Title of Invention	PIPERAZINYLPYRIDINE COMPOUNDS AND PHAMACEUTICAL COMPOSITION COMPRISING THE SAME
Abstract	The present invention relates to compounds of the general formula (I) wherein R<sup>1</sup>,R<sup>2</sup>,R<sup>3</sup> and R<sup>4</sup>' are as described in the specification. Further included are pharmaceutical compositions comprising the compounds, processes for their preparation, as well as the use of the compounds for the preparation of a medicament which particularly acts on the central nervous system, particularly for use as anti-obesity agents.

Title of Invention

PIPERAZINYLPYRIDINE COMPOUNDS AND PHAMACEUTICAL COMPOSITION COMPRISING THE SAME

Abstract

The present invention relates to compounds of the general formula (I) wherein R1,R2,R3 and R4' are as described in the specification. Further included are pharmaceutical compositions comprising the compounds, processes for their preparation, as well as the use of the compounds for the preparation of a medicament which particularly acts on the central nervous system, particularly for use as anti-obesity agents.

Full Text	NOVEL COMPOUNDS AND THEIR USE RELATED APPLICATIONS This application claims priority to Swedish application number 0201544-4, filed on May 17, 2002, and U.S. provisional application 60/410,038, filed on September 12, 2002, the contents of which are incorporated herein by reference. TECHNICAL FIELD 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 ART Many disorders and conditions of the central nervous system are influenced by the adrenergic, the dopaminergic, and the serotonergic neurotransmitter systems. For example, serotonin (5-HT; 5-hydroxytryptamine) has been implicated in a number of disorders 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, see for example Obes. Res. 1995.3, Suppl. 4,449S-462S and Drugs Future 2001. 26,383-393. The 5-HT2c receptor subtype is transcribed and expressed in hypothalamic structures assoC1ated with appetite regulation. It has been demonstrated that the 5-HT2c receptor agonist m-chlorophenylpiperazine (mCPP), which has some preference for the 5-HT2c receptor, reduces food intake in mice that express the nonmal 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,]-//]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 a novel 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, 45^-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 an effect on the 5-HT2c receptor may therefore have a therapeutic potential in the treatment of disorders like those mentioned above. INFORMATION DISCLOSURE. US-A-3,253,989 discloses the use of mCPP as an anorectic agent. EP-A1-863 136 discloses azetidine and pyrrolidine derivatives which are selective 5-HT2c receptor agonists having antidepressant activity and which can be ised for treating or preventing serotonin-related diseases, including eating disorders ind anxiety. EP-A-657 426 discloses tricyclic pyrrole derivatives having activity on the -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 '-ceptor and which may be used for treating eating disorders. EP-A-572 863 discloses pyrazinoindoles having activity on the 5-HT2c ceptor and which may be used for treating eating disorders. J. Med. Chem. 1978, 21, 536-542 and US-A-4,08l,542 disclose a series of prperazinylpyrazines having central serotonin-mimetic activity. US 4,078,063 discloses a series of piperazinylpyridines having anorexic activity. J. Med. Chem. 19S1, 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(trifludromethyI)-2-pyridinyljpiperazines as central nervous system agents. WO 98/33504 discloses a new medical use of l-[6-chloro-5-(trifluoromethyl)-2-pyridinyl]piperazine, in particular to a new method of treating urinary incontinence. WO 02/30902 discloses crystal forms of l-[6-chloro-5-(trifluoroipethyl)-2-pyridinyljpiperazine hydrochloride. EP 1213017 discloses the use of a 5-HT2c receptor agonist, e.g., l-[6-chloro-5-(trifluoromethyl)-2-pyridinyl]piperazine, for the treatment of hot flushes. J. Med Chem. 1987. 30, 1210-1214 disclosesN,N-disubstituted 6-alkoxy-2-pyridinamines as anticonvxilsant agents including l-(6-methoxy-2-pyridinyl)piperazine, 1 -(6-ethoxy-2-pyridinyl)piperazine, 1 -(6-isopropoxy-2-pyridinyl)piperazine, l-(6-isobutoxy-2-pyridinyl)piperazine, 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 1 -(6-butylthio-2-pyridinyl)piperazine, l-(6-cyclohexylmethyl-2-pyridinyI)piperazine and l-[6-(2-phenylethyl)-2-pyridinyl]piperazine. JP 07300474 discloses drugs for treatment of diseases related to serotoninergic nerve including l-(6-phenoxy-2-pyridiny!)piperazine 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)pyridine and 6-chloro-2-(4-methylpiperazinyl)pyridine. WO 00/12475 discloses indoline derivatives as 5-HT2b and/or 5-HT2c receptor ligands, espeC1ally for the treatment of obesity. wu uu/12510 discloses pyrroloindoles, pyridoindoles and azepinoindoles as 5-HT2c receptor agonists, particularly 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-l//-pyrazino[l,2-fl]quinoxalin-5(6//)ones as 5HT2c agonists, which may be used for the treatment of obesity. WO 00/44737 discloses aminoalkylbenzofurans 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; WO 02/40456 and WO 02/40457; heterocycle fused y-carbolines of the type described in WO 00/77001, WO 00/77002 and WO 00/77010; benzofurylpiperazines of the type described in WO 01/09111 and WO 01/09123; benzofiirans 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 and WO 02/44152; pyrazino(aza)indoles of the type described in WO 00/44753; diaza-cyclopenta[a]indenes of the type described in EP 1132389; piperazine derivatives of the type described in WO 02/10169; WO 02/72584 and WO 02/48124; quinoxalinones of the type described in US 6372745, and tricyclic pyrroles or pyrazoles of the type described in WO 98/56768. WO 95/01976 discloses indoline derivatives active as 5-HT2c antagonists and of potential use in the treatment of CNS disorders. WO 99/58490 discloses aryl-hydronaphthalen-alkanamines which may effectuate partial or complete blockage of serotonergic 5-HT2c receptors in an organism. WO 03/00666 discloses [l,2']bipyrazinyl 5-HT2 receptor ligands, in particular 5-HT2c receptor ligands, for the treatment of sexual dysfunction. wo 03/00663 discloses piperazinylpyrimidines as 5-HT2 receptor ligands, in particular 5-HT2(; receptor ligands, for the treatment of sexual disorders. WO 02/51844 discloses cycloalkyl fused indole derivatives and their use as 5-HT2b and 5-HT2c receptor ligands. WO 02/42304 discloses cyclopenta[b][l,4]diazepino[6,7-hi]indoles as selective S-HTic receptor agonists. WO 02/36596 discloses diazepinocarbazoles and related compounds as serotonin 5-HT2c agonists. SUMMARY OF THE INVENTION According to the invention novel compounds of the formula (I) ar? provided: wherein R is selected from H, CM alkyl, 2-hydroxyethyl, 2-cyanoethyl, tetrahydropyran-2-yl, and a nitrogen protecting group; R^ and R' each, independently, represent H or CH3; R" is selected from halogen, O-R^, NH-R^ or S-R^, wherein R^ is selected from aryl, aryl-C1.6-aIkyl, aryloxy-C2-6-aikyl, heteroaryl, heteroaryl-C1^-alkyl, heteroaryloxy-Cz^-alkyl, C3-6-cyC1oalkyl, Cs-e-cyclcalkyl-CM-alkyl, C1^-alkyl, 2-tetrahydrofuryl, 3-tetrahydrofuryl, 2-tetrahydroflirftiryl, 3-tetrahydrofurfiiryl, piperidine-4-yl, tetrahydropyran-4-yl, C3.6-alkynyl, Ca^-alkenyl, or fluoro-C2-4-alkyl; and wherein any aryl or heteroaryl residue, alone or as part of another group, may be unsubstituted or substituted with one or more of C1^-alkyl, CM-alkoxy, C\^-alkylthio, C2-i-acyl, C1^-alkylsulphonyl, cyano, nitro, hydroxy, C2.6-alkenyl, C2.6-alkynyl, fluoromethyl, trifluoromethyl, trifluoromethoxy, halogen, -N(R )(R ), aryl, aryloxy, arylthio, aryl-C1.4-alkyl, aryl-C2.4-alkenyl, aryl-C2^-alkynyl, heteroaryl. heteroaryloxy, heteroarylthio, heteroaryl-Cm-alkyl, aryl-CM-alkoxy, aryloxy-C1.4-alkyl, or dimethylamino-C2^-alkoxy„ wherein ' ■ R6 and R6 are, independently of each other^ hydrogen, methyl or ethyl; or form a pyrrolidine, piperazine, morpholine, thiomqrpholine or a piperidine ring together with, the nitrogen atom to which they :are bound; and wherein any aryl or heteroaryl residue as substituents on aryl or heteroaryl, alone or as part of another group, in turn may be substituted in one or more positions, preferably one, independently of each other by d -4-alkyl, C1 ^-alkoxy, halogen, trifluoromethyl, cyano, hydroxy or dimethylamino; and phamnaceutically acceptable salts, hydrates, solvates, geometrical isomers, tautomers, optical isomers, yV-oxides and prodrug forms thereof, with the proviso that, when R" is halogen at least one of R , R , or R is not hydrogen. When R" is halogen, it is preferred that either: (i) R is selected from C1-4 alkyl, 2-hydroxyethyI, 2-cyanoethyl, tetrahydropyran-2-yl, and a nitrogen protecting group; or (ii) R is selected from H, C1-4 alkyl, 2-hydroxyethyl, 2-cyanoethyI, tetrahydropyran-2-yl, and a nitrogen protecting group; and at least oneofR2andR3sCHa; In case the compounds of formula (I) 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, 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 prophylaxis or treatment of a serotonin-related disorder or condition> in a subject in need of such prophylaxis or treatment, the method comprising administering to the subject an effective amount of a compound of formula (I). It is preferred that the serotonin-related disorder or condition is a 5-HT2c receptor-related disorder or condition, espeC1ally memory disorders; Alzheimer's disease; schizophrenia; mood disorders; anxiety disorders; pain; substance abuse;'sexual dysfunction; epilepsy; glaucoma; urinary incontinence; menopausal and post-menopausal hot flushes; type II diabetes; eating disorders; binge eating disorders; anorexia nervosa; bulimia; or weight gain assoC1ated with antipsychotic drug administration; and most preferably obesity. The subject is preferably a human or an animal. The method includes administering an effective amount of a compound of formula (I), or a composition having a compound of formula (I) in it. Another aspect of the invention relates to the use of the compounds of formula (I) in the manufacture of a medicament for the prophylaxis or treatment of a serotonin-related disorder or condition. It is preferred that the serotonin-related disorder or condition is a 5-HT2c receptor-related disorder or condition, espeC1ally memory disorders; Alzheimer's disease; schizophrenia; mood disorders; anxiety disorders; pain; substance abuse; sexual dysfunction; epilepsy; glaucoma; urinary incontinence; menopausal and post-menopausal hot flushes; type II diabetes; eating disorders; binge eating disorders; anorexia nervosa; bulimia; or weight gain assoC1ated with antipsychotic drug administration; and most preferably obesity. Finally a method for modulating 5HT2c receptor function is an aspect of the invention. The methods delineated herein can also include the step of identifying that a subject is in need of treatment of serotonin-related disorders or conditions, particularly 5-HT2c receptor-related, in the subject. DETAILED DESCRIPTION OF THE INVENTION According to the present invention, a class of novel compounds that bind to the 5-HT2c receptor has been developed. The compounds may act as receptor agonists or antagonists at the 5-HT2c receptor and may therefore be used for the treatment of serotonin-related disorders or conditions, particularly 5-HT2c receptor-related. First, the various terms used, separately and in combinations, in the above definition of the compounds having the general formula (I) will be explained. The expression "C1-6 alkyl" refers to straight-chained and branched alkyl groups containing from 1 to 6 carbon atoms. Particular C1-6 alkyl groups are methyl, ethyl, n-propyl, isopropyl, tert-butyl, «-pentyl, isopentyl, «-hexyl, and isohexyl. Derived expressions such as "C1^ alkoxy" and "CM alkylthio" are to be constructed ■ accordingly. The expression "C:^ alkenyl" as used herein refers to straight-chained and branched alkenyl groups containing from 2 to 6 carbon atoms. Typical ej^amples include vinyl, allyl, 3,3-dimethylallyl, 1-butenyl, and 2-butenyl groups. The expression "€2^ alkynyl" as used herein refers to straight-chained and branched alkynyl groups containing from 2 to 6 carbon atoms. Typical examples include ethynyl and propargyl groups. 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, l-naphthyl, 2-naphthyl, 1,2,3,4-tetrahydronaphthyl, and indanyl. The aryl group 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 heteroatoms such as nitrogen, sulphur, oxygen and selenium and the remainder are carbon atoms. Examples of such heteroaryl rings are pyrrole, imidazole, thiophene, furan, thiazole, isothiazole, thiadiazole, oxazole, isoxazole, oxadiazole, pyridine, pyrazine, pyrimidine, pyridazine, pyrazole, triazole, tetrazole, chroman, isochrcman, coumarin, quinoline, quinoxaline, isoquinoline, phthalazine, C1nnoline, 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-1,4-benzodioxine, 1,3-benzodioxole, 1,2,3,4-tetrahydroquinoline, 3,4-dihydro-2//-1,4-benzoxazine, 1,5-naphthyridine, 1,8-naphthyridine, 3,4-dihydro-2//-pyrido[3,2-ii]-l,4-oxa2ine, and 2,3-dihydro-l,4-benzoxathiine.'If abicyclic aryl orheteroaryl ring is substituted, it may be substituted in any ring. Exemplary aryl-C1.6-alkyl, in which the alkyl portion of the group may be straight or branched, include benzyl, 2-naphthylmethyl, 2-phenylethyl, 3-phenyl-l-propyl, 1-phenylethyl, l-phenyl-2-propyl, 2-phenyl-l-propyl and the like. Exemplary aryloxy-C2-6-alkyl, in which the alkyl portion of the group may be straight or branched, include 2-phenoxyethyI, 2-(l-naphthyloxy)ethyl, 3-(2-naphthyloxy)-]-propyl, 3-phenoxy-l-propyl, 4-phenoxy-I-butyl, 5-phenoxy-l-pentyl, 1 -phenoxy-2-propyl and the like. Exemplary C3.6-cycloalkyl-C1.4-alkyl, in which the alkyl portion of the group may be straight or branched, include cyclopropylmethyl, cyclopentylmethyl, 2-cyclohexylethyl, 1-cyclohexylethyl, 1-eyelopropylethyl, 1-cyclobutylethyl and the like. Exemplary heteroaryloxy-C2.6-alkyl include 2-(8-quinolinyloxy)ethyl, 2-(3-pyridinyloxy)ethyl, 3-(8-quinolinyloxy)propyl and the like. Halogen includes fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine. Where it is stated above that aryl and heteroaryl residues may be substituted (in one or more positions), this applies to aryl and heteroaryl per se as well as to any combined groups containing aryl or heteroaryl residues, such as heteroaryIoxy-C2.6- alkyl, aryl-C1.6-alkyl etc. The term 'W-oxides" means that one or more nitrogen atoms, when present in a compound, are in TV-oxide form (N-^0). The term "prodrug forms" means a pharmacologically acceptable derivative, such as a carbamate or an amide, which derivative is biotransformed in the body to form the active drug. Reference is made to Goodman and Oilman's, The Pharmacological basis of Therapeutics, 8'^ ed., McGraw-Hill, hit. Ed. 1992, "Biotransformation of Drugs", p. 13-15. "Pharmaceutically acceptable" means being useful in preparing a pharmaceutical composition that is generally safe, non-toxic and neither biologically nor otherwise undesirable 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 aC1d addition salts formed with organic and inorganic aC1ds, such as hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric aC1d, phosphoric aC1d, acetic aC1d, glycolic aC1d, maleic aC1d, malonic aC1d, malic aC1d, oxalic aC1d, toluenesulphonic aC1d, methanesulphonic aC1d, fumaric aC1d, sucC1nic aC1d, tartaric aC1d, C1tric aC1d, benzoic aC1d, ascorbic aC1d and the like. The expression "comprising" means "including but not limited to." Thus, other non-mentioned substances, additives or carriers may be present. "A nitrogen protecting group" (z e a value for R') refers to a group covalently bonded to a nitrogen atom, or any group used to derivatize nitrogen atom (e.g., the nitrogen atom in an amino group). The group may be introduced or cleaved off by conventional methods such as those described in Protective Groups in Organic Synthesis, John Wiley & Sons, 1991. Examples of the nitrogen protecting groups include trityl or /-butoxycarbonyl and those delineated in Protective Groups in Organic Synthesis, John Wiley & Sons, 1991 and subsequent editions thereof. It is preferred that R' is hydrogen. It is also preferred that R is selected from chlorine, 0-R^, and S-R^. It is also preferred that R6 is selected from aryl-C1.6-alkyl, aryloxy-C2-6-alkyl. heteroaryl-C1.6-alkyl, heteroaryloxy-C2-6-alkyl, C3.6-cycloalkyl, C3- It is more preferred that R6 is selected from benzyl, 2-chlorobenzyl, 3-cyanobenzyl, 2-cyclohexylethyl, cyclopentyl, 2-cyclopentylethyl, 2,3-difluorobenzyl, 2,6-difluorobenzyl, 2-(2,6-difluorophenoxy)ethyl, 2,3-dihydrobenzo[I,4]dioxin-6-/Imethyl, ethyl, 5-fluoro-2-methoxybenzyl, furan-2-yhnethyl, methyl, a-■nethylbenzyl, 3-methylbenzyl, 2-(naphthalene-2-yIoxy)ethyl, 2-phenoxyethyl, 2- phenoxymethylbenzyl, n-propyl, 3-(pyridin-3-yl)-n-propyl, 2-(8-quinolinyloxy)etnyi, tetrahydrofliran-2-ylmethyl, or 3-thienylmethyl. It is also preferred that the carbon atom, to which R6 is attached, has the (S)-configuration when R6 is methyl and R' and R6 both are hydrogen. It is also preferred that the carbon atom, to which R' is attached, has the (R)-configuration when R"* is methyl and R' and R6 both are hydrogen. Preferred compounds of the general formula (I) above are the following compounds (corresponding to Examples 6-43 below): • l-(6-ChIoro-5-trifluoromethyl-pyridin-2-yl)-3-(5)-methyl-piperazine • l-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-3-(^)-methylpipera2ine • l-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-2-(y?)-methyl-piperazine • l-(6-Chloro-5-trifluororaethyl-pyridin-2-yl)-2-(5)-methyl-piperazine, hydrochloride • 1 -[6-(2-Phenoxy-ethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate • l-[6-(2,3-Dihydro-beruo[l,4]dioxin-6-ylmethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate • l-[6-(Thiophen-3-ylmethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate • 3-(6-Piperazin-l-yl-3-trifluoromethyl-pyridin-2-yloxymethyl)-benzonitrile, acetate • l-[6-(3-Methyl-benzylsulfanyl)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate • l-[6-(2-Chloro-benzylsulfanyl)-5-trifluoromethyI-pyridin-2-yl]-piperazine, acetate • l-[6-(2,3-Difluoro-benzyIoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate • 1 -(6-Ethylsulfanyl-5-trifluoromethyl-pyridin-2-yl)-pipera2ine, acetate • l-(6-Propoxy-5-trifluoromethyl-pyridin-2-yl)-piperazine, acetate • 1 -(6-Cyclopentyloxy-5-trifluoromethyl-pyridin-2-yl)-piperazine, acetate • l-[6-(l-Phenyl-ethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate • 8-[2-(6-Piperazin-l-yl-3-trifluoromethyl-pyridin-2-yloxy)-ethoxy]-quinoline, acetate • i-[6-(2,6-Difluoro-benzyloxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate • l-[6-(3-{Pyridin-3-yl}propoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate • 1 -(6-Benzyloxy-5-trifluoromethyl-pyridin-2-yl)-pipera2ine, acetate • 1 -[6-(Furan-2-ylmethoxy)-5-trifluoromethyl-pyndin-2-yl]-piperazine, acetate • l-{6-[2-(2,6-Difluoro-phenoxy)-ethoxy]-5-trifluoromethyl-pyridin-2-yl}-piperazine, acetate • l-[6-(2-Chloro-ben2ylsulfanyl)-5-trifluoromethyl-pyridin-2-yl]-2-(^)-methyl-piperazine, acetate • l-(6-Ethylsulfanyl-5-trifluoromethyl-pyridin-2-yl)-3-(5^-methyl-piperazine, acetate • l-(6-Ethylsulfanyl-5-trifluoromethyl-pyridin-2-yl)-3-(i?)-methyl-piperazine, acetate • l-(6-Ethylsulfanyl-5-trifluoromethyl-pyridin-2-yl)-2-(i?)-methyl-piperazine, acetate • l-(6-BenzyIoxy-5-trifluoromethyl-pyridin-2-yl)-3-(5)-methyl-piperazine, acetate • l-(6-Benzyloxy-5-trifluoromethyl-pyridin-2-yl)-3-(i?)-methyl-pipera2ine, acetate • l-(6-Benzyloxy-5-trifluoromethyl-pyridin-2-yl)-2-(/?)-methyl-piperazine, acetate • l-(6-Benzyloxy-5-trifluoromethyI-pyridin-2-yl)-2-(5)-methyl-pipera2ine, acetate • l-(6-Methoxy-5-trifluoromethyI-pyridin-2-yl)-piperazine, acetate • l-[6-(5-Fluoro-2-methoxy-benzyloxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate • l-{6-[2-(Naphthalen-2-yloxy)-ethoxy]-5-trifluoromethyl-pyridin-2-yl}-piperazine, acetate • l-[6-(2-Chloro-ben2ylsulfanyl)-5-trifluoromethyl-pyridin-2-yl]-3-C5>methyl-piperazine, acetate • l-[6-(2-Chloro-ben2ylsulfanyl)-5-trifluoromethyl-pyridin-2-yl]-2-f'S'>methyl-piperazine, acetate , , • l-[6-(2-Phenoxymethyl-benzyloxy)-5-trifluoromethyl-pyridin-2-yI]-piperazine, acetate • l-[6-Tetrahydro-furan-2-ylmethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate • ■l-[6-(2-Cyclopentyl-ethoxy)-5-tFifluoromethyl-pyridin-2-yl]-piperazine, acetate • l-[6-(2-Cyclohexyl-ethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate and their pharmacologically acceptable salts and solvates. The compounds corresponding to Examples 6, 8, 10-38, and 41-43 are even more preferred. As mentioned above, the compounds of the present invention are usefiil for the treatment, including prophylactic treatment, of serotonin-related, espeC1ally 5-HT2c receptor-related, disorders and conditions, in a human being or in an animal, including e.g. pets, such as memory disorders; 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 assoC1ated with substance abuse); pain; substance abuse; sexual dysfunction; epilepsy; glaucoma; urinary incontinence; menopausal and post¬menopausal hot flushes; type II diabetes; eating disorders; binge eating disorders; anorexia nervosa; bulimia; or weight gain assoC1ated with antipsychotic drug administration; and particularly obesity. The compounds of the present invention in radiolabelled form, may be used as a diagnostic agent. rrocesses lor preparaiion This invention also relates to a method for preparing, a pharmaceutical composition, the method comprising combining a compound of formula (I) with a pharmaceutically acceptable carrier. This invention also relates to methods of making compounds of any formulae delineated 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. The compounds of general formula (I) above maybe prepared by, or in analogy with, conventional methods, and espeC1ally according to or in analogy with the following method. Compounds of formula (I) above in which R" is halogen, 0-R^, NH-R^ or S- R6 are prepared by reacting a compound of the structural formula (II): wherein Hal is halogen; with 1 to 10 molar equivalents of an appropriate piperazine derivative of formula (III): wherein R , R , and R are as defined above; in a solvent such as dimethylsulfoxide (DMSO), acetonitrile, dioxane, tetrahydrofuran (THF), «-butanol, A^.A'-dimethylformamide (DMF), or in a mixture of solvents such as DMF/dioxane, optionally in the presence of a base, such as K2CO3, Na2C03, CS2CO3, NaOH, triethylamine, pyridine or the like, at 0-200 °C for 1-24 hours to produce a compound of formula (FV): wherein R' , R6, and R6 are as defined above and Hal is halogen. The compound of formula (IV) is reacted with an appropriate alcohol, amine, or thiol as defined by 0-R', NH-R^ or S-R^ above, or its corresponding anions to produce a compound of the formula (I) above. The appropriate alcohol, amine, or thiol may be converted completely or partially to its corresponding anion by treatment with bases, such as triethylamine, l,8-diazabicyclo[5.4.0]undec-7-ene, K2CO3, NaOH, NaH, KO-/-Bu, lithium diisopropylamide or the like. The reaction is carried out in a solvent, such as DMSO, dioxane, THF, rer/-butanol or DMF, at 0-200 °C for 1-24 hours. An obtained compound of formula (I) above may be converted to another compound of formula (I) by methods well known in the art. The chemicals used in the above-described synthetic routes may include, for example, solvents, reagents, catalysts, protecting group and deprotecting group reagents. The methods described above may also additionally include steps, either before or after the steps described speC1fically herein, to add or remove suitable protecting groups in order to ultimately allow synthesis of the compounds of formula (I). When R' is a nitrogen protecting group as defined above, the subsequent A'-deprotection is carried out by conventional methods. In addition, various synthetic steps may be performed in an alternate sequence or order to give the desired compounds. Synthetic chemistry transformations and protecting group methodologies (protection and deprotection) useful in synthesizing applicable compounds are known in the art and include, for example, those described in R. Larock, Comprehensive Organic Transformations, VCH Publishers (1989); T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 2" Ed., John Wiley and Sons (1991); L. Fieser and M. Fieser, Fieser and Fieser's Reagents for Organic Synthesis, John Wiley and Sons (1994); and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis, John Wiley and Sons (1995); and subsequent editions thereof. • , . . .The process that is described above may be carried out to give a compound of the invention in the form of a free base or as an aC1d addition salt. A pharmaceutically acceptable aC1d addition salt may be obtained by dissolving the free base in a suitable organic solvent and treating the solution with an aC1d, in accordance with conventional procedures for preparing aC1d addition salts from base compounds. Examples of addition salt forming aC1ds are maleic aC1d, fumaric aC1d, sucC1nic aC1d, methanesulfonic aC1d, acetic aC1d, malic aC1d, oxalic aC1d, benzoic aC1d, hydrochloric aC1d, sulphuric aC1d, phosphoric aC1d, 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) aC1ds or by chromatographic separation on chiral columns. The necessary starting materials for preparing the compounds of formula (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 form of free bases or salts with physiologically acceptable aC1ds, 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 assoC1ation with compatible pharmaceutically acceptable carrier materials, or diluents, as are well known in the art. The carriers 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, calC1um 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, flavoring 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, dispersible 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, espeC1ally 5-HT2c receptor-related disorders and conditions in a human being or an animal, such as memory disorders including Alzheimer's disease; schizophrenia; mood disorders; anxiety disorders; pain; substance abuse; sexual dysfunction; epilepsy; glaucoma; urinary incontinence; menopausal and post-menopausal hot flushes; type II diabetes; eating disorders, such as binge eating disorders, anorexia nervosa and bulimia; weight gain assoC1ated with antipsychotic drug administration; and particularly obesity. Also within the scope of this invention is a method for modulating (e.g., inhibiting or stimulating) 5-HT2c-receptor activity. The method includes administering to a subject in need thereof an effective amount of a compound of the formula (I). The methods delineated herein can also include the step of identifying that a subject is in need of treatment of serotonin-related, espeC1ally 5-HT2c receptor-related, disorders and conditions in the subject (e.g., a mammal, a human being, a horse, a dog, or a cat). "An effective amount" refers to an amount of a compound, which confers a therapeutic effect on the treated subject. The therapeutic effect may be objective (i.e., measurable by some test or marker) or subjective (i.e., subject gives an indication of or feels an effect). For clinical use, the compounds of the invention are formulated into pharmaceutical formulations for oral, rectal, parenteral or other mode of administration. Usually the amount of active compounds is between 0.1-95% by weight of the preparation, preferably between 0.2-20% by weight in preparations for parenteral use and preferably between 1 and 50% by weight in preparations for oral administration. ' The dose level and frequency of dosage of the speC1fic compound will vary depending oh a variety of factors including the potency of the speC1fic 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, drug combination, the severity of the condition to be treated, and the patient undergoing therapy. The daily dosage may, for example, range from 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 C1ted 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 Experimental Methods The 'H-and '^C-NMR-spectra were obtained with a Bruker DPX 400. The DPFGSE-NOE experiments were obtained with a Varian INOVA 400. The mixing time was 0.8 seconds. The preparative LC was performed on a preparative LC-MS Gilson-Fimiigan with a 50x20mm S 5 jim, 120A column. The flow was 30 mL/min and different gradients of 0.1% acetic aC1d in water and acetonitrile were used. The accurate masses were determined with a Micromass LCT with electrospray ionization. The elemental analyses were performed with a Vario EL instrument. A Koefler bench was used to measure the melting points, which are not corrected. Examples 1-5. Preparation of intermediates. General procedure for Examples 1-2. To a suspension of LiAlILt (1.2 g, 32 mmol) in dry THF (5 mL) was added the aldehyde or carboxylic aC1d (10 mmol) and the mixtures were stirred at room temperature for two hours. Mixtures with aldehydes as starting materials were put aside and the aC1ds were heated at 60 °C overnight. To each mixture was added in consecutive order water (1.2 mL), 2 M aqueous NaOH (1.2 mL), and water (3.6 mL). The preC1pitate was fihered off and the solvent was removed under reduced pressure to yield the target products as oils. EXAMPLE 1 . (5-Fluoro-2-methoxy-phenyl)-methano\|. The title compound was prepared starting from 5-fluoro-2-methoxybenzaldehyde and was obtained as a light red oil (94% yield). Fragmenting MS analysis supports the stated structure.. Purity 97% (GC). 'H NMR (CDC13) 5 3.28 (s, 3 H), 4.64 (s, 2 H), 6.78 (m, 1 H), 6.93 (m, 1 H), 7.02 (m, 1 H). '^C NMR (CDC13) 6 55.73, 61.34, 110.83 (d,J= 8.5 Hz), 114.22 (d, J= 22.6 Hz), 115.26 (d, J= 23.3 Hz), 138.68 (d, J= 6.4 Hz), 153.18 (d, /= 2.1 Hz), 156.95 (d,J= 238.8 Hz). EXAMPLE 2 (2-Phenoxymethyl-phenyl)-methanol. The title compound was prepared starting from 2-(phenoxymethyl)benzoic aC1d and was obtained as a light yellow oil (96% yield). Fragmenting MS analysis supports the stated structure. Purity 94% (GC). Previously reported in J. Chem. Soc, 1954,2819-2826. EXAMPLE 3 3-(5)-MethyH-trityl-piperazine. To a solution of 2-(S)-methylpiperazine (3.79 g, 37.9 mmol) in CHC13 (100 mL) was trityl chloride (10.56 g, 37.9 mmol) added in one portion. The exothermic reaction was stirred at ambient temperature for two hours, the organic phase was washed three times with water, dried (MgS04) and the solvent was evaporated at reduced pressure to give 12.5 g (96%) of a colorless foam that solidified to a crisp overnight.'H NMR(CDC13) 5 1.06 (d, J =5.5 Hz, 3 H), 1.35 (m, 1 H), 1.61 (m, 1 H), 3.01 (m, 3 H), 3.14 (m, 1 H), 3.31 (m, 1 H), 7.08 (m, 3 H), 7.16 (m, 6 H), 7.35 (m, 6 H).'^C NMR (CDC13) 5 18.17,44.46,46.68,51.59,54.03, 126.26, 127.13, 127.68, 129.07 br. The racemate of the title compound is reported in Bioorg. Med. Chem. Lett. 2000,10, 2643-2646. EXAMPLE 4 3-(R)-Methyl-l-trityl-piperazine. The title compound was prepared as described in WO 00/76984 starting from i 2-(R)-methyIpiperazine (5.51 g, 55.1 mmol). This gave 18.8 g (99%) of a white crisp. HRMS miz calcd for C24H26N2 (Mf 342.2096, found 342.2110. EXAMPLE 5 l-(6-ChIoro-5-trifluoromethyI-pyndin-2-yl)-piperazine. Step 1: 4-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-piperazine-l-carhoxylic aC1d tert-butyl ester. To a suspension of/er/-butyl-l-piperazine carboxylate (27.0 g, 145 mmol) and K2CO3 (40.0 g, 290 mmol) in DMSO (200 mL) were 2,6-dichloro-3-trifluoromethylpyridine (29.1 g, 135 mmol) and toluene (50 mL) added. The thick slurry was stirred at 80 °C for two hours, followed by addition of toluene (0.5 L) and water (1 L). The phases were separated and the organic phase was washed twice with water. The solvent from the dried (MgS04) organic phase was evaporated at reduced pressure. The solid residue was recrystallized from EtOAc/heptane to give white crystals (37 g). The filtrate from the recrystallization was concentrated and the residue chromatographed on a column of silica with hexane/EtOAc (90:10) to give further 6.0 g of product (total yield 85%). Purity 99% (HPLC); mp 125 °C. Anal. (C15H19ClF3N3O2)C,H.N. Step 2:1 -(6-Chloro-5-tri/luoromethyl-pyridin-2-yl)-piperazine.* The title compound was prepared from the product of Step 1 above using the N-deprotection procedure given in Example 6, Step 2. This fiimished 29.7 g (100%) of a light yellow oil that crystallized upon standing. A NOE between the methylene protons at C-2 in the piperazine ring and the C3-hydrogen in the pyridine ring was observed. Purity 99% (HPLC); mp 56 °C. Fragmenting MS analysis supports the stated structure. HRMS m/z calcd for C1oH, ,C1F3N3 (M)" 265.0594, found 265.0597. PreviousIy reported in EP 370560. EXAMPLE 6 l-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-3-(5)-niethyl-piperazine. Step 1: 4-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-2-(S)-methyl-piperazine-l-carboxylic aC1d tert-butyl ester. To a suspension of 2-(y)-methylpiperazine (2.65 g, 26.5 mmol) and K2CO3 (4.0 g, 29 mmol) in dry DMSO (50 mL) was slowly added 2,6-dichloro-3-trifluoromethylpyridine (5.70 g, 26.4 mmol). The reaction mixture was stirred at room temperature over night, filtered, diluted with water (ca 1 L) and extracted twice with EtOAc (100 mL). The solvent from the combined dried (MgS04) organic phases was evaporated at reduced pressure to give a yellow oil (7.4 g). This material was dissolved in MeOH (100 mL), BOC anhydride (6.0 g, 27.5 mmol) was added in one portion and the reaction mixture was stirred at room temperature for two hours. Excess BOC anhydride was quenched with pyridine (3 mL) and the mixture was left at room temperature over night. The solvent was removed at reduced pressure and the resulting oil was chromatographed on a column of silica (60x110 mm) with hexane/EtOAc (95:5, 1 L, followed by 90:10, 1 L and 80:20). Evaporation at reduced pressure of the pure fractions yielded a colorless oil (8.05 g, 80%) that solidified to a white solid over night. Purity 97% (HPLC); mp 86 °C. Fragmenting MS analysis supports the stated structure. HRMS mlz calcd for C16H21C1F3N3O2 (M)"^ 2>19.\11A, found 379.1286. Step 2: l-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-3-(S)-methyl-piperazine. A solution of 4-(6-chloro-5-trifluoromethyl-pyridin-2-yl)-2-(5)-methyl-piperazine-1-carboxylic aC1d /err-butyl ester (7.80 g, 26.4 mmol) was dissolved in CH2C12/TFA (50:50; 30 mL) and stirred at room temperature over night. The solvent was removed at reduced pressure and the resulting oil was taken up between alkaline water (NaOH) and CHC13. The aqueous phase was extracted once with CHC13, the combined organic phases were dried (MgS04) and the solvent was evaporated at reduced pressure to yield 5.79 g (78%) of a light yellow oil. A NOE between the methylene protons at C-2 in the piperazine ring and the C3-hydrogen in the pyridine ring was observed. Purity 100%> (HPLC). Fragmenting MS analysis supports the stated structure. HRMS mlz calcd for CnHuClFjNa (M)" 279.0750, found 279.0751 EXAMPLE? , ,, l-(6-Chloro-5-itrifluoromethyl-pyridin-2-yl)-3-(i?)-methylpiperazine. Step 1: 4-'(6-Chloro-5-triJluoromethyl-pyridin-2-yl)-2-(R)-methyl-piperazine-l- carboxylic aC1d tert-butyl ester. ;, The title compound was prepared starting from 2-(/?)-methylpiperazine using the procedure given in Example 6, Step 1, for the (iS)-isomer and was obtained as a white crystaUine solid. Yield 7.4 g (70%)'. Purity 99% (HPLC); mp 86 °C. Fragmenting MS analysis supports the stated structure. HRMS tniz calcd for C,6H2iClF3N302(M)^ 379.1274, found 379.1269. Step 2: l-(6-Chloro-5-trifIuoromethyl-pyridin-2-yl)-3-(R)-methylpiperazine. The title compound was prepared starting from the product of Step 1 above using the A^-deprotection procedure given in Example 6, Step 2, and was obtained as a light yellow oil. Yield 4.76 g (90%). Purity 99% (HPLC). Fragmenting MS analysis supports the stated structure. HRMS m/z calcd for CnHnClFaNa (M)"" 279.0750, found 279.0742. EXAMPLE 8 1 l-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-2-(/?)-methyl-piperazine. Step I: l-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-2-(R)-Tnethyl'4-trityl-piperazine. A suspension of 3-(/{)-methyl-l-trityl-piperazine (from Example 4; 7.80 g, 22.9 mmol), 2,6-dichloro-3-trifluoromethylpyridine (4.50 g, 20,8 mmol) and K2CO3 (4.0 g, 29 mmol) in DMSO (100 mL) was stirred at 80 °C over night. A mixture of EtOAc/toluene (50:50; 500 mL) was added to the filtered solution and the mixture were washed three times with water (1 L). The dried (MgS04) organic phase was concentrated under reduced pressure and the resulting brown oil was dissolved in heptane/EtOAc (90:10) and filtered through a plug (60x60 mm) of silica. Slow evaporation of about two thirds of the solvent at reduced pressure afforded light yellow crystals (6.11 g, 56%). Purity 100% (HPLC); mp 209 °C. Fragmenting MS analysis supports the stated structure. Anal. (C30H27C1F3N3) C, H, N. Step 2: l-(6-Chloro-5-trifliioromethyl-pyridin-2-yl)-2-(R)-melhyl-piperaiine. A suspension of l-(6-chloro-5-trifluoromethyl-pyridin-2-yl)-2-(^)-methyl-4-trityl-pipera2;ine (from Step 1 above; 5.70 g, 10.9 mmol) in EtOH (70 mL) was heated to 80 °C. Aqueous HCl (4 M;'6 mL) was added and the mixture was heated in an open vessel for one hour. To the clear solution was water added (100 mL) and the preC1pitate was filtered off. The solvent from thefiltrate was evaporated down to about 10 mL, the crystals were filtered off and the evaporation continued down to 3 mL and another portion of slightly pinkish crystals were filtered off The combined crystal fractions were taken up between alkaline water (NaOH)/CHCl3. The aqueous phase was washed twice with CHClj and the combined, dried (MgS04), organic phases were evaporated at reduced pressure to give a light yellow oil (1.75 g, 69%). A NOE between the methylene protons at C-2 in the piperazine ring and the C3-hydrogen in the pyridine ring was observed. Purity 99% (HPLC). Fragmenting MS analysis supports the stated structure. HRMS m/z calcd for C1 1H13C1F3N3 (M)"^ 279.0750, found 279.0744. EXAMPLE 9 l-(6-Chloro-5-trifIuoromethyl-pyridin-2-yl)-2-(iy)-methyl-piperazine, hydrochloride. Step J: l-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-2-(S)-methyl-4-trityl-piperazine. The title compound was prepared starting from 3-(5)-methyl-l-trityl-piperazine (obtained in Example 3) using the procedure given in Example 8 for the (i?)-isomer. Light yellow crystals; yield 5.1 g (43%). Purity 96% (HPLC); mp 210 °C. Fragmenting MS analysis supports the stated structure. Anal. (C30H27C1F3N3) C, H,N. Step 2: l-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-2-(S)-methyl-piperazine, Hydrochloride. The title compound was prepared starting from the product of Step 1 above using the N-detritylation procedure given in Example 8, Step 2, for the (j'?)-isomer. This produced 2.06 g (68%) of the free base of the title compound obtained as a pinkish oil. The free base was converted into its hydrochloride salt. Purity 99% (HPLC). Fragmenting MS analysis supports the stated structure. HRMS m/z calcd for C, iH,3ClF3N3 (Mf 279.0750, found 279.0738. Examples 10-43 General procedure Volumes are expressed as total volumes. To a 16 mm test tube was added; • 0.5 mmol of the appropriate alcohol or thiol • 0.4 mmol of the appropriate 6-chloro 5-trifluoromethyI-2-piperazinylpyridine in DMSO (0.5 mL) • 0.65 mmol of K-/-BuO in DMSO (1.0 mL) The reactions were stirred at room temperature for two hours followed by addition of HO Ac (1.25 mmol, 75 \|j.L). The solvent was evaporated at reduced pressure over night (Speed Vac). The remaining solids were dissolved in water/acetonitrile/HOAc, filtered, and the products were purified with preparative HPLC. Mass detection was obtained by a Micro Mass LCP with electrospray positive ionization mode. The analytical HPLC-chromatograms were performed on a Hewlett Packard 1100 with a 50x4.6mm Grom-SEL 100 ODS 0 AB, 3 ^m column and a 50x4.6 mm YMC-AQ 5 fim column. Different gradients of 0.1% TEA in water and acetonitrile were used and the peaks were detected at 254 nm. The area% under the largest peak was reported as the purity. Chart 1. Starting 6-chIoropyridines used in Examples 10-43. • EXAMPLE 10 l-(6-(2-Phenoxy-ethoxy)-5-trifluoromethyl-pyridin-2-yI]-piperazme, acetate. Starting materials A and 1, see Chart 1. Purity 99% (HPLC). MS m/z 368 (M+Hf. HRMS m/z calcd for C18H2oF3N302(M)* 367.1508, found 367.1508. EXAMPLE 11 l-[6-(2,3-Dihydro-benzo[l,4]dioxin-6-yImethoxy)-5-trifIuoromethyl-pyridin-2-yl]-piperazine, acetate. Starting materials A and 2, see Chart 1. Purity 94% (HPLC). MS m/z 396 (M+H)^ HRMS m/z calcd for C19H20F3N3O3 (M)* 395.1457, found 395.1468. EXAMPLE 12 l-[6-(Thiophen-3-ylmethoxy)-5-trifluoromethyl-pyridiii-2-yl]-piperazine, acetate. Starting materials A and 3, see Chart 1. Purity 98% (HPLC). MS miz 344 (M+H)^ HRMS mIz calcd for C15H16F3N3OS (Mf 343.0966, found 343.0971. EXAMPLE 13 3-(6-Piperazin-l-yI-3-trifluoromethyl-pyridin-2-yIo.\ymethyl)-benzoDitriIe, acetate. Starting materials A and 4, see Chart 1. Purity 95% (HPLC). MS mIz 363 (M+H)'. HRMS mIz calcd for C18Hi7F3N40(Mr 362.1354, found 362.1,365. EXAMPLE 14 l-(6-(3-Methyl-benzylsulfanyl)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate. Starting materials A and 5, see Chart 1. Purity 96% (HPLC). MS mlz 368 (M+H)^ HRMS mlz calcd for C18H20F3N3S (M)^ 367.1330, found 367.1322. EXAMPLE 15 l-(6-(2-ChIoro-benzy!sulfanyI)-5-trifluoroinethyl-pyndin-2-yl]-pipera2ine, acetate. Starting materials A and 6, see Chart 1. Purity 98% (HPLC). MS mlz 388 (M+H). HRMS mlz calcd for C17H17C1F3N3S (M) 387.0784, found 387.0773. EXAMPLE 16 l-(6-(23-Difluoro-benzyloxy)-5-trinuoromethyl-pyridiii-2-yl]-piperazine, acetate. Starting materials A and 7, see Chart 1. Purity 100% (HPLC). MS mlz 374 (M+H). EXAMPLE 17 l-(6-Ethylsulfanyl-5-trifluoromethyl-pyridin-2-yl)-piperazine, acetate. Starting materials A and 8, see Chart 1. Purity 96% (HPLC). MS m/z 292 (M+H^- HRMS m/z calcd for C12H,6F3N3S (Mf 291.1017, found 291.1018. EXAMPLE 18 l-(6-Propoxy-5-trinuoroniethyl-pyridin-2-yI)-piperazine, acetate. Starting materials A and 9, see page Chart 1. Purity 100% (HPLC). MS m/z 290 (M+H)^ EXAMPLE 19 l-(6-Cyclopentyloxy-5-trifluoroinethyl-pyridin-2-yl)-piperazine, acetate. Starting materials A and 10, see Chart 1. Purity 100% (HPLC). MS m/z 316 (M+H)^ HRMS m/z calcd for C\|5H2oF3N30(M)^ 315.1558, found 315.1551. EXAMPLE 20 l-16-(l-Phenyl-ethoxy)-5-trinuoromethyl-pyridin-2-yl]-piperazine, acetate. Starting materials A and 11, see Chart 1. Purity 100% (HPLC). MS m/z 352 (M+H)^ HRMS m/z calcd for C18H2oF3N30(M)^ 351.1558, found 351.1573. EXAMPLE 21 8-[2-(6-Piperazin-l-yI-3-trifluoromethyl-pyridin-2-yIoxy)-ethoxy]-quinoIine, acetate. Starting material A and 12, see page Chart 1. Purity 98% (HPLC). MS m/z 419 (M+H)^ HRMS m/z calcd for C2iH2iF3N402(M)* 418.1617, found 418.1625. Starting material 12 was prepared as described in WO 00/76984. EXAMPLE 22 l-[6-(2,6-Difluoro-benzyloxy)-5-trifluoromethyl-pyridin-2-yI]-piperazine, acetate. Starting material A and 13, see Chart I. Purity 96%o (HPLC). MS m/z 374 (M+H)^ HRMS m/z calcd for C17Hi6F5N30(M) 373.1214, found 373.1209. EXAMPLE 23 l-[6-(3-{Pyridin-3-yl}propoxy)-5-trifluoroinetbyl-pyridin-2-yI]-piperazine, acetate. Starting material A and 14, see Chart 1. Purity 99% (HPLC). MS miz 367 (M+Hf. HRMS mIz calcd for C18H2iF3N40(M)* 366.1667, found 366.1677. EXAMPLE 24 l-(6-Benzyloxy-5-trifluorotnethyI-pyridin-2-yl)-piperazine, acetate. Starting material A and 15, see Chart 1. Purity 99% (HPLC). MS mIz 338 (M+Hf. HRMS mIz calcd for C1jHigFaNaOCM)* 337.1402, found 337.1408. EXAMPLE 25 l-[6-(Furan-2-ylmethoxy)-5-trifluoromethyI-pyridia-2-yI]-piperazine, acetate. Starting material A and 16, see Chart 1. Purity 96% (HPLC). MS mIz 328 (M+H)^ HRMS m/z calcd for C15Hi6F3N302(M)* 327.1195, found 327.1195. EXAMPLE 26 l-{6-[2-(2,6-Difluoro-phenoxy)-ethoxy}-5-trifluoromethyl-pyridin-2-yl}-piperazine, acetate. Starting materials A and 17, see Chart 1. Purity 98% (HPLC). MS mIz 404 (M+H)^ HRMS mIz calcd for C18Hi8F5N302(M) 403.1319, found 403.1326. Starting material 17 was prepared from 2,6-diflurophenoI and ethylene carbonate according to the general procedure described in WO 00/76984 (Example 91). MS analysis supported the stated structure. HRMS m/z calcd for C8H8F2O2 (M) 174.0492, found 174.0491. EXAMPLE 27 l-[6-(2-Chloro-benzyIsuIfanyI)-5-trinuoromethyI-pyridiii-2-yIl-2-(/?)-methyl-piperazine, acetate. Starting materials D and 6, see Chart 1. Purity 96% (HPLC). MS m/z 402 (M+Uy. HRMS m/z calcd for C1gH\|9ClF3N3S (M)^ 401.0940, found 401.0926. EXAMPLE. 28 ,' , l-(6-Ethylsulfanyl-5-trifluoromethyl-pyridin-2-yl)-3-(5)-methyl-piperazine, acetate. Starting materials B and 8, see Chart 1. Purity 100% (HPLC). MS miz 306 {U+Kf. HRMS mIz calcd for CHHISFBNBSCM)^,305.1174, found 305.1163. EXAMPLE 29 ■ l-(6-Ethylsulfanyl-5-trifluoromethyI-pyridin-2-y!)-3-(/?)-inethyl-piperazine, acetate. Starting materials C and 8, see Chart 1. Purity 95% (HPLC). MS mIz 306 (M+H)^. HRMS mIz calcd for C13H18F3N3S (Mf 305.1174, found 305.1168. EXAMPLE 30 l-(6-EthyIsuIfanyl-5-tnfluoromethyl-pyridin-2-yl)-2-(/?)-methyI-piperazine, acetate. Starting materials D and 8, see Chart 1. Purity 100% (HPLC). MS mIz 306 (M+H)". HRMS mIz calcd for CnHigFsNsS (M)^ 305.1174, found 305.1160. EXAMPLES! l-(6-Benzyloxy-5-trifluoromethyl-pyridin-2-yI)-3-(5)-methyl-piperazine, acetate. Starting materials B and 15, see Chart \. Purity 100% (HPLC). MS mIz 352 (M+H)^ HRMS mIz calcd for C18H20F3N3O(M)^ 351.1558, found 351.1553. EXAMPLE 32 l-(6-Benzyloxy-5-trifluoromethyl-pyridin-2-yI)-3-(i?)-methyl-piperazine, acetate. Starting materials C and 15, see Chart 1. Purity 99% (HPLC). MS mIz 352 (M+H)^ HRMS w/z calcd for C18H2oF3N30(M)^ 351.1558, found 351.1541. EXAMPLE 33 l-(6-Benzyloxy-5-trinuoromethyl-pyridin-2-yI)-2-(i?)-methyl-piperazine, acetate. Starting materials D and 15, see Chart 1. Purity 99% (HPLC). MS miz 352 (M+Hf. HRMS m/2 calcd for C1SH20F3N3O (M)^ 351.1558, found 351.1551. EXAMPLE 34 l-(6-Benzyloxy-5-trifluoromethyl-pyridin-2-yl)-2-(5)-methyl-piperazine, acetate. , Starting materials E and 15, see Chart 1. Purity 100% (HPLC). MS mIz 352 (M+Hf. HRMS mIz calcd for C18H2oF3N30(M)^ 351.1558, found 351.1552. EXAMPLE 35 l-(6-lVIethoxy-5-trifluoromethyl-pyridin-2-yl)-piperazine, acetate. Starting materials A and 18, see Chart 1. Purity 100% (HPLC). MS mIz 262 (M+H)^ HRMS mIz calcd for C1 iHi4F3N30(M)* 261.1089, found 261.1100. EXAMPLE 36 l-[6-(5-Fluoro-2-methoxy-benzyloxy)-5-trifluorometbyl-pyridln-2-yI]-piperazine, acetate. Starting materials A and 19, see Chart 1. Purity 96% (HPLC). MS m/z 386 (M+H)". HRMS m/z calcd for C18H19F4N3O2 (M)* 385.1413, found 385.1408. EXAMPLE 37 l-{6-[2-(Naphthalen-2-yloxy)-ethoxy]-5-trifluoromethyI-pyridin-2-yI}-piperazine, acetate. Starting materials A and 20, see Chart 1. Purity 100% (HPLC). MS m/z 418 (M+H). HRMS m/z calcd for C22H22F3N3O2 (M)^ 417.1664, found 417.1658. EXAMPLE 38 l-(6-(2-Chloro-benzylsulfanyl)-5-trifluoroinethyl-pyridin-2-yI]-3-(S)-methyI-piperazine, acetate. Starting materials B and 6, see Chart 1. Purity 100% (HPLC). MS m/z 402 (M+Hf. HUMS m/z calcd for C18H19C1F3N3S (M)+ 401.0940, found 401.0950. EXAMPLE 39 l-[6-(2-Chloro-benzylsulfanyl)-5-trifluoromethyl-pyridiD-2-yl]-2-C5'>methyl-piperazine, acetate. Starting materials E and 6, see Chart 1. Purity 99% (HPLC). MS m/z 402 (M+Hf. HRMS m/z calcd for C1SH19F3N3S (Uf 401.0940, found 401.0942. EXAMPLE 40 l-[6-(2-Phenoxymethyl-benzyloxy)-5-trifluoroniethyl-pyridin-2-yI]-piperazine, acetate. Starting materials A and 21, see Chart 1. Purity 100% (HPLC). MS m/z 444 (M+H). HRMS m/z calcd for C24H24F3N3O2 (M)* 443.1821, found 443.1841. EXAMPLE 41 l-[6-Tetrahydro-furan-2-ylniethoxy)-5-trifluoroinethyl-pyridin-2-yI]-piperazine, acetate. Starting materials A and 22, see Chart 1. Purity 97% (HPLC). MS m/z 332 (M+H). HRMS m/z calcd for C15H20F3N3O2 (Uf 331.1508, found 331.1504. EXAMPLE 42 l-(6-(2-CyC1opentyl-ethoxy)-5-trifluoromethyl-pyridin-2-yI]-piperazine, acetate. Starting materials A and 23, see Chart 1. Purity 100%) (HPLC). MS m/z 344 (M+H). EXAMPLE 43 l-[6-(2-CyC1ohexyl-ethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate. Starting materials A and 24, see Chart 1. Purity 90% (HPLC). MS m/z 358 (M+H)^. HRMS m/z calcd for C18H26F3N3O (M)+ 357.2028, found 357.2040. PREPARATION OF A PHARMACEUTIGAL COMPOSITION I 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 METHODS The ability of a compound of the invention to bind or act at speC1fic 5-HT receptor subtypes can be determined using in vitro and in vivo assays knpwn 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 compound in serial dilution to displace 3H-labelledlabeled 5-HT, bound to membranes prepared from a transfected HEK293 cell line stably expressing the human 5-HT2c receptor protein, was monitored by SC1ntillation Proximity Assay technology. Non-speC1fic binding was defined using 5 \xM mianserin. Results obtained for exemplary compounds of the invention are illustrated in Table 1 below. The 5-HT2c receptor affinity values, expressed as percent inhibition of binding of the radioligand at 50 nM of test compound, were in the range of l0%-95%. The Kj values for the compounds towards the 5-HT2C receptor were in the range 0.5-5000 nM. 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 calC1um in transfected HEK293 cells, stably expressing the human 5-HT2c receptor protein, using the calC1um-chelating fluorescent dye FLUO-3 (Sigma, St. Louis, MO, U.S.A.). The maximum responses of the compounds in the Examples were in the range of 0-102% relative to the maximum response of 5-HT (serotonin) at a concentration of 1 µM. WE CLAIM : 1. A compound of the formula (I): wherein R1 is selected from H, 1-4 alkyl, 2-hydroxyethyl, 2-cyanoethyl, tetrahydropyran-2-yl, and a nitrogen protecting group; R2 and R3 each, independently, represent H or CH3; R4 is selected from 0-R5 NH-R5 or S-R5 wherein R5 is selected from aryl, aryl-C1.6-alkyl, aryloxy-C1-6-alkyl, heteroaryl, heteroaryl-C1.6-alkyl, heteroaryloxy-C2.6-alkyl, C3.6-cycloalkyl, C3.6-cycloalkyl-C1.4-alkyl, C1.6-alkyl, 2- tetrahydrofuryl, 3-tetrahydrofuryl, 2-tetrahydrofurfuryl, 3-tetrahydrofurfuryl, piperidine-4-yl, tetrahydropyran-4-yl, Cs-e-alkynyl, C3.6-alkenyl, or fluoro-C2-4-alkyl; and wherein any aryl or heteroaryl residue, alone or as part of another group, may be unsubstituted or substituted with one or more of Cj^-alkyl, C14-alkoxy, C1-4-alkylthio, C24- acyl, CM-alkylsulphonyl, cyano, nitro, hydroxy, C2.6-alkenyl, C2.6-alkynyl, fluoromethyl, trifluoromethyl, trifluoromethoxy, halogen, -N(R6)(R7), aryl, aryloxy, arylthio, aryl-C1.4-alkyl, aryl-C24-alkenyl, aryl-C2-4-alkynyl, heteroaryl, heteroaryloxy, heteroarylthio, heteroaryl-CM- alkyl, aryl-C1.4-alkoxy, aryloxy-CM-alkyl, or dimethylamino-C2-4-alkoxy, wherein R6 and R7 are, independently of each other, hydrogen, methyl or ethyl; or form a pyrrolidine, piperazine, morpholine, thiomorpholine or a piperidine ring together with the nitrogen atom to which they are bound; and wherein any aryl or heteroaryl residue as substituents on aryl or heteroaryl, alone or as part of another group, in turn may be substituted in one or more positions, preferably one. independently of each other by C1.4-alkyl, C1.4-alkoxy, halogen, trifluoromethyl, cyano, hydroxy or dimethylamino; and pharmaceutically acceptable salts, hydrates, solvates, geometrical isomers, tautomers, optical isomers, A'-oxides and prodrug forms thereof. 2. The compound as claimed in claim 1, wherein R' is hydrogen. 3. The compound as claimed in any one of claims 1-2, wherein R' is selected from 0-R^ and S-R^ 4. The compound as claimed in any one of claims 1-3, wherein R^ is selected from aryl-C1. 6-alkyl, aryloxy-C2-6-alkyl, heteroaryl-C1.6-alkyl, heteroaryloxy-C2.6-alkyl, C34s-e-cycloalkyl, C3.6-cycloalkyl-C14-alkyl, C1.6-alkyl, 2-tetrahydrofurftiryl, and wherein any aryl or heteroaryl residue, alone or as part of another group, may be unsubstituted or substituted with one or more of C1.4-alkyl, CM-alkoxy, cyano, halogen, or aryloxy-CM-alkyl. 5. The compound as claimed in any one of claims 1-4, wherein R^ is selected from benzyl, 2-chlorobenzyl, 3-cyanobenzyl, 2-cyclohexylethyl, cyclopentyl, 2-cyclopentylethyl, 2,3-difluorobenzyl, 2,6-difluorobenzyl, 2-(2,6-difluorophenoxy)ethyl, 2,3-dihydrobenzo[l,4]dioxin-6-ylmethyl, ethyl, 5-fluoro-2-methoxybenzyl, furan-2-ylmethyl, methyl, a-methylbenzyl, 3-methylbenzyl, 2-(naphthalene-2-yloxy)ethyl, 2-phenoxyethyl, 2-phenoxymethylbenzyl, n-propyl, 3-(pyridin-3-yl)-n-propyl, 2-(8-quinolinyloxy)ethyI, tetrahydrofuran-2-ylmethyl, or 3-thienylmethyl. 6. The compound as claimed in any one of claims 1-5, wherein R', R^, and R^ are selected from hydrogen. 7. The compound as claimed in any one of claims 1-6, wherein the carbon atom, to which R2 is attached, has the (51)-configuration when R2 is methyl and R1 and R3 both are hydrogen. 8. The compound as claimed in any one of claims 1-6, wherein the carbon atom, to which R3 is attached, has the (R)j-configuration when R3 is methyl and R1 and R2 both are hydrogen 9. The compound as claimed in any one of claims 1-6, wherein the compound is selected from • l-[6-(2-Phenoxy-ethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate; • l-[6-(2,3-Dihydro-benzo[l,4]dioxin-6-ylmethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate; • 1 -[6-(Thiophen-3-ylmethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate; • 3 -(6-Piperazin-1 -y 1-3 -trifluoromethyl-pyridin-2-yloxymethyl)-benzonitrile, acetate; • l-[6-(3-Methyl-benzylsulfanyl)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate; • l-[6-(2-Chloro-benzylsulfanyl)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate; • 1 -[6-(2,3-Difluoro-benzyloxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate; • l-(6-Ethylsulfanyl-5-trifluoromethyl-pyridin-2-yl)-piperazine, acetate; • 1 -(6-Propoxy-5-trifluoromethyl-pyridin-2-yl)-piperazine, acetate; • 1 -(6-Cyclopentyloxy-5-trifluoromethyl-pyridin-2-yl)-piperazine, acetate; • l-[6-(l-Phenyl-ethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate; • 8-[2-(6-Piperazin-1 -yl-3-trifluoromethyl-pyridin-2-yloxy)-ethoxy]-quinoline, acetate; • l-[6-(2,6-Difluoro-benzyloxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate; • l-[6-(3-{Pyridin-3-yl}propoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate; • 1 -(6-Benzyloxy-5-trifluoromethyl-pyridin-2-yl)-piperazine, acetate; • l-[6-(Furan-2-ylmethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate; • l-{6-[2-(2.6-Difluoro-phenoxy)-ethoxy]-5-trilluoromethyl-pyridin-2-yl}-piperazine, acetate; • l-[6-(2-Chloro-benzylsulfanyl)-5-tritluoromethyl-pyridin-2-yl]-2-(/?)-methyl-piperazine, acetate; • 1 -(6-Ethylsulfanyl-5-trifluoromethyl-pyridin-2-yl)-3-(S)-methy 1-piperazine, acetate; • l-(6-Ethylsulfanyl-5-trifluoromethyl-pyridin-2-yl)-3-(R?)-methyl-piperazine, acetate; • l-(6-Ethylsulfany!-5-trifluoromethyl-pyridin-2-yl)-2-(R)-methyl-piperazine, acetate; • l-(6-Benzyloxy-5-tritluoromethyl-pyridin-2-yl)-3-(.S')-methyl-piperazine. acetate; • l-(6-Benzyloxy-5-tritluoromethyl-pyridin-2-yl)-3-(R)-methyl-piperazine, acetate; • 1 -(6-Benzyloxy-5-trifluoromethyl-pyridin-2-yl)-2-(R)-methyl-piperazine, acetate; • 1 -(6-Benzyloxy-5-trifluoroniethyl-pyridin-2-yl)-2-(iS)-methy 1-piperazlne. acetate; • 1 -(6-Methoxy-5-trifluoromethyl-pyridin-2-yl)-piperazine, acetate; • l-[6-(5-Fluoro-2-methoxy-benzyloxy)-5-trifluoromethyI-pyridin-2-yl]-piperazine, acetate; • l-{6-[2-(Naphthalen-2-yloxy)-ethoxy]-5-trifluoromethyl-pyridin-2-yl}-piperazine, acetate; • l-[6-(2-Chloro-benzylsulfanyl)-5-trinuoroniethyl-pyridin-2-yl]-3-('S)-methyl-piperazine, acetate; • l-[6-(2-Chloro-benzylsulfanyl)-5-trifluoroniethyl-pyridin-2-yl]-2-(S)methyl-piperazine, acetate; • l-[6-(2-Phenoxymethyl-benzyIoxy)-5-tritluoromethyl-pyridin-2-ylj-piperazine, acetate; • l-[6-Tetrahydro-furan-2-ylmethoxy)-5-tritluoromethyl-pyridin-2-yl]-piperazine, acetate; • l-[6-(2-Cyclopentyl-ethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate; or • l-[6-(2-Cyclohexyl-ethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate. 10. A pharmaceutical composition comprising a compound as claimed in any one of claims 1 to 9 as an active ingredient, and a pharmaceutically acceptable carrier. 11. The method of making a compound as claimed in any one of claims 1-9. by reacting a compound of the following formula (11): wherein Hal is halogen; with an appropriate piperazine derivative of formula (III): wherein R1 is H or C1-4 alkyl, 2-hydroxyethyl, 2-cyanoethyl, tetrahydropyran-2-yl, or a nitrogen protecting group; and R and R each, independently, represent H or CH3; in a solvent such as DMSO, acetonitrile, dioxane. THF, n-butanol, DMF, or in a mixture of such solvents, optionally in the presence of a base such as K2CO3, NaiCO^, CsoCOj, NaOH, triethylamine or pyridine, at 0-200 °C for 1-24 hours; to produce a compound of formula (IV) wherein R', R and R3 have the same meaning as in formula (III); and Hal is halogen. where the compound of formula (IV) is reacted with an appropriate alcohol, amine or thiol, as defined by 0-R5 NH-R5 or S-R5 or its corresponding anions; in a solvent such as DMSO, dioxane, THF,tert-butanol or DMF, at 0-200 °C for 1-24 hours.

Full Text

NOVEL COMPOUNDS AND THEIR USE
RELATED APPLICATIONS This application claims priority to Swedish application number 0201544-4, filed on May 17, 2002, and U.S. provisional application 60/410,038, filed on September 12, 2002, the contents of which are incorporated herein by reference.
TECHNICAL FIELD 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 ART Many disorders and conditions of the central nervous system are influenced by the adrenergic, the dopaminergic, and the serotonergic neurotransmitter systems. For example, serotonin (5-HT; 5-hydroxytryptamine) has been implicated in a number of disorders 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, see for example Obes. Res. 1995.3, Suppl. 4,449S-462S and Drugs Future 2001. 26,383-393. The 5-HT2c receptor subtype is transcribed and expressed in hypothalamic structures assoC1ated with appetite regulation. It has been demonstrated that the 5-HT2c receptor agonist m-chlorophenylpiperazine (mCPP), which has some preference for the 5-HT2c receptor, reduces food intake in mice that express the nonmal 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,]-//]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 a novel 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, 45^-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 an effect on the 5-HT2c receptor may therefore have
a therapeutic potential in the treatment of disorders like those mentioned above.
INFORMATION DISCLOSURE.
US-A-3,253,989 discloses the use of mCPP as an anorectic agent.
EP-A1-863 136 discloses azetidine and pyrrolidine derivatives which are selective 5-HT2c receptor agonists having antidepressant activity and which can be ised for treating or preventing serotonin-related diseases, including eating disorders ind anxiety.
EP-A-657 426 discloses tricyclic pyrrole derivatives having activity on the -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
'-ceptor and which may be used for treating eating disorders.
EP-A-572 863 discloses pyrazinoindoles having activity on the 5-HT2c ceptor and which may be used for treating eating disorders.
J. Med. Chem. 1978, 21, 536-542 and US-A-4,08l,542 disclose a series of prperazinylpyrazines having central serotonin-mimetic activity.
US 4,078,063 discloses a series of piperazinylpyridines having anorexic activity.

J. Med. Chem. 19S1, 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(trifludromethyI)-2-pyridinyljpiperazines as central nervous system agents.
WO 98/33504 discloses a new medical use of l-[6-chloro-5-(trifluoromethyl)-2-pyridinyl]piperazine, in particular to a new method of treating urinary incontinence.
WO 02/30902 discloses crystal forms of l-[6-chloro-5-(trifluoroipethyl)-2-pyridinyljpiperazine hydrochloride.
EP 1213017 discloses the use of a 5-HT2c receptor agonist, e.g., l-[6-chloro-5-(trifluoromethyl)-2-pyridinyl]piperazine, for the treatment of hot flushes.
J. Med Chem. 1987. 30, 1210-1214 disclosesN,N-disubstituted 6-alkoxy-2-pyridinamines as anticonvxilsant agents including l-(6-methoxy-2-pyridinyl)piperazine, 1 -(6-ethoxy-2-pyridinyl)piperazine, 1 -(6-isopropoxy-2-pyridinyl)piperazine, l-(6-isobutoxy-2-pyridinyl)piperazine, 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 1 -(6-butylthio-2-pyridinyl)piperazine, l-(6-cyclohexylmethyl-2-pyridinyI)piperazine and l-[6-(2-phenylethyl)-2-pyridinyl]piperazine.
JP 07300474 discloses drugs for treatment of diseases related to serotoninergic nerve including l-(6-phenoxy-2-pyridiny!)piperazine 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)pyridine and 6-chloro-2-(4-methylpiperazinyl)pyridine.
WO 00/12475 discloses indoline derivatives as 5-HT2b and/or 5-HT2c receptor ligands, espeC1ally for the treatment of obesity.

wu uu/12510 discloses pyrroloindoles, pyridoindoles and azepinoindoles as 5-HT2c receptor agonists, particularly 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-l//-pyrazino[l,2-fl]quinoxalin-5(6//)ones as 5HT2c agonists, which may be used for the treatment of obesity.
WO 00/44737 discloses aminoalkylbenzofurans 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; WO 02/40456 and WO 02/40457; heterocycle fused y-carbolines of the type described in WO 00/77001, WO 00/77002 and WO 00/77010; benzofurylpiperazines of the type described in WO 01/09111 and WO 01/09123; benzofiirans 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 and WO 02/44152; pyrazino(aza)indoles of the type described in WO 00/44753; diaza-cyclopenta[a]indenes of the type described in EP 1132389; piperazine derivatives of the type described in WO 02/10169; WO 02/72584 and WO 02/48124; quinoxalinones of the type described in US 6372745, and tricyclic pyrroles or pyrazoles of the type described in WO 98/56768.
WO 95/01976 discloses indoline derivatives active as 5-HT2c antagonists and
of potential use in the treatment of CNS disorders.
WO 99/58490 discloses aryl-hydronaphthalen-alkanamines which may effectuate partial or complete blockage of serotonergic 5-HT2c receptors in an
organism.
WO 03/00666 discloses [l,2']bipyrazinyl 5-HT2 receptor ligands, in particular 5-HT2c receptor ligands, for the treatment of sexual dysfunction.

wo 03/00663 discloses piperazinylpyrimidines as 5-HT2 receptor ligands, in particular 5-HT2(; receptor ligands, for the treatment of sexual disorders.
WO 02/51844 discloses cycloalkyl fused indole derivatives and their use as 5-HT2b and 5-HT2c receptor ligands.
WO 02/42304 discloses cyclopenta[b][l,4]diazepino[6,7-hi]indoles as selective S-HTic receptor agonists.
WO 02/36596 discloses diazepinocarbazoles and related compounds as serotonin 5-HT2c agonists.
SUMMARY OF THE INVENTION According to the invention novel compounds of the formula (I) ar? provided:

wherein
R is selected from H, CM alkyl, 2-hydroxyethyl, 2-cyanoethyl, tetrahydropyran-2-yl, and a nitrogen protecting group;
R^ and R' each, independently, represent H or CH3;
R" is selected from halogen, O-R^, NH-R^ or S-R^, wherein
R^ is selected from aryl, aryl-C1.6-aIkyl, aryloxy-C2-6-aikyl, heteroaryl, heteroaryl-C1^-alkyl, heteroaryloxy-Cz^-alkyl, C3-6-cyC1oalkyl, Cs-e-cyclcalkyl-CM-alkyl, C1^-alkyl, 2-tetrahydrofuryl, 3-tetrahydrofuryl, 2-tetrahydroflirftiryl, 3-tetrahydrofurfiiryl, piperidine-4-yl, tetrahydropyran-4-yl, C3.6-alkynyl, Ca^-alkenyl, or fluoro-C2-4-alkyl;
and wherein any aryl or heteroaryl residue, alone or as part of another group, may be unsubstituted or substituted with one or more of C1^-alkyl, CM-alkoxy, C\^-alkylthio, C2-i-acyl, C1^-alkylsulphonyl, cyano, nitro, hydroxy, C2.6-alkenyl, C2.6-alkynyl, fluoromethyl, trifluoromethyl, trifluoromethoxy, halogen, -N(R )(R ), aryl, aryloxy, arylthio, aryl-C1.4-alkyl, aryl-C2.4-alkenyl, aryl-C2^-alkynyl, heteroaryl.

heteroaryloxy, heteroarylthio, heteroaryl-Cm-alkyl, aryl-CM-alkoxy, aryloxy-C1.4-alkyl, or dimethylamino-C2^-alkoxy„ wherein '
■ R6 and R6 are, independently of each other^ hydrogen, methyl or ethyl; or form a pyrrolidine, piperazine, morpholine, thiomqrpholine or a piperidine ring together with, the nitrogen atom to which they :are bound;
and wherein any aryl or heteroaryl residue as substituents on aryl or heteroaryl, alone or as part of another group, in turn may be substituted in one or more positions, preferably one, independently of each other by d -4-alkyl, C1 ^-alkoxy, halogen, trifluoromethyl, cyano, hydroxy or dimethylamino;
and phamnaceutically acceptable salts, hydrates, solvates, geometrical isomers, tautomers, optical isomers, yV-oxides and prodrug forms thereof, with the proviso that, when R" is halogen at least one of R , R , or R is not hydrogen.
When R" is halogen, it is preferred that either:
(i) R is selected from C1-4 alkyl, 2-hydroxyethyI, 2-cyanoethyl,
tetrahydropyran-2-yl, and a nitrogen protecting group; or
(ii) R is selected from H, C1-4 alkyl, 2-hydroxyethyl, 2-cyanoethyI,
tetrahydropyran-2-yl, and a nitrogen protecting group; and at least oneofR2andR3sCHa;
In case the compounds of formula (I) 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, 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 prophylaxis or treatment of a serotonin-related disorder or condition> in a subject in need of such prophylaxis or treatment, the method comprising administering to the subject an effective amount of a compound of formula (I). It is preferred that the serotonin-related disorder or condition is a 5-HT2c receptor-related disorder or condition, espeC1ally memory disorders; Alzheimer's disease; schizophrenia; mood disorders; anxiety disorders; pain; substance abuse;'sexual dysfunction; epilepsy; glaucoma; urinary incontinence; menopausal and post-menopausal hot flushes; type II diabetes; eating disorders; binge eating disorders; anorexia nervosa; bulimia; or weight gain assoC1ated with antipsychotic drug administration; and most preferably obesity. The subject is preferably a human or an animal.
The method includes administering an effective amount of a compound of formula (I), or a composition having a compound of formula (I) in it.
Another aspect of the invention relates to the use of the compounds of formula (I) in the manufacture of a medicament for the prophylaxis or treatment of a serotonin-related disorder or condition. It is preferred that the serotonin-related disorder or condition is a 5-HT2c receptor-related disorder or condition, espeC1ally
memory disorders; Alzheimer's disease; schizophrenia; mood disorders; anxiety disorders; pain; substance abuse; sexual dysfunction; epilepsy; glaucoma; urinary incontinence; menopausal and post-menopausal hot flushes; type II diabetes; eating disorders; binge eating disorders; anorexia nervosa; bulimia; or weight gain assoC1ated with antipsychotic drug administration; and most preferably obesity.
Finally a method for modulating 5HT2c receptor function is an aspect of the
invention.
The methods delineated herein can also include the step of identifying that a subject is in need of treatment of serotonin-related disorders or conditions, particularly 5-HT2c receptor-related, in the subject.
DETAILED DESCRIPTION OF THE INVENTION According to the present invention, a class of novel compounds that bind to the 5-HT2c receptor has been developed. The compounds may act as receptor agonists or antagonists at the 5-HT2c receptor and may therefore be used for the

treatment of serotonin-related disorders or conditions, particularly 5-HT2c receptor-related.
First, the various terms used, separately and in combinations, in the above definition of the compounds having the general formula (I) will be explained.
The expression "C1-6 alkyl" refers to straight-chained and branched alkyl groups containing from 1 to 6 carbon atoms. Particular C1-6 alkyl groups are methyl, ethyl, n-propyl, isopropyl, tert-butyl, «-pentyl, isopentyl, «-hexyl, and isohexyl. Derived expressions such as "C1^ alkoxy" and "CM alkylthio" are to be constructed ■ accordingly.
The expression "C:^ alkenyl" as used herein refers to straight-chained and branched alkenyl groups containing from 2 to 6 carbon atoms. Typical ej^amples include vinyl, allyl, 3,3-dimethylallyl, 1-butenyl, and 2-butenyl groups.
The expression "€2^ alkynyl" as used herein refers to straight-chained and branched alkynyl groups containing from 2 to 6 carbon atoms. Typical examples include ethynyl and propargyl groups.
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, l-naphthyl, 2-naphthyl, 1,2,3,4-tetrahydronaphthyl, and indanyl. The aryl group 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 heteroatoms such as nitrogen, sulphur, oxygen and selenium and the remainder are carbon atoms. Examples of such heteroaryl rings are pyrrole, imidazole, thiophene, furan, thiazole, isothiazole, thiadiazole, oxazole, isoxazole, oxadiazole, pyridine, pyrazine, pyrimidine, pyridazine, pyrazole, triazole, tetrazole, chroman, isochrcman, coumarin, quinoline, quinoxaline, isoquinoline, phthalazine, C1nnoline, 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-1,4-benzodioxine, 1,3-benzodioxole, 1,2,3,4-tetrahydroquinoline, 3,4-dihydro-2//-1,4-benzoxazine, 1,5-naphthyridine, 1,8-naphthyridine, 3,4-dihydro-2//-pyrido[3,2-ii]-l,4-oxa2ine, and 2,3-dihydro-l,4-benzoxathiine.'If abicyclic aryl orheteroaryl ring is substituted, it may be substituted in any ring.
Exemplary aryl-C1.6-alkyl, in which the alkyl portion of the group may be straight or branched, include benzyl, 2-naphthylmethyl, 2-phenylethyl, 3-phenyl-l-propyl, 1-phenylethyl, l-phenyl-2-propyl, 2-phenyl-l-propyl and the like.
Exemplary aryloxy-C2-6-alkyl, in which the alkyl portion of the group may be straight or branched, include 2-phenoxyethyI, 2-(l-naphthyloxy)ethyl, 3-(2-naphthyloxy)-]-propyl, 3-phenoxy-l-propyl, 4-phenoxy-I-butyl, 5-phenoxy-l-pentyl, 1 -phenoxy-2-propyl and the like.
Exemplary C3.6-cycloalkyl-C1.4-alkyl, in which the alkyl portion of the group may be straight or branched, include cyclopropylmethyl, cyclopentylmethyl, 2-cyclohexylethyl, 1-cyclohexylethyl, 1-eyelopropylethyl, 1-cyclobutylethyl and the like.
Exemplary heteroaryloxy-C2.6-alkyl include 2-(8-quinolinyloxy)ethyl, 2-(3-pyridinyloxy)ethyl, 3-(8-quinolinyloxy)propyl and the like.
Halogen includes fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine.
Where it is stated above that aryl and heteroaryl residues may be substituted (in one or more positions), this applies to aryl and heteroaryl per se as well as to any combined groups containing aryl or heteroaryl residues, such as heteroaryIoxy-C2.6-
alkyl, aryl-C1.6-alkyl etc.
The term 'W-oxides" means that one or more nitrogen atoms, when present in a compound, are in TV-oxide form (N-^0).
The term "prodrug forms" means a pharmacologically acceptable derivative, such as a carbamate or an amide, which derivative is biotransformed in the body to form the active drug. Reference is made to Goodman and Oilman's, The Pharmacological basis of Therapeutics, 8'*^ ed., McGraw-Hill, hit. Ed. 1992, "Biotransformation of Drugs", p. 13-15.

"Pharmaceutically acceptable" means being useful in preparing a pharmaceutical composition that is generally safe, non-toxic and neither biologically nor otherwise undesirable 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 aC1d addition salts formed with organic and inorganic aC1ds, such as hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric aC1d, phosphoric aC1d, acetic aC1d, glycolic aC1d, maleic aC1d, malonic aC1d, malic aC1d, oxalic aC1d, toluenesulphonic aC1d, methanesulphonic aC1d, fumaric aC1d, sucC1nic aC1d, tartaric aC1d, C1tric aC1d, benzoic aC1d, ascorbic aC1d and the like.
The expression "comprising" means "including but not limited to." Thus, other non-mentioned substances, additives or carriers may be present.
"A nitrogen protecting group" (z e a value for R') refers to a group covalently bonded to a nitrogen atom, or any group used to derivatize nitrogen atom (e.g., the nitrogen atom in an amino group). The group may be introduced or cleaved off by conventional methods such as those described in Protective Groups in Organic Synthesis, John Wiley & Sons, 1991. Examples of the nitrogen protecting groups include trityl or /-butoxycarbonyl and those delineated in Protective Groups in Organic Synthesis, John Wiley & Sons, 1991 and subsequent editions thereof.
It is preferred that R' is hydrogen.
It is also preferred that R* is selected from chlorine, 0-R^, and S-R^.
It is also preferred that R6 is selected from aryl-C1.6-alkyl, aryloxy-C2-6-alkyl. heteroaryl-C1.6-alkyl, heteroaryloxy-C2-6-alkyl, C3.6-cycloalkyl, C3- It is more preferred that R6 is selected from benzyl, 2-chlorobenzyl, 3-cyanobenzyl, 2-cyclohexylethyl, cyclopentyl, 2-cyclopentylethyl, 2,3-difluorobenzyl, 2,6-difluorobenzyl, 2-(2,6-difluorophenoxy)ethyl, 2,3-dihydrobenzo[I,4]dioxin-6-/Imethyl, ethyl, 5-fluoro-2-methoxybenzyl, furan-2-yhnethyl, methyl, a-■nethylbenzyl, 3-methylbenzyl, 2-(naphthalene-2-yIoxy)ethyl, 2-phenoxyethyl, 2-

phenoxymethylbenzyl, n-propyl, 3-(pyridin-3-yl)-n-propyl, 2-(8-quinolinyloxy)etnyi, tetrahydrofliran-2-ylmethyl, or 3-thienylmethyl.
It is also preferred that the carbon atom, to which R6 is attached, has the (S)-configuration when R6 is methyl and R' and R6 both are hydrogen.
It is also preferred that the carbon atom, to which R' is attached, has the (R)-configuration when R"* is methyl and R' and R6 both are hydrogen.
Preferred compounds of the general formula (I) above are the following compounds (corresponding to Examples 6-43 below):
• l-(6-ChIoro-5-trifluoromethyl-pyridin-2-yl)-3-(5)-methyl-piperazine
• l-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-3-(^)-methylpipera2ine
• l-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-2-(y?)-methyl-piperazine
• l-(6-Chloro-5-trifluororaethyl-pyridin-2-yl)-2-(5)-methyl-piperazine, hydrochloride
• 1 -[6-(2-Phenoxy-ethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate
• l-[6-(2,3-Dihydro-beruo[l,4]dioxin-6-ylmethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate
• l-[6-(Thiophen-3-ylmethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate
• 3-(6-Piperazin-l-yl-3-trifluoromethyl-pyridin-2-yloxymethyl)-benzonitrile, acetate
• l-[6-(3-Methyl-benzylsulfanyl)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate
• l-[6-(2-Chloro-benzylsulfanyl)-5-trifluoromethyI-pyridin-2-yl]-piperazine, acetate
• l-[6-(2,3-Difluoro-benzyIoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate
• 1 -(6-Ethylsulfanyl-5-trifluoromethyl-pyridin-2-yl)-pipera2ine, acetate
• l-(6-Propoxy-5-trifluoromethyl-pyridin-2-yl)-piperazine, acetate
• 1 -(6-Cyclopentyloxy-5-trifluoromethyl-pyridin-2-yl)-piperazine, acetate
• l-[6-(l-Phenyl-ethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate
• 8-[2-(6-Piperazin-l-yl-3-trifluoromethyl-pyridin-2-yloxy)-ethoxy]-quinoline, acetate

• i-[6-(2,6-Difluoro-benzyloxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate
• l-[6-(3-{Pyridin-3-yl}propoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate
• 1 -(6-Benzyloxy-5-trifluoromethyl-pyridin-2-yl)-pipera2ine, acetate
• 1 -[6-(Furan-2-ylmethoxy)-5-trifluoromethyl-pyndin-2-yl]-piperazine, acetate
• l-{6-[2-(2,6-Difluoro-phenoxy)-ethoxy]-5-trifluoromethyl-pyridin-2-yl}-piperazine, acetate
• l-[6-(2-Chloro-ben2ylsulfanyl)-5-trifluoromethyl-pyridin-2-yl]-2-(^)-methyl-piperazine, acetate
• l-(6-Ethylsulfanyl-5-trifluoromethyl-pyridin-2-yl)-3-(5^-methyl-piperazine, acetate
• l-(6-Ethylsulfanyl-5-trifluoromethyl-pyridin-2-yl)-3-(i?)-methyl-piperazine, acetate
• l-(6-Ethylsulfanyl-5-trifluoromethyl-pyridin-2-yl)-2-(i?)-methyl-piperazine, acetate
• l-(6-BenzyIoxy-5-trifluoromethyl-pyridin-2-yl)-3-(5)-methyl-piperazine, acetate
• l-(6-Benzyloxy-5-trifluoromethyl-pyridin-2-yl)-3-(i?)-methyl-pipera2ine, acetate
• l-(6-Benzyloxy-5-trifluoromethyl-pyridin-2-yl)-2-(/?)-methyl-piperazine, acetate
• l-(6-Benzyloxy-5-trifluoromethyI-pyridin-2-yl)-2-(5)-methyl-pipera2ine, acetate
• l-(6-Methoxy-5-trifluoromethyI-pyridin-2-yl)-piperazine, acetate
• l-[6-(5-Fluoro-2-methoxy-benzyloxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate
• l-{6-[2-(Naphthalen-2-yloxy)-ethoxy]-5-trifluoromethyl-pyridin-2-yl}-piperazine, acetate
• l-[6-(2-Chloro-ben2ylsulfanyl)-5-trifluoromethyl-pyridin-2-yl]-3-C5>methyl-piperazine, acetate

• l-[6-(2-Chloro-ben2ylsulfanyl)-5-trifluoromethyl-pyridin-2-yl]-2-f'S'>methyl-piperazine, acetate , ,
• l-[6-(2-Phenoxymethyl-benzyloxy)-5-trifluoromethyl-pyridin-2-yI]-piperazine, acetate
• l-[6-Tetrahydro-furan-2-ylmethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate
• ■l-[6-(2-Cyclopentyl-ethoxy)-5-tFifluoromethyl-pyridin-2-yl]-piperazine, acetate
• l-[6-(2-Cyclohexyl-ethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate
and their pharmacologically acceptable salts and solvates.
The compounds corresponding to Examples 6, 8, 10-38, and 41-43 are even more preferred.
As mentioned above, the compounds of the present invention are usefiil for the treatment, including prophylactic treatment, of serotonin-related, espeC1ally 5-HT2c receptor-related, disorders and conditions, in a human being or in an animal,
including e.g. pets, such as memory disorders; 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 assoC1ated with substance abuse); pain; substance abuse; sexual dysfunction; epilepsy; glaucoma; urinary incontinence; menopausal and post¬menopausal hot flushes; type II diabetes; eating disorders; binge eating disorders; anorexia nervosa; bulimia; or weight gain assoC1ated with antipsychotic drug administration; and particularly obesity.
The compounds of the present invention in radiolabelled form, may be used as a diagnostic agent.

rrocesses lor preparaiion
This invention also relates to a method for preparing, a pharmaceutical composition, the method comprising combining a compound of formula (I) with a pharmaceutically acceptable carrier.
This invention also relates to methods of making compounds of any formulae delineated 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. The compounds of general formula (I) above maybe prepared by, or in analogy with, conventional methods, and espeC1ally according to or in analogy with the following method.
Compounds of formula (I) above in which R" is halogen, 0-R^, NH-R^ or S- R6 are prepared by reacting a compound of the structural formula (II):

wherein Hal is halogen; with 1 to 10 molar equivalents of an appropriate piperazine derivative of formula (III):
wherein R , R , and R are as defined above; in a solvent such as dimethylsulfoxide (DMSO), acetonitrile, dioxane, tetrahydrofuran (THF), «-butanol, A^.A'-dimethylformamide (DMF), or in a mixture of solvents such as DMF/dioxane, optionally in the presence of a base, such as K2CO3, Na2C03, CS2CO3, NaOH, triethylamine, pyridine or the like, at 0-200 °C for 1-24 hours to produce a compound of formula (FV):

wherein R' , R6, and R6 are as defined above and Hal is halogen.
The compound of formula (IV) is reacted with an appropriate alcohol, amine, or thiol as defined by 0-R', NH-R^ or S-R^ above, or its corresponding anions to produce a compound of the formula (I) above. The appropriate alcohol, amine, or thiol may be converted completely or partially to its corresponding anion by treatment with bases, such as triethylamine, l,8-diazabicyclo[5.4.0]undec-7-ene, K2CO3, NaOH, NaH, KO-/-Bu, lithium diisopropylamide or the like. The reaction is carried out in a solvent, such as DMSO, dioxane, THF, rer/-butanol or DMF, at 0-200 °C for 1-24 hours.
An obtained compound of formula (I) above may be converted to another compound of formula (I) by methods well known in the art.
The chemicals used in the above-described synthetic routes may include, for example, solvents, reagents, catalysts, protecting group and deprotecting group reagents. The methods described above may also additionally include steps, either before or after the steps described speC1fically herein, to add or remove suitable protecting groups in order to ultimately allow synthesis of the compounds of formula (I). When R' is a nitrogen protecting group as defined above, the subsequent A'-deprotection is carried out by conventional methods. In addition, various synthetic steps may be performed in an alternate sequence or order to give the desired compounds. Synthetic chemistry transformations and protecting group methodologies (protection and deprotection) useful in synthesizing applicable compounds are known in the art and include, for example, those described in R. Larock, Comprehensive Organic Transformations, VCH Publishers (1989); T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 2" Ed., John Wiley and Sons (1991); L. Fieser and M. Fieser, Fieser and Fieser's Reagents for Organic Synthesis, John Wiley and Sons (1994); and L. Paquette, ed., Encyclopedia

of Reagents for Organic Synthesis, John Wiley and Sons (1995); and subsequent
editions thereof. • , .
. .The process that is described above may be carried out to give a compound of the invention in the form of a free base or as an aC1d addition salt. A pharmaceutically acceptable aC1d addition salt may be obtained by dissolving the free base in a suitable organic solvent and treating the solution with an aC1d, in accordance with conventional procedures for preparing aC1d addition salts from base compounds. Examples of addition salt forming aC1ds are maleic aC1d, fumaric aC1d, sucC1nic aC1d, methanesulfonic aC1d, acetic aC1d, malic aC1d, oxalic aC1d, benzoic aC1d, hydrochloric aC1d, sulphuric aC1d, phosphoric aC1d, 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) aC1ds or by chromatographic separation on chiral columns.
The necessary starting materials for preparing the compounds of formula (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 form of free bases or salts with physiologically acceptable aC1ds, 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 assoC1ation with compatible pharmaceutically acceptable carrier materials, or diluents, as are well known in the art. The carriers 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, calC1um 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, flavoring 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, dispersible 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, espeC1ally 5-HT2c receptor-related disorders and
conditions in a human being or an animal, such as memory disorders including Alzheimer's disease; schizophrenia; mood disorders; anxiety disorders; pain; substance abuse; sexual dysfunction; epilepsy; glaucoma; urinary incontinence; menopausal and post-menopausal hot flushes; type II diabetes; eating disorders, such as binge eating disorders, anorexia nervosa and bulimia; weight gain assoC1ated with antipsychotic drug administration; and particularly obesity.
Also within the scope of this invention is a method for modulating (e.g., inhibiting or stimulating) 5-HT2c-receptor activity. The method includes administering to a subject in need thereof an effective amount of a compound of the formula (I).
The methods delineated herein can also include the step of identifying that a subject is in need of treatment of serotonin-related, espeC1ally 5-HT2c receptor-related, disorders and conditions in the subject (e.g., a mammal, a human being, a horse, a dog, or a cat).
"An effective amount" refers to an amount of a compound, which confers a therapeutic effect on the treated subject. The therapeutic effect may be objective (i.e., measurable by some test or marker) or subjective (i.e., subject gives an indication of or feels an effect). For clinical use, the compounds of the invention are formulated into pharmaceutical formulations for oral, rectal, parenteral or other mode of administration. Usually the amount of active compounds is between 0.1-95% by weight of the preparation, preferably between 0.2-20% by weight in preparations for parenteral use and preferably between 1 and 50% by weight in preparations for oral administration.

' The dose level and frequency of dosage of the speC1fic compound will vary depending oh a variety of factors including the potency of the speC1fic 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, drug combination, the severity of the condition to be treated, and the patient undergoing therapy. The daily dosage may, for example, range from 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 C1ted 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
Experimental Methods
The 'H-and '^C-NMR-spectra were obtained with a Bruker DPX 400. The DPFGSE-NOE experiments were obtained with a Varian INOVA 400. The mixing time was 0.8 seconds. The preparative LC was performed on a preparative LC-MS Gilson-Fimiigan with a 50x20mm S 5 jim, 120A column. The flow was 30 mL/min and different gradients of 0.1% acetic aC1d in water and acetonitrile were used. The accurate masses were determined with a Micromass LCT with electrospray ionization. The elemental analyses were performed with a Vario EL instrument. A Koefler bench was used to measure the melting points, which are not corrected.
Examples 1-5. Preparation of intermediates.
General procedure for Examples 1-2.
To a suspension of LiAlILt (1.2 g, 32 mmol) in dry THF (5 mL) was added the aldehyde or carboxylic aC1d (10 mmol) and the mixtures were stirred at room temperature for two hours. Mixtures with aldehydes as starting materials were put

aside and the aC1ds were heated at 60 °C overnight. To each mixture was added in consecutive order water (1.2 mL), 2 M aqueous NaOH (1.2 mL), and water (3.6 mL). The preC1pitate was fihered off and the solvent was removed under reduced pressure to yield the target products as oils.
EXAMPLE 1 . (5-Fluoro-2-methoxy-phenyl)-methano|.
The title compound was prepared starting from 5-fluoro-2-methoxybenzaldehyde and was obtained as a light red oil (94% yield). Fragmenting MS analysis supports the stated structure.. Purity 97% (GC). 'H NMR (CDC13) 5 3.28 (s, 3 H), 4.64 (s, 2 H), 6.78 (m, 1 H), 6.93 (m, 1 H), 7.02 (m, 1 H). '^C NMR (CDC13) 6 55.73, 61.34, 110.83 (d,J= 8.5 Hz), 114.22 (d, J= 22.6 Hz), 115.26 (d, J= 23.3 Hz), 138.68 (d, J= 6.4 Hz), 153.18 (d, /= 2.1 Hz), 156.95 (d,J= 238.8 Hz).
EXAMPLE 2 (2-Phenoxymethyl-phenyl)-methanol.
The title compound was prepared starting from 2-(phenoxymethyl)benzoic aC1d and was obtained as a light yellow oil (96% yield). Fragmenting MS analysis supports the stated structure. Purity 94% (GC). Previously reported in J. Chem. Soc, 1954,2819-2826.
EXAMPLE 3 3-(5)-MethyH-trityl-piperazine.
To a solution of 2-(S)-methylpiperazine (3.79 g, 37.9 mmol) in CHC13 (100 mL) was trityl chloride (10.56 g, 37.9 mmol) added in one portion. The exothermic reaction was stirred at ambient temperature for two hours, the organic phase was washed three times with water, dried (MgS04) and the solvent was evaporated at reduced pressure to give 12.5 g (96%) of a colorless foam that solidified to a crisp overnight.'H NMR(CDC13) 5 1.06 (d, J =5.5 Hz, 3 H), 1.35 (m, 1 H), 1.61 (m, 1 H), 3.01 (m, 3 H), 3.14 (m, 1 H), 3.31 (m, 1 H), 7.08 (m, 3 H), 7.16 (m, 6 H), 7.35 (m, 6 H).'^C NMR (CDC13) 5 18.17,44.46,46.68,51.59,54.03, 126.26, 127.13, 127.68, 129.07 br. The racemate of the title compound is reported in Bioorg. Med. Chem. Lett. 2000,10, 2643-2646.

EXAMPLE 4 3-(R)-Methyl-l-trityl-piperazine.
The title compound was prepared as described in WO 00/76984 starting from i 2-(R)-methyIpiperazine (5.51 g, 55.1 mmol). This gave 18.8 g (99%) of a white crisp. HRMS miz calcd for C24H26N2 (Mf 342.2096, found 342.2110.
EXAMPLE 5 l-(6-ChIoro-5-trifluoromethyI-pyndin-2-yl)-piperazine.
Step 1: 4-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-piperazine-l-carhoxylic aC1d tert-butyl ester.
To a suspension of/er/-butyl-l-piperazine carboxylate (27.0 g, 145 mmol) and K2CO3 (40.0 g, 290 mmol) in DMSO (200 mL) were 2,6-dichloro-3-trifluoromethylpyridine (29.1 g, 135 mmol) and toluene (50 mL) added. The thick slurry was stirred at 80 °C for two hours, followed by addition of toluene (0.5 L) and water (1 L). The phases were separated and the organic phase was washed twice with water. The solvent from the dried (MgS04) organic phase was evaporated at reduced pressure. The solid residue was recrystallized from EtOAc/heptane to give white crystals (37 g). The filtrate from the recrystallization was concentrated and the residue chromatographed on a column of silica with hexane/EtOAc (90:10) to give further 6.0 g of product (total yield 85%). Purity 99% (HPLC); mp 125 °C. Anal. (C15H19ClF3N3O2)C,H.N.
Step 2:1 -(6-Chloro-5-tri/luoromethyl-pyridin-2-yl)-piperazine.*
The title compound was prepared from the product of Step 1 above using the N-deprotection procedure given in Example 6, Step 2. This fiimished 29.7 g (100%) of a light yellow oil that crystallized upon standing. A NOE between the methylene protons at C-2 in the piperazine ring and the C3-hydrogen in the pyridine ring was observed. Purity 99% (HPLC); mp 56 °C. Fragmenting MS analysis supports the stated structure. HRMS m/z calcd for C1oH, ,C1F3N3 (M)" 265.0594, found 265.0597. *PreviousIy reported in EP 370560.

EXAMPLE 6 l-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-3-(5)-niethyl-piperazine.
Step 1: 4-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-2-(S)-methyl-piperazine-l-carboxylic aC1d tert-butyl ester.
To a suspension of 2-(y)-methylpiperazine (2.65 g, 26.5 mmol) and K2CO3 (4.0 g, 29 mmol) in dry DMSO (50 mL) was slowly added 2,6-dichloro-3-trifluoromethylpyridine (5.70 g, 26.4 mmol). The reaction mixture was stirred at room temperature over night, filtered, diluted with water (ca 1 L) and extracted twice with EtOAc (100 mL). The solvent from the combined dried (MgS04) organic phases was evaporated at reduced pressure to give a yellow oil (7.4 g). This material was dissolved in MeOH (100 mL), BOC anhydride (6.0 g, 27.5 mmol) was added in one portion and the reaction mixture was stirred at room temperature for two hours. Excess BOC anhydride was quenched with pyridine (3 mL) and the mixture was left at room temperature over night. The solvent was removed at reduced pressure and the resulting oil was chromatographed on a column of silica (60x110 mm) with hexane/EtOAc (95:5, 1 L, followed by 90:10, 1 L and 80:20). Evaporation at reduced pressure of the pure fractions yielded a colorless oil (8.05 g, 80%) that solidified to a white solid over night. Purity 97% (HPLC); mp 86 °C. Fragmenting MS analysis supports the stated structure. HRMS mlz calcd for C16H21C1F3N3O2 (M)"^ 2>19.\11A, found 379.1286.
Step 2: l-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-3-(S)-methyl-piperazine.
A solution of 4-(6-chloro-5-trifluoromethyl-pyridin-2-yl)-2-(5)-methyl-piperazine-1-carboxylic aC1d /err-butyl ester (7.80 g, 26.4 mmol) was dissolved in CH2C12/TFA (50:50; 30 mL) and stirred at room temperature over night. The solvent was removed at reduced pressure and the resulting oil was taken up between alkaline water (NaOH) and CHC13. The aqueous phase was extracted once with CHC13, the combined organic phases were dried (MgS04) and the solvent was evaporated at reduced pressure to yield 5.79 g (78%) of a light yellow oil. A NOE between the methylene protons at C-2 in the piperazine ring and the C3-hydrogen in the pyridine ring was observed. Purity 100%> (HPLC). Fragmenting MS analysis supports the stated structure. HRMS mlz calcd for CnHuClFjNa (M)" 279.0750, found 279.0751

EXAMPLE? , ,, l-(6-Chloro-5-itrifluoromethyl-pyridin-2-yl)-3-(i?)-methylpiperazine.
Step 1: 4-'(6-Chloro-5-triJluoromethyl-pyridin-2-yl)-2-(R)-methyl-piperazine-l-
carboxylic aC1d tert-butyl ester. ;,
The title compound was prepared starting from 2-(/?)-methylpiperazine using the procedure given in Example 6, Step 1, for the (iS)-isomer and was obtained as a white crystaUine solid. Yield 7.4 g (70%)'. Purity 99% (HPLC); mp 86 °C. Fragmenting MS analysis supports the stated structure. HRMS tniz calcd for C,6H2iClF3N302(M)^ 379.1274, found 379.1269.
Step 2: l-(6-Chloro-5-trifIuoromethyl-pyridin-2-yl)-3-(R)-methylpiperazine.
The title compound was prepared starting from the product of Step 1 above using the A^-deprotection procedure given in Example 6, Step 2, and was obtained as a light yellow oil. Yield 4.76 g (90%). Purity 99% (HPLC). Fragmenting MS analysis supports the stated structure. HRMS m/z calcd for CnHnClFaNa (M)"*" 279.0750, found 279.0742.
EXAMPLE 8 1
l-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-2-(/?)-methyl-piperazine.
Step I: l-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-2-(R)-Tnethyl'4-trityl-piperazine.
A suspension of 3-(/{)-methyl-l-trityl-piperazine (from Example 4; 7.80 g, 22.9 mmol), 2,6-dichloro-3-trifluoromethylpyridine (4.50 g, 20,8 mmol) and K2CO3 (4.0 g, 29 mmol) in DMSO (100 mL) was stirred at 80 °C over night. A mixture of EtOAc/toluene (50:50; 500 mL) was added to the filtered solution and the mixture were washed three times with water (1 L). The dried (MgS04) organic phase was concentrated under reduced pressure and the resulting brown oil was dissolved in heptane/EtOAc (90:10) and filtered through a plug (60x60 mm) of silica. Slow evaporation of about two thirds of the solvent at reduced pressure afforded light yellow crystals (6.11 g, 56%). Purity 100% (HPLC); mp 209 °C. Fragmenting MS analysis supports the stated structure. Anal. (C30H27C1F3N3) C, H, N.

Step 2: l-(6-Chloro-5-trifliioromethyl-pyridin-2-yl)-2-(R)-melhyl-piperaiine.
A suspension of l-(6-chloro-5-trifluoromethyl-pyridin-2-yl)-2-(^)-methyl-4-trityl-pipera2;ine (from Step 1 above; 5.70 g, 10.9 mmol) in EtOH (70 mL) was heated to 80 °C. Aqueous HCl (4 M;'6 mL) was added and the mixture was heated in an open vessel for one hour. To the clear solution was water added (100 mL) and the preC1pitate was filtered off. The solvent from thefiltrate was evaporated down to about 10 mL, the crystals were filtered off and the evaporation continued down to 3 mL and another portion of slightly pinkish crystals were filtered off The combined crystal fractions were taken up between alkaline water (NaOH)/CHCl3. The aqueous phase was washed twice with CHClj and the combined, dried (MgS04), organic phases were evaporated at reduced pressure to give a light yellow oil (1.75 g, 69%). A NOE between the methylene protons at C-2 in the piperazine ring and the C3-hydrogen in the pyridine ring was observed. Purity 99% (HPLC). Fragmenting MS analysis supports the stated structure. HRMS m/z calcd for C1 1H13C1F3N3 (M)"^ 279.0750, found 279.0744.
EXAMPLE 9
l-(6-Chloro-5-trifIuoromethyl-pyridin-2-yl)-2-(iy)-methyl-piperazine,
hydrochloride.
Step J:
l-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-2-(S)-methyl-4-trityl-piperazine. The title compound was prepared starting from 3-(5)-methyl-l-trityl-piperazine (obtained in Example 3) using the procedure given in Example 8 for the (i?)-isomer. Light yellow crystals; yield 5.1 g (43%). Purity 96% (HPLC); mp 210 °C. Fragmenting MS analysis supports the stated structure. Anal. (C30H27C1F3N3) C, H,N.
Step 2: l-(6-Chloro-5-trifluoromethyl-pyridin-2-yl)-2-(S)-methyl-piperazine, Hydrochloride.
The title compound was prepared starting from the product of Step 1 above using the N-detritylation procedure given in Example 8, Step 2, for the (j'?)-isomer. This produced 2.06 g (68%) of the free base of the title compound obtained as a

pinkish oil. The free base was converted into its hydrochloride salt. Purity 99% (HPLC). Fragmenting MS analysis supports the stated structure. HRMS m/z calcd for C, iH,3ClF3N3 (Mf 279.0750, found 279.0738.
Examples 10-43
General procedure
Volumes are expressed as total volumes.
To a 16 mm test tube was added;
• 0.5 mmol of the appropriate alcohol or thiol
• 0.4 mmol of the appropriate 6-chloro 5-trifluoromethyI-2-piperazinylpyridine in
DMSO (0.5 mL)
• 0.65 mmol of K-/-BuO in DMSO (1.0 mL)
The reactions were stirred at room temperature for two hours followed by addition of HO Ac (1.25 mmol, 75 |j.L). The solvent was evaporated at reduced pressure over night (Speed Vac). The remaining solids were dissolved in water/acetonitrile/HOAc, filtered, and the products were purified with preparative HPLC.
Mass detection was obtained by a Micro Mass LCP with electrospray positive ionization mode. The analytical HPLC-chromatograms were performed on a Hewlett Packard 1100 with a 50x4.6mm Grom-SEL 100 ODS 0 AB, 3 ^m column and a 50x4.6 mm YMC-AQ 5 fim column. Different gradients of 0.1% TEA in water and acetonitrile were used and the peaks were detected at 254 nm. The area% under the largest peak was reported as the purity.
Chart 1. Starting 6-chIoropyridines used in Examples 10-43.

• EXAMPLE 10
l-(6-(2-Phenoxy-ethoxy)-5-trifluoromethyl-pyridin-2-yI]-piperazme, acetate.
Starting materials A and 1, see Chart 1. Purity 99% (HPLC). MS m/z 368 (M+Hf. HRMS m/z calcd for C18H2oF3N302(M)* 367.1508, found 367.1508.
EXAMPLE 11
l-[6-(2,3-Dihydro-benzo[l,4]dioxin-6-yImethoxy)-5-trifIuoromethyl-pyridin-2-yl]-piperazine, acetate.
Starting materials A and 2, see Chart 1. Purity 94% (HPLC). MS m/z 396 (M+H)^ HRMS m/z calcd for C19H20F3N3O3 (M)* 395.1457, found 395.1468.

EXAMPLE 12
l-[6-(Thiophen-3-ylmethoxy)-5-trifluoromethyl-pyridiii-2-yl]-piperazine, acetate.
Starting materials A and 3, see Chart 1. Purity 98% (HPLC). MS miz 344 (M+H)^ HRMS mIz calcd for C15H16F3N3OS (Mf 343.0966, found 343.0971.
EXAMPLE 13
3-(6-Piperazin-l-yI-3-trifluoromethyl-pyridin-2-yIo.\ymethyl)-benzoDitriIe,
acetate.
Starting materials A and 4, see Chart 1. Purity 95% (HPLC). MS mIz 363 (M+H)'. HRMS mIz calcd for C18Hi7F3N40(Mr 362.1354, found 362.1,365.
EXAMPLE 14
l-(6-(3-Methyl-benzylsulfanyl)-5-trifluoromethyl-pyridin-2-yl]-piperazine,
acetate.
Starting materials A and 5, see Chart 1. Purity 96% (HPLC). MS mlz 368 (M+H)^ HRMS mlz calcd for C18H20F3N3S (M)^ 367.1330, found 367.1322.
EXAMPLE 15
l-(6-(2-ChIoro-benzy!sulfanyI)-5-trifluoroinethyl-pyndin-2-yl]-pipera2ine,
acetate.
Starting materials A and 6, see Chart 1. Purity 98% (HPLC). MS mlz 388
(M+H)*. HRMS mlz calcd for C17H17C1F3N3S (M)* 387.0784, found 387.0773.
EXAMPLE 16
l-(6-(23-Difluoro-benzyloxy)-5-trinuoromethyl-pyridiii-2-yl]-piperazine,
acetate.
Starting materials A and 7, see Chart 1. Purity 100% (HPLC). MS mlz 374 (M+H)*.

EXAMPLE 17 l-(6-Ethylsulfanyl-5-trifluoromethyl-pyridin-2-yl)-piperazine, acetate.
Starting materials A and 8, see Chart 1. Purity 96% (HPLC). MS m/z 292 (M+H^- HRMS m/z calcd for C12H,6F3N3S (Mf 291.1017, found 291.1018.
EXAMPLE 18 l-(6-Propoxy-5-trinuoroniethyl-pyridin-2-yI)-piperazine, acetate.
Starting materials A and 9, see page Chart 1. Purity 100% (HPLC). MS m/z 290 (M+H)^
EXAMPLE 19 l-(6-Cyclopentyloxy-5-trifluoroinethyl-pyridin-2-yl)-piperazine, acetate.
Starting materials A and 10, see Chart 1. Purity 100% (HPLC). MS m/z 316 (M+H)^ HRMS m/z calcd for C|5H2oF3N30(M)^ 315.1558, found 315.1551.
EXAMPLE 20 l-16-(l-Phenyl-ethoxy)-5-trinuoromethyl-pyridin-2-yl]-piperazine, acetate.
Starting materials A and 11, see Chart 1. Purity 100% (HPLC). MS m/z 352
(M+H)^ HRMS m/z calcd for C18H2oF3N30(M)^ 351.1558, found 351.1573.
EXAMPLE 21
8-[2-(6-Piperazin-l-yI-3-trifluoromethyl-pyridin-2-yIoxy)-ethoxy]-quinoIine,
acetate.
Starting material A and 12*, see page Chart 1. Purity 98% (HPLC). MS m/z 419 (M+H)^ HRMS m/z calcd for C2iH2iF3N402(M)* 418.1617, found 418.1625. *Starting material 12 was prepared as described in WO 00/76984.
EXAMPLE 22
l-[6-(2,6-Difluoro-benzyloxy)-5-trifluoromethyl-pyridin-2-yI]-piperazine,
acetate.
Starting material A and 13, see Chart I. Purity 96%o (HPLC). MS m/z 374 (M+H)^ HRMS m/z calcd for C17Hi6F5N30(M)* 373.1214, found 373.1209.

EXAMPLE 23
l-[6-(3-{Pyridin-3-yl}propoxy)-5-trifluoroinetbyl-pyridin-2-yI]-piperazine, acetate.
Starting material A and 14, see Chart 1. Purity 99% (HPLC). MS miz 367
(M+Hf. HRMS mIz calcd for C18H2iF3N40(M)* 366.1667, found 366.1677.
EXAMPLE 24 l-(6-Benzyloxy-5-trifluorotnethyI-pyridin-2-yl)-piperazine, acetate.
Starting material A and 15, see Chart 1. Purity 99% (HPLC). MS mIz 338 (M+Hf. HRMS mIz calcd for C1jHigFaNaOCM)* 337.1402, found 337.1408.
EXAMPLE 25 l-[6-(Furan-2-ylmethoxy)-5-trifluoromethyI-pyridia-2-yI]-piperazine, acetate.
Starting material A and 16, see Chart 1. Purity 96% (HPLC). MS mIz 328 (M+H)^ HRMS m/z calcd for C15Hi6F3N302(M)* 327.1195, found 327.1195.
EXAMPLE 26
l-{6-[2-(2,6-Difluoro-phenoxy)-ethoxy}-5-trifluoromethyl-pyridin-2-yl}-piperazine, acetate.
Starting materials A and 17*, see Chart 1. Purity 98% (HPLC). MS mIz 404 (M+H)^ HRMS mIz calcd for C18Hi8F5N302(M)* 403.1319, found 403.1326. *Starting material 17 was prepared from 2,6-diflurophenoI and ethylene carbonate according to the general procedure described in WO 00/76984 (Example 91). MS analysis supported the stated structure. HRMS m/z calcd for C8H8F2O2 (M)* 174.0492, found 174.0491.
EXAMPLE 27
l-[6-(2-Chloro-benzyIsuIfanyI)-5-trinuoromethyI-pyridiii-2-yIl-2-(/?)-methyl-piperazine, acetate.
Starting materials D and 6, see Chart 1. Purity 96% (HPLC). MS m/z 402 (M+Uy. HRMS m/z calcd for C1gH|9ClF3N3S (M)^ 401.0940, found 401.0926.

EXAMPLE. 28 ,' ,
l-(6-Ethylsulfanyl-5-trifluoromethyl-pyridin-2-yl)-3-(5)-methyl-piperazine,
acetate.
Starting materials B and 8, see Chart 1. Purity 100% (HPLC). MS miz 306 {U+Kf. HRMS mIz calcd for CHHISFBNBSCM)^,305.1174, found 305.1163.
EXAMPLE 29 ■
l-(6-Ethylsulfanyl-5-trifluoromethyI-pyridin-2-y!)-3-(/?)-inethyl-piperazine,
acetate.
Starting materials C and 8, see Chart 1. Purity 95% (HPLC). MS mIz 306 (M+H)^. HRMS mIz calcd for C13H18F3N3S (Mf 305.1174, found 305.1168.
EXAMPLE 30
l-(6-EthyIsuIfanyl-5-tnfluoromethyl-pyridin-2-yl)-2-(/?)-methyI-piperazine,
acetate.
Starting materials D and 8, see Chart 1. Purity 100% (HPLC). MS mIz 306 (M+H)". HRMS mIz calcd for CnHigFsNsS (M)^ 305.1174, found 305.1160.
EXAMPLES! l-(6-Benzyloxy-5-trifluoromethyl-pyridin-2-yI)-3-(5)-methyl-piperazine, acetate.
Starting materials B and 15, see Chart \. Purity 100% (HPLC). MS mIz 352 (M+H)^ HRMS mIz calcd for C18H20F3N3O(M)^ 351.1558, found 351.1553.
EXAMPLE 32
l-(6-Benzyloxy-5-trifluoromethyl-pyridin-2-yI)-3-(i?)-methyl-piperazine,
acetate.
Starting materials C and 15, see Chart 1. Purity 99% (HPLC). MS mIz 352 (M+H)^ HRMS w/z calcd for C18H2oF3N30(M)^ 351.1558, found 351.1541.

EXAMPLE 33
l-(6-Benzyloxy-5-trinuoromethyl-pyridin-2-yI)-2-(i?)-methyl-piperazine,
acetate.
Starting materials D and 15, see Chart 1. Purity 99% (HPLC). MS miz 352 (M+Hf. HRMS m/2 calcd for C1SH20F3N3O (M)^ 351.1558, found 351.1551.
EXAMPLE 34 l-(6-Benzyloxy-5-trifluoromethyl-pyridin-2-yl)-2-(5)-methyl-piperazine, acetate. ,
Starting materials E and 15, see Chart 1. Purity 100% (HPLC). MS mIz 352 (M+Hf. HRMS mIz calcd for C18H2oF3N30(M)^ 351.1558, found 351.1552.
EXAMPLE 35 l-(6-lVIethoxy-5-trifluoromethyl-pyridin-2-yl)-piperazine, acetate.
Starting materials A and 18, see Chart 1. Purity 100% (HPLC). MS mIz 262 (M+H)^ HRMS mIz calcd for C1 iHi4F3N30(M)* 261.1089, found 261.1100.
EXAMPLE 36
l-[6-(5-Fluoro-2-methoxy-benzyloxy)-5-trifluorometbyl-pyridln-2-yI]-piperazine, acetate.
Starting materials A and 19, see Chart 1. Purity 96% (HPLC). MS m/z 386 (M+H)". HRMS m/z calcd for C18H19F4N3O2 (M)* 385.1413, found 385.1408.
EXAMPLE 37
l-{6-[2-(Naphthalen-2-yloxy)-ethoxy]-5-trifluoromethyI-pyridin-2-yI}-piperazine, acetate.
Starting materials A and 20, see Chart 1. Purity 100% (HPLC). MS m/z 418 (M+H)*. HRMS m/z calcd for C22H22F3N3O2 (M)^ 417.1664, found 417.1658.

EXAMPLE 38
l-(6-(2-Chloro-benzylsulfanyl)-5-trifluoroinethyl-pyridin-2-yI]-3-(S)-methyI-piperazine, acetate.
Starting materials B and 6, see Chart 1. Purity 100% (HPLC). MS m/z 402 (M+Hf. HUMS m/z calcd for C18H19C1F3N3S (M)+ 401.0940, found 401.0950.
EXAMPLE 39
l-[6-(2-Chloro-benzylsulfanyl)-5-trifluoromethyl-pyridiD-2-yl]-2-C5'>methyl-piperazine, acetate.
Starting materials E and 6, see Chart 1. Purity 99% (HPLC). MS m/z 402 (M+Hf. HRMS m/z calcd for C1SH19F3N3S (Uf 401.0940, found 401.0942.
EXAMPLE 40
l-[6-(2-Phenoxymethyl-benzyloxy)-5-trifluoroniethyl-pyridin-2-yI]-piperazine,
acetate.
Starting materials A and 21, see Chart 1. Purity 100% (HPLC). MS m/z 444 (M+H)*. HRMS m/z calcd for C24H24F3N3O2 (M)* 443.1821, found 443.1841.
EXAMPLE 41
l-[6-Tetrahydro-furan-2-ylniethoxy)-5-trifluoroinethyl-pyridin-2-yI]-piperazine,
acetate.
Starting materials A and 22, see Chart 1. Purity 97% (HPLC). MS m/z 332 (M+H)*. HRMS m/z calcd for C15H20F3N3O2 (Uf 331.1508, found 331.1504.
EXAMPLE 42 l-(6-(2-CyC1opentyl-ethoxy)-5-trifluoromethyl-pyridin-2-yI]-piperazine, acetate.
Starting materials A and 23, see Chart 1. Purity 100%) (HPLC). MS m/z 344 (M+H)*.
EXAMPLE 43 l-[6-(2-CyC1ohexyl-ethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate.
Starting materials A and 24, see Chart 1. Purity 90% (HPLC). MS m/z 358 (M+H)^. HRMS m/z calcd for C18H26F3N3O (M)+ 357.2028, found 357.2040.

PREPARATION OF A PHARMACEUTIGAL COMPOSITION
I
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 METHODS
The ability of a compound of the invention to bind or act at speC1fic 5-HT receptor subtypes can be determined using in vitro and in vivo assays knpwn 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 compound in serial dilution to displace 3H-labelledlabeled 5-HT, bound to membranes prepared from a transfected HEK293 cell line stably expressing the human 5-HT2c receptor protein, was monitored by SC1ntillation Proximity Assay technology. Non-speC1fic binding was defined using 5 \xM mianserin. Results obtained for exemplary compounds of the invention are illustrated in Table 1 below. The 5-HT2c receptor affinity values, expressed as percent inhibition of binding of the radioligand at 50 nM of test

compound, were in the range of l0%-95%. The Kj values for the compounds towards the 5-HT2C receptor were in the range 0.5-5000 nM.

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 calC1um in transfected HEK293 cells, stably expressing the human 5-HT2c receptor
protein, using the calC1um-chelating fluorescent dye FLUO-3 (Sigma, St. Louis, MO, U.S.A.).
The maximum responses of the compounds in the Examples were in the range of 0-102% relative to the maximum response of 5-HT (serotonin) at a concentration of 1 µM.

WE CLAIM :
1. A compound of the formula (I):
wherein
R1 is selected from H, 1-4 alkyl, 2-hydroxyethyl, 2-cyanoethyl, tetrahydropyran-2-yl, and a
nitrogen protecting group;
R2 and R3 each, independently, represent H or CH3;
R4 is selected from 0-R5 NH-R5 or S-R5 wherein
R5 is selected from aryl, aryl-C1.6-alkyl, aryloxy-C1-6-alkyl, heteroaryl, heteroaryl-C1.6-alkyl,
heteroaryloxy-C2.6-alkyl, C3.6-cycloalkyl, C3.6-cycloalkyl-C1.4-alkyl, C1.6-alkyl, 2-
tetrahydrofuryl, 3-tetrahydrofuryl, 2-tetrahydrofurfuryl, 3-tetrahydrofurfuryl, piperidine-4-yl,
tetrahydropyran-4-yl, Cs-e-alkynyl, C3.6-alkenyl, or fluoro-C2-4-alkyl;
and wherein any aryl or heteroaryl residue, alone or as part of another group, may be
unsubstituted or substituted with one or more of Cj^-alkyl, C14-alkoxy, C1-4-alkylthio, C24-
acyl, CM-alkylsulphonyl, cyano, nitro, hydroxy, C2.6-alkenyl, C2.6-alkynyl, fluoromethyl,
trifluoromethyl, trifluoromethoxy, halogen, -N(R6)(R7), aryl, aryloxy, arylthio, aryl-C1.4-alkyl,
aryl-C24-alkenyl, aryl-C2-4-alkynyl, heteroaryl, heteroaryloxy, heteroarylthio, heteroaryl-CM-
alkyl, aryl-C1.4-alkoxy, aryloxy-CM-alkyl, or dimethylamino-C2-4-alkoxy, wherein
R6 and R7 are, independently of each other, hydrogen, methyl or ethyl; or form a pyrrolidine,
piperazine, morpholine, thiomorpholine or a piperidine ring together with the nitrogen atom to
which they are bound;
and wherein any aryl or heteroaryl residue as substituents on aryl or heteroaryl, alone or as part
of another group, in turn may be substituted in one or more positions, preferably one.

independently of each other by C1.4-alkyl, C1.4-alkoxy, halogen, trifluoromethyl, cyano, hydroxy or dimethylamino;
and pharmaceutically acceptable salts, hydrates, solvates, geometrical isomers, tautomers, optical isomers, A'-oxides and prodrug forms thereof.
2. The compound as claimed in claim 1, wherein R' is hydrogen.
3. The compound as claimed in any one of claims 1-2, wherein R' is selected from 0-R^ and S-R^
4. The compound as claimed in any one of claims 1-3, wherein R^ is selected from aryl-C1. 6-alkyl, aryloxy-C2-6-alkyl, heteroaryl-C1.6-alkyl, heteroaryloxy-C2.6-alkyl, C34s-e-cycloalkyl, C3.6-cycloalkyl-C14-alkyl, C1.6-alkyl, 2-tetrahydrofurftiryl, and wherein any aryl or heteroaryl residue, alone or as part of another group, may be unsubstituted or substituted with one or more of C1.4-alkyl, CM-alkoxy, cyano, halogen, or aryloxy-CM-alkyl.
5. The compound as claimed in any one of claims 1-4, wherein R^ is selected from benzyl, 2-chlorobenzyl, 3-cyanobenzyl, 2-cyclohexylethyl, cyclopentyl, 2-cyclopentylethyl, 2,3-difluorobenzyl, 2,6-difluorobenzyl, 2-(2,6-difluorophenoxy)ethyl, 2,3-dihydrobenzo[l,4]dioxin-6-ylmethyl, ethyl, 5-fluoro-2-methoxybenzyl, furan-2-ylmethyl, methyl, a-methylbenzyl, 3-methylbenzyl, 2-(naphthalene-2-yloxy)ethyl, 2-phenoxyethyl, 2-phenoxymethylbenzyl, n-propyl, 3-(pyridin-3-yl)-n-propyl, 2-(8-quinolinyloxy)ethyI, tetrahydrofuran-2-ylmethyl, or 3-thienylmethyl.
6. The compound as claimed in any one of claims 1-5, wherein R', R^, and R^ are selected from hydrogen.

7. The compound as claimed in any one of claims 1-6, wherein the carbon atom, to which R2 is attached, has the (51)-configuration when R2 is methyl and R1 and R3 both are hydrogen.
8. The compound as claimed in any one of claims 1-6, wherein the carbon atom, to which R3 is attached, has the (R)j-configuration when R3 is methyl and R1 and R2 both are hydrogen
9. The compound as claimed in any one of claims 1-6, wherein the compound is selected from

• l-[6-(2-Phenoxy-ethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate;
• l-[6-(2,3-Dihydro-benzo[l,4]dioxin-6-ylmethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate;
• 1 -[6-(Thiophen-3-ylmethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate;
• 3 -(6-Piperazin-1 -y 1-3 -trifluoromethyl-pyridin-2-yloxymethyl)-benzonitrile, acetate;
• l-[6-(3-Methyl-benzylsulfanyl)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate;
• l-[6-(2-Chloro-benzylsulfanyl)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate;
• 1 -[6-(2,3-Difluoro-benzyloxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate;
• l-(6-Ethylsulfanyl-5-trifluoromethyl-pyridin-2-yl)-piperazine, acetate;
• 1 -(6-Propoxy-5-trifluoromethyl-pyridin-2-yl)-piperazine, acetate;
• 1 -(6-Cyclopentyloxy-5-trifluoromethyl-pyridin-2-yl)-piperazine, acetate;
• l-[6-(l-Phenyl-ethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate;
• 8-[2-(6-Piperazin-1 -yl-3-trifluoromethyl-pyridin-2-yloxy)-ethoxy]-quinoline, acetate;
• l-[6-(2,6-Difluoro-benzyloxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate;
• l-[6-(3-{Pyridin-3-yl}propoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate;
• 1 -(6-Benzyloxy-5-trifluoromethyl-pyridin-2-yl)-piperazine, acetate;
• l-[6-(Furan-2-ylmethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate;

• l-{6-[2-(2.6-Difluoro-phenoxy)-ethoxy]-5-trilluoromethyl-pyridin-2-yl}-piperazine, acetate;
• l-[6-(2-Chloro-benzylsulfanyl)-5-tritluoromethyl-pyridin-2-yl]-2-(/?)-methyl-piperazine, acetate;
• 1 -(6-Ethylsulfanyl-5-trifluoromethyl-pyridin-2-yl)-3-(S)-methy 1-piperazine, acetate;
• l-(6-Ethylsulfanyl-5-trifluoromethyl-pyridin-2-yl)-3-(R?)-methyl-piperazine, acetate;
• l-(6-Ethylsulfany!-5-trifluoromethyl-pyridin-2-yl)-2-(R)-methyl-piperazine, acetate;
• l-(6-Benzyloxy-5-tritluoromethyl-pyridin-2-yl)-3-(.S')-methyl-piperazine. acetate;
• l-(6-Benzyloxy-5-tritluoromethyl-pyridin-2-yl)-3-(R)-methyl-piperazine, acetate;
• 1 -(6-Benzyloxy-5-trifluoromethyl-pyridin-2-yl)-2-(R)-methyl-piperazine, acetate;
• 1 -(6-Benzyloxy-5-trifluoroniethyl-pyridin-2-yl)-2-(iS)-methy 1-piperazlne. acetate;
• 1 -(6-Methoxy-5-trifluoromethyl-pyridin-2-yl)-piperazine, acetate;
• l-[6-(5-Fluoro-2-methoxy-benzyloxy)-5-trifluoromethyI-pyridin-2-yl]-piperazine, acetate;
• l-{6-[2-(Naphthalen-2-yloxy)-ethoxy]-5-trifluoromethyl-pyridin-2-yl}-piperazine, acetate;
• l-[6-(2-Chloro-benzylsulfanyl)-5-trinuoroniethyl-pyridin-2-yl]-3-('S)-methyl-piperazine, acetate;
• l-[6-(2-Chloro-benzylsulfanyl)-5-trifluoroniethyl-pyridin-2-yl]-2-(S)methyl-piperazine, acetate;
• l-[6-(2-Phenoxymethyl-benzyIoxy)-5-tritluoromethyl-pyridin-2-ylj-piperazine, acetate;
• l-[6-Tetrahydro-furan-2-ylmethoxy)-5-tritluoromethyl-pyridin-2-yl]-piperazine, acetate;
• l-[6-(2-Cyclopentyl-ethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate; or
• l-[6-(2-Cyclohexyl-ethoxy)-5-trifluoromethyl-pyridin-2-yl]-piperazine, acetate.
10. A pharmaceutical composition comprising a compound as claimed in any one of claims 1 to 9 as an active ingredient, and a pharmaceutically acceptable carrier.

11. The method of making a compound as claimed in any one of claims 1-9. by reacting a compound of the following formula (11):

wherein Hal is halogen;
with an appropriate piperazine derivative of formula (III):

wherein
R1 is H or C1-4 alkyl, 2-hydroxyethyl, 2-cyanoethyl, tetrahydropyran-2-yl, or a nitrogen
protecting group; and
R and R each, independently, represent H or CH3;
in a solvent such as DMSO, acetonitrile, dioxane. THF, n-butanol, DMF, or in a mixture of
such solvents, optionally in the presence of a base such as K2CO3, NaiCO^, CsoCOj, NaOH,
triethylamine or pyridine, at 0-200 °C for 1-24 hours;
to produce a compound of formula (IV)

wherein
R', R and R3 have the same meaning as in formula (III); and
Hal is halogen.

where the compound of formula (IV) is reacted with an appropriate alcohol, amine or thiol,
as defined by 0-R5 NH-R5 or S-R5 or its corresponding anions;
in a solvent such as DMSO, dioxane, THF,tert-butanol or DMF, at 0-200 °C for 1-24 hours.

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Patent Number

229569

Indian Patent Application Number

2586/CHENP/2004

PG Journal Number

13/2009

Publication Date

27-Mar-2009

Grant Date

18-Feb-2009

Date of Filing

17-Nov-2004

Name of Patentee

BIOVITRUM AB (publ)

Applicant Address

SE-112 76 STOCKHOLM,

Inventors:

#	Inventor's Name	Inventor's Address
1	NILSSON, Bjorn	Igeldammsgatan 20, 5 trp., S 112 76 Stockholm,
2	RINGBERG, Erik	Gröna gatan 23F, S 754 26 Uppsala,

PCT International Classification Number

C07D401/04

PCT International Application Number

PCT/SE2003/000795

PCT International Filing date

2003-05-16

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	60/410,038	2002-09-12	U.S.A.
2	0201544-4	2002-05-17	U.S.A.