Title of Invention	COMPOUNDS OF GENERAL FORMULA I FOR SEROTONIN RELATED DISEASE
Abstract	A compound of the general formula (I), wherein R¿1?, R¿2?, X, Y and Z are as described in the specification

Full Text

PIPERAZINYLPYRAZINE COMPOUNDS AS A AGONIST OR ANTAGONIST OF SEROTONIN 5HT-2 RECEPTOR. Field of the Invention The present invention relates to novel compounds, to pharmaceutical compositions comprising the compounds, to processes for their preparation, as well as to the use of the compounds for the preparation of a medicament which particularly acts on the central nervous system. Background of the Invention Many diseases of the central nervous system are influenced by the adrenergic, the dopaminergic, and the serotonergic neurotransmitter systems. For example, serotonin has been implicated in a number of diseases and conditions which originate in the central nervous system. A number of pharmacological and genetic experiments involving receptors for serotonin strongly implicate the 5-HT2c receptor subtype in the regulation of food intake (Obes. Res. 1995, 3, Suppl. 4,449S-462S). The 5-HT2c receptor subtype is transcribed and expressed in hypothalamic structures associated with appetite regulation. It has been demonstrated that the 5-HT2c receptor agonist m-chlorophenylpiperazine (mGPP), which has some preference for the 5-HT2c receptor, reduces food intake in mice that express the normal 5-HT2c receptor while the compound lacks activity in mice expressing the mutated inactive form of the 5-HT2c receptor (Nature 1995,374, 542-546). In a recent clinical study, a slight but sustained reduction in body weight was obtained after 2 weeks of treatment with mCPP in obese subjects (Psychopharmacology 1997,133,309-312). Recently, a series of pyrrolo[3,2,l-ij]quinoline derivatives was identified to be 5-HT2C receptor agonists having selectivity over the 5-HT2A receptor (Isaac M., et al., Bioorg, Med. Chem. Lett 2000,10,919-921). The compounds are said to offer anovel approach to the treatment of obesity and epilepsy. Weight reduction has also been reported from clinical studies with other "serotonergic" agents (see e.g. IDrugs 1998.1,456-470). For example, the 5-HT reuptake inhibitor fluoxetine and the 5-HT releasing agent/reuptake inhibitor dexfenfluramine have exhibited weight reduction in controlled studies. However, currently available drugs that increase serotonergic transmission appear to have only a moderate and, in some cases, transient effects on the body weight The 5-HT2c receptor subtype has also been suggested to be involved in CNS disorders such as depression and anxiety (Exp. Opin. Invest, Drugs 1998.7,1587-1599; IDrugs, 1999,2,109-120). The 5-HT2c receptor subtype has further been suggested to be involved in urinary disorders such as urinary incontinence (IDrugs, 1999,2,109-120). Compounds which have a selective effect on the 5-HT2c receptor may therefore have a therapeutic potential in the treatment of disorders like those mentioned above. Of course, selectivity also reduces the potential for adverse effects mediated by other serotonin receptors. Information Disclosure US-A-3,253,989 discloses the use of mCPP as an anorectic agent. ' EP-Al-863 136 discloses azetidine and pyrrolidine derivatives which are selective 5-HT2c receptor agonists having antidepressant activity and which can be used for treating or preventing serotonin-related diseases, including eating disorders and anxiety. EP-Al-330 263 discloses piperazinylalkylpyrimidines as hypoglycemic agents. WO 87/04928 discloses 2-(l-piperazinyl)pyrimidines as agents for treating neuropathy. EP-A2-226842 discloses 1,4-naphthalenedione heterocyclic derivatives as antiallergics and antiasthmatics including 2-(3-bromophenyl)-4-(l-pipera2inyl)-pyrimidine. EP-A-657 426 discloses tricyclic pyrrole derivatives having activity on the 5-HT2c receptor and which inter alia may be used for treating eating disorders. EP-A-655 440 discloses 1-aminoethylindoles having activity on the 5-HT2c receptor and which may be used for treating eating disorders. EP-A-572 863 discloses pyrazinoindoles having activity on the 5-HT2c receptor and which may be used for treating eating disorders. J. Med. Chem. 1978,21,536-542 and US-A-4,081,542 disclose a series of piperazinylpyrazines having central serotonin-mimetic activity. US 4,078,063 discloses a series of piperazinylpyridines having anorexic activity. J. Med. Chem. 1981,24,93-101 discloses a series of piperazinylquinoxalines with central serotoninmimetic activity. ES 514549 discloses piperazine derivative with anorexigenic action. EP 370560 discloses l-[mono- or bis(trifluoromethyl)-2-pyridinyl]piperazines as central nervous system agents. J. Med. Chem. 1987,30,1794-1798 discloses 2-(4-heterocyclylpiperazin-l-yl) derivatives including 2-phenoxy-4-piperazin-l-ylpyrimidine. DB 2202385 discloses antimicrobial (5-nitro-2-fuiyl)pyrimidines and -thiadiazoles including 2-(5-nitro-2-fuiyl)-4-(4-methyl-l-piperazinyl)pyrimidine and 2-(5-nitro-2-furyl)-4-[4-(2-hydroxyethyl)-1 -piperazinyljpyrimidine, J. Med Chem. 1987.30,1210-1214 discloses N,N-disubstituted 6-alkoxy-2-pyridinamines as anticonvulsant agents including l-(6-methoxy-2-pyridinyl)piperazine, 1 -(6-ethoxy-2-pyridinyl)piperazine, 1 -(6-isopropoxy-2-pyridinyl)piperazine, 1 -(6-isobutoxy-2-pyridiayI)pipera2ine, l-(6-cyclopropylmethoxy-2-pyridinyl)piperazine, l-(6-cyclohexylmethoxy-2-pyridinyl)piperazine, and l-(6-cyclohexyloxy-2-pyridinyl)piperazine. J. Med. Chem. 1989.32,1237-1242 discloses 6-alkyl-N,N-disubstituted-2-pyridinamines as anticonvulsant agents including l-(6-butylthio-2-pyridinyl)piperazine, l-(6-cycIohexylmethyl-2-pyridinyl)piperazine and l-[6-(2-phenylethyl)-2-pyridinyljpiperazine, JP 07300474 discloses drugs for treatment of diseases related to serotoninergic nerve including l-(6-phenoxy-2-pyridinyl)pipera2ine and l-[6-(substituted)phenoxy-2-pyridinyl]piperazines, 1 -(6-benzyloxy-2-pyridinyl)piperazine, l-(6-cyclobutyloxy-2-pyridinyl)piperazine, and l-(6- cyclopentyloxy-2-pyridinyl)piperazine EP 580465 discloses heterocyclic piperazines as 5-HT3 agonists including 6-Chloro-2-(3-methylpiperazinyl)pyridme and 6-cliloro-2-(4-methylpiperazinyl)pyridine. WO 00/12475 discloses indoline derivatives as 5-HT2b and/or 5-HT2c receptor ligands, especially for the treatment of obesity. WO 00/12510 discloses pyrroloindoles, pyridoindoles and azepinoindoles as 5-HT2C receptor agonists, particluarly for the treatment of obesity. WO 00/12482 discloses indazole derivatives as selective, directly active 5-HT2c receptor ligands, preferably 5-HT2c receptor agonists, particularly for use as anti-obesity agents. WO 00/12502 discloses pyrroloquinolines as 5-HT2c receptor agonists, particularly for use as anti-obesity agents. WO 00/35922 discloses 2,3,4,4a-tetrahydro-lF-pyrazino[l,2-a]quinoxaIin-5(6H)ones as 5HT2c agonists, which may be used for the treatment of obesity. WO 00/44737 discloses aminoalkylbenzoforans as 5-HT2c agonists, which may be used for the treatment of obesity. Further compounds reported to be 5HT2c receptor agonists are, for example, indazolylpropylamines of the type described in WO 00/12481; indazoles of the type described in WO 00/17170; piperazinylpyrazines of the type described in WO 00/76984; heterocycle iused y-carbolines of the type described in WO 00/77001, WO 00/77002 and WO 00/77010; benzofuiylpiperazines of the type described in WO 01/09111 and WO 01/09123; benzofurans of the type described in WO 01/09122; benzothiophenes of the type described in 01/09126; aminoalkylindazoles of the type described in WO 98/30548; indoles of the type described in WO 01/12603; indolines of the type described in WO 01/12602; pyrazino(aza)indoles of the type described in WO 00/44753 and tricyclic pyrroles or pyrazoles of the type described in WO 98/56768. WO 96/11920 discloses CNS-active pyridinylurea derivatives. WO 95/01976 discloses indoline derivatives active as 5-HT2c antagonists and of potential use in the treatment of CNS disorders. WO 99/58490 disloses aryI-hydronaphthalen-alkanamines which may effectuate partial or complete blockage of serotonergic 5-HT2c receptors in an organism. Summary of the Invention According to the invention novel compounds of the general formula (I) are provided: wherein (i) X and Y represent both nitrogen and Z represents CH, forming a pyrazine derivative, or (ii) X and Z represent both CH and Y represents nitrogen, forming a pyridine derivative, or (iii) X represents C-CF3, Z represents CH, and Y represents nitrogen, forming a 4-trifluoromethylpyridine derivative, or (iv) Y and Z represent both nitrogen and X represents CH, foraiing a pyrimidine derivative, and wherein Ri and R2 are each, independently, selected from a group A, consisting of or from a group B, consisting of aryl--alkyl, aryl--alkoxy, heteroaryl-Cr Ce-alkoxy, aryloxy-C2-C6-alkoxy, heteroaryloxy-C2-C6-alkoxy, 1-indanyloxy, 2-indanyloxy, aryloxy, heteroaryloxy, arylthio, heteroarylthio, C5-C6-cycloalkylthio, C5-C8-alkoxy, C5-C8-alkylthio, C5-C6-alkynyloxy, C5-C6-alkenyloxy, fluoro-C2-C4-alkoxy, C4-C8-cycloalkyloxy, C3-C8-cycloalkyl-CrC4-alkoxy, halogen, aryl-C1-C4-alkylthio, heteroaryl-C1-C4-alkylthio, aryl-C1-C4-alkylamino, heteroaryl-C1-C4- alkylamino, heteroaryl and aryl; with the proviso that: (i) R1 and R2 are different and are not both selected from group A or group B at the same time; (ii) when formula (I) is a pyrazine derivative R1 or R2 are other than, phenylthio, phenylmethylthio, phenyl or phenyl substituted by halogen; (iii) R1 in formula (I) is halogen, especially chloro, only when (I) is a pyrazine derivative and when R2 simultaneously is 2-methylpiperazin-l-yl, 2-ethylpipera2in- 1-yl or trans-2,5-dimethyIpipera2in-l-yI; (iv) when fonnula (I) is a pyrazine derivative and R1 is 4-piperidinyloxy, R2 is other than 3-pyridinyhnethoxy, 4-quinolinylmethoxy, 2,4-dimethoxybenzyloxy and 3-(4-pyridinyl)propoxy; (v) when both X and Z are CH and Y is N in formula (I), forming a pyridine derivative, and R1 is 1-piperazinyl or 4-methylpiperazin-l-yl, then R2 is other than, 2-phenylethyl, benzyloxy, benzylamino, phenylthio, phenoxy, substituted phenoxy, C4-C8-cycloalkyloxy and C3-C8-cycloalkylmethoxy; (vi) when X is CH and Z and Y both are nitrogen in formula (T), forming a pyrimidine derivative, and R2 isl-piperazinyl, then R1 is other than phenoxy, phenyl or phenyl substituted by bromo, and C5-C8 alkoxy; and when R2 is 4- methylpiperazin-1-yl or 4-(2-hydroxyethyl)piperazin-l-yl, then R1 is other than 5- nitro-2-furyl; (vii) when X is CH and Z and Y both are nitrogen in formula (I), forming a pyrimidine derivative, and R1 is 1-piperazinyl, then R2 is other than Cs-C^ alkoxy; and where R3 is H or C1-4-alkyl, allyl, 2-hydroxyethyI, or 2-cyanoethyl, or a nitrogen protecting group, or a prodrug moiety such as an acyl- or an alkoxycarbonyl group forming a cleavable amide or carbamate linkage; R3 is preferably hydrogen; R4 is hydrogen or C1-4 alkyl, preferably hydrogen, methyl or ethyl, more preferably hydrogen or methyl; and wherein any aryl or heteroaryl residue, alone or as part of another group, in R1 or R2 may be independently substituted in one or more positions, preferably one or two, by C1-4-alkyl, C1-4-alkoxy, C1--alkylthio, C2-4-acyl, C1--alkylsulphonyl, cyano, nitro, hydroxy, C2-6-alkenyl, C2-6-alkynyl, fluoromethyl, tiifluoromethyl, trifluoromethoxy, halogen, -N(R5)(R5), aryl, aryloxy, arylthio, aryl-C1-4-alkyl, aryl-C2.4-alkenyl, aryl-C2-4-alkynyl, heteroaryl, heteroaryloxy, heteroarylthio or heteroaryl-C1-4-alkyl, aryI-C1-4-aIkoxy, aryloxy-C1-4-alkyl, dimethylamino-C2_4-alkoxy; and wherein any aryl or heteroaryl residue as substituents on aryl or heteroaryl, alone or as part of another group, in R1 or R2 in tum may be substituted in one or more postions, preferably one, independently of each other by C1-4-alkyl, C1-4-alkoxy, halogen, trifluoromethyl, cyano, hydroxy or dimethylamino; and R5 and R5 independently of each other are hydrogen, methyl or ethyl, or together with the nitrogen atom to which they are bound form a pyrrohdine, piperazine, moipholine, thiomoipholine or apiperidine ring; and phannaceutically acceptable salts, hydrates, geometrical isomers, tautomers, optical isomers, iV-oxides and prodrug forms thereof. When R3 serves as a nitrogen protecting groiq) R3 is f-butoxycarbonyl (t-BOC), benzyl or trityl. la case the compounds of formula (L) can be in the form of optical isomers, the invention comprises the racemic mixture as well as the individual enantiomers as such. In case the compounds of formula (I) contain groups, which may exist in tautomeric forms, the invention comprises the tautomeric forms of the compounds as well as mixtures thereof In case the compounds of formula (I) can be in the form of geometrical isomers, the invention comprises the geometrical isomers as well as mixtures thereof. According to another aspect, the invention provides the compounds according to formula (I) above for use in therapy. Still another aspect of the invention provides a pharmaceutical composition comprising a compound according to formula (I) above as the active ingredient, J. preferably together with a pharmaceutically acceptable carrier and, if desired, other pharmacologically active agents. In yet another aspect, the invention provides a method for the treatment of a human or animal subject suffering from a serotonin-related disease, particularly 5-HT2c receptor-related, especially eating disorders, particularly obesity; memory disorders, schizophrenia, mood disorders, anxiety disorders, pain, substance abuse, sexual dysfunctions, epilepsy, and urinaxy disorders. Another aspect of the invention provides for the use of the compounds according to formula (I) above for the manufacture of a medicament for the treatment of a serotonin-related disease, particularly 5-HT2c receptor-related, especially eating disorders, particularly obesity, memory disorders; schizophrenia, mood disorders, anxiety disorders, pain, substance abuse, sexual dysfunctions, epilepsy and urinary disorders. Finally a method for modulating 5HT2c receptor function is an aspect of the invention. Detailed Description of the Invention According to the present invention, a class of novel compounds has been developed which compounds bind to the 5-HT2c receptor (agonists and antagonists) and which therefore may be used for the treatment of serotonin-related disorders. First, the various terms used, separately and in combinations, in the above definition of the compounds having the general foraiula (I) will be explained. By "heteroatom" is meant nitrogen, oxygen, sulphur, and in heterocyclic rings (including heteroaromatic as well as saturated and partially saturated heterocyclic rings), also selenium. The term "aryl" is intended to include aromatic rings (monocyclic or bicyclic) having from 6 to 10 ring carbon atoms, such as phenyl, 1-naphthyl, 2-naphthyl, 1,2,3,4-tetrahydronaphthyl (can be linked to the remainder of the molecule via a carbon atom in any ring) and indanyl (can be linked to the remainder of the molecule via a carbon atom in any ring). The term "heteroaryl" means a mono- or bicyclic aromatic ring system, only one ring need be aromatic, and which can be linked to the remainder of the molecule via a carbon or nitrogen atom in any ring, and having from 5 to 10 ring atoms (mono-or bicyclic), in which one or more of the ring atoms are other than carbon, such as nitrogen, sulphur, oxygen and selenium. Examples of such heteroaryl rings are pyrrole, imidazole, thiophene, furan, thiazole, isothiazole, thiadiazole, oxazole, isoxazole, oxadiazole, pyridine, pyrazine, pyrimidine, pyridazine, pyrazole, triazole, tetrazole, chroman, isochroman, coimiarin, quinoline, quinoxaline, isoquinoline, phthalazine, cinnoline, quinazoline, indole, isoindole, indoline, isoindoline, benzothiophene, benzofuran, 2,3-dihydrobenzofuran, isobenzofuran, benzoxazole, 2,1,3-benzoxadiazole, benzothiazole, 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, benzimidazole, indazole, 2,3-dihydro-l,4-benzodioxine, 1,3-benzodioxole, 1,2,3,4-tetrahydroquinoIine, 3,4-dihydro-2H'-l,4-ben2oxazine, 1,5-naphtfayridine, 1,8-n^hthyridine, 3,4-dihydro-2H-pyrido[3,2-6]-l,4-oxazine, and 2,3"dihydro-l,4-benzoxathiine. If a bicyclic aryl or heteroaryl ring is substituted, it may be substituted in any ring. Exemplary aryl-C1-C6-alkyl, in which the alkyl portion of the group may be straight or branched, include benzyl, 2-phenylethyl, 3-phenyl-l-propyl, 1-phenylethyl, l-phenyl-2-propyl and the like. Exemplary aryl--alkoxy, in which the alkyl portion of the group may be straight or branched, include benzyloxy, 2-naphthylmethoxy, 2-phenylethoxy, 3-phenyl-1-propoxy, 1-phenylethoxy, l-phenyl-2-propoxy, 2-phenyl-l-propoxy and the like. Exemplary aryloxy-C2-C6"alkoxy, in which the alkyl portion of the gcoxcp may be straight or branched, include 2-phenoxyethoxy, 2-(l-naphthyloxy)ethoxy, 3-(2- naphthyloxy)-l-propoxy, 3-phenoxy-l-propoxy, 4-phenoxy-l-butoxy, 5-phenoxy-1-pentoxy, l-phenoxy-2-propoxy and the like. Exemplary C3-Cg-cycloalkyl-C]-C4-aIkoxy, in which the alkyl portion of the group may be straight or branched, include cyclopropylmethoxy, cyclopentyhnethoxy, 2-cyclohexylethoxy, 1-cyclohexylethoxy, l-cyclopropylethoxy, 1-cyclobutylethoxy and the like. Exemplary heteroaryl-CrC4-alkyIamino include 2-(2-pyridinyl)ethylamino, 3-pyridinylmethylamino, 2-(2-thienyl)ethylamino, 2-(lH-indol-3-yl)ethylamino and the like. Exemplary heteroaryloxy-C2-C6-alkoxy include 2-(8-quinolinyloxy)ethoxy, 2-(3-pyridinyloxy)ethoxy, 3-(8-quinolinyloxy)propoxy and the like Exemplary C5-C6-alkynyloxy include propargyloxy, 1-hexynyloxy, 2-hexynyloxy, 3-butynyloxy, 3-pentynyloxy and the like. 5-C8 alkoxy may be straight or branched. Exemplary alkoxy groups include pentyloxy, isopentyloxy, hexyloxy, and isohexyloxy. Halogen includes fluorine, chlorine or bromine. Where it is stated above that aryl and heteroaryl residues may be substituted (in one or more postions), this applies to aryl and heteroaryl per se as well as to any combined groups containing aryl or heteroaryl residues, such as heteroaryloxy-C2-C6-alkoxy, heteroaryloxy, aryl--alkoxy etc. The term 'N-oxides" means that one or more nitrogen atoms, when present in a compound, are in N-oxide form (N→-O). The term "prodrug forms" means a pharmacologically acceptable derivative, such as a carbamate or an amide, which derivative is biotransfonned in the body to form the active drug. Reference is made to Goodman and Gilman's, The Pharmacological basis of Therapeutics, 8th ed., McGraw-Hill, Int. Ed. 1992, "Biotransformation of Drugs, p. 13-15. 'Tharmaceutically accqjtable" means being useful in preparing a pharmaceutical composition that is generally safe, non-toxic and neither biologically nor otherwise desirable and includes being useful for veterinary use as well as human pharmaceutical use. "Pharmaceutically acceptable salts" mean salts which are pharmaceutically acceptable, as defined above, and which possess the desired pharmacological activity- Such salts include acid addition salts formed with organic and inorganic acids, such as hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, phosphoric acid, acetic acid, glycolic acid, maleic acid, malonic acid, oxalic acid, toluenesulphonic acid, methanesulphonic acid, fiimaric acid, succinic acid, tartaric acid, citric acid, benzoic acid, ascorbic acid and the like. Preferred embodiments of the invention are: - a compound of formula (I) wherein X and Y represent both nitrogen and Z represents CH, forming a pyrazine derivative; - a compound of formula (I) wherein Y and Z both represent nitrogen and X represents CH, forming a pyrimidine derivative; - a compound of formula (I) wherein R1 or R2 is selected from and wherein R3 is hydrogen; - a compound of formula (I) wherein R] or R2 is selected from and where R3 is hydrogen and R4 is selected from hydrogen or methyl or ethyl; - a compound of formula (I) wherein R1 or R2 is and where R3 is hydrogen and R4 is selected from hydrogen or methyl or ethyl; and - a compoimd of formula (T) wherein R1 or R2 is selected from In a iurther preferred embodiment, the compoimds of formula (I) are selected from compounds in which X and Y both are nitrogen and Z is CH giving pyrazine derivatives of formula (II): wherein R2 and R3 are as defined above wherein any aryl and heteroaryl residue, alone or as part of another group, in R2 in turn may be substituted in one or more positions, preferably one or two, independently of each other by C1--alkyl, C1--alkoxy, C1--alkylthio, C2-4"acyl, C1--alkylsulphonyl, cyano, nitro, hydroxy, C2-5-alkenyl, C2-6-alkynyl, fluoromethyl, trifluoromethyl, trifluoromethoxy, halogen, -N(R5)(R6), aryl, aryloxy, arylthio, aryl-C1--alkyl, aryl-C2-4-alkenyl, aryl-C2-4-alkyayl, heteroaryl, heteroaryloxy, heteroarylthio or heteroaryl-C1--alkyl, aryl-C1, 4-alkoxy, aryloxy-C1--alkyl, dimethylamino-C2-4-alkoxy; wherein any aryl or heteroaryl residue as substituents on aryl or heteroaryl, alone or as part of another group, in R2 in turn may be substituted in one or more postions, preferably one, independently of each other by C1-4-alkyl, C1--alkoxy, halogen, trifluoromethyl, cyano, hydroxy or dimethylamino; R5 and R6 are as defined above; and R7 is hydrogen or C1-4 alkyl. Another aspect of the invention is a compound of any of the formulae herein wherein R3 is hydrogen; or wherein R7 is hydrogen, methyl, or ethyl; or wherein R7 is methyl and is attached to the C2-position of the piperazine ring; or wherein R? is hydrogen. In formula (II), R3 is preferably hydrogen, and R7 is preferably hydrogen or C1-4-alkyl. When R7 is C1--alkyl, it is most preferably substituted in flie 2-postion of the piperazine ring. R7 is most preferably hydrogen or methyl-Preferred compounds of the general formula (T) above are: 2-(Benzyloxy)-6-(l -piperazinyl)pyrazine, 2-[(2-Methoxybrazyl)oxy]-6-(l -piperazinyl)pyrazine, 2-[(3-Methoxybenzyl)oxy]-6-(l-piperazinyl)pyrazine, and their pharmacologically acceptable salts and solvates; and and their pharmacologically acceptable salts and solvates. As mentioned above, the compounds of the present invention are useful for the treatment (including prophylactic treatment) of serotonin-related disorders, especially 5-HT2c receptor-related, in a human being or in an animal (including e.g. pets), such as eating disorders, especially obesity; memory disorders, such as Alzheimer's disease; schizophrenia; mood disorders, including, but not restricted to, major depression and bipolar depression, including both mild and manic bipolar disorder, seasonal affective disorder (SAD); anxiety disorders, including situational anxiety, generalized anxiety disorder, primary anxiety disorders (panic disorders, phobias, obsessive-compulsive disorders, and post-traumatic stress disorders), and secondary anxiety disorders (for example anxiety associated with substance abuse); pain; substance abuse; sexual dysfunctions; epilepsy; and urinary disorders, such as urinary incontinence. Additionally, the compounds of the present invention are generally useful in treatment of diseases and disorders of the central nervous system (CNS). The compounds of the present invention in radiolabelled form, may be used as 8 diagnostic agent. This invention relates to methods of making compounds of any fonnulae herein comprising reacting any one or more of the compounds or formulae delineated herein including any processes delineated herein. In one aspect, the invention is a method of making a compound of formula (I) delineated herein, taking a compound of the following formula: wherein; (i) X and Y rq)resent both nitrogen and Z rq)resents CH, forming a pyrazine derivative, or (ii) X and Z represent both CH and Y represents nitrogen, forming a pyridine derivative, or (iii) X represents C-CF3, Z represents CH, and Y represents nitrogen, forming a 4-trifluoromethylpyridine derivative, or (iv) Y and Z represent both nitrogen and X represents CH, forming a pyrimidine deriviative, and wherein each Hal is independently a halogen; and reacting the compound with one or more chemical reagents in one or more steps to produce a compound of general formula (I) delineated herein. The compounds of general formula (T) above may be prepared by, or in analogy with, conventional methods, and especially according to or in analogy with the following methods. Method A: Compounds of formula (I) above in which R1 (or R2) are bound to the pyrazine-, pyridine- or pyrimidine ring in (I) via an O, S or N atom in R1 (or R2), are prepared by reacting a compound of the structural formula (EI), (IV), (V), or (VI) wherein Hal is halogen, with an appropriate amine, alcohol or thiol or its corresponding anion to produce a compound of formula (VII), (VHI), (DQ, or (X): wherein R1 (or R2) is as defined above and with the proviso that R1 (or R2) is not any of the following groups The appropriate alcohol, amine, or thiol may be converted completely or partially to its corresponding anion by treatment with bases, such as triethylamine, 1,8- diazabicyclo[5.4.0]undec-7-ene, K2CO3, NaOH, NaH, KO-r-Bu, lithium diisopropylamide or the like. The reaction is carried out in a solvent, such as dioxane, tetrahydrofuran, tert-butanol or N,N-dimethylformamide (DMF), at 0-200 °C for 1-24 hours. The compound of fonnula (VII), (VIII), (DC), or (X) is reacted with 1 to 10 molar equivalents of an appropriate amine selected from and where R3 and R4 are as defined above, in a solvent such as acetonitrile, dioxane, tetrahydrofuran, n-butanol, DMF, or in a mixture of solvents such as DMF/dioxane, optionally in the presence of a base, such as K2CO3, Na2CO3, CS2CO3, NaOH, triethylamine, pyridine or the like, at 0-200 °C for 1-24 hours to produce the compound of formula (I). When R3 is a nitrogen protecting group as defined above, the subsequent iV-deprotection is carried out by conventional methods such as those described in Protective Groups in Organic Synthesis, John Wiley & Sons, 1991 or subsequent editions thereof Method B: Compounds of formula (I) are prepared by reacting a compound of formula (Vn), (Vni), (EX) or (X) above with a 4-hydroxysubstituted piperidine compound of formula (XI) wherein R3 is as defined above. The reaction is carried out in a solvent, such as toluene, DMF, tert-hntsnol or dioxane, in the presence of a base, such as l,8-diazabicyclo[5,4.0]undec-7-ene, KOH, KOz-Bu, NaH or the like, at 0-200 °C for 1-24 hours. The nitrogen atom in (XT) may be protected with a suitable protecting group, preferably tert-butoxycarbonyl, trityl or benzyl. iV-Deprotection is then carried out by conventional methods such as those described in Protective Groups in Organic Synthesis, John Wiley & Sons, 1991 or subsequent editions thereof. Method C: Compounds of formula (I) are prepared by reacting a compound of formula (in), (IV), (\0, or (VT) above with an appropriate amine, selected firom or a 4-hydroxysubstituted piperidine compound (XI) and where R3 and R4 are as defined above to produce a compound of formula (XII) wherein Hal is as defined above, and X, Y, Z have the same meaning as in formula (I), and Am is an amine residue selected from and where R3 and R4 are as defined above. The reaction conditions may be those described for methods A and B above. The compound of formula (XII) or (XIII) is reacted with an appropriate alcohol, amine (other than those defined for Am above) or thiol or its corresponding anions to produce a compound of the formula (I). The reaction conditions may be those described for method A above. When R3 is a nitrogen protecting group as defined above, the subsequent N-deprotection is carried out by conventional methods such as those described in Protective Groups in Organic Synthesis, John Wiley & Sons, 1991 or subsequent editions thereof Method D. According to another general process (the Suzuki reaction; for a review, see: Chem. Rev. 1995.95,2457-2483), the compounds of formula (I) wherein R1 or R2 are aryl or heteroaryl may be prepared by reacting a compound of foraiula (ID), (IV), (V), or (VT) with a boronic acid derivative of the type heteroaryl-B(OH)2 or aryl-B(0H)2, where heter, ryl and aryl are as defined above, in the presence of a transition metal catalyst such as (Ph3P)4Pd, where Ph represents phenyl, in a suitable solvent such as an ether (e.g., 1-2-dimethoxyethane or tetrahydrofuran), in the presence or absence of water, or an aromatic hydrocarbon (e.g., toluene). The reaction is preferably carried out in the presence of a base such as an alkali or alkaline earth metal carbonate (e.g, sodium carbonate) at a suitable temperature up to reflux to provide a compound of formula (XIV) or (XV) The compound of formula (XIV) or (XV) is reacted with 1 to 10 molar equivalents of an appropriate amine selected from or a 4-hydroxysubstituted piperidine compound (XI) to produce a compound of formula (I) and where R3 and R4 are as defined above. The reaction conditions may be those described for methods A and B above. Method E, A compoimd of formula (XU) or (XHI) is reacted with a boronic acid derivative heteroaryl-B(OH)2 or aryl-B(0H)2 to provide a compound of formula (I). Heteroaryl and aryl are as defined above. The reaction conditions may be those described in method D. An obtained compound of formula (I) may be converted to another compound of formula CO by methods well known in the art. The processes described above may be carried out to give a compound of the invention in the form of a free base or as an acid addition salt A pharmaceuticaliy acceptable acid addition salt may be obtained by dissolving the free base in a suitable organic solvent and treating the solution with an acid, in accordance with conventional procedures for preparing acid addition salts from base compounds. Examples of addition salt forming acids are maleic acid, fumaric acid, succinic acid, methanesulfonic acid, acetic acid, oxalic acid, benzoic acid, hydrochloric acid, sulphuric acid, phosphoric acid, and the like. The compounds of formula (I) may possess one or more chiral carbon atoms, and they may therefore be obtained in the form of optical isomers, e.g. as a pure enantiomer, or as a mixture of enantiomers (racemate) or as a mixture containing diastereomers. The separation of mixtures of optical isomers to obtain pure enantiomers is well known in the art and may, for example, be achieved by fractional crystallization of salts with optically active (chiral) acids or by chromatographic separation on chiral columns. The necessary starting materials for preparing the compounds of fonnula (I) are either known or may be prepared in analogy with the preparation of known compounds. In accordance with the present invention, the compounds of formula (I), in the formof free bases or salts with physiologically acceptable acids, can be brought into suitable galenic forms, such as compositions for oral use, for injection, for nasal spray administration or the like, in accordance with accepted pharmaceutical procedures. Such pharmaceutical compositions according to the invention comprise an effective amount of the compounds of formula (I) in association with compatible pharmaceutically acceptable carrier materials, or diluents, as are well known in the art The earners may be any inert material, organic or inorganic, suitable for enteral, percutaneous, subcutaneous or parenteral administration, such as: water, gelatin, gum arabicum, lactose, microcrystalline cellulose, starch, sodium starch glycolate, calcium hydrogen phosphate, magnesium stearate, talcum, colloidal silicon dioxide, and the like. Such compositions may also contain other pharmacologically active agents, and conventional additives, such as stabilizers, wetting agents, emulsifiers, flavouring agents, buffers, and the like. The compositions according to the invention can e.g. be made up in solid or liquid form for oral administration, such as tablets, pills, capsules, powders, syrups, elixirs, dispersable granules, cachets, suppositories and the like, in the form of sterile solutions, suspensions or emulsions for parenteral administration, sprays, e.g. a nasal spray, transdermal preparations, e.g. patches, and the like. As mentioned above, the compounds of the invention may be used for the treatment of serotonin-related disorders in a human being or an animal, such as eating disorders, particularly obesity, memory disorders, schizophrenia, mood disorders, anxiety disorders, pain, substance abuse, sexual dysfunctions, epilepsy, and urinary disorders. The dose level and frequency of dosage of the specific compound will vary depending on a variety of factors including the potency of the specific compound employed, the metabolic stability and length of action of that compound, the patient's age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drag combination, the severity of the condition to be treated, and the patient undergoing therapy. The daily dosage may, for example, range fi:om about 0,001 mg to about 100 mg per kilo of body weight, administered singly or multiply in doses, e.g. from about 0.01 mg to about 25 mg each. Normally, such a dosage is given orally but parenteral administration may also be chosen. All references cited herein, whether in print, electronic, computer readable storage media or other form,, are expressly incorporated by reference in their entirety, including but not limited to, abstracts, articles, journals, publications, texts, treatises, internet web sites, databases, patents, and patent publications. The invention will now be illustrated with the following examples, which however, are for illustrative purposes are not intended to limit the scope of the invention. EXAMPLES General: The structures of the prepared compounds were confirmed by standard spectroscopical methods, and elemental analysis and/or high resolution MS. The NMR data were obtained on a JEOLINM-EX 270, a Bruker 400 DPX or a Bruker DRX 500 spectrometer, IR spectra were obtained on a Peridn Elmer SPECTRUM 1000 FT-IR spectrometer. High resolution MS was obtained on a Micromass LCT spectrometer. Elemental analysis was performed by Mikro Kemi AB, Uppsala, Sweden or at Pharmacia AB, Stockholm, Sweden. Melting points, when given, were obtained on a Bu chi or a Gallenkamp melting point apparatus and are uncorrected. EXAMPLE1 2-(l-Naphthylmethoxy)-6-(l-piperazinyl)pyrazine. To a solution of 2,6-dichloropyrazine (298 mg, 2.00 mmol) and 1-naphthylmethanol (348 mg, 2.20 mmol) in dioxane (5 mL) was added NaH (55 % in mineral oil, 96 mg, 2.2 mmol) at room temperature. The reaction was stirred at room temperature and monitored by GC, After 3 h, piperazine (189 mg, 2.20 mmol) and NaH (55% in oil, 96 mg, 2.2 mmol) was added into the reaction flask at room temperature. The reaction mixture was stirred at room temperature for 24 h. The solvent was evaporated off. To the residue was added piperazine (671 mg, 7.80 mmol) and acetonitrile (5 xnL) and the solution was heated imder reflux for 5 h. The reaction mixture was directly loaded on a short column of silica gel for flash column chromatography. Elution with MeOH/dichloromethane (1:9) ftimished 0.41 g (64%) of the title compound. HRMS m/z calcd for C19H20N4O (M)+ 321,1715, found 321.1721. Anal. (C19H20N4O • 0.1 H2O) C, H, N. EXAMPLE 2 2-[l-(3-Fluorophenyl)ethoxyJ-6-(l-piperazinyI)pyrazine. Step 1:2-Chloro-6-[1-(3-fluorophenyl)ethoxy]pyrazme, To a solution of 2,6-dichloropyrazine (298 mg, 2,00 mmol) and l-(3-fluorophenyl)ethanol (308 mg, 2.2 mmol) in dioxane (5 mL) was added NaH (55 % in oil, 96 mg, 2,2 mmol) at room temperature. The reaction mixture was stirred over night. Water (0.5 mL) was added and the mixture was stirred for 15 min. Drying (K2CO3), filtration, and concentration in vacuo gave the title compound as an oil (0.55 g) that was used directly in the next step. MS m/z 254 (M+H)+. Step 2:2-[l-(3-Fluorophenyl)ethoxy]-6-(l-piperazinyl)pyrazme. A mixture of the product from step 1 above (cmde, 1.09 g, -- 4.3 mmol), piperazine (1.03 g, 12,0 mmol) and K2CO3 (1.00 g, 7.2 mmol) in acetonitrile (5 mL) was heated under reflux overnight (20 h). After cooling, ethyl acetate (15 mL) and water (5 mL) were added. The ethyl acetate layer was filtered through a short column of silica gel using MeOH/ethyl ether (1:1) as eluent to give 0.72 g (55%) of the title compound as an oil. HRMS m/z calcd for C16H19N4O4F (M)+ 302.1543, found 302.1528. Anal. (C16H19N4OF • 0.5 H2O) C, H, N. EXAMPLE 3 2-(l,3-Beenzodioxol-5-ylmethoxy)-6-(l-piperazinyI)pyrazine, Acetate. Step 1: 2-(l,3-Benzodioxol-5-yImethoxy)-6-chloropyra2ine. To a solution of 2,6"dichloropyra2ine (298 mg, 2,00 mmol) and piperonyl alcohol (335 mg, 2.20 mmol) in dioxane (5 mL) was added NaH (55 % in mineral oil, 96 mg, 2.2 mmol) at room temperature. The reaction mixture was stirred overnight. Water (0.5 mL) was added and the mixture was stirred for 15 min. Drying, Na2C03, filtration and concentration in vacuo furnished an oil (0.54 g) that was used directly in the next step. HRMS m/z calcd for C12H9CIN2O3 (M)"^ 264.0302, found 264.0303. Step 2: 2-(l,3-BenzodioxoI-5-ylmethoxy)-6-(l-piperazinyI)pyrazme, Acetate. Amixture of the product from step 1 above (0.54 g, 2.0 mmol), piperazine (0.86 g, 10 mmol) and K2CO3 (1.00 g, 7,2 mmol) in acetonitrile (5 mL) was heated imder reflux for 5 h. After cooling, ethyl acetate (20 mL) and water (5 mL) were added. The saved ethyl acetate layer was filtered through a short column of silica gel using methanoVethyl ether (1:1) as eluent. This furnished the free base of the title compound as an oil (0.43 g). This material was dissolved in methanol and acetic acid (0.5 mL) was added. The solution was concentrated. Diethyl ether (25 mL) was added and the flask was shaken until crystallization started. The crystals was collected, washed with diethyl ether and dried in air to give 0.34 g (45%) of the title compound: mp 124-127°C . HRMS m/z calcd for C16H18N4O3 (M)+ 314.1379, found 314.1308. Anal. (C16H18N4O3 • CH3COOH • I.6H2O) C, H,N. EXAMPLE4 2-[(3-Methoxybenzyl)oxy]-6-(l-pipera2inyl)pyra2ine,Acetate. Step 1: 2-Chloro-6-[(3-methoxybenzyl)oxy]pyrazine. To a solution of 2,6-dichloropyrazine (444 mg, 3.00 mmol) and 3-methoxybenzyl alcohol (455 mg, 3.30 mmol) in dioxane (5 mL) was added NaH (55 % in oil, 144 mg, 3.30 mmol) at room temperature. The reaction mixture was stirred ovemigiht. Water (0.5 mL) and ethyl acetate (10 mL) were added and the mixture was stirred for 15 min and then filtered. The filtrate was dried over K2CO3 and concentrated to give an oil (0.86 g) that was used directly in the next step. MS m/z 250 (M+H)+.. Step 2; 2-[(3-MethoxybenzyI)oxy]-6-(l-piperazinyl)pyrazinee Acetate. A mixture of the product from step 1 above (0.57 g, - 2.0 mmol), piperazine (0.86 g, 10 mmol) and K2CO3 (1.00 g, 7.2 mmol) in acetonitrile (5 mL) was heated under reflux for 10 h. After cooling, ethyl acetate (30 mL) was added. The ethyl acetate layer was washed with water and brine, dried over Na2CO3, and concentrated under reduced pressure. The residue was dissolved in diethyl ether. Acetic acid (0.5 mL) was added and the solution was left at room temperature for crystallization. The crystals were collected, washed with diethyl ether and dried in vaccum to give 0.54 g (75%) of the title compound: mp 111-113 °C HRMS m/z calcd for C16H20N4O2 (Mf 300.1586, found 300.1589. Anal. (C16H20N4O2 • CH3COOH) C, H, N- EXAMPLES 2-[(2-Methoxybenzyl)oxy]-6-(I-piperazinyl)pyrazine,Dihydrochloridc Step 1:2-Chloro-6-[(2-methoxybenzyl)oxylpyrazine, The title compound was prepared according to the procedure of example 4, step 1 starting from 2,6-dichloropyra2ine (298 mg, 2.00 mmol), 2-methoxybenzyl alcohol (303 mg, 2.20 mmol) and NaH (55 % in mineral oil, 96 mg, 2.2 mmol). The yield of the crude product was 0.49 g (98%) and was used directly as such in the next step. MS mIz 250 (M)+ HRMS m/z calcd for C12H11CIN2O2 (M)+ 250.0509, found 250.0522, Step 2:2-I(2-Methoxybenzyl)oxy]-6-(l-piperazinyl)pyrazine, Dihydrochloride. The title compound was prepared according to the procedure of example 4, step 2 starting from the product of step 1 above (0.49 g), piperazine (0.86 g, 10 mmol) and K2CO3 (1-00 g, 12 rmnol). This gave the free base of the title compound as an oil. Yield 0.43 g (73%), The free base was dissolved in ethyl ether and a solution of HQ in diethyl ether was added until no more precipitate was formed. The precipitate was collected, washed with diethyl ether, and dried in vaccum to give 0.41 g (56%) of the title compomid: mp 171-173 °C). HRMS m/z calcd for C16H20N4O2 (M)+ 300.1586, found 300.1586, Anal. (C16H20N4O2 ' 2HC1) C, H, N. EXAMPLE 6 2-[(3,5-Difluorobenzyl)o3y]-6-(l-pipera2myl)pyrazme5 Acetate, Step 1: 2-Chloro-6-[(3,5-difluoroben2yl)oxy]pyrazine. The title compound was prepared according to the procedure of example 4, step 1 starting from 2,6-dichIoropyra2ine (444 mg, 3.00 mmol), 3,5-difluorobenzyl alcohol (475 mg, 3.30 mmol) and NaH (55% in mineral oil, 144 mg, 3.30 mmol). The solid product was collected, washed with water, and dried to give 0,77 g (100%) of the crude product that was used directly in the next step. An analytical sample was recrystallized from diethyl ether/hexane: mp 70-71°C . MS mlz 257 (M+H)+. Anal. (Ci iH7ClPN20)C,H,N. Step 2: 2-[(3,5-Difluorobenzyl)oxy]76-(l-pipera2inyl)pyra2ine, Acetate. The title compound was prepared according to the procedure of example 4, step 2 starting from the product of step 1 above (0.51 g, -- 2.0 nmaol), piperazine (0.86 g, 10 mmol) and K2CO3 (1.00 g, 7.2 mmol). Yield 0,49 g, (67%); mp 70-72 X; HRMS Tti/z calcd for C15H16F2N4O (M)+ 306.1292, found 306.1292. Anal. (C15H16F2N4O • CH3COOH-H20)C,H,N. EXAMPLE 7 2-([l,l '-Biphenyl]-4-ylmethoxy)-6-(l-piperazinyl)pyra2ine, Acetate. Step 1: 2-([l,l'-Biphenyl]-4-ylmethoxy)-6-chloropyrazme. The title compound was prepared according to the procedure of example 4, stq) 1 starting from 2,6-dichloropyrazine (444 mg, 3.00 mmol),p-phenylbenzyl alcohol (607 mg, 3.30 mmol) and NaH (55% in mineral oil, 144 mg, 3,30 mmol). Recrystallization from hexane gave 0.55 g (88%) of the title compound: mp 86-87 °C . MS mlz; 297 (M+H)+. Anal. (C17H13CIN2O) C, H, N. Step 2:2-(fl,l'-Biphenyl]-4-ylmethoxy)-6-(l-piperazinyl)pyrazine, Acetate. The title compound was prepared according to the procedure of example 4, step 2 starting from the product of step 1 above (0.54 g, 1.87 mmol), piperazine (0.86 g, 10.0 mmol) and K2CO3 (1.00 g, 12 mmol). Yield: 0,35 g (44%); mp 102404 °C . HRMS m/z calcd for C21H22N4O (M)+ 346.1794, found U6Ani. Anal. (C21H22N4O • CH3COOH • O.55H2O) C, H, N. EXAMPLE 8 2-[2-(3-ChlorophenyI)ethoxy]-6-(l -piperazinyl)pyrazine, Acetate. Step 1:2-Chloro-6-[2-(3-chlorophenyl)ethoxy]pyrazuie, The title compoimd was prq)ared according to the procedure of example 4, step 1 starting from 2,6-dichloropyrazine (444 mg, 3.00 mmol) and m-chlorophenethyl alcohol (515 mg, 3.30 mmol) and NaH (55% in mineral oil, 144 mg, 3.30 mmol). The crude product (0.92 g) was used directly in the next step. MS mlz 269 (M+H)+. Step 2: 2-[2-(3-Chlorophenyl)ethoxy]-6-(l-piperazinyl)pyrazine, Acetate. The title compound was prepared according to the procedure of example 4, step 2 starting from the product of step 1 above (0.81 g, 3.02 mmol), piperazine (0.86 g, 10 mmol) and K2CO3 (1.00 g, 7,2 mmol). Yield: 0.75 g (65%); mp 118-119 X. HRMS m/z calcd for C16H19CIN4O (M)+318.1247, found 318,1249. Anal. (C16H19CIN4O • CH3COOH) C, H, N. EXAMPLE 9 6-(l-Piperazinyl)-2-pyrazinyI 1,2^54-tetrahydro-l-naphthalenyI ether, Acetate. Step 1:2-Chloro-6-(l,2,3,4-tetrahydro-l-naphthaIenyloxy)pyrazme. The title compound was prepared according to the procedure of example 4, step 1 starting from 2,6-dichloropyrazine (444 mg, 3.00 mmol) and 1,2,3,4-tetrahydro-l-naphthol (488 mg, 3.30 mmol) and NaH (55% in oil, 144 mg, 3.30 mmol). The crude product (0,86 g) was used directly in the next step. MS mlz 261 (M-+H)+. Step 2:6-(l-Pipera2myI)-2-pyrazinyl 1,2,3,4-tetrahydro-l-naphthalenyl ether, Acetate. The title compound was prepared according to the procedure of example 4, step 2 starting from the product of step 1 above (0.75 g, 2.88 mmol), piperazine (0,86 g, 10 mmol) and K2CO3 (1.00 g, 7.2 mmol). Yield: 0.59 g (55%); mp 160-162 °C. MS m/z 310 (M)+. HRMS m/z calcd for C18H22N4O (M)+310.1794, found 310.1799. Anal. (C18H22N4O • CH3COOH) C, H, N. EXAMPLE 10 2-(l-Piperazmyl)-6-{[4-(trifluoromethyl)benzyl]oxy}pyra2me, Acetate. Step 1: 2-Chloro-6-{[4-(trifluoromethyI)benzyI]oxy}pyrazine. The title compound was prepared according to the procedure of example 4, step 1 starting from 2,6-dichloropyrazine (444 mg, 3.00 mmol) and 4-trifluoromethylbenzyl alcohol (581 mg, 3.30 mmol) and NaH (55% in mineral oil, 144 mg, 3.30 mmol). Recrystallization from hexane gave 0.81 g (93%) of the title compound: mp 67-69 °C . MS nt/z 289 (M+H)+, Anal. (C12H8ClF3N2O) C, H, N. Step 2: 2-(l-Piperazinyl)-6-{[4-(trifluoromethyl)benzyl]oxy}pyra2me, Acetate. The title compound was prepared according to the procedure of example 4, step 2 starting from the product of step 1 above (0.54 g, 1.89 mmol), piperazine (0.86 g, 10 mmol) and K2CO3 (1.00 g, 7.20 mmol). Yield: 0.36 g (48%); mp 84-85 °C . MS m/z 338 (M)". HRMS m/z calcd for C16H17F3N4O (M)+ 338.1054, found 338.1063. Anal. (C16H17CIF3N4O • CH3COOH) C, H, N. EXAMPLE 11 2-(l-Piperazinyr)-6-(3-pyridmylmethoxy)pyrazine, Acetate. Step 1:2-Chloro-6-(3-pyridmylmethoxy)pyrazme. The title compound was prepared according to the procedure of example 4, step 1 starting from 2,6-dichloropyrazine (444 mg, 3.00 mmol), nicotinic alcohol (360 mg, 3.30 mmol) in dioxane (5 mL) and NaH (55 % in oil, 144 mg, 3.30 mmol). The crade product, obtained as an oil (0.72 g), was used directly in the next step. MS m/z 221 Step 2:2-(l-Piperazmyl)-6-(3-pyridmylmethoxy)pyrazme, Acetate. The title compound was prepared according to the procedure of example 4, step 2 starting from the product of stqp 1 above (0.74 g, 3.35 mmol), piperazine (0.86 g, 10 mmol) and K2CO3 (1,00 g, 7,2 mmol). Yield: 0.73 g (44 %); mp 98-99 '°C ; MS m/z 271(M)+ HRMS ni/z calcd for C14H17N5O (M)+ 271.1433, found 271.1425. Anal. (C14H17N5O • CH3COOH) C, H, N. EXAMPLE 12 2-(l -Piperazinyl)-6-I2-(3-pyridinyl)ethoxy]pyrazine, Acetate. Step 1: 2-ChIoro-6-[2-(3-pyridinyI)ethoxy]pyra2ine. The title compound was prepared according to the procedure of example 4, step 1 starting from 2,6-dichloropyrazine (444 mg, 3.00 mmol) and 2-(3-pyridyl)ethanol (405 mg, 3.30 mmol) and NaH (55% in mineral oil, 144 mg, 3.30 mmol). The crude product, obtained as an oil (0.62 g, 88% yield), was used directly in the next step. MS miz 235 (M)+. Step 2: 2-(l-Piperazinyl)-6-[2-(3-pyridinyI)ethoxylpyrazine, Acetate- The title compoimd was prepared according to the procedure of example 4, step 2 starting from the product of step 1 above (0.62 g, 2.64 mmol), piperazine (0.86 g, 10 mmol) and K2CO3 (1.00 g, 7.2 mmol). Yield: 0.40 g (44%); mp 90-91°C . MS rn/z 285 (Mf. HRMS m/z calcd for Ci5H]9N50 (M)+285.1590, found 285.1598. Anal. (C15H19N5O • CH3COOH) C, H, N. EXAMPLE 13 2-(2-FuryImethoxy)-6-(l-piperazmyl)pyrazine. Step 1: tert-Butyl 4-(6-chIoro-2-pyra2inyl)-l-piperazinecarboxyIate. A mixture of rert-butyl 1-piperazinecarboxylate (5.07 g, 27.2 mmol), 2,6- dichloropyrazine (3,38 g, 22.7 mmol), and K2CO3 (4.09 g, 30.0 mmol) in acetonitrile (20 mL) was stirred at 65 °C for 12.5 h and for a further 15 h at room temperature. Ether was added and the suspension was filtered. Concentration in vacuo iumished the crude product as an oil that crystallized upon standing. Purification by chromatograhy on silica gel using ethyl acetate/n-hexane (6:4) as eluent gave 6.1 g (90%) of the title compound as a solid, HRMS mlz calcd for C13H19ClN4O2 (M)+ 298.1197, found 298.1211. Anal. (C13H19CIN4O2) C, H, N, Step 2: 6-Chloro-2-(l-piperazmyI)pyrazine. A solution of triiluoroacetic acid (TFA; 6 mL) in dichloromethane (24 mL) was added to a stirred solution of the product of step 1 above (5.79 g, 19.4 mmol) in dichloromethane (20 mL) at 0 °C. After 1 h and 1.5 h of stirring, additional portions (10 mL and 5 mL) of TFA were added. Crushed ice and 5 M aqueous NaOH were added and the mixture was extracted with dichloromethnae (12 x 200 mL). The combined organic layers were dried (K2CO3), filtered and concentrated in vacuo. This furnished 3.48 g (90%) of the title compound as a light yellow solid, Previously described in a) J. Med. Chem. 1978.27,536-542; b) US 4,082,844 Step 3: 2-(2-Furylmethoxy)-6-(l-piperaziayJ)pyra2me. K-/-BuO (1.55 g, 13.8 mmol) was added to a mixture of the product from step 2 above (1.40 g, 7.05 namol) and 2-furancnethanol (5.3 g, 54 mmol). After being stirred for 7.5 h at 110 °C, the mixture was applied onto a bed of silica (16 x 6 cm). Elution with CHCb/MeOH (95:5 followed by 90:10) furnished 1.35 g (74%) of the title compound as an oil. HRMS m/z calcd for C13H16N4O2 (M)+ 260.1273, found 260.1276. Anal. (C13H16N4O2) C, H, N. EXAMPLE 14 2-(2-PhenyIethoxy)-6-(l-piperazmyI)pyrazine,Maleate. K-t-BuO (0,80 g, 7.13 mmol) was added to a mixture of the product from example 13, step 2 (0.638 g, 3.21 mmol) and 2-phraylethanol (5.62 g, 46.0 namol). After being stirred for 5 h at 105 °C in a sealed flask, the mixture was applied onto a bed of siUca (16x5 cm). Elution with CHCla/MeOH (97:3 followed by 90:10) furnished 0,68 g of an thick beige colored oil. This material was redissolved in ethyl acetate and K2CO3 was added. Filtration and concentration in vacuo furnished 0.67 g (74%) of the free base of the title compound as an oil. HRMS m/z calcd for C16H20N40 (M)+ 284.1637, found 284.1630, The free base was converted into its maleate salt which was recrystallized from MeOH/ether mp 166-168 °C. Anal. (C16H20N4O • C4H4O4) C, H, N. EXAMPLE 15 2-(2-Furyl)-6-(l-piperazinyl)pyrazine. Step 1: 2-Chloro-6-(2-furyI)pyrazine. 1,2-Dimethoxyethane (130 mL) was added to a mixture of tetrakis(triphenylphosphine)palladium (0) (0.93 g, 0.80 mmol) and 2,6-dichloropyrazine (2.55 g, 17-1 mmol). After 5 min of stirring at room temperature, furan-2-boronic acid (1.91 g, 17.1 mmol) followed by aqueous Na2CO3 (30 mL; 2 M) were added. The mixture was heated at reflux for 1 h [TLC monitoring by SiO2/n-hexane/ethyl acetate (90:10)]. The layers were separated and the light brownish water layer was extracted with dichloromethane (2 x 200 mL). The combined organic layers were dried (K2CO3), filtered and concentrated in vacuo. The brown-yellow oil obtained was purified by silica gel chromatography (18.5 x 4 cm) eluting with n-hexane/ethyl acetate (90:10). This furnished 1.47 g (48%) of the title compound as a light yellow solid. HRMS m/z calcd for CSH5CIN2O (Mf 180.0090, found 180.0092. Anal. (C8H5CIN2O) C, H, N. Step 2:2-(2-Furyl)-6-(l-piperazinyl)pyrazine. A mixture of the product from step 1 above (0,94 g, 5.2 mmol), piperazine (1.28 g, 14.9 mmol, K2CO3 (0.87 g, 6.3 mmol) in acetonitrile (5 mL) was heated in a sealed pyrex flask at 85 °C for 3 h. The mixture was diluted with dichloromethane, filtered, and concentrated in vacuo. The oily residue was purified by silica gel chromatography (18x4 cm) to fiimish a yellow oil. This material was redissolved in a small volume of CHCls/ether (9:1) and filtered through a short (4 cm) plug of alumina eluting with ether/MeOH (96:4). The filtrate was concentrated in vacuo to afford 0.77 g (64%) of the title compound as a light yellow solid. HRMS m/z calcd for C12H14N4O (M)+ 230.1168, found 230.1170. Anal. (C12H14N4O) C, H, N. EXAMPLE 16 2-(l-Piperazinyl)-6-(3-thienyl)pyrazine, Step 1:2-Chloro-6-(3-thienyl)pyrazine. 1,2-Dimethoxyethane (120 mL) was added to a mixture of tetra3ds(triphenylphosphine)palladimn (0) (0.87 g, 0.75 mmol) and 2,6- dichloropyrazine (2.43 g, 16.3 mmol). After 15 min of stirring at room temperature, thiophene-3- boronic acid (2.09 g, 16.3 mmol) followed by aqueous Na2CO3 (2 M; 25 mL) were added. The mixture was heated at reflux for 2 h [TLC monitoring by SiO2/n-hexane/ethyl acetate (85:15)], The layers were separated and the light brownish water layer was extracted with ether (2 x 100 mL). The combined organic layers were dried (K2CO3), filtered and concentrated in vacuo. The brownish oil obtained was purified by silica gel chromatography (18x5 cm) eluting with n-hexane/ethyl acetate (85:15). This furnished 1.46 g (45%) of the title compound as an oflF-white solid. HRMS m/z calcd for C8H5CIN2S (Mf 195.9862, found 195.9868. Anal. (C8H5CIN2S) C, H, N. Step 2:2-(l-Pipera2inyl)-6-(3-thienyl)pyrazine. A mixture of the product from step 1 above (1.04 g, 5.29 mmol), piperazine (1.32 g, 15.3 mmol), and K2CO3 (0.81 g, 5.82 mmol) in acetonitrile (6 xnL) was heated in a sealed pyrex flask at 85 °C for 8.5 h. The reaction mixture was diluted with dichloromethane, filtered, and concentated in vacuo. The semi-solid residue was purified by column chromatography on silica gel (18x5 cm) using CHCl3/MeOH (9:1) as eluent to furnish an oil. This material was redissolyed in ethyl acetate, filtered, and concentrated in vacuo. This gave 0.98 g (75%) of the title compound as a yellow sticky oil. HRMS m/z calcd for C12H14N4S (M)+246.0939, found 246.0943. Anal. (C12H14N4S)C,H,N. EXAMPLE 17 iV-Benzyl-6-(l-piperazinyl)-2-pyrazinamme. Step 1: N- Benzyl-d-chloro-l-pyrazinamine. A mixture of 2,6-dichloropyrazine (1.31 g, 8.0 mmol), benzylamine (1.15 g, 10.7 mmol) and K2CO3 (1.65 g, 11.9 mmol) in acetonitrile (6 mL) was heated at 85 °C for 13 h in a sealed pyrex flask. The reaction mixture was diluted with dichloromethane, filtered and concentrated in vacuo. The yellow solid residue was dissolved in a small volume of methanol and purified by silica gel chromatography (18x4 cm) using CHCl3/MeOH (98:2) as eluent. A second purification (Si02; 16x4 cm) using CHCI3 as eluent furnished 1.55 g (81%) of the title compound as a light yellow soUd. HRMS m/z calcd for C11H10CIN3 (M)+219.0563, found 219.0568. Anal. (C11H10CIN3) C, H,N. Step 2: N-Benzyl-6-(l-pipera2inyI)-2-pyrazmamine. A mixture of the product from step 1 above (1.25 g, 5.7 mmol), piperazine (1.0 g, 11.6 mmol), and K2CO3 (1.0 g, 7.3 mmol) in dioxane (3 mL) was heated at 160 °C for 11 h in a sealed pyrex flask. The reaction mixture was diluted with dichloromethane, filtered and concentrated in vacuo. The red-brownish residue was dissolved in a small volume of CHCl3/MeOH (9:1) and purified by silica gel chromatography (15 x 4 cm) using CHCl3/MeOH (95:5, followed by 9:1) as eluent. The free base was obtained as a brownish solid (0,9 g, 3.33 mol) that was redissolved in methanol (10 mL). Maleic acid (0.45 g, 3.83 mmol) in methanol (5 mL) was added and the salt was precipitated out by addition of ether. The salt was recrystallized from MeOH-ether and finally converted back to the free base by alkalinization (10% aqueous Na2CO3) and extraction with ether (5 x 60 mL). The combined ether layers were dried (K2CO3), filtered and concentrated. This furnished 0.36 g (23%) of the title compound as a light yellow powder. HRMS m/z calcd for C15H19N5 (M)+ 269.1640, found 269.1641. Anal. (C15H19N5) C, H, N. EXAMPLE 18 l-[6-(2-Thienylmethoxy)-2-pyridinyI]piperazine. Step 1:2-ChIoro-6-(2-thienylmethoxy)pyridine. K-t-BuO (1-70 g, 15.1 mmol) was added portionwise to a stirred mixture of 2-thiophenemethanol (2.14 g, 18.7 mmol) and 2,6-dichloropyridine (2.13 g, 14.4 mmol) in dioxane (3 mL) at room temperature. An exotennic reaction started and more dioxane (3 mL) was added. After 3 h of stirring at room temperature, the reaction mixture was passed through a column of silica using n-hexane/ethyl acetate (85:15) as eluent. A second purification on silica (16 x 4 cm) using n-hexane/ethyl acetate (9:1) furnished 3,0 g (93%) of the title compound as a light beige oil. HRMS mlz calcd for C10H8ClNOS (M)+225.0015, found 225.0022, Anal. (C10H8ClNOS) C, H, N. *Previously described in EP 693490. Step 2: l-[6-(2-ThienyImethoxy)-2-pyridinyl]piperazine. A mixture of the product from step 1 above (L35 g, 5.98 mmol), piperazine (1.55 g, 17.9 mmol) and K2CO3 (0.91 g, 6.58 mmol) in acetonitrile (5 mL) was heated at 125 125 °C for 6.5 h in a sealed pyrex flask. The reaction mixture was diluted with dichlorometane, filtered and concentrated in vacuo. The semi-solid residue was purified by silica gel (16x4 cm) chromatography using CHCls/MeOH (9:1) as eluent. Solvents were evaporated and the oily residue was redissolved in CHCl3/ether (1:1). Filtration and concentration in vacuo furnished 0.78 g (47%) of the title compoxmd as a beige oil. HRMS m/z calcd for C14H17N3OS (M)+275.1092, found 275.1101. Anal. (C14H17N3OS) C, H, N. EXAMPLE 19 2-(2-Phenoxyethoxy)-6-(l-piperazinyI)pyrazine, Step 1:2-Chloro-6-(2-phenoxyethoxy)pyrazine, K-t-BuO (1,61 g, 14.3 mmol) was added portionwise to a stirred mixture of 2,6-dichloropyrazine (2.03 g, 13.6 mmol) and 2-phenoxyethanol (2.54 g, 18.4 mmol) in dioxane (8 mL) at 0 °C (ice-bath). After 5 min of stirring, the ice-bath was removed and the mixture was stirred at room temperature for 1 h. The reaction mixture was diluted with ether, filtered and concentrated in vacuo. The oily residue was purified by silica gel chromatogr^hy (18x5 cm) using n-hexane/ethyl acetate (92:8) as eluent This furnished 2.92 g (86%) of the title compound as a white solid. HRMS m/z calcd for C12H11CIN2O2 (M)+250.0509, found 250.0511. Anal. (C12H11CIN2O2) C, H, N. Step 2:2-(2-Phenoxyethoxy)-6-(l-piperazinyl)pyrazine. A mixture of the product from step 1 above (1.29 g, 5.15 mmol), piperazine (1.30 g, 15.1 mmol) and K2CO3 (0.71 g, 5.14 mmol) in acetonitrile (5 mL) was heated in a sealed pyrex flask at 100°C for 4 h. The reaction mixture was diluted with dichloromethane, filtered, and concentrated in vacuo. The light-brown semi-sohd residue was purified by silica gel chromatography (15x4 cm) using CHCls/MeOH (9:1) as eluent. Solvents were evaporated off and the residue was redissolved in ether/CHCl3 (1:1). Filtration and concentration in vacuo furnished 1.05 g (68%) of the title compound as a white solid. HRMS m/z calcd for C16H20N4O2 (M)+ 300.1586, found 300.1578. Anal. (C16H20N4O2) C, H, N. EXAMPLE 20 2-(Benzyloxy)-6-(l-pipera2inyl)pyrazine.* A mixture of the product from example 13, step 2 (0.73 g, 3.68 mmol), benzyl alcohol (9.4 g, 87 mmol) and K-f-BuO was stirred at 125 °C for 4.5 h. The reaction mixture was purified by silica gel chromatograhy (13x5 cm) using CHClj/MeOH (7:3 followed by 9:1) as eluent. Solvents were evaporated off and the residue was redissolved in ethyl acetate. Filtration and concentration in vacuo furnished 0.90 g (90%) of the title compound as a beige oil. HRMS m/z calcd for C15H18N4O (M)+ 270.1481, found 270.1482. Anal. (C15H18N4O) C, H, N. This compound was also characterized as its maleate salt: mp 155-156 °C . HRMS in/z calcd for C15H18N4O (M)+270.1481, found 270.1482. Anal. (C15H18N4O • C4H4O4) C, H, N. EXAMPLE 21 2-Phenoxy-6-(l-piperazinyl)pyrazine. A mixture of the product obtained in example 13, step 2 (1.97 g, 9.92 mmol), phenol (2.43 g, 25.8 mmol), CuO (1.0 g, 12.6 mmol), and K2CO3 (1.43 g, 10,3 mmol) in dioxane (2 mL) was stirred for 4.5 h at 165 ^'C in a sealed pyrex tube. The reaction mixture was diluted with CHCIl3 and filtered through a pad of Celite. The pad was washed with several portions of CHCl3/MeOH (95:5). Solvent removal in vacuo furnished a dark brown oil which was purified by column chromatography on silica gel (14 X 5 cm) using CHCl3/MeOH (95:5, followed by 90:10) as eluent The brown oil (1.66 g) was subjected to repeated column chromatograhy, first on silica gel (18 X 4 cm) using CHCl3/MeOH (9:1) as eluent and finally on alumina (4x5 cm) using ether/MeOH (95:5) as eluent. This furnished 1.37 g (54%) of the title compound as a light beige oil, HRMS m/z calcd for C14H16N4O (M)+ 256.1324, found 256.1321. Anal.(C14H16N4O)C,H,N. EXAMPLE 22 2-(l-Phenylethoxy)-6-(l-piperazmyl)pyrazine. Step 1:2-Chloro-6-(l-phenyIethoxy)pyrazine. K-t-BuO (2.1 g, 1S.7 mmol) was added to a stirred solution of 1-phenyl-l-ethanol (2.45 g, 20.1 mmol) in dioxane (30 mL) at 0 °C (ice-bath). After 10 min of stirring, 2,6-dichloropyrazine (2.49 g, 16.7 mmol) was added whereupon the reaction mixture turned orange colored. After being stirrred for a further 1.5 h, ether was added and the mixture was filtered. Concentration in vacuo finished an orange colored oil that was purified by silica gel chromatography (15x5 cm) using n-hexane ethyl acetate. (9:1) as eluent. This gave 3.29 g (84%) of the title compound as a colorless oil. HRMS miz calcd for C12H11CIN2O (M)+234.0560, found 234.0551. Step 2:2-(l-Phenylethoxy)-6-(l-piperazinyI)pyrazme, A mixture of the product firom step 1 above (1.53 g, 6.5 mmol), piperazine (1.62 g, 18.9 mmol) and K2CO3 (0.90 g, 6.5 mmol) in acetonitrile (6 mL) was heated in a sealed pyrex flask at 90°C for 3.5 h. The reaction mixture was diluted with dichloromethane, filtered and concentrated in vacuo. The semi-solid residue was purified by silica gel chromatography (13 x 4 cm) using CHCl3/MeOH (9:1) as eluent. Solvents were evaporated off and the remaining oil was redissolved in CHCI3, filtered through a short plug of alumina and concentrated in vacuo. This gave 1.34 g (72%) of the title compound as an oil that solidified when refiigerated. HRMS mIz calcd for C16H20N4O (M)+284.1637, found 284.1650. Anal. (C16H20N4O -C4H4O4) C, H, N. EXAMPLE 23 2-(2-Fluoroethoxy)-6-(l-plperazinyI)pyra2ine,MaIeate. Step 1: 2-Chloro-6-(2-fluoroethoxy)pyrazine. K-t-BuO (1.32 g, 11,8 mmol) was added portionwise to a stirred mixture of 2-fluoroethanol (2.16 g, 33.7 mmol) and 2,6-dichloropyrazine (1.61 g, 10.8 mmol) in dioxane (2 mL) at 0 °C (ice-bath). The reaction mixture was then stirred at room temperature for 1 hour, diluted with dichloromethane, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (19x4 cm) using n-hexane/ethyl acetate (85:15) as eluent. This furnished 1.49 g (78%) of the title compound as a beige liquid. Anal. (C6H6 CIN2O) C, H, N. Step 2: 2-(2-Fluoroethoxy)-6-(l-piperazinyl)pyra2me, Maleate. A mixture of the product from step 1 above (0.94 g, 5.31 mmol), piperazine (1.40 g, 16.3 mmol) and K2CO3 (0.81 g, 5,9 mmol) in acetonitrile (5 mL) was stirred at room temperature for 8.5 h and at 65 °C for 4 L The reaction mixture was diluted with dichloromethane, filtered and concentrated m vacuo. The semi-solid residue was purified by silica gel chromatography (17 x 4 cm) using CHCl3/MeOH (9:1) as eluent. Solvents were evaporated off and the remaining oil (0,73 g) was redissolved in ether/CHCl3 (1:1) and filtered through a short (4 cm) plug of alumina using ether/MeOH (96:4) as eluent Solvents were evaporated off and the residue was redissolved in ether and K2CO3 was added. Filtration and concentration in vacuo fiimished 0.57 g (47%) of the free base of the title compound as an oil which was converted into its maleate salt Recrystallization from MeOH/ether furnished 0.58 g of the title compound as a white powder. Anal. (C10H15FN4O • C4H4O4) C, H, N. EXAMPLE 24 2-(CycIopentylmethoxy)-6-(l-piperazmyl)pyrazine. Step 1: 2-Chloro-6-(cyclopentylmethoxy)pyrazine. K-t-BuO (1.65 g, 14.7 mmol) was added portionwise to a stirred mixture of cyclopentanemethanol (2.99 g, 29.9 mmol) and 2,6-dichloropyrazine (1.90 g, 12.8 mmol) in dioxane (6 mL) at 0 °C (ice-bath). The reaction mixture was then stirred for 2.5 h, while the temperature was allowed to reach room temperature. The reaction mixture was diluted with dichloromethane/ether (1:1), filtered, and concentated in vacuo. The beige liquid was purified by column chromatography on silica gel (18 x 4 cm) using n-hexane/ethyl acetate (94:6) as eluent. Two chromatographic runs afforded 1.66 g (61%) of the title compound as a colorless oil. HRMS m/z calcd for C10H13CIN2O (M)+212.0716, found 212.0723. Anal. (C10H13C1N2O) C, H, N. Step 2:2-(Cyclopentylmethoxy)-6-(l-piperazinyl)pyrazine. A mixture of the product firom step 1 above (1.12 g, 5.27 mmol), piperazine (1.36 g, 15.8 mmol) and K2CO3 (0.77 g, 5.6 mmol) in acetonitrile (5 mL) was stirred at 100 "'C for 4.5 h in a sealed pyrex flask. The reaction mixture was diluted with dichloromethane, filtered and concentrated in vacuo. The semi-solid residue was purified by silica gel chromatography (15 x 4 cm) using CHCl3/MeOH (9:1) as eluent. Solvents were evaporated off and the remaining thick oil was redissolved in ether. Filtration and concentration in vacuo furnished 1.02 g (74%) of the title compound as a beige oil. HRMS m/z calcd for C14H22N4O (M)+262.1794, found 262.1800. Anal. (C14H22N4O) C, H, N. EXAMPLE 25 2-Benzyl-6-(l-piperazinyl)pyrazine. Step 1:2-Chloro-6-ben2ylpyrazine The title compound was prepared in a 20 mmol-scale according to the procedure described in WO 94/26715 with a slight modification. The reaction was carried out at 50 °C for 8 h followed by 10 h at room temperature. Yield: 0.75 g (18%). HRMS m/z calcd for C11H9CIN2 (M)+204,0454, found 204.0450. Step 2:2-Benzyl-6-(l-piperazinyI)pyrazine. A mixture of - product firom step 1 above (0.83 g, 4.0 mmol), piperazine (1.1 g, 12.8 mmol) and K2CO3 (0.62 g, 4.49 mmol) in acetonitrile (7 mL) was stirred at 85 °C for 8.5 h. Thr reaction mixture was diluted with dichloromethane, filtered and concentrated in vacuo. The semi-solid residue was purified by silica gel chromatography (20 x 4 cm) using CHCl3/MeOH (9:1) as eluent. The resulting oil was redissolved in CHCl3 and filtered through a short (4 cm) plug of alumina using ether/MeOH (96:4) as eluent. Solvent removal in vacuo furnished 0.59 g (57%) of the title compound as an oil which became semi-solid upon refrigeration. HRMS m/z calcd for C15H18N4 (M)+254.1531, found 254.1527. Anal. (C15H18N4) C, H, N. EXAMPLE 26 2-(3,4-Dihydro-2fr-chromen-4-yIoxy)-6-(l-piperazmyl)pyrazme,Maleate. Step 1:2-Chloro-6-(3,4-dihydro-2iEr-chromen-4-yloxy)pyrazine. K-t-BuO (1.28 g, 11.42 mmol) was added to a stirred solution of 4-chromanol (1.81 g, 12.0 mmol) in dioxane (30 mL) at 0 °C (ice-bath). After being stirred for 5 min at room temperature, the mixture was chilled to 0 °C (ice-bath) and 2,6-dichloropyrazine (1.49 g, 10.0 mmol) was added. The reaction mixture was stirred at room temperature for 15 min and diluted with dichloromethane. Filtration and concentration m vacuo furnished an orange thick oil which was purified by chromatography on sihca gel (15 x 4 cm) using n-hexane/ethyl acetate (8:2) as eluent. This furnished 1.87 g (71%) of the title compound as a colorless oil. HRMS m/z calcd for C13H11CIN2O2 (M)+262.0509, found 262.0520. Anal. (C13H11CIN2O2) C, H, N. Step 2:2-(3,4-Dihydro-lH-chromen-4-yIoxy)-6-(l-piperazinyl)pyrazine, Maleate. A mixture of the product from step 1 above (1.53 g, 5.81 mmol), piperazine (1.45 g, 16.9 mmol) and K2CO3 (0.80 g, 5.81 mmol) in acetonitrile (10 mL) was heated in a sealed pyrex flask at 110°C for 6.5 h. The reaction mixture was diluted with CHCI3, filtered and concentrated in vacuo. The semi-sohd residue was purified by column chromatography on sihca (13 x 4 cm) using CHCl3/MeOH (9:1) as eluent. The free base of the title compound was obtained as a viscous oil (1.76 g, 97%) which was converted to its maleate salt. Recrystallization from MeOH/ether furnished 1.78 g (74%) of the title compound as a light yellow powder: mp 179.5-182°C. HRMS m/z calcd for C17H20N4O2 (M)+312.1586, found 312.1581. Anal. (C17H20N4O2 • C4H4O4) C, H, N. EXAMPLE 27 2-[2-(4-Dimethylaminophenyl)ethoxy]-6-(l-piperazinyl)pyra2ine,Maleate. Step 1: 2-Chloro-6-[2-(4-dimethylaminophenyI)ethoxy]pyra2ine. K-r-BuO (2.27 g, 20.3 mmol) was added to a stirred solution of 4-(dimethylamino)phenethyl alcohol (3.55 g, 21.5 mmol) in dioxane (35 mL) at 0 °C (ice-bath). After being stirred for 5 min at 0 °C and 12 min at room temperature, the mixture was chilled to 0 °C (ice-bath) and 2,6-dichloropyrazine (2.62 g, 17.6 mmol) was added. The reaction mixture was stirred at 0 °C for 5 min and at room temperature for 20 min and diluted with dichloromethane/ether (1:1). Filtration through a pad of Celite, covered with K2CO3, and concentration in vacuo furnished a yellow oil. This material was purified by chromatography on silica gel (15x5 cm) using n-hexane/ethyl acetate (85:15). A second chromatograhic run on silica gel (14 X 5 cm) using n-hexane/ethyl acetate (88:12) furnished 3.91 g (80%) of the title compound as a colorless oil. Anal. (C14H16CIN3O) C, H, N. Step 2: 2-[2-(4-DimethylaminophenyI)ethoxy]'6-(l-pipera2inyI)pyra2me, Maleate. A mixture of the product from step 1 above (1.83 g, 6,59 mmol), piperazine (1.69 g, 19,6 mmol) and K2CO3 (0.92 g, 6.7 mmol) in acetonitrile (25 mL) was heated under reflux for 8.5 h. The reaction mixture was diluted with dichloromethane, filtered through a pad of Celite, and concentrated in vacuo. The semi-solid residue was purified by column chromatography on silica (13x4 cm) using CHCl3/MeOH (92:8) as eluent. The free base of the title compound was obtained as a beige viscous oil (1.17 g, 54%) which was converted into its maleate salt Recrystallization from MeOH/ether fiimished 1.33 g of the titie compound as a light yellow powder. HRMS m/z calcd for C18H25N5O (M)+327.2059, found 327.2066. Anal. (C18H25N5O • C4H4O4) C, H, N. EXAMPLE 28 2-[2-(lH-Indol-l-yl)ethoxy]-6-(l-pipera2myl)pyrazine, Maleate. Step 1:2-(lH-Indol-1-yl)ethanol.* A mixture of indole (5.71 g, 48.7 mmol), ethylene carbonate (4.72 g, 53.6 mmol) and K2CO3 (6.73 g, 48.7 mmol) in DMF (20 mL) was heated under reflux for 2 h. The reaction mixture was diluted with dichloromethane, filtered, and concentrated in vacuo. The Ught brown oily residue was purified by chromatography on silica gel (13x6 cm) using 7z-hexane/ethyl acetate (1:1) as eluent. This gave 1.78 g (23%) of the title compound as a beige oil. HRMS m/z calcd for C10HnNO (M)+161.0841, found 161.0849. Anal. (C10HnNO- O.IH2O) C, H, N. *Previously described in a) J. Med. Chem. 1992,35, 994-1001; b) ibid. 1998.41,1619-1630. Step 2: 2-Chloro-6-[2-(li?-indol-l-yl)ethoxy]pyrazine. K-t-BuO (0.67 g, 5.93 mmol) was added to a stirred solution of the product obtained in step 1 above (0.67 g, 5.93 mmol) in dioxane (20 mL) at 0 °C (ice-bath). After being stirred for 7 min at 0 °C and 5 mm at room temperature, the mixture was chilled to 0 °C (ice-bath) and 2,6-dichloropyrazine (2.62 g, 17.6 mmol) was added. The yellowish reaction mixture was stirred at 0 °C for 20 min and at room temperature for 10 min and then diluted with dichloromethane. Drying (K2CO3), filtration, and concentration in vacuo furnished a beige oil. This material was purified by chromatography on silica gel (13 x 4 cm) using n-hexane/ethyl acetate (80:20). This furnished 1.39 g (94%) of the title compound as an oil that soUdified upon standing. HRMS m/z calcd for C14H12CIN3O (M)+273.0669, found 273.0671. Anal. (C14H12C]N30) C, H, N. Step 3:2-p-(lH-Indol-l-yl)ethoxy]-6-(l-piperazinyl)pyrazine, Maleate. A mixture of the product from step 1 above (1.05 g, 3.84 mmol), piperazine (0.96 g, 11.1 mmol) and K2CO3 (0.53 g, 3.84 mmol) was heated at 85 °C for 7 h. The reaction mixture was diluted with CHCI3, filtered, and concentrated in vacuo. The semi-solid residue was purified by chromatography on silica gel (11x4 cm) using CHCI3/MeOH (9:1) as eluent. The resulting oil was redissolved in CHCI3 and filtered through a short (4 cm) plug of alumina covered by K2CO3 using CHCI3 as eluent Solvent removal in vacuo furnished 1.02 g (82%) of the free base of the title compound as a beige oil which was converted into its maleate. Recrystallization from MeOH/ether furnished 1.00 g (75%) of the title compound as a light yellow powder: mp 160.5-163 °C. HRMS m/z calcd for C18H21N5O (M)+323.1746, found 323.1757. Anal. (C18H21N5O • C4H4O4) C, H, N. EXAMPLE 29 2-[2-(l^-IndoI-3-yl)ethoxy]-6-(l-piperazinyl)pyra2me. Step 1: 2-Chloro-6-[2-(l£r-indol-3-yl)ethoxy]pyrazme. K-t-BuO (2.32 g, 20.6 mmol) was added to a stirred solution of tryptophol (1.7 g, 10.6 mmol) in dioxane (30 mL) at 0°C (ice-bath). After being stirred for 10 min at 0 °C and 10 min at room temperature, the mixture was chilled to 0 °C (ice-bath) and 2,6-dichloropyrazine (1.37 g, 9.17 mmol) was added. The yellowish reaction mixture was stirred at 0 °C for 30 min and for a further 20 min at room temperature. The mixture was diluted with dichloromethane,filtered, and concentrated in vacuo to furnish a brownish oil. This material was purified by chromatography on silica gel (14 X 5 cm) using n-hexane/ethyl acetate (75:25). This furnished 1.38 g (55%) of the title compound as a beige solid. Purity >90% by ^H NMR m CDCI3. Step 2: 2-[2-(l-H-Indol-3-yl)ethoxy]-6-(l-piperazinyl)pyrazine. A mixture of the product from Stqp 1 above (1.07 g, 3.90 mmol), piperazine (0.98 g, 11.3 mmol) and K2CO3 (0.54 g, 3.9 mmol) in acetonitrile (11 mL) was heated at 85 °C for 5 h and at 110°Cfor 8 h in a sealed pyrex flask. The reaction mixture was diluted with CHCI3, filtered, and concentrated in vacuo. The semi-solid residue was purified by chromatography on silica gel (11x4 cm) using CHCl3/MeOH (9:1) as eluent The resulting oil was redissolved in CHCl3 and filtered througih a short plug of alumina, covered by K2CO3, using CHCl3 as eluent. Solvent removal in vacuo furnished 0.50 g (23%) of the title compound as an oil that solidified upon standing: mp 133-135 °C . HRMS m/z calcd for C18H21N5O (M)+323.1746, found 323.1763. Anal. (C18H21N5O) C,H,N. EXAMPLE 30 4-[(4-Fluorobenzyl)oxy]-2-(l-piperazinyl)pyrimidme,Dihydrochloride. K-t-BuO (0.224 g, 2.00 mmol) was added to a solution of 4-fluoroben2yl alcohol (0.252 g, 2.00 mmol) in tert-butanol (5.4 mL). After being stirred for 30 min at room temperature, 2,4-dichloryrimidine (0.298 g, 2.00 mmol) in tert-bntanol (2 mL) was added. The reaction mixture was stirred over night, poured into 5% aqueous NaOH and extracted with ethyl acetate. The organic layer was dried (MgSO4) and concentrated in vacuo. A solution of piperazine (0.516 g, 6.00 mmol) in THF (5 mL) was added and the resulting mixture was stirred over night. The reaction mixture was concentrated and purified by chromatography on silica using dichloromethane/MeOH (1% HCl) (using gradient 99:1 to 9:1) to give 0.24 g (33%) of the title compound. MS m/z 288 (M)+and 5 fragments supporting the stated structure. HRMS m/z calcd for C15H17FN4O (M)+288.1386, found 288.1378, EXAMPLE 31 4-[(2-MethoxybenzyI)oxy]-2-(l-piperazinyl)pyrimidine, Dihydrochloride. The title compound was prepared according to the procedure of example 30 starting from 2-methoxybenzyl alcohol (0.28 g, 2.0 mmol) to give 0.30 g (40%) of the title compoimd. MS m/z 300 (M)+and 3 fragments supporting the stated structure. HDRMS m/z calcd for C16H20N4O2 (M)+300,1586, found 300.1586, EXAMPLE 32 4-(BenzyIoxy)-2-(l-piperazinyl)pyrimidine, Dihydrochloride. The title compound was prepared according to the procedure of example 30 starting from benzyl alcohol (0.22 g, 2.0 mmol) to give 0,23 g (31%) of the title compound. MS m/z 270 (M)+ and 6 fragments supporting the stated structure. HRMS m/z calcd for C15H18N4O (M)+270.1481, found 270,1488, EXAMPLE 33 4-(l-PiperazinyI)-2-{[3-(trifluoromethoxy)benzyl]oxy}pyrimidine, Trifluoroacetate, - step 1: 2-Chloro-4-[l-(4-tert-butoxycarbonyl)piperazinyl]pyrimidine.* l-tert-Butoxycarbonylpiperazine (3.72 g, 0.02 mol) was added to a stirred solution of 2,4-dichloropyrimidine (2.98 g, 0.02 mol) and diisopropylethylamine (2.58 g, 0.02 mol) in dichloromethane (200 mL). The reaction mixture was stirred at ambient temperature for 48 h and then concentrated under reduced pressure. The residue obtained was flash-chromatographed over silica using dichloromethane/ether (4:1) as eluent to afford 3.44 g (58%) of the title compound as a colourless solid whose NMR and MS spectra were in agreement with the expected structure. MS (ES+) m/z 299 and 301 (M+H)+. *Previously described in WO 9911657. Step 2: 2-Chloro-4-(l-piperazinyI)pyrimidme,* 2-Chloro-4-[l-(4-tert-butoxycarbonyl)piperazinyl]pyriinidine. (2.00 g, 6.7 mmol; obtained in step 1 above) was dissolved in a 25% v/v solution of trifluoroacetic acid in dichloromethane (25 mL). The solution was stirred at room temperature for 40 min then the solvent was removed by evaporation under reduced pressure. The oily residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic extract was dried and evaporated imder reduced pressure to afford 1.04 g (79%) of the title compoimd as a colourless solid whose NMR and MS spectra were in agreement with the expected stmcture. MS (ES+) m/z 199 and 301 (M+H)+. *Previously described in WO 9535293. Step 3: 4-(l-PiperazinyI)-2-{[3-(trifluoromethoxy)beenylloxy}pyrimidine, Trifluoroacetate. A solution of 2-chloro-4-(l-pipera2inyl)pyrimidine (0.04 g, 0.2 mmol; obtained in Step 2 above) and 3-trifluoromethoxyben2yl alcohol (0.077 g, 0.4 nunol) in tetrahydrofuran (4.0 ml) was treated with a solution of K-t-BuO in tertAmtanol (IM; 0.4 mL, 0.4 mmol). The resulting mixture was heated at 70 **C overnight then allowed to cool. The solvent was evaporated under reduced pressure then the cmde reaction mixture partitioned between ethyl acetate (4,0 mL) and water (2.0 mL). The organic phase was evaporated then purified by preparative C-18 HPLC using CH3CN/H2O/TFA (gradient: CH3CN 20% to 97%, TFA 0.1 %) to afford 11 mg (12%) of the title compound. Purity 85% (HPLC). MS (ES+) miz 355 (M+H)+. EXAMPLE 34 2-[(3-MethoxybenzyI)oxy]-4-(l-piperazinyI)pyrimidine, Trifluoroacetate. The title compound was prepared according to the procedure of example 33, step 3 starting from 3-methoxyben2;yl alcohol (0.055 g, 0.40 mmol) to give 5 mg (6%) of the expected product. Purity >90% (HPLC). MS (ES+) miz 301 (M+H)+. EXAMPLE 35 2-{[3-(BenzyIoxy)benzyl]oxy}-4-(l-piperazinyI)pyriraidine5 Trifluoroacetate. The title compound was prepared according to the procedure of example 33, step 3 starting from 3-benzyloxybenzyl alcohol (0.086 g, 0.40 mmol) to give 10 mg (10%) of the expected product. Purity >90% (HPLC). MS (ES+) m/z 377 (M+H)+. EXAMPLE 36 2-[(3-Phenoxybenzyl)oxy]-4'(l-piperazinyl)pyrimidme, Trifluoroacetate. The title compound was prepared according to the procedure of example 33, step 3 starting from 3-phenoxybenzyl alcohol (0.08 g, 0.4 mmol) to give 8 mg (8%) of the expected product. Purity > 90% (HPLC). MS (ES+) mIz 363 (M+H)+. EXAMPLE 37 2-(2-Naphthylmethoxy)-4-(l-piperazmyI)pyrimidine, Trifluoroacetate, The title compound was prepared according to the procedure of example 33, step 3 starting from 2-n-naphthylmethyl alcohol (0.063 g, 0.4 mmol) to give 10 mg (12%) of the expected product. Purity >90% (HPLC). MS (ES+) mIz 321 (M+H)+ EXAMPLE 38 4-(l-Piperazmyl)-2-{[3-(2-TrifluoromethyI)benzyI]oxy}pyrimidine, Trifluoroacetate. A solution of 2-chloro-4-[l-(4-tert-butoxycarbonyl)piperazinyl]pyrimidine (obtained in example 33, step 1; 0.04 g, 0.2 mmol) and 2-trifluoromethylbenzyl alcohol (0.035 g, 0.20 mmol) in tetrahydrofuran (2.0 mL) was treated with K-r-BuO in tert-butanol (IM; 0.2 mL, 0.2 mmol). The resulting mixture was heated at 65 °C overnight then allowed to coo!. The solvent was evaporated under reduced pressure then the crude reaction mixtures partitioned between ethyl acetate (4.0 mL) and water (2.0 mL). The organic phase was evaporated then purified by preparative C-18 HPLC using CH3CN/H2O/TFA (gradient: CH3CN 20% to 97%, TFA 0.1%) to afford the BOC protected product. This material was then dissolved in a 25% (v/v) solution of trifluoroacetic acid in dichloromethane (5.0 mL) and allowed to stand at room temperature for 30 min. Removal of the solvent under reduced pressure gave 40 mg (44 %) of the title compound. Purity >90% (HPLC). MS (ES+) mlz 339 (M+H)+. EXAMPLE 39 (25)-l-[6-(Benzyloxy)-2-pyrazinyl]-2-methylpiperazine. Step 1: (35)-3-Methyl-l-trityIpiperazine- To a solution of 2-(iS)-methylpiperazine (2,62 g, 26.2 mmol) in dichloromethane (100 mL) was trityl chloride (7.30 g, 26.2 mmol) added and the mixture was stirred at ambient temperature for 1.5 h. The organic phase was washed (x 1) with 1 M aqueous K2CO3, water, and brine. Drying (MgSO4) and solvent removal in vacuo furnished a quantitative yield of the title compound as a glassy oil which solidified upon standing. This material was used directly in the next step. Step 2: (25)-l-(6-Chloro-2-pyrazinyl)-2-methylpiperazme. A mixture of 2-6-dichloropyrazine (1.10 g, 7.39 mmol), and the product firom step 1 above (2.30 g, 6.72 mmol) and K2CO3 (1.0 g, 7.39 mmol) in dry DMF (40 mL) was stirred at 110 °C over night. The dark reaction mixture was filtered through a plug of silica and the solvent was removed under reduced pressure. The remaining oil was dissolved in CHCVn-heptane (1:1) and filtered through a second plug of silica. The solvent was evaporated and the remaining yellow oil was suspended in EtOH (80 mL). 4 M aqueous HCl (2 mL) was added and the mixture was ultrasonicated for 20 min. The solvent was evaporated and the remaining oil was taken up between water/CHCl3. The organic phase was made alkaline (11 M aqueous NaOH) and extracted twice with CHCl3. The combined dried (MgSO4) organic layers were concentrated in vacuo to afford 0.75 g (54%) of the title compound as a yellow oil. MS m/z 212/214 (M)+(35C l/ 37C l-isotope pattern). HRMS miz calcd for C9H13CIN4 (M)+ 212.0829, found 212.0827. Step 3: (25)-l-[6-(Benzyloxy)-2-pyrazinyl]-2-methylpiperazine5 Acetate. To a solution of (25)-l-(6-chloro-2-pyrazinyl)-2-methylpiperazine (prepared in step 2 above; 0.16 g, 0.72 mmol) and benzyl alcohol (0.12 g, 1.1 mmol) in DMF (4 mL) was Na-t-BuO (0.14 g, 1.4 mmol) added and the mixture was stirred at 150 °C overnight. The solvent was evaporated off under reduced pressure and the residue taken up between CHCI3/H2O. The organic phase was concentrated and the crude product was purified by preparative C18-HPLC using acetonitrile/H20/HOAc with UV detection at 254 ma. Yield: 1 mg (0.4%). MS m/z 284 (M)+. HRMS mIz calcd for C16H20N4O (M)+284.1637, found 284.1640. EXAMPLE 40 (2iS)-l-[6-(BenzyIoxy)-4-(trilluoromethyl)-2-pyridinyl]-2-methylpiperazine, Acetate. Step 1: (2iS)-l-[6-Chloro-4-(trifluoromethyl)-2-pyridinyI]-2-methylpiperazme. The title compoimd, obtamed as an oil, was prepared firom the product of example 39, step 1 (2.62 g, 7.62 mmol) and 2,6-dichloro-4-trifluoromethylpyridine (LSI g, 8.38 mmol) according to the procedure of example 39, step 2. Yield: 0.24 g (11%). MS mIz 279/281 (M)+ (°C l/37C-isotope pattem). HRMS mIz calcd for C11H13CIF3N3 (M)+279.0750, found 279.0751. Step 2: (25)-l-[6-(Benzyloxy)-4-(trifluoromethyl)-2-pyridinyl]-2-methylpiperazine, Acetate. The title compund was prepared from the product of step 1 above (0.24 g, 0.86 mmol), benzyl alcohol (0.14 g, 1.29 mmol) and Na-r-BuO (0.165 g, L72 mmol) according to the procedure of example 39, step 3. MS mIz 351 (M)+". HRMS m/z calcd for C18H20F3N3O (M)+351.1558, found 351.1555. EXAMPLE 41 l-[6-(Benzyloxy)-2-pyrazinyI]-2-ethylpiperazine, Acetate. step 1: l-Benzyl-3-ethylpiperazme.* Benzyl bromide (38.7 g, 0.22 mol) was added in portions to a chilled (-- 0 °C) solution of 2-ethylpipera2me (25 g, 0.22 mol) in DMF (150 mL) with such a rate that the temperature did not exceed 20 °C. The mixture was stirred for 1 h, the solvent was evaporated and the residue was partitioned between CHCI3/O.5 M aqueous HCL The aqueous phase was made alkaline (11 M NaOH) and extracted three times with CHCI3. The combined organic phases were dried (MgSO4) and concentrated. The resulting oil was purified by column chromatography on silica using CHCI3, followed by CHCl3/MeOH/NH40H (95:5:0.3) as eluents to give 31.6 g (70%) of the title compound as a yellowish oil. Anal. (C13H20N2) H, N; C: calcd, 76.42; found, 75.85. *Described in WO 00/76984. Step 2: 4-BenzyI-l-(6-chloro-2-pyrazinyl)-2-ethylpiperazine, The title compoimd was prepared according to the procedure of example 39, step 2, starting fi-om the product obtained in step 1 above (4.'60 g, 22.5 mmol), 2,6-dichloropyrazine (3.90 g, 26.2 mmol) and K2CO3 (6.22 g, 45.0 mmol). Yield: 6.15 g (86%). MS m/z 316/318 (M)+(35C l/ 37C l-isotope pattern). HRMS m/z calcd for C17H21CIN4 (M)+316.1455, found 316.1455. Step 3: l-(6-Chloro-2-pyrazinyl)-2-ethylpiperazine. 1-Choroethyl chloroformate (4.16 g, 29.1 mmol) was added dropwise under 2 h to a stirred solution of the product obtained in step 2 above (6.15 g, 19.4 mmol) in dry dichloromethane (75 mL) at 0 °C. After being stirred at room temperature for 15 h, the reaction mixture was concentrated in vacuo and methanol was added. The mixture was heated at reflux for 2 h and concentrated. The residue was dissolved in CHCI3 and passed through a short (4 cm) plug of silica gel using CHCl3/MeOU (8:2) as eluent Solvents were evaporated off and the residue was purified by chromatography on silica gel (12 x 5 cm) using CHCl3/MeOH/EtsN (95:5:0.2) as eluent. This provided 1.9 g (43%) of the title compound as an oil. MS m/z 226/228 (M)+(35Cl/37Cl l-isotope pattern). HRMS m/z calcd for C10H15CIN4 (M)+226.0985, found 226.0986. step 4: l-[6-(Benzyloxy)-2-pyrazmyl]-2-ethylpiperazme, Acetate. The title compund was prepared according to the procedure of example 39, step 3, starting from the product of step 3 above (0.163 g, 0.72 romol), benzyl alcohol (0.12 g, 1.08 mmol) and Na-t-BuO (0.14 g, 1.4 mmol). Purity 90% (HPLC). MS m/z 298 (M)+. HRMS miz calcd for C17H22N4O (M)+ 298.1794, found 298.1802. EXAMPLE 42 2-[(4-FluorobenzyI)oxy]-6-(l-pipera2inyl)pyrazine. 4-Fluorobenzyl alcohol (0.189 g, 1.50 mmol) was dissolved m THF (1 mL) and treated with NaH (0.065 g, 55% dispersion in mineral oil, 1.5 mmol). The reaction mixture was stirred at room temperature for 3 h. A solution of 2,6-dichloropyrazine (1.57 g, 10.5 mmol) in THF (7 mL) was added and the resulting mixture was stirred for 4 h at room temperature. Piperazine (0.580 g, 6.75 mmol) and K2CO3 (0.43 g, 4.5 mmol) were added and the mixture was stired at 60 °C over night. Filtration,' concentration, and purification by chromatography on silica gel using ethyl acetate/acetic acid/methanol/water (24:3:3:2) as eluent furnished 0.20 g (46%) of the title compound as a white solid: mp 183 °C , HRMS m/z calcd for C15H17FN40 (M)+" 288.1386, found 288.1380. Anal. (C15H17FN4O. 2.6H2O) C, H, N. EXAMPLE 43 2-((4-MethoxybenzyI)oxy]-6-(l-pipera2inyl)pyrazine, Acetate. The title compound was prepared according to the procedure of example 42 starting fi-om 4-methoxybenzyl alcohol (0.207 g, 1.50 mmol) and was isolated as a yellow solid. Yield: 0.79 g (67%). HRMS m/z calcd for C16H20N4O2 (M)+ 300.1586, found 300.1584. EXAMPLE 44 2-I2-(4-Fluorophenyl)ethoxyJ-6-(l-piperazinyI)pyrazme, 0.5 Acetate The title compound was prepared according to the procedure of example 42 starting from 2-(4-fluorophenyl)ethanol (0.210 g, 1-50 mmol) and was isolated as a yellow solid. Yield: 0.145 g (27%). HRMS m/z calcd for C16H19FN4O (M)+302.1543, found 302.1554. Anal. (C16H19FN4O • 0,5CH3COOH • H2O) C, H, N. EXAMPLE 45 2-[2-(3--Methoxyphenyl)ethoxy]-6-(4-piperidinyIoxy)pyrazine. Step 1: tert-Butyl 4-[(6-chloro-2-pyrazinyl)oxy]-l-piperidinecarboxylate. A mixture of 2,6-dichloropyra2ine (5.00 g, 33.6 mmol), tert-butyl 4-hydroxy-l-piperidinecarboxylate (6.76 g, 33.6 mmol) and K-t-BuO (1 M in tert-butanol; 35 mL, 35 mmol) in Et3N (200 mL) was stirred at room temperature for 12 h. The reaction was quenched with water (50 mL) and concentrated in vacuo. The residue was dissolved in ethyl acetate, washed with saturated aqueous KH2PO4, dried (MgSO4), and concentrated in vacuo. The residue was recrystallized from ethanol/water to give 9.50 g (90 %) of the title compound as a white solid: mp 86-87 °C; MS m/z 313 (M)"". Anal. (C14H20CIN3O3) C, H, N. Step 2:2-Chloro-6-(4-piperidinyloxy)pyrazine. Aqueous 3.0 M HCl (12 mL) was added to a solution of the product obtained in Step 1 above (5.00 g, 15.9 mmol) in methanol (200 mL). The reaction mixture was stirred at 50 °C for 5 h and concentrated in vacuo. The residue was dissolved in water (50 mL) and basified with K3PO4. The aqueous phase was e: /acted with ethyl acetate (5 X 40 mL), dried (MgS04), and concentrated m vacuo. This gave 3.08 g (91%) of the titie compound as a colorless oil which slowly decomposed upon standing. HRMS m/z calcd for C9H12CIN3O (M)+213.0669, found 213.0663. Step 3:2-[2-(3-Methoxyphenyl)ethoxyl-6-(4-piperidmyloxy)pyrazine. A solution of the product obtained in Step 2 above (0.043 g, 0.20 mmol) in DMF (1.1 mL) was added to a mixture of 3-methoxyphenethyl alcohol (0.061 g, 0.40 mmol) and K--t-BuO (1.0 M in tert-butanl; 0.4 mL, 0.40 mmol) in DMF (0.8 mL). The reaction mixture was vortexed for 16 h at 50 °C under nitrogen, quenched with water (0.1 mL) and concentrated in vacuo. The residue was partitioned between water (2 mL) and 4 ethyl acetate (4 mL) and poured through a hydromatrix column, which was eluted with ethyl acetate/EtsN (95:5). Solvents were evaporated off and the residue was dissolved in methanol/ water (50 mL) and loaded onto a conditioned weak cation exchange SPE column (1 g, Amberiyst CG-50 J). The column was washed with water (10 mL) and methanol (10 mL). The compound was eluted with aqueous 2.0 M NH3 in methanol (20 m) and concentrated in vacuo. The residue was analysed for identity and purity by LC-UV/MS. Yield: 8 mg (12%). HRMS m/z calcd for C18H23N3O3 (M)+329.1739, found329.1743. EXAMPLE 46 2-(2-Phenylethoxy)-6-(4-piperidinyloxy)pyrazine. The title compound was prepared according the procedure of example 45, step 3, starting from 2-phenylethanol (49 mg, 0.40 mmol). The product was analysed for identity and purity by LC-UV/MS. Yield: 7 mg (12%). HRMS m/z calcd for C17H21N3O2 (M)+299.1634, found 299.1630. EXAMPLE 47 2-(3-Phenoxypropoxy)-6-(4-piperidinyloxy)pyrazine. The title compound was prepared according the procedure of example 45, step 3, starting from 3-phenoxy-l-propanol (61 mg, 0.40 mmol). The product was analysed for identity and purity by LC-UV/MS. Yield: 28 mg (43%). HRMS m/z calcd for C18H23N3O3 (M)+329.1739, found 329.1743. EXAMPLE 48 2-[(5-PhenyIpentyI)oxy]-6-(4-piperidinyloxy)pyrazine. The title compound was prepared according the procedure of example 45, step 3, starting from 5-phenyl-l-pentanol (66 mg, 0.40 mmol). The product was analysed for identity and purity by LC-UV/MS. Yield: 17 mg (25%). EXAMPLE 49 2-{[3-(BenzyIoxy)benzyI]oxy}-6-(4-piperidinyloxy)pyrazine. The title compound was prepared according the procedure of example 45, step 3, starting from 3-benzyloxybenzyl alcohol (86 mg, 0.40 mmol). The product was analysed for identity and purity by LC-UV/MS. Yield: 43 mg (55%). HRMS m/i calcd for C23H25N3O3 (M)+" 391.1896, found 391.1905. EXAMPLE 50 2-[l-(2-Methoxyhenyl)ethoxy]-6-(l-piperazinyI)pyra2me, Step 1: 2-Chloro-6-Il-(-methoxyphenyl)ethoxy]pyrazine. K-t-BuO (0.67 g, 5.97 mmol) was added to a stirred solution of l-(2-methoxyphenyl)ethanol (0.96 g, 6.28 mmol) in dioxane (15 mL) at 0 °C (ice-bath). After 5 min of stirrg at room temperature, the reaction mixture was chilled to 0°C (ice-bath) and 2,6-dichloropyrazine (0.78 g, 5.23 mmol) was added whereupon the reaction mixture turned yellow. After being stirrred for 35 min, dichloromethane and K2CO3 were added and the mixture was filtered. Concentration in vacuo furnished a yellow oil that was purified by sihca gel chromatography (15x4 cm) using /z-hexane ethyl acetate (8:2) as eluent. This gave 1.21 g (92%) of the title compoimd as a colorless oil. HRMS m/z calcd for C13H13CIN2O2 (M)+ 264,0666, found 264.0677. Anal. (C13H13CIN2O2) C, H, N. Step 2: 2-[l-(2-MethoxyphenyI)ethoxy]-6-(l-piperazinyl)pyrazme. A mixture of the product from step 1 above (0.93 g, 3.53 mmol) piperazine (0.88 g, 10.2 mmol) and K2CO3 (0.49 g, 3.53 mmol) in acetonitrile (7 mL) was heated in a sealed pyrex flask at 90 °C for 6.5 h. The reaction mixture was diluted with dichloromethane, filtered and concentrated in vacuo. The semi-solid residue was purified by silica gel chromatography (13 x 4 cm) using CHCl2/MeOH (9:1) as eluent. Solvents were evaporated ofif and the remaining oil was redissolved in CHCI3, filtered through a short plug of alumina, covered with K2CO3, using CHCI3 as eluent Solvent removal in vacuo gave 0.74 g (67%) of the title compound as a beige oil. HRMS mlz calcd for C17H22N4O2 (M)+ 314.1743, found 314.1733, Anal. (C17H22N4O2 • O.5H2O) C, H, N. EXAMPLE 51 l-[6-(Benzyloxy)-2-pyrazinyl]-trans-2,5-dimethylpipera2me, Step 1: l-(6-Chloro-2-pyrazinyl)-trans-2,5-dimethylpiperazine. A mixture of 2,6-dichloropyrazine (0,40 g, 2.68 mmol), trans'-2,5-dimethylpiperazine (0.62 g, 5.43 mmol), K2CO3 (0.41 g, 3.0 mmol) in acetonitrile (5 mL) was stirred at 90 °C for 6 h in a sealed pyrex tube. After cooling, the reaction mixture was filtered and concentrated in vacuo. The oily residue was purified by column chromatography on silica gel using CHCl3/MeOH (9:1) as eluent This furnished 0.15 g (25%) of the title compound as an oil. HRMS m/z calcd for C10H15CIN4 (M)+ 226.0985, found 226.0983. Step 2: l-[6-(Benzyloxy)-2-pyrazinyl]-rra/i5-2,5-dimethylpiperazine. The title compound was prepared according to the procedure of example 20, starting from l-(6-chloro-2-pyrazinyl)-trans-2,5-dimethylpipera2ine (1.23 g, 5.40 mmol; obtained in step 1 above), benzyl alcohol (8.36 g, 77.3 mmol), and K-BuO (1.99 g, 17.7 mmol). The reaction mixture was heated at 95 °C for 5.5 h. The yield of the title compound was 0.47 g (29%) which was obtamed as an oil. Purity 99% (HPLC), MS m/z 298 (Mf. HRMS m/z calcd for .C17H22N4O (M) ^ 298.1794, found 298,1798. EXAMPLE 52 2-[2-(2,3-DimethoxyphenyI)ethoxyl-6-(l-pipera2myl)pyrazme,Maleate, The title compound Was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-[2-(2,3-dimethoxyphenyl)ethoxy]pyrazine [0.65 g, 2.2 mmol; obtained according to the procedure of example 50, step 1, starting firom 2-(2,3-dimethoxyphenyl)ethan-l-ol], piperazine (0.57 g, 6.7 mmol) and K2CO3 (0.31 g, 2.22 mmol). The free base of the title compound was converted into its maleate salt Recrystallization firom MeOH-ether furnished 0.45 g (44%) of the title compound. Purity 98% (HPLC). MS m/z 345 (M + H)+ HRMS m/z calcd for C18H24N4O3 (M)+344.1848, found 344.1861. EXAMPLE 53 2-[2-(2-FIuorophenyI)ethoxy]-6-(l -piperazinyl)pyrazine, Maleate. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-[2-(2-fluorophenyl)ethoxy]pyrazine (2.76 g, 10.9 mmol; obtained according to the procedure of example 50, step 1, starting from 2-fluorophenethyl alcohol), piperazine (2.91 g, 33.8 mmol) and K2CO3 (1.51 g, 10.9 mmol). The yield of the free base of the title compound was 1.88 g (57%) which was converted into its maleate salt. Recrystallization from MeOH-ether furnished 2.11 g of the title compound. Purity 100% (HPLC). MS miz 303 (M + H)+. HRMS miz calcd for C16H19FN4O (M)+302.1543, found 302.1550. EXAMPLE 54 2-[(2,3-Dimethoxybenzyl)oxy]-6-(l-piperazinyI)pyrazine. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-[(2,3-dimethoxybenzyl)oxy]pyrazine (2.51 g, 8.93 mmol; obtained according to the procedure of example 50, step 1, starting from 2,3- dimethoxybenzyl alcohol), piperazine (2.38 g, 27.7 mmol) and K2CO3 (1.23 g, 8.9 mmol). The yield of the title compound was 1.66 g (56%) which was obtained as an oil. Purity 100% (HPLC). MS m/z 331 (M + H)+. HRMS m/z calcd for C17H22N4O3 (M)+ 330.1692, found 330.1690. EXAJvlPLE55 2-(2,3-Dihydro-1H'-mden-l-ylmethoxy)-6-(l-piperazinyl)pyrazme, Maleate. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-(2,3-dihydro-lH-inden-l-yhnethoxy)pyrazine (3.22 g, 13.1 mmol; obtained according to the procedure of example 50, step 1, starting from 1-indanol), piperazine (3.49 g, 40.5 mmol) and K2CO3 (1.8 g, 13.0 namol). The yield of the free base of the title compound was 2.19 g (57%) which was obtained as an oil. The free base was converted into its maleate salt. Purity 100% (HPLC). MS miz 296 (M)+. HRMS m/z calcd for C17H20N4O (M)" 296.1637, found 296.1643. EXAMPLE 56 2-(4-Phenoxybutoxy)-6-(l-piperazinyl)pyrazine. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-(4-phenoxybutoxy)pyrazine (1.99 g, 7.14 mmol; obtained according to the procedure of example 50, step 1, starting from 4-phenoxy-l-butanol*), piperazine (1.84 g, 21.4 mmol) and K2CO3 (0.99 g, 7.14 mmol). The yield of the title compound was 1.52 g (65yo) which was obtained as an oil. Purity 100% (HPLC). MS ni/z 329 (M+ H)+. HRMS m/z calcd for C18H24N4O2 (M)+328.1899, found 328.1894. *Prepared by reduction (LiAfflLj) of the corresponding acid (cf J. Org. Chem. 1965,30,2441-2447; ibid 1968.33,2271-2284). EXAMPLE 57 2-[(5-Phenoxypentyl)oxy]-6-(l-piperazinyl)pyrazine The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-[(5-phenoxypentyl)oxy]pyra2ine (2.06 g, 7.03 mmol; obtained according to the procedure of example 50, step 1, starting from 5-phenoxy- 1-pentanol*), piperazine (1.88 g, 21,8 mmol) and K2CO3 (0.97 g, 7.03 mmol). The yield of the title compound was 1.15 g (48%) which was obtained as a white solid. Purity 100% (HPLC). MS m/z 343 (M + H)"". HRMS m/z calcd for C19H26N4O2 (M)+342.2056, found 342,2054. *Described ia J, Org. Chem. 1968,33,2271-2284. EXAMPLE 58 2-[(2^-DimethoxybenzyI)oxyy]-6-piperazinyl)pyrazine. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-[(2,5-dimethoxyben2yl)oxy]pyra2ine (1.02 g, 3.63 mmol; obtained according to the procedure of example 50, step 1, starting from 2,5-dimethoxybenzyl alcohol), piperazine (0,94 g, 10.9 mmol) and K2CO3 (0.50 g, 3.63 mmol). The yield of the title compound was 0.64 g (53%) which was obtained as a beige solid. Purity 100% (HPLC). MS m/z 331 (M + H)+. HRMS m/z calcd for C17H22N4O3 (M)+330.1692, found 330.1692. EXAMPLE 59 2-[2-(3,4-Dimethoxypheny])ethoxy]-6-(l-piperazinyl)pyrazine,Maleate. The title compoimd was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-[2-(3,4-dimethoxyphenyl)ethoxy]pyrazine [2.13 g, 7.23 mmol; obtained according to the procedure of example 50, step 1, starting from 2- (3,4-dimethoxyphenyl)ethan-l-olj, piperazine (1.93 g, 22A mmol) and K2CO3 (1.0 g, 7.2 mmol). The yield of the title compound was 1.72 g (69%) which was obtained as a beige oil. Purity 1 100% (HPLC). MS miz ZAS (M + H)"". The free base was converted into ints maleate salt. HRMS mIz calcd for C18H24N4O3 (M)+344.1848, found 344.1832. EXAMPLE 60 2-{[2-(2-Phenylethyl)benzylloxy}-6-(l-piperazinyl)pyrazine. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-{[2-(2-phenylethyl)benzyl]oxy}pyra2ine (1.72 g, 5.30 mmol; obtained according to the procedure of example 50, step 1, startmg from 2- phenethylbenzyl alcohol), piperazine (1,37 g, 16.0 mmol) and K2CO3 (0.73 g, 5.3 mmol). The yield of the title compound was 1.38 g (69%) which was obtained as an oil. Purity 100% (HPLC). MS mIz 375 (M + H)-". HRMS mIz calcd for C23H26N4O (M)+374.2107, found 374.2113. EXAMPLE 61 2-f(3-Phenoxyben2yl)oxy]-6-(l-piperazinyl)pyrazine. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-f(3-phenoxyben2yl)oxy]pyrazine (1.99 g, 6.36 mmol; obtained according to the procedure of example 50, step 1, starting from 3- phenoxybenzyl alcohol), piperazine (1.94 g, 22.5 mmol) and K2CO3 (0.88 g, 6.4 mmol). The yield of the title compound was 1.58 g (69%) which was obtained as an oil. Purity 100% (HPLC). MS m/z 363 (M + H)+. HRMS m/z calcd for C21H22N4O2 (M)+362.1743, found 362.1739. EXAMPLE 62 (2.R)-l-(6-(Benzyloxy)-2-pyrazinyll-2-methylpiperazine, Maleate. Step 1: (3R)-3-Methyl-l-tritylpipera2ine. The title compound was prepared according to the procedure of Example 39, step 1, with the exception that (2R)-methylpipera2ine was substituted for (2S)-methylpiperazine. The title compound was obtained as a light yellow crispy solid. Step 2: (2i?)-l-(6-ChIoro-2-pyrazinyl)-2-methylpiperazine5 Maleate. A mixture of 2.6-dichloropyrazine (2.33 g, 15.7 mmol), the product from step 1 above (5.11 g, 14.9 mmol) and K2CO3 (3.09 g, 22.4 mmol) in dry DMF (50 mL) was stirred at 120 °C for 7.5 h. The dark reaction mixture was diluted with ether and solids were filtered off. The filter cake was washed with CHCI3. The filtrate was concentrated under reduced pressure. The residue was redissolved in CHCI3 (150 mL) and 5M aqueous HCl (20 mL) was added and the mixture was stirred at room .temperature 8.5 h. A solution of 5 M aqueous NaOH (25 mL) was added carefully and the layers were separated. The aqueous layer was extracted with CHCI3 (2 x 150 mL). The combined, dried (K2CO3), organic phases were concentrated in vacuo. The brownish oily residue was purified by silica gel chromatography (bed size: 11x6 cm) using CHCl3/McOH (92:8) as eluent. The yield of the free base of the title compound was 1.74 g (55%) which was obtained as a tan colored oil. A portion (0.41 g, 1.9 mmol) of the free base was converted into its maleate salt. Purity 99% (HPLC). HRMS 7n/z calcd for C9H13CIN4 (M)+212.0829, found 212.0819. Step 3: (2if)-l-[6-(Ben2yloxy)-2-pyra2myl]-2-methylpiperazine, Maleate. K-r-BuO (2.07 g, 18.4 mmol) was added to a mixture of (2R)-H6-cliloro-2-pyrazinyl)-2-methylpipera2ine (prepared in step 2 above; 1.31 g, 6.15 mmol) and benzyl alcohol (10.0 g, 92.5 mmol). After being stirred for 7 h at 95 °C, the mixture was applied onto a bed of silica (12 x 6 cm). Elution with CHCl3/MeOH (97:3 followed by 92:8) furnnished 1.44 g (82%) of the free base of the title compound as a light yellow oil. The free base was converted into its maleate salt Purity 99% (HPLC). MS m/z 284 (M)+ HRMS TW/Z calcd for C16H20N4O (M)+284.1637, found 284.1633. EXAMPLE 63 (2R)-l-l6-(Benzyloxy)-(trifluoromethyI)-2-pyridinyl]-2-methylpiperazine. The title compound was prepared according to the procedure of example 40 with the exceptions that (ZR)-methylpiperazine was substituted for (25)-methylpiperazine in step I and that N-deprotection (N-detritylation) in step 2 was carried out using trifluoroacetic acid in dichloromethaue (3:1). MS m/z 352 (M + H)+. HRMS m/z calcd for C18H20F3N3O (M)+351.1558, found 351.1549. EXAMPLE 64 (2R)-l-[6-(Benzyloxy)-2-pyridinyl]-2-methylpipera2ine. The title compound was prepared according to the procedure of example 39 with the exceptions that (2i?)-methy]piperazine was substituted for (2iS)"methylpipera2ine in step 1, and that 2,6-dichloropyridine was substituted for 2,6-dichIoropyrazine in step 2, and further that N-deprotection (A'-detritylation) in step 2 was carried out using trifluoroacetic acid in dichloromethane (3:1). MS mlz 284 (M + H)"*". EXAMPLE 65 2-(l-PiperazinyI)-6-{[3-(lH-pyrrol-l-yl)-2-thienyl]methoxy}pyrazine. Step 1: 2-Chloro-6-{f3-(1H-pyrroH-yl)-2-thienyl]methoxy}pyra2me. The title compound was prepared according to the procedure of example 50, step 1, starting from 3-(pyrrol-yl)thiophene-2-methanol (2.5 g, 14 mmol), K-f-BuO (1.43 g, 12.7 mmol) and 2,6-dichloropyrazine (1.73 g, 11.6 mmol). The yield of the title compound was 3.05 g (90%) and was obtained as an oil. Anal. (C13H10CIN3OS) C, H,N. Step 2:2-(l-PiperazinyI)-6-{[3-(lH-pyrrol-1-yl)-2-thienyI]methoxy}pyrazine The title compound was prepared according to the procedure of example 50, step 2, starting from the product obtained in step 1 above (1.78 g, 6.10 mmol), piperazine (1.58 g, 18.3 mmol) and K2CO3 (0.86 g, 6.2 mmol). The yield of the title compound was 1.43 g (69%) and was obtained as a beige solid. HRMS m/z calcd for C17H19N5OS (M)+341.1310, found 341.1301. EXAMPLE 66 2-{[3-(Benzyloxy)benzyl]oxy}-6-(l-piperazinyl)pyrazine. Step 1: 2-{[3-(Ben2yloxy)benzyIloxy}-6-chloropyrazine, The title compound was prepared according to the procedure of example 50, step 1, starting from 3-benzyloxybenzyl alcohol (3.46 g, 16.2 mmol), K-BuO (1.69 g, 15.1 mmol) and 2,6-dichloropyrazine (1.97 g, 13.2 mmol). The yield of the title compoimd was 2.64 g (61%) and was obtained as a semisolid. Anal. (C18H15ClN2O2) C, H, N. Step 2: 2-{[3-(Benzyloxy)benzyl]oxy}-6-(l-piperazinyl)pyra2me. The title compound was prepared according to the procedure of example 50, step 2, starting from the product obtained in step 1 above (1.62 g, 4.96 mmol), piperazine (1.28 g, 14.9 mmol) and K2CO3 (0.70 g, 5.1 mmol). The yield of the title compound was 1.16 g (62%) and was obtained as an oil. HRMS ni/z calcd for C22H24N4O2 (M) +376.1899, found 376.1890. Anal. (C22H24N4O2) C, H, N. EXAMPLE 67 2-(l-PiperazmyI)-6-[3-(2-pyridinyl)propoxy]pyrazine, Maleate. Step 1:2-Chloro-6-[3-(2-pyridinyI)propoxy]pyrazine, The title compound was prepared according to the procedure of example 50, step 1, starting from 2-pyridinepropanol (4.08 g, 29.7 mmol), K-r-BuO (3.17 g, 28.3 mmol) and 2,6-dichloropyra2ine (3.69 g, 24.8 mmol). The yield of the title compoimd was 5.18 g (84%) and was obtained as an oil. Anal. (C12H12CIN3O) C, H, N. Step 2:2-(l-Piperazinyl)-6-[3-(2-pyridmyl)propoxylpyrazine, Maleate. The title compound was prepared according to the procedure of example 50, step 2, starting from the product obtained in step 1 above (1.80 g, 7.20 mmol), piperazine (1.87 g, 21.6 mmol) and K2CO3 (1.0 g, 7,2 mmol). The free base (L23 g) of the title compoimd was converted into its maleate. Recrystallization from MeOH-ether furnished 1.32 g (38%) of the title compound. HRMS m/z calcd for C16H21N5O (M)+ 299.1758, found 299.1748. Anal. (C16H21N5O • L5C4H4O4 • O.5H2O) C, H, N. EXAMPLE 68 2-[(3,5-Dimethoxybenzl)oxy]-6-(l-piperazinyl)pyrazinaleate. Step 1: 2-Chloro-6-I(3,5-dimethoxybenzyl)oxy]pyrazne, The title compound was prepared according to the procedure of example 50, step 1, starting from 3,5-dimethoxyben2yl alcohol (2.16 g, 12.8 mmol), K-t-BuO (1.34 g, 11.9 mmol) and 2,6-dichloropyrazine (1.59 g, 10.7 mmol). The yield of the title compound was 2.56 g (84%) and was obtained as a white soli HRMS m/z calcd for C13H13CIN2O3 (M)+280.0615, found 280.0627. Anal. (C13H13CIN2O3) C, H, N. Step 2: 2-[(3,5-Dimethoxyben2yl)oxy]-6-(l-pipera2inyI)pyrazine, Maleate. The title compound was prepared according to the procedure of example 50, step 2, starting from the product obtained in step 1 above (1.26 g, 4.50 mmol), piperazine (1.12 g, 13.0 mmol) and K2CO3 (0.62 g, 4.5 mmol). The free base (1.14 g) of the title compound was converted into its maleate salt. Recrystallization from MeOH-ether fumished 1.05 g (68%) of the title compound: mp 134-137 °C . HRMS m/z calcd for C17H22N4O3 (M)+330.1692, found 330.1699. Anal. (C17H22N4O3 • C4H4O4) C, H, N. EXAMPLE 69 2-(2-(4-MethoxyphenyI)ethoxy]--6-(l-piperazinyI)pyrazine, Maleate. Step 1:2-Chloro-6-[2-(4-methoxyphenyl)ethoxy]pyrazine. The title compound was prepared according to the procedure of example 50, step 1, starting from 4-methoxyphenethyl alcohol (1.99 g, 13.1 mmol), K-BuO (1.34 g, 12.0 mmol) and 2,6-dichloropyra2ine (1.56 g, 10.5 mmol). The yield of the title compound was 2.14 g (77%) and was obtained as a white solid. Anal. (Ci3Hi3aN202)C,H,N. Step 2:2-[2-(4-MethoxyphenyI)ethoxy]-6-(l-piperazinl)pyrazme, Maleate. The title compound was prepared according to the procedure of example 50, step 2, starting from the product obtained in step 1 above (1-31 g, 4.95 mmol), piperazine (1.24 g, 14.4 mmol) and K2CO3 (0.68 g, 4.9 mmol). The free base (1.29 g) of the title compound was converted into its maleate salt. Recrystallization from MeOH-eiher furnished 1.41 g (79%) of the title compound: mp 149-151 °C . HRMS m/z calcd for C17H22N4O2 (M)+ 314.1743, found 314.1727. Anal. (C17H22N4O2 • C4H4O4) C, H, N. EXAMPLE 70 2-[2-(4-Methyl-l,3-thia2oI-5-yI)ethoxy]-6-(l-piperazinyl)pyra2ine, Acetate. The title compound was prepared according to the procedure of example 42 starting from 4-methyl-5-hydroxyethyl thiazole (0.215 g, 1.50 mmol) and was isolated as a brown oil. Yield: 0,41 g (66%). HRMS m/z calcd for C14H19N5OS (M)+ 305.1310, found 300.1325. Anal. (C14H19N5OS • I.5CH3COOH • O.7H2O). General procedure for synthesis of the title compounds described in Examples 71-96. To the appropriate alcohol or thiol (1.8 mmol) in dry DMF (5 mL) was added Na-t-BuO (1.20 ml, 2.5 M in DMF) and the mixture was stirred at room temperature for 15 minutes. To the mixture was added a solution of the appropriate piperazino-substituted chloro heterocycle (0.625 mL, 2.0 M in DMF) and the mixture were stirred at 100 °C for 5 h. The reactions were quenched with water (0.2 mL) and the solvent was removed under reduced pressure. The residue was taken up in water/CHCl3 (20:80; 5 mL) and applied onto a column of Hydromatrix (40 mL) to which water (5 mL) had been added. Elution with CHCI3 (4x8 mL) furnished the crude products. Concentration under reduced pressure and purification of the residues by preparative HPLC furnished the desired products as their acetic acid salts. EXAMPLE 71 2-[2-(3-Methoxyphenoxy)ethoxy]-6-(l-piperazinyl)pyrazme, Acetic acid salt Starting materials, 2-chloro-6-(l-piperazinyl)pyrazine*, and 2-(3-methoxyphenoxy)-ethanol. Purity 90% (HPLC). Fragmenting mass analysis supports the stated structure. HRMS m/z calcd for C17H22N4O3 (M)+330.1692, found 330.1681, *Obtained in Example 13, step 2. EXAMPLE 72 2-[2-(2,6-Difluorophenoxy)ethoxy]-6-(l-piperazinyl)pyrazine, Acetic acid salt Starting materials, 2-chloro-6-(l-piperazinyl)pyrazine and 2-(2,6-difluorophenoxy)-ethanol. Fragmenting mass analysis supports the stated structure. Purity 90% (HPLC). HRMS w/z calcd for C16H18F2N4O3 (M)+336.1398, found 336.1403. EXAMPLE 73 2-[2-(Quinolin-8-yloxy)ethoxy]-6-(l-piperazinyl)pyrazine, Acetic acid salt Starting materials, 2-chloro-6-(l-piperazinyl)pyrazine and 2-(quinoIin-8- yloxy)ethanoI,* Fragmenting mass analysis supports the stated structure. Purity 90% (HPLC). HRMS m/z calcd for C19H21N5O2 (M)+"351.1695, found 351.1683. *Described in WO 00/76984. EXAMPLE 74 2-[(2if)-2^-Dihydro-l,4-ben2odioxin-2-ylmethoxyJ-6-(l-piperazinyI)pyrazine, Acetic acid salt Starting materials, 2-chloro-6-(l-piperazinyl)pyrazine and (2R)-2-hydroxymethyl-1,4-benzodioxan*. Fragmenting mass analysis supports the stated structure. Purity 90% (HPLC). HRMS m/z calcd for C17H20N403 (M)+328.1535, found 328.1524. *Described in Tetrahedron Lett. 1988,29,3671-4. EXAMPLE 75 2-[2-(2-NaphthyIoxy)ethoxy]-6-(l-piperazmyl)pyraziiie, Acetic acid salt Starting materials, 2-chloro-6-(l-piperazinyl)pyrazine and 2-(naphthalen"2-yloxy)-ethanol. Fragmenting mass analysis supports the stated structure. Purity 90% (HPLC). HRMS ni/z calcd for C20H22N4O2 (M)'350.1743, found 350.1752 EXAMPLE 76 2-{2-[(2-Ethoxy-3-pyridinyl)oxy]ethoxy}-6-(l-piperazinyl)pyra2ine, Acetic acid salt Starting materials, 2-Chloro-6-(l-piperazinyl)pyra2ine and 2-(2-ethoxypyridin-3-yloxy)-ethanol*. Fragmenting mass analysis supports the stated structure. Purity 80% (HPLC). HRMS m/z calcd for C17H23N5O3 (M)+ 345.1801, found 345.1793. *Described in WO 00/76984. EXAMPLE 77 2-{[4-(Benzyloxy)-3-methoxybenzyl]oxy}-6-(l-piperazinyl)pyrazine, Acetic acid salt Starting materials, 2-chloro-6-(l-piperazinyl)pyra2ine and (4-benzyloxy-3-methoxyphenyl)_-methanol. Fragmenting mass analysis supports the stated structure. Purity 90% (HPLC). HRMS in/z calcd for C23H26N4O3 (M)+406.2005, found 406.1967. EXAMPLE 78 2-{[5-(Phenylethynyl)-2-thienyl]raethoxy}-6-(l-piperazinyl)pyrazine, Acetic acid salt Starting materials, 2-chloro-6"(l-piperazinyl)pyrazine and (5-phenylethynyl-thiophen-2-yl)-methanol. Fragmenting mass analysis supports the stated structure Purity 80% (HPLC). HRMS nx/z calcd for C21H20N4OS (M)+376.1358, found 376.1346. EXAMPLE 79 2-(23-Dihydro-l ,4-benzodioxiln-6-ylmethoxy)-6-(l-piperazinyl)pyrazine5 Acetic acid salt. Starting materials, 2-chloro-6-(l-piperazinyl)pyrazine and (2,3-dihydro-l,4-ben2odioxin-6-yl)-methanol. Fragmenting mass analysis supports the stated structure. Purity 90% (HPLQ. HRMS m/z calcd for C17H20N4O3 (M)+ 328.1535, found 328.1543. EXAMPLE 80 2-(l-Methyl-2-phenyIethoxy)-6-(l-piperazinyI)pyrazine, Acetic add salt The general procedure was followed with the exception that the reaction mixture was heated at 100 overnight Starting materials, 2-chloro-6-(l-piperazinyl)pyra2ine and l-phenylpropan-2-ol. Fragmenting mass analysis supports the stated structure. Purity 70% (HPLC), HRMS m/z calcd for C17H22N4O (M)+298.1794, found 298.1801, EXAMPLE 81 2-[(2-ChlorobenzyI)sulfanyl]-6-(l-piperazinyl)pyrazine, Acetic acid salt. Starting materials, 2-chloro-6-(l-piperazinyl)pyrazine and (2-chlorophenyl)-methanethiol. Fragmenting mass analysis supports the stated structure. Purity 90% (HPLC). HRMS m/z calcd for C15H17CIN4S (M)+" 320.0862, found 320.0868 EXAMPLE 82 2-[(2-Phenylethyl)sulfanyl]-6-(l-piperazinyl)pyra2ine, Acetic acid salt. Starting materials, 2-chloro-6-(l-piperazinyl)pyrazine and 2-phenyl-ethanethiol. Fragmenting mass analysis supports the stated structure. Purity 90% (HPLC). HRMS m/z calcd for C16H20N4S (M)+" 300.1409, found 300.1419. EXAMPLE 83 2-[(4-Phenoxyben2yI)oxy]-6-(l-piperazinyl)pyrazinee Acetic acid salt Starting materials 2-chloro-6-(l-piperazinyl)pyra2ine and 4-phenoxyben2yl alcohol*. Fragmenting mass analysis supports the stated structure. Purity 90% (HPLC). HRMS m/z calcd for C21H22N4O2 (M)+"362.1743, found 362.1738. ^Prepared by reduction of 4-phenoxybenzaldehyde. EXAMPLE 84 2-{[4-(3-Dimethylamino-propoxy)benzyl]oxy}-6-(l-piperazinyl)pyra2ine5 Acetic acid salt. Starting materials, 2-chloro-6-(l-piperazinyl)pyra2ine and [4-(3-dimethylainino-propoxy)-phenyl]-methanol. Fragmenting mass analysis supports the stated structure. Purity 90% (HPLC). HRMS m/z calcd for C20H29N5O2 (M)+ 371.2321, found 371.2314. EXAMPLE 85 2-{2-[2-(Ben2yloxy)phenyl]ethoxy}-6-(l-piperazinyl)pyrazine, Acetic acid salt Starting materials, 2-chloro-6-(l-piperazinyl)pyrazine and 2-(2-benzyloxy-phenyl)-ethanol.* Fragmenting mass analysis supports the stated structure. Purity 70% (HPLC). HRMS m/z calcd for C23H26N4O2 (M)""390.2056, found 390.2043. *Prepared by reduction of (2-benzyloxy-phenyl)-acetic acid. EXAMPLE U 2-[2-(2,5-Dimethoxyphenyl)ethoxy]-6-(l-piperazinyl)pyrazine, Acetic acid salt Starting materials, 2"Chloro-6"(l-piperazinyl)pyra2ine and 2-(2,5-dimethoxy-phenyl)-ethanol*. Fragmenting mass analysis supports the stated structure. Purity 80% (HPLC). HRMS m/z calcd for C18H24N4O3 (M)+344.1848, found 344.186L ♦Prepared by reduction of (2,5-dimethoxy-phenyl)-acetic acid. EXAMPLES? 2-(l-Ben2ofuraii-2-ylmethoxy)-6-(l-piperazinyI)pyra2ine, Acetic acid salt Starting materials, 2-chloro-6-(l-piperazinyl)pyrazine and benzofiiran-2-yi- methanol* Fragmenting mass analysis supports the stated structure. Purity 80% (HPLC). HRMS m/z calcd for C17H18N4O2 (M)+310.1430, found 310,1419. *Prepared by reduction ofben2ofuran-2-carbaldehyde. EXAMPLE 88 2-{2-[3-Methoxy-2-(phenoxymethyl)phenyl]ethoxy}-6-(l-piperazinyI)pyrazine, Acetic acid salt Starting materials, 2-chloro-6-(l"pipera2dnyl)pyrazine and (3-methoxy-2-phenoxymethyl"phenyl)-methanoL* Fragmenting mass analysis supports the stated structure. Purity 90% (HPLC). HRMS wz/z calcd for C23H26N4O3 (M)+ 406.2005, found 406.2011. *Prepared by reduction of 3-methoxy-2-phenoxymethyl-benzaldehyde, EXAMPLE 89 2-{2-(Isoqiiinolin-7-yIoxy)ethoxy]-6-(l-piperazinyI)pyrazine, Acetic acid salt Step 1:2-(7-Isoquinolinyloxy)ethanoL A mixture of 7-hydroxyisoquinoline (1.15 g, 7.9 mmol), ethylene carbonate (0.98 g, ILl mmol), powdered K2CO3 (0.65 g, 4.7 mmol) in dry DMF (20 mL) was stirred at 145 °C for two hours. The reaction was quenched with MeOH (1 mL), filtered and the solvent was removed under reduced pressure. The residue was taken up between alkaline water (K2CO3) and CHCI3. Concentration of the dried (MgSO4) organic phase afforded 1.4 g (94%) of the title compound as a yellow oil that solidified upon standing. Purity 91 % (HPLC). Fragmenting mass analysis supports the stated structure. Step 2:2-[2-(Isoquinolin-7-yIoxy)ethoxy]-6-(l-piperazinyI)pyrazine, Acetic acid salt The general procedure was followed starting 2'ChIoro-6-(l-piperazinyl)pyra2ine and 2-(7-isoquinolinyloxy)ethanol. Fragmenting mass analysis supports the stated structure. Purity 80% (HPLC). HRMS m/z calcd for C19H21N5O2 (M)+351.1695, found 351.1696. EXAMPLE 90 2-(2,3-Dihydro-1H-inden-2-yloxy)-6-(l-piperazinyl)pyrazine Acetic acid salt Starting materials, 2-chloro-6-(l-piperazinyl)pyrazine and 2-indanol. The general procedure was followed with the exception that the reaction mixture was heated at 100 °C overm'ght. Fragmenting mass analysis supports the stated structure. Purity 90% (HPLC). HRMS m/z calcd for C17H20NAO (M)+296.1637, found 296.1652, EXAMPLE 91 2-{[2-(PhenoxymethyI)benzyl]oxy}-6-(l-piperazinyl)pyra2ine, Acetic acid salt Starting materials, 2-chIoro-6"(l-piperazinyl)pyra2ine and 2-phenoxymethyl-benzyl alcohol.* Fragmenting mass analysis supports the stated structure. Purity 90% (HPLC). HRMS m/z calcd for C22H24N4O2 (M)+" 376.1899, found 376,1889. *Prepared by reduction of 2-phenoxymethylbenzoic acid by lithium aluminum - * hydride in THF, cf Chem. Soc. 1954.2819, EXAMPLE 92 2-(2-Cyclohexylethoxy)-6-(l-piperazinyl)pyraziiie, Acetic add salt Starting materials, 2-chloro-6-(l-piperazinyl)pyra2ine and 2-cyclohexyl-ethanoL Fragmenting mass analysis supports the stated structure. Purity 90% (HPLc). HRMS nx/z calcd for C16H26N4O (M)+290.2107, found 290.2109. EXAMPLE 93 2-[2-(2-Amino-quinolin-8-yIoxy)ethoxy]-6-(l-piperazinyl)pyrazine, Acetic acid salt Starting materials, 2-chloro-6-(l-piperazinyl)pyrazine and 2-(2"amino-quinolin-8-yloxy)-ethanol.* Fragmenting mass analysis supports the stated structure. Purity 90% (HPLC). HRMS m/z calcd for C19H22N6O2 (M)+366.1804, found 366.179L *Prepared as described in WO 00/76984. EXAMPLE 94 2-{(3-CyanobenzyI)oxy]-6-(l-pipera2inyr)pyrazuie. Starting materials, 2-chloro-6-(l-piperazinyl)pyrazine and 3-cyanobenzyl alcohol. Fragmenting mass analysis supports the stated structure. Purity 90% (HPLC). HRMS m/z calcd for C16H17N5O (M)+295.1433, found 295.1431. EXAMPLE 95 2-[(5-Fluoro-2-methoxyben2yl)oxy]-6-(l-piperazinyl)pyra2ine5 Acetic acid salt Starting materials, 2-chloro-6-{l"piperazinyl)pyrazine and (5-fluoro-2"methoxy-phenyl)-methanol. * Fragmenting mass analysis supports the stated structure. Purity 90% (HPLC). HRMS m/z calcd for C16H19FN4O2 (M)+318.1492, found 318.1490. *Prepared by reduction of 5-£luoro-2-methoxybenzaldehyde. EXAMPLE 96 2-(l-Cyclopentylethoxy)-6-(l-piperazinyl)pyrazine, Acetic acid salt Starting materials, 2-chloro-6-(l-piperazinyl)pyra2ine and 1-cyclopentyl-ethanol. The general procedure was followed with the exceptions that dioxane was used as solvent and that the reaction mixture was heated in a sealed tube with microwaves at 160 °C for 20 minutes. Fragmenting mass analysis supports the stated structure. Purity 90% (HPLC). HRMS m/z calcd for C15H24N4O (M+)276.1950, found 276.1955. EXAMPLE 97 2-[(2-DifluorobenzyI)oxy]-6-(l-piperazinyl)pyrazine,Maleate, The title compound was prepared according to the procedure of example 50, step 2, starting from 2-Chloro-6-[(2,5-difluorobenzyI)oxy]pyrazine (3.43 g, 13.4 mmol; obtained according to the procedure of example 50, step 1, starting from 2,5- difluorobenzyl alcohol), piperazine (3.51 g, 40.7 mmol) and K2CO3 (1.94 g, 14.0 mmol) with the exception that the final filtration through alumina was omitted. The yield of the free base of the title compound was 2.84 g (69%) which was obtained as an oil. The free base was converted into its maleate salt. Purity 100% (HPLC). MS m/z 306 (M)+ HRMS m/z calcd for C15H16F2N4O (M)+306.1292, found 306.1297. EXAMPLE 98 2-[(3-DimethylaminobenzyI)oxy]-6-(l-piperazinyl)pyra2ine. The title compoimd was prepared according to the procedure of example 50, step 2, starting from 2-chIoro-6-[(3-dimethylaminoben2:yl)oxy]pyrazine (3.04 g, 11.5 mmol; obtained according to the procedure of example 50, step 1, starting from 3- dimethyIaminobenzyl alcohol), piperazine (3.08 g, 35.7 mmol) and K2CO3 (1.59 g, 11.5 mmol) with the exception that the final filtration through alumina was omitted The yield of the of the title compoimd was 2.06 g (57%) which was obtained as a beige colored oil that solidified when refiigerated. Purity 98% (HPLC). MS m/z 313 (M)+ HRMS m/z calcd for C17H23N5O (M)+313.1903, found 313.1910. EXAMPLE 99 2-I{4-(2-PyridinyI)ben2yI}oxyJ-6-(l-pipera2myl)pyrazme, The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chIoro-6-[(4-(2-pyridinyl)benzyl}oxy]pyra2ine (2,73 g, 9.16 mmol; obtained according to the procedure of example 50, step 1, starting from 4-(2-pyridinyl)benzyl alcohol*), piperazine (2.41 g, 27.9 mmol) and K2CO3 (1.33 g, 9.62 mmol) with the exception that the final filtration through alumina was omitted. The yield of the of the title compound was 2,06 g (65%) which was obtained as a beige' colored oil that solidified when refrigerated. Purity 100% (HPLC). MS m/z 347 (M)+ HRMS m/z calcd for C20H21N5O (M)+347,1746, found 347.1749. *Obtained by reduction (NaBH4) of 4.(2-pyridyl)benzaldehyde, EXAMPLE 100 2-I(2-Fluorobenzyl)oxy]-6-(l-piperazinyl)pyrazine, Maleate. The title compound was prepared according to the procedure of example 50, step 2, Starting from 2-chlorO"6-[(2-£luorobenzyl)oxy]pyra2ine (3.68 g, 15.4 mmol; obtained according to the procedure of example 50, step 1, starting from 2-fluorobenzyl alcohol), piperazine (4.06 g, 47.1 mmol) and K2CO3 (2.24 g, 16.2 mmol) with the exception that the final filtration through alumina was omitted. The yield of the free base of the title compound was 3.28 g (74%) which was obtained as an oil. The free base was converted into its maleate salt Purity 100% (HPLC). MS mlz 288 (M)+". HRMS miz calcd for Ci5H,7FN40 (M)+288.1386, found 288.1378. EXAMPLE 101 2-(Benzo[b]thiophen-3-ylmethoxy)-6-(l-piperazinyl)pyra2ine, Maleate, The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-(benzo[6]thiophen"3-yknethoxy)pyra2ine (2.88 g, 10.4 mmol; obtained according to the procedure of example 50, step 1, starting from benzo[6]thiophene-3-methanoI), piperazine (2.73 g, 31.7 mmol) and K2CO3 (1.51 g, 10.9 mmol) with the exception that the final filtration through alumina was omitted. The yield of the free base of the title compound was 2.34 g {69VQ) which was obtained as a beige colored oil. The free base was converted into its maleate salt. Purity 99% (HPLC). MS miz 326 (M)"". HRMS miz calcd for C17H18N4OS (M)"" 326.1201, found 326.1207. EXAMPLE 102 2-(3-Phenoxy-thiophen-2-ylmethoxy)-6-{l-piperazinyr)pyrazine, Maleate. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-(3-phenoxy-thiophen-2-ylmethoxy)pyrazine [2.83 g, 8.88 mmol; obtained according to the procedure of example 50, step 1, starting from (3- phenoxy-2-thienyl)methanol], piperazine (2.33 g, 27.1 mmol) and K2CO3 (1.29 g, 9.3 mmol) with the exception that the final filtration through alumina was omitted. The yield of the free base of the title compound was 1.80 g (55%) which was obtained as a beige colored oil. The free base was converted into its maleate salt. Purity 98% (HPLC). MS m/z 368 (M)"". HRMS m/z calcd for C19H20N4O2S (M)+368.1307, found 368.1306. EXAMPLE 103 2-[5-(2-Pyridinyl)-thiophen-2-ylmethoxy)]-6-(l-piperazuiyl)pyrazine, Maleate. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-[5-(2-pyridinyl)-thiophen-2-ylmethoxy)]pyrazine [2.17 g, 7,13 mmol; obtained according to the procedure of example 50, step 1, starting from 5-(pyridin-2-yl)tlhophene-2-methanol], piperazine (1.84 g, 21.4 mmol) and K2CO3 (0.99 g, 7.1 mmol) with the exception that the final filtration through alumina was omitted. The yield of the free base of the title compound was 1.66 g (66%) which was obtained as a beige colored oil. The free base was converted into its maleate salt. Purity 100% (HPLC). MS m/z 353 (Mf, HRMS m/z calcd for C18H19N5OS (M)+353.1310, found 353.1307. EXAMPLE 104 2-I2-(5-Methyl-2-phenyl-oxazol-yl)-ethoxy]-6-(l-piperazmyI)pyrazine. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]pyrazine [2.90 g, 9.18 mmol; obtained according to the procedure of example 50, step 1, starting from 2-(5-methyl-2-phenyloxazol-4-yl)ethanol], piperazine (2.37 g, 27.5 mmol) and K2CO3 (1-27 g, 9.19 mmol) with the exception that the final filtration through alumina was omitted. The yield of the of the title compound was 2.09 g (62%) which was obtained as a light yellow oil that solidified when refrigerated. Purity 100% (HPLC). MS 7n/z 365 (M)+". HRMS m/z calcd for C2QH23N5O2 (M)+365.1852, found 365.1855. EXAMPLE 105 2-[l-(2,6-Difluora-phenyl)-ethoxyl-6-(l-piperazinyl)pyrazine5 Maleate. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-[l-(2,6-difluoro-phenyl)-ethoxy]pyra2ine (3.20 & 11.8 mmol; obtained according to the procedure of example 50, step 1, starting from 2,6- difluoro-a-methylbenzyl alcohol), piperazine (3.05 g, 35.4 mmol) and K2CO3 (1.63 g, 11.8 mmol) with the exception that the final filtration through alumina was omitted. The yield of the free base of the title compound was 2.95 g (78%) which was obtained as a colorless oil. The free base was converted into its maleate salt. Purity 100% (HPLC). MS m/z 320 (M)+ HRMS miz calcd for C16H18F2N4O (M)+320.1449, found 320.1447. EXAMPLE 106 2-(2-NaphthaIen-2-yl-ethoxy)-6-(l-pipera2myl)pyrazine, Maleate. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chIoro-6-(2-naphthalen-2-yl-ethoxy)pyrazine (2,73 g, 9.60 mmol; obtained according to the procedure of example 50, step 1, starting from 2- naphthalene-ethanol), piperazine (2.89 g, 33.5 mmol) and K2CO3 (1.39 g, 10.1 mmol) with the exception that the final filtration through alumina was omitted. The . yield of the free base of the title compound was 2.63 g (82%) which was obtained as a colorless oil. The free base was converted into its maleate salt. Purity 99% (HPLC). MS miz 334 (M)+^. HRMS miz calcd for C20H22N4O (M)+ 334.1794, found 334.1794. EXAMPLE 107 2-[3-(Naphthalen-2-yloxy)-propoxyJ-6-(l-piperazinyl)pyrazine, Maleate. The title compoimd was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-[3-(naphthalen-2-yloxy)-propoxy]pyra2ine [2.24 g, 7.12 mmol; obtained according to the procedure of example 50, step 1, starting from 3- (naphthalen-2-yloxy)-propan-l-ol*], piperazine (1.90 g, 22.1 mmol) and K2CO3 (1.03 g, 7.45 mmol) with the exception that the final filtration through alumina was omitted. The yield of the free base of the title compound was 1.10 g (42%) which was obtained as a light beige colored oil. The free base was converted into its maleate salt. Purity 100% (HPLC). MS miz 364 (M)"". HRMS miz calcd for C21H24N4O2 (M)+ 364.1899, found 364.1895. *Described in J. Amu Chem Soc. 1929, 51,3417 and ibid. 1954.76,56, EXAMPLE 108 2-(4-Phenylethynyl-thiophen-2-ylmethoxy)-6-(l-piperazinyl)pyrazine,Maleate. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-(4-phenylethynyl-thiophen-2-ylmethoxy)pyrazine [2.05 g, 6.28 mmol; obtained according to the procedure of example 50, step 1, starting jfrom 4-(phenylethyDyl)thiophene-2-methanol*], piperazine (1.62 g, 18.8 mmol) and K2CO3 (0.89 g, 6.4 mmol) with the exception that the final filtration through alumina was omitted. The yield of the fi-ee base of the title compound was 1.80 g (76%) which was obtained as a light beige colored oil. The fi:ee base was converted into its maleate salt Purity 100% (HPLC). MS m/z 376 (M)+". HRMS m/z calcd for C21H20N4OS {Mf 376.1358, found 376.1351. *Obtained by reduction (NaBH4) of 4-(phenylethynyl)thiophene-2-carboxaldehyde. EXAMPLE 109 2-(l-Cyclopropyl-ethoxy)-6-(l-piperazinyl)pyrazine, Maleate. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-(l-cyclopropyl-ethoxy)pyra2ine (2.38 g, 12.0 mmol; obtained according to the procedure of example 50, step 1, starting from a- methylcyclopropanemethanol), piperazine (3.60 g, 41.8 mmol) and K2CO3 (1.75 g, 12.7 mmol) with the exception that the final filtration through alumina was omitted. The yield of the free base of the title compound was 2.05 g {69Vo) which was obtained as a colorless oil. The free base was converted into its maleate salt Purity 100% (HPLC). MS miz 248 (M)+ HRMS m./z calcd for C13H20N4O (M)+ 248.1637, found 248.1636. EXAMPLE 110 2-p-(6-Methoxy-naphthaIen-2-yloxy)-ethoxyJ-6-(l-piperazmyI)pyrazine. The title compoxmd was prepared according to the procedure of example 50, step 2, starting from 2-chlorO"6-[2-(6-methoxy-naphthalen-2-yloxy)-ethoxy]pyra2ine [0.94 g, 2.8 mmol; obtained according to the procedure of example 50, step 1, starting from 2-(6-methoxy-naphthalen-2-yloxy)ethanol*], piperazine (1.00 g, 11.6 mmol) and K2CO3 (0.50 g, 3.6 mmol) with the exception that the final filtration through alumina was omitted. The yield of the of the title compound was 0.52 g (48%) which was obtained as a beige colored solid. Purity 100% (HPLC). MS nilz 380 (M)+". HRMS m/z calcd for C2]H24N403 (M)+380.1848, found 380.1845. *Prepared from 6-methoxy-2-naphthol and ethylene carbonat according to the procedure of Example 134, step 1, in WO 00/76984. The reaction mixture was refluxed for 2 h. Pure 2-(6-methoxy-naphthalen-2-yloxy)ethanol was obtained by recrystallization from MeOH/CHCl3/w-hexane. EXAMPLE 111 2-[2(7--Methoxy-naphtbalen-2-yloxy)-ethoxy]-6-(l-piperazinyl)pyrazine. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-cliloro-6-[2-(7-methoxy-naphthalen-2-yloxy)-ethoxy]pyra2me [1.19 g, 3.60 mmol; obtained accordmg to the procedure of example 50, step 1, starting from 2-(7-methoxy-naphthalen-2-yloxy)ethanoI*], piperazine (1.25 g, 14.5 mmol) and K2CO3 (0.60 g, 4.3 mmol) with the exception that the final filtration through alumina was omitted. The yield of the of the title compound was 0.98 g (71%) which was obtained as an oil that solidified when refiigerated. Purity 100% (HPLC). MS miz 380 (M)+ HRMS miz calcd for C21H24N4O3 (M)+380.1848, found 380.1851, *Prepared from 7-methoxy-2-naphtho] and ethylene carbonat according to the procedure of Example 134, step 1, in WO 00/76984. The reaction mixture was refluxed for 2 h. Pure 2-(7-methoxy-naphthalen-2-yloxy)ethanol was obtained after column chromatography on silica gel using «-hexane/ethyl acetate (6:4) as eluent EXAMPLE 112 2-[5-(4-ChlorophenyI)-2-methylfuran-3-ylmethoxy]-6-(l-pipera2inyI)pyrazine. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-[5-(4-chlorophenyl)-2-raethylfuran-3-ylmethoxy]pyrazine [3.14 g, 9.39 mmol; obtained according to the procedure of example 50, step 1, starting from 5-(4-chlorophenyl)-3-hydroxymethyl-2-methylfuran], piperazine (2.47 g, 28,6 mmol) and K2CO3 (1.36 g, 9.86 mmol) with the exception that the final filtration through alumina was omitted. The yield of the of the title compound was 2.11 g (58%) which was obtained as a beige colored solid Purity 100% (HPLC). MS m/z 384 (Mf. HRMS m/z calcd for C20H21CIN4O2 (M)" 384.1353, found 384.1357. EXAMPLE 113 2-(lH-Indol-4-ylmethoxy)-6-(l-piperazinyl)pyrazine, Maleate. The title compound was prepared according to the procedure of example 50, step 2, starting, from 2-chloro-6-(lHindol-4-ylmethoxy)pyra2ine [0.486 g, 1.87 mmol; obtained according to the procedure of example 50, step 1, starting from (lH-indol-4-yl)"methanol*], piperazine (0.491 g, 5.71 mmol) and K2CO3 (0.272 g, 1.96 mmol) with the exception that the final filtration through alumina was omitted. The yield of the free base of the title compound was 0.198 g (34%) which was obtained as an oil. The firee base was converted into its maleate salt. Purity 100% (HPLC). MS jn/z 309 (Mf, HRMS m/z calcd for C17H19N5O (M)+" 309.1590, found 309.1582, *The reaction was carried out using (lH-indol-4-yl)-methanol (0.712 g, 4.84 mmol), Krt-BuO (0.517 g, 4.61 mmol), and 2,6-dichloropyrazine (0.687 g, 4.61 mmol). EXAMPLE 114 2-(2-Phenyl-propoxy)-6-(l-piperazinyI)pyrazine, Maleate. The title compoimd was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-(2-phenyl-propoxy)pyra2ine (2.39 g, 9.61 mmol; obtained according to the procedure of example 50, step 1, starting from 2-phenyl-l-propanol),piperazine (2.90 g, 3.36 mmol) and K2CO3 (L40 g, 10.1 mmol) with the exception that the final filtration througih alumina was omitted. The yield of the free base of the title compoimd was 1.66 g (58%) which was obtained as a colorless oil. The free base was converted into its maleate salt. Purity 99% (HPLC). HRMS m/z calcd for C17H22N4O (M)+ 298.1794, found 298.1795. EXAMPLE 115 2-[2-(2-Methoxyphenyl)ethoxy]-6-(l-piperazinyl)pyrazine, Maleate. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-[2-(2-methoxyphenyl)ethoxy]pyrazine (0.967 g, 3.65 mmol; obtained according to the procedure of example 50, step 1, starting from 2- methoxyphenethyl alcohol), piperazine (0.913 g, 10.6 mmol) and K2CO3 (0.505 g, 3.65 mmol). The yield of the free base of the title compound was 0.63 g (55%) which was obtained as a colorless oil. The free base was converted into its maleate salt Purity 100% (HPLC), MS mIz 314 (M)"". HRMS mIz calcd for C17H22N4O2 (M)+314.1743, found 314.1750. EXAMPLE 116 2-I2-(3-Methoxyphenyl)ethoxy]-6-(l-piperazinyl)pyrazine. The title compound was prepared according to the procedure of example 50, step 2, starting from 2"chloro-6-[2-(3"methoxyphenyl)ethoxy]pyrazine (1.12 g, 4.23 mmol; obtained according to the procedure of example 50, step 1, starting from 3- methoxyphenethyl alcohol), piperazine (1.06 g, 12.3 mmol) and K2CO3 (0.585 g, 4.23 mmol). The yield of the title compound was 0.91 g (69%) which was obtained as light beige oil. HRMS mIz calcd for C17H22N4O2 (M)+314.1743, found 314.1759. Anal.(Ci7H22N402)C,H,N. EXAMPLE 117 2-I(2-Phenoxyben2yl)oxy]-6-(l-pipera2inyI)pyrazine, Maleate- The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-[(2-phenoxyben2yl)oxy]pyrazine (0.981 g, 3.14 mmol; obtained according to the procedure of example 50, step 1, starting from 2- phenoxybenzyl alcohol), piperazine (0.784 g, 9.10 mmol) and K2CC)3 (0.434 g, 3.14 mmol) with the exception that the final filtration through alumina was omitted. The yield of the free base of the title compound was 0.80 g (70%) which was obtained as a colorless oil. The free base was converted into its maleate salt. Anal. (C21H22N4O2 C4H4O4) C, H, N. EXAMPLE 118 2-Benzylamino-4-(l-piperazmyl)pyrimidine, Hydrochloride, Step 1: 2-Benzylamlno-4-[l-(4-tert-butoxycarbonyI)piperazinyl]pyrimidme* A mixture of 2-chloro-4-[l-(4-/err-butoxycarbonyl)pipera2inyI]pyrimidine (obtained in Example 33, step 1; 1.80 g, 6.02 mmol), benzylamine (10 mL, large excess) and potassium carbonate (0.91 g, 6.62 mmol) was stiired in 50 mL of propionitnle at 110 ""C for 1.5 h. the mixture was poured into water (200 mL) and left over night. The title compound was collected, washed with water + 10% methanol and dried. Yield: 2.08 g (94%). Purity >90% (HPLC). HRMS m/z calcd for C20H27N5O2 (M)+369.2165, found 369.2152. Step 2: 2-Benzylamino-4-(l-piperazinyl)pyrimidine, Hydrochloride. To a solution of 2-benzylamino-4-[l-(4-tert-butoxycarbonyl)piperazinyl]pyrimidine (37 mg, 0.10 mmol) in a mixture of methyl tert butyl ether (3 mL) and methanol (1 mL) was 4.0 M HCl in dioxane (1 mL) added. The reaction was shaken over nigiht Methyl tert butyl ether (2 mL) was added. The title compound was collected as a white solid. Yield: 29 mg (95%). Purity >90% (HPLC). MS mIz 270 (M+H)"". EXAMPLE 119 (2i?)-l-[6-{(2-Chloroben^l)sulfanyI}-2-pyrazinyll-2-methyIpipera2ine, Hydrochloride. Na-r-BuO (8.7 mmol 0.84 g) was added to a solution of 2-chloroben2ylihiol (5.7 mmol 0.90 g) in dry DMF (25 mL) and the mixture was stirred at room temperature for 10 minutes. (2i2)-l-(6-chloro-2-pyrazinyl)-2-methylpiperazine (0.92 g, 4.35 mmol; obtained in Example 62, step 2) was added and the reaction was stiired at 70 °C for 2 h. The mixture was filtered through a plug of silica and the solvent from the filtrate was evaporated at reduced pressure. The brown residue was chromatographed over silica gel using CHCl3/MeOH/aq NH3 90/10/0.25 as eluent This furnished the free base of the title compound as a yellow oil. The free base was precipitated as its HCl salt with HCl/ether to give 1.10 g (68%) of the title compound as light yellow crystals. Purity 98% (HPLC). HRMS miz for C16H19CIN4S (M)" calcd for 334.1019, found 334.1036. f EXAMPLE 120 2-(3-Thienylmethoxy)-6-(l-piperazinyl)pyrazine, The title compound was prepared according to the procedure of Example 20 starting from 3-thiophenemethanol (6.05 g, 53.0 mmol), K-r-BuO (0.897 g, 7.99 mmol) and 6-chloro-2"(l-piperazinyl)pyrazine (0.845 g, 4.25 mmol: obtained in Example 13, step 2). The reaction mixture was stirred at 105 °C for 7.5 h. Following chromatography on silica, solvents were evaporated off. The remaining oil was redissolved in ethyl acetetate and filtered through a short plug of alumina (5x3 cm) using ether/MeOH (96:4) as eluent. Solvent removal in vacuo gave 0.76 g (64%) of the title compound as a colorless oil. HRMS mIz for C13H16N4OS (M) calcd for 276.1045, found 276.1037. AiiaL (C13H16N4OS • 0.25 H2O) C, H, N. EXAMPLE 121 2-(3-Phenoxypropoxy)-6-(l-pipera2inyr)pyrazine, Maleate, The title compoimd was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-(3-phenoxypropoxy)pyrazine (1.04 g, 3.93 mmol; obtained according to the procedure of example 50, step 1, starting from 3-phenoxy-l- propanol), piperazine (0.981 g, 11.4 mmol) and K2CO3 (0.543 g, 3.93 mmol). Following chromatography on silica, solvents were evaporated off. The semi-solid residue (0.83 g) was redissolved in CHCI3 and filtered. The clear solution was concentrated in vacuo and the resulting free base of the title compoimd was converted into its maleate salt. Yield: 0.90 g (53%). HRMS mIz calcd for C17H22N4O2 (M)+314.1743, found 314.1728. Anal. (C17H22N4O2 • C4H4O4) C, H, N. EXAMPLE 122 2-{[4-(Benzyloxy)benzyl]oxy}-6-(l-piperazinyl)pyrazine. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-{[4-(benzyloxy)benzyl]oxy}pyrazine (1.15 g, 3.52 mmol; obtained according to the procedure of example 50, step 1, starting from 4-benzyloxybenzyl alcohol), piperazine (0.894 g, 10.4 mmol) andK2C03 (0.486 g, 3.52 mmol). The yield of the title compound was 0.57 g (43%) which was obtained as a colorless viscous oil that solidified upon standing. Fragmenting mass analysis supports the stated structure. HRMS mIz calcd for C22H24N4O2 (M)+ 376.1899, found 376.1892, EXAMPLE 123 2-(n-Hexyloxy)-6-(l-piperazinyl)pyrazine. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-(n-hexyloxy)pyrazine (1.54 g, 7.17 mmol; obtained according to the procedure of example 50, step 1, starting from n-hexanol), piperazine (1.90 g, 22.1 mmol) and K2CO3 (0.99 g, 7.16 mmol). The yield of the title compound was 1.21 g (64%) which was obtained as a colorless oil. HRMS mIz calcd for C14H24N4O (M)+264.1950, found 264.1953. Anal. (C14H24N4O) C, H, N. EXAMPLE 124 2-(Propargyloxy)-6-(l-piperazinyl)pyrazine,MaIeate. The title compound was prepared according to the procedure of example 50, step 2, starting from 2-chloro-6-(propargyloxy)pyrazine (1.70 g, 10.1 mmol; obtained according to the procedure of example 50, step 1, starting from propargyl alcohol), piperazine (1.91 g, 22.2 mmol) and K2CO3 (1.39 g, 10.1 mmol) with the exception that the final filtration through alumina was omitted. Following repeated chromatography on silica, solvents were evaporated off. The yield of the free base of the title compound was 0.48 g (22%) which was obtained as a beige oil. The free base was converted into its maleate salt HRMS mIz calcd for C21H14N4O (M)+" 218.1168, found 218.1158. Anal. (C11H14N4O • C4H4O4) C, H, N. PREPARATION OF PHARMACEUTICAL COMPOSITIONS EXAMPLE: Preparation of tablets Ingredients me/tablet 1. Active compound 10.0 2. Cellulose, microcrystalline 57.0 3, Calcium hydrogen phosphate 15.0 4. Sodium starch glycolate 5.0 5. Silicon dioxide, colloidal 0.25 6. Magnesium stearate 0.75 The active ingredient 1 is mixed with ingredients 2,3,4 and 5 for about 10 minutes. The magnesium stearate is then added, and the resultant mixture is mixed for about 5 minutes and compressed into tablet form with or without film-coating. Pharmacological tests The ability of a compound of the invention to bind or act at specific 5-HT receptor subtypes can be determined using in vitro and in vivo assays known in the art. The biological activity of compounds prepared in the Examples was tested using different tests. Affinity assay The 5-HT2c receptor affinity of compounds in the Examples was determined in competition experiments, where the ability of each compoxmd in serial dilution to displace 3H-labelled 5-HT, bound to membranes prepared from a transfected HEK293 cell line stably expressing the human 5-HT2c receptor protein, was monitored by Scintillation Proximity Assay technology. Non-specific binding was defined using 5 µM mianserin. Results obtained for exemplary compounds of the invention are illustrated in Table 1 below. Typically, the 5-HT2c receptor affinity values (Ki, DM) were in the range of 1 nM to 1500 nM. Table 1. 5-HT2c receptor Affinity Compound Ki (nM) Example 2 8 Example 12 197 Example 15 616 Example 18 92 Example 20 28 Example 23 478 Example 32 48 Example 48 37 Efficacy assay The agonist efficacy at the 5-HT2c receptor of the compounds in the Examples was determined by the ability of each compound to mobilise intracellular calcium in transfected HEK293 cells, stably expressing the human 5-HT2c receptor protein, using the calcium-chelating fluorescent dye FLUO-3 (Sigma, St. Louis, MO, U.S.A.). Typically, the maximum responses of 5-HT2c agonists were in the range of 20-100% relative to the maximum response of 5-HT (serotonin) at a concentration of lµM. WE CLAIM : 1. A compound of the general formula (I): wherein (i) X and Y represent both nitrogen and Z represents CH, forming a pyrazine derivative, or (ii) X and Z represent both CH and Y represents nitrogen, forming a pyridine derivative, or (iii) X represents C-CF3, Z represents CH, and Y represents nitrogen, forming a 4-trifluoromethylpyridine derivative, or (iv) Y and Z represent both nitrogen and X represents CH, forming a pyrimidine derivative, and wherein R1 and R2 are each, independently, selected from a group A consisting of or from a group B, consisting of aryl-C1-C6-alkyl, aryl-C1-Ce-alkoxy, heteroaryl-C1-C6-alkoxy, aryloxy-C2-C6-alkoxy, heteroaryloxy-C2-C6-alkoxy, 1-indanyloxy, 2-indanyloxy, aryloxy, heteroaryloxy, arylthio, heteroarylthio, C5-C6-cycloalkylthio, C5-C8-alkoxy, C3-C8-alkylthio, C3-C6-alkynyloxy, C3-C6-alkenyloxy, fluoro-C2-C4-alkoxy, C4-C8-cycloalkyloxy, C3-C8-cycloalkyl-C1-C4-alkoxy, halogen, aryl-C1-C4-alkylthio, heteroaryl-C1-C4-alkylthio, aryl-C1-C4-alkylamino, heteroaryl-C1-C4-alkylamino, heteroaryl and aryl; with the proviso that: (i) R1 and R2 are different and are not both selected from group A or group B at the same time; (ii) when formula (I) is a pyrazine derivative R1 or R2 are other than phenylthio, phenylmethylthio, phenyl or phenyl substituted by halogen; (iii) R1 in formula (I) is halogen, only when (I) is a pyrazine derivative and when R2 simultaneously is 2-methylpiperazin-l-yl, 2-ethylpiperazin-l-yl, or trans-2,5-dimethylpiperazin-1 -yl; (iv) when formula (I) is a pyrazine derivative and R1 is 4-'piperidinyloxy, R2 is other than 3-pyridinylmethoxy, 4-quinolinylmethoxy and 3-(4-pyridinyl)propoxy; (v) when both X and Z are CH and Y is N in formula (I), forming a pyridine derivative, and R1 is 1-piperazinyl or 4-methylpiperazin-l-yl, then R2 is other than 2-phenylethyl, benzyloxy, benzylamino, phenylthio, phenoxy, substituted phenoxy, C4-C8-cycloalkyloxy and Ca-C3-Cycloalkylmethoxy; (vi) when X is CH and Z and Y both are nitrogen in formula (I), forming a pyrimidine derivative, and R2 is 1-piperazinyl, then R1 is other than phenoxy, phenyl or phenyl substituted by bromo, and C5-C8 alkoxy; and when R2 is 4-methylpiperazin-l-yl or 4-(2-hydroxyethyl)piperazin-l-yl, then R\ is other than 5-nitro-2-furyl; (vii) when X is CH and Z and Y both are nitrogen in formula (I), forming a pyrimidine derivative, and R1 is 1-piperazinyl, then R2 is other than C3-C8 alkoxy; and where R3 is H or C-14-alkyl, allyl, 2-hydroxyethyl, 2-cyanoethyl, or a nitrogen protecting group, or a prodrug moiety such as an acyl- or an alkoxycarbonyl group forming a cleavable amide or carbamate linkage; R4 is hydrogen, or C 1.4 alkyl; and wherein any aryl or heteroaryl residue, alone or as part of another group, in R\ or R2 may be independently substituted in one or more positions, by --alkyl, C1-4- alkoxy, --alkylthio, C2-4-acyl, --alkylsulphonyl, cyano, nitro, hydroxy, C2-6- alkenyl, C2-6-alkynyl, fluoromethyl, trifluoromethyl, trifluoromethoxy, halogen, -N(R5)(R6), aryl, aryloxy, arylthio, aryl---alkyl, aryl-C2-4-alkenyl, aryl-C2-4- alkynyl, heteroaryl, heteroaryloxy, heteroarylthio or heteroaryl---alkyI, aryl--- alkoxy, aryloxy---alkyl, dimethylamino-C2-4-alkoxy; and wherein any aryl or heteroaryl residue as substituents on aryl or heteroaryl, alone or as part of another group, in R1 or R2 in turn may be substituted in one or more postions, independently of each other by --alkyl, --alkoxy, halogen, trifluoromethyl, cyano, hydroxy or dimethylamino; and R5 and R6 independently of each other are hydrogen, methyl or ethyl, or together with the nitrogen atom to which they are bound form a pyrrolidine, piperazine, morpholine, thiomorpholine or a piperidine ring; and pharmaceutically acceptable salts, hydrates, geometrical isomers, tautomers, optical isomers, A^-oxides and prodrug forms thereof 2. The compound as claimed in claim 1, wherein X and Y are both nitrogen and Z is CH, forming a pyrazine derivative. 3. The compound as claimed in claim 1, wherein X and Z are both CH and Y is nitrogen, forming a pyridine derivative. 4. The compound as claimed in claim 1, wherein formula (I) is a 4-trifluoromethylpyridine derivative. 5. The compound as claimed in claim 1 wherein Y and Z are both nitrogen and X is CH, forming a pyrimidine derivative. 6. The compound as claimed in claim 1 wherein R3 is hydrogen and R\ or R2 is selected from 7. The compound as claimed in claim 1 wherein R1 or R2 is selected from and where R3 is hydrogen and R4 is selected from hydrogen, methyl or ethyl. 8. The compound as claimed in claim 1 wherein Rj or R2 is and where R3 is hydrogen and R4 is selected from hydrogen, methyl or ethyl. 9. The compound as claimed in claim 1, wherein R1 or R2 is selected from 10. The compound as claimed in claim 1 with the general formula (II): wherein R2 and R3 are as defined above; R7 is hydrogen or C 1- ,4-alkyl; and any aryl and heteroaryl residue, alone or as part of another group, in R2 may be substituted in one or more positions, preferably one or two, independently of each other by C1-4-alkyl, --alkoxy, --alkylthio, C2-4-acyl, C4-alkylsulphonyl, cyano, nitro, hydroxy, C2-6"alkenyl, C2-6-alkynyl, fluoromethyl, trifluoromethyl, trifluoromethoxy, halogen, -N(R5)(R5), aryl, aryloxy, arylthio, aryl---alkyl, aryl- C2-4-alkenyl, aryl-C2-4-alkynyl, heteroaryl, heteroaryloxy, heteroarylthio or heteroaryl-C1-4-alkyl, aryl-C1-4-alkoxy, aryloxy---alkyl5 dimethylamino-C2-4- alkoxy; and any aryl or heteroaryl residue as substituents on aryl or heteroaryl, alone or as part of another group, in R2 in turn may be substituted in one or more postions, preferably one, independently of each other by --alkyl, --alkoxy, halogen, trifluoromethyl, cyano, hydroxy or dimethylamino; R5 and R6 are as defined above. 11. The compound as claimed in claim 10 wherein R3 is hydrogen. 12. The compound as claimed in claim 10 wherein R7 is selected from hydrogen, methyl or ethyl. 13. The compound as claimed in claim 10 wherein R7 is methyl and where said methyl is attached to the C2-position of the piperazine ring. 14. The compound as claimed in claim 10 wherein R7 is hydrogen. 15. The compound as claimed in claim 1, which is selected from the group consisting of: 2-(Benzyloxy)-6-(l-piperazinyl)pyrazine, 2-[(2-Methoxybenzyl)oxy]-6-(l-piperazinyl)pyrazine, 2- [(3 -Methoxybenzyl)oxy]-6-( 1 -piperazinyl)pyrazine, 2-[(3,5-Difluorobenzyl)oxy]-6-( 1 -piperazinyl)pyrazine. 2-( 1 -Naphthylmethoxy)-6-(l -piperazinyl)pyrazine, 2-( 1 -Pheny lethoxy)-6-( 1 -piperazinyl)-pyrazine, 2-[ 1 -(3-Fluorophenyl)ethoxy]-6-( 1 -piperazinyl)pyrazine, 2-[ 1 -(2-Methoxyphenyl)ethoxy]-6-( 1 -piperazinyl)pyrazine, 2-(3,4-Dihydro-2H-chromen-4-yloxy)-6-(l-piperazinyl)pyrazine, 2-(2-Phenylethoxy)-6-(l-piperazinyl)pyrazine, 2-[(2-Phenoxybenzyl)oxy]-6-(l-piperazinyl)pyrazine, 2-[2-(3-Chlorophenyl)ethoxy]-6-(l-piperazinyl)pyrazine, 2-[2-(2-Methoxyphenyl)ethoxy]-6-(l-piperazinyl)pyrazine, 2-[2-(3-Methoxyphenyl)ethoxy]-6-( 1 -piperazinyl)pyrazine, 2-[2-(4-Methoxyphenyl)ethoxy]-6-(l-piperazinyl)pyrazine, 2-[2-(2,5-Dimethoxyphenyl)ethoxy]-6-( 1 -piperazinyl)pyrazine, 2-[(2-Phenylethyl)sulfanyl]-6-(l-piperazinyl)pyrazine, 2-[(5-Fluoro-2-methoxybenzyl)oxy]-6-(l-piperazinyl)pyrazine, 2-[(3-Cyanobenzyl)oxy]-6-(l-piperazinyl)pyrazine, 2-[(2-Chlorobenzyl)sulfanyl]-6-( 1-piperazinyl)pyrazine, 2-[2-(4-Dimethy laminophenyl)ethoxy]-6-( 1 -piperazinyl)pyrazine, 2-[2-(lH-Indol-3-yl)ethoxy]-6-(l-piperazinyl)pyrazine, 2-[2-( lH-Indol-1 -yl)ethoxy]-6-( 1 -piperazinyl)pyrazine, 4-(Benzyloxy)-2-(l-piperazinyl)pyrimidine, 4-[(2-Methoxybenzyl)oxy]-2-( 1 -piperazinyl)pyrimidine, 2- {[3"(Benzyloxy)benzyl]oxy} -4-( l-piperazinyl)pyrimidine, 2-Benzyl-6-( 1 -piperazinyl)pyrazine, 2-[(3,5-Dimethoxybenzyl)oxy]-6-(l-piperazinyl)pyrazine, l-[6-(Benzyloxy)-2-pyrazinyl]-2-methylpiperazine, 1 - [6-(Benzy loxy)-2-pyrazinyl]-2-ethy Ipiperazine l-[6-(Benzyloxy)-2-pyrazinyl]-trans-2,5-dimethylpiperazine. 2-[2-(2-Fluorophenyl)ethoxy]-6-( 1 -piperazinyl)pyrazine, 2-(2,3-Dihydro- lH-inden-1 -ylmethoxy)-6-( 1 -piperazinyl)pyrazine 2-(4-Phenoxybutoxy)-6-( 1 -piperazinyl)pyrazine. 2-[(5-Phenoxypentyl)oxy]-6-(l-piperazinyl)pyrazine. 2-[(2,5-Dimethoxybenzyl)oxy]-6-(l-piperazinyl)pyrazine. 2- {[2-(2-Phenylethyl)benzyl]oxy} -6-( 1 -piperazinyl)pyrazine (27?)-l-[6-(Benzyloxy)-2-pyrazinyl]-2-methylpiperazine, 2-[2-(2,6-Difluorophenoxy)ethoxy]-6-(l-piperazinyl)pyrazine 2-[2-(2-Naphthyloxy)ethoxy]-6-(l-piperazinyl)pyrazine 2-( 1 -Methyl-2-phenylethoxy)-6-( 1 -piperazinyl)pyrazine 2- {[2-(Phenoxymethy l)benzyl]oxy} -6-( 1 -piperazinyl)pyrazine 2-[(5-Fluoro-2-methoxybenzyl)oxy]-6-(l-piperazinyl)pyrazine 2-[(2,5-Difluorobenzyl)oxy]-6-(l-piperazinyl)pyrazine 2-[(2-Fluorobenzyl)oxy]-6-(l-piperazinyl)pyrazine 2-(Benzo(b)]thiophen-3-ylmethoxy)-6-( 1 -piperazinyl)pyrazine, 2-[2-(5-Methyl-2-phenyl-oxazol-4-yl)-ethoxy]-6-(l-piperazinyl)pyrazine, 2-[ 1 -(2,6-Difluoro-phenyl)-ethoxy]-6-( 1 -piperazinyl)pyrazine, 2-(2-Naphthalen-2-yl-ethoxy)-6-( 1 -piperazinyl)pyrazine, 2-[3-(Naphthalen-2-yloxy)-propoxy]-6-(l-piperazinyl)pyrazine, 2-[2-(7-Methoxy-naphthalen-2-yloxy)-ethoxy]-6"(l-piperazinyl)pyrazine, 2-[5-(4-Chlorophenyl)-2-methylfuran-3-ylmethoxy]-6-(l-piperazinyl)pyrazine, 2-( 1 H-Indol-4-ylmethoxy)-6-( 1 -piperazinyl)pyrazine, and their pharmacologically acceptable salts and solvates. 16. A pharmaceutical composition comprising a compound according to any one of claims 1 to 15 as an active ingredient, together with a pharmaceutically acceptable carrier. 17. A method for producing a compound as claimed in claim 1, in which.R1 or-R2 are bound to the pyrazine-, pyridine- or pyrimidine nng in Formula (I) via an O, S or N atom in R1 or R2, by reacting a compound of the structural formula (III), (IV), (V), or (VI) wherein Hal is halogen, with an appropriate amine, alcohol or thiol or its corresponding anion to produce a compound of formula (VII), (VIII), (IX), or (X): wherein R1 or R2 is as defined above and with the proviso that R1 or R2 is not any of the following groups and further reacting the compound of formula (VII), (VIII), (IX), or (X) with 1 to 10 molar equivalents of an appropriate amine selected from and where R3 and R4 are as defined above to produce the compound of formula (I). 18. A method for producing a compound as claimed in claim 1, by reacting a compound of formula (VII), (VIII), (IX) or (X) as defined above with a 4-hydroxysubstituted piperidine compound of formula (XI) wherein R3 is as defined above to produce the compound of claim 1. 19. A method for producing a compound as claimed in claim 1, by reacting a compound of formula (III), (IV), (V), or (VI) as defiend above with an appropriate amine, selected from and where R3 and R4 are as defined above to produce a compound of formula (XII) or (XIII): wherein Hal is as defined above, and X, Y, Z have the same meaning as m formula (I), and Am is an amine residue selected from and where R3 and R4 are as defined abov , further reacting the compound of formula (XII) or (XIII) with an appropriate alcohol, amine (other than those defined for Am above) or thiol or its corresponding anions to produce a compound of claim 1. 20. A method for producing a compound as claimed in claim 1, wherein R, or R2 are aryl or heteroaryl, by reacting a compound of formula (III), (IV), (V), or (VI) with a boronic acid derivative of the type heteroary]-B(OH)2 or aryl-B(0H)2, where heteroaryl and aryl are as defined in claims 1, in the presence of a transition metal catalyst such as (Ph3P)4Pd, where Ph represents phenyl, to provide a compound of formula (XIV) or (XV), where R3 and R4 are as defined above to produce a compound of claim 1. 21. A method for producing a compound as claimed in claim 1 by reacting a compound formula (XII) or (XIII) as defined above with a boronic acid derivative heteroaryl- B(OH)2 or aryl-B(OH)2, where heteroaryl and aryl are as defined above, to provide a compound of formula (I).

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