Novel piperidine and piperazine derivatives

Abstract

The invention provides piperidine and piperazine derivatives of general formula (I), processes for their preparation, pharmaceutical compositions containing them, a process for preparing the pharmaceutical compositions, and their use in therapy.

1 . A compound of general formula  
     
       
         
         
             
             
         
       
     
     wherein, 
 X represents a nitrogen atom or a group C(R 5 );  
 Y represents an oxygen or sulphur atom or a group NR 6 ;  
 either R 1  and R 2  each independently represent a hydrogen atom or a C 1 -C 4  alkyl group but do not both simultaneously represent a hydrogen atom; or R 1  and R 2  together represent a group —CH 2 ZCH 2 —;  
 Z represents a bond, an oxygen or sulphur atom or a group CH 2  or NR 7 ;  
 m is 0 or 1;  
 R 3  represents a 5- to 10-membered unsaturated ring system which may comprise from 1 to 4 ring heteroatoms independently selected from nitrogen, oxygen and sulphur, the ring system being optionally substituted by one or more substituents independently selected from halogen, nitro, cyano, NR 8 R 9 , C 1 -C 4  alkyl C(O)NH—, NHR 12 C(O), C 1 -C 4  alkyl-SO 2 —, C 1 -C 4  alkyl-SO 2 NH—, C 1 -C 4 alkyl-NHSO 2 —, C 1 -C 1  alkoxy, and C 1 -C 4  alkyl optionally substituted by one or more fluorine atoms;  
 R 4  represents a phenyl or pyridinyl group, each of which is substituted in an ortho position with a substituent selected from halogen, C 1 -C 4  alkoxy, C 1 -C 4  alkylthio, and C 1 -C 4  alkyl-optionally substituted by one or more fluorine atoms, the phenyl or pyridinyl group being optionally further substituted by one or more substituents independently selected from halogen, cyano, hydroxyl, C 1 -C 4  alkylthio, C 1 -C 4  alkyl-NH—, NHR 13 -C 1 -C 4  alkyl-, C 1 -C 4  alkyl-SO 2 —, C 1 -C 4  alkyl-SO 2 NH—, C 1 -C 4  alkyl-NHSO 2 —, C 1 -C 4  alkyl-C(O)NH—, C 1 -C 4 alkyl-NHC(O)—, -D-G, C 1 -C 4  alkoxy optionally substituted by —NR 14 R 15  or by R 16 , and C 1 -C 4  alkyl optionally substituted by one or more fluorine atoms or by one or more hydroxyl groups,  
 or R 4  represents a 9- or 10-membered unsaturated bicyclic ring system which may comprise from 1 to 4 ring heteroatoms independently selected from nitrogen, oxygen and sulphur, the bicyclic ring system being optionally substituted by one or more substituents independently selected from halogen, oxo, C 1 -C 4 alkyl, C 1 -C 4  alkoxy, C 1 -C 4  alkylthio and —NR 10 R 11 ;  
 D represents an oxygen atom or a group (CH 2 ) n , or CH 2 NH;  
 n is 1, 2 or 3;  
 G represents a piperazinyl, morpholinyl or 2,5-diazabicyclo[2.2.1]heptyl group, or G represents a piperidinyl group optionally substituted by amino;  
 R 5  represents a hydrogen atom, or a hydroxyl or C 1 -C 4  alkoxy group;  
 R 6  represents a hydrogen atom, or a cyano, nitro, hydroxyl C 1 -C 4  alkyl or C 1 -C 4  alkoxy group;  
 R 7 , R 8  and R 9  each independently represent a hydrogen atom or a C 1 -C 4  alkyl group;  
 R 10  and R 11  each independently represent a hydrogen atom or a C 1 -C 4  alkyl group, or R 10  and R 11  together with the nitrogen atom to which they are attached form a 5- or 6 membered saturated heterocyclic ring comprising one or two ring nitrogen atoms;  
 R 12  represents a hydrogen atom, or a C 1 -C 4  alkyl group optionally substituted by amino;  
 R 13  represents a hydrogen atom, or a C 1 -C 4  alkyl group optionally substituted by hydroxyl;  
 R 14  and R 15  each independently represent a hydrogen atom or a C 1 -C 4  alkyl group optionally substituted by hydroxyl, or R 14  and R 15  together with the nitrogen atom to which they are attached form a 5- or 6-membered saturated heterocyclic ring comprising one or two ring nitrogen atoms; and R 16  represents a 1-(C 1 -C 4 -alkyl)-piperidinyl group;  
 with the proviso that when m is 0, X is N and Y is O, then R 4  does not represent 2-benzothiazolyl;  
 or a pharmaceutically acceptable salt or solvate thereof.  
 
   
   
       2 . A compound according to  claim 1 , wherein X represents a nitrogen atom.  
   
   
       3 . A compound according to  claim 1  or  claim 2 , wherein Y represents an oxygen atom.  
   
   
       4 . A compound according to any one of  claims 1  to  3 , wherein, in R 3 , the 5- to 10 membered unsaturated ring system is selected from phenyl, pyridinyl, pyrimidinyl naphthyl, furanyl, pyrryl, thienyl, isothiazolyl, imidazolyl, benzimidazolyl, tetrazolyl, pyrazinyl, quinolinyl, isoquinolinyl, benzofuranyl, isobenzofuranyl, benzothienyl, pyrazolyl, indolyl, isoindolyl, purinyl, oxazolyl, isoxazolyl, thiazolyl, triazinyl benzothiazolyl, benzooxazolyl, imidazopyrazinyl, triazolopyrazinyl, naphthyridinyl, furopyridinyl, thiopyranopyrimidinyl, pyridazinyl, quinazolinyl pteridinyl triazolopyrimidinyl, triazolopyrazinyl, thiapurinyl, oxapurinyl, deazapurinyl, thiazolopyrimidinyl, indolinyl, benzooxadiazolyl, benzothiadiazolyl, tetrahydroisoquinilinyl, 2-(isoxazol-3-yl)thienyl, and thienopyrimidinyl.  
   
   
       5 . A compound according to any one of the preceding claims, wherein, in R 3 , the ring system is optionally substituted by one or more substituents independently selected from methyl, amino, cyano, methoxy, chloro, nitro, NH 2 C(O), CH 3 C(O)NH—, CH 3 SO 2 —, CH 3 SO 2 NH— and NH 2 CH 2 CH 2 NHC(O)—.  
   
   
       6 . A compound according to any one of the preceding claims, wherein, in R 4 , an ortho substituent in the phenyl or pyridinyl group is halogen or C 1 -C 4  alkyl optionally substituted by one or more fluorine atoms.  
   
   
       7 . A compound according to any one of  claims 1  to  5 , wherein, R 4 , the 9- or 10-membered unsaturated bicyclic ring system is selected from naphthyl, benzimidazolyl, quinolinyl, indolinyl, isoquinolinyl, benzofuranyl, isobenzofuranyl, benzothienyl, indolyl, isoindolyl, benzthiazolyl, benzoxazolyl and quinazolinyl.  
   
   
       8 . A compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof as defined in  claim 1  which is selected from: 
 (±)-N-(2,6-Dimethylphenyl)-2-(3-methyl-4-(thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)acetamide,    cis-[2-(3,5-Dimethyl-4-(thieno[2,3-d]pyrimidinyl)piperazin-1-yl)]-N-(2,6-dimethylphenyl)acetamide,    (±)-2-[3-Methyl-4-(4-methylphenyl)piperazin-1-yl]-N-(2,6-dimethylphenyl) acetamide,    cis-N-[3-Hydroxymethyl-2-methylphenyl]-2-(3,5-dimethyl-4-(thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)acetamide,    (R)-2-[4-(1-Methylimidazol-4-sulphonyl-4-yl)-3-ethylpiperazin-1-yl]-N-quinolin-5-yl)acetamide,    cis-2-[3,5-Dimethyl-4-thieno[2,3-d]-pyrimidin-1-yl]-N-(2-methylphenyl)acetamide,    cis-N-(2 Chlorophenyl)-2-[3,5-dimethyl-4-(thieno[2,3-d]pyrimidin-4-yl-piperazin-1-yl]acetamide,    cis-N-(2-Chlorophenyl)-2-[3,5-dimethyl-4-(9-methyl-9H-purin-6-yl)piperazin-1-yl]acetamide,    cis-2-3,5-Dimethyl-4-thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)-N-isoquinolin-5-yl)acetamide,    cis-2-(3,5-Dimethyl thieno[2,3-d]pyrimidin-4-yl-N-quinolin-5-yl-[acetamide,    cis-2-(3,5-Dimethyl-4-(thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)-N-2-methyl-5-methylsulphonamidophenyl)acetamide,    cis-2-(3,5-Dimethyl-4-(thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl]-N-(2-trifluoromethylphenyl)acetamide,    cis-2-(3,5-Dimethyl-4-(thieno[2,3 d]pyrimidin-4-piperazin-1-yl)-N-(3-methylpyridin-2-yl)acetamide,    cis-2-3,5-Dimethyl-4-(thieno[2,3-d])pyrimidin-4-yl)piperazin-1-yl)-N-(isoquinolin-1-yl)acetamide,    cis-4-(4-Amino-5-cyanopyrimidin-2-yl)-3,5-dimethylpiperazin-1-yl)-N-(2-chlorophenyl)acetamide,    cis-2-(4-Benzenesulphonyl-3,5-dimethylpiperazin-1-yl)-N-(2 chloro-phenyl)acetamide,    (±)-N-(2,6-Dimethylphenyl)-2-[(3,5-methyl-4-thiazolo(5,4-d)pyrimidin-7-yl)piperazin-1-yl]acetamide,    cis-N-(2-Chlorophenyl)-2-[(3,5-dimethyl-quinazolin-4-yl)piperazin-1-yl]acetamide,    N-(2-Chlorophenyl)-2-[(8-thieno[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]acetamide,    N-(2-Methylphenyl)-2-[(8-(9-methyl-9H-purin-6-yl)-3,8 diazabicyclo[3.2.1]oct-3-yl]acetamide,    2-[8-(9-Methyl-9H-purin-6-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(quinolin-5-yl)acetamide,    N-(Quinolin-5-yl)-2-[8-thiazolo[5,4-d]pyrimidin-7-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]acetamide,    N-(2-Methylphenyl)-2-[(8-thiazolo[5,4-pyrimidin-7-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]acetamide,    N-(2-Methyl-5-methylsulphonyl)amidophenyl)-2-(8-(9-methyl-9H-purin-6-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]acetamide,    N-[2-Methyl-5-methylsulphonyl)amidophenyl]-2-[(8-thiazolo[5,4-d]pyrimidin-7-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]acetamide,    N-[2-Methyl-5-methylsulphonyl)amidophenyl]-2-[4-thieno[2,3-pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]acetamide,    cis-2-3,5-Dimethyl-4-(thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)-N-2-methyl-5-(1-piperazinylmethyl)phenyl)acetamide, hydrochloride salt,    N-(2-Methylphenyl)-2-[(8-(thieno[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]acetamide,    N-[5-(Methanesulphonylamido-2-methylphenyl)-2-[8-(thieno[2,3-d]pyrimidin-4-yl)-8-azabicyclo[3.2.1]oct-3-yl]acetamide,    N-(2-Methyl-5-(1-piperazinylmethyl)phenyl)-2-[(8-(thieno[2,34]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]acetamide,    cis-N-(5-(2-Aminoethoxy)-2-methyl-phenyl)-2-(3,5-ethyl(thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)acetamide, hydrochloride salt,    cis-N-5-(2-(N-Methylamino)ethoxy)-2-methyl-phenyl)-2-3,5-dimethyl-4-(thieno[2,3 d]pyrimidin-4-yl)piperazin-1-yl)acetamide, hydrochloride salt,    cis-N-(5-(2-Methylamino)ethoxy)-2-methyl-phenyl)-2-(4-benzenesulphonyl)-3,5-dimethyl)piperazin-1-yl)acetamide,    cis-N-[5(2-Aminoethoxy)-2-methyl-phenyl)-2(4-benzenesulphonyl-3,5-dimethyl)piperazin-1-yl]acetamide, hydrochloride salt,    N-(2-Oxo-2,3 dihydro-1H-indol-4-yl)-2-(8-thieno[2,3-d]pyrimidin-4-yl-3,8-diazabicyclo[3.2.1]oct-3-yl)acetamide,    N-3-Fluoro-2-methyl-phenyl)-2-((8 quinazolin-4-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl)acetamide,    N-(2-Methylphenyl)-2-[8(benzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]acetamide,    N-(3-Fluoro-2-methylphenyl)-2-[8-(benzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]acetamide,    cis-N-(3-Fluoro-2-methyl-phenyl)-2-(4-benzenesulphonyl)-3,5-dimethyl)piperazin-1-yl)acetamide,    N-(2-Methylphenyl)-2-[8-(3-cyanobenzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]acetamide,    2-[8-(3-Methoxybenzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-2-methylphenyl)acetamide,    2-[8-Benzo[1,2,5]oxadiazole-4-sulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2-methylphenyl)acetamide 2-[8-(Benzo[1,2,5]thiadiazole-4-sulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-2-methylphenyl)acetamide,    2-[8-(5-Chlorthieno-2-yl)sulphonyl)-3,8-d]diazabicyclo[3.2.1]oct-3-yl]-N-(2-methylphenyl)acetamide,    2-[8(2-Chlorobenzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-2-methylphenyl)acetamide,    2-[8-(5-Chloro-2-methoxybenzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2-methylphenyl)acetamide, (2-methylphenyl)acetamide,    N-(2-Methylphenyl)-2-[(8-(3-methylthieno[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]acetamide,    cis-2-(3,5-Dimethyl-4-(thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)-N-(1-methyl-1H-benzoimidazol-2-yl)acetamide,    cis-2-(3,5-Dimethyl(thieno[2,3-d]pyrimidin-4-yl)piperazin-1-yl)-N-2-methyl-5-(4-piperidinyloxy)phenyl)acetamide, hydrochloride salt,    cis-2-(3,5-Dimethyl-4-benzenesulphonyl)piperazin-1-yl)-N-(2-methyl-5-(4-piperidinyloxy)phenyl)acetamide,    cis-2-3,5-Dimethyl(quinazolin-4-yl)piperazin-1-yl)-N-2-methyl-5-(4-piperidinyloxy)phenyl)acetamide,    cis-2-3,5-Dimethyl-4-(4-quinazolinyl)piperazin-1-yl)-N-2-methyl-5-(piperazin-4-yl-methyl)phenyl) acetamide,    cis-2-(3,5-Dimethyl-4-(quinazolinyl)piperazin-1-yl)-N-2-methyl-5-(2-(N-methylamino)ethoxy)phenyl)acetamide,    cis-2-043 Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-(2-methylphenyl)acetamide,    cis-N-2-Methylphenyl)-2-[4-(3-nitrobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-acetamide,    cis-2-[4-(3-Aminobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-(2-methylphenyl)acetamide    cis-2-(3,5-Dimethyl-4-(3-cyanobenzenesulphonyl-1-yl)piperazin-1-yl)-N-quinolin-5-yl)acetamide,    cis-2-(3,5-Dimethyl-4-(4-cyanobenzenesulphonyl-1-yl)-N-quinolin-5-yl) acetamide,    cis-2-(4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl)-N-3-fluoro-2-methylphenyl)acetamide,    cis-2-(4-(4-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl)-N-3-fluoro-2-methylphenyl)acetamide,    cis-2-[4-(3-Acetylaminobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-2-methylphenyl)acetamide,    cis-2-[4-(3-Aminocarbonylbenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-(2-methylphenyl)acetamide,    cis-2-[4-(3-Methanesulphonylalminobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-(2-methylphenyl)acetamide,    cis-2-[4-(2-Methanesulphonylbenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-3-methoxy-2-methylphenyl)acetamide,    cis-2-[4-(2-Methanesulphonylbenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-3-fluoro-2-methylphenyl) acetamide,    cis-2-[4-(1-Methylimidazol-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-1-yl]-N-(quinolin-5-yl)acetamide,    cis-2-[4-(1-Methylimidazol-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-1-yl]-N-3-methoxy-2-methylphenyl)acetamide,    cis-2-[4-(1-Methylimidazol-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-1-yl]-N-(3-fluoro-2-methylphenyl)acetamide, trifluoromethylphenyl)acetamide,    cis-2-[4-2-Aminoethylaminocarbonylbenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-(2-methylphenyl)acetamide,    cis-2-[4-(1,1,2,2-Tetrahydroisoquinilin-7-sulphonyl-7-yl)-3,5-dimethylpiperazin-1-yl]-N-2,6-dimethylphenyl)acetamide,    cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-(2,6-dimethylphenyl)acetamide,    cis-2-[4-(4-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-2-methylphenyl)acetamide,    cis-2-[4-(2-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-(2,6 dimethylphenyl)acetamide, hydrochloride salt,    cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-(2-chlorophenyl)acetamide,    2-[8(Isquinolin-1-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-2-methylphenyl)acetamide,    cis-2-[4-(4-Acetamidobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl-N-(2-methylphenyl)acetamide,    cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-N-yl]-N-(2-trifluoromethylphenyl)acetamide,    cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1]-yl]-N-2-methyl-5-methanesulphonamidophenyl)acetamide,    2-[8-(4-Benzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-2-methylphenyl)acetamide,    2-[8-(2-Benzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-2-methylphenyl)acetamide,    cis-2-[4-(1,2-Dimethylimidazol-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-1-yl]-N-(quinolin-5-yl)acetamide,    cis-2-[4-(5-Chloro-1,3-dimethylpyrazole-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-1-yl]-N-(3-methoxy-2-methylphenyl)acetamide,    2-[8-(2(Isoxazol-3-yl)thiophen-5-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2-methylphenyl)acetamide,    2-[8-(1,1,2,2-Tetrahydroisoquinilin-7-sulphonyl)-3,8 diazabicyclo[3.2.1]oct-3-yl]-N-(2-methylphenyl) acetamide,    cis-2-[4-(5-Chloro-1,3-dimethylpyrazole-4-yl)-3,5-dimethylpiperazin-1-yl]-N-(2-methylphenyl)acetamide,    cis-2-[4-3,5-Dimethylisoxazole-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-1-yl]-N-(2-methylphenyl)acetamide,    cis-2-[4-(2-Methanesulphonylbenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-2-methylphenyl)acetamide,    cis-2-[4-(3-Cyanobenzenesulphonyl)-N-(3,5-dimethylpiperazin-1-yl]-N-3-methoxy-2-methylphenyl)acetamide,    cis-2-[4-Methanesulphonylbenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-(2-methylphenyl)acetamide,    cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-5-cyano-2-methylphenyl)acetamide,    cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-5-acetamido-2-methylphenyl)acetamide,    (R)-2-[4-(4-Cyanobenzenesulphonyl)3-methylpiperazin-1-yl]-N-quinolin-5-yl)acetamide,    (S)-2-[4-(4-Cyanobenzenesulphonyl)-3-methylpiperazin-1-yl]-N-quinolin-5-yl)acetamide,    cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-2-methyl-5-methanesulphonylphenyl)acetamide,    cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-(2-methyl-5-(4 amino-1-piperidinyl)methyl)phenyl]acetamide,    (R)-2-[4-(Methanesulphonylbenzenesulphonyl)-3-methylpiperazin-1-yl]-N-(quinolin-5-yl)acetamide,    (R)-2-[4-(4-Acetamidobenzenesulphonyl)-3-methylpiperazin-1-yl]-N-quinolin-5-yl)acetamide,    cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl-]-N-2-methyl-5-piperazinymethyl)phenyl)acetamide,    cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-2-methyl-5-(4-piperidinylamino)methyl)phenyl)acetamide,    cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-2-methyl-5-morpholinyl)methyl)phenyl)acetamide,    cis-2-[4-(3-Cyanobenzenesulphonyl)-3.5 methylpiperazin-1-yl]-N-2-methyl-5-(2-hydroxyethylamino)methyl)phenyl)acetamide,    cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-2-methyl-5-(S,S)-(2,5 diazabicyclo[2,2,1]hept-2-yl)methyl)phenyl)acetamide,    (R)-2-[4-(2-Pyridinesulphonyl)-3-methylpiperazin-1-yl]-N-(quinolin-5-yl)acetamide,    cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-(2-methyl-3-(4-amino-1-piperidinyl)methyl)phenyl]acetamide,    cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-2-methyl-3-(4-piperidinylamino)methyl)phenyl)acetamide,    cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-(2-methyl-3-(1-piperazinylmethyl)phenyl)acetamide,    cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-2-methyl-3-(S,S-(2,5-diazabicyclo[2,2,1]hept-2-yl)methyl)phenylacetamide,    cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-((2-methyl-3-(1-morpholinyl)methyl)phenyl)acetamide,    cis-2-[4-(3 Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-((2-methyl-3-(2-(1-pyrrolidinyl)ethoxy)phenyl)acetamide,    (±)cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-((2-methyl-3-(1-methylpiperidin-3-yl)methoxy)phenyl)acetamide,    cis-2-[4-(3 Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-(2-methyl-4-(2-(1-pyrrolidinyl)ethoxy)phenyl)acetamide,    (±) cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1 yl]-N-(2-methyl-4-(1-methylpiperidin-3-yl)methoxy)phenyl)acetamide,    (±) cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-((2-methyl-5-(1-methylpiperidin-3-yl)methoxyphenyl)acetamide,    (±)cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-1-yl]-N-((2-methyl-6-methylpiperidin-3-yl)methoxy)phenyl)acetamide, and    cis-2-[4-(1-Methylimidazol-4-sulphonyl 4-yl)-3,5-dimethylpiperazin-1-yl]-N-((2-methyl-3(2-(1-pyrrolidinyl)ethoxyphenyl)acetamide.    
   
   
       9 . A process for the preparation of a compound of formula (I) as defined in  claim 1 , which comprises 
 (a) reacting a compound of general formula                          wherein X, Y, R 1 , R 2  and R 4  are as defined in formula (I), with a compound of general formula (III), R 3 —(SO 2 ) m —L 1 , wherein L 1  represents a leaving group and m and R 3  are as defined in formula (1); or    (b) when X represents a nitrogen atom and Y represents an oxygen atom, reacting a compound of general formula                          wherein m, R 1 , R 2  and R 3  are as defined in formula (I), with a compound of general formula                          wherein L 2  represents a leaving group and R 4  is as defined in formula (I); or    (c) reacting a compound of general formula                          wherein L 3  represents a leaving, group and m, X, Y, R 1 , R 2  and R 3  are as defined in formula (I), with a compound of general formula (VII), H 2 N-R 4  wherein R 4  is as defined in formula (I);    and optionally after (a), (b) or (c) converting the compound of formula (I) obtained to a pharmaceutically acceptable salt or solvate thereof.    
   
   
       10 . A pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of  claims 1  to  8  in association with a pharmaceutically acceptable adjuvant, diluent or carrier.  
   
   
       11 . A process for the preparation of a pharmaceutical composition as claimed in  claim 10  which comprises mixing a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as defined in any one of  claims 1  to  8  with a pharmaceutically acceptable adjuvant, diluent or carrier.  
   
   
       12 . A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of  claims 1  to  8  for use in therapy.  
   
   
       13 . A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof; 
 as claimed in any one of  claims 1  to  8  for use in the treatment of rheumatoid arthritis.    
   
   
       14 . A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof; 
 as claimed in any one of  claims 1  to  8  for use in the treatment of chronic obstructive pulmonary disease.    
   
   
       15 . Use of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof; as claimed in any one of  claims 1  to  8  in the manufacture of a medicament for use in therapy.  
   
   
       16 . Use of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of  claims 1  to  8  in the manufacture of a medicament for use in tang rheumatoid arthritis.  
   
   
       17 . Use of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof as claimed in any one of  claims 1  to  8  in the manufacture of a medicament for use in beating chronic obstructive pulmonary disease.  
   
   
       18 . A method of effecting immunosuppression which comprises administering a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof as claimed in any one of  claims 1  to  8  to a patient in need thereof.  
   
   
       19 . A method of treating rheumatoid arthritis which comprises administering a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of  claims 1  to  8  to a patient in need thereof.  
   
   
       20 . A method of treating chronic obstructive pulmonary disease which comprises administering a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of  claims 1  to  8  to a patient in need thereof.