MXPA01009665A - Novel compounds - Google Patents

Abstract

The invention provides compounds of general formula (I) wherein:R1 represents optionally substituted C1-C12 alkyl or optionally substituted 3- to 10-membered saturated or unsaturated ring system comprising up to two ring carbon atoms that form carbonyl groups and comprising up to 4 ring heteroatoms independently selected from nitrogen, oxygen and sulfur;m is 0-1;Q represents OCH2, C1-C4 alkylene or C2-C4 alkenylene;T represents C(O)NH, or when m is 0, T may additionally represent a bond or NH, or when m is 1 and Q represents C1-C4 alkylene, T may additionally represent NH;n is 1-4;each R2 and R3 independently represents H or C1-C4 alkyl;V represents N, and W represents N or CH;X represents O, C(O), CH(OH), SO2, NH or N(C1-C6 alkyl), provided that when W represents N, then X represents either C(O) or SO2 and when W represents CH, then X is other than SO2;R4 represents optionally substituted phenyl;R5 and R6 each independently represent H, C1-C6 alkyl or hydroxyC1-C6 alkyl, or R5 and R6 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;R7 and R8 each independently represent H or C1-C6 alkyl;and R9 represents OH or -NR7R8;processes for their preparation, pharmaceutical compositions containing them and their use in therapy.

Description

NOVEL COMPOSITIONS OF CHEMIOCINES DESCRIPTION OF THE INVENTION The present invention relates to novel compounds, to the processes for their preparation, to the pharmaceutical compositions containing them and to their use in therapy. Chemokines play an important role in immune and inflammatory responses in various diseases and disorders, including asthma and allergic diseases, as well as immune pathologies such as rheumatoid arthritis and atherosclerosis. These small secreted molecules are a growing superfamily of 8-14 kDa proteins characterized by a conserved 4-cysteine portion. The chemokine superfamily can be divided into two main groups that show characteristic structural portions, the families, Cys-X-Cys (C-X-C) and Cys-Cys (C-C). These are distinguished based on a simple amino acid insertion between the NH-proximal pair of the cysteine residues and the sequence similarity. C-X-C chemokines include several chemoattractants and potent activators of neutrophils such as interleukin-8 (IL-8) and neutrophil activating peptide 2 (NAP-2). C-C chemokines include potent chemoattractants of monocytes and lymphocytes but not of REF: 131782 neutrophils, such as 1-3 human chemotactic proteins of monocytes (MCP-1, MCP-2 and MCP-3), RANTES (Expressed and Secreted by Normal T cells, Regulated on Activation), eotaxin and macrophage inflammatory proteins la and lß (MlP-la and MlP-lß). Studies have shown that the actions of chemokines are mediated by subfamilies of G-protein coupled receptors, among which are the receptors designated CCR1, CCR2, CCR2A, CCR2B, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8 , CCR9, CCR10, CXCR1, CXCR2, CXCR3 and CXCR4. These receptors represent good targets for the development of drugs, since the agents that modulate these receptors could be useful in the treatment of disorders and diseases such as those mentioned above. Certain piperidinyl derivatives and piperazinyl derivatives are known from US Pat. Nos. 3 787 419, 4 559 349 and 5 210 086 for use respectively as central nervous system depressants, antipsychotic agents and as adrenoreceptor antagonists. . According to the present invention, there is thus provided a compound of the general formula: R4 (i: wherein: R1 represents an alkyl group of 1 to 12 carbon atoms optionally substituted with one or more substituents independently selected from the groups cyano, hydroxyl, alkoxy of 1 to 6 carbon atoms, alkylthio of 1 to 6 carbon atoms and alkoxycarbonyl of 1 to 6 carbon atoms, or R1 represents a saturated or unsaturated ring system of 3 to 10 members which may comprise up to 2 carbon atoms of the ring forming the carbonyl groups, and which may comprise up to 4 heteroatoms in the ring, independently selected from nitrogen, oxygen and sulfur, the ring system is optionally substituted with one or more substituents independently selected from halogen atoms, and the cyano, nitro, hydroxyl, alkyl groups of 1 to 6 carbon atoms, cycloalkyl 3 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, alloalkoxy of 1 to 6 carbon atoms, -NR5R6, cycloalkylamino of 3 to 6 carbon atoms, alkylthio of 1 to 6 carbon atoms, (alkylthio of 1 to 6 carbon atoms) (alkyl of 1 to 6 carbon atoms) , alkylcarbonylamino of 1 to 6 carbon atoms, -C (0) NR7R8, sulfonamido (-S02NH2), (di) alkylsulfonamido of 1 to 6 carbon atoms, phenyl, phenylamino, nitrophenyl, pyridyl, pyridylthio, benzodioxanil, thienyl, furanyl , and alkyl of 1 to 6 carbon atoms substituted with C (0) R9 or alkoxy of 1 to 6 carbon atoms; m is 0 or 1; Q represents a group OCH2, alkylene of 1 to 4 carbon atoms or alkenylene of 2 to 4 carbon atoms; T represents a C (0) NH group, or when m is 0, T may additionally represent a bond or an NH group, or when m is 1 and Q represents alkylene of 1 to 4 carbon atoms, T may additionally represent a group NH; n is 1, 2, 3 or 4; each R2 independently represents a hydrogen atom or an alkyl group of 1 to 4 carbon atoms; each R3 independently represents a hydrogen atom or an alkyl group of 1 to 4 carbon atoms; V represents a nitrogen atom; represents a nitrogen atom or a CH group; X represents an oxygen atom or a group C (O), CH (OH), NH or N (alkyl of 1 to 6 carbon atoms), with the proviso that when W represents a nitrogen atom, then X represents C (O); R4 represents a phenyl group optionally substituted with one or more substituents independently selected from halogen atoms, and from amino, nitro, cyano, sulfonyl (-S03H), sulfonamido (-S02NH2), alkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, haloalkoxy of 1 to 6 carbon atoms and alkylsulfonyl of 1 to 6 carbon atoms; R5 and R6 each independently represents a hydrogen atom or an alkyl group of 1 to 6 carbon atoms, hydroxy- (alkyl of 1 to 6 carbon atoms), or R5 and R6 together with the nitrogen atom to which they are attached form a saturated 4 to 7 membered heterocyclic ring; R7 and R8 each independently represents a hydrogen atom or an alkyl group of 1 to 6 carbon atoms; and R9 represents a hydroxyl group or -NR7R8; with the conditions that: a) when m is 0, T is CONH, n is 2, 3 or 4 and when R2 and R3 represent hydrogen, W is CH, X is C (O) or CH (OH) and R1 represents an unsaturated ring system of 3 to 10 members, substituted, then one or more substituents in the ring system do not include hydroxyl, halogen, alkoxy of 1 to 6 carbon atoms or haloalkoxy of 1 to 6 carbon atoms, and b) when W is N, X is C (O), R4 represents 3-trifluoromethylphenyl, • m is 0 and T is bond, then R1 and (CR2R3) n taken together do not represent an alkyl group of 1 to 6 carbon atoms, and c) when it is CH, X is O, n is 2 or 3 and each R2 and R3 represents hydrogen, m is 0 and T is NH, then R1 does not represent a group or a pharmaceutically acceptable salt or solvate thereof. In the context of the present specification, an alkyl substituent group or an alkyl moiety in a substituent group may be linear or branched. In addition, the alkyl portions in the dialkylamino, di (hydroxyalkyl) amino or dialkylsulfonamido groups, as a substituent, may be the same or different. R1 represents an alkyl group of 1 to 12 carbon atoms, preferably 1 to 10 carbon atoms, optionally substituted by one or more (for example, 1, 2, 3 or 4) substituents independently selected from the groups cyano, hydroxyl, alkoxy of 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms (for example, methoxy, ethoxy, propoxy, butoxy, pentoxy or hexoxy), alkylthio of 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms; carbon (for example, methyl-, ethyl-, propyl-, butyl-, pentyl- or hexylthio) and alkoxycarbonyl having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms (eg, methoxy-, ethoxy-, propoxy-, butoxy-, pentoxy- or hexoxycarbonyl), or R1 represents a saturated or unsaturated ring system of 3 to 10 members comprising up to 2 carbon atoms of the ring forming carbonyl groups, and comprising up to 4 heteroatoms in the ring independently selected from nitrogen, oxygen and sulfur, the ring system is optionally substituted by one or more heteroatoms (for example 1, 2, 3 or 4) substituents independently selected from the halogen atoms (fluorine, chlorine, bromine or iodine), and the cyano, nitro, hydroxyl, alkyl groups from 1 to 6 carbon atoms (for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl or hexyl), cycloalkyl of 3 to 6 carbon atoms (cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl), alkoxy from 1 to 6 carbon atoms (for example methoxy, ethoxy, propoxy, butoxy, pentoxy or hexoxy), alkoxycarbonyl of 1 to 6 carbon atoms (for example methoxy-, ethoxy-, propoxy-, butoxy-, pentoxy- or hexoxycarbonyl) ), haloalkyl of 1 to 6 carbon atoms (for example trifluoromethyl), haloalkoxy of 1 to 6 carbon atoms (for example, trifluoromethoxy), -NR5R6, cycloalkylamino of 3 to 6 carbon atoms (cyclopropyl-, cyclobutyl-, cyclopentyl) - or cyclohexylamino), alkylthio of 1 to 6 carbon atoms bond (for example methylthio, ethylthio, propylthio, butylthio, pentthylthio or hexylthio), (alkylthio of 1 to 6 carbon atoms) (alkyl of 1 to 6 carbon atoms) (for example methylthiomethyl), alkylcarbonylamino of 1 to 6 carbon atoms carbon (for example methylcarbonylamino, ethylcarbonylamino, propylcarbonylamino, butylcarbonylamino, pentylcarbonylamino or hexylcarbonylamino), -C (0) NR7R8, sulfonamido (-S02NH2), (di) alkylsulfonamido of 1 to 6 carbon atoms (for example (di) methylsulfonamido or (di) ethylsulphonamido), phenyl, phenylamino, nitrophenyl, pyridyl, pyridylthio, benzodioxanyl, thienyl, furanyl, and the alkoxy groups of 1 to 6 carbon atoms or alkyl of 1 to 6 carbon atoms substituted by C (0) R 9, the alkyl and alkoxy portions are as defined above. The saturated or unsaturated ring system of 3 to 10 members in the group R1 can be monocyclic or polycyclic comprising 2 or more fused rings, examples of which include cyclobutyl, cyclopentyl, cyclohexyl, norbornylnyl, adamantyl, piperidyl, phenyl, naphthyl, naphthyridinyl , 1,3-benzodioxolyl, pyrazolyl, furanyl, pyridyl, thienyl, benzoxazolyl, benzothiazolyl, chromonyl, imidazolyl, quinolinyl, isoquinolinyl, benzimidazolyl, pyrimidinyl, pyrazolopyrimidinyl, thienopyrimidinyl, thiazolopyrimidinyl, pyrimidinedione, pyrazinyl, pyridazinyl, purinyl, quinoxalinyl, thiazolyl, isothiazolyl and 2,4-dioxo-3,4-dihydro-quinazolinyl. Preferably, R1 represents an alkyl group of 1 to 10 carbon atoms, optionally substituted by one or two substituents independently selected from the cyano, hydroxyl groups, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms and alkoxycarbonyl of 1 to 4 carbon atoms, or R1 represents a saturated or unsaturated ring system of 3 to 10 members which can comprise up to 2 atoms carbon ring forming the carbonyl groups, and which may comprise up to 4 ring heteroatoms, independently selected from nitrogen, oxygen and sulfur, the ring system is optionally substituted with one or more substituents independently selected from halogen atoms, and the groups cyano, nitro, hydroxyl, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkoxycarbonyl of 1 to 4 carbon atoms, haloalkyl of 1 to 3 carbon atoms, haloalkoxy of 1 to 3 carbon atoms, -NR5R6, cycloalkylamino of 3 to 6 carbon atoms, alkylthio of 1 to 4 carbon atoms, (alkylthio of 1 to 4 carbon atoms) (alkyl of 1 to 4 carbon atoms), alkylcarbonylamino of 1 to 4 carbon atoms, -C (0) NR7R8, phenyl, phenylamino, nitrophenyl, pyridyl, pyridylthio, benzodioxanyl, thienyl, furanyl, and alkyl of 1 to 4 carbon atoms substituted with C ( 0) R9 or alkoxy of 1 to 4 carbon atoms. Preferably, Q represents a group OCH2, alkylene of 1 to 3 carbon atoms or alkenylene of 2 to 3 carbon atoms. Each R2 independently represents a hydrogen atom or an alkyl group of 1 to 4 carbon atoms (for example methyl, ethyl, propyl, isopropyl or butyl) and is especially a hydrogen atom. Each R3 independently represents a hydrogen atom or an alkyl group of 1 to 4 carbon atoms (for example methyl, ethyl, propyl, isopropyl or butyl), and is especially a hydrogen atom. Preferably n is 2 or 3. X represents an oxygen atom or a C (O) or NH group.

R4 represents a phenyl group optionally substituted by one or more (eg, one, two, three or four) independently selected from halogen atoms (fluorine, chlorine, bromine or iodine), and amino, nitro, cyano, sulfonyl (-S03H ), sulfonamido (-S02NH2), alkyl of 1 to 6 carbon atoms, preferably of 1 to 4 carbon atoms (for example methyl, ethyl, propyl, butyl, pentyl or hexyl), haloalkyl of 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms (for example, trifluoromethyl), haloalkoxy of 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms (for example trifluoromethoxy) and alkylsulfonyl of 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms (for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, butylsulfonyl, pentylsulfonyl or hexylsulfonyl) Preferably, R4 represents a phenyl group optionally substituted by one or two halogen atoms, particularly chlorine atoms. R5 and R6 each independently represent a hydrogen atom or an alkyl group of 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms or a hydroxy group (alkyl of 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms), or R5 and R6 together with the nitrogen atom to which they are attached form a 4 to 7 membered saturated heterocyclic ring. The alkyl portion in each case can, for example, be a methyl, ethyl, propyl, butyl, pentyl or hexyl group. In the hydroxyalkyl group, the hydroxyl group may be attached to any suitable carbon atom of the alkyl portion. R7 and R8 each independently represent a hydrogen atom or an alkyl group of 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms (for example methyl, ethyl, propyl, butyl, pentyl or hexyl). Preferably, R7 and R8 each independently represent a hydrogen atom or a methyl group. R9 represents a hydroxyl group or, preferably, -NR5R6. Examples of particularly preferred compounds of the invention include 4-chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2- [2- (dimethylamino) -2-oxoethoxy] benzamide, N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-ethoxybenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - 4 - isopropoxybenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4-ethoxybenzamide, N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3- (trifluoromethoxy) benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4-methoxybenzamide, N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -4- (trifluoromethoxy) benzamide, N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2-furamide, N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2-phenylacetamide, N- hydrochloride. { 2 - [4 - (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-methoxybenzamide, 3-chloro-N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4-fluorobenzamide, N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-fluorobenzamide, N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-hydroxybenzamide, N- hydrochloride. { 2- [4- (4-chlorobenzoyl) -1-piperidinyl] ethyl} -3- [2- (methylamino) -2-oxoethoxy] benzamide, 2- [3-. { 2- [4- (4-fluorobenzoyl) -1-piperidinyl] ethyl} -2,4-dioxo-3, 4-dihydro-1 (2H) -quinazolinyl] -N, N-dimethylacetamide, N- (2- [4- (3,4-dichlorobenzoyl) -1-piperazinyl] ethyl hydrochloride .3. -3-methoxybenzamide, 3,4-dichloro-N- { 2- [4- (3,4-dichlorobenzoyl) -1-piperazinyl] ethyl} benzamide, 4-chloro-N- hydrochloride {.2- [4- (3, 4-dichlorobenzoyl) -l-piperazinyl] ethyl} -2- [2- (dimethylamino) -2-oxoethoxy] benzamide, N-7-. {2- [2- 4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl.} - 5-methyl [1,3] thiazolo [4,5-d] pyrimidin-2, 7-diamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -9-methyl-9H-purin-6-amine, N- [2 - [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -1, 3-benzothiazol-2 -amine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -1, 3-benzoxazol-2-amine, 6-chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2-pyrazinamine, 6-chloro-N- (2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl]. 3-pyridazinamine, 6- (. {2- 2- [4- ( 3,4-dichlorophenoxy) -l-piperidinyl] ethyl.}. -amino) -1,3-dimethyl-2,4 (1H, 3H) -pyrimidinedione, hydrochloride salt of N-. {L- [4- (3,4-dichlorophenoxy) -piperidin-1-ylmethyl] -2-methyl-propyl.} -4-methyl-1-benzamide, hydrochloride salt of N-. {L- [4- (3,4-dichloro -phenoxy) -piperidin-1-ylmethyl] -2-methyl-propyl.} - 3-methoxy-benzamide, N-. {2- [4- (3,4-dichloroanilino) -1-piperidinyl] dihydrochloride] ethyl.}. -3-methoxybenzamide, N-. {2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl-N- (3-methoxybenzyl) amine dihydrochloride, 3- { 2 - [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl.} - 6-methoxy-2,4 (1 H, 3 H) -quinazolindione, N- { 2- [4- (3, 4 -dichlorophenoxy) -l-piperidinyl] ethyl.} - 3 -fluorobenzamide, N- { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -benzamide, 4-chloro- N- { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl ] ethyl} benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4-methoxybenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2-methoxybenzamide, N-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl} - 3-methoxybenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2-nitrobenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2-methylbenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 3- (trifluoromethyl) benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -3, 5-dinitrobenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - 2-iodobenzamide, 4-cyano-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, 4-bromo-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4-methylbenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4-nitrobenzamide, 3-bromo-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, 3, 4-dichloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4-fluorobenzamide, 2,4-dichloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -3-methylbenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 4-iodobenzamide, 4-chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-nitrobenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 4-methyl-3-nitrobenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2-fluoro-5- (trifluoromethyl) benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -3- (trifluoromethoxy) benzamide, 3,5-dichloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4- (trifluoromethyl) benzamide, 3-cyano-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, 2-bromo-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -5-methoxybenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2-furamide, 3-chloro-N- (2- [4- (3, -dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, 2-chloro-N-. {2- [4- (3 , 4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, N-. {2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl] -3,5-difluorobenzamide, , 3-dichloro-N- { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, N- { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl-2-naphthamide, N- { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- (methylsulfanyl) nicotinamide, N-. 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2-fluoro-6- (trifluoromethyl) benzamide, N- { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl.} -2,4-difluorobenzamide, N- { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2-thiophenecarboxamide, N- {2- [4- (3, 4-dichlorophenoxy) -l-piperidinyl] ethyl.} - 2-quinoxalinecarboxamide, 4- (. {2- 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl} ] methyl ethyl] -amino) -4-oxobutanoate, N-. {2- [4- (3, 4-dichlorophenoxy) -l-piperidinyl] ethyl} -bicyclo [2.2.1] hept-5-en-2-carboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -cyclobutanecarboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2-methoxyacetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} cyclohexanecarboxamide, (E) -N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -3-phenyl-2-propenamide, 2-chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyljnicotinamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2-phenylacetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} • Cyclopentanecarboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2-phenoxyacetamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -benzamide, N-. { 2- [4- (4-chlorobenzoyl) -piperidinyl] ethyl} -3- (trifluoromethyl) benzamide, 4- (tert-butyl) -N-. { 2- [4- (4-chlorobenzoyl) -1-piperidinyl] ethyl} benzamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -4-methylbenzamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -4-nitrobenzamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -3-methylbenzamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -4-methyl-3-nitrobenzamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -3-cyanobenzamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -2-furamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -3-nitrobenzamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -2-naphthamide, N- [2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -2- (methylsulfanyl) nicotinamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -2- (2,3-dihydro-1,4-benzodioxin-2-yl) -1,3-thiazole-4-carboxamide, N-2-cyclopropyl-N-4-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2, 4-pyrimidindiamine, 2-. { [4- ( { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] -ethyl} amino) -2-pyrimidinyl] amino} -1-ethanol, 2- [[4- ( { 2- [4- (3,4-Dichlorophenoxy) -1-piperidinyl] ethyl} amino) -2-pyrimidinyl] (methyl) amino] -1 -ethanol, N-4-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -N-2-phenyl-2,4-pyrimidinediamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2- (methylsulfanyl) -4-pyrimidinamine, N-4-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -6-methyl-2, 4-pyrimidindiamine, N-4-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -N-2, 6-dimethyl-2,4-pyrimidinediamine, 2-chloro-N-4-cyclopropyl-N-6-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl} -4, 6-pyrimidindiamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4-phenyl-2-pyrimidinamine, N-2-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -N-4-N-4,6-trimethyl-2,4-pyrimidinediamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4- (trifluoromethyl) -2-pyrimidinamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 4- (propylsulfanyl) -2-pyrimidinamine, N-2-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -N-4-phenyl-2,4-pyrimidinediamine, N-4-cyclopropyl-N-2-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2, 4-pyrimidindiamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} [1,8] naphthyridin-2-amine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4- (3-pyridinyl) -2-pyrimidinamine, N-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl} -2-pyrimidinamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4,6-dimethoxy-2-pyrimidinamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 4- (3-furyl) -2-pyrimidinamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -1-methyl-lH-pyrazolo [3,4-d] pyrimidin-4-amine, N-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl} -lH-purin-6-amine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -5-methylthieno [2, 3-d] pyrimidin-4-amine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -7-methylthieno [3,2-d] pyrimidin-4-amine, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -2-thiophenecarboxamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -2-quinoxalinecarboxamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -bicyclo [2.2.1] hept-5-en-2-carboxamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -cyclohexanecarboxamide, (E) -N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -3-phenyl-2 -propenamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -2-phenoxyacetamide, (E) -N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} 3- (4-nitrophenyl) -2-propenamide, 2- (1-adamantyl) -N-. { 2- [4- (4-chlorobenzoyl) -1-piperidinyl] ethyl} acetamide, (4-chlorophenyl) (L-. {2- 2- [(2-fluoro-4,5-dimethoxybenzyl) amino] ethyl] -4-piperidinyl) methanone, (4-chlorophenyl) (l-. { 2- [(3,4,5-trimethoxybenzyl) -amino] ethyl] -4-piperidinyl) methanone, (4-chlorophenyl) (l- { 2- [(3-nitrobenzyl) amino] ethyl} -4-piperidinyl) methanone, (4-chlorophenyl). { 1- [2- (isobutylamino) ethyl] -4-piperidinyl} methanone, 4 - [( { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl.}. -amino) methyl] -4-ethylhexan-nitrile, (4-chlorophenyl) (l-. { 2- [(7-hydroxy-3,7-dimethyloctyl) amino] ethyl] -4-piperidinyl) methanone, (4-chlorophenyl) [1- (2- {[[6-nitro-1, 3-benzodioxol-5-yl) methyl] amino.} Ethyl) -4-piperidinyl] methanone, [1- (2. {[[(5-chloro-1,3-dimethyl-lH-pyrazole-4- il) -methyl] amino.} ethyl) -4-piperidinyl] (4-chlorophenyl) methanone, (4-chlorophenyl) [1- (2 { [3-nitro-4- (2-pyridinyl sulfaniD-benzyl) amino] .) ethyl) -4-piperidinyl] -methanone, (4-chlorophenyl) [1- (2 { [(E) -3- (4-nitrophenyl) -2-propenyl] amino.} ethyl) -4-piperidinyl] methanone, (4-chlorophenyl). {L- [2- ( { [5- (3-Nitrophenyl) -2-furyl] methyl} amino) ethyl] -4-piperidinyl} methanone, (4-chlorophenyl) [1- (2 { [5-nitro-2- (2-pyridinylsulfanyl) benzyl] amino} ethyl) -4-piperidinyl] -methanone, 6- [( {. 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -amino) methyl] -2- (methylsulfanyl) nico tinonitrile,. { l- [2- ( { [5-chloro-l-methyl-3- (trifluoromethyl) -1H-pyrazol-4-yl] methyl} amino) ethyl] -4-piperidinyl} (4-chlorophenyl) methanone, (4-chlorophenyl) [1- (2. {[[3- (methylsulfanyl) butyl] -amino} ethyl) -4-piperidinyl] methanone, (4-chlorophenyl) [1 - (2- { [(4-phenyl-4-piperidinyl) -methyl] amino} ethyl) -4-piperidinyl] methanone, (4-chlorophenyl) [1- (2- { [(1 phenyl-lH-pyrazol-5-yl) methyl] amino.} ethyl) -4-piperidinyl] methanone, 3- [(. {2- 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} - amino) methyl] cyclohexanecarboxylate, N-. { 4- [( { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] -ethyl} amino) methyl] phenyl} acetamide, (4-chlorophenyl) (L-. {2- 2- [(2,5-difluorobenzyl) amino] -ethyl} -4-piperidinyl) methanone, (4-chlorophenyl) (1- (2-) [(4-Nitrobenzyl) amino] ethyl] 4-piperidinyl) ethanone, (4-chlorophenyl) (1- {2- (2,6-dichlorobenzyl) amino] -ethyl} -4-piperidinyl methanone(4-chlorophenyl) (1- {2- [2-pyridinylmethyl) amino] -ethyl} -4-piperidinyl) methanone, (4-chlorophenyl) [1- (2- {[[( 3-methyl-2-thienyl) methyl] -amino.} Ethyl) -4-piperidinyl] methanone, (4-chlorophenyl) (l- { 2- [(3-hydroxy-4-methoxybenzyl) -amino] ethyl.} -4-piperidinyl) methanone, 3- [(. {2- 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -amino) methyl] -4H-chromen-4-one , [1- (2- { [(5-Chloro-1,3-dimethyl-lH-pyrazol-4-yl) -methyl] amino} ethyl) -4-piperidinyl] (4-chlorophenyl) methanone (4-chlorophenyl) [1- (2. {[[(2,6-dichloro-4-pyridinyl) -methyl] amino} ethyl) -4-piperidinyl] methanone (4-chlorophenyl) [1 - (2- { [(2-phenyl-lH-imidazol-4-yl) methyl] aminojetyl) -4-piperidinyl] methanone, (4-chlorophenyl) [1- (2- { [(5- ethyl-2-thienyl) methyl] -amino.} ethyl) -4-piperidinyl] methanone, (4-chlorophenyl) [1- (2. {[[(2-chloro-3-quinolinyl) -methyl] amino] .) ethyl) -4-piperidinyl] methanone, (4-chlorophenyl) [1- (2. {[[(6-methyl-2-pyridinyl) -methyl] amino}. ethyl) -4-piperidinyl] methanone, (4-chlorophenyl) (l- { 2- [(3-quinolinylmethyl) amino] -ethyl} -4-piperidinyl) methanone, 4- [(. {2 - [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl] -amino) methyl] -1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one, (4 chlorophenyl) (l- { 2- [(4-pyridinylmethyl) amino] -ethyl} -4-piperidinyl) methanone, (4-chlorophenyl) (1- {2 - [(3-hydroxy) 4-Nitrobenzyl) -amino] ethyl.} -4-piperidinyl) methanone, (4-chlorophenyl) (1 -. {2- [(3,5-difluorobenzyl) amino] -ethyl} -4-piperidinyl ) methanone, (1- { 2- [(2-chloro-6-fluorobenzyl) amino] ethyl} -4-piperidinyl) (4-chlorophenyl) methanone, [1- (2- { [( 4-bromo-lH-pyrazol-3-yl) methyl] amino.}. -ethyl) -4-piperidinyl] (4-chlorophenyl) methanone, 3- [(. {2- 2- [4- (4-chlorobenzoyl)] -l-piperidinyl] ethyl.}. -amino) methyl] -6,7-dimethyl-4H-chromen-4-one, 2- acid. { 2- [( { 2- [4- (4-chlorobenzoyl) -1-piperidinyl] ethyl} amino) methyl] -4-nitrophenoxy} acetic acid, (4-chlorophenyl) [1- (2. {[[(1-methyl-1H-benzimidazol-2-yl) methyl] amino] ethyl) -4-piperidinyl] methanone, (4-chlorophenyl) [1- (2-. {[[(2,4-dimethoxy-5-pyrimidinylmethyl] amino]} ethyl) -4-piperidinyl] methanone, N- { 2- [4- (3,4-dichlorophenoxy ) -l-piperidinyl] ethyl.} -4- (methylamino) benzamide, 4-chloro-N- { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl.} -3 -methoxybenzamide, N- { 2- [4- (3, 4-dichlorophenoxy) -l-piperidinyl] ethyl}. 3-methoxy-4-methylbenzamide, 3-amino-N-. {2- [4 - (3,4-dichlorophenoxy) -1-piperidinyl] ethyl.} -4-methoxybenzamide, N- { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl}. 3-benzodioxol-5-carboxamide, 4-amino-N-. {- 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-methoxybenzamide, N-. {2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl] -3-fluoro-4-methoxybenzamide, 5-bromo-N-. {2- [4- (3,4-dichlorophenoxy) - 1-piperidinyl] ethyl.} -2-furamide, N- { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - 3 -meti1-2-furamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4, 5-dimethyl-2-furamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -7-ethoxy-1-benzofuran-2 -carboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -5-methoxy-1-benzofuran-2-carboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -7-methoxy-1-benzofuran-2-carboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2- (4-fluorophenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2- (2-methoxyphenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2- (3-methylphenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2- (2-methylphenyl) acetamide, 2- (3-bromophenyl) -N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} acetamide, 2- (2-chlorophenyl) -N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} acetamide, 2- (4-chlorophenyl) -N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - 2- [2- (trifluoromethyl) phenyl] acetamide, 2- (3-chlorophenyl) -N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- (3, 4-dimethoxyphenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- (4-methoxyphenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- (3,4-dichlorophenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2- (3-fluoro-4-methoxyphenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2- (4-ethoxyphenyl) acetamide, 2- (1, 3-benzodioxol-5-yl) -N-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl} acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- [4- (dimethylamino) phenyl] acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- (4-methylphenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- (3, 4-difluorophenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- (3-methoxyphenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - 4-phenylbutanamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -3-phenylpropanamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -3- (3-methoxyphenyl) propanamide, 2 -Amino-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -1, 3-thiazole-4-carboxamide, 2- (acetylamino) -N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -1, 3-thiazole-4-carboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- (4-pyridinyl) -1,3-thiazole-4-carboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2,4-dimethyl-l, 3-thiazole-5-carboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - 2,5-dimethyl-l, 3-oxazole -4 -carboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -1H- imidazole -4 -carboxamide, N- hydrochloride salt. { 2- [4- (3,4-chlorophenoxy) l-piperidinyl] ethyl} -3-methoxybenzamide, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -1-methyl -1H-pyrazolo [3,4-d] pyrimidin-4-amino, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -2, 6-dimethoxy-4-pyrimidinamine, N-4-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -N-2-N-2-dimethyl-2,4-pyrimidinediamine, N-. { 3- [4- (3,4-dichlorophenoxy) -1-piperidinyl] propyl} -2- [(methylsulfanyl) ethyl] -4-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -2- (methylsulfanyl) -6- (trifluoromethyl) -4-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -5-methoxy-2- (methylsulfanyl) -4-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -6-methyl-2- (methylsulfanyl) -4-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -5-methoxy-2-methyl-4-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -2- (ethylsulfanyl) -6-methyl-4-pyrimidinamine, N-2-cyclopropyl-N-4-. { 3- [4- (3,4-dichlorophenoxy) -1-piperidinyl] propyl} -2, 4-pyrimidindiamine, 2-. { [4- ( { 3- [4- (3, 4-dichlorophenoxy) -l-piperidinyl] -propyl.} Amino) -2-pyrimidinyl] amino} -1-ethanol, 2- [[4- ( { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} amino) -2-pyrimidinyl] (methyl) amino] - 1-ethanol, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -2- (methylsulfanyl) -4-pyrimidinamine, N-4-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -6-methyl-2, 4-pyrimidindiamine, N-4-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -N-2, 6-dimethyl-2, 4-pyrimidindiamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -4-phenyl-2-pyrimidinamine, N-2-. { 3- [4- (3, 4-dichlorophenoxy) -l-piperidinyl] -propyl} -5-fluoro-2, 4-pyrimidindiamine, N-2-. { 3- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] -propyl} -N-4-N-4,6-trimethyl-2,4-pyrimidinediamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl-4- (trifluoromethyl) -2-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl-4- (propylsulfanyl) -2-pyrimidinamine, N-2-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl-N-4-phenyl-2,4-pyrimidinediamine, N-2-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl-N-4,6-dimethyl-2,4-pyrimidinediamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl [1,8) naphthyridin-2-amine, 2-. { [2- ( { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl amino) -4-pyrimidinyl] amino} -1-ethanol. 2- [[2- ( { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl amino) -4-pyrimidinyl (methyl) amino] -1-ethanol, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl-4- (3-pyridinyl) -2-pyrimidinamine, N-. { 3- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] -propyl-4- (3-thienyl) -2-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl-2-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl -4,6-dimethoxy-2-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl-4- (3-furyl) -2-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -4- (2-thienyl) -2-pyrimidinamine, N-. { 3- [4- (3, 4-dichlorophenoxy) -l-piperidinyl] -propyl lH-purin-6-amine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl 5-methylthieno [2,3-d] pyrimidin-4-amine, N-. { 3- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] -propyl 7-methylthieno [3,2-d] pyrimidin-4-amine, N-7-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl 5-methyl [1,3] thiazolo [4,5-d] pyrimidin-2,7-diamine, N-. { 3- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] -propyl 9-methyl-9H-purin-6-amine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -2-pyridinamine, 5-chloro-N-. { 3- [4- (3,4-dichlorophenoxy) -1-piperidinyl] propyl} -2-pyridinamine, 6-chloro-N-. { 3- [4- (3,4-dichlorophenoxy) -1-piperidinyl] propyl} -2-pyridinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -6-methyl-2-pyridinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -1, 3-benzothiazol-2-amine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl] -1,3-benzoxazol-2-amine, 6-chloro-N-. { 3- [4- (3,4-dichlorophenoxy) -1-piperidinyl] propyl} -2-pyrazinamine, 6-chloro-N-. { 3- [4- (3,4-dichlorophenoxy) -1-piperidinyl] propyl} -3-pyridazinamine, 6- ( { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl.} Amino) -1,3-dimethyl-2,4 (1H, 3H) -pyrimidinedione, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2, 6-dimethoxy-4-pyrimidinamine, N-4-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -N-2-N-2-dimethyl-2,4-pyrimidinediamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- [(methylsulfanyl) methyl] -4-pyrimidinamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -5-methoxy-2- (methylsulfanyl) -4-pyrimidinamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - 6-methyl-2- (methylsulfanyl) -4-pyrimidinamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -5-methoxy-2-methyl-4-pyrimidinamine, and N-4-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -6-methyl-N-2-phenyl-2,4-pyrimidindiamine. The present invention further provides a process for the preparation of a compound of the formula (I) comprising: (i) when T represents a C (0) NH group, a compound of the general formula R1 - (Q) is reacted m -COL1 (II) where L1 represents a leaving group (for example, a hydroxyl group or halide, such as chloride) and R1, m and Q are as defined in formula (I), with a compound of the general formula H2N- (CR2R3) n-V G? W-X-R (III) or a salt by addition of the acid thereof (eg, trifluoroacetate) wherein n, R 2, R 3, V, X and R 4 are as defined in formula (I); or (ii) when T represents a C (0) NH group and W represents a nitrogen atom, a compound of the general formula is reacted R Q) m-T- (CR 3R33) n-VX NH (IV) where R1, m, Q, T, n, R2, R3 and V are as defined in formula (I), with a compound of the general formula L2-X-R4 (V) where L2 represents a leaving group (per example, a halogen atom) and X and R4 are as defined in formula (I); or (iii) when T represents an NH group and m is 0, a compound of the general formula is reacted R1 - L3 (vi; where L3 represents a leaving group (eg, a halogen atom) and R1 is as defined in formula (I), with a compound of formula (III) as defined in subparagraph (i) above; or (iv) when T represents an NH group, m is 1 and Q represents alkylene of 1 to 4 carbon atoms, by reacting a compound of the general formula R1 - (CH2) P -CHO (VII) wherein p is 0, 1, 2 or 3 and R1 is as defined in formula (I), with a compound of formula (III) as defined in subparagraph ( i) previous; or (v) when T represents a bond and m is 0, a compound of the general formula R1 - (CRR3) n-L4 (VIII) is reacted where L4 represents a leaving group such as a halogen atom (eg, chlorine) and n, R1, R2 and R3 are as defined in formula (I), with a compound of the general formula ~ \. HN -X-R4 (IX) where, X and R4 are as defined in the formula (i); and optionally after (i), (ii), (iii), (iv) or (v) the compound of the formula (I) is converted to a further compound of the formula (I) and / or a salt is formed or pharmaceutically acceptable solvate of the compound of the formula (I). The processes of the invention can conveniently be carried out in a solvent, for example, an organic solvent such as dimethylformamide or dichloromethane at a temperature for example of 15 ° C. or higher, such as a temperature in the range of 20 to 100 ° C.

The compounds of the formula (III) in which represents a nitrogen atom can be prepared by the reaction of a compound of the general formula wherein R2, R3 and V are as defined in formula (I) with a compound of formula (V) as defined above. The compounds of the formula (X) can be prepared by the reaction of the piperazine with a compound of the general formula H2? - (CR2R3) n-L5 (XI) where L5 represents a halogen atom such as a bromine atom and n, R2 and R3 are as defined in formula (I). The compounds of the formula (III) in which W represents a group CH and X represents an oxygen atom, can be prepared by the reaction of a compound of the general formula (XII) wherein R4 is as defined in formula (I), with a compound of formula (XI). The compounds of the formula (XII) can be prepared by the reaction of the 4-piperidinol with a compound of the general formula (XIII), R 4 -OH, where R 4 is as defined in the formula (I), in the presence of a coupling agent such as diethyl azodicarboxylate and triphenylphosphine and in a solvent such as benzene or tetrahydrofuran at a temperature typically in the range of 20 to 30 ° C. The compounds of the formula (III) in which represents a group CH and X represents a group C (0) can be prepared by the reaction of a compound of the general formula (XIV) where R4 is as defined in formula (I), with a compound of formula (XI). The compounds of the formula (III) in which represents a group CH and X represents a group CH (OH) can be prepared by reduction / hydrogenation of a corresponding compound of the formula (III), in which X represents C ( 0) using techniques known in the art. The compounds of the formula (III) in which W represents a group CH and X represents an NH group, can be prepared by the reaction of a compound of the general formula (XV) wherein R4 is as defined in formula (I), with a compound of formula (XI). The compounds of the formula (XV) can be prepared by the reaction of 4-piperidone with a compound of the general formula (XVI), R 4 -NH 2, wherein R 4 is as defined in the formula (I), in the presence of a reducing agent such as sodium cyanoborohydride or sodium borohydride and in a solvent such as methanol or benzene at a temperature typically in the range of 20 to 90 ° C. The compounds of the formula (III) in which represents a group CH and X represents a group N (alkyl of 1 to 6 carbon atoms) can be prepared by the alkylation of a corresponding compound of the formula (III) in which X represents an NH group, using conventional techniques in the art. The compounds of the formula (IV) can be prepared by the reaction of a compound of the formula (II) with a compound of the formula (X). The compounds of formulas II, V, VI, VII, VIII, IX, XI, XIV and XVI are either commercially available, or are well known in the literature or can be prepared easily using known techniques. The compounds of the formula (I) can be converted to additional compounds of the formula (I) using standard procedures. For example, the compounds of the formula (I) in which R 1 represents a phenyl group substituted with alkoxy can be converted to the compounds of the formula (I) in which R 1 represents a phenyl group substituted with hydroxyl, by reaction with tribromide of boron in a solvent such as dichloromethane. In addition, the compounds of the formula (I) in which X represents C (0) can be converted to compounds of the formula (I) in which X represents CH (OH) by reaction with triethylsilane and trifluoroacetic acid in a solvent such as as dichloromethane.

It will be appreciated by those skilled in the art that in the processes of the present invention certain functional groups such as hydroxyl groups or amino groups in. the initial reagents or in the intermediary compounds, they may need to be protected by protective groups. Thus, the preparation of the compounds of the formula (I) may involve, at an appropriate stage, the removal of one or more protecting groups. The protection and deprotection of the functional groups are described in "Protective Groups in Organic Chemistry", edited by J.F. McOmie, Plenum Press (1973) and Protective Groups in Organic Synthesis, 2nd edition, TW Greene and PGM Wuts. , Wiley-Interscience (1991) The compounds of formula (I) above can be converted to a pharmaceutically acceptable salt or solvate thereof, preferably an acid addition salt such as hydrochloride, hydrobromide, phosphate, acetate, fumarate, maleate, tartrate, citrate, oxalate, methanesulfonate or p-toluenesulfonate Certain compounds of the formula (I) are capable of existing in stereoisomeric forms It will be understood that the invention encompasses the use of all geometric and optical isomers of the compounds of the invention. Formula (I) and mixtures thereof including racemates The use of tautomers and mixtures thereof also forms an aspect of the present invention The compounds of formula (I) have activity of pharmaceutical products, in particular, as modulators of chemokine receptor activity (especially CCR1 and / or CCR3) and can be used in the treatment of autoimmune, inflammatory, proliferative and hyperproliferative diseases and in immunologically mediated diseases, including rejection of transplanted organs or tissues and Acquired Immune Deficiency Syndrome (AIDS). Examples of these conditions are: (1) (the respiratory tract) obstructive airway diseases including chronic obstructive pulmonary disease (COPD) such as irreversible COPD; asthma, such as bronchial, allergic, intrinsic, extrinsic and dust asthma, particularly chronic or inveterate asthma (eg, late asthma and hyper-responsiveness of the respiratory tract); bronchitis, atrophic rhinitis, allergic, acute and chronic rhinitis including rhinitis caseosa, hypertropic rhinitis, purulent rhinitis, dry rhinitis, rhinitis medicamentosa; Membranous rhinitis including croupy rhinitis, fibrinous rhinitis, pseudomembranous rhinitis and scrofulous rhinitis; seasonal rhinitis including rhinitis nervosa (hay fever) and vasomotor rhinitis; sarcoidosis, farmer's lung diseases and related diseases, idiopathic interstitial pneumonia and fibroid pulmonary. (2) (bones and joints) rheumatoid arthritis, seronegative spondyloarthropathies (including ankylosing spondylitis, psoriatic arthritis and Reiter's disease), Behcet's disease, Sjogren's syndrome and systemic sclerosis. (3) (skin) psoriasis, atopic dermatitis, contact dermatitis and other eczematous dermatitis, seborrheic dermatitis, lichen planus, pemphigus, pemphigus bullosa, epidermolysis bullosa, urticaria, angioderma, vasculitides, erythema, cutaneous eosinophilia, uveitis, alopecia areata and conjunctivitis vernal; (4) (gastrointestinal tract) Celiac disease, proctitis, eosinophilic gastro-enteritis, mastocytosis, Crohn's disease, ulcerative colitis, food-related allergies that have remote effects of the intestine, for example, migraine, rhinitis and eczema; (5) (other tissue and systemic diseases) multiple sclerosis, atherosclerosis, Acquired Immunodeficiency Syndrome (AIDS), lupus erythematosus, systemic lupus erythematosus, Hashimoto's thyroiditis, myasthenia gravis, type I diabetes, nephrotic syndrome, eosinophilia fasciitis, eosinophilia syndrome, hyper-IgE, lepromatous leprosy, Sezary's syndrome and idiopathic thrombocytopenic purpura; and (6) (allograft rejection) acute and chronic, for example, after transplantation of kidney, heart, liver, lung, bone marrow, skin and cornea; and chronic graft versus host disease. Thus, the present invention provides a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as defined hereinbefore for use in therapy. In a further aspect, the present invention provides the use of a compound of the formula (I), or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore defined in the manufacture of a medicament for use in therapy. In the context of the present specification, the term "therapy" also includes "prophylaxis" unless there are specific indications to the contrary. The terms "therapeutic" and "therapeutically" should be considered accordingly. The invention also provides a method for treating an inflammatory disease in a patient suffering from, or at risk of, said disease, comprising administering to the patient a therapeutically effective amount of a compound of the formula (I), or a salt or pharmaceutically acceptable solvate thereof, as defined hereinbefore. For the therapeutic uses mentioned above, the dose administered will of course vary with the compound employed, the mode of administration, the treatment desired and the disorder indicated. The compounds of the formula (I) and the pharmaceutically acceptable salts and solvates thereof can be used by themselves but in general will be administered in the form of a pharmaceutical composition in which the compound / salt / solvate of the formula (I) ) (active ingredient) is in association with a pharmaceutically acceptable adjuvant, diluent or carrier. Depending on the mode of administration, the pharmaceutical composition will preferably comprise from 0.05 to 99% by weight (% p), more preferably from 0.05 to 80% by weight, still more preferably from 0.10 to 70% by weight, and even more preferably from 0.10. to 50% by weight, of active ingredient, all percentages by weight are based on the total composition. The present invention also provides a pharmaceutical composition comprising a compound of the formula (I), or a pharmaceutically acceptable salt or solvate thereof, as defined hereinbefore, in association with a pharmaceutically acceptable adjuvant, diluent or carrier. The invention further provides a process for the preparation of a pharmaceutical composition of the invention, comprising the mixture of a compound of the formula (I), or a pharmaceutically salt or solvate thereof, as defined hereinbefore, with a pharmaceutically acceptable adjuvant, diluent or carrier. The pharmaceutical compositions can be administered topically (for example to the lung and / or the respiratory tract or to the skin) in the form of solutions, suspensions, heptafluoroalkane aerosols and dry powder formulations, - or systemically, for example, by oral administration in the form of tablets, capsules, syrups, powders or granules, or by parenteral administration in the form of solutions or suspensions, or by subcutaneous administration or by rectal administration in the form of suppositories or transdermally. The invention will now be further explained by reference to the following illustrative examples.

Example 1 4-Chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2- [2- (dimethylamino) -2-oxoethoxy] benzamide (i) tert-butyl 4- (3,4-dichlorophenoxy) -1-piperidinecarboxylate (12.6 ml) of diethyl azodicarboxylate was added to a solution of 20.8 g of triphenylphosphine in 300 ml of tetrahydrofuran at 0 ° C. After 15 minutes 12.9 g of 3,4-dichlorophenol were added, after an additional 10 minutes 14.5 g of tert-butyl 4-hydroxy-l-piperidinecarboxylate in 100 ml of tetrahydrofuran were added dropwise in 0.5 hours. The solution was stirred at room temperature for 5 hours and concentrated to a small volume. The residue was partitioned between ether and brine. The organic phase was separated, dried and evaporated to a gum. Purification by chromatography (ethyl acetate: isohexane 95: 5) gave the subtitle product as an oil (20 g). Mass Spectrum (MS): APCI (+ ve): 246 (M-BOC + 2H) (ii) 4- (3,4-dichlorophenoxy) piperidine The product of step (i) was dissolved in 200 ml of dichloromethane and 100 ml of trifluoroacetic acid was added. After 18 hours at room temperature, the solution was evaporated and the resulting gum was triturated with ether to give the subtitle product as a solid (16.2 g). (iii) Tert-Butyl 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethylcarbamate The product from step (ii) (6.55 g) was dissolved in 50 ml of DMF and 7.9 ml of triethylamine were added. 4.3 g of tert-butyl 2-bromoethylcarbamate in 5 ml of DMF were added and the solution was stirred at room temperature for 3 days. Ethyl acetate and water were added, the organic phase was separated, dried and evaporated to a gum. Purification by chromatography (dichloromethane: methanol 95: 5) gave the subtitle product as a gum (5.7 g). Mass Spectrum (MS): APCl (+ ve): 389 (M + H) (iv) 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethylamine trifluoroacetate The product of step (iii) is dissolved in 200 ml of dichloromethane and 100 ml of trifluoroacetic acid were added. After 18 hours at room temperature, the solvent was evaporated and the resulting gum was triturated with ether to give the subtitle product as a solid product (5.7 g). Mass Spectrum (MS): APCI (+ ve): 290 (M + H) (v) 2- (dimethylamino) -2-oxoethyl 4-chloro-2- [2- (dimethylamino) -2-oxoethoxy] benzoate A mixture of 5 g of 4-chloro-2-hydroxybenzoic acid, 17.5 g of carbonate of cesium and 6.6 g of 2-chloro-N, N-dimethylacetamide were stirred and heated to 70 ° C. For 3 hours. Water and ethyl acetate were added, the organic phase was separated, and then concentrated to a gum, which was purified by chromatography (ethyl acetate: methanol, 9: 1) to give the subtitle product as a solid ( 8.0 g). Mass Spectrum (MS): APCI (+ ve) 343 (M + H) Melting Point: 140-141 ° C. (vi) 4-chloro-2- [2- (dimethylamino) -2-oxoethoxy] benzoic acid One gram of the product from step (v) was dissolved in a 15 ml mixture of 2: 1 aqueous methanol and LiOHH »H20 was added. . After 2 hours they were added to an aqueous solution of 2 M HCl and ethyl acetate, the organic phase was separated, separated and concentrated to give the subtitle product as a solid (1.2 g). Mass Spectrum (MS): APCI (+ ve) 258 (M + H) Melting point: 141-142 ° C. (vii) 4-chloro-N-. { 2- [4- (3,4-Dichlorophenoxy) -1-piperidinyl] ethyl} -2- [2- (dimethylamino) -2-oxoethoxy] benzamide 0. 3 g of the product from step (vi) and 0.19 g of N, N-carbonyldiimidazole was dissolved in 20 ml of DMF and the solution was stirred at room temperature for 1 hour. The product of step (iv) (0.42 g) and 0.32 ml of triethylamine were added. After 20 hours water and ether were added, the organic phase was separated, then concentrated to a gum which was purified by chromatography (dichloromethane: methanol, 93: 7) to give the title product as a solid (0.38 g. ). Mass Spectrum: ESI 528.12 (M + H) RMN'H: d (DMSO) 9.17 (t, lH), 7.88 (d, lH), 7.48 (d, lH), 7.38 (d, lH), 7.24 (d , lH), 7.13 (dd, 1H), 6.99 (dd, 1H), 5.11 (S, 2H), 4.32 (m, 1H), 3.42 (m, 2H), 2.99 (s, 3H), 2.88 (s, 3H), 2.73 (m, 2H), 2.50 (m, 2H), 2.30 (m, 2H), 1.90 (m, 2H), 1.59 (m, 2H). Fusion Point: 139-40 ° C.

Example 2 N- Hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3- ethoxybenzamide 0. 4 g of the product of Example 1 step (iv) were dissolved in 10 ml of DMF, 0.541 g of PyBrop, 0.167 g of 3-ethoxybenzoic acid and 0.5 g of N, N-diisopropylethylamine were added. After 18 hours at room temperature, chloroform and an aqueous solution of sodium hydrogen carbonate were added. The organic phase was separated, dried and concentrated to leave a gum which was purified by chromatography (ethyl acetate: methanol 97: 3) to give an oil. Addition of 1.0 M ethereal hydrogen chloride solution gave the title product as a solid (0.14 g). Mass Spectrum (MS): ESI 437.14 (M + H) NMR1 !!: d (DMSO) 8.87 (broad s, 1H), 7.50 (m, 3H), 7. 40 (m, 2H), 7.06 (m, 2H), 4.83 / 4.62 (m, 1H), 4.08 (q, 2H), 3. 67 (m, 3H), 3.17 (m, 3H), 2.20 (m, 2H), 2.03 (m, 2H), 1.34 (t, 3H) Melting point: 191-193 ° C: Example 3 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4-isopropoxybenzamide Prepared by the same method with Example 2, using 4-isopropoxybenzoic acid without the addition of the 1.0 M hydrogen chloride ether solution to give the title product as a solid (0.12 g). Mass Spectrum: ESI 451.14 (M + H) RMN ^ H: d (DMSO) 8.22 (t, lH), 7.8 (m, 2H), 7.49 (d, lH), 7.25 (d, lH), 7.00 (m, 3H), 4.7 (m, 1H), 4.45 (m, 1H), 3.36 (m, 2H), 2.73 (m, 2H), 2.48 ( m, 2H), 2.29 (m, 2H), 1.91 (m, 2H), 1.60 (m, 2H), 1.28 (s, 3H), 1.27 (s, 3H) Melting point: 113-15 ° C.

Example 4 N-. { 2 - [4- (3,4-dichloro-enoxy) -l-piperidinyl] ethyl} 4-ethoxybenzamide Prepared by the same method as in Example 2, using 4-ethoxybenzoic acid without the addition of the l.O M hydrogen chloride ether solution to give the title product as a solid (0.1 g). MS: ESI 437.14 (M + H) XH NMR: d (DMSO) 8.22 (t, 1H), 7.79 (d, 2H), 7.49 (d, 1H), 7.25 (d, 1H), 7.00 (m, 3H) , 4.5 (m, 1H), 4.07 (q, 2H), 3.37 (q, 2H), 2.73 (m, 2H), 2.47 (m, 2H), 2.30 (m, 2H), 1.91 (m, 2H), 1.60 (m, 2H), 1.34 (t, 3H). Melting point: 118-20 ° C Example 5 N- Hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3- (trifluoromethoxy) benzamide Prepared by the same method as in Example 2, using 3-trifluoromethoxybenzoic acid to give the title product as a solid (0.12 g). MS: ESI 477.09 (M + H) NMR U: d (DMSO) 10.42 (broad s, 1H), 9.11 (broad m, 1H), 8.0 (d, 1H), 7.888 (s, 1H), 7.6 (m, 3H), 7.37 (m, 1H), 7.06 (m, 1H), 4.70 (m, 1H), 3.71 (m, 3H), 3.48 (d, 1H), 3.20 (m, 4H), 2.2 (m, 4H) ). Melting point: 180-82 ° C Example 6 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - 4-methoxybenzamide Prepared by the same method as in Example 2, using 4-methoxybenzoic acid without the addition of the 1.0 M hydrogen chloride ether solution to give the title product as a solid (0.11 g). MS: ESI 423.12 (M + H) NMR E: d (DMSO) 8.42 (t, 1H), 7.81 (m, 2H), 7.49 (d, 1H), 7.25 (d, 1H), 6.98 (s, 3H) , 4.4 (m, 1H), 3.8 (s, 3H), 3.35 (q, 2H), 2.73 (m, 2H), 2.47 (m, 2H), 2.30 (m, 2H), 1.91 (m, 2H), 1.60 (m, 2H). Melting point: 110-12 ° C Example 7 N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -4- (trifluoromethoxy) benzamide Prepared by the same method as in the Example 2, using 4-trifluoromethoxybenzoic acid to give the title product as a solid (0.19 g). MS: ESI 477 (M + H) X H NMR: d (DMSO) 10.5 (broad s, 1H), 9.06 (m, 1H), 8.07 (dd, 2H), 7.55 (t, 1H), 7.49 (d, 2H ), 7.36 (dd, 1H), 7.10-7.02 (m, 1H), 4.72 (m, 1H), 3.70 (m, 3H), 3.47 (d, 1H), 3.14 (m, 2H), 2.25 (m, 2H), 2.02 (m, 2H). Melting point: 184-187 ° C Example 8 N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2-furamide Prepared by the same method as in Example 2, using furan-2-carboxylic acid to give the title product as a solid (0.14 g). MS: ESI 383.09 (M + H) 1 H NMR: d (DMSO) 10.43 (broad m, 1H), 8.76 (t, 1H), 7.87 (s, 1H), 7.55 (t, 1H), 7.36 (dd, 1H ), 7.21 (d, 1H), 7.06 (m, 1H), 6.64 (dd, 1H), 4.83-4.61 (m, 1H), 3.65 (m, 3H), 3.45 (d, 1H), 3.08 (m, 4H), 2.1 (m, 4H). Melting point: 225-28 ° C Example 9 N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2-phenylacetamide Prepared by the same method as in Example 2, using phenylacetic acid to give the title product as a solid (0.12 g). MS: ESI 407 (M + H) 1 H NMR: d (DMSO) 10.28 (broad m, 1H), 8.46 (broad m, 1H), 7.56 (t, 1H), 7.3 (m, 6H), 7.10 (m, 1H), 4.81 / 4.58 (m, 1H), 3.58 (d, 1H), 3.46 (m, 4H), 3.10 (m, 4H), 2.15 (m, 5H). Melting point: 135-38 ° C Example 10 N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-methoxybenzamide The product of Example 1 step (vi) (2.0 g) was dissolved in 490 ml of dichloromethane, and 1.85 ml of triethylamine and 0.66 g of 3-methoxybenzoyl chloride were added. After 72 hours at room temperature, water was added, the organic phase was separated, dried and concentrated to give a gum. The product was dissolved in dichloromethane and treated with ethereal hydrogen 1.0 M solution to give the title product as a solid (0.88 g). MS: ESI 423.12 (M + H) 1 H NMR: d (DMSO) 10.6-10.5 (m, 1H), 9.92 (s, 1H), 7. 54 (m, 3H), 7.38 (m, 2H), 7.08 (m, 2H), 4.84 / 4.62 (m, 1H), 3.82 (s, 3H), 3.45 (m, 8H), 2.27 (m, 4H) . Melting point: 72-73 ° C Example 11 3-chloro-N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} benzamide The product from Example 11 step (iv) (0.15 g) was dissolved in 3 ml of dimethylformamide, and 0.3 ml of N, N-di-isopropylethylamine and 0.054 ml of 3-chlorobenzoyl chloride were added. After 2 hours at room temperature, water and ethyl acetate were added, the organic phase was separated, dried and concentrated. The residue was purified by chromatography (dichloromethane: methanol, 95: 5) to give an oil which was dissolved in ether and 1.0 M hydrogen chloride ether solution to give the title product as a solid (0.12 g). MS: ESI 427.07 (M + H) 1 H NMR: d (DMSO) 8.42 (t, 1H), 7.94-7.84 (m, 2H), 7.49 (d, 1H), 7.29 (m, 3H), 6.98 (dd, 1H), 4.44 (m, 1H), 3.36 (m, 2H), 2.74 (m, 2H), 2.48 (m, 2H), 2.29 (broad t, 2H), 1.92 (m, 2H), 1.60 (m, 2H). Melting point: 118 ° C Example 12 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4-fluorobenzamide Prepared by the same method as in the Example 11, using 4-fluorobenzoyl chloride without the addition of the 1.0 M hydrogen chloride ether solution to give the title product as a solid (0.1 9) - MS: ESI 411.10 (M + H) 1 H NMR: d (DMSO) 10.46 (broad s, 1H), 9.04 (s, 1H), 7.98 (s, 1H), 7.90 (d, 1H), 7.58 ( m, 3H), 7.36 (dd, 1H), 7.05 (m, 1H), 4.84 / 4.60 (m, 1H), 3.69 (m, 3H), 3.48 (broad d, 1H), 3.20 m, 4H), 2.15 (m, 4H). Melting point: 192 ° C Example 13 N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-fluorobenzamide Prepared by the same method as in Example 11, using 3-fluorobenzoyl chloride to give the title product as a solid (0.09 g). MS: ESI 411.10 (M + H) 1 H NMR: d (DMSO) 10.67 (broad s, 1H), 9.06 (s, 1H), 7.80 (m, 2H), 7.55 (m, 2H), 7.40 (m, 2H) ), 7.05 (m, 1H), 4.84 / 4.63 (m, 1H), 3.70 (m, 3H), 3.28 (m, 3H), 2.20 (m, 4H).

Melting point: 225 ° C Example 14 N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-hydroxybenzamide The product of Example 10 (0.15 g) was dissolved in 10 ml of dichloromethane and a solution of 1.0 M BBr3 in 4 ml of dichloromethane was added. After 16 hours at room temperature, the solvent was removed by evaporation, methanol was added and the solution was concentrated. The residue was dissolved in 2 M aqueous hydrochloric acid solution, concentrated to dryness and the residue was triturated under ether to give the title product as a solid (0.1 g). MS: ESI 409.10 (M + H) 1 H NMR: d (DMSO) 9.98-9.4 (broad s, 2H), 8.71 (t, 1H), 7.6 (dd, 1H), 7.4-7.2 (m, 4H), 7.05. (m, 1H), 6.95 (dd, 1H), 4.65 (m, 1H), 3.40 (m, 8H), 2.0 (m, 4H). Melting point: 83-4 ° C Example 15 N- hydrochloride. { 2- [4- (4-chlorobenzoyl) -1-piperidinyl] ethyl} -3- [2- (Methylamino) -2-oxoethoxy] benzamide (i) [1- (2-aminoethyl) -4-piperidinyl] (4-chlorophenyl) methanone trifluoroacetate To a solution of 2.5 g of (4-chlorophenyl) (4-piperidinyl) methanone hydrochloride and 2.1 g of 2- tert-butyl bromoethylcarbamate in dimethylformamide was added 2.9 g of triethylamine, after 72 hours at room temperature water and ether were added. The organic phase was separated, dried and concentrated. The residue was dissolved in 40 ml of dichloromethane, 10 ml of trifluoroacetic acid were added and the solution was allowed to stand for 20 hours. Evaporation of the solvent gave a sticky solid which was triturated with ether to give the subtitle product as a solid (2.5 g). (ii) N- hydrochloride. { 2- [4- (4-chlorobenzoyl) -1-piperidinyl] ethyl} -3-methoxybenzamide The product of step (i) (2.5 g) was dissolved in 20 ml of dichloromethane, 0.75 ml of triethylamine and 0.276 g of 3-methoxybenzoyl chloride were added. After 16 hours, water was added, the organic phase was separated, dried and concentrated to a gum. Purification by chromatography (ethyl acetate) gave a gum, which was treated with 1.0 M ethereal hydrogen chloride solution to give the subtitle product as a solid (0.3 g). MS: ESI 401.16 (M + H) 1 H NMR: d (DMSO) 10.3 (broad m, 1H), 8.95 (t, 1H), 8.0 (m, 2H), 7.6 (m, 2H), 7.5 (m, 2H ), 7.4 (t, 1H), 7.05 (m, 1H), 3.8 (s, 3H =, 3.68 (m, 4H), 3.28 (m, 5H), 2.0 (m, 4H) Melting point: 196- 7 ° C (iii) N- hydrochloride. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -3-hydroxybenzamide Prepared by the method of Example 14, using the product of step (ii) above (0.24 g) to give the subtitle product as a solid (0.20 g). MS: ESI 387.14 (M + H) 1 H NMR: d (DMSO) 8.62 (t, 1H), 8.05 (dd, 2H), 7.6 (dd, 2H), 7.25 (m, 3H), 6.95 (m, 1H) , 4.26 (m, 9H), 2.0 (m, 4H). Melting point: 90-91 ° C (iv) N- hydrochloride. { 2- [4- (4-chlorobenzoyl) -1-piperidinyl] ethyl} -3- [2- (Methylamino) -2-oxoethoxy] benzamide The product of step (iii) above (0.10 g) was dissolved in 3 ml of dimethylformamide, 0.23 g of cesium carbonate and 0.26 g of 2-chloro were added. -N-methylacetamide and the mixture was heated at 80 ° C for 16 hours. The mixture was cooled to room temperature, water and ethyl acetate were added, and the organic phase was separated. Evaporation of the solvent gave a gum which was treated with an ethereal 1.0 M hydrogen chloride solution to give the title product as a solid (0.05 g). MS: ESI 458.18 (M + H) 1 H NMR: d (DMSO) 10.6-10.2 (broad m, 1H), 8.95 (broad m, 1H), 8.1 (m, 2H), 7.55 (m, 8H), 7.14 ( d broad, 1H), 4.54 (s, 2H), 4.0 (m, 1H), 3.4 (m, 8H), 2.65 (d, 3H), 2.0 (m, 4H). Melting point: 69-70 ° C Example 16 2- [3-. { 2- [4- (4-fluorobenzoyl) -1-piperidinyl] ethyl} -2,4-dioxo-3, 4-dihydro-l (2H) quinazolinyl-N, N-dimethylacetamide The 3-. { 2- [4- (4-fluorobenzoyl) -l-piperidinyl] ethyl} -2,4 (1H, 3H) -quinazolindione was dissolved in 5 ml of dimethylformamide and sodium hydride (60% dispersion in mineral oil) was added. After 0.5 hours, 2-chloro-N, N-dimethylacetamide was added and the solution was stirred at room temperature for 16 hours. Water and ethyl acetate were added, the organic phase was separated, dried and concentrated to an oil. Purification by chromatography (dichloromethane: methanol 95: 5) gave an oil which was treated with 1.0 M ethereal hydrogen chloride solution to give the title compound as a solid (0.015 g). MS: ESI 481.22 (M + H) XH NMR: d (DMSO) 8.08 (m, 3H), 7.76 (t, 1H), 7.40 (t, 2H), 7.32 (m, 2H), 5.05 (s, 2H) , 4.36 (m, 1H), 3.76 (m, 3H), 3.39 (m, 2H), 3.15 (s, 3H), 2.87 (s, 3H), 2.02 (m, 2H), 1.81 (, 2H), 1.28 (m, 2H). Melting point: 245-246 ° C Example 17 N- hydrochloride. { 2- [4- (3,4-dichlorobenzoyl) -1-piperazinyl] ethyl} -3-methoxybenzamide (i) tert-butyl 2- (l-piperazinyl) ethylcarbamate A mixture of 21 g of benzaldehyde and 25.8 g of 1- (2-aminoethyl) piperazine was stirred and heated under a Dean and Stark water separator for 20 hours. The cooled solution was treated in portions with 48 g of di-tert-butyl dicarbonate, was stirred for 72 hours and concentrated. The residue was treated with 220 ml of an aqueous solution of 1 M potassium hydrogen sulfate, stirred for 24 hours, ether was added and the organic phase was separated. The aqueous phase was treated with a 2M sodium hydroxide solution, dichloromethane was added and the organic phase was separated.

The combined organic phase was washed with brine, dried and concentrated to give the subtitle product as an oil (30 g). MS: APCl (+ ve) 230 (M + H) NMR XH: d (CDCl 3) 3.43 (t, 4 H =, 2.8 (t, 2H), 2.45 (m, 6), 1.5 (s, 9H). (ii) tert-butyl 2- [4- (3,4-dichlorobenzoyl) -l-piperazinyl] -ethylcarbamate The product of step (i) above (3 g) was dissolved in 12 ml of pyridine, 2.05 g was added. of 3,4-dichlorobenzoyl chloride and the mixture was stirred at room temperature for 18 hours. A mixture was collected by filtration and purified by chromatography (dichloromethane: methanol: 0.880 NH4OH, 90: 9: 1) to give the subtitle product as an oil (3.59 g). MS: APCl (+ ve) 364 (M + H) 1 H NMR: d (CDC13) 7.33 (m, 3H), 7.04 (m, 1H), 6.76 (broad s, 1H), 3.86 (s, 3H), 3.55 (q, 2H), 3.45 (t, 4H), 2.61 (t, 3H, 2.46 (t, 4H), 1.46 (s, 9H) (iii) [4- (2-aminoethyl) -1-piperazinyl] (3, 4-dichlorophenyl) methanone trifluoroacetate The product of step (ii) above (3.3 g) was dissolved in 50 ml of dichloromethane and 10 ml was added of trifluoroacetic acid. After 16 hours at room temperature, the solvent was removed to give the subtitle product as an oil (5.9 g). MS: APCl (+ ve) 264 (M + H) (iv) N- hydrochloride. { 2- [4- (3,4-dichlorobenzoyl) -l-piperazinyl] ethyl} -3-methoxybenzamide The product of step (iii) above (0.15 g) was dissolved in 2 ml of pyridine and 0.064 g of 3-methoxybenzoyl chloride was added. After 16 hours at room temperature, water and ethyl acetate were added, the organic phase was separated, dried and concentrated to an oil. Purification by chromatography (dichloromethane: methanol, 95: 5) gave an oil which was treated with an ethereal solution of l.O M hydrogen chloride to give the title product as a solid (0.43 g). MS: ESI 436.12 (M + H) X H NMR: d (DMSO) 8.8 (broad t, 1H), 7.34 (m, 2H), 7.43 (m, 4H), 7.14 (m, 1H), 3.82 (s, 3H) ), 3.48 m, 12H) -Fusion point: 230 ° C Example 18 3, 4-dichloro-N-. { 2- [4- (3,4-dichlorobenzoyl) -1-piperazinyl] ethyl} benzamide A solution of 5.3 g of benzaldehyde and 6.45 g of 1- (2-aminopiperazine) in 100 ml of toluene, was heated under a Dean and Stark water separator for 4 hours. The solution was cooled to room temperature and 5.05 g of triethylamine was added. A solution of 10.48 g of 3,4-dichlorobenzoyl chloride in 50 ml of toluene was added dropwise, the solution was stirred at room temperature for 18 hours and water was added. The organic phase was separated, dried and concentrated to a residue which was treated with 65 ml of an aqueous solution of 1 N potassium hydrogen sulfate. The mixture was stirred vigorously for 4 hours, ether was added, the aqueous phase it was separated and sodium hydroxide was added. Chloroform was added, the organic phase was separated, dried and concentrated to a gum. Purification by chromatography (dichloromethane: triethylamine, 95: 5) gave the title product as a foam (0.25 g). MS: ESI 474.03 (M + H) X H NMR: d (DMSO) 8.8 (broad t, 1H), 7.34 (m, 2H), 7.43 (m, 4H), 7.14 (m, 1H), 3.82 (s, 3H) ), 3.48 (m, 12H).

Example 19 4-chloro-N- hydrochloride. { 2- [4- (3,4-dichlorobenzoyl) -1-piperazin] ethyl} -2- [2- (dimethylamino) -2-oxoethoxy] benzamide The product of Example 26 step (ii) (0.3 g), 0.1 g of 3,4-dichlorobenzoyl chloride and 0.15 g of triethylamine were dissolved in 15 ml of dichloromethane. After 20 hours at room temperature, water was added, the organic phase was separated, dried and evaporated to give a gum. Purification by chromatography (dichloromethane: methanol, 20: 1) gave a solid which was treated with an ethereal solution of l.O M hydrogen chloride to give the title product as a solid (0.1 g). MS: ESI 541.11 (M + H) XH NMR: d (DMSO-D6) 9.54 (t, 1H), 7.91 (d, 1H), 7.74 (m, 2H), 7.43 (m, 2H), 7.18 (d, 1H), 5.12 (s, 2H), 3.2-3.8 (m, 12H), 2.99 (s, 3H), 2.88 (s, 3H). Melting point: 226-7 ° C Example 20 N-7-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] -ethyl} -5-methyl [1,3] thiazolo [4, 5-d] pyrimidin-2,7-diamine MS: APCl (+ ve) 453 (M + 1.

Example 21 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 9-methyl-9H-purin-6-amine MS: APCl (+ ve) 421 (M + l) Example 22 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} , 3-benzothiazole -2 -amine MS: APCI (+ ve) 422 (M + 1) Example 23 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 3-benzoxazole -2-amino MS: APCl (+ ve) 406 (M + l) Example 24 6-chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2-pyrazinamine MS: APCl (+ ve) 403 (m + 1.

Example 25 6-chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-pyridazinamine MS: APCl (+ ve) 403 (M + l ' Example 26 6- ( { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl} amino) -1,3-dimethyl-2,4 (1H, 3H) -pyrimidinedione MS: APCI (+ ve) 427 (M + 1) Example 27 N- hydrochloride. { 1- [4- (3,4-dichlorophenoxy) piperidin-1-ylmethyl] -2-methyl-propyl} -4-methyl-benzamide (i) N-. { l-. { 4- (3, -dichlorophenoxy) -piperidine-1-carbonyl] -2-methyl-propyl} -acetamide 1.13 g of N-Boc-Valine were dissolved in 5 ml of dichloromethane and 0.99 g of EDC were added, after 5 minutes the product according to Example 1 step (ii) (1.44 g) in 5 ml of dichloromethane was added. added in a single portion. After 3 hours at room temperature, aqueous solution of sodium bicarbonate and ethyl acetate were added. The organic phase was separated and the solvent was removed to give the subtitle compound as an oil (1.57 g) which was used in the next step without further purification. (ii) 2-amino-l- [4- (3,4-dichlorophenoxy) -piperidin-1-yl] -3-methyl-butan-1-one The product of step (i) (1.57 g) was dissolved in 14 ml of dichloromethane and 4 ml of trifluoroacetic acid were added. After 2 hours at room temperature, the solvent was removed, ethyl acetate and a 2 N aqueous sodium hydroxide solution were added to give pH 8.0. The organic phase was separated and concentrated to give the subtitle product as an oil (1.24 g) which was used in the next step without further purification. (iii) 1- [4- (3,4-dichlorophenoxy) -piperidin-1-ylmethyl] -2-methyl-propylamine The product of step (ii) (1.12 g) was dissolved in 10 ml of tetrahydrofuran and 22.7 was added ml of borane / THF complex. The mixture was refluxed for 2 hours and cooled. The solvent was evaporated, the product was dissolved in 5 ml of methanol and an aqueous solution of 50% HCl was added. The mixture was heated to 70 ° C for 1 hour and cooled to room temperature. The solvent was removed, ethyl acetate and 2 N sodium hydroxide aqueous solution were added to give pH 9.0. The organic phase was separated and the solvent was evaporated to give the subtitle compound as an oil (0.98 g) which was used without further purification. (iv) N- hydrochloride. { 1- [4- (3,4-dichlorophenoxy) -piperidin-1-ylmethyl] -2-methyl-propyl} -4-methyl-benzamide The product of step (iii) (0.2 g) was dissolved in ml of dichloromethane, 0.126 ml of triethylamine and 0.097 ml of 4-methylbenzoyl chloride were added.

After 2 hours at room temperature, ethyl acetate and aqueous sodium carbonate aqueous solution were added, the organic phase was separated and the solvent was removed to leave an oil. Purification by reverse phase high performance liquid chromatography (HPLC) (with a gradient eluent system (25% of MeCN / aqueous ammonium acetate (0.1%) up to 95% of MeCN / aqueous ammonium acetate (0.1%)) gave a gum. Addition of ethereal 1.0M hydrogen chloride solution gave the title product as a solid (0.104 g). Melting point: 131-132 ° C MS: ESI 450 (M + H) XH NMR: d (DMSO) 8.45 (t, 1H), 7.00-7.90 (m, 7H), 4.79 (broad s, 1H), 4.24 -4.30 (m, 1H), 3.1-3.42 (m, 5H), 2.36 (s, 3H), 1.88-2.40 (m, 5H), 0.92 (t, 6H).

Example 28 N- hydrochloride. { l- [4- (3,4-dichloro-phenoxy-piperidin-1-ylmethyl] -2-methyl-propyl] -3-methoxy-benzamide The product according to Example 27 step (iii) dissolved in 4 ml of dichloromethane was added 0.090 ml of triethylamine and 0.077 ml of 3-methoxybenzoyl chloride. After 2 hours at room temperature, sodium hydrogen carbonate was added, the product was extracted with ethyl acetate, the combined organic extracts were dried with sodium sulfate and concentrated. Purification with reverse phase HPLC (with a gradient eluent system (25% MeCN / NH4Oacac (0.1%) to 95% MeCN // NH4Acac (0.1%)) gave a gum.The product was dissolved in methanol and it was treated with ethereal solution of 1.0 M hydrogen chloride to give the product as a solid (0.045 g) MS: ESI 465 (M + H) XH NMR: d (DMSO) 8.58-8.63 (m, 1H), 7.01- 7.58 (m, 6H), 4.80 (broad s, 1H), 4.23-4.59 (m, 1H), 3.83 (s, 3H), 3.04-3.60 (m, 4H), 1.89-2.14 (m, 5H), 0.85 (m, 6H).

Example 29 N- dihydrochloride. { 2- [4- (3,4-dichloroanilino) -1-piperidinyl] ethyl} -3-methoxybenzamide (i) 4- (3,4-dichloroanilino) -1-piperidine-carboxylate of tert-butyl A solution of 5 g of 3,4-dichloroaniline, 11.7 g of N-tert-butoxycarbonyl-4-piperidone, 19.7 g of Sodium triacetoxyborohydride and 7 ml of acetic acid in 150 ml of dichloroethane was stirred for 16 hours. A solution of 2 M sodium hydroxide and ether was added, the organic phase was separated, dried and concentrated. The residue was triturated under a mixture of isohexane: ethyl acetate, 4: 1 and the subtitle product was collected as a solid (7.25 g). MS: APCl (+ ve) 345 (M + H) XH NMR: d (DMSO) 7.23 (d, 1H), 6.77 d, 1H), 6.57 (dd, 1H), 5.99 (d, 1H), 3.85 (d broad, 2H), 3.40 (m, 1H), 2.90 (broad m, 2H), 1.85 (m, 2H), 1.39 (s, 9H), 1.19 (m, 2H). (ii) N- (3,4-dichlorophenyl) -4-piperidinamine trifluoroacetate The product of step (i) above (6.5 g) was dissolved in 75 ml of dichloromethane and 25 ml of trifluoroacetic acid were added. After 72 hours at room temperature, the solution was evaporated and the residue was triturated under ether to give the subtitle compound as a solid (6.3 g). MS: APCl + ve 245/7 (M + H) 1 H NMR: d (DMSO) 8.65 (broad s, 1H), 8.50 s broad, 1H), 7.26 (d, 1H), 6.81 (d, 1H), 6.60 (dd, 1H), 6.19 (broad s, 1H), 3.53 (broad s, 1H), 3.30 (m, 2H), 3.0 (m, 2H), 2.02 (m, 2H), 1.50 (m, 2H). (iii) 2- [4- (3,4-dichloroanilino) -1-piperidinyl] ethylcarbamate tert-butyl The product from step (ii) above (2.0 g), N-tert-butoxycarbonyl-2-bromoethanamine (1.0 g) ) and N, N-diisopropylethylamine (3.7 ml) were dissolved in 25 ml of dimethylformamide and stirred for 16 hours. Water and ethyl acetate were added, the organic phase was separated, dried and evaporated to give a gum. Purification by chromatography (dichloromethane: methanol, 95: 5) gave the subtitle product as a solid (1.25 g). MS: APCl (+ ve) 388/90 (M + H) 1 H NMR: d (DMSO) 7.22 (d, 1H), 6.73 (d, 1H), 6.62 (t, 1H), 6.54 (5.94 (d, 1H ), 3.17 (m, 1H), 3.02 (m, 2H), 2.77 (broad d, 2H), 2.31 (t, 3H), 2.06 (t, 2H), 1.84 (broad d, 2H), 1.35 (m, 11H). (iv) 1- (2-aminoethyl) -N- (3,4-dichlorophenyl) -4-piperidinamine trifluoroacetate The product of step (iii) above (1.2 g) was dissolved in 30 ml of dichloromethane and 10 ml was added of trifluoroacetic acid. After 72 hours at room temperature, the reaction mixture was evaporated and the residue was triturated with ether to give the subtitle product as a solid (1.6 g). MS: APCl (+ ve) 288/90 (M + H) (v) N- dihydrochloride. { 2- [4- (3,4-dichloroanilino) -l-piperidinyl] ethyl} -3-methoxybenzamide The product of step (iv) above (0.5 g) and 1.1 ml of triethylamine were dissolved in 10 ml of dimethylformamide, 0.11 ml of 3-methoxybenzoylchloride was added dropwise. After 2 hours, water and ethyl acetate were added, the organic phase was separated, dried and evaporated. Purification of the residue by chromatography (dichloromethane: methanol, 95: 5) gave an oil which was treated with an ether solution of 1.0 M hydrogen chloride to give the title product as a solid (0.15 g). MS: ESI 422.14 (M + H) 1 H NMR: d (DMSO) 10.44 (broad s, 1H), 8.93 (t, 1H), 7.51 (m, 2H), 7.40 (t, 1H), 7.26 (d, 1H ), 7.11 (dd, 1H), 6.81 (d, 1H), 6.60 (dd, 1H), 3.82 (s, 3H), 2.68 (m, 4H), 3.25 (m, 5H), 2.09 (broad d, 2H) ), 1.76 (m, 2H). Melting point: 170 ° C Example 30 N- dihydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -N- (3-methoxybenzyl) amine A suspension of the product from Example 1 step (iv) (0.11 g) in a mixture of 1.5 ml of dimethylformamide and 3 ml of 1,2-dichloroethane was stirred under a nitrogen atmosphere. 0.097 g of sodium triacetoxyborohydride, 0.041 g of 3-methoxybenzaldehyde and 0.046 g of triethylamine were added and the mixture was stirred for 18 hours at room temperature. Chloroform and an aqueous solution of sodium hydrogen carbonate were then added, the organic phase was separated, dried and concentrated to a gum. Purification by chromatography (chloroform: triethylamine: methanol, 89: 10: 1) gave an oil which was treated with an ethereal solution of 1.0 M hydrogen chloride to give the title compound as a solid (0.067 g). MS: ESI 409.14 (M + H) X H NMR: d (DMSO) 7.50 (d, 1 H), 7.30 m, 3 H), 7.12 (d, 1 H), 7.03 (dd, 1 H), 6.97 (dd, 1 H), 4.71 (broad m, 1H), 4.18 (s, 2H), 3.80 (s, 3H), 3.45 (broad m, 4H), 2.23 (m, 6H), 2.04 (m, 2H). Melting point: 247-51 ° C Example 31 3-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - 6-methoxy-2,4 (1H, 3H) -quinazolinedione (i) 2-amino-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -5-methoxybenzamide Prepared by the method of Example 2, using the product of Example 1 step (iv) (1.0 g) and 0.418 g of 2-amino-5-methoxybenzoic acid without the addition of the ethereal solution of hydrogen chloride 1.0 M to give an oil which was purified by chromatography (dichloromethane: methanol, 95: 5) to give the subtitle product as an oil (0.82 g). MS: APCl (+ ve) 438 (M + H) (ii) 3-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -6-methoxy-2,4 (1H, 3H) -quinazolindione The product of step (i) above was dissolved in ml of toluene. A solution of 2.0 M phosgene in 10 ml of toluene was added, the solution was heated to reflux for 1 hour and cooled. Ethyl acetate and an aqueous sodium hydrogen carbonate solution were added, the organic phase was separated, dried and concentrated to leave a residue which was purified by chromatography (dichloromethane: methanol, 95: 5). The title product was obtained as a solid (0.11 g). MS: ESI 464.11 (M + H) 1 H NMR: d (DMSO) 7.49 (dd, 1H), 7.36 (d, 1H), 7.30 (dd, 1H), 7.24 (d, 1H), 6.98 (dd, 1H), 4.44 (m, 1H), 4.03 (t, 3H), 3.80 (s, 3H), 2.76 (m, 2H), 2.32 ( m, 2H), 1.89 (m, 2H), 1.57 (m, 2H). Melting point: 190 ° C The compounds of the following Examples 32 to 125 were prepared by methods analogous to the method of Example 10.

Example 32 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -3 - fluorobenzamide MS: APCl (+ ve) BP 411 Example 33 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} benzamide MS: APCl (+ ve) BP 393 Example 34 4 -chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide MS: APCl (+ ve) BP 429 Example 35 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -methoxybenzamide MS: APCl (+ ve) BP 423 Example 36 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -methoxybenzamide MS: APCl (+ ve) BP 423 Example 37 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -methoxybenzamide MS: APCl (+ ve) BP 423 Example 38 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -nitrobenzamide MS: APCl (+ ve) BP 438 Example 39 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -methylbenzamide MS: APCl (+ ve) BP 407 Example 40 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 3- (trifluoromethyl) benzamide MS: APCl (+ ve) BP 461 Example 41 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 3, 5-dinitrobenzamide MS: APCl (+ ve) BP 483 Example 42 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2-Iodobenzamide MS: APCl (+ ve) BP 519 Example 43 4-cyano-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide MS: APCl (+ ve) BP 418 Example 44 4-bromo-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide MS: APCl (+ ve) BP 473 Example 45 N-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl} 4-methylbenzamide MS: APCl (+ ve) BP 407 Example 46 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 4-nitrobenzamide MS: APCl (+ ve) BP 431 Example 47 3-bromo-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide MS: APCl (+ ve) BP 473 Example 48 3, 4-dichloro-N-. { 2- [4- (3, -dichlorophenoxy) -1-piperidinyl] ethyl} benzamide MS: APCl (+ ve) BP 463 Example 49 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 4-fluorobenzamide MS: APCl (+ ve) BP 411 Example 50 2, 4-dichloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide MS: APCl (+ ve) BP 463 Example 51 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 3-methylbenzamide MS: APCl (+ ve) BP 407 Example 52 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 4-Iodobenzamide MS: APCl (+ ve) BP 519 Example 53 4-chloro-N-. { 2- [4- (3,4-Dichlorophenoxy) -1-piperidinyl] ethyl} -3-nitrobenzamide MS: APCl (+ ve) BP 472 Example 54 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 4-methyl-3-nitrobenzamide MS: APCl (+ ve) BP 452 Example 55 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2-fluoro-5- (trifluoromethyl) benzamide MS: APCl (+ ve) BP 479 Example 56 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 3- (trifluoromethoxy) benzamide MS: APCl (+ ve) BP 477 Example 57 3, 5-dichloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide MS: APCl (+ ve) BP 463 Example 58 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 4- (trifluoromethyl) benzamide MS: APCl (+ ve) BP 461 Example 59 3-cyano-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide MS: APCl (+ ve) BP 41I Example 60 2 -bromo-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -5-methoxybenzamide MS: APCl (+ ve) BP 503 Example 61 N-. { 2- [4- (3, -dichlorophenoxy) -l-piperidinyl] ethyl} 2-furamide MS: APCl (+ ve) BP 383 Example 62 3 -chloro-N-. { 2- [4- (3,4-Dichlorophenoxy) -1-piperidinyl] ethyl-benzamide MS: APCl (+ ve) BP 427 Example 63 2-chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide MS: APCl (+ ve) BP 429 Example 64 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 3, 5-difluorobenzamide MS: APCl (+ ve) BP 429 Example 65 2, 3-Dichloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide MS: APCl (+ ve) BP 463 Example 66 N-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl-2-naphthamide MS: APCl (+ ve) BP 442 Example 67 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2- (methylsulfanyl) nicotinamide MS: APCl (+ ve) BP 440 Example 68 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -fluoro-6- (trifluoromethyl) benzamide MS: APCl (+ ve) BP 479 Example 69 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} , 4-difluorobenzamide MS: APCl (+ ve) BP 429 Example 70 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2-thiophenecarboxamide MS: APCl (+ ve) BP 399 Example 71 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2 -quinoxalinecarboxamide MS: APCl (tve) BP 445 Example 72 4- (. {2- 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl.}. 4-oxobutanoate methyl MS: APCl (+ ve) BP 403 Example 73 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} bicyclo [2.2.1] hept- 5 -en-2-carboxamide MS: APCl (+ ve) BP 409 Example 74 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} cyclobutanecarboxamide MS: APCl (+ ve) BP 371 Example 75 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2-methoxyacetamide MS: APCl (+ ve) BP 361 Example 76 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} cyclohexanecarboxamide MS: APCl (+ ve) BP 399 Example 77 (E) -N-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl} -3-phenyl -2 -propenamide MS: APCl (+ ve) BP 419 Example 78 2-chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} nicotinamide MS: APCl (+ ve) BP 430 Example 79 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -phenylacetamide MS: APCl (+ ve) BP 407 Example 80 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} cyclopentanecarboxamide MS: APCl (+ ve) BP 385 Example 81 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2-phenoxyacetamide MS: APCl (+ ve) BP 423 Example 82 N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} benzamide MS: APCl (+ ve) BP 371 Example 83 N-. { 2- [4- (4-chlorobenzoyl) -piperidinyl] ethyl} -3- (trifluoromethyl) benzamide MS: APCl (+ ve) BP 439 Example 84 '4- (tert-butyl) -N-. { 2- [4- (4-chlorobenzoyl) -1-piperidinyl] ethyl} benzamide MS: APCl (+ ve) BP 427 Example 85 N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -4-methylbenzamide MS: APCl (+ ve) BP 385 Example 86 N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -4-nitrobenzamide MS: APCl (+ ve) BP 416 Example 87 N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -3-methylbenzamide MS: APCl (+ ve) BP 385 Example 88 N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -4- methyl-3-nitrobenzamide MS: APCl (+ ve) BP 430 Example 89 N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -3-cyanobenzamide MS: APCl (+ ve) BP 396 Example 90 N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -2-furamide MS: APCl (+ ve) BP 361 Example 91 N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -3-nitrobenzamide MS: APCl (+ ve) BP 416 Example 92 N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -2-naphtamide MS: APCl (+ ve) BP 421 Example 93 N- [2- [4- (4-Chlorobenzoyl) -l-piperidinyl] ethyl} -2- (methylsulfanyl) nicotinamide MS: APCl (+ ve) BP 418 Example 94 N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -2- (2,3-dihydro-1,4-benzodioxin-2-yl) -1,3-thiazole-4-carboxamide MS: APCl (+ ve) BP 512 EXAMPLE 95 N-2-Cyclopropyl-N-4-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2, 4-pyrimidindiamine MS: APCl (+ ve) BP 422 (M + l.

Example 96 2-. { [4- (. {2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl} amino) -2-pyrimidinyl] amino} -1-ethanol MS: APCl (+ ve) BP 426 (M + 1) Example 97 2- [[4- ( { 2- [4- (3,4-Dichlorophenoxy) -1-piperidinyl] ethyl} amino) - 2-pyrimidinyl] (methyl) amino] -1-ethanol MS: APCl (+ ve) 440 (M + l) Example 98 N-4-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -N-2-pheny1-2, 4-pyrimidinediamine MS: APCl (+ ve) 458 (M + l) Example 99 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2- (methylsulfanyl) -4-pyrimidinamine MS: APCl (+ ve) 413 (M + l) Example 100 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -methyl-2, 4-pyrimidindiamine MS: APCl (+ ve) 396 (M + 1) Example 101 N-4-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -N-2, 6-dimethyl-2,4-pyrimidinediamine MS: APCl (+ ve) BP 410 (M + l) Example 102 2-chloro-N-4-cyclopropyl-N-6-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl} -4, 6-pyrimidindiamine MS: APCl (+ ve) 456 (M + l) Example 103 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 4-phenyl-2-pyrimidinamine MS: APCl (+ ve) 443 (M + l) Example 104 N-2-. { 2- [4- (3, -dichlorophenoxy) -l-piperidinyl] ethyl} -N-4-N-4,6-trimethyl-2,4-pyrimidinediamine MS: APCl (+ ve) 424 (M + l) Example 105 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - (trifluoromethyl) -2-pyrimidinamine MS: APCl (+ ve) 435 (M + l) Example 106 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} (propylsulfanyl) -2-pyrimidinamine MS: APCl (+ ve) 441 (M + l) Example 107 N-2-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -N-4- phenyl -2,4-pyrimidinediamine MS: APCl (+ ve) 458 (M + 1) Example 108 N-4-cyclopropyl-N-2-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2, 4-pyrimidindiamine MS: APCl (+ ve) 422 (M + l) Example 109 N-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl} [1,8] naphthyridin-2-amine MS: APCl (+ ve) 417 (M + l) Example 110 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 4- (3-pyridinyl) -2-pyrimidinamine MS: APCl (+ ve) 444 (M + l ' Example 111 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2-pyrimidinamine MS: APCl (+ ve) 367 (M + 1) 10 Example 112 N-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl} 4, 6-dimethoxy-2-pyrimidinamine MS: APCl (+ ve) 427 (M + 1) 25 Example 113 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - (3-furyl) -2-pyrimidinamine MS: APCl (+ ve) 433 (M + l) Example 114 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -methyl-lH-pyrazolo [3, 4-d] pyrimidin-4-amino MS: APCl (+ ve) 421 (M + l) Example 115 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} lH-purin-6-amine MS: APCl (+ ve) 407 (M + l) Example 116 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 5-methylthieno [2,3-d] pyrimidine-amine MS: APCl (+ ve) 437 (M + l) Example 117 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 7-methylthieno [3,2-d] pyrimidin-4-amine MS: APCl (+ ve) 437 (M + l) Example 118 N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -2-thiophenecarboxamide MS: APCl (+ ve) BP 377 Example 119 N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -2-quinoxalinecarboxamide MS: APCl (+ ve) BP 423 Example 120 N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} bicyclo [2.2.1] hept -5-en-2 -carboxamide MS: APCl (+ ve) BP 387 Example 121 N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} cyclohexanecarboxamide MS: APCl (+ ve) BP 377 Example 122 (E) -N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -phenyl -2 -propenamide MS: APCl (+ ve) BP 397 Example 123 N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -2-phenoxyacetamide MS: APCl (+ ve) BP 401 Example 124 (E) -N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} 3- (4-nitrophenyl) -2-propenamide MS: APCl (+ ve) BP 442 Example 125 2- (1-adamantyl) -N-. { 2- [4- (4-chlorobenzoyl) -1-piperidinyl] ethyl} acetamide MS: APCl (+ ve) BP 443 The compounds of the following Examples 126 to 168 were prepared by methods analogous to the method of Example 30.

Example 126 (4-chlorophenyl) (1 -. {2- [(2-fluoro-4,5-dimethoxybenzyl) amino] ethyl] -4-piperidinyl) methanone MS: APCl (+ ve) BP 435 Example 127 (4-chlorophenyl) (1 -. {2- [(3,4,5-trimethoxybenzyl) amino] ethyl] -4-piperidinyl) methanone MS: APCl (+ ve) BP 447 Example 128 (4-chlorophenyl) (1- {2 - [(3-nitrobenzyl) amino] ethyl} - piperidinyl) methanone MS: APCl (+ ve) BP 402 Example 129 (4-chlorophenyl). { 1- [2- (isobutylamino) ethyl] -4-piperidinyl} methanone MS: APCl (+ ve) BP 323 Example 130 4- [( { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} amino) methyl] -4-ethylhexan-nitrile MS: APCl (+ ve) BP 404 Example 131 (4-chlorophenyl) (1 -. {2- [(7-hydroxy-3,7-dimethyloctyl) amino] ethyl] -4-piperidinyl) methanone MS: APCl (+ ve) BP 423 Example 132 (4-chlorophenyl) [1- (2 { [6-nitro-1,3-benzodioxol-5-yl) methyl] amino} ethyl) -4-piperidinyl] methanone MS: APCl (+ ve) BP 446 Example 133 [1- (2- { [(5-Chloro-1,3-dimethyl-lH-pyrazol-4-yl) methyl] amino.} Ethyl) -4-piperidinyl] (4-chlorophenyl) methanone MS: APCl (+ ve) BP 409 Example 134 (4-chlorophenyl) [1- (2 { [3-nitro-4- (2-pyridinylsulfanyl) benzyl] amino} ethyl) -4-piperidinyl] methanone MS: APCl (+ ve) BP 511 Example 135 (4-chlorophenyl) [1- (2 { [(E) -3- (4-nitrophenyl) -2-propenyl] amino} ethyl) -4-piperidinyl] methanone MS: APCl (+ ve) BP 428 Example 136 (4-chlorophenyl). { l- [2- ( { [5- (3-Nitrophenyl) -2-furyl] methyl.}. amino) ethyl] -4-piperidinyl J-methanone MS: APCl (+ ve) BP 468 Example 137 (4-chlorophenyl) [1- (2 { [5-nitro-2- (2-pyridinylsulfanyl) benzyl] amino} ethyl) -4-piperidinyl] methanone MS: APCl (+ ve) BP 511 Example 138 6- [( { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} amino) methyl] -2- (methylsulfanyl) nicotinonitrile MS: APCl (+ ve) BP 429 Example 139 { 1- [2- ( { [5-chloro-1-methyl-3- (trifluoromethyl) -1H-pyrazol-4-yl] methyl} amino) ethyl] -4-piperidinyl} (4-chlorophenyl) methanone MS: APCl (+ ve) BP 463 Example 140 (4-chlorophenyl) [1- (2- {[[3- (methylsulfanyl) butyl] amino} ethyl) -4-piperidinyl] methanone MS: APCl (+ ve) BP 369 Example 141 (4-chlorophenyl) [1- (2. {[[(4-phenyl-4-piperidinyl; methyl] amino]} ethyl) -4-piperidinyl] methanone MS: APCl (+ ve) BP 440 Example 142 (4-chlorophenyl) [1- (2. {[[(1-phenyl-lH-pyrazol-5-yl) methyl] amino} ethyl) -4-piperidinyl] methanone MS: APCl (+ ve) BP 423 Example 143 Ethyl 3- [(. {2- 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl]} amino) methyl] cyclohexanecarboxylate MS: APCl (+ ve) BP 435 Example 144 N-. { 4- [( { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} amino) methyl] phenyl} acetamide MS: APCl (+ ve) BP 414 Example 145 (4-chlorophenyl) (1- {2- [(2,5-difluorobenzyl) amino] ethyl} -4-piperidinyl) methanone MS: APCl (+ ve) BP 393 EXAMPLE 146 (4-Chlorophenyl) (1 - { 2- [(4-nitrobenzyl) amino] ethyl] 4-piperidinyl) methanone MS: APCl (+ ve) BP 402 Example 147 (4-chlorophenyl) (1 -. {2- [(2,6-dichlorobenzyl) amino] ethyl] -4-piperidinyl) methanone MS: APCl (+ ve) BP 425 EXAMPLE 148 (4-Chlorophenyl) (1- {2 - [(2-pyridinylmethyl) amino] ethyl} -4-piperidinyl) methanone MS: APCl (+ ve) BP 358 Example 149 (4-Chlorophenyl) [1- (2. {[[(3-methyl-2-thienyl) methyl] amino} ethyl) -4-piperidinyl] methanone MS: APCl (+ ve) BP 377 Example 150 (4-chlorophenyl) (1 - { 2- [(3-hydroxy-4-methoxybenzyl) amino] ethyl] -4-picperidinyl) methanone MS: APCl (+ ve) BP 403 Example 151 3- [( { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} amino) methyl] -4H-chromen-4-one MS: APCl (+ ve) BP 425 Example 152 [1- (2-. {[[(5-Chloro-1,3-dimethyl-lH-pyrazol-4-yl) methyl] amino} ethyl) -4-piperidinyl] (4-chlorophenyl) methanone MS: APCl (+ ve) BP 409 Example 153 (4-Chlorophenyl) [1- (2. {[[(2,6-dichloro-4-pyridinyl) methyl] amino.} Ethyl) -4-piperidinyl] methanone MS: APCl (+ ve) BP 428 Example 154 (4-chlorophenyl) [1- (2. {[[(2-phenyl-lH-imidazol-4-yl) methyl] amino} ethyl) -4-piperidinyl] methanone MS: APCl (+ ve) BP 423 Example 155 (4-chlorophenyl) [1- (2. {[[(5-ethyl-2-thienyl) methyl] amino} ethyl) -4-piperidinyl] methanone MS: APCl (+ ve) BP 391 Example 156 (4-chlorophenyl) [1- (2. {[[(2-chloro-3-quinolinyl) methyl] amino} ethyl) -4-piperidinyl] methanone MS: APCl (+ ve) BP 442 Example 157 (4-chlorophenyl) [1- (2. {[[(6-methyl-2-pyridinyl) methyl] amino} ethyl) -4-piperidinyl] methanone MS: APCl (+ ve) BP 372 Example 158 (4-chlorophenyl) (1 -. {2- [3-quinolinylmethyl) amino] ethyl] -4-piperidinyl) methanone MS: APCl (+ ve) BP 408 Example 159 4- [( { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -amino) methyl] -1,5-dimethyl-2-phenyl-1,2-dihydro- 3H-pyrazole-3-one MS: APCl (+ ve) BP 467 Example 160 (4-chlorophenyl) (1 -. {2- [4-pyridinylmethyl) amino] ethyl] -4-piperidinyl) methanone Example 161 (4-chlorophenyl) (1 - { 2- [(3-hydroxy-4-nitrobenzyl) amino] ethyl] -4-piperidinyl) methanone MS: APCl (+ ve) BP 418 EXAMPLE 162 (4-Chlorophenyl) (1 - {2- [(3,5-difluorobenzyl) amino] ethyl] -4-piperidinyl) methanone MS: APCl (+ ve) BP 393 Example 163 (1- (2- (2-chloro-6-fluorobenzyl) amino] ethyl) -4-piperidinyl) (4-chlorophenyl) methanone MS: APCl (+ ve) BP 409 Example 164 [1- (2-. {[[(4-bromo-lH-pyrazol-3-yl) methyl] amino] ethyl) -4-piperidinyl] (4-chlorophenyl) methanone MS: APCl (+ ve) BP 427 Example 165 3- [( { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} amino) methyl] -6,7-dimethyl-4H-chromen-4 -one MS: APCl (+ ve) BP 453 Example 166 2- acid. { 2 - [( { 2- [4- (4-chlorobenzoyl) -1-piperidinyl] ethyl} amino) methyl] -4-nitrophenoxy} acetic MS: APCl (+ ve) BP 476 Example 167 (4-chlorophenyl) [1- (2. {[[(1-methyl-1H-benzimidazol-2-ylmethyl] amino]} ethyl) -4-piperidinyl] methanone MS: APCl (+ ve) BP 411 Example 168 (4-chlorophenyl) [1- (2. {[[(2,4-dimethoxy-5-pyrimidinyl) methyl] amino} ethyl) -4-piperidinyl] methanone MS: APCl (+ ve) BP 419 The compounds of the following Examples 169 to 209 were prepared by methods analogous to the method of Example 2.

Example 169 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - 4- (methylamino) benzamide MS: APCl (+ ve) BP 422 Example 170 4-chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-methoxybenzamide MS: APCl (+ ve) BP 459 Example 171 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 3-methoxy-4-methylbenzamide MS: APCl (+ ve) BP 437 Example 172 3 -amino-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -4-methoxybenzamide MS: APCl (+ ve) BP 438 Example 173 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 1,3-benzodioxol-5-carboxamide MS: APCl (+ ve) BP 437 Example 174 4-amino-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-methoxybenzamide MS: APCl (+ ve) BP 438 Example 175 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 3-fluoro-4-methoxybenzamide MS: APCl (+ ve) BP 441 Example 176 5-bromo-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2-furamide MS: APCl (+ ve) BP 463 Example 177 N-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl} 3-methyl-2-furamide MS: APCl (+ ve) BP 397 Example 178 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 4, 5-dimethyl-2-furamide MS: APCl (+ ve) BP 411 Example 179 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 7-ethoxy-1-benzofuran-2-carboxamide MS: APCl (+ ve) BP 477 Example 180 N-. { 2- [4- (3, -dichlorophenoxy) -l-piperidinyl] etiX-methoxy-1-benzofuran-2-carboxamide MS: APCl (+ ve) BP 463 Example 181 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -methoxy-1-benzofuran-2-carboxamide MS: APCl (+ ve) BP 463 Example 182 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - (4-fluorophenyl) acetamide MS: APCl (+ ve) BP 425 Example 183 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - (2-methoxyphenyl) acetamide MS: APCl (+ ve) BP 437 Example 184 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - (3-methylphenyl) acetamide MS: APCl (+ ve) BP 421 Example 185 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - (2-methylphenyl) acetamide MS: APCl (+ ve) BP 421 Example 186 2- (3-bromophenyl) -N-. { 2- [4- (3,4-dichlorophenoxy) -1- piperidinyl] ethyl} acetamide MS: APCl (+ ve) BP 487 Example 187 2- (2-chlorophenyl) -N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} acetamide MS: APCl (+ ve) BP 441 Example 188 2- (4-chlorophenyl) -N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} acetamide MS: APCl (+ ve) BP 443 Example 189 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - [2- (trifluoromethyl) phenyl] acetamide MS: APCl (+ ve) BP 475 Example 190 2- (3-chlorophenyl) -N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} acetamide MS: APCl (+ ve) BP 441 Example 191 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2- (3,4-dimethoxyphenyl) acetamide MS: APCl (+ ve) BP 467 Example 192 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - (4-methoxyphenyl) acetamide MS: APCl (+ ve) BP 437 Example 193 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - (3,4-dichlorophenyl) acetamide MS: APCl (+ ve) BP 477 Example 194 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - (3-fluoro-4-methoxyphenyl) acetamide MS: APCl (+ ve) BP 455 Example 195 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - (4-ethoxyphenyl) acetamide MS: APCl (+ ve) BP 451 Example 196 2- (1,3-Benzodioxol-5-yl) -N-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl} acetamide MS: APCl (+ ve) BP 451 Example 197 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - [4- (dimethylamino) phenyl] acetamide MS: APCl (+ ve) BP 450 Example 198 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - (4-methylphenyl) acetamide MS: APCl (+ ve) BP 421 Example 199 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - (3,4-difluorophenyl) acetamide MS: APCl (+ ve) BP 443 Example 200 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - (3-methoxyphenyl) acetamide MS: APCl (+ ve) BP 437 Example 201 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -phenylbutanamide MS: APCl (+ ve) BP 435 Example 202 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -phenylpropanamide MS: APCl (+ ve) BP 421 Example 203 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - (3-methoxyphenyl) propanamide MS: APCl (+ ve) BP 451 Example 204 2 -Amino-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -1, 3-thiazole-4-carboxamide MS: APCl (+ ve) BP 416 EXAMPLE 205 2- (Acetylamino) -N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -1, 3-thiazole-4-carboxamide MS: APCl (+ ve) BP 457 Example 206 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - (4-pyridinyl) -1, 3-thiazole -4 -carboxamide MS: APCl (+ ve) BP 477 Example 207 N-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl} , 4-dimethyl-l, 3-thiazole-5-carboxamide MS: APCl (+ ve) BP 428 Example 208 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2,5-dimethyl-l, 3-oxazole-4-carboxamide MS: APCl (+ ve) BP 412 Example 209 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 1H-imidazole-4-carboxamide MS: APCl (+ ve) BP 385 Example 210 N- hydrochloride. { 2- [4- (3,4-chlorophenoxy) -1-piperidinyl] ethyl} -3-methoxybenzamide (i) 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethylamine trifluoroacetate Prepared by the method of Example 1 steps (i) to (iv), using 3-chlorophenol to give the product as an oil (0.5 g) which was used directly in the next step without further purification. (ii) N- hydrochloride. { 2- [4- (3,4-chlorophenoxy) -1-piperidinyl] ethyl} -3-methoxybenzamide The product of step (i) above (0.3 g) was dissolved in 490 ml of dichloromethane, 4 equivalents of triethylamine and 1 equivalent of 3-methoxybenzoyl were added. After 72 hours at room temperature, water was added, the organic phase was separated, dried and concentrated to a gum. The product was dissolved in dichloromethane and treated with an ethereal solution of 1.0 M hydrogen chloride to give the title product as a solid (0.1 g).

Melting point: 175-176 ° C MS: APCl (+ ve): 389 (M + H) XH NMR: d (DMSO) 8.87 (t, 1H), 7.5 (m, 2H), 7.42 (m, 1H), 7.32 (m, 1H), 7.13 (m, 2H), 6.98 (m, 2H), 4.82 (m, 1 / 2H), 4.61 (m, 1 / 2H), 3.81 (s, 3H) ), 3.69 (m, 3H), 3.68 (m, 3H), 3.47 (m, 1H), 3.13-3.22 (m, 4H), 2.27 (m, 1H), 2.14 (m, 1H), 2.03 (m, 1H), 1.90 (m, 1H).

Example 211 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -1-methyl-lH-pyrazolo [3,4-d] pyrimidin-4-amine (i) 2-. { 3- [4- (3,4-Dichlorophenoxy) -1-piperidinyl] propyl} -lH-isoindol-1,3 (2H) -dione A solution of the product of example 1 step (ii) (2.0 g), 1.61 g of 2- (3-bromopropyl) -lH-isoindol-1,3 (2H) -dione and 2.5 ml of triethylamine in 40 ml of dichloromethane were heated to reflux for 48 hours. The reaction mixture was partitioned between ethyl acetate / water, the organic layer was dried and evaporated under reduced pressure. Purification was by chromatography eluting with 4% methanol / dichloromethane. Yield 0.839 g. MS: APCl (+ ve) 433 (M + 1) (ii) 3- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] propylamine dihydrochloride salt The product of step (i) (0.83 g) and 0.1 ml of hydrazine hydrate in ethanol was heated to reflux for 6 hours. The precipitate was filtered and partitioned between 2M hydrochloric acid and dichloromethane, the solid was filtered and the aqueous layer was made alkaline with aqueous potassium hydroxide solution and extracted with dichloromethane. The organic layer was dried, evaporated under reduced pressure and the dihydrochloride salt was formed using ethereal hydrogen chloride. Yield 0.28 g. 1H-NMR: d (DMSO-d6) 11.1 (broad s, 1H), 8.13 (broad s, 3H), 7.56 (d, 1H), 7.37 (s, 1H), 7.10-7.06 (broad m, 1H), 4.84 (s broad, 0.5H), 4.65 (s broad, 0.5H), 3.60-2.90 (m, 8H), 2.24-2.01 (m, 6H). (iii) N-. { 3- [4- (3,4-dichlorophenoxy) -1-piperidinyl] propyl} -1-methyl-lH-pyrazolo [3,4-d] pyrimidin-4-amine The product of step (ii) (0.08 g), 0.054 g of 4-chloro-1-methyl-lH-pyrazolo [3, 4 -d] pyrimidine and 0.082 g of diisopropylethylamine in 2 ml of l-methyl-2-pyrrolidinone were heated at 50 ° C for 3 hours. The reaction mixture was diluted with ethyl acetate and washed with water. The organic layer was dried and the solvent was removed under reduced pressure. Purification was by chromatography eluting with 9% methanol / dichloromethane. Yield 0.052 g. MS: APCl (+ ve) 435 (M + 1) 1 H NMR: d (DMS0-d 6) 8.25-8.22 (m, 2H), 8.07 (s, 1H), 7.49 (d, 1H), 7.25 (d, 1H), 6.97 (dd, 1H), 4.46-4.42 (m, 1H), 3.88 (s, 3H), 3.49 (q, 2H), 2.70-2.66 (m, 2H), 2.40-2.36 (m, 2H), 2.27-2.22 (m, 2H), 1.92-1.88 (m, 2H), 1.81-1.74 (m, 2H), 1.62-1.59 (m, 2H) . Melting point: 120-124 ° C Examples 212-255 The product from Example 211 step (ii) (1.5 mg), the appropriate halo-aromatic compound activated (1.25 equivalents), diisopropylethylamine (10 equivalents) in 0.15 ml of l-methyl-2-pyrrolidinone were heated at 100 ° C for 24 hours. hours. The reaction mixture was evaporated to dryness and the residue was dissolved in 0.4 ml of dimethyl sulfoxide.

Example 212 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -2, 6-dimethoxy-4-pyrimidinamine MS: APCl (+ ve) 441 (M + l) Example 213 N-4-. { 3- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] propyl} -N-2-N-2-dimethyl-2,4-pyrimidindiamine MS: APCl (+ ve) 424 (M + 1) Example 214 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -2- [(Methylsulfanyl) methyl] -4-pyrimidinamine MS: APCl (+ ve) 441 (M + l) Example 215 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -2- (methylsulfanyl) -6- (trifluoromethyl) -4-pyrimidinamine MS: APCl (+ ve) 495 (M + l) Example 216 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -5-methoxy -2- (methylsulfanyl) -4-pyrimidinamine MS: APCl (+ ve) 457 (M + l) Example 217 N-. { 3- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] propyl} -6-methyl-2- (methylsulfanyl) -4-pyrimidinamine MS: APCl (+ ve) 441 (M + l) Example 218 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -5-methoxy-2-methyl-4-pyrimidinamine MS: APCl (+ ve) 425 (M + l) Example 219 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -2- (Ethylsulfanyl) -6-methyl-4-pyrimidinamine MS: APCl (+ ve) 455 (M + l) Example 220 N-2-cyclopropyl-N-4-. { 3- [4- (3,4-dichlorophenoxy) -1-piperidinyl] propyl} -2,4 -pyrimidindiamine MS: APCl (+ ve) 436 (M + l] Example 221 2-. { [4- ( { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} amino) -2-pyrimidinyl] amino} -1-ethanol MS: APCl (+ ve) 440 (M + 1) Example 222 2- [[4- ( { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl] amino] -2 -pyrimidinyl] (methyl) amino] -1-ethanol MS: APCl (+ ve) 454 (M + l) Example 223 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -2- (methylsulfanyl) -4-pyrimidinamine MS: APCl (+ ve) 427 (M + 1) Example 224 N-4-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -6-methyl-2, 4-pyrimidindiamine MS: APCl (+ ve) 410 (M + l) Example 225 N-4-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -N-2, 6-dimethyl-2,4-pyrimidindiamine MS: APCl (+ ve) 424 (M + l) Example 226 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -4-phenyl-2-pyrimidinamine MS: APCl (+ ve) 457 (M + l) Example 227 N-2-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -5-fluoro-2, 4-pyrimidindiamine MS: APCl (+ ve) 414 (M + l) Example 228 N-2-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -N-4-N-4,6-trimethyl-2,4-pyrimidinediamine MS: APCl (+ ve) 438 (M + l) Example 229 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -4- (trifluoromethyl) -2-pyrimidinamine MS: APCl (+ ve) 449 (M + l) Example 230 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -4- (propylsulfanyl) -2-pyrimidinamine MS: APCl (+ ve) 455 (M + l) Example 231 N-2-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -N-4-phenyl-2,4-pyrimidinediamine MS: APCl (+ ve) 472 (M + l) Example 232 N-2-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -N-4, 6-dimethyl-2,4-pyrimidinediamine MS: APCl (+ ve) 424 (M + l) Example 233 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} [1,8] naphthyridin-2-amine MS: APCl (+ ve) 431 (M + l) Example 234 2-. { [2- (. {3- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] propyl} amino) -4-pyrimidinyl] amino} -1-ethanol MS: APCl (+ ve) 440 (M + l) EXAMPLE 235 2 - [[2- ( { 3- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] propyl} amino) -4-pyrimidinyl (methyl) amino] -1-ethanol, MS: APCl (+ ve) 454 (M + l) Example 236 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -4- (3-pyridinyl) -2-pyrimidinamine MS: APCl (tve) 458 (M + l) Example 237 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -4- (3-thienyl) -2-pyrimidinamine MS: APCl (+ ve) 463 (M + l) Example 238 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -2-pyrimidinamine MS: APCl (+ ve) 381 (M + 1) Example 239 N-. { 3- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] propyl} -4,6-dimethoxy-2-pyrimidinamine MS: APCl (+ ve) 441 (M + l) Example 240 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -4- (3-furyl) -2-pyrimidinamine MS: APCl (+ ve) 447 (M + l) Example 241 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -4- (2-thienyl) -2-pyrimidinamine MS: APCl (+ ve) 463 (M + l) Example 242 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -lH-purin-6-amine MS: APCl (tve) 421 (M + l) Example 243 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -5-methylthieno [2, 3-d] pyrimidin-4-amino MS: APCl (+ ve) 451 (M + 1) Example 244 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -7-methylthieno [3,2-d] pyrimidin-4-amino MS: APCl (+ ve) 451 (M + l) Example 245 N-7-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -5-methyl [1,3] thiazolo [4,5-d] pyrimidin-2,7-diamine MS: APCl (+ ve) 467 (M + l) Example 246 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -9-methyl-9H-purin-6-amine MS: APCl (+ ve) 435 (M + l) Example 247 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -2-pyridinamine MS: APCl (+ ve) 379 (M + l) Example 248 5-chloro-N-. { 3- [4- (3,4-dichlorophenoxy) -1-piperidinyl] propyl} -2-pyridinamine MS: APCl (+ ve) 414 (M + l) Example 249 6-chloro-N-. { 3- [4- (3,4-dichlorophenoxy) -1-piperidinyl] propyl} -2-pyridinamine MS: APCl (+ ve) 414 (M + l) Example 250 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -6-methyl-2-pyridinamine MS: APCl (+ ve) 494 (M + l) Example 251 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -1, 3-benzothiazol-2-amine MS: APCl (+ ve) 436 (M + l) Example 252 N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl] -1,3-benzoxazole -2-amino MS: APCl (+ ve) 420 (M + l) Example 253 6 -chloro-N-. { 3- [4- (3,4-dichlorophenoxy) -1-piperidinyl] propyl} -2-pyrazinamine MS: APCl (+ ve) 415 (M + 1) Example 254 6-chloro-N-. { 3- [4- (3,4-dichlorophenoxy) -1-piperidinyl] propyl} -3-pyridazineamine MS: APCl (+ ve) 417 (M + l) Example 255 6- ( { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} amino) -1,3-dimethyl-2,4 (1H, 3H) -pyrimidinedione MS: APCl (+ ve) 441 (M + l) Examples 256-262 The product of Example 1 step (iv) (2.07 mg), the appropriate activated halo-aromatic compound (1.25 equivalents), diisopropylethylamine (10 equivalents) in 0.15 ml of l-methyl-2-pyrrolidinone were heated to 100 ° C for 24 hours. The reaction mixture was evaporated to dryness and the residue was dissolved in 0.4 ml of dimethyl sulfoxide.

Example 256 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -2, 6-dimethoxy-4-pyrimidinamine MS: APCl (+ ve) 427 (M + 1) Example 257 N-4-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} -N-2-N-2-dimethyl-2,4-pyrimidinediamine MS: APCl (+ ve) 410 (M + l) Example 258 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} 2- [(Methylsulfanyl) methyl] -4-pyrimidinamine MS: APCl (+ ve) 427 (M + l) Example 259 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -methoxy-2- (methylsulfanyl) -4-pyrimidinamine MS: APCl (+ ve) 443 (M + l) Example 260 N-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] -ethyl} -methyl-2- (methylsulfanyl) -4-pyrimidinamine MS: APCl (+ ve) 427 (M + l) Example 261 N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -methoxy-2-methyl-4-pyrimidinamine MS: APCl (+ ve) 411 (M + 1) Example 262 N-4-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -6-methyl-N-2-phenyl-2,4-pyrimidindiamine MS: APCl (+ ve) 472 (M + l) Pharmacological Analysis Calcium flow assay [Ca2 +] _. a) Human eosinophils Human eosinophils were isolated from peripheral blood anticoagulated with EDTA as previously described (Hanser et al., "Immuno 1 Methods, 1991, 145, 105-110) .The cells were resuspended (5xl06 ml" 1) and loaded with 5 μM of FLUO-3 / _M + Pluronic F127 2.2 μl / ml (Molecular Probes) in low potassium solution (LKS; 118 mM sodium chloride, 0.8 mM magnesium sulfate, 5.5 mM glucose, 8.5 mM sodium carbonate, 5 mM potassium chloride, 20 mM HEPES, 1.8 mM calcium chloride, 0.1% BSA, pH 7.4) for one hour at room temperature ambient. After loading, the cells were centrifuged at 200 g for 5 minutes and resuspended in LKS at 2.5 x 0.06 ml. "1 The cells were then transferred to 96-well FLIPr plates (pre-incubated Becton Dickinson Poly-D-Lysine plates). with 5 μM fibronectin for two hours) at 100 ml / well.The plate was centrifuged at 200 g for 5 minutes and the cells were washed twice with LKS (200 μl, room temperature). dissolved in DMSO and added to a final concentration of 0.1% (v / v) DMSO The assays were initiated by the addition of an A50 concentration of eotaxin and the transient increase in fluorescence of fluo-3 (lEx = 490 nm and lEm = 520 nm) was periodically verified using a FLIPR (Fluorometric Image Formation Plate Reader, Molecular Devices, Sunnyvale, USA). b) Human Monocytes Human monocytes were isolated from peripheral blood coagulated with EDTA as previously described (Cunoosamy &Holbrook, J. Leukocyte Biology, 1998, S2, 13). Cells were resuspended (5xl06 ml "1) in LKS and loaded with 5 μM of FLU0-3 / AM + Pluronic F127 2.2 μl / ml (Molecular Probes) for one hour at room temperature After loading, the cells were centrifuged at 200 g for 5 minutes and resuspended in LKS at 0.5xl06 ml "1. The cells were then transferred to 96-well FLIPr plates (Costar). To each well, 100 μl of cells were added at a concentration of 0.5 x 106 ml. "1 The plates were centrifuged (200 g, 5 minutes, room temperature) to allow the cells to adhere After the centrifugation, the cells washed twice with LKS (200 μl, room temperature) A compound of the Examples was pre-dissolved in DMSO and added to a final concentration of 0.1% (v / v) of DMSO The tests were initiated by the addition of a A50 concentration of MlP-la and the transient increase in fluorescence of fluo-3 (lEx = 490 nm and lEm = 520 nm) was verified periodically using a FLIPR (Fluorometric Imaging Plate Reader, Molecular Devices, Sunnyvale, USA) The compounds of the Examples were found to be antagonists of [Ca 2+] _ mediated by eotaxin in human eosinophils and / or antagonists of [Ca 2+] mediated by MlP-la in human monocytes.

Chemotaxis of human eosinophils Human eosinophils were isolated from peripheral blood anticoagulated with EDTA as previously described (Hanser et al., J. Immunol Methods, 1991, 145, 105-110). Cells were resuspended at lOxlO6 ml "1 in RPMI containing 200 IU / ml penicillin, 200 μg / ml streptomycin sulfate and supplemented with 10% HIFCS, at room temperature, 700 μl of eosinophils were preincubated for 15 minutes at room temperature. 37 ° C with 7 μl of vehicle or compound (final concentration required lOOx in 10% DMSO). The chemotaxis plate (ChemoTx, 3 μm pore, Neuroprobe) was loaded by the addition of 28 μl of an eotaxin concentration (0.1 to 100 nM) containing a concentration of a compound according to the Examples or solvents to the wells inferiors of the chemotaxis plate. The filter was then placed on the wells and 25 μl of the eosinophil suspension was added to the top of the filter. The plate was incubated for 1 hour at 37 ° C in a humidified incubator with 95% air / 5% C02 to allow chemotaxis. The middle, which contained the cells that had not migrated, was carefully sucked up from the filter and discarded. The filter was washed once with phosphate buffered saline (PBS) containing 5 mM EDTA to remove any adherent cells. The cells that had migrated through the filter were concentrated by centrifugation (300xg for 5 minutes at room temperature) and the filter was removed, and the supernatant was transferred to each well of a 96-well plate (Costar). Concentrated cells were lysed by the addition of 28 μl of PBS containing 0.5% Triton xlOO, followed by two freeze / thaw cycles. The cell lysate was then added to the supernatant. The number of eosinophils that migrate was quantified according to the method of Strath et al., J. Immunol. Methods, 1985, 83_, 209 by measuring peroxidase activity of the eosinophils in the supernatant. It was found that certain compounds of theExamples are antagonists of the chemotaxis of human eosinophils mediated by eotaxin.

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

Claims (15)

CLAIMS Having described the invention as above, the content of the following claims is claimed as property:

1. A compound of the general formula:

R1- (Q) m-T- (CR2R3) n-V rx -X-R "^ (I) characterized in that: R1 represents an alkyl group of 1 to 12 carbon atoms optionally substituted with one or more substituents independently selected from the groups cyano, hydroxyl, alkoxy of 1 to 6 carbon atoms, alkylthio of 1 to 6 carbon atoms and alkoxycarbonyl of 1 to 6 carbon atoms, or R1 represents a saturated or unsaturated ring system of 3 to 10 members which may comprise up to 2 carbon atoms of the ring forming the carbonyl groups, and which may comprise up to 4 heteroatoms in the ring, independently selected from nitrogen, oxygen and sulfur, the ring system is optionally substituted with one or more substituents independently selected from halogen atoms, and the cyano, nitro, hydroxyl, alkyl groups of 1 to 6 carbon atoms, cycloalkyl 3 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms carbon, haloalkoxy of 1 to 6 carbon atoms, -NR5R6, cycloalkylamino of 3 to 6 carbon atoms, alkylthio of 1 to 6 carbon atoms, (alkylthio of 1 to 6 carbon atoms) (alkyl of 1 to 6 carbon atoms), alkylcarbonylamino of 1 to 6 carbon atoms, -C (0) NR7R8, sulfonamido, (di) alkylsulfonamido of 1 to 6 carbon atoms, phenyl, phenylamino, nitrophenyl, pyridyl, pyridylthio, benzodioxanil, thienyl, furanyl, and alkyl of 1 to 6 carbon atoms substituted with C (0) R9 or alkoxy of 1 to 6 carbon atoms; m is 0 or 1; Q represents a group OCH2, alkylene of 1 to 4 carbon atoms or alkenylene of 2 to 4 carbon atoms; T represents a C (0) NH group, or when m is 0, T may additionally represent a bond or an NH group, or when m is 1 and Q represents alkylene of 1 to 4 carbon atoms, T may additionally represent a group NH; n is 1, 2, 3 or 4; each R2 independently represents a hydrogen atom or an alkyl group of 1 to 4 carbon atoms; each R3 independently represents a hydrogen atom or an alkyl group of 1 to 4 carbon atoms; V represents a nitrogen atom; W represents a nitrogen atom or a CH group; X represents an oxygen atom or a group C (0),

CH (OH), NH or N (alkyl of 1 to 6 carbon atoms), with the proviso that when W represents a nitrogen atom, then X represents C (0); R4 represents a phenyl group optionally substituted with one or more substituents independently selected from halogen atoms, and from the amino, nitro, cyano, sulfonyl, sulfonamido, alkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms , haloalkoxy of 1 to 6 carbon atoms and alkylsulfonyl of 1 to 6 carbon atoms; R5 and R6 each independently represents a hydrogen atom or an alkyl group of 1 to 6 carbon atoms, hydroxy- (alkyl of 1 to 6 carbon atoms), or R5 and R6 together with the nitrogen atom to which they are attached form a saturated 4 to 7 membered heterocyclic ring; R7 and R8 each independently represents a hydrogen atom or an alkyl group of 1 to 6 carbon atoms; and R9 represents a hydroxyl group or -NR7R8; with the conditions that: a) when m is 0, T is CONH, n is 2, 3 or 4 and when R2 and R3 represent hydrogen, W is CH, X is C (O) or CH (OH) and R1 represents an unsaturated ring system of 3 to 10 members, substituted, then one or more substituents in the ring system do not include hydroxyl, halogen, alkoxy of 1 to 6 carbon atoms or haloalkoxy of 1 to 6 carbon atoms, and b) when W is N, X is C (O), R4 represents 3-trifluoromethylphenyl, m is 0 and T is bond, then R1 and (CR2R3) n taken together do not represent an alkyl group of 1 to 6 carbon atoms, and c) when W is CH, X is O, n is 2 or 3 and each R2 and R3 represents hydrogen, m is 0 and T is NH, then R1 does not represent a group or a pharmaceutically acceptable salt or solvate thereof. 2. A compound according to claim 1, characterized in that R1 represents an alkyl group of 1 to 10 carbon atoms, optionally substituted by one or two substituents independently selected from the groups cyano, hydroxyl, alkoxy of 1 to 4 carbon atoms , alkylthio of 1 to 4 carbon atoms and alkoxycarbonyl of 1 to 4 carbon atoms, or R 1 represents a saturated or unsaturated ring system of 3 to 10 members comprising up to 2 carbon atoms of the ring forming the carbonyl groups, and which comprise up to 4 heteroatoms in the ring, independently selected from nitrogen, oxygen and sulfur, the ring system is optionally substituted with one, two or three substituents independently selected from halogen atoms, and the cyano, nitro, hydroxyl, alkyl groups from 1 to 4 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkoxycarbonyl of 1 to 4 atoms of carbon, haloalkyl of 1 to 3 carbon atoms, haloalkoxy of 1 to 3 carbon atoms, -NR5R6, cycloalkylamino of 3 to 6 carbon atoms, alkylthio of 1 to 4 carbon atoms, (alkylthio of 1 to 4 carbon atoms) carbon) (alkyl of 1 to 4 carbon atoms), alkylcarbonylamino of 1 to 4 carbon atoms, -C (0) NR7R8, phenyl, phenylamino, nitrophenyl, pyridyl, pyridylthio, benzodioxanyl, thienyl, furanyl, and alkyl of 1 to 4 carbon atoms substituted with C (0) R9 or alkoxy of 1 to 4 carbon atoms. 3. A compound according to claim 1 or claim 2, characterized in that m is 1 and Q represents a group OCH2, alkylene of 1 to 3 carbon atoms or alkenylene of 2 to 3 carbon atoms.

4. A compound according to any of claims 1 to 3, characterized in that T represents a C (0) NH group.

5. A compound according to any of the preceding claims, characterized in that n is 2 or 3.

6. A compound according to any of the preceding claims, characterized in that V represents a nitrogen atom and W represents a CH group.

7. A compound according to any of the preceding claims, characterized in that X represents an oxygen atom or a group C (O) or NH.

8. A compound according to any of the preceding claims, characterized in that R4 represents a phenyl group optionally substituted by one or two halogen atoms.

9. A compound of the formula (I), or a pharmaceutically acceptable salt or solvate thereof, according to claim 1, characterized in that it is selected from: 4-chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2- [2- (dimethylamino) -2-oxoethoxy] benzamide, N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-ethoxybenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4-isopropoxybenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - 4-ethoxybenzamide, N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3- (trifluoromethoxy) benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4-methoxybenzamide, N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -4- (trifluoromethoxy) benzamide, N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2-furamide, N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2-phenylacetamide, N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-methoxybenzamide, 3-chloro-N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4-fluorobenzamide, N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-fluorobenzamide, N- hydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-hydroxybenzamide, N- hydrochloride. { 2- [4- (4-chlorobenzoyl) -1-piperidinyl] ethyl} -3- [2- (Methylamino) -2-oxoethoxy] benzamide, 2- [3-. { 2- [4- (4-fluorobenzoyl) -1-piperidinyl] ethyl} -2,4-dioxo-3, 4-dihydro-1 (2H) -quinazolinyl] -N, N-dimethylacetamide, N- hydrochloride. { 2- [4- (3,4-dichlorobenzoyl) -1-piperazinyl] ethyl} -3-methoxybenzamide, 3,4-dichloro-N-. { 2- [4- (3,4-dichlorobenzoyl) -1-piperazinyl] ethyl} benzamide, 4-chloro-N- hydrochloride. { 2- [4- (3,4-dichlorobenzoyl) -l-piperazinyl] ethyl} -2- [2- (dimethylamino) -2-oxoethoxy] benzamide, N-7-. { 2- [4- (3,4-Dichlorophenoxy) -1-piperidinyl] ethyl} -5-methyl [1,3] thiazolo [4, 5-d] pyrimidin-2,7-diamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -9-methyl-9H-purin-6-amine, N-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl} -1,3-benzothiazol-2-amine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -1, 3-benzoxazol-2-amine, 6-chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2-pyrazinamine, 6-chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-pyridazinamine, 6- ( { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -amino) -1,3-dimethyl-2,4 (1H, 3H) -pyrimidinedione, salt of N-hydrochloride. { l- [4- (3,4-Dichlorophenoxy) -piperidin-1-ylmethyl] -2-methyl-propyl} -4-methy1-benzamide, N- hydrochloride salt. { 1- [4- (3,4-dichloro-phenoxy) -piperidin-1-ylmethyl] -2-methyl-propyl} -3-methoxy-benzamide, N- dihydrochloride. { 2- [4- (3,4-dichloroanilino) -1-piperidinyl] ethyl} -3-methoxybenzamide, N- dihydrochloride. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl-N- (3-methoxybenzyl) amine, 3-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - 6-methoxy-2,4 (1H, 3H) -quinazolindione, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -3-fluorobenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -benzamide, 4-chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4-methoxybenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2-methoxybenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -3-methoxybenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - 2-nitrobenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2-methylbenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -3- (trifluoromethyl) benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -3, 5-dinitrobenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2-iodobenzamide, 4-cyano-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, 4-bromo-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4-methylbenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4-nitrobenzamide, 3-bromo-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, 3, 4-dichloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 4-fluorobenzamide, 2,4-dichloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 3-methylbenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 4-iodobenzamide, 4-chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-nitrobenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4-methyl-3-nitrobenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - 2-fluoro-5- (trifluoromethyl) benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -3- (trifluoromethoxy) benzamide, 3,5-dichloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4- (trifluoromethyl) benzamide, 3-cyano-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, 2-bromo-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -5-methoxybenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2-furamide, 3-chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, 2 -chloro-N-. { 2- [4- (3, 4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -3,5-difluorobenzamide, 2,3-dichloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl-2-naphthamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2- (methylsulfanyl) nicotinamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2-fluoro-6- (trifluoromethyl) benzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2, 4-difluorobenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2-thiophenecarboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2-quinoxalinecarboxamide, methyl 4- ({2- (4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -amino) -4-oxobutanoate, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -bicyclo [2.2.1] hept-5-en-2-carboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -cyclobutanecarboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2-methoxyacetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -cyclohexanecarboxa ida, (E) -N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -3-pheny1-2-propenamide, 2-chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} nicotinamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - 2-phenylacetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -cyclopentanecarboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2-phenoxyacetamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -benzamide, N-. { 2- [4- (4-chlorobenzoyl) -piperidinyl] ethyl} -3- (trifluoromethyl) benzamide, 4- (tert-butyl) -N-. { 2- [4- (4-chlorobenzoyl) -1-piperidinyl] ethyl} benzamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl. -4-methylbenzamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl nitrobenzamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl methylbenzamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl methyl-3-nitrobenzamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl cyanobenzamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl furamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -3-nitrobenzamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl. -2-naphthamide, N- [2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl (methylsulfanyl) nicotinamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -2- (2,3-dihydro-1,4-benzodioxin-2-yl) -1,3-thiazole-4-carboxamide, N-2-cyclopropyl-N-4-. { 2- [4- (3,4-dichlorophenoxy) -1 piperidinyl] ethyl} -2, 4-pyrimidindiamine, 2-. { [4- ( { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} amino) -2-pyrimidinyl] amino} -1-ethanol, 2- [[4- ( { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} amino) -2-pyrimidinyl] (methyl) amino] -1 -ethanol, N-4-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -N-2-phenyl-2,4-pyrimidindiamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2- (methylsulfanyl) -4-pyrimidinamine, N-. { 4- [2 - (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 6-methyl-2, 4-pyrimidindiamine, N-4-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -N-2, 6-dimethyl-2,4-pyrimidinediamine, 2-chloro-N-4-cyclopropyl-N-6-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl} -4, 6-pyrimidindiamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 4-pheny1-2-pyrimidinamine, N-2-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -N-4-N-4,6-trimethyl-2,4-pyrimidinediamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 4- (trifluoromethyl) -2-pyrimidinamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} • 4- (propylsulfanyl) -2-pyrimidinamine, N-2-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -N-4-phenyl-2,4-pyrimidinediamine, N-4-cyclopropyl-N-2-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2, 4-pyrimidindiamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} [1,8] naphthyridin-2-amine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 4- (3-pyridinyl) -2-pyrimidinamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2-pyrimidinamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4,6-dimethoxy-2-pyrimidinamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4- (3-furyl) -2-pyrimidinamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -1-methyl-lH-pyrazolo [3,4-d] pyrimidin-4-amine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -lH-purin-6-amine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -5-methylthieno [2, 3-d] pyrimidin-4-amine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -7-methylthieno [3,2-d] pyrimidin-4-amine, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -2-thiophenecarboxamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -2-quinoxalinecarboxamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -bicyclo [2.2.1] hept-5-en-2-carboxamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -cyclohexanecarboxamide ,. (IN- . { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} 3 - . 3-phenyl-2 -propenamide, N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -2-phenoxyacetamide, (E) -N-. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -3- (4-nitrophenyl) -2-propenamide, 2- (1-adamantyl) -N-. { 2- [4- (4-chlorobenzoyl) -1-piperidinyl] ethyl} acetamide, (4-chlorophenyl) (l- { 2- [(2-fluoro-4,5-dimethoxybenzyl) amino] ethyl} -4-piperidinyl) methanone, (4-chlorophenyl) (1- { 2- [(3,4,5-trimethoxybenzyl) -amino] ethyl] -4-piperidinyl) methanone, (4-chlorophenyl) (l- { 2- [(3-nitrobenzyl) amino] ethyl} -4-piperidini1) methanone, (4-chlorophenyl). { 1- [2- (isobutylamino) ethyl] -4-piperidinyl} methanone, 4- [( { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl.}. -amino) methyl] -4-ethylhexan-nitrile, (4-chlorophenyl) (1-) 2- [(7-hydroxy-3,7-dimethyloctyl) amino] ethyl] -4-piperidinyl) methanone, (4-chlorophenyl) [l- (2- {[[6-nitro-l, 3-benzodioxol-5-yl) methyl] amino.} Ethyl) -4-piperidinyl] methanone, [1- (2. {[[(5-chloro-l, 3-dimethyl-lH-pyrazole-4- il) -methyl] amino.} ethyl) -4-piperidinyl] (4-chlorophenyl) methanone, (4-chlorophenyl) [1- (2 { [3-nitro-4- (2-pyridinylsulfanyl) benzyl) ] amino.} ethyl) -4-piperidinyl] -methanone, (4-chlorophenyl) [1- (2 { [(E) -3- (4-nitrophenyl) -2-propenyl] amino}. ethyl) -4-piperidinyl] methanone, (4-chlorophenyl). { 1- [2- ( { [5- (3-nitrophenyl) -2-furyl] methyl.}. amino) ethyl] -4-piperidinyl} methanone, (4-chlorophenyl) [1- (2 { [5-nitro-2- (2-pyridinylsulfanyl) benzyl] amino} ethyl) -4-piperidinyl] -methanone, 6- [(. { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -amino) methyl] -2- (methylsulfanyl) nicotinonitrile,. { l- [2- ( { [5-chloro-l-methyl-3- (trifluoromethyl) -1H-pyrazol-4-yl] methyl} amino) ethyl] -4-piperidinyl} (4-chlorophenyl) methanone, (4-chlorophenyl) [1- (2. {[[3- (methylsulfanyl) butyl] -amino} ethyl) -4-piperidinyl] methanone, (4-chlorophenyl) [1 - (2- { [(4-phenyl-4-piperidinyl) -methyl] amino} ethyl) -4-piperidinyl] methanone, (4-chlorophenyl) [1- (2- { [(1 phenyl-lH-pyrazol-5-yl) methyl] amino.} ethyl) -4-piperidinyl] methanone, 3- [(. {2- 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -amino) ethyl] cyclohexancarboxylate ethyl, N-. { 4 - [( { 2- [4- (4-chlorobenzoyl) -l-piperidinyl] -ethyl} amino) methyl] phenyl} acetamide, (4-chlorophenyl) (1- {2- [(2,5-difluorobenzyl) amino] -ethyl} -4-piperidinyl) methanone, (4-chlorophenyl) (1- {2- [(4-Nitrobenzyl) amino] ethyl] -4-piperidinyl) methanone, (4-chlorophenyl) (1- {2 - [(2,6-dichlorobenzyl) amino] -ethyl} -4- piperidinyl) methanone, (4-chlorophenyl) (1- { 2- [(2-pyridinylmethyl) amino] -ethyl} -4-piperidinyl) methanone, (4-chlorophenyl) [1- (2-. { [(3-methyl-2-thienyl) methyl] -amino} ethyl) -4-piperidinyl] methanone, (4-chlorophenyl) (1- {2 - [(3-hydroxy-4-methoxybenzyl)] -amino] ethyl.} -4-piperidinyl) methanone, 3- [(. {2- 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl} -amino) methyl] -4H-chromen- 4-one, [1- (2-. {[[(5-chloro-l, 3-dimethyl-lH-pyrazol-4-yl) -methyl] amino} ethyl) -4-piperidinyl] (4- chlorophenyl) methanone, (4-chlorophenyl) [1- (2. {[[(2,6-dichloro-4-pyridinyl) -methyl] amino} ethyl) -4-piperidinyl] methanone, (4-chlorophenyl) ) [1- (2- { [(2-phenyl-lH-imidazol-4-yl) methyl] amino.} Ethyl) -4-pi peridinyl] methanone, (4-chlorophenyl) [1- (2-. { [(5-ethyl-2-thienyl) methyl] -amino} ethyl) -4-piperidinyl] methanone, (4-chlorophenyl) [1- (2 { [(2-chloro-3-quinolinyl) -methyl] aminojetyl) -4-piperidinyl] methanone, (4-chlorophenyl) [1- (2- { [(6-Methyl-2-pyridinyl) -methyl] amino.} Ethyl) -4-piperidinyl] methanone, (4-chlorophenyl) (l-. {2- 2- [( 3-quinolinylmethyl) amino] -ethyl.} -4-piperidinyl) methanone, 4- [(. {2- 2- [4- (4-chlorobenzoyl) -l-piperidinyl] ethyl] -amino) methyl] - 1, 5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one, (4-chlorophenyl) (1- {2 - [(4-pyridinylmethyl) amino] - | ethyl} .-4-piperidinyl) methanone, (4-chlorophenyl) (1- {2 - [(3-hydroxy-4-nitrobenzyl) -amino] ethyl} -4-piperidinyl) methanone, (4-chlorophenyl) (l- { 2- [(3,5-difluorobenzyl) amino] -ethyl.} -4-piperidinyl) methanone, (1- {2 - [(2-chloro-6-fluorobenzyl) amino] ethyl.} -4-piperidinyl) (4-chlorophenyl) methanone, [1- (2 { [(4-bromo-lH-pyrazol-3-yl) methyl] amino.}. -ethyl) -4 -piperidinyl] (4-chlorophenyl) methanone, 3- [( { 2- [4- (4-chlorobenzoyl) -l] -piperidinyl] ethyl} -amino) methyl] -6,7-dimethyl-4H-chromen-4-one, 2- acid. { 2 - [( { 2- [4- (4-chlorobenzoyl) -1-piperidinyl] ethyl} amino) methyl] -4-nitrophenoxy} acetic acid, (4-chlorophenyl) [1- (2. {[[(1-methyl-1H-benzimidazol-2-yl) methyl] amino] ethyl) -4-piperidinyl] methanone, (4-chlorophenyl) [1- (2-. {[[(2,4-dimethoxy-5-pyrimidinyl) methyl] amino} ethyl) -4-piperidinyl] methanone, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - 4- (methylamino) benzamide, 4-chloro-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-methoxybenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -3-methoxy-4-methylbenzamide, 3-amino-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -4-methoxybenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -1, 3-benzodioxol-5-carboxamide, 4-amino-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -3-methoxybenzamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -3-fluoro-4-methoxybenzamide, 5-bromo-N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -2-furamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -3-methyl-2-furamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4, 5-dimethyl-2-furamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 7-ethoxy-1-benzofuran-2-carboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -5-methoxy-1-benzofuran-2-carboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} - 7-methoxy-1-benzofuran-2-carboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- (4-fluorophenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- (2-methoxyphenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- (3-methylphenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- (2-methylphenyl) acetamide, 2- (3-bromo-phenyl) -N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} acetamide, 2- (2-chlorophenyl) -N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} acetamide, 2- (4-chlorophenyl) -N-. { 2- [4- (3, 4-dichlorophenoxy) -1-piperidinyl] ethyl} acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- [2- (trifluoromethyl) phenyl] acetamide, 2- (3-chlorophenyl) -N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2- (3, 4-dimethoxyphenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- (4-methoxyphenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2- (3,4-dichlorophenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- (3-fluoro-4-methoxyphenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} • 2- (4-Ethoxyphenyl) acetamide, 2- (1, 3-benzodioxol-5-yl) -N-. { 2- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] ethyl} acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- [4- (dimethylamino) phenyl] acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2- (4-methylphenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- (3, 4-difluorophenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- (3-methoxyphenyl) acetamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -4-phenylbutanamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -3-phenylpropanamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -3 - (3-methoxypheni1) propanamide, 2-Amino-N-. { 2- [4- (3, -dichlorophenoxy) -1-piperidinyl] ethyl} -l, 3-thiazole-4-carboxamide, 2- (acetylamino) -N-. { 2- [4- (3,4-dichlorophenoxy) -1-piperidinyl] ethyl} -1, 3-thiazole-4-carboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2- (4-pyridinyl) -1,3-thiazole-4-carboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2,4-dimethyl-l, 3-thiazole-5-carboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -2,5-dimethyl-1,3-oxazole-4-carboxamide, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} -1H-imidazole-4-carboxamide, N- hydrochloride salt. { 2- [4- (3,4-chlorophenoxy) l-piperidinyl] ethyl} -3-methoxybenzamide, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -1-methyl-lH-pyrazolo [3,4-d] pyrimidin-4-amine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -2, 6-dimethoxy-4-pyrimidinamine, N-4-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -N-2-N-2-dimethyl-2,4-pyrimidindiamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -2- [(methylsulfanyl) methyl] -4-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -2- (methylsulfanyl) -6- (trifluoromethyl) -4-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -5-methoxy-2- (methylsulfanyl) -4-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -6-methyl-2- (methylsulfanyl) -4-pyrimidinamine, N-. { 3- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] -propyl} -5-methoxy-2-methyl-4-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -2- (ethylsulfanyl) -6-methyl-4-pyrimidinamine, N-2-cyclopropyl-N-4-. { 3- [4- (3,4-dichlorophenoxy) -1-piperidinyl] propyl} -2, 4-pyrimidindiamine, 2-. { [4- ( { 3- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] -propyl.} Amino) -2-pyrimidinyl] amino} -1-ethanol, 2- [[4- ( { 3- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] -propyl} amino) -2-pyrimidinyl] (methyl) amino] - 1-ethanol, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -2- (methylsulfanyl) -4-pyrimidinamine, N-4-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -6-methyl-2, 4-pyrimidindiamine, N-4-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -N-2, 6-dimethyl-2, 4-pyrimidindiamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -4-pheny1-2-pyrimidinamine, N-2-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -5-fluoro-2, 4-pyrimidindiamine, N-2-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -N-4-N-4,6-trimethyl-2,4-pyrimidinediamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -4- (trifluoromethyl) -2-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -4- (propylsulfanyl) -2-pyrimidinamine, N-2-. { 3- [4- (3,4-Dichlorophenoxy) -l-piperidinyl] -propyl} -N-4-phenyl-2,4-pyrimidinediamine, N-2-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -N-4, 6-dimethyl-2, 4-pyrimidindiamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} [1,8] naphthyridin-2-amine, 2-. { [2- ( { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] propyl} amino) -4-pyrimidinyl] amino} -1-ethanol. 2- [[2- ( { 3- [4- (3, 4-dichlorophenoxy) -l-piperidinyl] propyl} amino) -4-pyrimidinyl (methyl) amino] -1-ethanol, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -4- (3-pyridinyl) -2-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -4- (3-thienyl) -2-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -2-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -4,6-dimethoxy-2-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -4- (3-furyl) -2-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -4- (2-thienyl) -2-pyrimidinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -lH-purin-6-amine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl-5-methylthieno [2,3-d] pyrimidin-4-amine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl-7-methylthieno [3,2-d] pyrimidin-4-amine, N-7-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -5-methyl [1,3] thiazolo [4,5-d] pyrimidin-2,7-diamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -9-methyl-9H-purin-6-amine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -2-pyridinamine, 5-chloro-N-. { 3- [4- (3,4-dichlorophenoxy) -1-piperidinyl] propyl} -2-pyridinamine, 6-chloro-N-. { 3- [4- (3,4-dichlorophenoxy) -1-piperidinyl] propyl} -2-pyridinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -6-methyl-2-pyridinamine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl} -1, 3-benzothiazol-2-amine, N-. { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl] -1,3-benzoxazol-2-amine, 6-chloro-N-. { 3- [4- (3,4-dichlorophenoxy) -1-piperidinyl] propyl} -2-pyrazinamine, 6-chloro-N-. { 3- [4- (3,4-dichlorophenoxy) -1-piperidinyl] propyl} -3-pyridazinamine, 6- ( { 3- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -propyl.} Amino) -1,3-dimethyl-2,4 (1H, 3H) -pyrimidinedione, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2, 6-dimethoxy-4-pyrimidinamine, N-4-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -N-2-N-2-dimethyl-2,4-pyrimidinediamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 2- [(methylsulfanyl) methyl] -4-pyrimidinamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 5-methoxy-2- (methylsulfanyl) -4-pyrimidinamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 6-methyl-2- (methylsulfanyl) -4-pyrimidinamine, N-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] ethyl} 5-methoxy-2-methyl-4-pyrimidinamine, and N-4-. { 2- [4- (3,4-dichlorophenoxy) -l-piperidinyl] -ethyl} -6-methyl-N-2-phenyl-2,4-pyrimidinediamine.

10. A process for the preparation of a compound of the formula (I) according to claim 1, characterized in that it comprises: (i) when T represents a C (0) NH group, a compound of the general formula is reacted R1"(Q) m -COL1 (II) where L1 represents a leaving group (for example, a hydroxyl group or halide, such as chloride) and R1, m and Q are as defined in formula (I), with a compound of the general formula or a salt by addition of the acid thereof (for example trifluoroacetate) wherein n, R 2, R 3, V, W, X and R 4 are as defined in formula (I); or (ii) when T represents a C (0) NH group and W represents a nitrogen atom, a compound of the general formula is reacted R1- (Q) mT- (CR 2Rj3) nV G? NH \ - / (IV) where R1, m, Q, T, n, R2, R3 and V are as defined in formula (I), with a compound of the general formula X - R * (V) where L2 represents a leaving group (eg, a halogen atom) and X and R4 are as defined in formula (I); or (iii) when T represents an NH group and m is 0, a compound of the general formula is reacted R1 - L3 (VI) where L3 represents a leaving group (eg, a halogen atom) and R1 is as defined in formula (I), with a compound of formula (III) as defined in subparagraph (i) above; or (iv) when T represents an NH group, m is 1 and Q represents alkylene of 1 to 4 carbon atoms, by reacting a compound of the general formula R1 - (CH2) P -CHO (VII) wherein p is 0, 1, 2 or 3 and R1 is as defined in formula (I), with a compound of formula (III) as defined in subparagraph ( i) previous; or (v) when T represents a bond and m is 0, a compound of the general formula is reacted R1 - (CR2R3) n-L4 (VIII) where L4 represents a leaving group such as a halogen atom (eg, chlorine) and n, R1, R2 and R3 are as defined in formula (I), with a compound of the general formula where W, X and R4 are as defined in formula (I); and optionally after (i), (ii), (iii), (iv) or (v) the compound of the formula (I) is converted to a further compound of the formula (I) and / or a salt is formed or pharmaceutically acceptable solvate of the compound of the formula (I).

11. A pharmaceutical composition, characterized in that it comprises a compound of the formula (I), or a pharmaceutically acceptable salt or solvate thereof, according to any of claims 1 to 9, in association with a pharmaceutically acceptable adjuvant, diluent or carrier.

12. A process for the preparation of a pharmaceutical composition according to claim 11, characterized in that the process comprises the mixture of a compound of the formula (I), or a pharmaceutically acceptable salt or solvate thereof, in accordance with any of Claims 1 to 9, with a pharmaceutically acceptable adjuvant, diluent or carrier.

13. A compound of the formula (I), or a pharmaceutically acceptable salt or solvate thereof, according to any of claims 1 to 9 for use in therapy. The use of a compound of the formula (I), or a pharmaceutically acceptable salt or solvate thereof, according to any one of claims 1 to 9, in the manufacture of a medicament for use in therapy. 15. The use of a compound of the formula (I), or a pharmaceutically acceptable salt or solvate thereof, according to any of claims 1 to 9, in the manufacture of a medicament for the treatment of human diseases or conditions in which modulates the activity of the chemokine receptor. SUMMARY OF THE INVENTION The invention provides the compounds of the general formula (I) wherein: R 1 represents alkyl of 1 to 12 carbon atoms optionally substituted by a saturated or unsaturated ring system of 3 to 10 members, optionally substituted, comprising up to 2 carbon atoms; Carbon in the ring forming carbonyl groups, and comprising up to 4 heteroatoms in the ring independently selected from nitrogen, oxygen and sulfur; m is 0-1; Q represents OCH2, alkylene of 1 to 4 carbon atoms or alkenylene of 2 to 4 carbon atoms; T represents C (0) NH, or when m is 0, T may additionally represent a bond or NH, or when m is 1 and Q represents alkylene of 1 to 4 carbon atoms, T may additionally represent NH; n is 1-4; each R2 and R3 independently represents hydrogen or alkyl of 1 to 4 carbon atoms; V represents N, and W represents N or CH; X represents O, C (O), CH (OH), S02, NH or N (alkyl of 1 to 6 carbon atoms) with the proviso that when W represents N, then X represents either C (O) or S02 , and when W represents CH, then X is different from S02; R4 represents optionally substituted phenyl; R5 and R6 each independently represent hydrogen, alkyl of 1 to 6 carbon atoms, or hydroxy-alkyl of 1 to 6 carbon atoms, or R5 and R6 together with the nitrogen atom to which they are attached form a saturated heterocyclic ring of 4 to 7 members; R7 and R8 each independently represent hydrogen or alkyl of 1 to 6 carbon atoms; and R9 represents OH or -NR7R8; the processes for its preparation, the pharmaceutical compositions that contain them and their use in therapy. ^ ¡^ ¡¡¡¡¡^ ^ ^^^^^ ¿^ ^^^^