in hexane) to give 32 as a pale yellow solid (95% yield): mp (methanol) 84-85 ° C; XH NMR, 200 MHz, (CDC13) d 1.41 (s, 9H), 2.31 (s, 3H), 3.42 (m, 8H), 6.37 (m, 2H), 7.28 (m, 1H). ESI-MS m / z 300 [M + Na +], 278 [M + H +] (100). Anal. (Ci5H23 302) C, H, N. 1- (6-Methylpyridin-2-yl) piperassin trifluoroacetate (4i). Trifluoroacetic acid (4 mL) was added at 32, cooling in an ice bath, and the mixture was stirred for 60 minutes at room temperature. The crude was concentrated and washed with diethyl ether until the solid became colorless.

N- (4- (4- (6-ethylpyridin-2-yl) piperazin-1-yl) butyl) isoquinoline-3-carboxamide (Compound 1-25). Starting from 72 and 4i, the title compound was prepared following the procedure described to obtain 13. Compound 125 was obtained as a white solid (70% yield): mp (methanol) 124-125 ° C. X H R, 200 MHz, (CDC13) d 1.71 (m, 4 H), 2.38 (s, 3 H), 2.47 (m, 2 H), 2.56 (m, 4 H), 3.55 (m, 6 H), 6.44 (m, 2 H) ), 7.30 (m, 1H), 7.72 (m, 2H), 8.00 (m, 2H), 8.33 (br s, 1H), 8.60 (m, 1H), 9.14 (m, 1H). ESI-MS m / z 426 [M + Na +], 404 [M + H +] (100). Anal (C24H29N50) C, H, N.

N- (4- (4-Phenyl-piperazin-1-yl) butyl) -isoquinoline-3-carboxamide (Compound 1-26) 126. NF863 Starting from 72 and 1-phenylpiperazine, the title compound was prepared following the procedure described to obtain 13. Compound 126 was obtained as a white solid (76% yield): mp (methanol) 153-154 ° C. X H NMR, 300 MHz, (CDCl 3) d 1.71 (m, 4 H), 2.46 (m, 2 H), 2.62 (m, 4 H), 3.21 (m, 4 H), 3.57 (m, 2 H), 6.88 (m, 3 H) ), 7.26 (m, 2H), 7.72 (m, 2H), 8.00 (m, 2H), 8.36 (br s, 1H), 8.61 (m, 1H), 9.14 (m, 1 H). ESI-MS m / z 411 [M + Na +], 389 [M + H +] (100). Anal. (C24H28 4O) C, H, N.

N- (4- (4- (6-Methylpyridin-2-yl) piperazin-1-yl) butyl) benzofuran-2-carboxamide (Compound 1-27) Starting from 7i and 4 ?, the title compound was prepared following the procedure described to obtain 17. Compound 127 was obtained as a white solid (75% yield): mp (methanol) 107-109 ° C. 1 H NMR, 200 MHz, (CDC13) d 1.70 (m, 4 H), 2.39 (s, 3 H), 2.45 (m, 2 H), 2.58 (m, 4 H), 3.54 (m, 6 H), 6.45 (m, 2 H) ), 7.02 (br s, 1H), 7.35 (m, 5H), 7.65 (m, 1H). ESI-MS m / z 415 [M + Na +], 393 [M + H +] (100). Anal (C23H28N402) C, H, N.

Experimental procedure for the compound Ter-butyl-4- (naphthalen-1-yl) piperazine-1-carboxylate O 3).

Starting from 1-bromonaphthalene (200 mg, 0.97 mmol) the title compound was prepared following the procedure described to obtain 32: XH NMR, 200 MHz, (CDC13) d 1.55 (s, 9H), 3.05 (m, 4H ), 3.72 (m, 4H), 7.05 (m, 1H), 7.49 (m, 4H), 7.82 (m, 1H), 8.22 (m, 1 H). ESI-MS m / z 335 [M + Na +], 313 [M + H +] (100). Anal. (Ci9H24 202) C, H, N.

Trifluoroacetate of 1- (naphthalen-1-yl) piperazine (42). Starting from 33, the title compound was prepared following the procedure described to obtain 4 ?.

N- (4- (4- (Naphthalen-1-yl) piperazin-1-yl) butyl) benzamide (Compound 1-28). Starting from 75 and 42, the title compound was prepared following the procedure described to obtain 13. Compound 128 was obtained as a yellow oil (70% yield): X H NMR, 200 MHz, (CDCl 3) d 1.68 ( m, 4H), 2.49 (m, 4H), 2.70 (m, 4H), 3.34 (m, 2H), 7.01 (m, 2H), 7.43 (m, 6H), 7.78 (m, 3H), 8.18 (m , 1 HOUR) . ESI-MS m / z 410 [M + Na +], 388 [M + H +], (100). Anal (C25H29N30) C, H, N.

N- (4- (4-Phenylpiperazin-1-yl) butyl) quinoline-2-carboxamide (Compound 1-29) 129. NF872 Starting from 72 and 1-phenylpiperazine, the title compound was prepared following the procedure described to obtain 13. Compound 129 was obtained as a white solid (70% yield): mp (methanol) 120-121 ° C. X H NMR, 200 MHz, (CDC13) d 1.69 (m, 4 H), 2.46 (m, 2 H), 2.61 (m, 4 H), 3.20 (m, 4 H), 3.56 (m, 2 H), 6.86 (m, 3 H) ), 7.24 (m, 2H), 7.59 (m, 1H). 7.75 (m, 1H), 7.85 (m, 1H), 8.09 (m, 1H), 8.29 (m, 2H). ESI-MS m / z 411 [M + Na +], 389 [M + H +] (100). Anal (C24H28N40) C, H, N.

N- (4- (4-M-Tolyl-piperazin-1-yl) butyl) quinoline-2-carboxamide (Compound 1-30) 130. NF874 Starting from 72 and 4- (3-methylphenyl) piperazine, the title compound was prepared following the procedure described to obtain 13. Compound 13 was obtained as a yellow oil: ½ NMR, 200 MHz, (CDC13) d 1.72 (m, 4H), 2.30 (s, 3H), 2.47 (m, 2H), 2.61 (m, 4H), 3.19 (m, 4H), 3.47 (m, 2H), 6.69 (m, 4?), 7.11 (m, 1?), 7.59 (mi 1H), 7.75 (mi 1H), 7.85 (m, 1H), 8.09 (m, 1H), 8.33 (m, 2H). ESI-MS m / z 403 [M + H +] (100). Anal (C25H30N4O) C, H, N.

N- (4- (4- (3-Methoxyphenyl) piperazin-1-yl) butyl) -1-methyl-1 H -indole-2-carboxamide (Compound 1-31) Starting from 77 and 4- (3-methoxyphenylDiperazine, the title compound was prepared following the procedure described to obtain 13. Compound I31 was obtained as a white solid (60% yield): mp (methanol) 141-142 ° C. XH RM, 200 MHz, (CDC13) d 1.69 (m, 4H), 2.48 (m, 2H), 2.65 (m, 4H), 3.08 (m, 4H), 3.47 (m, 2H), 3.84 ( s, 3H), 4.03 (s, 3H), 6.90 (m, 5H), 7.16 (m, 1H), 7.32 (m, 2H), 7.60 (m, 1 H) ESI-MS m / z 421 [M + H +] (100) Anal (C25H32N4O2) C, H, N.

Experimental procedure for compound 1-32 132. NF876 4- (4- (3-Methoxyphenyl) piperazin-1-yl) butanitrile. (37) To a stirred solution of 1- (3-methoxyphenyl) piperazine (36) (100.0 mg, 0.52 mmol) in acetonitrile (10.0 mL), 4-bromobutanitrile (84.7 mg, 0.57 mmol) and potassium carbonate (101.6 mg, 0.78 mmol) ) were added at room temperature. The mixture was heated to reflux overnight then filtered and evaporated. The crude product was purified by flash chromatography (10% methanol in chloroform) to give 98.0 mg (73% yield) of 37 as a yellow oil: ?? KMN, 200 MHz, (CDC13) d 1.83 (m, 2H), 2.49 (m, 8H), 3.17 (m, 4H), 3.77 (s, 3H), 6.48 (m, 3H), 7.16 (m, 1H) . ESI-MS m / z 282 [M + H "] 260 [M + H *] (100) Anal (Ci5H21N30) C, H, N. 4- (4- (3-Methoxyphenyl) piperazin-1-yl) butan-1-amine. (38) To a stirred solution of 37 (300.0 mg, 1.16 mmol) in dry methanol (15.0 mL), at 0 ° C, nickel (II) chloride hexahydrate (28.0 mg, 0.12 mmol) and sodium borohydride (307.2 mg, 8.12 mmol). The mixture was stirred at room temperature for 90 min., then filtered over Celite®, washing with methanol, and the filtrate was evaporated under reduced pressure. The residue was extracted with EtOAc (3 x 30 mL), the organic layers were dried and concentrated and the crude product was chromatographed (15% n-hexane in EtOAc) to give 38 (60% yield): XH NMR, 200 MHz, (CDC13) d 1.54 (m, 4H), 2.40 (m, 4H), 2.58 (m, 4H), 3.19 (m, 4H), 3.76 (s, 3H), 6.46 (m, 3H) , 7.16 (m, 1 H). ESI-MS m / z 286 [M + H +] 264 [M + H +] (100). Anal (C15H25N3O) C, H, N.

IH-indol-3-carbonyl chloride (40). To a solution of lH-indole-3-carboxylic acid (39) (100.0 mg, 0.6 mmol) in dry benzene (2.0 mL), thionyl chloride (130.0 μ, 1.80 mmol) was added and the mixture was heated to reflux for 120 minutes. The crude was washed with benzene (2 x 10 mL) and evaporated to give 40 in quantitative yield. 1 H NMR, 200 MHz, (CDCl 3) d 10.85 (br s, 1 H), 8.20 (m, 1 H), 7.48 (m, 1 H), 7.30 (m, 1 H), 7.19 (m, 1 H), 7.03 (m, 1 HOUR) . Anal (C9H6C1N0) C, H, N.

N- (4- (4- (3-Methoxyphenyl) piperazin-1-yl) butyl) -lH-indole-3-carboxamide (Compound 1-32). To a stirred solution of 40 (100.0 mg, 0.6 mmol) and 37 (158.0 mg, 0.6 mmol) was added dry dichloromethane (15.0 mL), pyridine (145) iL, 1.8 mmol). The mixture was stirred at room temperature overnight. A solution of saturated sodium bicarbonate was added and the mixture was extracted with EtOAc (3 x 15 mL), dried and evaporated. The crude product was purified by flash chromatography (10% methanol in chloroform) to give I32 (50% yield) as a white solid: mp (methanol) 154-155 ° C. X H NMR, 200 MHz, (CDC13) d 1.65 (m, 4 H), 2.41 (m, 2 H), 2.56 (m, 4 H), 3.13 (m, 4 H), 3.50 (m, 2 H), 3.77 (s, 3 H) ), 6.45 (m, 2H), 7.19 (m, 3H), 7.38 (m, 1H), 7.66 (m, 1H), 7.95 (m, 1H), 9.79 (br s, 1H). ESI-MS m / z 429 [M + Na +], 407 [M + H +] (100). Anal (C24H30N4O2) C, H, N.

N- (4- (4-Benzylpiperazin-1-yl) butyl) benzofuran-2-carboxamide (Compound 1-33) 1". NF877 Starting from 7i and 1-benzylpiperazine, the title compound was prepared following the procedure described to obtain 17. Compound 133 was obtained as a yellow oil (70% yield): X H NMR, 200 MHz, (CDCl 3) d 1.64 (m, 4H), 2.39 (m, 2H), 2.50 (m, 8H), 3.49 (m, 4H), 7.04 (br s, 1H), 7.36 (m, 10H), 7.65 (m, 1 H) . ESI-MS m / z 414 [M + Na +], 392 [M + H +] (100). Anal (C24H29 302) C, H, N. 7- (5- (4-Phenylpiperazin-1-yl) pentyloxy) pyrrolo [1,2,2-a] quinoxalin-4 (5H) -one (Compound 1-34) Beginning from 262 and 1-phenylpiperazine, the title compound was prepared following the procedure described to obtain li4. Compound 134 was obtained as an amorphous solid (60% yield). ?? NMR (CDC13) d 1.56 (m, 4H), 1.86 (m, 2H), 2.45 (m, 2H), 2.64 (m, 4H), 3.22 (m, 4H), 4.03 (m, 2H), 6.66 (m , 1H), 6.79 (m, 3H), 6.91 (m, 2H), 7.25 (m, 3H), 7.56 (m, 2H), 10.19 (br s, 1H). ESI-MS m / z 453 [M + Na +], 431 [+ H +] (100). Anal. (C26H30NO2) C, H, N.

(S) -1, 2, 3, 4-Tetrahydro-N- (4- (4-phenylpiperazin-1-yl) butyl) quinoline-2-carboxamide (Compound 1-35) Starting from (S.sup.) - 34 and 1-phenylpiperazine, the title compound was prepared following the procedure described to obtain 12 I. Compound I35 was obtained as an oil (70% yield): XH NMR (CDC13) d 1.25-1.36 (m, 4H), 2.20-2.45 (m, 4?), 2.482.59 (m, 4?), 2.64-2.80 (m, 2?), 3.12-3.21 (m, 6?), 4.98 (t, 1 ?, J = 6.65 Hz), 5.16-5.31 (m, 2H), 6.02 (br s, 1H), 6.74-6.85 (m, 3H), 7.04-7.21 (m, 3H), 7.25 ( s, 1H), 7.34 (m, 5H), 7.63 (d, 1H, J = 7.97 Hz), ESI-MS m / z 584 [M + Na +], 561 [M + H +] (100). [] 20D -31 ° (c = 0.18, CHC13) Anal. (C23H32N4O) C, H, N.

Experimental procedure for compound 1-36 ter-Butyl-4- (quinolin-3-yl) piperazine-1-carboxylate (34). Starting from 3-bromoquinoline, the title compound was prepared following the procedure described to obtain 4? . Compound 34 was obtained as a white solid: mp (methanol) 114-115 ° C. R, 200 MHz, (CDC13) d 1.46 (s, 9H), 3.18 (m, 4H), 7.28 (m, 1H), 7.43 (m, 2H), 7.63 (m, 1H), 7.96 (m, 1H) ), 8.74 (m, 1H). ESI-MS m / z 336 [M + Na +] (100). Anal. (Ci8H23N302) C, H (N. 3- (4-Methylpiperazin-1-yl) quinoline trifluoroacetate (43). Starting from 34, the title compound was prepared following the procedure described to obtain (4i).

N- (4- (4- (Quinolin-3-yl) piperazin-1-yl) butyl) benzamide (Compound 1-36). Starting from 75 and 43i the title compound was prepared following the procedure described to obtain 13. Compound 136 was obtained as a white solid (70% yield): mp (methanol) 124-125 ° C. ¾ NMR, 200 MHz, (CDC13) d 1.68 (m, 4H), 2.45 (m, 2H), 2.65 (m, 4H), 3.27 (m, 4H), 3.53 (m, 2H), 6.63 (br s, 1H), 7.38 (m, 6H), 7.65 (m, 1H), 7.75 (m, 2H), 7.97 (m, 1H), 8.76 (m, 1H). ESI-MS m / z 389 [M + H +] (100). Anal (C24H28N4O) C, H, N.

N- (4- (4-m-Tolylpiperazin-1-yl) butyl) picolinamide (Compound 1-37) Starting from 78 and 4- (3-methylphenyl) piperazine, the title compound was prepared following the procedure described to obtain 13. Compound 137 was obtained as a yellow oil (70% yield): XH NMR, 200 MHz , (CDC13) d 1.67 (m, 4H), 2.30 (s, 3H), 2.45 (m, 2H), 2.61 (m, 4H), 3.20 (m, 4H), 3.51 (m, 2H), 6.70 (m , 3H), 7.14 (m, 1H), 7.40 (m, 1H), 7.84 (m, 1H), 8.19 (m, 2H), 8.52 (m, 1 H). ESI-MS m / z 375 [M + Na +], 353 [M + H +] (100). Anal (C21H28 O) C, H, N. 7- (4- (4-Phenylpiperazin-1-yl) butoxy) pyrrolo [1,2-a] quinoxalin-4 (5H) -one (Compound 1-38) 13B.NF905 Starting from 26i and 1-phenylpiperazine, the title compound was prepared following the procedure described to obtain 114. Compound 138 was obtained as an amorphous solid (60% yield). XH NMR (CDC13) d 1.81 (m, 4H), 2.49 (m, 2H), 2.65 (m, 4H), 3.21 (m, 4H), 4.06 (m, 2H), 6.66 (m, 1H), 6.74 ( m, 3H), 6.89 (m, 2H), 7.23 (m, 3H), 7.56 (m, 2H), 10.27 (br s, 1H). ESI-MS m / z 440 [M + Na +], 417 [M + H +] (100). Anal. (C ^ s ^ C ^) C, H, N.

N- (4- (4- (quinolin-3-yl) piperazin-1-yl) butyl) isoquinoline-3-carboxamide (Compound 1-39) Starting from 72 and 43 (the title compound was prepared following the procedure described to obtain 13. Compound 139 was obtained as a white solid (70% yield): mp (methanol) 153-154 ° C. , 200 MHz, (CDC13) d 1.80 (m, 4H), 2.37 (m, 2H), 2.67 (m, 4H), 3.32 (m, 4H), 3.75 (m, 2H), 7.30 (m, 1H), 7.45 (m, 2H), 7.67 (m, 4H), 7.93 (m, 2H), 8.33 (br s, 1H), 8.60 (m, 1H), 8.78 (m, 1H), 9.12 (m, 1 H) ESI-MS m / z 462 [M + Na +], 440 [M + H +] (100) Anal (C27H29N50) C, H, N.

N- (4- (4- (3-Methoxyphenyl) piperazin-1-yl) butyl) -6-methylpyridine-2-carboxamide (Compound 1-40) Starting from 79 and 4- (3-methoxyphenyl) piperazine, the title compound was prepared following the procedure described to obtain 13. Compound I40 was obtained as a yellow oil (78% yield): XH NMR, 200 MHz , (CDC13) d 1.64 (m, 4H), 2.41 (m, 2H), 2.53 (s, 3H), 2.59 (m, 4H), 3.17 (m, 4H), 3.49 (m, 2H), 3.75 (s) , 3H), 6.45 (m, 3H), 7.17 (m, 2H), 7.67 (m, 1H), 7.97 (m, 1H), 8.14 (br s, 1H). ESI-MS m / z 405 [M + Na +], 383 [M + H +] (100). Anal (C22H3o 402) C, H, N.

N- (4- (4- (3-Methoxyphenyl) piperazin-1-yl) butyl) quinoline-3-carboxamide (Compound 1-41) Starting from and 4- (3-methoxyphenyl) piperazine, the title compound was prepared following the procedure described to obtain 13. Compound I41 was obtained as a yellow oil (78% yield): XH NMR, 200 MHz, (CDCl 3) d 1.63 (m, 4H), 2.41 (m, 2H), 2.56 (m, 4H), 3.15 (m, 4H), 3.54 (m, 2H), 3.73 (s, 3H), 6.43 (m, 4H), 7.13 (m, 1H), 7.55 (m (1H), 7.70 (m, 1H), 7.81 (m, 1H), 8.06 (m, 1H), 8.26 (m, 1H), 8.31 (br s, 1H) ESI-MS m / z 441 [M + Na +], 419 [M + H +] (100) Anal (C25H3oN402) C, H, N.

N- (4- (4- (Pyridin-2-yl) piperazin-1-yl) butyl) quinoline-3-carboxamide (Compound 1-42) Starting from 76 and 1- (pyridin-2-yl) piperazine, the title compound was prepared following the procedure described to obtain 13. Compound 142 was obtained as a yellow oil (70% yield): XH RN, 200 MHz, (CDC13) d 1.82 (ra, 4H), 2.39 (m, 2H), 2.50 (m, 4H), 3.52 (m, 6H), 6.55 (m, 2H), 7.40 (m, 1H), 7.53 (m, 1H), 7.69 (m, 1H), 7.80 (m, 1H), 8.17 (m, 5H). ESI-MS m / z 412 [M + Na +], 390 [M + H +] (100). Anal (C23H27N50) C, H, N.

N- (4- (4-Phenylpiperazin-1-yl) butyl) picolinamide (Compound 1-43) Starting from 78 and 1-phenylpiperazine, the title compound was prepared following the procedure described to obtain 13. Compound 13 was obtained as a yellow oil (82% yield): XH NMR, 400 MHz, (CDC13) d 1.63 (m, 4H), 2.39 (m, 2H), 2.56 (m, 4H), 3.17 (m, 4H), 3.47 (m, 2H), 6.80 (m, 1H), 6.88 (m, 2H), 7.21 (m, 2H), 7.35 (m, 1H), 7.78 (m, 1H), 8.16 (m, 1H), 8.48 (m, 1H). ESI-MS m / z 361 [M + Na +], 339 [M + H +] (100). Anal (C2oH26 40) C, H, N.

N- (4- (4- (3-Methoxyphenyl) piperazin-1-yl) butyl) icolinamide (Compound 1-44) Starting from 7a and 4- (3-methoxyphenyl) piperazine, the title compound was prepared following the procedure described to obtain 13. Compound 144 was obtained as a yellow oil (72% yield): XH NMR, 400 MHz , (CDC13) d 1.57 (m, 4H), 2.33 (m, 2H), 2.49 (m, 4H), 3.11 (m, 4H), 3.43 (m, 2H), 3.68 (s, 3H), 6.32 (m , 2H), 6.38 (ra, 1H), 6.45 (m, 1H), 7.07 (m, 1H), 7.30 (m, 1H), 7.72 (m, 1H), 8.11 (m, 1H), 8.43 (m, 1 HOUR) . ESI-MS m / z 369 [M + H +] (100). Anal (C2iH28N402) C, H, N.

N- (4- (4- (3-Methoxyphenyl) piperazin-1-yl) butyl) benzamide (Compound 1-45) Starting from 75 and 4- (3-methoxyphenyl) iperazine, the title compound was prepared following the procedure described to obtain 13. Compound I45 was obtained as a white solid (79% yield): mp (methanol) 111 -112 ° C: ½ RM, 400 MHz, (CDC13) d 1.62 (m, 4H), 2.39 (m, 2H), 2.54 (m, 4H), 3.13 (m, 4H), 3.42 (m, 2H), 3.75 (s, I 3 H), 6.40 (m, 2 H), 6.49 (m, 1 H), 6.83 (br s, 1 H), 7.14 (m, 1 H), 7.36 (m, 1 H), 7.44 (m, 1 H) 7.74 (m, 2H). ESI-MS m / z 390 [M + Na +], 368 [M + H +] (100). Anal (C22H29N3O2) C, H, N.

N- (4- (4-m-Tolylpiperazin-1-yl) butyl) benzamide (Compound 1-46) Starting from 75 and 4- (3-methylphenyl) piperazine, the title compound was prepared following the procedure described to obtain 13. Compound 146 was obtained as a white solid (77% yield): mp (methanol) 126 -127 ° C. XH NMR, 400 MHz, (CDC13) d 1.64 (m, 4H), 2.30 (s, 3H), 2.40 (m, 2H), 2.55 (m, 4H), 3.13 (m, 4H), 3.45 (m, 2H) ), 6.68 (m, 3H), 6.90 (br s, 1H), 7.13 (m, 1H), 7.37 (m, 2H), 7.43 (m, 1H), 7.75 (m, 2H). ESI-MS m / z 374 [M + Na +], 352 [M + H +] (100). Anal (C22H29 30) C, H, N.

N- (4- (4-Phenylpiperazin-1-yl) butyl) nicotinamide (Compound 1-) Beginning from 7i0 and 1-phenylpiperazine, the title compound was prepared following the procedure described to obtain 13. Compound 147 was obtained as a white solid (80% yield): mp (methanol) 119-120 ° C. XH RJN, 400 MHz, (CDC13) d 1.65 (m, 4H), 2.42 (m, 2H), 2.56 (m, 4H), 3.12 (m, 4H), 3.46 (m, 2H), 6.84 (m, 3H) ), 7.11 (br s, 1H), 7.23 (m, 2H), 7.31 (m, 1H), 8.07 (m, 1H), 8.65 (m, 1H), 8.94 (m, 1H). ESI-MS m / z 339 [M + H +] (100). Anal (C 20 H 26 4 O) C, H, N.

N- (4- (4- (6-Methylpyridin-2-yl) piperazin-1-yl) butyl) benzamide (Compound 1-48) Starting from 75 and 4i, the title compound was prepared following the procedure described to obtain 13. Compound 14e was obtained as a white solid (82% yield): mp (methanol) 102-103 ° C. 1H RN, 200 MHz, (CDC13) d 1.59 (m, 4H), 2.34 (m, 5H), 2.46 (m, 4H), 3.46 (m, 6H), 6.39 (m, 2H), 7.07 (br s, 1H), 7.33 (m, 4H), 7.73 (m, 2H). ESI-MS m / z 375 [M + Na +], 353 [M + H +] (100). Anal (C21H28 4O) C, H, N.

Experimental procedure for the compound Ter-butyl-4- (6-methoxypyridin-2-yl) piperazine-1-carboxylate (3s). Starting from 2-bromo-6-methoxypyridine, the title compound was prepared following the procedure described to obtain 32: XH NMR, 200 MHz, (CDC I3) d 1.42 (s, 9H), 3.19 (m, 4H), 3.73 (s, 3H), 3.79 (m, 4H), 5.70 (m, 1H), 5.90 (m, 1H), 7.44 (m , 1H), ESI-MS m / z 316 [M + Na +], 294 [M + H +] (100). Anal (C15H23N3O3) C, H, N. 1- (6-Methoxypyridin-2-yl) piperazine (^). Starting from 3s, the title compound was prepared following the procedure described to obtain 4 ?.

N- (4- (4- (6-Methoxypyridin-2-yl) piperazin-1-yl) butyl) benzamide (Compound 1-49). Starting from 75 and 44, the title compound was prepared following the procedure described to obtain 13. Compound I49 was obtained as a white solid (85% yield): mp (methanol) 120-121 ° C. XH RM, 200 MHz, (CDC13) d 1.61 (m, 4H), 2.37 (m, 2H), 2.47 (m, 4H), 3.43 (m, 6H), 3.81 (s, 3H), 6.06 (m, 2H) ), 6.85 (br s, 1H), 7.38 (m, 4H), 7.72 (m, 2H). ESI-MS m / z 391 [M + Na +], 369 [M + H +] (100). Anal (C2iH28N402) C, H, N.

N- (4- (4- (6-Methoxypyridin-2-yl) piperazin-1-yl) butyl) picolinamide (Compound 1-50) Starting from 78 and 44, the title compound was prepared following the procedure described to obtain 13. Compound I50 was obtained as a yellow oil (80% yield): XH NMR, 300 MHz, (CDC13) d 1.63 ( m, 4H), 2.37 (m, 2H), 2.48 (m, 4H), 3.47 (m, 4H), 3.80 (m, 3H), 6.05 (m, 2H), 7.34 (m, 2H), 7.77 (m , 1H), 8.14 (m, 2H), 8.47 (m, 1H). ESI-MS m / z 429 [M + Na +], 407 [M + H +] (100). ESI-MS m / z 376 [M + Na +], 354 [M + H +] (100). Anal (C20H27N5O2) C, H, N.

N- (4- (4- (6-Methylpyridin-2-yl) piperazin-1-yl) butyl) icolinamide (Compound 1-51) Starting from 78 and 4i, the title compound was prepared following the procedure described to obtain 13. Compound I51 was obtained yellow (90% yield): 1 H NMR, 300 MHz, (CDC13) d 1.58 (m, 4H ), 2.31 (m, 5H), 2.45 (m, 4H), 3.43 (m, 6H), 6.36 (m, 2H), 7.29 (m, 2H), 7.72 (m, 1H), 8.11 (m, 2H) 8.43 (m, 1H). ESI-MS m / z 376 [M + Na +], 354 [M + H +] (100). Anal (C20H27N5O) C, H (N.

Experimental procedure for compound 1-52 1, 6-Bis (4- (3-chlorophenyl) piperazin-1-yl) hexane (Compound 1-52). To a solution of 3-chlorophenylpiperazine (40d) (100.0 mg, 0.51 mmol) in dry acetonitrile (15.0 mL), 1,6-dibromohexane (34.72 μ?, 0.25 mmol) and TEA (71.1 μ ??, 0.51) were added. mmol) and the mixture was stirred at room temperature overnight. The crude was extracted with dichloromethane (3 x 10 mL), dried and evaporated. The residue was subjected to chromatography (10% methanol in chloroform) to yield 152 (90% yield) yellow: H RM, 200 MHz, (CDC13) d 1.37 (m, 4H), 1.52 (m, 4H), 2.37 (m, 4H), 2.57 (m, 8H), 3.20 (m, 8H), 6.77 (m, 4H), 6.86 (m, 2H), 7.14 (m, 2H). ESI-MS m / z 475 [M + H +] (100). Anal (C26H36C12N4) C, H, N. 1,6-Bis (4- (3-methoxyphenyl) piperazin-1-yl) hexane (Compound 1-53) Starting from 4- (3-methoxyphenyl) piperazine, the title compound was prepared following the procedure described to obtain 152. Compound 153 was obtained as a white solid (85% yield): mp (methanol) 109-110 ° C. X H NMR, 200 MHz, (CDC13) d 1.36 (m, 4 H), 1.54 (m, 4 H), 2.38 (m, 4 H), 2.58 (m, 8 H), 3.20 (m, 8 H), 3.77 (m, 8 H) ), 6.44 (m, 6H), 7.15 (m, 2H), ESI-MS m / z 467 [M + H +] (100). Anal (C28H42N402) C, H, N. 1,6-Bis (4-phenylpiperazin-1-yl) hexane (Compound 1-54) Starting from 1-phenylpiperazine the title compound was prepared following the procedure described to obtain I52- Compound 154 was obtained as yellow (95% yield): ?? NMR, 200 MHz, (CDCl 3) d 1.39 (m, 4 H), 1.57 (m, 4 H), 2.41 (m, 4 H), 2.62 (m, 8 H), 3.22 (m, 8 H), 6.89 (m, 6 H) , 7.27 (m, 6H). ESI-MS m / z 429 [M + Na +], 407 [M + H +] (100). Anal (C26H38N4) C, H, N. 1, 6-Bis (4- (pyridin-2-yl) piperazin-1-yl) hexane (Compound 1-55) Beginning from 1- (pyridin-2-yl) piperazine, the title compound was prepared following the procedure described to obtain I52. Compound I55 was obtained as a yellow oil: XH NMR, 400 MHz. (CDC13) d 1.32 (m, 4H), 1.50 (m, 4H), 2.32 (m, 4H), 2.49 (m, 8H), 3.50 ( m, 8H), 6.56 (m, 4H), 7.40 (m, 2H), 8.14 (m, 2H). ESI-MS m / z 431 [M + Na +], 409 [M + H +] (100). Anal (C24H36 6) C. H. N. 1,6-Bis (4-m-tolylpiperazin-1-yl) hexane (Compound 1-56) Starting from 4- (3-methylphenyl) piperazine, the title compound was prepared following the procedure described to obtain 152. Compound 156 was obtained as a yellow oil (95% yield): 1 H NMR, 400 MHz. (CDC13) d 1.37 (m, 4H), 1.55 (m, 4H), 2.31 (s, 6H), 2.39 (m, 4H), 2.60 (m, 4H), 3.20 (m, 4H), 6.71 (m, 6H), 7.14 (m, 2H). ESI-MS m / z 435 [M + H +] (100). Anal (C28H42 4) C. H, N.

Experimental procedure for compound 1-57 1- (6-Bromohexyl) -4- (3-methoxyphenyl) piperazine (42?). To a solution of 3-methoxyphenylpiperazine (41i) (200.0 mg, 1.04 mmol) in dry acetonitrile (15.0 ml), 1,6-dibromohexane (212.4 μ ?, 1.56 mmol) and TEA (145.0 μL, 1.04 mmol) were added and the mixture was stirred at room temperature overnight. The crude was extracted with dichloromethane (3 x 10 mL), dried and evaporated. The residue was chromatographed (15% n-hexane in EtOAc) to give 42i (65% yield): 1 H NMR. 300 MHz. (CDC13) d 7.12 (m, 1H), 7.02 (m, 1 H). 6.76 (m, 1H), 6.60 (m, 1H), 6.47 (m, 1 H), 6.39 (m, 1H), 6.27 (m, 1H), 6.15 (m, 1H), 3.73 (m, 3H), 3.44 (m, 4H), 2.59 (m, 4H), 2.36 (m, 4H), 1.39 (m, 4H), 1.29 (m, 4H). ESI-MS m / z 493 [M + Na +], 471 [M + H +] (100). Anal (C27H39C1N40) C, H, N. 1- (3-Chlorophenyl) -4- (6- (4- (3-methoxyphenyl) piperazin-1-yl) hexyl) piperazine (Compound 1-57). To a solution of 42x (100.0 mg, 0.52 mmol) in dry acetonitrile (10.0 mL), 3-chlorophenylpiperazine (101.9 mg, 0.52 mmol) and TEA (72.5 yL, 0.52 mmol) were added and the mixture was stirred at room temperature for the night. The crude was extracted with dichloromethane (3 x 10 mL), dried and evaporated. The residue was subjected to chromatography (10% methanol in chloroform) to give 157 (80% yield) as a yellow oil: 1 H NMR, 300 MHz, (CDC13) d 1.35 (m, 4H), 1.54 (m, 4H ), 2.39 (m, 4H), 2.59 (m, 8H), 3.20 (m, 8H), 3.78 (s, 3H), 6.42 (m, 2H), 6.53 (m, 1H), 6.78 (m, 2H) , 6.86 (m, 1H), 7.15 (m, 2H). ESI-MS m / z 493 [M + Na +], 471 [M + H +] (100). Anal (C27H39C IN4O) C, H, N. l-Phenyl-4- (6- (4- (pyridin-2-yl) iperazin-1-yl) hexyl) iperazine (Compound 1-58) Beginning from 422 and 1- (pyridin-2-yl) piperazine, the title compound was prepared following the procedure described to obtain I57. Compound 158 was obtained as a yellow oil (60% yield):: H NMR, 400 MHz, (CDC13) d 1.39 (m, 4H), 1.58 (m, 4H), 2.43 (m, 4H), 2.64 ( m, 8H), 3.24 (m, 8H), 6.88 (m, 1H), 6.96 (m, 4H), 7.28 (m, 4H). ESI-MS m / z 430 [M + Na +], 408 [M + H +] (100). Anal (C25H37 5) C, H, N. 1- (6-Methylpyridin-2-yl) -4- (6- (4-m-tolyl-piperazin-1-yl) hexyl) -perazine (Compound 1-59) Starting from 423 and 1- (6-methylpyridin-2-yl) piperazine, the title compound was prepared following the procedure described to obtain 157. Compound 159 was obtained as a yellow oil (63% yield): NMR, 400 MHz, (CDC13) d 1.39 (m, 4H), 1.58 (m, 4 2.33 (s, 3H), 2.40 (m, 7H), 2.59 (m, 8H), 3.22 4H), 3.56 (m, 4H), 6.47 (m, 2H), 6.69 (m, 1H), 6 (m, 2H), 7.16 (m, 1H), 7.38 (m, 1H). ESI-MS m / z [M + Na +], 436 [M + H +] (100). Anal (C27H 1 5) C, H, N. 1- (6-Methylpyridin-2-yl) -4- (6- (4-phenylpiperazin-1-yl) hexyl) piperazine (Compound 1-60) Beginning from 422 and 1- (6-methyl-pyridin-2-yl) piperazine, the title compound was prepared following the procedure described to obtain ls7. The compound 1¾? It was obtained as a yellow oil (60% yield): XH NMR, 400 MHz, (CDC13) d 1.39 (m, 4H), 1.58 (m, 4H), 2.41 (m, 7H), 3.23 (m, 4H), 3. 58 (m, 4H), 6.47 (m, 2H), 6.87 (m, 1H), 6.95 (m, 2H), 7.28 (m, 2H), 7.38 (m, 1H). ESI-MS m / z 422 [M + H +] (100). Anal (C26H39N5) C, H, N. l-Phenyl-4- (6- (4-m-tolyl-piperazin-1-yl) hexyl) piperazine (Compound 1-61) Starting from 422 and 4- (3-methylphenyl) piperazine, the title compound was prepared following the procedure described to obtain 157. The l6i compound was obtained as a yellow oil (70% yield): ¾ NMR, 400 MHz , (CDCI3) d 1.39 (m, 4H), 1.57 (m, 4H), 2.34 (s, 3H), 2.42 (m, 4H), 2.63 (m, 8H), 3.23 (m, 8H), 6.73 (m, 1H), 6.78 (m, 2H), 6.88 (m, 1H), 6.96 (m, 2H), 7.18 (m, __H), 7.29 (m, 2H). ESI-MS m / z 435 [M + Na +], 413 [M + H +] (100). Anal (C27H32N4) C, H, N. 4- (4- (6- (4-Phenyl-piperazin-1-yl) hexyl) piperazin-1-yl) quinoline (Compound 1-62) Ter-Butyl-4- (quinolin-4-yl) piperazine-l-carboxylate (36).

Starting from 4-bramoquinoline, the title compound was prepared following the procedure described to obtain 32. Compound 36 was obtained as a yellow oil: ¾ NMR, 200 MHz, (CDC13) d 1.38 (5, 9?), 2.98 (m, 4?), 3.56 (m, 4?), 6.62 (m, IH), 7.54 (m, IH), 7.72 (m, 1H), 7.85 (m, 1H), 7.93 (m, 1H) 8.57 (m, 1H). ESI-MS m / z 336 [M + Na +], 314 [M + H +] (100). Anal. (Ci8H23N302) C, H, N. 4- (Piperazin-1-yl) quinoline (45). Starting from 3e, the title compound was prepared following the procedure described to obtain 4. 4- (4- (6- (4-Phenyl-piperazin-1-yl) hexyl) piperazin-1-yl) quinoline (Compound 1-62). Starting from 422 and 45 / the title compound was prepared following the procedure described to obtain 157. Compound 162 was obtained as a yellow oil (65% yield): ¾ NMR, 400 MHz, (CDCl 3) d 1.40 ( m, 4H), 1.65 (m, 8H), 2.46 (m, 4H), 2.68 (m, 8H), 3.26 (m, 8H), 6.90 (m, 4H), 7.27 (m, 2H), 7.49 (m , IH), 7.66 (m, IH), 8.28 (m, 2H), 8.74 (m, IH). ESI-MS m / z 480 [M + Na +], 458 [M + H *] (100). Anal (C29H39N5) C, H, N. 4- (4- (6- (4-m-Tolylpiperazin-1-yl) hexyl) piperazin-1-yl) quinoline (Compound 1-63) Starting from 423 and 45, the title compound was prepared following the procedure described to obtain 157. Compound 163 was obtained as a yellow oil (70% yield):? NMR, 400 MHz, (CDC13) d 1.33 (m, 4H), 1.59 (m, 4H), 2.32 (5, 3H), 2.47 (m, 4H), 2.63 (m, 4H), 2.72 (m, 4H) , 3.23 (m, 8H), 6.72 (m, 3H), 6.85 (m, 1H), 7.15 (m, 1H), 7.49 (m, 1H), 7.66 (m, 1H), 8.04 (m, 2H), 8.73 (m, 1H). ESI-MS m / z 494 [M + Na +], 472 [M + H +] (100). Anal. (C3oH4iN5) C, H, N. 1- (Pyridin-2-yl) -4-. { 6- (4-m-tolylpiperazin-1-yl) hexyl) piperazine (Compound 1-64) Starting from 423 and 1- (pyridin-2-yl) piperazine the title compound was prepared following the procedure described to obtain 157. Compound 164 was obtained as yellow (68% yield): XH NMR, 200 MHz, (CDCl 3) d 1.36 (m, 4H), 1.55 (m, 4H), 2.30 (s, 3H), 2.38 (m, 4H), 2.57 (m, 8H), 3.19 (m, 4H), 3.55 (m, 4H), 6.66 (m, 5H), 7.14 (m, 1H), 7.43 (m, 1H), 8.18 (m, 1H). ESI-MS m / z 422 [M + H +] (100). Anal. (C26H39 5) C, H, N. 1- (3-Methoxyphenyl) -4- (6- (4-m-tolyl-piperazin-1-yl) hexyl) piperazine (Compound 1-65) Starting from 423 and 4- (3-methoxyphenyl) piperazine, the title compound was prepared following the procedure described to obtain 157. Compound 165 was obtained as yellow (80% yield): 1 H NMR, 200 MHz, ( CDC13) d 1.37 (m, 4H), 1.55 (m, 4H), 2.31 (s, 3H), 2.39 (m, 4H), 2.60 (m, 8H), 3.20 (m, 8H), 3.78 (s, 3H) ), 6.43 (m, 2H), 6.53 (m, 2H), 6.71 (m, 2H), 7.15 (m, 2H), ESI-MS m / z 451 [M + H +] (100). Anal. (C28H42 4O) C, H, N.

Biological Activity irt-vitro binding studies This example demonstrates the affinity of the compounds of the invention for the subtypes of the dopamine and serotonin receptor. These binding tests were carried out according to the procedure of Campiani et al .; J. Med. Chem. 2003 46 3822-3839.

CRL rats: male CD (SD) BR-COBS (Charles River, Italy) were sacrificed by decapitation; their brains were rapidly dissected in several areas (striatum for the Di and D2 receptors / olfactory tubercle for the D3 receptors and cortex for the 5-HT2 receptors) and stored at -80 ° C until the test. Tissues were homogenized in approximately 50 volumes of ice-cold, 50 mM Tris HC1, pH 7.4 (for Di, D2 and 5-HT2 receptors) or 50 mM Hepes Na, pH 7.5 (for D3 receptors) using an Ultra homogenizer -Turrax TP-1810 (2x20 s), and centrifuged at 48,000 g for 10 minutes (Beckman Avanti J-25 centrifuge). Each pellet was resuspended in the same volume of fresh buffer, incubated at 37 ° C for 10 minutes, and centrifuged again at 48,000 g for 10 minutes. The granulate was then washed once by resuspension in the fresh buffer and centrifuged as above. The resulting granules were resuspended just prior to the binding test in the appropriate incubation buffer (50 mM Tris HC1, pH 7.4, containing 10 uM pargyline, 0.1% ascorbic acid, 120 mM NaCl, 5 mM KC1, 2 mM CaCl2. , 1 mM MgCl2 for Di and D2 receptors, 50 mM Hepes Na, pH 7.5, containing 1 mM EDTA, 0.005% ascorbic acid, 0.1% albumin, 200 nM eliprodil for D3 receptors and 50 mM Tris HC1, pH 7.7 for 5-HT2 receptors). [3 H] -SCH 23390 (specific activity, 71.1 Ci / mmol; NEN), a reference substance for the determination of binding to the Di receptors, was tested in a final incubation volume of 0.5 inL, consisting of 0.25 mL of membrane suspension (2 mg tissue / sample), 0.25 mL of [3 H] ligand (0.4 nM) and 10] i of agent or displacement solvent. The non-specific binding was obtained in the presence of (-) cis-flupenthixol 10 μ ?. [3] - Spiperone (specific activity, 16.5 Ci / mmol, NEN), a reference substance for the determination of binding to D2 receptors, was tested in a final incubation volume of 1 mL, consisting of 0.5 mL of membrane suspension (1 mg of tissue / sample), 0.5 mL of [3H] -ligand (0.2 nM) and 20 L of displacement agent or solvent. The non-specific binding was obtained in the presence of (-) sulpiride 100 μ ?. [3 H] -7-OH-DPAT (specific activity, 159 Ci / mmol; Amersham), a reference substance for the determination of binding to D3 receptors, was tested in a final incubation volume of 1 mL, consisting of 0.5 mL of membrane suspension (10 g of prot. dopamine cloned from rat D3 in Sf9 cells (Signal Screen)), 0.5 mL of [3H] -ligand (0.7 nM) and 20 ih of agent or displacement solvent. The non-specific binding was obtained in the presence of 1 μ ?. dopamine. [3H] -Ketanserin (specific activity, 63.3 Ci / mmol; Amersham), a reference substance for the determination of binding to 5-HT2 receptors, was tested in a final incubation volume of 1 mL, consisting of 0.5 mL of membrane suspension (5 mg tissue / sample), 0.5 mL of [3H] -ligand (0.7 nM) and 20 ih of agent or displacement solvent. The non-specific binding was obtained in the presence of methysergide 1 μ ?. The incubations (15 minutes at 37 ° C for the Di, D2 and 5-HT2 receptors, 60 minutes at 25 ° C for the D3 receptors) were interrupted by rapid filtration in vacuum, through GF / B filters (for the receptors Di, D2 and 5-HT2) or GF / C (for D3 receptors), which were then washed with 12 mL (4x3 times) of ice-cooled buffer (50 mM Tris HCl, pH 7.7) using a Brandel cell harvester M-48R. The radioactivity trapped in the filters was counted in 4 mL of Ultima Gold MV (Packard) in a LKB 1214 liquid beta scintillation spectrometer, with a count efficiency of 50%.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (44)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. An arylpiperazine derivative represented by the formula I: an enantiomer thereof or a mixture of its enantiomers, or a pharmaceutically acceptable salt thereof or an N-oxide thereof, characterized in that, R1, R2 and R3, independently of each other, represent hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro, cyano and / or carboxy; - represents an optional double bond; if - represents a simple bond, then A represents CH or N; yes -_. represents a double bond, then A represents C; --B-- may be absent or present; --B-- is absent; and Z represents CH or N; or --B-- is present and represents a methylene bridge (-CH2-), an ethylene bridge (-CH = CH-), or a -NH- bridge, linked as indicated in the figure; and Z represents C (carbon); W represents CH, N or CR4, wherein R4 represents hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro or cyano; m and n, independently of each other, is 0, 1 or 2; and X may be absent or present; X is present and represents O, S, NR ', CO, S02, CH2, CH2-0, 0-CH2, CH2-S, S-CH2, CH2-NR', CH2-CO, CH2-S02 and NR'-CO , CO-NR ', NR'-S02, S02-NR', CH2-CH2, O-CO, CO-0, 0-CH = CH, S-CH = CH, NR'-CH = CH, CO-CH = CH, S02-CH = CH, CH2-0-CH = CH, CH2-S-CH = CH, CH2-NR '-CH = CH, CH2-CO-CH = CH, CONHCH2CH2 or CH2-S02-CH = CH, wherein R 'represents hydrogen or alkyl; and Y represents phenyl or a monocyclic or polycyclic aromatic heterocyclic group, such phenyl or heterocyclic group can be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo , haloalkyl, haloalkoxy, amino, nitro and cyano; or Y represents a hydrogenated heterocyclic group, such a hydrogenated heterocyclic group may be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino , nitro and cyano; or Y represents a group of formula III: wherein R7 represents hydrogen, alkyl, alkoxy, halo or haloalkyl; or X is absent; and Y represents a diazacyclic group of the formula II, where, or is 1, 2 or 3; D represents alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano; and E represents alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano; or D and E together with the diazacyclic group form a fused ring system, this fused ring system can be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano; or Y represents a group of formula IV: where A 'represents CH or N; and R8 represents hydrogen, alkyl, alkoxy, halo or haloalkyl.
2. 2. The arylpiperazine derivative according to claim 1, characterized in that - represents a single bond, and A represents CH or N.
3. 3. The arylpiperazine derivative according to claim 1, characterized in that it represents a double bond, and A represents C (carbon).
4. 4. The arylpiperazine derivative according to any of claims 1-3, characterized in that W represents CH, N or CR4, wherein R4 represents hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl , haloalkoxy, amino, nitro or cyano.
5. 5. The arylpiperazine derivative according to any of claims 1-4, characterized in that --B-- is absent, and Z represents CH or N.
6. 6. The arylpiperazine derivative according to any of claims 1-5 , characterized in that --B-- is present and represents a methylene bridge (-CH2-), an ethylene bridge (-CH = CH-), or a -NH- bridge, linked as indicated in the figure; and Z represents C (carbon).
7. 7. The arylpiperazine derivative according to claim 6, characterized in that: --B-- is present and represents a methylene bridge (-CH2-), an ethylene bridge (-CH = CH-) or a bridge -NH- , linked as indicated in the figure; and Z represents C (carbon); and W represents CR 4, wherein R 4 represents hydrogen, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, amino, nitro or cyano.
8. 8. The arylpiperazine derivative according to any of claims 1-7, characterized in that myn, independently of each other, is 0, 1 or 2.
9. 9. The arylpiperazine derivative according to claim 8, characterized in that: m is 1 or 2; and n is 0 or 2.
10. 10. The arylpiperazine derivative according to any of claims 1-9, characterized in that: R1, R2 and R3, independently of each other, represent hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro, cyano and / or carboxy;
11. 11. The arylpiperazine derivative according to claim 10, characterized in that: R1 represents alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro, cyano or carboxy; and R2 and R3 represent hydrogen. The arylpiperazine derivative according to claim 10, characterized in that: R 2 represents alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro or cyano; and R1 and R3 represent hydrogen. 13. The arylpiperazine derivative according to any of claims 1-12, characterized in that: X is present and represents 0, S, NR ', CO, S02, CH2, CH2-0, O-CH2, CH2-S, S-CH2, CH2-NR ', CH2-C0, CH2-S02, NR'-CO, CO-NR', CH2-CH2, 0-CO, CO-0, CH-CH = CH, CH-CH = CH , NR'-CH = CH, CO-CH = CH, S02-CH = CH, CH2-0-CH = CH, CH2-S-CH = CH, CH2-NR '-CH = CH, CH2-CO-CH = CH, CONHCH2CH2 or CH2-S02-CH = CH, where R 'represents hydrogen or alkyl. 14. The arylpiperazine derivative according to claim 13, characterized in that X represents 0, CH2-0, O-CH2, CH2-S, S-CH2, CH2-NR ', CH2-C0, CH2-S02, NR' -CO, CO-NR ', NR'S02, SO2-NR', 0-CO or CH2-0-CH = CH; wherein R 'represents hydrogen or alkyl. 15. The arylpiperazine derivative according to claim 14, characterized in that X represents 0, CH2- 0, NR'-CO, CO-NR ', NR'-S02 or 0-CO; wherein R 'represents hydrogen or alkyl. 16. The arylpiperazine derivative according to any of claims 13-15, characterized in that: Y represents phenyl or a monocyclic or polycyclic aromatic heterocyclic group, such phenyl or heterocyclic group can be optionally substituted one or more times with substituents selected from the group it consists of alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano; or Y represents a hydrogenated heterocyclic group, such a hydrogenated heterocyclic group can be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino , nitro and cyano. 17. The arylpiperazine derivative according to claim 16, characterized in that Y represents phenyl, wherein the phenyl group can be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy , cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano. 18. The arylpiperazine derivative according to any of claims 13-15, characterized in that Y represents an aromatic monocyclic heterocyclic group selected from furanyl, thienyl, pyrrolyl, oxazolyl, imidazolyl, pyridyl, pyridazinyl and pyrimidinyl, such monocyclic aromatic heterocyclic group can optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano. 19. The arylpiperazine derivative according to claim 18, characterized in that Y represents furanyl, thienyl or pyridyl, wherein the monocyclic aromatic heterocyclic group can be optionally substituted once or twice with substituents selected from the group consisting of alkyl, alkoxy, chlorine , trifluoromethyl and trifluoromethoxy. 20. The arylpiperazine derivative according to any of claims 13-15, characterized in that Y represents an aromatic bicyclic heterocyclic group selected from indolyl, isoindolyl, benzo [b] furanyl, benzo [b] thienyl, benzimidazolyl, benzthiazolyl, quinolinyl and isoquinolinyl, this aromatic bicyclic heterocyclic group can be optionally substituted once or twice with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl , hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano. 21. The arylpiperazine derivative according to claim 20, characterized in that Y represents indolyl, in particular indol-2-yl or indol-3-yl.; benzo [b] furanyl, in particular, benzo [b] furan-2-yl or benzo [b] furan-3-yl; benzo [b] thienyl, in particular benzo [b] thien-2-yl or benzo [b] thien-3-yl; quinolinyl, in particular quinolin-2-yl, quinolin-3-yl or quinolin-4-yl; or isoquinolinyl, in particular isoquinolin-1-yl, isoquinolin-3-yl or isoquinolin-4-yl; such an aromatic bicyclic heterocyclic group can be optionally substituted once or twice with substituents selected from alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano. 22. The arylpiperazine derivative according to claim 21, characterized in that Y represents ind, in particular indol-2-yl or indol-3-yl; benzo [b] furanyl, in particular benzo [b] furan-2-yl or benzo [b] furan-3-yl; quinolinyl, in particular quinolin-2-yl, quinolin-3-yl or quinolin-4-yl; or isoquinolinyl, in particular isoquinolin-1-yl, isoquinolin-3-yl or isoquinolin-4-yl; wherein the benzo [b] furanyl or isoquinolinyl can be optionally substituted once or twice with substituents selected from alkyl, hydroxy, alkoxy, chloro, trifluoromethyl, trifluoromethoxy, amino, nitro and cyano. 23. The arylpiperazine derivative according to claim 22, characterized in that Y represents indol-2-yl, benzo [b] furan-2-yl or isoquinolin-3-yl; wherein the benzo [b] furanyl or isoquinolinyl can be optionally substituted once or twice with substituents selected from alkyl, hydroxy, alkoxy, chloro, trifluoromethyl, trifluoromethoxy, amino, nitro and cyano. 24. The arylpiperazine derivative according to claim 23, characterized in that Y represents ind, benzo [b] furanyl or isoquinolinyl. 25. The arylpiperazine derivative according to any of claims 13-15, characterized in that Y represents a hydrogenated heterocyclic group, such a hydrogenated heterocyclic group can be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl -alkyl, alkenyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano. 26. The arylpiperazine derivative according to claim 25, characterized in that Y represents tetrahydroquinolinyl or tetrahydroisoquinolinyl, such heterocyclic group can be optionally substituted once or twice with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, hydroxy , alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano. 27. The arylpiperazine derivative according to claim 26, characterized in that Y represents tetrahydroquinolinyl or tetrahydroisoquinolinyl. 28. The arylpiperazine derivative according to claim 13, characterized in that: X represents O, CH2-0, NH-CO, CO-NH, NR'-S02 or CO-O; and Y represents phenyl, methyl-phenyl, pyridyl, indolyl, methyl-indolyl, benzo [b] furanyl, tetrahydroquinolinyl, isoquinolinyl or tetrahydroisoquinolinyl. 29. The arylpiperazine derivative according to claim 28, characterized in that: X represents 0, CH2-0, NH-CO, CO-NH, NR'-S02 or CO-0; Y represents phenyl, methyl-phenyl, pyridyl, methyl-pyridyl, indolyl, methyl-indolyl, benzo [b] furanyl, tetrahydroquinolinyl, isoquinolinyl or tetrahydroisoquinolinyl; R1 represents alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro or cyano; and R2 and R3 represent hydrogen. 30. The arylpiperazine derivative according to claim 28, characterized in that it is N- [4- [4- (3-Trifluoromethylphenyl) iperazin-1-yl] butyl] indole-2-carboxamide; N- [2- (1H-indol-3-yl) ethyl] -3- (4-m-tolyl-piperazin-1-yl) propanamide; N- [2- (1H-indol-3-yl) ethyl] -3- [4- (3-methoxyphenyl) piperazin-1-yl] propanamide; . { 4- [4- (3-methoxy-phenyl) -piperazin-1-yl] -butyl} benzo [b] furan-2-carboxylic acid amide; N- [4- [4- (3-Cyanophenyl) piperazin-l-yl] butyl] benzo [b] furan-2-carboxamide; . { 4- [4- (3-Chloro-phenyl) -piperazin-1-yl] -butyl} -amide; of benzo [b] furan-2-carboxylic acid; . { 4- [4- (3-carboxy-phenyl) -piperazin-1-yl] -butyl} benzo [b] furan-2-carboxylic acid amide; N- [4- [4- (m-Tolyl) piperazin-1-yl] butyl] benzo [b] furan-2-carboxamide; . { 4- [4- (3-cyano-phenyl) -piperazin-1-yl] -butyl} isoquinoline-3-carboxylic acid amide; N- [4- [4- (3-Chlorophenyl) piperazin-1-yl] butyl] isoquinoline-3-carboxamide; N- [4- [4- (m-Tolyl) piperazin-1-yl] butyl] isoquinoline-3-carboxamide; N- [4- [4- (3-Methoxyphenyl) piperazin-1-yl] butyl] isoquinoline-3-carboxamide; 3- [5- [4- (3-Chlorophenyl) piperazin-1-yl] pentyloxy] isoquinoline; 3-. { 5- [4- (3-Methoxy-phenyl) -piperazin-1-yl] -pentyloxy} -isoquinoline; 3- [5- (4-m-Tolylpiperazin-1-yl) pentyloxy] isoquinoline; 3-. { 5- [4- (3-Cyano-phenyl) -piperazin-1-yl] -pentyloxy} -isoquinoline; N- [4- (1,2,3,4-Tetrahydro-5-methoxy ^ -carbolin-2-yl) butyl] isoquinoline-3-carboxamide; N- [4- (3,4-Dihydro-6-methoxypyrazino [1,2-a] indol-2 (1 H) -yl) butyl] isoquinoline-3-carboxamide; N- [4- [4- (Pyridin-2-yl) piperazin-1-yl] butyl] isoquinoline-3-carboxamide; 1,2,3,4-Tetrahydro-quinoline-2-carboxylic acid [4- (4-phenyl-piperazin-1-yl) -butyl] -amide; (S) - (-) - N - [4- [4- (m-Tolyl) piperazin-1-yl] butyl] -1,2,4,4-tetrahydroisoquinoline-2-carboxamide; (R) - (+) - N- [4- [4- (m-Tolyl.}. Piperazin-1-yl] butyl] -1,2,4,4-tetrahydroisoquinoline-2-carboxamide; [1- (2, 4-dichloro-phenyl) -piperazin-1-yl] -butyl} -amide of lH-indole-2-carboxylic acid; {. 4- [4- (2, 4- 5-Chloro-1H-indole-2-carboxylic acid dichloro-phenyl) -piperazin-1-yl] -butyl} -amide;. {4- [4- (2, 3-dichloro-phenyl) - piperazin-1-yl] -butyl} -amide of isoquinoline-3-carboxylic acid; 3- {4- [4- (2, 3-dichloro-phenyl} -piperazin-1-yl] - butoxy.}. -isoquinoline; 3- {5- [4- (2,3-dichloro-phenyl) -piperazin-1-yl} -pentyloxy} -isoquinoline; 1H-indole-2-carboxylate; - [4- (2,3-dichlorophenyl) piperazin-1-yl] butyl; N- (4- (4- (phenylpiperazin-1-yl) butyl] benzo [b] furan-2-carboxamide; Benzo [b] furan-2-carboxylic acid {4 - [4- (2, 3-dimethyl-phenyl] -piperazin-1-yl] -butyl} -amide; N- (4- (4- (3-methoxyphenyl) piperazin-1-yl) butyl) benzo [b] furan-2-carboxamide; N- (4- (4- (6-methylpyridin-2-yl) piperazin-1-yl) butyl) isoquinoline-3-carboxamide; N- (4- (4-phenylpiperazin-1-yl) butyl) isoquinoline-3-carboxamide; N- (4- (4- (6-methylpyridin-2-yl) piperazin-1-yl) butyl) benzo [b] furan-2-carboxamide; N- (4- (4-phenylpiperazin-1-yl) butyl) quinoline-2-carboxamide; N- (4- (4-m-tolyl-piperazin-1-yl) butyl) quinoline-2-carboxamide; N- (4- (4- (3-methoxyphenyl) piperazin-1-yl) butyl) -1-methyl-1H-indol-2-carboxamide; N- (4- (4- (3-methoxyphenyl) piperazin-1-yl) butyl) -lH-indole-3-carboxamide; (S) -1, 2, 3, 4-Tetrahydro-N- (4- (4-phenylpiperazin-1-yl) butyl) quinolin-2-carboxamide; N- (4- (4-m-tolyl-piperazin-1-yl) butyl) picolinamide; N- (4- (4- (quinolin-3-yl) piperazin-1-yl) butyl) isoquinoline 3-carboxamide; N- (4- (4- (3-methoxyphenyl) piperazin-1-yl) butyl) -6-methylpyridine-2-carboxamide; N- (4- (4- (3-methoxyphenyl) piperazin-1-yl) butyl) uinoline-3-carboxamide; N- (4- (4- (pyridin-2-yl) piperazin-1-yl) butyl) quinoline-3-carboxamide; N- (4- (4-phenylpiperazin-1-yl) butyl) picolinamide; N- (4- (4- (3-methoxyphenyl) piperazin-1-yl) butyl) picolinamide; N- (4- (4- (3-methoxyphenyl) piperazin-1-yl) butyl) benzamide; N- (4- (4-m-tolyl-piperazin-1-yl) butyl) -benzamide; N- (4- (4-phenylpiperazin-1-yl) butyl) nicotinamide; N- (4- (4- (6-methylpyridin-2-yl) piperazin-1-y1) buti1) benzamide; N- (4- (4- (6-methoxypyridin-2-yl) piperazin-1-yl) butyl) benzamide; N- (4- (4- (6-methoxypyridin-2-yl) piperazin-1-yl) butyl) picolinamide; or N- (4- (4- (6-methylpyridin-2-yl) piperazin-1-yl) butyl) picolinamide; or a pharmaceutically acceptable salt thereof. 31. The arylpiperazine derivative according to any of claims 13-15, characterized in that Y represents a group of the formula III: wherein R7 represents hydrogen, alkyl, alkoxy, halo or haloalkyl. 32. The arylpiperazine derivative according to claim 31, characterized in that it is: 7- [4- [4- (2, 3-dichloro-phenyl) -piperazin-1-yl] -butoxy] -pyrrolo [1, 2] -a] quinoxalin-4 (5H) -one; 7- (5- (4-phenylpiperazin-1-yl) pentyloxy) pyrrolo [1,2-a] quinoxalin-4 (5H) -one; or 7- (4- (4-phenylpiperazin-1-yl) butoxy) pyrrolo [1,2-a] quinoxalin-4 (5H) -one; or a pharmaceutically acceptable salt thereof. 33. The arylpiperazine derivative according to any of claims 1-12, characterized in that X is absent; and Y represents a diazacyclic group of Formula II: where, or is 1, 2 or 3; D represents alkyl, cycloalkyl, cycloalkyl-alkyl hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy amino, nitro and cyano; and E represents alkyl, cycloalkyl, cycloalkyl-alkyl hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano; or D and E together with the diazacyclic group form a fused ring system, this fused ring system can be optionally substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and cyano. 34. The arylpiperazine derivative according to claim 33, characterized in that: Y represents a bicyclic heterocyclic group (ie, a fused ring system) selected from the following group: wherein R5 and R6, independently of each other, represent hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and / or cyano. 35. The arylpiperazine derivative according to claim 34, characterized in that: Y represents a bicyclic heterocyclic group selected from: wherein R5 and R6, independently of each other, represent hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, hydroxy, alkoxy, cycloalkoxy, halo, haloalkyl, haloalkoxy, amino, nitro and / or cyano. 36. The arylpiperazine derivative according to claim 35, characterized in that: Y represents wherein R 5 represents hydrogen, alkyl, halo, trifluoromethyl or trifluoromethoxy. 37. The arylpiperazine derivative according to claim 36, characterized in that it is: 2-. { 4- [4- (3-cyano-phenyl) -piperazin-1-yl] -butyl} -3,4-dihydro-2H-pyrazino [1,2-a] indol-1-one; 2- [4- [4- (3-chlorophenyl) piperazin-1-yl] -butyl] -3,4-dihydropyrazino [1,2-a] indole-1 (2H) -one; 2- . { 4- [4- (3-methoxy-phenyl) -piperazin-1-yl] -butyl} -3,4-dihydro-2H-pyrazino [1,2-a] indol-1-one; 2- [4- (4-M-tolyl) piperazin-1-yl] -butyl] -3,4-dihydropyrazino [1,2-a] indole-1 (2H) -one; 3, 4-dihydro-2- [4- (3,4-dihydro-6-methoxypyrazino [1,2-a] indol-2 (1H) -yl) butyl] pyrazino [1,2-a] indole-1 (2H) -one; 2-. { 4- [4- (2-methoxy-phenyl) -piperazin-1-yl] -butyl} -3,4-dihydro-2H-pyrazino [1,2-a] indol-1-one; or 2-. { 4- [4- (2,3-dichloro-phenyl) -piperazin-1-yl] -butyl} -3,4-dihydro-2H-pyrazino [1,2-a] indol-1-one; or a pharmaceutically acceptable salt thereof. 38. The arylpiperazine derivative according to any of claims 1-12, characterized in that: X is absent; and Y represents a group of formula IV: where A 'represents CH or N; and R8 represents hydrogen, alkyl, alkoxy, halo haloalkyl. 39. The arylpiperazine derivative according to claim 38, characterized in that it is: 1,6-bis (4- (3-chlorophenyl) piperazin-1-yl) hexane; 1, 6-bis (4- (3-methoxyphenyl) iperazin-1-yl) exano; 1,6-bis (4-phenylpiperazin-1-yl) hexane; 1- (3-chlorophenyl) -4- (6- (4- (3-methoxyphenyl) piperazin-1-yl) hexyl) piperazine; l-phenyl-4- (6- (4- (pyridin-2-yl) piperazin-1-yl) hexyl) piperazine; 1- (6-methylpyridin-2-yl) -4- (6- (4-m-tolyl-piperazin-1-yl) hexyl) piperazine; 1- (6-methylpyridin-2-yl) -4- (6- (4-phenylpiperazin-1-yl) hexyl) piperazine, 1-phenyl-4- (6- (4-m-tolyl-piperazin-1-yl) ) hexyl) piperazine 4- (4- (6- (4-phenylpiperazin-1-yl) hexyl) piperazin-1-yl) quinoline; 1, 6-Bis (4- (pyridin-2-pi) piperazin-1-yl) hexane; 4- (4- (6- (4-m-tolyl-piperazin-1-yl) hexyl) piperazin-1-yl) quinoline; 1,6-bis (4-m-tolylpiperazin-1-yl) hexane; 1- (pyridin-2-yl) -4- (6- (4-m-tolyl-piperazin-1-yl) hexyl) piperazine; or 1- (3-methoxyphenyl) -4- (6- (4-m-tolyl-piperazin-1-yl) hexyl) -perazine; or a pharmaceutically acceptable salt thereof. 40. A pharmaceutical composition, characterized in that it comprises a therapeutically effective amount of an arylpiperazine derivative according to any of claims 1-39, or a pharmaceutically acceptable addition salt thereof, or a prodrug thereof, together with at least a pharmaceutically acceptable carrier or diluent. 41. Use of the arylpiperazine derivative according to any of claims 1-39 or a pharmaceutically acceptable salt thereof or a prodrug thereof, for the manufacture of a pharmaceutical composition. 42. Use of the arylpiperazine derivative according to any of claims 1-39 or a pharmaceutically acceptable salt thereof, for the manufacture of a pharmaceutical composition for the treatment, prevention or alleviation of a disease or disorder or condition of a mammal, including a human, wherein the disease, disorder or condition is sensitive to the modulation of the dopamine and serotonin receptors. 43. Use according to claim 42, wherein the disease or disorder or condition is a neurological or psychiatric disorder, in particular psychotic disorders, schizophrenia, depression, Parkinson's disease, Huntington's disease, movement disorders, diston a , anxiety, restless legs syndrome, obsessive-compulsive disorders, mania, geriatric disorders, dementia, sexual dysfunction, musculoskeletal pain symptoms, pain associated with fibromyalgia, sleep disorders, substance abuse or addiction and withdrawal symptoms in drug addicts, abuse or addition of cocaine. 44. The use according to claim 43, wherein the disease or disorder or condition is a neurological or psychiatric disorder, in particular a psychotic disorder, preferably schizophrenia.