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.

Description: Novel piperidine and piperazine derivatives The present invention relates to piperidine and piperazine derivatives, processes for their preparation, pharmaceutical compositions containing them, a process for preparing the pharmaceutical compositions, and their use in therapy. The P2X 7 receptor (previously known as P2Z receptor), which is a ligand-gated ion channel, is present on a variety of cell types, largely those known to be involved in the inflarmnatory/immune process, specifically, macrophages, mast cells and lymphocytes (T and B). Activation ofthe P2X 7 receptor by extracellular nucleotides, in particular adenosine triphosphate, leads to the release of interleukin- lβ (IL-lβ) and giant cell formation (macrophages/ icroglial cells), degranulation (mast cells) and L-selectin shedding (lymphocytes). P2X 7 receptors are also located on antigen-presenting cells (APC), keratinocytes, salivary acinar cells (parotid cells), hepatocytes, erythrocytes, erythroleukaemic cells, monocytes, fibroblasts, bone marrow cells, neurones and renal mesangial cells. It would be desirable to make compounds effective as P2X 7 receptor antagonists for use in the treatment of inflammatory, immune or cardiovascular diseases, in the aetiologies of which the P2X 7 receptor may play a role. In accordance with the present invention, there is therefore provided a compound of general formula wherein, X represents a nitrogen atom or a group C(R ); Y represents an oxygen or sulphur atom or a group NR , preferably an oxygen atom; 1 2 either R and R each independently represent a hydrogen atom or a Cι-C alkyl 1 2 group but do not both simultaneously represent a hydrogen atom, or R and R together represent a group -CH 2 ZCH 2 -; Z represents a bond, an oxygen or sulphur atom or a group CH 2 or NR , and is preferably a bond; is O or 1; R 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 r C 4 alkyl-C(O)NH-, NHR 12 C(O)-, C r C 4 alkyl-SO 2 -, C r C 4 alkyl-SO 2 NH-, C r C 4 alkyl-NHSO 2 -, C r C 4 alkoxy, and C; [ -C 4 alkyl optionally substituted by one or more fluorine atoms; R represents a phenyl or pyridinyl group, each of which is substituted in an ortho position with a substituent selected from halogen, C^-Q^ alkoxy, 0^4 alkylthio, and C r 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 r C 4 alkylthio, C r C 4 alkyl-NH-, NHR 13 -C r C 4 alkyl-, C r C 4 alkyl-SO 2 -, C r C 4 alkyl-SO 2 NH-, C r C 4 alkyl-NHSO 2 -, C r C 4 alkyl-C(O)NH-, C r C 4 alkyl-NHC(O)-, -D-G, C r Q 4 alkoxy optionally substituted by -NR R or by R , and Ci -C 4 alkyl optionally substituted by one or more fluorine atoms or by one or more hydroxyl groups, or R 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 r C 4 alkyl, C r C 4 alkoxy, Cι-C 4 alkylthio and -NR 10 R π ; D represents an oxygen atom or a group (CH 2 ) n or CH 2 NH; n is i, 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 (-NH 2 ); R represents a hydrogen atom, or a hydroxyl or C 1 -C 4 alkoxy group; R represents a hydrogen atom, or a cyano, nitro, hydroxyl, Cι-C 4 alkyl or C 1 -C alkoxy group; R 7 , R 8 and R 9 each independently represent a hydrogen atom or a C r C 4 alkyl group; R and R each independently represent a hydrogen atom or a C r C alkyl group, or R and R 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 Ci -C 4 alkyl group optionally substituted by amino (-NH 2 ); R 13 represents a hydrogen atom, or a C C 4 alkyl group optionally substituted by hydroxyl; R and R each independently represent a hydrogen atom or a C 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 represents a l-(Cι-C 4 -alkyι)-piperidinyl group; with the proviso that when m is 0, X is N and Y is O, then R does not represent 2-benzothiazolyl; or a pharmaceutically acceptable salt or solvate thereof. In the context ofthe present specification, unless otherwise indicated, an alkyl substituent or alkyl moiety in a substituent group may be linear or branched. In the present invention, an alkyl group or moiety may contain up to 4 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl and t-butyl. When the substituent group is NHR 13 -C 1 -C 4 alkyl-, it should be appreciated that the NHR 13 moiety may be attached to a terminal or internal carbon atom ofthe alkyl moiety and when the substituent group is alkoxy substituted by -NR R , the alkoxy group will contain at least 2 carbon atoms and the group -NR R is not attached to the same carbon atom to which the oxygen atom is attached. 3 R represents a 5- to 10-membered unsaturated ring system which may comprise 1, 2, 3 or 4 ring heteroatoms independently selected from nitrogen, oxygen and sulphur, the ring system being optionally substituted by one or more (i.e. at least one), e.g. one, two or three, substituents independently selected from halogen (e.g. fluorine, chlorine, bromine or iodine), nitro, cyano, NR δ R 9 , C r C 4 alkyl-C(O)NH- (e.g. CH 3 C(O)NH-), NHR 12 C(O)- (e.g. NH 2 C(O)-, NH(CH 3 )C(O)-, (CH 3 ) 2 NC(O)-, NH 2 CH 2 CH 2 NHC(O)-), C r C 4 alkyl- SO 2 - (e.g. CH 3 SO 2 -), C r C 4 alkyl-SO 2 NH- (e.g. CH 3 SO 2 NH-), C r C 4 alkyl-NHSO 2 - (e.g. CH 3 NHSO 2 -), C r C 4 , preferably C r C 2 , alkoxy, and C r C 4 , preferably ^-C^ alkyl optionally substituted by one or more (i.e. at least one), e.g. one, two, three or four, fluorine atoms (e.g. trifluoromethyl). Specific substituents that may be mentioned include: methyl, amino (-NH 2 ), cyano, methoxy, chloro, nitro, NH 2 C(O)-, CH 3 C(O)NH-, CH 3 SO 2 -, CH 3 SO 2 NH- andNH 2 CH 2 CH 2 NHC(O)-. The ring system may be monocyclic or poly cyclic. If polycyclic, e.g. bicyclic, the two rings may " be fused to one another or may be joined by a bond. If the ring system is bicyclic, it is preferred that the rings are fused to one another. Examples of ring systems that may be used include phenyl, pyridinyl, pyrimidinyl, naphthyl, furanyl, pyrryl, thieiryl, isothiazolyl, imidazolyl, benzimidazolyl, tetrazolyl, pyrazinyl, quinolinyl, isoquinolinyl, benzofuranyl, isobenzofuranyl, benzothienyl, pyrazolyl, indolyl, isoindolyl, purinyl, oxazolyl, isoxazolyl, thiazolyl, triazinyl, benzothiazolyl, benzooxazolyl, imidazopyrazinyl, triazolopyrazinyl, naphthyridinyl, furopyridinyl, ύuopyranopyrimidinyl, pyridazinyl, quinazolinyl, pteridinyl, triazolopyrimidinyl, triazolopyrazinyl, thiapurinyl, oxapurinyl, deazapurinyl, Mazolopyrimidinyl, indolinyl, benzooxadiazolyl, benzothiadiazolyl, tetrahydroisoquinilinyl, 2-(isoxazol-3-yl)thienyl, and thienopyrimidinyl. Preferred ring systems are phenyl, thienopyrimidinyl, purinyl, pyrimidinyl, thiazolopyrimidinyl, quinazolinyl, benzooxadiazolyl, benzothiadiazolyl, thienyl, imidazolyl, tetrahydroisoquinilinyl, isoquinolinyl, pyrazolyl, isoxazolyl, 2-(isoxazol-3-yl)thienyl and pyridinyl. 4 R may represent a phenyl or pyπdmyl group comprising at least one substituent selected from halogen (e.g. fluorine, chlorine, bromine or iodine), Cι-C , preferably C r C 2 , alkoxy, C r C , preferably C 1 -C 2 , alkylthio or C r C 4 , preferably C r C 2 , alkyl optionally substituted by one or more (i.e. at least one) fluorine atoms (e.g. trifluoromethyl), which substituent is attached to the phenyl or pyridinyl group at a position ortho (*) with respect to the point of attachment of R to the rest ofthe molecule, for example as illustrated below. Examples of preferred ortho substituents include chloro, methyl and trifluoromethyl. or or The phenyl or pyridinyl group may be optionally further substituted by one or more (i.e. at least one) (e.g. one, two, three or four) substituents independently selected from halogen (e.g. fluorine, chlorine, bromine or iodine), cyano, hydroxyl, Cι-C alkylthio (e.g. methylthio or ethylthio), -C4 alkyl-NH- (e.g. methylamino or ethylamino), NHR 13 -C r C 4 alkyl-, C r C 4 , preferably C r C 2 , alkyl-SO 2 -, C r C 4 , preferably C r C 2 , alkyl-SO 2 NH-, C r C 4 , preferably C r C 2 , alkyl-NHSO 2 -, C r C 4 , preferably C r C 2 , alkyl-C(O)NH-, C,-C 4 , preferably C r C 2 , alkyl-NHC(O)-, -D-G, C r C 4 alkoxy optionally substituted by -NR R or by R , and Cι-C 4 , preferably C r C 2 , alkyl optionally substituted by one or more (i.e. at least one) fluorine atoms (e.g. trifluoromethyl) or by one or more (i.e. at least one) hydroxyl groups (e.g. hydroxymethyl). Alternatively, R may represent a 9- or 10-membered unsaturated fused bicyclic ring system which may comprise 1, 2, 3 or 4 ring heteroatoms independently selected from nitrogen, oxygen and sulphur, the ring system being optionally substituted by one or more (i.e. at least one) (e.g. one, two, three or four) substituents independently selected from halogen (e.g. fluorine, chlorine, bromine or iodine), oxo, C C 4 , preferably Cι-C 2 , alkyl, C' 1 -C 4 , preferably C C 2 , alkoxy, C r C , preferably Cι-C , alkylthio and NR R . Examples of suitable bicyclic ring systems include naphthyl, benzimidazolyl, quinolinyl, indolinyl, isoquinolinyl, benzofuranyl, isobenzofuranyl, benzothienyl, indolyl, isoindolyl, benzthiazolyl, benzoxazolyl and quinazolinyl. An example of an unsaturated fused bicyclic ring system substituted by an oxo group is oxindolyl. D represents an oxygen atom or a group (CH 2 ) n or CH 2 NH (in that orientation), where 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 at least one amino group (e.g. 1 -piperidinyl, 4-piperidinyl, 1 -piperazinyl, 1 -morpholinyl or 4-amino-l -piperidinyl). R represents a hydrogen atom, or a hydroxyl or Cι-C alkoxy group. In a preferred embodiment, R represents a hydrogen atom. R represents a hydrogen atom, or a cyano, nitro, hydroxyl, preferably C 1 -C 2 , alkyl or C j - i, preferably Cj-02, alkoxy group. R 7 , R 8 and R 9 each independently represent a hydrogen atom or a C C 4 , preferably C 1 -C 2 , alkyl group. R and R each independently represent a hydrogen atom or a Cι-C , preferably C 1 -C 2 , alkyl group, or R and R together with the nitrogen atom to which they are attached form a 5- or 6-membered saturated heterocyclic ring comprismg one or two ring nitrogen atoms (e.g. pyrrolidinyl, piperidinyl or piperazinyl). 12 R represents a hydrogen atom, or a C 1 -C 4 , preferably Cι-C 2 , alkyl group optionally substituted by at least one amino group (-NH 2 ). 13 R represents a hydrogen atom, or a C r C 4 , preferably C r C 2 , alkyl group optionally substituted by at least one hydroxyl group. 14 15 R and R each independently represent a hydrogen atom or a C r C 4 , preferably C -C 2 , alkyl group optionally substituted by at least one hydroxyl group, or R and R 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 (e.g. pyrrolidinyl, piperidinyl or piperazinyl). R represents a l-(C 1 -C 4 -alkyl)-piperidinyl group, e.g. 1-methylpiperidinyl, specifically l-methylpiperidin-3-yl. Preferred compounds ofthe invention include: (+)-N-(2,6-Dimethylphenyl)-2-(3-methyl-4-(thieno[2,3-<flpyrimidin-4-yl)piperazin-l- yl)acetamide, cw-[2-(3,5-Dimethyl-4-(tMeno[2,3-^pyrimidin-4-yl)piperazin-l-yl)]-N-(2,6- dimethylρhenyl)acetamide, (+)-2-[3-Methyl-4-(4-methylphenyl)piperazin-l-yl]-N-(2,6-dimethylphenyl) acetamide, cz5-N-[3-Hydroxymethyl-2-memylρhenyl]-2-(3,5-dime l-4-(thieno[2,3- ]pyrimidin-4-yl)piperazin- 1 -yl)acetamide, (R)-2-[4-(l-Methylimidazol-4-sulphonyl-4-yl)-3-ethylpiperazin-l-yl]-N-(quinolin-5- yl)acetamide, cz ' s-2-[3,5-Djmemyl-4-(thieno[2,3-βTlpyrimidin-4-yl)piperazin-l-yl]-N-(2- methylphenyl)acetamide, cw-N-(2-CUorophenyl)-2-[3,5-dimethyl-4-(tMeno[2,3- t pyrimidin-4-yl)ρiperazin- 1 - yl]acetamide, c -?-N-(2-Chlorophenyl)-2-[3,5-dimethyl-4-(9-methyl-9H-ρurin-6yl)piperazin-l- yl] acetamide, cw-2-(3,5-Dimeώyl-4-(tm^no[2,3--φyrir^ 5-yl)acetamide, c/5-2-(3,5-Dimemyl-4-thieno[2,3-ύTIpyrimidin-4-yl)piperazin-l-yl)-N-(quinolin-5- yl)acetamide, c^-2-(3,5-Dimethyl-4-(thieno[2,3-rf]pyrimidin-4-yl)piperazin-l-yl)-N-(2-methyl-5- methylsulphonamidophenyl)acetamide, cw-2-(3,5-Dimethyl-4-(thieno[2,3- ]pyrimidin-4-yl)piperazin-l-yl]-N-(2- trifluoromethylphenyl)acetamide, ew-2-(3,5-Dimemyl-4-(tMeno[2,3-<^pyrimidin-4-yl)piperazin-l-yl)-N-(3- methylpyridin-2-yl)acetamide, cw-2-(3,5-Dimethyl-4-(thieno[2,3-c Ipyrimidin-4-yl)piperazin-l-yl)-N-(isoquinolin- l-yl)acetamide, cw-4-(4-Amino-5-cy-mopyrimidin-2-yl)-3,5-dimethylpiperazin-l-yl)-N-(2- chlorophenyl)acetamide, cϊ5-2-(4-Benzenesulphonyl-3,5-dimethylpiperazin-l-yl)-N-(2-chloro- phenyl)acetamide, (+)-N-(2,6-Dimemylphenyl)-2-[(3-memyl-4-tWazolo(5,4-(^pyrimidin-7-yl)ρiperazin- l-yl]acetamide, ct-f-N-(2-Chlorophenyl)-2-[(3,5-dimethyl-4-quinazolin-4-yl)piperazin-l- yl] acetamide, N-(2-Chlorophenyl)-2-[(8-(thieno[2,3-(i]ρyrimidin-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- lpyrimidin-7-yl)-3,8-diazabicyclo[3.2.1]oct-3- yl] acetamide, N-(2-Methylphenyl)-2-[(8-thiazolo[5,4-(i]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-Memyl-5-(methylsulphonyl)amidophenyl]-2-[(8-thiazolo[5,4-(i]pyrimidin-7-yl)- 3,8-diazabicyclo[3.2.1]oct-3-yl]acetamide, N-[2-Methyl-5-(memylsulphonyl)amidophenyl]-2-[4-(thieno[2,3-(i]pyrimidin-4-yl)- 3,8-diazabicyclo[3.2. l]oct-3-yl] acetamide, cw-2-(3,5-Dimethyl-4-(thieno[2,3-d]pyrimidin-4-yl)piperazin-l-yl)-N-(2-methyl-5- (l-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, 5 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-(l-ρiperazinylmethyl)phenyl)-2-[(8-( ieno[2,3-d]pyrimidin-4-yl)-3,8- diazabicyclo[3.2.1 ]oct-3-yl]acetamide, cw-N-(5-(2-Aminoemoxy)-2-methyl-ρhenyl)-2-(3,5-dimethyl-4-(thieno[2,3- i o d]pyrimidin-4-yl)piperazin- 1 -yl)acetamide, hydrochloride salt, cz5-N-(5-(2-(N-Methylamino)e oxy)-2-methyl-phenyl)-2-(3,5-dimethyl-4-(thieno[2,3- d]pyrimidin-4-yl)piperazin-l-yl)acetamide, hydrochloride salt, cz5-N-(5-(2-(N-Memylamino)ethoxy)-2-methyl-phenyl)-2-(4-benzenesulphonyl)-3,5- dimethyl)piρerazin- 1 -yl)acetamide, is cz'5'-N-[5-(2-Aminoethoxy)-2-methyl-phenyl)-2-(4-benzenesulphonyl-3,5- dimethyl)piρerazin- 1-yl] acetamide, hydrochloride salt, N-(2-Oxo-2,3-dihydro-lH-indol-4-yl)-2-(8-thieno[2,3-d3pyrimidin-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- 20 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-diazabicycIo[3.2.1]oct-3- yl] acetamide, 25 cz5-N-(3-Fluoro-2-methyl-phenyl)-2-(4-benzenesulphonyl)-3,5-dimethyl)piperazin-l- 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- 30 methylphenyl)acetamide, 2-[8-(Benzo[l,2,5]oxadiazole-4-sulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2- methylphenyι)acetamide, 2-[8-(Benzo[l,2,5]thiadiazole-4-sulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2- methylphenyl)acetamide, 2-[8-(5-Chlorothieno-2-yl)sulphonyl)-3,8-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-[8-(4-Acetylaminomethoxybenzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N- (2-methylphenyl)acetamide, N-(2-Methylρhenyl)-2-[(8-(3-methylthieno[2,3-d]pyrimidin-4-yl)-3,8- diazabicyclo[3.2.1 ]oct-3-yl]acetamide, cw-2-(3,5-Dimethyl-4-(tMeno[2,3-d]pyrimidin-4-yl)piperazin-l-yl)-N-(l-methyl-lH- benzoimidazol-2-yl)acetamide, cώ-2-(3,5-Dimethyl-4-(thieno[2,3-d]pyrimidin-4-yl)piperazin-l-yl)-N-(2-methyl-5- (4-piperidinyloxy)phenyl)acetamide, hydrochloride salt, cz5-2-(3,5-Dimethyl-4-benzenesulphonyl)piperazin-l-yl)-N-(2-methyl-5-(4- piperidinyloxy)phenyl)acetamide, cis-2-(3 ,5-Dimethyl-4-(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, cz5-2-(3,5-Dimethyl-4-(4-quinazolinyl)piperazin- 1 -yl)-N-(2-methyl-5-(2-(N- methylamino)ethoxy)phenyl)acetamide, cz -2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide, cw-N-(2-Methylphenyl)-2-[4-(3 -nitrobenzenesulphonyl)-3 ,5-dimethylpiperazin- 1 -yl]- acetamide, cz5-2-[4-(3-Aminobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide, cw-2-(3,5-Dimethyl-4-(3-cyanobenzenesulphonyl)piperazin-l-yl)-N-(quinolin-5- yl)acetamide, cw-2-(3,5-Dimethyl-4-(4-cyanobenzenesulphonyl)piperazin-l-yl)-N-(quinolin-5- yl)acetamide, ct>s-2-(4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl)-N-(3-fluoro-2- methylphenyl)acetamide, ew-2-(4-(4-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl)-N-(3-fluoro-2- methylphenyl)acetamide, cι-?-2-[4-(3-Acetylaminobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide, cz * 5 , -2-[4-(3-Aπιmocarbonylbenzenesulphonyl)-3,5-dimemylpiperazin-l-yl]-N-(2- methylphenyl)acetamide, cw-2-[4-(3-Methanesulphonylaminobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]- N-(2-methylphenyl)acetamide, cz ' 5'-2-[4-(2-Methanesulphonylbenzenesulphonyl)-3,5-dimethylpiρerazin-l-yl]-N-(3- methoxy-2-methylphenyl)acetamide, c 5'-2-[4-(2-Melhanesulphonylbenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(3- fluoro-2-methylphenyl)acetamide, fis-2-[4-( 1 -Methylimidazol-4-sulphonyl-4-yl)-3 ,5-dimethylpiperazin- 1 -yl]-N- (quinolin-5-yl)acetamide, cz5-2-[4-( 1 -Methylimidazol-4-sulphonyl-4-yl)-3 ,5-dimethylpiperazin- 1 -yl]-N-(3 - methoxy-2-methylphenyl)acetamide, cz ' -?-2-[4-( 1 -Methylimidazol-4-sulphonyl-4-yl)-3 ,5-dimethylpiperazin- 1 -yl]-N-(3- fluoro-2-methylphenyl)acetamide, czi'-2-[4-(3-Methanesulphonylbenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- trifiuoromethylphenyl)acetamide, cz ' -?-2-[4-(2-Aminoethylaminocarbonylbenzenesulphonyl)-3,5-dimethylpiperazin-l- 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, ezi"-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2,6- dimethylρhenyl)acetamide, ezi , -2-[4-(4-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide, cz5-2-[4-(2-Cyanobenzenesulphonyl)-3 5 5-dimethylpiperazin-l-yl]-N-(2,6- dimethylphenyl)acetamide, hydrochloride salt, cz's-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- chlorophenyl)acetamide, 2-[8-(Isquinolin-l-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2- methylphenyl)acetamide, cw-2-[4-(4-Acetamidobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide, cz'5'-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- trifluoromethylphenyl)acetamide, cw-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-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, cz5-2-[4-(l,2-Dimethylimidazol-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-l-yl]-N- (quinolin-5-yl)acetamide, cz5-2-[4-(5-CMoro-l,3-dimemylpyrazole-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-l- 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-(l,l,2,2-Tetrahydroisoquinilin-7-sulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N- (2-methylphenyl)acetamide, cw-2-[4-(5-Chloro- 1 ,3-dimethylpyrazole-4-sulphonyl-4-yl)-3 ,5-dimethylpiperazin- 1 - yl] -N-(2-methylphenyl)acetamide, eZ5-2-[4-(3,5-Dimethylisoxazole-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide, cis-2- [4-(2-Methanesulphonylbenzenesulphonyl)-3 ,5 -dimethylpiperazin- 1 -yl] -N-(2- methylphenyl)acetamide, cz5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(3-methoxy-2- methylphenyl)acetamide, cw-2-[4-(4-Methanesulρhonylbenzenesulphonyl)-3 ,5-dimethylpiperazin- 1 -yl]-N-(2- methylphenyl)acetamide, cz5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(5-cyano-2- methylphenyl)acetamide, cw-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-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-l-yl]-N-(quinolin-5- yl)acetamide, cw-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5- methanesulphonylphenyl)acetamide, * czs-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5-(4- amino- 1 -piperidinyl)methyl)phenyl]acetamide, (R)-2-[4-(4-Methanesulphonylbenzenesulphonyl)-3-methylpiperazin- 1 -yfJ-N- (quinolin-5-yl)acetamide, (R)-2-[4-(4-Acetamidobenzenesulphonyl)-3 -methylpiperazin- 1 -yl]-N-(quinolin-5- yl)acetamide, ct-?-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5-(l- piperazinylmethyl)phenyl)acetamide, cw-2-[4-(3-Cyanobenzenesulρhonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5-(4- piperidinylamino)methyl)ρhenyl)acetamide, cz5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5-(l- morpholinyl)methyl)phenyl)acetamide, cw-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5-(2- hydroxyethylamino)methyl)phenyl)acetamide, cw-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-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-l-yl]-N-(quinolin-5-yl)acetamide, cz -2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-3-(4- amino- 1 -piperidinyl)methyl)phenyl] acetamide, cz5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-3-(4- piperidinylamino)methyl)phenyl)acetamide, cw-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-3-(l- piperazinylmethyl)phenyl)acetamide, cz ' 5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-3- (S,S)-(2,5-diazabicyclo[2.2.1 ]hept-2-yl)methyl)phenyl)acetamide, cz ' 5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl-3-(l- morpholinyl)methyl)phenyl)acetamide, cw-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl-3-(2- (l-pyrrolidinyl)ethoxy)phenyl)acetamide, (±) cw-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl- 3-(l ?methylpiρeridin-3-yl)methoxy)phenyl)acetamide, cw-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl-4-(2- ( 1 -pyrrolidinyl)ethoxy)phenyl)acetamide, (±) cw-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl- 4-( 1 -methylpiperidin-3 -yl)methoxy)phenyl)acetamide, (±) cz ' i'-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl- 5 -( 1 -methylpiperidin-3 -yl)methoxy)phenyl)acetamide, (±) c/5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl- 6-(l -methylpiρeridin-3-yl)methoxy)phenyl)acetamide, and cz5-2-[4-(l-Methylimidazol-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-l-yl]-N-((2- methyl-3 -(2-( 1 -pyrrolidinyl)ethoxy)phenyl)acetaπιide, and their pharmaceutically acceptable salts and solvates. The present invention further provides a process for the preparation of a compound of formula (I) as defined above which comprises: (a) reacting a compound of general formula wherein X, Y, R , R and R 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 (e.g. a halogen atom 3 or triflate) and m and R are as defined in formula (I); or (b) when X represents a nitrogen atom and Y represents an oxygen atom, reacting a compound of general formula wherein m, R 1 , R2 and R 3 are as defined in formula (I), with a compound of general fdrmula wherein L 2 represents a leaving group such as a halogen atom and R 4 • is as defined in formula (I); or (c) reacting a compound of general formula 3 wherein L represents a leaving group such as a halogen atom or hydroxyl group and m, X, Y, R 1 , R2 and R 3 are as defined in formula (I), with a compound of general formula (Nil), H 2 Ν - R , wherein R 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. Processes (a) and (b) are conveniently carried out in the presence of a base, e.g. a metal carbonate such as potassium or caesium carbonate or a trialkylamine such as triethylamine, preferably N,N-diisopropylethylamine, and in the presence of a polar solvent (e.g. l-methyl-2-pyrrolidinone, dimethylformamide, ethanol, tetrahydrofuran or 1,4-dioxane). Process (c) is conveniently carried out in the presence of a base and a polar solvent as described above for processes (a) and (b). In addition, a coupling reagent is suitably used, for Example, l,r-carbonyldiimidazole, 1,3-dicyclohexylcarbodiimide or bromo-tris-oxy- tripyrrolidinophosphonium hexafluorophosphate. Compounds of formulae (II), (III), (IN), (N), (NI) and (Nil) are either commercially available, are well known in the literature or may be prepared easily using known techniques. It will be appreciated by those skilled in the art that in the processes ofthe present invention certain functional groups such as hydroxyl, carboxyl or amino groups in the starting reagents or intermediate compounds may need to be protected by protecting groups. Thus, the preparation ofthe compounds of formula (I) may involve at a certain stage the removal of one or more protecting groups. The protection and deprotection of functional groups is described in 'Protective Groups in Organic Chemistry', edited by J.W.F. McOmie, Plenum Press (1973) and 'Protective Groups in Organic Synthesis', 2nd edition, T.W. Greene and P.G.M. Wuts, Wiley-Interscience (1991). It will be appreciated that certain compounds of formula (I) may be converted to further compounds of formula (I) by techniques known in the art such as alkylation, hydrolysis, amide bond formation, esterification or reductive amination. The compounds of formula (I) above may be converted to a pharmaceutically acceptable salt or solvate thereof, preferably an acid addition salt such as a hydrochloride, hydrobromide, phosphate, acetate, furnarate, maleate, tartrate, citrate, oxalate, methanesulphonate or jp-toluenesulphonate, or an alkali metal salt such as a sodium or potassium salt. Certain compounds of formula (I) are capable of existing in stereoisomeric forms. It will±ie understood that the invention encompasses all geometric and optical isomers ofthe compounds of formula (I) and mixtures thereof including racemates. Tautomers and mixtures thereof also form an aspect ofthe present invention. The compounds of the present invention are advantageous in that they possess pharmacological activity and have utility as modulators of P2X 7 receptor activity. They are therefore indicated as pharmaceuticals for use in the treatment or prevention of rheumatoid arthritis, osteoarthritis, psoriasis, allergic dermatitis, asthma, hyperresponsiveness ofthe airway, chronic obstructive pulmonary disease (COPD), bronchitis, septic shock, glomerulonephritis, irritable bowel disease, Crohn's disease, ulcerative colitis, atherosclerosis, growth and metastases of malignant cells, myoblastic leukaemia, diabetes, neurodegenerative disease, Alzheimer's disease, meningitis, osteoporosis, burn injury, ischaemic heart disease, stroke, peripheral vascular disease and varicose veins. Accordingly, the present invention provides a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore defined for use in therapy. In another aspect, the invention provides the use of a compound of 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 ofthe present specification, the term "therapy" also includes "prophylaxis" unless there are specific indications to the contrary. The terms "therapeutic" and "therapeutically" should be construed accordingly. Prophylaxis is expected to be particularly relevant to the treatment of persons who have suffered a previous episode of, or are otherwise considered to be at increased risk of, the disease or condition in question. Persons at risk of developing a particular disease or condition generally include those having a family history ofthe disease or condition, or those who have been identified by genetic testing or screening to be particularly susceptible to developing the disease or condition. The invention further provides a method of effecting immunosuppression (e.g. in the treatment of rheumatoid arthritis, irritable bowel disease, atherosclerosis, psoriasis, pulmonary disease, e.g. COPD or bronchitis, or diseases ofthe central nervous system, e.g. Alzheimer's disease or stroke) which comprises administering a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore defined to a patient. For the above-mentioned therapeutic uses the dosage administered will, of course, vary with the compound employed, the mode of administration, the treatment desired and the disease or condition indicated. For effecting immunosuppression, the daily dosage of the compound of formula (I) will typically be in the range from 0.001 mg/kg to 30 mg/kg. The compounds of formula (I) and pharmaceutically acceptable salts and solvates thereof may be used on their own but will generally be administered in the form of a pharmaceutical composition in which the formula (I) compound/salt solvate (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 %w (per cent by weight), more preferably from 0.10 to 70 %w, of active ingredient, and, from 1 to 99.95 %w, more preferably from 30 to 99.90 %w, of a pharmaceutically acceptable adjuvant, diluent or carrier, all percentages by weight being based on total composition. Thus, the present invention also provides a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore defined in association with a pharmaceutically acceptable adjuvant, diluent or carrier. The invention further provides a process for the preparation of a pharmaceutical composition ofthe invention which comprises mixing a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore defined with a pharmaceutically acceptable adjuvant, diluent or carrier. The pharmaceutical composition ofthe invention may be administered topically (e.g. to the lung and/or airways or to the skin) in the form of solutions, suspensions, heptafluoroalkane aerosols and dry powder formulations; or systemically, e.g. 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 present invention will now be further explained by reference to the following illustrative examples. Example 1 (+)-N-(2,6-DimethyIphenyl)-2-(3-methyI-4-(thieno[2,3-ιiIpyrimidin-4-yl)piperazin-l- yl)acetamide i) (+)-l,l-Dimethylethyl, 3-methyI-4-(thieno[2,3-</]pyrimidin-4-yl)piperazine-l- carboxylate A solution of 4-ctøoro-thieno[2,3- ]pyrimidine (0.2g) and (+)- 1,1-dimethylethyl, 3-methylpiperazine-l-carboxylate (J. Med. Chem., 1993, 36, 690-698) (0.23g) in ethanol (50ml) was heated under reflux for 24 hours. The solvent was evaporated and the residue purified by flash column chromatography eluting with ethyl acetate/iyσhexane (3:7) to give the subtitle compound as a yellow gum. Yield 0.33g. MS: APCI(+ve) 335 (M+l, 100%) ii) (+)-2-Methyl-l-(thieno[2,3-(flpyrimidine-4-yl)piperazine, trifluoroacetic acid salt A mixture ofthe product from step (i) (0.33g) and trifluoroacetic acid (4 ml) in dichloromethane (5 ml) was stirred at room temperature for 2 hours. The solvent was evaporated under reduced pressure. Toluene (20 ml) was added to the residue and then evaporated under reduced pressure to give the crude subtitle compound as a gum. The product was used without further purification in the next step. MS: APCI(+ve) 235 (M+l, 100%) iii) (+)-N-(2,6-Dimethylphenyl)-2-(3-methyl-4-(thieno [2,3-d] pyrimidin-4-yl)piperazin- l-yl)acetamide A mixture ofthe product from step (ii) (0.23g), N,N-diisopropylethylamine (0.65g) and 2-chloro-N-(2,6-dimethylphenyl)acetamide (0.2g) in dimethylformamide (4ml) was heated at 80°C for 18 hours. The reaction mixture was cooled and diluted with ethyl acetate. The organic solution was washed with a small volume of water and the solvent evaporated under reduced pressure. The residue was purified by flash cliromatography eluting with ethyl acetate/tsohexane (6:4) to give the product as a gum. The gum was further purified by reverse phase high pressure liquid chromatography (methanol / 0.1% aqueous ammonium acetate, gradient elution 15% to 85% organic phase) to give the title product, after freeze drying, as a beige solid. Yield 0.095g. MS: APCI(+ve) 396 (M+l ,100%) lK NMR: δ (CDC1 3 ) 8.5(2H, s); 7.32(2H, q); 7.13(3H, m); 4.98(1H, bs); 4.60(1H, bd); 3.59(1H, dt); 3.25(2H,q); 3.12(1H, bd); 2.98(1H, d); 2.72(1H, dd); 2.55(1H, dt); 2.28(6H, s); 1.53(3H, d). MP: 184-185 °C Example 2 ci5-[2-(3,5-Di ethyl-4-(thieno[2,3-ιi]pyriιαidin-4-yl)piperazin-l-yl)]-N-(2,6- dimethylphenyl)acetamide i) c&-l,l-DimethyIethyl, 3,5-dimethyI-4-(thieno [2,3-d] pyrimidine-4-yl)piperazin-l- carboxylate A solution of 4-chloro-thieno[2,3-<i]pyrimidine (4.0g), cis- 1,1-dimethylethyl, 3,5- dimethylpiperazine-1 -carboxylate (J. Med. Chem., 1999, 4(7), 1123-1114) (12g) and N,N-diisopropylethylamine (10ml) in l-methyl-2-pyrrolidinone (30ml) was heated at 120 °C for 5 days under nitrogen. The reaction mixture was cooled and diluted with ethyl acetate. The organic solution was washed with water, dried (MgSO 4 ) and the solvent evaporated under reduced pressure. The residue was purified by flash column chromatography eluting with ethyl acetate/zsohexane (2:8) to give the subtitle compound as a beige solid. Yield 5.5g. MS: APCI(+ve) 349 (M+l, 100%) ii) α 2,6-Dimethyl-l-(thieno[2,3-rflpyriιnidin-4-yl)piperazine, trifluoroacetic acid salt The subtitle compound was prepared from the product of step (i) (0.15g) by the method of Example 1 step (ii) as a gum. This was used without purification in the next step. MS: APCI(+ve) 249 (M+1,100%). ) cz5-[2-(3,5-Dimethyl-4-(thieno[2,3-^pyrimidin-4-yl)piperazin-l-yl)]-N-(2,6- dimethylphenyl)acetamide A mixture ofthe product from step (ii), N,N-diisopropylethylamine (0.37ml) and 2-chloro- N-(2,6-dimethylphenyl)acetamide (0.08g) in l-methyl-2-pyrrolidinone (5ml) was heated at 100°C for 24 hours. The reaction mixture was cooled and diluted with ethyl acetate. The organic solution was washed with a small volume of water, dried (MgSO 4 ) and the solvent evaporated under reduced pressure. The residual red oil was purified by reverse phase high pressure liquid chromatography (acetonitrile / 0.1% aqueous ammonium acetate, gradient elution 20% to 80% organic phase) to give the title product, after freeze drying, as a cream solid. Yield 0.05g. MS: APCI(+ve) 410 (M+l, 100%) ^ NMR: δ (CDC1 3 ) 8.5(2H, s); 7.38(1H, d); 7.26(1H, d); 7.14(3H, m); 5.10(2H, bs); 3.29(2H, s); 3.01(2H,d); 2.65(2H, dd); 2.30(6H, s); 1.56(6H, d). MP: 186-189 °C Example 3 (+)-2-[3-Methyl-4-(4-methylphenyl)piperazin-l-yl]-N-(2,6-dimethylphenyl) acetamide The title compound was prepared from (+)-3-methyl-4-(4-methylphenyl)ρiperazine (0.1 g) and 2-chloro-N-(2,6-dimethylphenyl)acetamide (0.1 g) by the method of Example 1 step (iii) as a white solid. Yield 0.056g. MS: APCI(+ve) 352 (M+1,100%). ^ NMR: δ (CDCI 3 ) 8.63(1H, s); 7.09(5H, m); 6.87(2H, d); 3.78(1H, bm); 3.24(2H, d); 3.17(2H, m); 2.95(1H, m); 2.88(1H, dd); 2.72(2H, m); 2.29(3H, s); 2.26(6H, s); 1.08(3H, d). Example 4 αs-N-[3-Hydroxymethyl-2-methylphenyl]-2-(3,5-^ 4-yl)piperazin-l-yl)acetamide i) s-N-[3 (l,l-Dimet yl)-l-dimethylethyl)silyloxymethyl-2-methylphenyl]-2-(3,5- dimethyl-4-(thieno[2,3-^pyrimidjm-4-yl)piperazin-l-yl)acetamide The subtitle compound was prepared from N-(3-((l,l-dimethyl-l- dimethylethyl)silyloxymethyl)-2-methylphenyl)-2-chloroacetamide (Chem. Abs., 1997, 765311) (O.lg) and the product from Example 2 step (ii) (O.lg) by the method of Example 2 step (iii) as a red oil. This was used directly in the next step without further purification. ii) 5-N-[3-Hydroxymethyl-2-methylphenyl]-2-(3,5-dimethyl-4-(thieno[2,3- < ]pyrimidin-4-yl)piperazin-l-yl)acetamide The subtitle product from step (i) (0.15g) in anhydrous tetrahydrofuran was treated with a 1M solution of tetrabutyl ammonium fluoride in tetrahydrofiαran (0.31ml) and the mixture stirred at room temperature for 1 hour. The solvent was removed under reduced pressure and the residue purified by high pressure liquid chromatography (acetonitrile / 0.1% aqueous ammonium acetate, gradient elution 20% to 80% organic phase) to give the title compound as a white solid. Yield 0.025g. MS: APCI(+ve) 426 (M+l, 100%) ^ NMR: δ (CDCI 3 /DMSO) 8.97(lH,s), 8.49(lH,s), 7.89(lH,d), 7.32(1H, d), 7.26(3H, m), 5.09(2H, bs), 4.74(2H, s), 3.27(2H, s), 2.96(2H, d), 2.63(2H, dd), 2.36(3H, s), 1.58(6H, bs) MP: 203-204°C Example 5 (R)^-[4-(l-Methylimidazol-4-sulphonyl-4-yl)-3-ethylpiperazm-l-yl]-N-(qumolin-5- yl)acetamide i) (R)-3-Eth l-l -(phenylmethyl)-2,5-piperazinedione To a stirred solution of (R)-N-BOC-2-aminobutyric acid (3.36g) and ethyl N-benzylglycine (4.52g) in dichloromethane (50ml) at 15 °C was added dicyclohexylcarbodiimide (3.59g). The temperature was maintained at 10-15 °C for a further 2h and then allowed to stir at ambient temperature for a further 16h. The mixture was filtered and the mother liquor collected and solvent evaporated under reduced pressure. The residue was re-dissolved in dichloromethane (20ml) and hydrogen chloride gas passed through the mixture for 20 minutes. The mixture was quenched with aq. saturated sodium bicarbonate solution and extracted with ethyl acetate, collected, dried (MgSO 4 ) and solvent evaporated under reduced pressure to leave a colourless oil. This was purified by crystallisation from ether/iso-hexane mixtures to give the subtitle compound as a white solid. Yield: 1.35g Η NMR δ (DMSO) 8.30(s, IH), 7.24-7.39(m, 5H), 4.60(d, IH), 4.44(d, IH), 3.92(t, IH), 3.78(d, 3H), 1.75(m, 2H), 0.84(t, 3H) ϋ) (R)-3-Ethyl-l-phenylmethylpiperazine A stirred solution ofthe product from step (i) (6.0g) in tetrahydrofuran (250ml) at 0 °C was treated with lithium aluminium hydride (3.44g). The mixture was allowed to stir at ambient temperature for 24h and then set at reflux for 4h. The mixture was carefully quenched with 10% aq. sodium hydroxide solution (10ml). After stirring for 30 minutes the mixture was filtered and the mother liquor partitioned between ethyl acetate and brine. The organic layer collected, dried (MgSO 4 ) and solvent evaporated under reduced pressure to give the subtitle compound as a pale yellow oil. Yield: 5.8g l H NMR δ (CDC1 3 ) 7.32(s, 5H), 3.50(dd, 2H), 2.62-3.0(m, 5H), 2.00(m, IH), 1.70(t, IH), 1.57(s, IH), 1.27(m, 2H), 0.90(t, 3H) iii) (R)-l -(1 -Methylimidazol-4-sulphonyl-4-yI)-2-ethyl-4-phenylmetIιyl)piper azine The subtitle compond was prepared from the product of step (ii) (0.5g) and 1- methylimidazole-4-sulphonyl chloride (0.5g) by the method of Example 80 step (i) as a pale yellow solid. Yield: 0.53g Η NMR δ (CDCI 3 ) 7.46(s, IH), 7.38(s, IH), 7.29(m, 5H), 3.80(s, 2H), 3.47(d, IH), 3.3(d+m, 2H), 2.64(4 2H), 2.08(m, 2H), 1.79(m, 2H), 0.82(t, 3H) iv) (R)-l-(l-Methylimidazol-4-sulphonyl-4-yl)-2-ethyl)piperazine The subtitle compound was prepared from the product of step (iii) (0.49g) by the method of Example 80 step (ii) as a pale yellow solid. Yield: 0.32g Η NMR δ (CDCI 3 ) 7.6(d, 2H), 7.5(m, 4H), 4.05(s, IH), 3.73(s, 3H), 3.42(4 IH), 3.04(4 2H), 2.87(m, IH), 2.32(m, IH), 1.87(m, 2H), 0.91(t, 3H) v) (R)-2-[4-(l-Methyljimidazol-4-sulphonyl-4-yl)-3-ethylpiperaz -l-yl]-N-(qum yl)acetamide The title compound was prepared from the product of step (iv) (0.23g) and 2-chloro-N- (quinolin-5-yl)acetamide (0.21 g)) (J. Indian Chem Soc, 1940, 17, 619-621 ) by the method of Example 80 step (iii) as a cream solid. Yield: 21mg MS: APCI (+ve) 443 (M+l) Η NMR δ (CD 3 OD) 9.16(d, IH), 9.07(4 IH), 8.10(s, 3H), 7.97(t, IH), 7.81(4 IH), 7.70(t, IH), 7.50(dd, IH), 4.29(m, 2H), 4.10(m, 2H), 3.81(s, 3H), 3.69(m, 2H), 3.32(m, 2H), 3Λ5j(m, 2H), 1.84(m, 2H), 0.99(t, 3H) Example 6 c/5-2-[3,5-Dimethyl-4-(thieno[2,3-ciIpyriιnidin-4-yl)piperazin-l-yl]-N-(2- methylphenyl)acetamide The title compound was prepared from the product of Example 9 step (ii) (0.316g) and 2-methylaniline (0.09g) by the method of Example 8 step (v) as a white solid. Yield 0.202g MS : APCI(+ve) 396 (M+l , 100%) 1 1Λ NMR: δ (DMSO) 9.25(1H, s), 8.40(1H, d), 7.60-7.67(3H,m), 7.26(2H, m), 7.10(1H, ), 5.01(2H, bs), 3.23(2H, s), 2.96(2H, d), 2.45(2H, m), 2.29(3H, s), 1.50(6H, m) MP: 174-175 °C Example 7 ds-N-(2-Chlorophenyl)-2-[3,5-dimethyl-4-(thieno[2,3-^pyrjinιidm-4-yl)piperaziιι-l- yl] acetamide The title compound was prepared from the product of Example 8 step (ii) (0.316g) and 2-chloroaniline (0.107g) by the method of Example 1 step (iii) as a white solid. Yield 0.119g. MSr APCI(+ve) 416(M+1, 100%) H NMR: δ(DMSO) 9.70(1H, s), 8.55(1H, d), 7.27-7.42(3H, m), 7.26(2H, s), 7.08(1H, t), 5 t ,08(2H, bs), 3.26(2H, s), 2.94(2H, d), 2.60(2H, m), 1.63(6H, d) MP: 206-207 °C Example 8 5-N-(2-Chlorophenyl)-2-[3,5-dimethyl-4-(9-methyl-9H-purin-6yl)piperazin-l- yl] acetamide i) 5-l,l-Dimethylethyl, 3,5-dimet yl-4-(9-methyl-9H-purin-6-yl)piperazine-l- carboxylate The subtitle compound was prepared from 6-chloro-9-methyl-9H-purine (J. Org. Chem., 1983, 48(6), 850-5) (2g) and cis- 1,1-dimethylethyl, 3,5-dimethylpiperazine-l-carboxylate (2.74g) by the method of Example 2 step (i) as beige solid. Yield 0.2g. H NMR: δ (CDCL 3 ) 8.40(1H, S), 7.73(1H, S), 4.20-4.00(3H, BRM), 3.30-3.00(3H, BRM), 1.5(9H, S), 1.40(6H, D) ii) c/5~2,6-Dimethyl-l-(9-methyl-9H-purm-6-yl)piperazme, trifluoroacetic acid salt The subtitle compound was prepared from the product of step (i) (0.2g) by the method of Example 1 step (ii) as a red gum. This was used directly in the next step. MS: APCI(+ve) 247 (M+l,100%) iii) c/s-l,l-Dimethylethyl, 2-(3,5-dimethyl-4-(9-methyl-9H-purin-6-yl)piperazin-l- yl)aeetate A mixture ofthe product from step (ii) (0.34g), tert-butyl bromoacetate (0.13g) and sodium bicarbonate (0.8g) in acetone was heated at 45°C for 18 hours. The reaction mixture was filtered and the filtrate evaporated under reduced pressure. The residual brown gum was purified by flash chromatography eluting with ethyl acetate/z ' -rohexane/ triethylamine (7:2.5:0.5) to give the subtitle compound as a pale yellow gum. Yield 0.12g. MS: APCI(+ve) 361 (M+l , 100%) iv) c s-2-(3,5-Dimethyl-4(9-methyl-9H-purin-6-yl)piperazm-l-yl)acetic cid, hydrochloride salt The product from step (iii) (0.12g) in dichloromethane was treated with 1M hydrogen chloride in diethyl ether (12 ml). The mixture was stirred at room temperature for 18 hours. The solvent was evaporated under reduced pressure to give the subtitle product as a pale yellow solid. Yield 0.15g. MS: APCI(+ve) 305 (M+l, 100%) v) c/5-N-(2-Chlorophenyl)-2-[3,5-dimethyl-4-(9-methyl-9H-purin-6yl)piperazin-l- yl] acetamide Bromo-tris-oxy-tripyrrolidinophosphonium hexafluorophosphate (known as PyBroP) (0.18g) was added to a stirred solution ofthe product from step (iv) (0.14g), 2-chloroaniline (0.05g) and N,N-diisopropylethylamine (0.3g) in anhydrous dimethylformamide (6ml). After stirring for 4 hours a further aliquot of 2-chloroaniline (0.1ml) and PyBroP (0.18g) were added and the mixture further stirred at room temperature for four days. Water was added and the precipitate filtered to give the crude product as a brown solid (0.07g). This was purified by high pressure liquid chromatography (acetonitrile / 0.1% aqueous ammonium acetate, gradient elution 25% to 75% organic phase) to give the title product as a white solid. Yield 0.04g. MS: APCI(+ve) 414/416 (M+l, 100%) H NMR: δ (CDCI 3 /DMSO) 9.76(lH,s), 8.52(1H, dd), 8.39(1H, s), 7.78(1H, s), 7.40(1H, dd), 7.31(1H, dt), 7.07(1H, dt), 5.50(2H, bs), 3.83(3H, s), 3.26(2H, s), 2.94(2H, d), 2.59(2H, m), 1.58(6H, d) MP: 221-222 °C Example 9 c/5-2-(3,5-Dimethyl-4-(thieno[2,3-ι jpyrimidm-4-yl)piperazm-l-yl)-N-(isoqumolin-5- yl)acetamide i) c 5-l,l-Dimethylethyl, 2-(3,5-dimethyl-4-(thieno[2,3-< ]pyrimidin-4-yl)piperaziιι-l- yl)acetate The subtitle compound was prepared from the product of Example 2 step (ii) (3.0g) and tert-butyl bromoacetate (1.15g) by the method of Example 8 step (iii) as a white solid. Yield l.Og. MS: APCI(+ve) 363 (M+l, 100%) ii) c 5-2-(3,5-Dmιethyl-4-(thieno[2,3-^pyrimidi-4-yl)piperazin-l-yl)acetic acid, hydrochloride salt The product from step (i) (1.0g) in 1,4-dioxane was treated with 4M hydrogen chloride in 1,4-dioxane (40 ml). The mixture was stirred at room temperature for 18 hours. The solvent was evaporated under reduced pressure to give the subtitle compound as a white solid. Yield 1.9g. MS APCI(+ve) 307 (M+l, 100%) iii) cw-2-(3,5-Dimethyl-4-(thieno[2,3-^pyriιm^in-4-yl)piperazm-l-yl)-N-(isoqumolin- 5-yl)acetamide The title product was prepared from the product of step (ii) (0.2g) and 5-aminoisoquinoline (0.084g) by the method of Example 8 step (v) as a white solid. Yield 0.1 lg. MS: APCI(+ve) 433 (M+l, 100%) L H NMR: δ (CDCI 3 ) 9.62(lH,bs), 9.30(1H, s), 8.59(1H, d), 8.51(1H, s), 8.46(1H, d), 7.85(lH,d), 7.68(2H, m), 7.38(1H, d), 7.28(1H, m), 5.13(2H, bs), 3.38(2H, s), 3.03(2H, d), 2.70(2H, dd), 1.65(6H, d) MP: 213-216 °C Example 10 c 5-2-(3,5-Dmιethyl-4-thieno[2,3-^pyrimidm-4-yl)piperazm-l-yl)-N-(quinolin-5- yl)acetamide The title compound was prepared from the product of Example 9 step (ii) (0.207g) and 5-aminoquinoline (0.072g) by the method of Example 8 step (v) as a white solid. Yield 0.1 lg. MS: APCI(+ve) 433 (M+l, 100%) H NMR: δ (CDC1 3 ) 9.53(lH,s), 8.97(1H, s), 8.51(lH,s), 8.28(lH,s). 8.00(1H, s), 7.77(lH,t), 7.47(1H, m), 7.42(lH,d), 7.37(1H, d), 5.13(2H,s), 3.38(2H,s), 3.03(2H,d), 2.7l(2H,d), 2.29(3H,s), 1.63(6H,d) MP: 194-195 °C Example 11 c 5-2-(3,5-Dimethyl-4-(thieno[2,3-rfJpyrimidin-4-yl)piperazm-l-yl)-N-(2-methyl-5- methylsulphonamidophenyl)acetamide i) 2-Methyl-5-bis(methylsulphonyl)amido-l-nitrobenzene To a mixture of 5-nitro-4-methylaniline (3.04g) and N,N-diisopropylethylamine (5.2ml) in dichloromethane (40ml) was added dropwise a solution of methanesulphonyl chloride (2.29g) in dichloromethane (10ml) over 40mins. After stirring for 16 hours the mixture was poured into 2% aq. HCl. The organic phase collected and further washed with brine, dried (Na j SO and solvent evaporated under reduced pressure to leave the crude product. This was purified by silica-gel chromatography eluting with dichloromethane to give the subtitle compound as a pale yellow solid. Yield 4.46g. This was used directly in the next step. u) 2-Methyl-5-bis(methylsulphonyl)amido-l-aniline A mixture ofthe product from step (i) (3.8g), ammonium chloride (3.8g), reduced iron powder (3.8g) in ethanol (30ml) and water (10ml) were stirred at 80 °C for 5 minutes. The mixture was filtered through Celite and further washed with ethanol and dichloromethane. The filtrate was concentrated to a quarter ofthe volume and then water added to give a brown precipitate. This was filtered to give the subtitle compound as a brown solid. Yield 1.25g. The mother liquor was further partitioned between water and ethyl acetate. The organic phase collected, dried (Na^O^ and evaporated to give a second batch ofthe subtitle compound as an orange solid. Yield l.lg. ! H NMR: δ (DMSO) 6.98 (IH, d), 6.65 (IH, s), 6.56 (IH, d), 2.50 (6H, s), 2.06 (3H, s) iii) c/s-2-(3,5-Dimethyl-4-(thieno[2,3-^pyrimidin-4-yl)piperazin-l-yl)-N-(2-methyl-5- bis(methylsulphonyl)amidophenyl)acetamide The subtitle product was prepared from the product of Example 9 step (ii) (0.318g) and the product of step (ii) (0.172g) by the method of Example 8 step (v) as a white solid. Yield 0.2 lg. This product was used directly in the next step without further purification. iv) czs-2-(3,5-Dimethyl-4-(thieno [2,3-d] pyrimidin-4-yl)piperazm-l -yl)-N-(2-methyl-5- methylsulphonamidophenyl)acetamide A mixture ofthe product from step (iii) (0.2 lg) and potassium carbonate (0.5g) was stirred in methanol (20ml) and water (10ml) over 24 hours at room temperature. The solid product was filtered and purified by reverse phase HPLC to give the title compound as white solid. Yield 0.058g. MS: APCI(+ve) 489(M+1, 100%) Ti NMR: δ (DMSQ) 9.66(lH,s), 9.23(lH,s), 8.40(lH,s), 7.60(3H,s),7.17(lH,d), 6.94(lH,d),4.50(2H,bs),3.22(2H,s),2.93(2H,s),2.43(2H,m),2.22(3H,s),1.49(6H,d) Example 12 c s-2-(3,5-Dmιethyl-4-(thieno[2,3-^pyrimidiιι-4-yl)piperazin-l-yl]-N-(2- trifluoromethylphenyl)acetamide i) c 5-2-(3,5-Dimethyl-4-(thieno[2,3-^pyrimidin-4-yl)piperazin-l-yl)acetyl chloride, hydrochloride salt A mixture ofthe product from Example 9 step (ii) (1.15g) and oxalyl chloride (1.2ml) in dichloromethane (100 ml) was treated with 2 drops of dimethylformamide. After 24 hours at room temperature a further aliquot of oxalyl chloride (3.6ml) was added and the mixture heated under reflux for 48 hours. The solvent was evaporated under reduced pressure. Toluene was added to the residue and then evaporated under reduced pressure to give the subtitle product as a yellow oil (0.95g). MS : (methanol added to give the methyl ester) : APCI(+ve) 320 (M(methyl ester)+l , 100%) ii) c s-2-(3,5-DimethyI-4-(thieno[2,3-^pyrimidin-4-yl)piperazin-l-yI]-N-(2- trifluoromethylphenyl)acetamide A mixture ofthe product from step (i) (0.2g), 2-trifluoromethylaniline (0.1 lg) and N,N-diisopropylethylamine in 1,4-dioxane (5ml) was heated at 80°C forlδ hours. LC mass spectrum analysis showed cz ' -(3,5-dimethyl-4-(thieno[2,3-ύ ]pyrimidin-4-yl)piperazin- 1 - yljacetic acid present. PyBroP (0.18g) and 4-dimethylaminopyridine (0.05g) were added and the mixture further stirred at room temperature for 18 hours. The solvent was evaporated under reduced pressure and the residue purified by high pressure liquid chromatography (acetonitrile / 0.1% aqueous ammonium acetate, gradient elution 25% to 75% organic phase) to give the title product as a white solid. Yield 0.08g. MS: APCI(+ve) 450 (M+l, 100%) H NMR: δ (CDC1 3 ) 9.41(lH,bs), 8.49(1H, s), 8.34(1H, d), 7.65(1H, d), 7.60(1H, t), 7.37(1H, d), 7.27(2H, m), 5.06(2H, bs), 3.24(2H, s), 2.92(2H, d), 2.59(2H,dd), 1.55(6H, d) MP: 154-155 °C Example 13 -2-(3,5-Dimethyl-4-(thieno[2,3-^ρyriιmdin-4-yl)piperazin-l-yl)-N-(3- methylpyridin-2-yl)acetamide The title compound was prepared by from the product of Example 12 step (i) (0.2g) and 2-amino-3-methylpyridine (0.076g) by the method of Example 12 step (ii) as a cream solid. Yield 0.025g. MS: APCI(+ve) 397 (M+l, 100%) ϊ NMR: δ (CDCI 3 ) 9.13(lH,s), 8.47(1H, s), 8.31(1H, d), 7.60(1H, d), 7.40(1H, m), 7.27(1H, d), 7.13(1H, m), 5.09(2H, bs), 3.28(2H, s), 2.91(2H, d), 2.61(2H, m), 2.3(3H, s), 1.60(6H, d) MP: 157-159 °C Example 14 c 5-2-(3,5-Dimethyl-4-(thieno[2,3-^pyriιnidm-4-yl)piperazm-l-yl)-N-(isoqumolin-l- yl)acetamide The title product was prepared by from the product of Example 12 step (i) (0.2g) and isoquinolin-1-ylamine (O.lg) by the method of Example 12 step (ii) as a cream solid. Yield 0.055g. MS : APCI(+ve) 433 (M+l, 100%) lR NMR: δ (CDC1 3 ) 9.65(1H, bs); 8.49(1H, s); 8.37(1H, bs); 8.05(1H, bd); 7.72(1H, t); 7.60(2H, t); 7.39(1H, d); 7.26(1H, m); 5.12(2H, bs); 3.39(2H, s); 3.07(2H, d); 2.6?(2H, dd); 1.63(6H, d). MP: 206-207 °C Example 15 c/5-2-(4-(4-Am o-5-cyanopyrimidin-2-yl)-3,5-dimethyl-piperazin-l-yl)-N-(2- chlorophenyl) acetamide i) 2-Chloro-N-(2-chlorophenyl)acetamide 2-Chloroaniline (5g) was dissolved in dichloromethane (100ml) and chloroacetyl chloride (3.1 lml) and N,N-diisopropylethylamine (13.65ml) were added at 0 °C under a nitrogen atmosphere. The mixture was stirred for 1 hour at 0 °C and 12 hours at room temperature, then quenched with water. The product was extracted with dichloromethane. The organic layer was washed with water, brine, dried (MgSO 4 ) and concentrated under reduced pressure to leave the subtitle product as a beige solid. Yield 7.5g. This was used in the next step without further purification. MS: ES(-ve) 203 (M-1, 100%) ii) cis-N-(2-Chlorophenyl)-2-(3,5-dimethylpiperazin-l-yl)acetamide The product of step (i) (5.9g) was dissolved in ethanol (50ml) and cz5-2,6-dimethylpiperazine (3g) and sodium hydrogencarbonate (6.63g) were added at room temperature under a nitrogen atmosphere. The mixture was heated under reflux for 24 hours and the cooled solution was filtered and the filtrate was evaporated under reduced pressure. The residue was dissolved in 1M HCl (22ml) and washed with dichloromethane. The aqueous solution was then basified to pH13 with a solution of sodium hydroxide and the product was extracted with dichloromethane. The organic layer was washed with water, brine, collected, dried (MgSO 4 ) and concentrated under reduced pressure to give the subtitle compound as a beige solid. Yield 4g. MS: ES(+ve) 282(M+1,100%) iii) c s-2-(4-(4-Ammo-5-cyanopyriπύdm-2-yl)-3,5-dimethylpiperazin-l-yl)-N-(2- chlorophenyl)acetamide A mixture ofthe product from step (ii) (0.5g), 4-amino-2-chloro-5-cyanopyrimidine (0.275g) and N,N-diisopropylethylamine (1.55ml) in l-methyl-2-pyrrolidinone (5ml) was heated under nitrogen at 120 °C for 3 days. The cooled mixture was partitioned between ethyl acetate and water. The organic phase collected was dried (MgSO 4 ) and the solvent evaporated. The crude product purified by silica-gel chromatography eluting with 2% ethyl acetate in z'sohexane to give the title compound as white solid. Yield O.lg. MS: APCI (+ve) 400 (M+l, 100%) lH NMR: δ (DMSO) 9.67(1H, s), 8.32(1H, dd), 8.29(1H, s), 7.53(1H, dd), 7.37(1H, t), 7.23(2H, brs), 7.15(1H, t), 4.76-4.72(2H, m), 3.23(2H, s), 2.86(2H, d), 2.38(2H, dd), 1.36(6H, d) Example 16 c s-2-(4-Benzenesulphonyl-3,5-dimethylpiperazin-l-yl)-N-(2-chloro-phenyl)acetamide Benzenesulphonyl chloride (0.124g) was added to a solution ofthe product from Example 15 step (ii) (0.2g) in pyridine (2ml). The mixture was stirred at room temperature for 16 hours and then the solvent was evaporated under reduced pressure. The residue was purified by flash silica-gel chromatography eluting with 1% EtOH, 1% Et 3 N, 98%CH 2 C1 2 followed by trituration with ethyl acetate to give the title compound. Yield 0.03 g. MS; APCI(+ve) 422 (M+l, 100%) ^ MR: δ (CDC1 3 ) 9.49 (brs, IH), 8.48 (dd,lH), 7.82 (dd,2H), 7.60-7.50 (m,3H), 7.37 (dd,lH), 7.30 (m,lH), 7.05 (dt,lH), 4.17 (quin,2H), 3.07 (s,2H), 2.65 (d,2H), 2.15 (dd,2H), 1.55 (s,6H). M.P: 182-3°C Example 17 (+)-N-(2,6-Dimethylphenyl)-2-[(3-methyl-4-thiazolo(5,4-^pyrimidin-7-yl)piperazin-l- yl] acetamide i) (+)-N-(2,6-Dimethylphenyl)-2-(3-methylpiperazin-l-yl)acetamide The subtitle compound was prepared from 2-chloro-N-(2,6-dimethylphenyl)acetamide (7g) and (+)-2-methyl-piperazine (3.55g) by the method of Example 15 step (ii) as a white solid, s Yield 7g. MS: ES(+ve) 262(M+1,100%) u) (+)-Ν-(2,6-Dimethylphenyl)-2-[(3-methyl-4-thiazolo(5,4-ιi)pyrimidin-7-o yl)piperazin-l-yl] acetamide The title compound was prepared from the product of step (i) (0.38 lg) and 7-chloro- thiazolo[5,4,d]pyrimidine (Chem. Pharm. Bull. 1968, (16(4), 750-755) (0.25g) by the method of Example 15 step (iii) as a beige solid. Yield 0.0 lg. s MS: ES(+ve) 397(M+1, 100%) ^ NMR: δ (CDC1 3 ) 8.84(1H, s), 8.77(1H, s), 8.48(1H, s), 7.18-7.06(3H, m), 3.14(2H, s), 3.88-2.68(7H, br ), 2.26(6H, s), 1.25(3H, m) Example 18 0 α>-N-(2-Chlorophenyl)-2-[(3,5-dimethyl-4-quinazolin-4-yl)piperazin-l-yl]acetamide A mixture ofthe product from Example 15 step (ii) (2.1g), 4-chloroquinazoline (1.23g) (J. Chem. Soc, 1944, 619-623) and N,N-diisopropylethylamine (6.15ml) in l-methyl-2- pyrrolidinone (14ml) under nitrogen was heated at 120 °C for 4 days. The cooled mixture was partitioned between ethyl acetate and water. The organic layer was further washed with water, brine, dried (MgSO 4 ) and concentrated under reduced pressure. The residue was purified by silica-gel chromatography eluting with ethyl acetate/ isohexane (4:6) to give the title compound as a white solid. Yield 0.08g. MS: ES(+ve) 410(M+1,100%), ES(-ve) 408(M-1,100%) ! H NMR: δ (DMSO) 9.81(1H, s), 8.82(1H, brs), 8.30(1H, dd), 8.18(1H, d), 7.87(2H, d), 7.63-7.58(lH, m), 7.55(1H, dd), 7.38(1H, t), 7.17(1H, t), 4.38(2H, brs), 3.26(2H, s), 2.69(4H, brs), 1.30-1.15(6H, m) Example 19 N-(2-Chlorophenyl)-2-[(8-(thieno[2,3-^pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]oct-3- yl] acetamide i) 1,1-Dimethylethyl, 3-[(2-chlorophenylcarbamoyI)methyl]-3,8-diaza- bicy clo [3.2.1] octane-8-car b oxylate A mixture of 1,1-dimethylethyl, 3,8-diaza-bicyclo[3.2.1]octane-8-carboxylate (0.048g) (J. Med. Chem., 1998, 41(5), 674-681), sodium bicarbonate (0.058g), potassium iodide (Q.003g) and the product of Example 15 step (i) (0.05 lg) in ethanol (0.5ml) was heated at 70°C for 3 hours. The cooled mixture was partitioned between ethyl acetate and water and the organic phase was washed with water and brine, dried (MgSO 4 ) and the solvent evaporated under reduced pressure. Purification was by flash silica-gel chromatography eluting with 2%EtOH, l%Et 3 N, 97%CH 2 C1 2 . Yield 0.068g. MS: ES(+ve) 380 (M+l, 100%) ii) N-(2-Chlorophenyl)-2-(3,8-diaza-bicyclo [3.2.1] oct-3-yl)acetamide trifluoroacetic acid salt The subtitle compound was prepared from the product of step (i) (0.068g) by the method of Example 1 step (ii) as a white solid. Yield 0.06 lg. MS: ES(+ve) 280 (M+l, 100%) iϋ) N-(2-Chlorophenyl)-2-[(8-(thieno[2,3-ιi]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]oct- 3-yl] acetamide The title compound was prepared from the product of step (ii) (0.06 lg) by the method of Example 15 step (iii), with heating for 1 hour only, as a white solid. Yield 0.04g. MS: APCI(+ve) 414 (M+l, 100%) LH NMR: δ (CDC1 3 ) 9.65 (s,lH), 8.53 (dd,lH), 8.49 (s,lH), 7.41 (dd,lH),7.33-7.28 (m,3H), 7.07 (t,lH), 5.02 (brs,lH), 3.18 (s,2H), 2.95 (d,2H), 2.77 (d,2H), 2.32 (m,2H), 2.12 (m,2H). M.P: 164 °C Example 20 N-(2-Methylphenyl)-2-[8-(9-methyl-9H-purin-6-yl)-3,8-diazabicyclo[3.2.1]oct-3- yl] acetamide i) 1,1-Dimethylethyl, 3-phenylmethyl-3,8-diazabicyclo[3.2.1]oct-8-carboxylate 3-Phenylmethyl-3,8-diazabicyclo[3.2.1]octane hydrochloride salt (1.15g) was dissolved in dichloromethane (16ml) and water (16ml) and sodium hydrogencarbonate (1.61g) were added. The mixture was stirred rapidly for 10 minutes at room temperature and then di-tert-butyl dicarbonate (1.15g) was added in portions. The mixture was stirred rapidly for an additional 2 hours. The organic layer was separated, dried over magnesium sulphate, filtered and concentrated to afford a white crystalline solid. Yield 1.45g. MS: ES(+ve) 303 (M+l, 100%) ii) 1,1-Dimethylethyl, 3,8-diazabicyclo[3.2.1]oct-8-carboxylate hydrochloride salt A solution ofthe product from step (i) (1.45g) was dissolved in ethyl acetate (12ml) and cooled at -10 °C under a nitrogen atmosphere. IM HCl in diethyl ether (4.81ml) was added dropwise, causing the salt to precipitate out of solution. The mixture was stirred an additional 1 hour and the crystalline product was collected by filtration and dried in a vacuum oven. This white solid was dissolved in methanol (18ml) and 10% palladium on carbon (0. lg) added under a nitrogen atmosphere. The mixture was then stirred vigorously under an hydrogen atmosphere for 12 hours. After completion ofthe reaction, the mixture was filtered through Celite and the mother liquor concentrated to afford the subtitle compound as a white crystalline solid. Yield 1.18g. H NMR: δ (CDC1 3 ) 4.34(2H, brs), 3.16(4H, brs), 2.27-2.09(4H, m), 1.47 (9H, s) iii) X,l-Dimethylethyl, 3-[(2-methylphenylcarbamoyl)methyl]-3,8-diaza- bicyclo[3.2.1]octane-8-carboxylate A mixture ofthe product from step (ii) (0.16g), 2-chloro-N-(2-methyl)acetamide (Synthesis, 1982, (9), 795-796) (0.13g), sodium hydrogencarbonate (0.16g), and potassium iodide (8mg) in ethanol (2ml) under a nitrogen atmosphere was heated at 70 °C for 4 hours. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with water, brine, dried (MgSO 4 ) and concentrated under reduced pressure. The residue was purified by silica-gel chromatography eluting with 2% ethanol 1% triethylamine in dichloromethane to give the subtitle compound as beige solid. Yield 0.23g. MS: ES(+ve) 360 (M+l, 100%) iv) N-(2-Methylphenyl)-2-[3,8-diazabicyclo[3.2.1]oct-3-yl] acetamide, trifluoroacetic acid salt A mixture ofthe product from step (iii) (0.23g) in dichloromethane (30ml) and trifluoroacetic acid (1.80ml) under a nitrogen at room temperature was stirred for 24 hours. The mixture was concentrated under reduced pressure to leave brown gum. This was used in the next step without further purification. MS: ES(+ve) 260 (M+l, 100%) v) N-(2-Methylphenyl)-2-[8-(9-methyl-9H-purin-6-yl)-3,8-diazabicyclo[3.2.1]oct-3- yl] acetamide A mixture ofthe product from step (iv) (0.12g), 6-chloro-9-methylpurine (0.06g) (J. Org. Chem., 1983, 48(6), 850-855), and N,N-disopropylethylamine (1ml) in 1,4-dioxane (5ml) were heated together at reflux for 5 hours. The volatiles were removed under reduced pressure and the residue purified by reverse phase HPLC eluting with a gradient from 5% acetonitrile in aqueous 1% ammonium acetate to 75% over 7min. The title product was obtained, by freeze drying, as a white solid. Yield: 0.027g. MS: APCI(+ve) 392 (M+l, 100%) ^ NMR: δ (DMSO); 9.16(s, IH), 8.27(s, IH), 8.15(s, IH), 7.75(d, IH), 7.10(t, IH), 7.08(t, IH), 3.74(s, 3H), 5.70(bs, IH), 5.00(bs, IH), 3.74(s, 3H), 3.07(s, 2H), 2.90(m, 2H), 2.50-1.80(m, 6H), 2.30(s, 3H) Example 21 2-[8-(9-Methyl-9H-purin-6-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(quinoliιι-5- yl)acetamide i) 1,1-Dimethlethyl, 3-[(quinolin-5-ylcarbamoyl)methyl]-3,8-diaza- bicyclo [3.2.1] octane-8-carboxylate The subtitle compound was prepared from the product of Example 20 step (ii) (0.24g) and 2-chloro-N-(quinolin-5-yl)acetamide (J. Indian Chem. Soc, 1940, 17, 619-621) (0.234g) by the method of Example 20 step (iii) as a pale yellow solid. Yield 0.38g. MS: ES(+ve) 397 (M+l, 100%) ii) 2-(3,8-Diazabicyclo[3.2.1]oct-3-yl)-Ν-(qumoIin-5-yl)acetamide, trifluroacetic acid salt The subtitle compound was prepared from the product of step (i) (0.38g) by the method Example 20 step of step (iv) as a pale yellow gum. This was used directly in the next step. MS: ES(+ve) 297 (M+l , 100%) ) 2-[8-(9-Methyl-9H-purm-6-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(qumolin-5- yl)acetamide A mixture ofthe product from step (ii) (0.20g), 6-chloro-9-methylpurine (O.lg) (J. Org. Chem., 1983, 48(6), 850-855), and N,N-disopropylethylamine (1ml) in 1,4-dioxane (5ml) were heated together at reflux for 4 hours. The volatiles were removed under reduced pressure and the residue purified by reverse phase HPLC eluting with a gradient from 5% acetonitrile in aqueous 1% ammonium acetate to 75% over 7min. The title product was obtained, by freeze drying, as a white solid. Yield: 0.047g. MS: APCI(+ve) 429(M+100%), APCI(-ve) 427(M-1,100%) ! H NMR: δ (DMSO); 9.9(bs, IH), 8.90(m, IH), 8.40(4 IH), 8.30(s, IH), 8.18(s, IH), 7.90(d, IH), 7.80(d, IH), 7.75(t, IH), 7.60(m, IH), 5.78(bs, IH), 5.00(bs, IH), 3.78(s, 3H), 3.30(s, 2H), 2.90(m, 2H), 2.70-1.80(m, 6H). Example 22 N-(Qumol -5-yl)-2-[8-thiazolo[5,4-^pyrimidm-7-yl)-3,8-diazabicyclo[3.2.1]oct-3- yl] acetamide The title compound was prepared from the product Example 21 step (ii) (O.lg) and 7-chlorothiazolo[5,4-u pyrimidine (Chem. Pharm. Bull, 1968, 16(4), 750-755) (0.06g) by the method of Example 21 step (iii) as a pale yellow solid. Yield O.lg. MS: ES(+ve) 432 (M+l, 100%) H NMR: δ (CDC1 3 ) 9.62(1H, s), 8.99-8.98(lH, m), 8.77(1H, s), 8.50(1H, s), 8.26(1H, d), 8.16(1H, d), 7.99(1H, d), 7.75(1H, t), 7.52-7.49(lH, m), 6.04(1H, brs), 5.29(1H, brs), 3.27(2H, s), 3.03(2H, d), 2.83(2H, brs), 2.22(2H, brs), 1.70(1H, brs), 1.45(1H, dd) Example 23 N-(2-Methylphenyl)-2-[(8-thiazolo[5,4- t]pyrimidin-7-yl)-3,8-diazabicyclo[3.2.1]oct-3- yl] acetamide The title compound was prepared from the product of Example 20 step (iv) (O.lg) and 7-chlorothiazolo[5,4- ]pyrimidine (Chem. Pharm. Bull, 1968, 16(4), 750-755) (0.06g) by the method of Example 21 step (iii) as a white solid. Yield 0.06g. MS: ES(+ve) 395 (M+l , 100%) H NMR: δ (CDClj) 8.99(1H, s), 8.75(1H, s), 8.48(1H, s), 8.08(1H, d), 7.27-7.21(2H, m), 7.08(1H, t), 6.00(1H, brs), 5.29(1H, brs), 3.15(2H, s), 2.95(2H, d), 2.74(2H, brs), 2.38(3H, s), 2.27-2.07(4H, m) Example 24 N-(2-Methyl-5-(methylsulphonyl)amidophenyl)-2-[8-(9-methyl-9H-purin-6-yl)-3,8- diazabicyclo [3.2.1] oct-3-yl] acetamide i) 2-Chloro-N-(5-bis(methylsulphonyl)amido-2-methylphenyl)acetamide A mixture ofthe product from step (ii) (0.62g) and N,N-diisopropylethylamine (1.04ml) in dichloromethane (40ml) at 10 °C was treated with chloroacetyl chloride (0.19ml) dropwise. After stirring for 4 hours the mixture was poured into saturated sodium bicarbonate solution and the organic phase collected and further washed with brine, collected, dried (CaCl 2 ) and solvent evaporated under reduced pressure to leave a yellow gum. This was purified by silica-gel chromatography eluting with 10% diethyl ether in dichloromethane to give the subtitle product as a white solid. Yield 0.7 lg. MS: APCI (-ve) 353 (M-1, 100%) ii) 1,1-Dimethylethyl, 3-[(5-bis(methylsulphonyI)amido-2-methyl phenylcarbamoyl)methyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate The subtitle compound was prepared from the product of step (i) (0.266$) and the product from Example 20 step (ii) (0.2g) by the method of Example 20 step (iii) as a white solid. Yield 0.45g. MS : ES(+ve) 531 (M+l , 100%) ϋi) 2-(3,8-Diazabicyclo[3.2.1]oct-3-yl)-N-[5-bis(methylsulphonyl)amido-2- methylphenyl] acetamide, trifluoroacetic acid salt The subtitle compound was prepared from the product of step (ii) (0.45 g) by the method of Example 20 step (iv) as a white solid. Yield 0.42g. MS: ES(+ve) 431 (M+l, 100%) iv) N-[5-Bis(methylsulphonyl)amido-2-methylphenyl]-2-[8-(9-methyl-9H-purm-6-yl)- 3,8-diazabicyclo[3.2.1]oct-3-yl]acetamide The subtitle compound was prepared from the product of step (iii) (0.2g) and 6-chloro-9- methylpurine (J. Org. Chem., 1983, 48(6), 850-855) (O.lg) by the method of Example 20 step (v) as white solid. Yield O.lg. MS: ES(+ve) 563 (M+l , 100%) v) N 2-Methyl-5-(methylsulphonyl)amidophenyl)-2-[8-(9-methyl-9 T-purin-6-yl)-3,8- diazabicyclo[3.2.1]oct-3-yl]acetamide A mixture ofthe product from step (iv) (O.lg) and sodium bicarbonate (0.05g) in wet ethanol (2ml) was heated at reflux for 1.5 hours, cooled and filtered. Purification was by flash silica-gel chromatography eluting with 2.5% EtOH, l%aq. NH 3 , 96.5% CH 2 C1 2 followed by trituration with ethyl acetate to give the title product as a white solid. Yield 0.066g. MS: AP(+ve) 485 (M+l, 100%) ! H NMR: δ (CDCI 3 ): 9.19 (s,lH), 8.40 (s,lH), 8.14 (d,lH), 7.74 (s,lH), 7.20 (d,lH), 7.12 (dd,lH), 7.08 (s,lH), 3.84 (s,3H), 3.17 (s,2H), 2.97 (s,3H), 2.90 (d,2H), 2.75 (d,2H), 2.37 (s,3H), 2.15 (brm, 4H). M.P: 216-217°C Example 25 N-[2-Methyl-5-(methylsulphonyl)aιnidophenyl]-2-[(8-thiazolo[5,4-^pyrimidin-7-yl)- 3,8-diazabicyclo[3.2.1]oct-3-yl]acetamide i) N-[5-Bis(methylsulphonyl)amido-2-methylphenyl]-2-[(8-thiazolo[5,4- |pyrimidm-7- yl)-3,8-diazabicyclo [3.2.1] oct-3-yl] acetamide The subtitle compound was prepared from the product of Example 24 step (iii) (0.2 lg) and 7-chloro-thiazolo[5,4-d]pyrimidine (Chem. Pharm. Bull, 1968, 16(4), 750-755) (0.069g) by the method of Example 20 step (v) as a white solid. Yield 0.113g. MS: APCI(+ve) 566 (M+l, 100%) u) N-[2-Methyl-5-(methylsulphonyl)amidophenyl]-2-[(8-thiazolo[5,4-flpyrimidin-7- yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]acetamide The title compound was prepared from the product of step (i) (0.113g) by the method of Example 24 step (v) as a white solid. Yield 0.085g. MS: APCI(+ve) 488 (M+l, 100%) L H NMR: δ (CDCI 3 ) 9.18 (s,lH), 8.76 (s,lH), 8.48 (s,lH), 8.17 (d,lH), 7.31 (s,lH), 7.20 (d,lH), 7.13 (dd,lH), 3.21 (s,2H), 2.95 (s,3H), 2.92 (m,2H), 2.76 (m,2H), 2.38 (s,3H), 2.17(br m, 4H). MP: 145-187 °C Example 26 N-[2-Methyl-5-(methylsulphonyl)amidophenyl]-2-[4-(thieno[2,3-^pyrimidin-4-yl)- 3,8-diazabicyclo [3.2.1] oct-3-yl] acetamide i) N-[(5-Bis(methylsulphonyl)a)mido-2-methylphenyl]-2-[4-(thieno[2,3-^pyriιnidin-4- yl)-3,8-diazabicyclo [3.2.1] oct-3-yl] acetamide The subtitle compound was prepared from the product of Example 24 step (iii) (0.216g) and 4-chlorothieno[2,3--f]pyrimidine (0.056g) by the method of Example 20 step (v) as a white solid. Yield 0.13g. MS: ESI (+ve) 565 (M+l, 100%) ϋ) N-[2-Methyl-5-(methylsulphonyl)amidophenyl]-2-[4-(thieno[2,3-^pyrimidm-4-yl)- 3,8-diazabicyclo[3.2.1]oct-3-yl] acetamide The title compound was prepared from the product of step (i) (0.130g) by the method of Example 24 step (v) as a white solid. Yield 0.025g. MS : APCI(+ve) 487 (M+l , 100%) lE NMR: δ (DMSO) 9.18(1H, s), 8.38(1H, s), 7.71-7.62(3H, m), 7.17(1H, d), 6.93(1H, dd), 5.04(2H, brs), 3.12(2H, s), 2.93(3H, s), 2.90(2H, d), 2.58(2H, d), 2.23(3H, s), 2.13(2H, d), 1.98-1.95(2H, m) Example 27 C 5-2-(3,5-Dimethyl-4-(thieno[2,3-</Jpyrimidm-4-yl)piperazin-l-yl)-N-(2-methyl-5-(l- piperazinylmethyl)phenyl)acetamide, hydrochloride salt i) 1,1-Dimethylethyl, 4-((4-methyl-3-nitrophenyl)methyl)piperazine-l-carboxylate A mixture of 4-methyl-3-nitrobenzyl chloride (5.55g), 1,1-dimethylethyl, piperazine-1- carboxylate (5.6g), N,N-diisopropylethylamine (5ml) in N,N-dimethylformamide (25ml) were heated at 110 °C for 3h. After cooling to ambient temperature the mixture was partitioned between dichloromethane and water. The organic phase collected, dried (MgSO 4 ) and solvent evaporated under reduced pressure to leave the subtitle compound as a pale yellow oil. Yield: 9.6g MS: APCI(+ve) 336 (M+l) ϋ) 1,1-Dimethylethyl, 4-((3-amino-4-methylphenyl)methyl)piperaziιιe-l-carboxylate The product from step (i) (9.6g), 10% palladium on charcoal (lOOmg) in ethanol (100ml) was stirred under an atmosphere of hydrogen gas for 24h. The catalyst was filtered through celite and the mother liquor collected and solvent evaporated under reduced pressure to give the subtitle compound as a pale yellow oil. Yield. 9g MS: APCI(+ve) 322 (M+l) iii) c/s-2-(3,5-Dimethyl-4-(thieno [2,3-d\ pyrimidin-4-yl)piperazin-l-yl-N-(2-methyl-5- ((4-(l,l-dimethylethyloxycarbonyl)piperazin-l-yl)methyl)phenyl)acetamide The product from Example 9 step (ii) (0.21g), the product from step (ii) (0.15g), benzotriazol-l-yl-pxy-tripyrrolidinophosphonium hexfluorophosphate (PyBrop) (0.24g), N,N-diisopropylethylamine (0.36ml) in dry N.N-dimethylformamide were stirred together under nitrogen for 20h. The mixture was poured into water and the resulting precipitate filtered as an off white solid. Purification was by silica gel chromatography eluting with ethyl acetate to give the subtitle compound as a white solid. Yield: 0.2 lg MS: APCI (+ve) 594 (M+l) iv) C/5-2-(3,5-Dimethyl-4-(thieno [2,3-d] pyrimidin-4-yl)piperazin-l-yl)-N-(2-methyl-5- (l-piperazinylmethyl)phenyl)acetamide, hydrochloride salt The product from step (iii) (0.17mg) was dissolved in 4M hydrogen chloride in 1,4- dioxane (2ml). After 48h the solvents were evaporated under reduced pressure to leave the title compound as a white solid. Yield: 0.16g MS: APCI (+ve) 494(M+1) 'H NMR: δ (DMSO) 8.50(s, IH), 7.78(s, IH), 7.65(4 IH), 7.58(4 IH), 7.39(4 IH), 7.31(d, IH), 5.25(m, IH), 5.05(bs, 2H), 4.23(s, 2H), 3.77(bs, 2H), 3.43(s, 4H), 3.18(m, 6H), 3.04(m, 2H), 2.71(s, IH), 2.30(s, 3H), 1.47(d, 6H) Example 28 N-(2-Methylphenyl)-2-[(8-(thieno[2,3-< Jpyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]oct-3- yl] acetamide The title compound was prepared from the product of Example 20 step (iv) (0.45g) and 4- chloro-thieno[2,3-cfjpyrimidine by the method of Example 1 step (i). Yield: 0.22g. MS: APCI(+ve) 394 (M+l) ! H NMR: δ (DMSO) 9.17 (IH, brs), 8.39 (IH, s), 7.73-7.62 (3H,m), 7.25-7.15 (2H,m), 7.07 (lH,m), 5.05 (2H,brs), 3.12 (2H,s), 2.92 (2H,d), 2.58 (2H,d), 2.28 (3H,s), 2.15 (2H,m), 1.97 (2H,m). Example 29 N-[5-(Methanesulphonylamido-2-methylphenyl)-2-[8-(thieno[2,3-^pyriπύdin-4-yl)-8- azabicyclo[3.2.1]oct-3-yl]acetamide i) Ethyl, 2-(8-(thieno[2,3-έ lpyrimidin-4-yl)-8-azabicyclo[3.2.1]oct-3-yl)ethanoate Ethyl, 2-(8-azabicyclo[3.2.1]oct-3-yl)ethanoate (0.64g) (Arch. Pharm., 1976, 309(6), 447. Arch. Pharm., 1975, 308(5), 365), 4-chlorotωeno[2,3-φyrimidine (0.55g), N,N- diisopropylethylamine (1.7ml) in 1,4-dioxane (10ml) were heated at 105 °C for 4h. The precipitate was filtered and the mother liquor collected, the solvent evaporated under reduced pressure to leave a brown oil. Purification was by silica gel chromatography eluting with ethyl acetate/iso-hexane (3:7) to give the subtitle compound as a colourless oil. Yield: 0.35g. MS: APCI(+ve) 332 (M+l) u) 2-(8-(Thieno[2,3-rf|pyrmιidin-4-yl)-8-azabicyclo[3.2.1]oct-3-yl)ethanoic acid The product from step (i) (0.14g) in ethanol (0.3ml) was treated with IN sodium hydroxide (0.6ml) at ambient temperature for 48h. The mixture was acidified to pH4 with 2N hydrochloric acid and the solvents evaporated under reduced pressure. The residue was treated with ethanol (5ml) and inorganic salts filtered. The mother liquor collected and solvent evaporated under reduced pressure to leave a gummy residue. Purification was by trituration with diethyl ether. Yield: 0.097g MS: APCI(+ve) 304 (M+l) iu) N-[5-bis((Methanesulphonyl)aιmdo-2-methylphenyl)-2-[8-(thieno[2,3-^pyrimidm- 4-yl)-8-azabicyclo[3.2.1]oct-3-yl]acetamide The product from step (ii) (0.097g), the product from Example 11 step (ii) (0.089g), benzotriazol-1-yl-oxy-triρyrrolidinoρhosphonium hexfluorophosphate (PyBrop) (0.16g), 4-N,N-dimethylaminopyridine (0.04g), N,N-diisopropylethylamine (0.28ml) in dichloromethane (10ml) were stirred at ambient temperature for 48h. The mixture was partitioned between water and dichloromethane. The organic phase collected, dried (MgSO 4 ) and solvent evaporated under reduced pressure. Purification was by reverse phase HPLC eluting with 1% aq. ammonium acetate/acetonitrile (90% to 50%) to give the subtitle compound as a white solid. Yield: O.lg MS: APCI (+ve) 564 (M+l) iv) N-[5-(Methanesulphonylaιnido-2-methyIphenyl)-2-[8-(thieno[2,3-^pyrimidin-4- yl)-8-azabicyclo[3.2.1]oct-3-yi]acetamide The product from step (iii) (O.lg), potassium carbonate (0.14g), water (5ml) and 1,4- dioxane (5ml) were heated at 110 °C for Ih. The mixture was treated with acetic acid (2ml) and solvents evaporated under reduced pressure. Purification was by silica gel chromatography eluting with ethyl acetate to give the title compound as a white solid. Yield: 0.01 lg MS: APCI (+ve) 486 (M+l) 'H NMR: δ (DMSO) 9.33(bs, IH), 9.16(bs, IH), 8.38(2xs, IH), 7.6(m, 3H), 7.30(m, IH), 7.15(t, IH), 6.90(m, IH), 5.0(bm, 2H), 2.90(s, 3H), 2.30-1.89(bm, 4H), 2.10(s, 3H), 1.5- 0.9(bm, 2H) Example 30 N-(2-Methyl-5-(l-piperazmylmethyl)phenyl)-2-[(8-(thieno[2,3-( |pyrimidin-4-yl)-3,8- diazabicyclo[3.2.1]oct-3-yl]acetamide i) Methyl, 2-(8-(l,l-dimethylethyloxycarbonyl)-3,8-diazabiyclo[3.2.1]oct-3-yl)acetate A mixture of 1,1-dimethylethyl, 3,8-diazabicyclo[3.2.1]oct-8-carboxylate (0.35g), sodium bicarbonate (84mg), potassium iodide (20mg) and methyl bromoacetate (355mg) in ethanol (5ml) were heated at 70 °C for 6h. The reaction mixture was partitioned between ethyl acetate and water. The organic phase collected, dried (MgSO 4 ) and the solvent evaporated under reduced pressure to leave the subtitle compound as a pale yellow solid. Yield: 380mg Η NMR: δ (DMSO) 4.01 (bs, 2H), 3.58 (s, 2H), 3.29 (s, 3H), 2.62-2.49 (m, 4H), 1.82- 1.64(m, 4H), 1.40 (s, 9H) ϋ) Methyl, 2-(3,8-diazabiyclo[3.2.1]oct-3-yl)acetate, trifluoroacetic acid salt The subtitle compound was prepared from the product of step (i) (380mg) by the method of Example 1 step (ii). The product was used without further purification directly in next step. iii) Methyl, 2-(8-(thieno[2,3-rf]pyrimidin-4-yl)-(3,8-diazabiyclo[3.2.1]oct-3-yl)acetate The subtitle compound was prepared from the product of step (ii) (400mg) and 4-chloro- thieno[2,3-< ]pyrimidine (288mg), N,N-diisopropylethylamine (232ul) in 1,4-dioxane at 100 °C for 48h. Solvent was evaporated under reduced pressure. Purification was by silica gel chromatography eluting with 2% ethanol in dichloromethane to give the subtitle compound as a beige solid. Yield: 170mg. MS: APCI (+ve) 319 (M+l, 100%) iv) 2-(8-(Thieno[2,3-< |pyrimidin-4-yl)-(3,8-diazabiyclo[3.2.1]oct-3-yl)acetic acid The product from step (iii) (170mg) was dissolved in ethanol (1ml) and treated with IN sodium hydroxide solution (0.8ml) at room ambient temperature. After 3h the mixture was acidified with 2M hydrochloric acid to pH4. The solvents were then evaporated under reduced pressure and the residue treated with ethanol and filtered to remove inorganic salts. The mother liquor was collected and evaporated under reduced pressure to leave the subtitle compound as a white solid. Yield: 160mg. MS: APCI(+ve) 305 (M+l) v) N-(5-(4-(l,l-Dimethylethyloxycarbonyl)piperazin-l-yhnethyl)-2-methyl)phenyl)-2- [(8-(thieno[2,3-^pyrimidm-4-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]acetamide The product of step (iv) (83mg), the product of Example 27 step (ii) (92mg), benzotriazol- 1-yl-oxy-tripyrrolidinophosphonium hexafluorophosphate (PyBrop) (153mg) and N,N- diisopropylethylamine (95ul) were stirred in N,N-dimethylformamide (5ml) at ambient temperature for 12h. The solvents were evaporated under reduced pressure and purification was by silica gel chromatography eluting with iso-hexane/acetone (7:3) containing 1% triethylamine to give the subtitle compound as a white solid. Yield: 40mg. 'H NMR δ (DMSO) 9.15(s, IH), 8.38(s, IH), 7.67-7.66(m, 2H), 7.17(d, IH), 7.00(4 IH), 5.04(bs, 2H), 3.41 (s, 2H), 3.29(s, 4H), 3.1 l(s, 2H), 2.90(4 2H), 2.29(t, 4H), 2.24(s, 3H), 2.14(d, 2H), 2.00-1.93(m, 2H), 1.38(s, 9H) vi) N-(2-Methyl-5-(l-piperazinylmethyl)phenyl)-2-[(8-(thieno [2,3-f jpyrimidm-4-yl)- 3,8-diazabicyclo[3.2.1]oct-3-yI]acetamide The title compound was prepared from the product of step (v) (35mg) by the method of Example 8 step (iv) as a white solid. Yield: 35mg MS: APCI(+ve) 492 (M+l) 'H NMR: δ (DMSO) 9.66(bs, IH), 8.53(s, 1H), " 7.75 (s, 2H), 7.63(bs, IH), 7.42(4 IH), 7.33(d, IH), 5.21(bs, 2H), 4.33 (bs, 2H), 3.79-3.13(bm, 10H), 2.40-2.26(bm, 4H), 2.23(s, 3H), 2.20-2.10(bm, 4H). Example 31 C5-N-(5-(2-Aminoethoxy)-2-methyl-phenyl)-2-(3,5-dimethyl-4-(thieno[2,3- ^pyrimidin-4-yl)piperazin-l-yl)acetamide, hydrochloride salt i) 1,1-Dimethylethyl, 2-(4-methyl-3-nitro-phenoxy)ethylammo-l-carboxylate The subtitle compound was prepared from 4-methyl-3-nitrophenol (2g) and 1,1- dimethylethyl, 2-hydroxyethylamino-l -carboxylate (2.5g) by the method of Example 50 step (i) as a beige solid. Yield: 3g Ti NMR δ (CDCl j ) 7.50(s, IH), 7.22(4 IH), 7.05(dd, IH), 4.96(bs, IH), 4.07(t, 2H), 3.56(q, 2H), 2.52(s, 3H), 1.46(s, 9H) ii) 1,1-Dimethylethyl, 2-(3-amino-4-methyl-phenoxy)ethylamino-l-carboxylate The subtitle compound was prepared from the product of step (i) (lg) by the method of Example 50 step (ii) as an off white solid. Yield: 0.9g s MS: APCI (+ve) 267 (M+l) iii) cis-N-(5-(2-(l,l-Dimethylethyloxycarbonylaminoethoxy))-2-methyl-phenyl)-2-(3,5- dimethyl-4-(thieno[2,3-ήfjpyrimidin-4-yl)piperazin-l-yl)acetamide The product of Example 9 step (ii) (0.54g), the product from step (ii) (0.35g), benzotriazol-0 1-yl-oxy-tripyrrolidinophosphonium hexafluorophosphate (PyBrop) (0.59g), N,N- diisopropylethylamine (0.8ml) in dry N,N-dimethylformamide (15ml) were stirred together under nitrogen for 24h. The mixture was poured onto water (50ml) and the resulting precipitate filtered as a pale yellow solid. Purification was by silica gel chromatography eluting with diethyl ether/ethyl acetate (9:1) as eluant to give the subtitle compound as as white solid. Yield: 0.5 lg MS: APCI(+ve) 555 (M+l) iv) C5-N-(5-(2-Aminoethoxy)-2-methyl-phenyl)-2-(3,5-dimethyl-4-(thieno[2,3-0 ^pyriιnidin-4-yl)piperazin-l-yl)acetamide, hydrochloride salt Thβ title compound was prepared from the product of step (iii) (0.42g) according to the method of Example 27 step (iv) as a white solid. Yield: 0.36g MS: APCI(+ve) 455 (M+l) 5 'HNMR δ (DMSO) 9.57(bs, IH), 8.50(s, IH), 8.15(bs, 2H), 7.65(d, IH), 7.57(d, IH), 7.37(s, IH), 7.15(d, IH), 6.75(dd, IH), 5.05(bs, 2H), 4.17(t, 2H), 3.77(bs, 2H), 3.27(d, 2H), 3.19(4 2H), 3.00(bs, 2H), 2.22(s, 3H), 1.48(d, 6H) Example 32 C5-N-(5-(2-(N-Methylamino)ethoxy)-2-methyl-phenyl)-2-(3,5-dimethyl-4-(thieno[2,3- ^pyrinιidin-4-yl)piperazin-l-yl)acetamide, hydrochloride salt i) 1,1-Dimethylethyl, 2-(4-methyl-3-nitro-phenoxy)ethyl(N-methylaιnino)-l- carboxylate The subtitle compound was prepared from 4-methyl-3-nitrophenol (0.5g) and 1,1- dimethylethyl, 2-hydroxyethyl-(N-methylamino)-l -carboxylate (0.69g) by the method of Example 50 step (i) as a beige solid. Yield: 0.67g 'H NMR δ (CDCI 3 ) 7.5(s, IH), 7.24(4 IH), 7.61(dd, IH), 4.12(bs, 2H), 3.64(t, 2H), 2.98(s, 3H), 2.53(s, 3H), 1.46(s, 9H) ii) 1,1-Dimethylethyl, 2-(3-aniino-4-methyl-phenoxy)ethyl(N-methylammo)-l- carboxylate The subtitle compound was prepared from the product of step (i) (lg) by the method of Example 50 step (ii) as an off white solid. Yield: 0.95g MS: APCI (+ve) 281 (M+l) j iu) N-(5-(2-(l,l-Dimethylethoxycarbonyl(N-methylarjtύno)ethoxy))-2-methyl-phenyl)- 2-(3,5-dimethyl-4-(thieno[2,3-ti]pyriijrύdin-4-yl)piperazin-l-yl)acetamide The subtitle compound was prepared from the product of Example 9 step (ii) (0.26g), the product of step (ii) (0.175g) by the method of Example 31 step (iii). Purification was by silica gel chromatography eluting with diethyl ether/ethyl acetate (9:1) as eluant to give the subtitle compound as a white solid. Yield: 0.25g MS: APCI(+ve) 569 (M+l) iv) cis-N-(5-(2-(N-Methylamino)ethoxy)-2-methyl-phenyl)-2-(3,5-dimethyl-4- (thieno[2,3-rf]pyrimidin-4-yl)piperazin-l-yl)acetamide, hydrochloride salt The title compound was prepared from the product of step (iii) (0.189g) by the method of Example 27 step (iv) as a white solid. Yield: 0.077g MS: APCI(+ve) 469 (M+l) 'HNMR δ (DMSO ) 9.50(bs, IH), 9.00(bs, IH), 8.49(s, IH), 7.64(4 IH), 7.57(d, IH), 7.39(s, IH), 7.17(d, IH), 6.76(4 IH), 5.05(bs, 2H), 4.24(s, 2H), 3.22-3.30(m, 4H), 2.95(bs, 2H), 2.62(s, 2H), 2.22(s, 3H), 1.48(4 6H) Example 33 Cw-N-(5-(2-(N-Methylamiαo)ethoxy)-2-methyl-phenyl)-2-(4-benzenesuIphonyl)-3,5- dimethyl)piperazin-l-yl)acetamide i) cis-l,l-DimethyIethyl, (4-benzenesuIphonyl-3,5-dimethyI)piperazine-l -carboxylate A of solution of cir- 1,1 -dimethyl, 3,5-dimethylpiperazine-l -carboxylate (5g) in pyridine (60ml) was treated with benzene sulphonyl chloride (3ml). After 48h the solvent was evaporated under reduced pressure and purification ofthe residue was by silica gel chromatography eluting with ethyl acetate containing 1% triethylamine to give the subtitle compound as a yellow solid. Yield: 5g MS: APCI(+ve) 255 (M-99) ii) " s-l-Benzenesulphonyl-3,5-dimethylpiperazine, trifluoroacetic acid salt The subtitle compound was prepared from the product of step (i) (5g) by the method Example 1 step (ii). Purification was by recrystallisation from ethanol. Yield: 2g MS: APCI(+ve) 255 (M+l) iii) C5-2-chloro-N-[5-(2-(l,l-dimethylethoxycarbonyl)-N-methylamino)ethoxy)-2- methyl-phenyl] acetamide A solution ofthe product from Example 32 step (ii) (0.65g), N,N-diisopropylethylamine (lml) in dichloromethane (30ml) at 0 °C under nitrogen was treated with chloroacetyl chloride (202ul). After 2h the mixture was partitioned with water and the product extracted into dichloromethane. The organic phase collected, dried (MgSO 4 ) and solvent removed under reduced pressure to give the subtitle compound as a beige foam. Yield: 0.9g MS: APCI (-ve) 355 (M-1) iv) C/5-N-(5-(2-((l,l-dimethylethoxycarbonyl)-N-methylamino)ethoxy)-2-methyl- phenyI)-2-(4-benzenesulphonyl)-3,5-dimethyl)piperazin-l-yl)acetamide The product of step (ii) (lOOmg), sodium bicarbonate (99mg), potassium iodide (5mg) in ethanol (6ml) was treated with the product of step (iii) at 70 °C for 12h. The mixture was partitioned between ethyl acetate and water. The organic phase collected, dried (MgSO 4 ) and Solvent evaporated under reduced pressure. Purification was by silica gel chromatography eluting with iso-hexane/acetone (7:3) containing 1% triethylamine to give the subtitle compound as a white solid. Yield: 126mg MS: APCI(+ve) 575 (M+l), APCI(-ve) 573 (M-1) v) C5-N-(5-(2-(N-Methylamino)ethoxy)-2-methyl-phenyl)-2-(4-benzenesulphonyl)-3,5- dimethyl)piperazin-l-yl)acetamide, hydrochloride salt The title compound was prepared from the product of step (iv) (120mg) by the method of Example 27 step (ii) as a white solid. Yield: 107mg MS: APCI(+ve) 475 (M+l), APCI (-ve) 473 (M-1) 'H NMR δ (DMSO) 9.01(bs, 2H), 7.85(4 2H), 7.69(t, IH), 7.62(t, 2H), 7.30(bs,lH), 7.15(d, IH), 6.74(dd, IH), 4.18(t,4H), 4.01(bs,2H), 3.56(s, 2H), 3.31-3.25(m, 2H), 2.61- s 2.58(m,3H), 2.50 (m, 2H), 2.15(s, 3H), 1.44 (d, 6H) Example 34 N-[5-(2-Amiιιoethoxy)-2-methyl-phenyl)-2-(4-benzenesulphonyl-3,5- dimethyl)piperazin-l-yl]acetamide, hydrochloride salt i) Ci5-2-chloro-N-[5-(2-(l,l-dimethylethyloxycarbonyl)amino)ethoxy-2-methyl- phenyl] acetamide The subtitle compound is prepared from the product of Example 31 step (ii) (650mg) and chloroacetyl chloride (213ul) by the method of Example 33 step (iii) as a beige foam,s Yield: 900mg MS: APCI(-ve) 341 (M-1) ii) Cw-N-[5-(2-(l,l-Dimethylethoxycarbonyl)amino)ethoxy-2-methyl-phenyl)-2-(4-0 bjfenzenesulphonyl-3,5-dimethyI)piperazin-l-yl] acetamide The subtitle compound was prepared from the product of step (i) (148mg) and the product of Example 33 step (ii) by the method of Example 33 step (iv) as a pale yellow solid. Yield: 150mg. 5 MS: APCI(+ve) 561 (M+l), APCI (-ve) 559 (M-1) iii) Cs-N-[5-(2-(Aminoethoxy)-2-methyl-phenyl)-2-(4-benzenesulphonyl-3,5- dimethyl)piperazin- 1-yl] acetamide, hydrochloride salt The title compound was prepared from the product of step (ii) (150mg) by the method Example 27 step (iv) as a white solid. Yield: 150mg MS: APCI (+ve) 461 (M+l), APCI (-ve) 459 (M-1) Η NMR δ (DMSO) 8.13(bs, 2H), 7.85(d, 2H), 7.70-7.59(m, 3H), 7.32(bs,lH), 7.14(d, IH), 6.73(dd, IH), 4.16(bs, 2H), 4.10(t, 2H), 3.56(s, 2H), 3.19(4 2H), 3.10-3.03(m, 2H), 2.50(m, 2H), 2.15(s, 3H), 1.43 (d, 6H) Example 35 N-(2-Oxo-2,3-d ydro-lH-mdol-4-yl)-2-(8-thieno[2,3-^pyrimidin-4-yl-3,8- diazabicyclo [3.2.1] oct-3-yl) acetamide i) 2-ChIoro-N-(2-oxo-2,3-dihydro-lJy-indol-4-yl)acetamide The subtitle compound was prepared from 4-amino-oxindole (0.19g) (J. Org. Chem., 1983, 48 (15), 2468-72) and chloroacetyl chloride (0.1ml) by the method of Example 15 step (i). Yield: 0.25g MS: ES(-ve) 223 (M-l) u) 3-[(2-Oxo-2,3-dihydro-l J H-indol-4ylcarbamoyl)-methyl]-3,8- diazabicyclo[3.2.1]octane-8-carboxylic acid, 1,1-dimethylethyl ester The subtitle compound was prepared from the product of step (i) (0.24g) and 1,1 -dimethyl, 3,8-diaza-bicyclo[3.2. l]octane-8-carboxylate (0.26g) by the method of Example 19 step (i) Yield: 0.8g ! H NMR: δ (DMSO) 10.45 (lH,s), 9.26 (lH,s), 7.39 (lH,d), 7.15 (lH,t), 6.62 (lH,d), 4.06 (2H,brs), 3.45 (2H,s), 3.10 (2H,s), 2.72 (2H,d), 2.38 (2H,d), 1.95 (2H,d), 1.79 (2H,m), 1.41 (9H,s). m) 2-(3,8-Diazabicyc!o[3.2.1]oct-3-yI)-N-(2-oxo-2,3-d ydro-liϊ-indol-4-yl)acetamide, hydrochloride salt The product of step (ii) (0.8g) was dissolved in 2M hydrogen chloride in 1,4-dioxane (10ml), 1,4-dioxane (10ml), methanol (10ml) and the reaction mixture was stirred at ambient temperature for 2 hours. The solvents evaporated under reduced pressure to dryness. Yield: 0.8g MS: ES(+ve) 301 (M+l) iv) N-(2-Oxo-2,3-d ydro-l/r-mdol-4-yl)-2-(8-thieno[2,3-ci]pyrimidin-4-yl-3,8- diazabicycIo[3.2.1]oct-3-yI)acetamide The title compound was prepared from the product of step (iii) (0.8g) by the method of Example 1 step (i). Yield: O.lg MS-; ES(+ve) 435 (M+l) 2 H NMR: δ (DMSO) 10.43 (lH,s), 9.27 (lH,s), 8.39 (lH,s), 7.66 (lH,d), 7.62 (lH,d), 7.40 (JH,d), 7.15 (lH,t), 6.62 (lH,d), 5.04 (2H,brs), 3.47 (2H,s), 3.12 (2H,s), 2.87 (2H,d), 2.57 (2H,d), 2.15 (2H,m), 1.97 (2H,m). M.P. 265°C decomp. Example 36 N-(3-Fluoro-2-methyl-phenyl)-2-((8-quinazolin-4-yl)-3,8-diazabicyclo[3.2.1]oct-3- yl)acetamide i) 2-ChIoro-N-(3-fluoro-2-methyl-phenyl)acetamide The subtitle compound was prepared from 3-fluoro-2-methylaniline (0.232g) and chloroacetyl chloride (0.164ml) by the method of Example 33 step (iii) as a beige solid. 5 Yield: 0.3g MS: APCI(-ve) 200 (M-1) ii) N-(3-Fluoro-2-methyl-phenyl)-2-(l,l-dimethylethyloxycarbonyl)-3,8- l o diazabicyclo [3.2.1 ] oct-3-yl] acetamide The subtitle compound was prepared from the product of step (i) (179mg) and 1,1- dimethyl-3,8-diaza-bicyclo[3.2.1]octane-8-carboxylate (0.2g) by the method of Example 33 step (iv) as a white solid. Yield: 305mg is MS: APCI (+ve) 378 (M+l) iii) V-(3-Fluoro-2-methyl-phenyl)-2-(3,8-diazabicyclo[3.2.l]oct-3-yl)acetamide, hydrochloride salt The subtitle compound was prepared from the product of step (ii) (303mg) by the method 20 of Example 27 step (iv) as a white solid. Yield: 305mg MS: APCI(+ve) 278 (M+l), APCI (-ve) 276 (M-1) iv) N-(3-Fluoro-2-methyl-phenyl)-2-((8-quinazolin-4-yl)-3,8-diazabicyclo[3.2.1]oct-3- 25 yl)acetamide The title compound was preapred from the product of step (iii) (223mg) and 4- chloroquinazoline (133mg) by the method of Example 2 step (i) as a white solid. Yield: 120mg MS: APCI(+ve) 406 (M+l) Η NMR δ (DMSO) 9.34 (s, IH), 8.57(s, IH), 8.09(d, IH), 7.84-7.77(m, 2H), 7.60-7.53(m, 2H), 7.22(q, IH), 6.99(t, IH), 4.87(bs, 2H), 3.24(s, 2H), 2.97(dd, 2H), 2.77(dd, 2H), 2.17(s, 3H), 2.12-2.04(m, 2H), 1.91-1.85(m, 2H) Example 37 N-(2-Methylphenyl)-2-[8-(benzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct-3- yl] acetamide The trifluoroacetate salt of Example 20 step (iv) was converted to the free base by use of aqueous 2N NaOH solution followed by extraction with ethyl acetate. The extracts were dried (MgSO 4 ), filtered and evaporated to dryness, leaving an oil which crystallised on standing. MS: ES(+ve) 260 (M+l, 100%) The amine free base (0.075g) was stirred in acetone (15ml) and a solution of K 2 CO 3 (0.08g) in water (0.5ml) was added, followed by benzenesulphonyl chloride (0.047g) dissolved in acetone (5.0ml). The solution was stirred for 1 hour, quenched with water and the white solid was collected by filtration, washed with water and dried in vacuo, to give the title compound. Yield 0.037g. MS: APCI(+ve) 487 (M+l, 100%) ! H NMR: δ (CDC1 3 ) 1.55 (s, H 2 O), 1.70 (2H, m), 1.85(2H, m), 2.26(3H, s), 2.67 (2H, m), 2.85(2H, d of d), 3.18(2H, s), 7.05(2H, m), 7.2(2H, m), 7.52(2H, m), 7.6(1H, m), 7.9(2H, d) MP: 169-170 °C Example 38 N-(3-Fluoro-2-methylphenyl)-2-[8-(benzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct-3- yl] acetamide i) Methyl, (3,8-Diazabicyclo [3.2.1] oct-3-yl)acetate, hydrochloride salt A mixture ofthe product from Example 30 step (i), 2M HCl in 1,4-dioxane (10ml) and methanol (10ml) was stirred at ambient temperature for 2 hours and evaporated to dryness. Yield 0.54g. Used directly in the next step. ii) Methyl, (8-benzenesulphonyl-3,8-diazabicyclo [3.2.1] oct-3-yl)acetate A mixture ofthe product of step (i) (0.53g), potassium carbonate (0.66g) and benzenesulphonyl chloride (0.32ml) in acetone (10ml) and 1,4-dioxane (10ml) was stirred at ambient temperature for 4 hours. The mixture was partitioned between ethyl acetate and water. The organic phase was washed with water, saturated sodium bicarbonate and brine, dried (MgSO 4 ) and evaporated. The product was purified by silica gel chromatography eluting with 0.5% ethanol in dichloromethane. Yield 0.29g. l U NMR: δ (DMSO) 7.86 (2H,d), 7.69 (lH,m), 7.59 (2H,m), 4.13 (2H,brs), 3.59 (3H,s), 3.29 (2H,s), 2.67 (2H,dd), 2.57 (2H,d), 1.59 (2H,q), 1.13 (2H,m). iii) (8-Benzenesulphonyl-3,8-diazabicyclo[3.2.1]oct-3-yl)acetic acid A solution ofthe product of step (ii) (0.29g) in ethanol (5ml) was treated with 1ml of IN sodium hydroxide solution. After 1 hour at ambient temperature the reaction mixture was acidified with 2N hydrochloric acid to pH4 and evaporated to dryness to give a white solid. This was dried at 40° C in vacuo over phosphorous pentoxide for 2 hours and used directly in the next step. iy N-(3-Fluoro-2-methylphenyl)-2-[8-(benzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct- 3-yl] acetamide A mixture ofthe product of step (iii) (0.45mmol), 2-fluoro-2-methylaniline (60μl), PyBroP (0.25g), NN-dimethylaminopyridine (54mg) and NN-diisopropylethylamine (0.23ml) in Ν,Ν-dimethylformamide (5ml) was stirred at ambient temperature for 16 hours. The reaction mixture was partitioned between ethyl acetate and water. The organic phase was washed with water and brine, dried (MgSO 4 ) and evaporated. The residue was purified by flash chromatography eluting with 1% ethanol in dichloromethane followed by further chromatography with 20% ethyl acetate /iso-hexane to give the title compound as a white solid. Yield: 30mg. MS: AP (+ve) 418 (M+l) lH NMR: δ (DMSO) 9.20 (lH,s), 7.88 (2H,d), 7.70 (lH,m), 7.60 (2H,m), 7.49 (lH,d), 7.20 (lH-q), 6.97 (lH,t), 4.17 (2H,brs), 3.17 (2H,s), 2.81 (2H,dd), 2.50 (2H,d), 2.09 (3H,s), 1.78 (2H,m), 1.20 (2H,m). M.P. 168-9°C Example 39 C5-N-(3-Fluoro-2-methyl-phenyl)-2-(4-benzenesulphonyl)-3,5-dimethyl)piperazin-l- yl) acetamide i) Cis-N-(3-Fluoro-2-methyI))phenyl)-2-(4-benzenesulphonyl)-3,5-dimethyl)piperazin- l-yl)acetamide The title compound was prepared from the product of Example 33 step (ii) (152mg) and the product of Example 36 step (i) (132mg) by the method of Example 33 step (iv) as a white solid. Purification was by silica gel chromatography eluting with iso-hexane/acetone (7:3). Yield: 58mg. MS: APCI(+ve) 420 (M+l) 'H NMR δ (DMSO) 9.23(s, IH), 7.83(d, 2H), 7.69-7.58(m, 3H), 7.34(d, IH), 7.20(q, IH), 6.99(t, 1H)„ 4.06-3.99(m, 2H), 3.03(s, 2H), 2.64(d, 2H), 2.08(s, 3H), 1.90(dd, 2H), 1.42(d, 6H) Example 40 N-(2-Methylphenyl)-2-[8-(3-cyanobenzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct- 3-yl] acetamide The title compound was prepared from the product of Example 20 step (iv) and 3- cyanobenzenesulphonyl chloride by the method of Example 37 as a white solid. Yield O. lOlg. MS: APCI(+ve) 425 (M+l, 100%) ! H NMR: δ (CDCI 3 ) 1.76(2H, m), 1.92(2H, m), 2.27(3H, s), 2.64(2H, d), 2.85(2H, m), 3.20(2H, s), 4.26(2H, s), 7.06(1H, m), 7.20(2H, m), 7.68(1H, m), 7.87(1H, ), 8.02(1H, d), 8.13(1H, m), 8.18(1H, s), 8.68(1H, s) MP: 166-8 °C Example 41 2-[8-(3-Methoxybenzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2- methylphenyl)acetamide The title compound was prepared from the product of Example 20 step (iv) and 3- methoxybenzenesulphonyl chloride by the method of Example 37 as a white solid Yield 0.095g. MS: APCI(+ve) 430 (M+l, 100%) ! H NMR: δ (CDCI 3 ) 1.75(2H, m), 1.82(2H, m), 2.26(3H, s), 2.65(2H, d), 2.82(2H, d of d), 3.18(2H, s), 3.86(3H, s), 4.25(2H, br s), 7.02-7.25(4H, m), 7.40-7.50(3H, m), 8.02(lH, d), 8.75(lH, br s) MP: 163-5 °C Example 42 2-[8-(Benzo[l,2,5]oxadiazole-4-sulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2- methylphenyl)acetamide The title compound was prepared from the product of Example 20 step (iv) by the method of Example 37 as a white solid. Yield: 0.088g. MS: APCI(+ve) 442 (M+l, 100%) ! H NMR: δ (CDC1 3 ) 1.90-2.02(4H, m), 2.28(3H, s), 2.65(2H, m), 2.90(2H, m), 3.16(2H, s), 4.55(2H, s), 7.06(1H, m), 7.19(2H, m), 7.54(1H, m), 8.08(3H, d), 8.75(1H, br s) MP: 167-8 °C Example 43 2-[8-(Benzo[l,2,5]thiadiazole-4-sulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2- methylphenyl)acetamide The title compound was prepared from, the product of Example 20 step (iv) by the method of Example 37 as a white solid. Yield 0.108g. MS: APCI(+ve) 458 (M+l, 100%) lU NMR: δ (CDCI 3 ) 1.75(2H, m), 1.93(2H, m), 2.27(3H, s), 2.62(2H, m), 2.85(2H, d of d), 3.14(2H, s), 4.61(2H, br s), 7.05(1H, m), 7.20(2H, m), 7.70(1H, m), 8.02(1H, d), 8.26(2H, d of d), 8.77(1H, br s) MP: 169-70 °C Example 44 2-[8-(5-ChIorothieno-2-yl)sulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2- methylphenyl)acetamide The title compound was prepared from the product of Example 20 step (iv) and 2-chloro-5- chlorosulphonyl-thiophene by the method of Example 37 as a white solid. Yield 0.108g. MS: APCI(+ve) 440 (M+l, 100%) !H NMR: δ (CDC1 3 ) 1.90(4H, m), 2.28(3H, s), 2.70(2H, d), 2.86(2H, m), 3.21(2H, s), 4.27(2H, br s), 6.94(1H, d), 7.05(1H, m), 7.20(2H, m), 7.42(1H, d), 8.04(1H, d), 8.73(1H, br s) MP: 150-2 °C Example 45 2-[8-(2-ChlorobenzenesuIphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2- methylphenyl)acetamide The title compound was prepared from the product of Example 20 step (iv) and 2- chlorobenzenesulphonyl chloride by the method of Example 37 as a white solid. Yield 0.085g. MS: APCI(+ve) 434 (M+l, 100%) l B NMR: δ (CDCI 3 ) 2.07(4H, m), 2.31(3H, s), 2.66(2H, d), 2.82(2H, m), 3.18(2H, s), 4.31(2H, br s), 7.05(1H, m), 7.22(2H, ), 7.40(1H, m), 7.53(2H, m), 8.05(1H, d), 8.12(1H, d ofd), 8.80(lH, br s) MP: 170-1 °C Example 46 2-[8-(5-Chloro-2-methoxybenzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2- methylphenyl)acetamide The title compound was prepared from the product of Example 20 step (iv) and 3-chloro-6- methoxybenzenesulphonyl chloride by the method of Example 37 as a white solid Yield 0.105g. MS: APCI(+ve) 464 (M+l, 100%) H NMR: δ (CDC1 3 ) 1.93(4H, m), 2.30(3H, s), 2.62(2H, m), 2.85(2H, m), 3.17(2H, s), 3.95(3H, s), 4.35(2H, br s), 6.95(1H, d), 7.05(1H, ), 7.20(2H, m), 7.46(1H, d of d), 7.91(1H, d), 8.05(1H, d), 8.80(1H, br s) MP', 180-1 °C Example 47 2-[8-(4-Acetylammomethoxybenzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2- methylphenyl)acetamide The title compound was prepared from the product of Example 20 step (iv) and 4- acetylamidobenzenesulphonyl chloride by the method of Example 37 as a white solid. Yield 0.108g. MS: APCI(+ve) 457 (M+l, 100%) *H NMR: δ (CDC1 3 ) 1.60(2H, m), 1.82(2H, m), 2.18(3H, s), 2.26(3H, s), 2.65(2H, d), 2.80(2H, d of d), 3.18(2H, s), 4.20(2H, br s), 7.05(1H, m), 7.18(2H, m), 7.78(4H, s), 8.00(1H, d), 8.77(1H, br s), 9.64(1H, s) MP: 205-6 °C Example 48 N-(2-Methylphenyl)-2-[(8-(3-methylthieno[2,3-< ]pyrimidm-4-yl)-3,8- diazabicyclo[3.2.1]oct-3-yl]acetamide The trifluoroacetate salt of Example 20 step (iv) was converted to the free base by use of aqueous 2N NaOH solution followed by extraction with ethyl acetate. The extracts were dried (MgSO 4 ), filtered and evaporated to dryness, leaving an oil which crystallised on standing. MS: ES(+ve) 260 (M+l , 100%) A mixture ofthe amine free base (0.13g), N,N-disopropylethylamine (0.5ml), 4- dimethylatninopyrimidine (0.06g) and 4-chloro-3-methylthieno[2,3-d]pyrimidine was heated in N-methylpyrrolidin-2-one (5.0ml) at 100 °C for 5 hours. The solvent was evaporated under high vacuum and the residue was slurried with water, filtered and dried. Purification was by chromatography on silica gel eluting with dichloromethane containing ethanol (1%) to give the title compound as a white solid. Yield (0.053g). MS: APCI(+ve) 408 (M+l, 100%) lR NMR: δ (CDC1 3 ) 1.98(4H, m), 2.35(3H, s), 2.62(3H, s), 2.95(4H, m), 3.26(2H, s), 4.46(2H, br s), 7.00(1H, s), 7.10(1H, m), 7.20(2H, m), 8.10(1H, d), 8.53(1H, s), 8.96(1H, br s) MP: 199-200 °C Example 49 c s-2-(3,5-Dimethyl-4-(thieno[2,3-« lpyrimidm-4-yl)piperazin-l-yl)-N-(l-methyl-l J H- benzoimidazol-2-yl)acetamide The title compound was prepared from the product of Example 9 step (ii) (0.2g) and 2- amino- 1-methyl-benzimidazole (0.14g) by the method of Example 38 step (iv). Purification was, by silica gel chromatography followed by recrystallisation from methanol. Yield 45mg. MS: APCI (+ve) 436 (M+l) ! H NMR: δ (CDCI 3 ) 8.47 (lH,s), 7.41 (lH,d), 7.26 (3H,m), 5.01 (2H,brs), 3.68 (3H,s), 3.40 (2H,s), 3.05 (2H,d), 2.50 (2H,d), 1.61 (6H,s). M.P. 200°C Example 50 C5-2-(3,5-Dimethyl-4-(thieno[2,3-d]pyrinιidm-4-yl)piperazin-l-yl)-N-(2-methyl-5-(4- piperidmyloxy)phenyl)acetamide, hydrochloride salt i) 1,1-Dimethylethyl, 4-(4-methyI-3-nitro)phenoxypiperidme-l-carboxylate A solution of 4-methy 1-3 -nitrophenol (2g), 1,1-dimethylethyl, 4-hydroxypiperidine-l- carboxylate (2.6g), triphenylphosphine (4.11 g) in tetrahydrofuran (40ml) under nitrogen at 0 °C was treated with diethylazidodicarboxylate (2.3ml) over 1 minute. The cooling bath was removed and the mixture allowed to stir at ambient temperature for 48h. The solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography eluting with dichloromethane containing 1% triethylamine to give the subtitle product as a pale yellow oil. Yield: 3.46g 'H NMR δ (CDC1 3 ) 7.52(dd, IH), 7.21(dd, IH), 7.08(dd, IH), 4.50(m, IH), 3.70(m, 2H), 3.55(m, 2H), 2.50(s, 3H), 2.0-1. (m, 4H), 1.5 (s,9H) ϋ) 1,1-Dimethylethyl, 4-(3-aιnino-4-methyl)phenoxypiperidine-l-carboxylate A solution ofthe product from step (i) (2g), 10% Palladium on charcoal (300mg) were stirred under a lbar atmosphere of hydrogen at ambient temperature. The mixture was filtered through celite and solvent removed under reduced pressure to leave the subtitle product as a beige solid. Yield: 1.88g 'H NMR δ (CDCI 3 ) 6.9(d, IH), 6.3(m, 2H), 4.4(m, IH), 3.7(m, 2H), 3.6(bs, 2H), 3.3(m, 2H), 2.10(s, 3H), 1.9-1.6(m, 4H), 1.50(s, 9H) iϋ) 2-Chloro-N-5-(l-(l,l-dimethylethoxycarbonyl)-4-piperidmyloxy)-4-methyl-5- nitro) acetamide A solution ofthe product from step (ii) (1.4g), N,N-diisopropylethylamine (2ml) in dichloromethane( 30ml) under nitrogen at 0 °C was treated with chloroacetylchloride (0.4ml). After 4h the reaction mixture was partitioned between water and dichloromethane. The organic phase collected, dried (MgSO 4 ) and solvent reduced under reduced pressure to leave the subtitle compound as a brown oil. Yield: 1.8g This was used directly in the next step. iv) C5-2-(3,5-Dimethyl-4-(thieno[2,3-d]pyrimidm-4-yl)piperazin-l-yl)-N-(2-methyl-5- (l-(l,l-dimethylethoxycarbonyl)-4-piperidinyloxy)phenyl)acetamide The subtitle compound was prepared from the product of Example 2 step (ii) (0.4g) and the product of step (iii) (0.56g) by the method of Example 33 step (iv) as a pale yellow gum. Yield: 0.25g MS: APCI(+ve) 595 (M+l), APCI(-ve) 593(M-1) v) C s-2-(3,5-Dimethyl-4-(thieno[2,3-d]pyrimidm-4-yl)piperazin-l-yl)-N-(2-methyl-5- (4-piperidinyloxy)phenyl)acetamide, hydrochloride salt The title compound was prepared from the product of step (iv) (0.24g) by the method of Example 27 step (iv) as a white solid. Purification was by reverse phase HPLC eluting with aq. l%ammonium acetate/acetonitrile (95% to 60%). Yield. 80mg MS: APCI(+ve) 495(M+1), APCI(-ve) 493 (M-1) 'HNMR δ (DMSO) 8.97(bs, IH), 8.52(s, IH), 7.7(d, IH), 7.62(d, IH), 7.26(s, IH), 7.18(d, IH), 6.84(d, IH), 5.30(bs, 2H), 4.60(bs, IH), 3.30-3.00(2xbs, 4H), 2.20(s, 3H), 2.15- 1.80(m, 4H), 1.60(d, 6H) Example 51 C5-2-(3,5-Dimethyl-4-benzenesulphonyl)piperazin-l-yl)-N-(2-methyl-5-(4- piperidiαyloxy)phenyl)acetamide i) C s-2-(3,5-Dimethyl-4-benzenesulphonyl)pip dimethylethoxycarbonyl)4-piperidinyloxy)phenyl)acetamide The subtitle compound was prepared from the product of Example 33 step (ii) (0.42g) and the product of Example 50 step (iii) (0.55g) by the method of Example 33 step (iv). Purification was by silica gel chromatography eluting with dichloromethane/ethyl acetate (95:5) to give the subtitle compound as colourles gum. Yield: 0.23g MS: APCI(+ve) 601 (M+l), APCI(-ve) 599 (M-1) ii) C5-2-(3,5-Dimethyl-4-benzenesulphonyI)piperazin-l-yl)-N-(2-methyl-5-(4- piperidinyloxy)phenyl)acetamide The title compound was prepared from the product of step (i) (0.2g) by the method of Example 27 step (iv) as a white solid after purification by reverse phase HPLC eluting with 1% aq. ammonium acetate/acetonitrile (95% to 60%). Yield: 50mg MS: APCI(+ve) 501 (M+l), APCI(-ve) 499 (M-1) 'HNMR δ (DMSO) 8.8(bs, IH), 7.8(d, 2H), 7.7(m, 3H), 7.25(s, IH), 7.15(d, IH), 6.75(d, IH), 4.60(m, IH), 4.2-4.0(bs, 2H), 3.3-3.0(2xm, 4H), 2.2(s, 3H), 2.15-1.70(m, 4H), 1.5(d, 6H) Example 52 Cs'-2-(3,5-Djlmethyl-4-(qumazojun-4-yl)piperazin-l-yl)-N-(2-methyl-5-(4- piperidinyloxy)phenyl)acetamide i) 1,1-Dimethylethyl, 4-(4-quinazoliιιyl)-3,5-dimethylpiperazine-l-carboxylate 4-Chloroquinazoline (6g), cis- 1,1 -diethyl ethyl, 3,5-dimethylpiperazine-l -carboxylate (7.8g), N,N-diisopropylethylamine (32ml) in l-methyl-2-pyrrolidinone (70ml) were heated at 120 °C for 6 days under nitrogen. The mixture was partitioned between ethyl acetate and brine. The organic phase collected and further washed with brine (x2), collected, dried (MgSO 4 ) and solvent evaporated under reduced pressure to leave a pale brown solid. Purification was by silica gel chromatograpy eluting with ethyl acetate/iso-hexane (3:7) to give the subtitle compound as a pale yellow oil. Yield: l.lg MS: APCI(+ve) 343 (M+l) ii) c 5-4-(4-Quinazolinyl)-2,6-dimethylpiperazine, hydrochloride salt The subtitle compound was prepared from the product of step (i) (lg) by the method of Example 27 step (iv) as cream solid. Yield: 1.8g MS: APCI(+ve) 243 (M+l) iii) C5-2-(3,5-Dimethyl-4-(4-quinazolinyl)piperazin-l-yl)-N-(2-methyl-5-(l-(l,l- dimethylethoxycarbonyl)4-piperidinyloxy)phenyl)acetamide The subtitle compound was prepared from the product of step (ii) (0.56g) and the product of Example 50 step (iii) (0.37g) by the method of Example 33 step (iv). Purification was by silica gel chromatography eluting with ethyl acetate/iso-hexane (9:1) to give the subtitle compound as a white solid. Yield. 0.18g MS: APCI(+ve) 589 (M+l) iv) C/5-2-(3,5-Dimethyl-4-(qumazojlin-4-yl)piperazin-l-yl)-N-(2-methyl-5-(4- piperadinyloxy)phenyl)acetamide The title compound was prepared from the product of step (iii) (0.18g) by the method of Example 27 step (iv). Purification was by reverse phase HPLC eluting qith 1% aq. ammonium acetate/acetonitrile (99% to 50%) to give the title compound as a white solid. Yield: 0.079g MS: APCI(+ve) 489 (M+l) 'H NMR δ (CDC1 3 ) 9.26(bs, IH), 9.08(bs, IH), 8.35(4 IH), 8.00(d, IH), 7.95(s, IH), 7.90(t, IH), 7.60(t, IH), 7.10(4 IH), 6.61(4 IH), 4.57(m, IH), 3.25(m+s, 4H), 3.05(m, 2H), 2.90(d, 2H), 2.60(m, 2H), 2.30(s, 3H), 2.10(m, 2H), 2.0(m, 2H), 1.0(4 6H) Example 53 C/ 2-(3,5-Dimethyl-4-(4-qumazojlmyl)piperazin-l-yl)-N-(2-methyl-5-(piperazm-4-yl- methyl)phenyl)acetamide i) 2-Chloro-N-5-((l-(l,l-dimethylethyloxycarbonyl)piperazin-4-yI)methyl)phenyl-2- methyl)acetamide The subtitle compound was prepared from the product of Example 27 step (ii) (O.lg) by the method of Example 33 step (iii) as a beige foam. Yield:0.15g MS: APCI(+ve) 382 (M+l) ύ Cw-2-(3,5-Dimethyl-4-(4-quinazolinyl)piperazin-l-yl)-N-(2-methyl-5-(l-(l,l- dimethylethyloxycarbonyl)piperazin-4-yl-methyl)phenyl)acetamide The subtitle compound was prepared from the product of Example 52 step (ii) (0.2g) and the product of step (i) (0.21g) by the method of Example 33 step (iv). Purification was by silica gel chromatography eluting with ethyl acetate/iso-hexane (9:1) to give the subtitle compound as a white solid. Yield. 0.068g MS: APCI(+ve) 588 (M+l) iii) C5-2-(3,5-Dimethyl-4-(4-qumazojlmyl)piperazin-l-yl)-N-(2-methyl-5-(piperazin-4- yl-methyl)phenyl)acetamide The title compound was prepared from the product of step (ii) (0.069g) by the method of Example 27 step (iv). Purification was by reverse phase HPLC eluting with 1% aq. ammonium acetate/acetonitrile (99% to 50%) to give the title compound as a white solid. Yield: 0.072g MS: APCI(+ve) 488 (M+l) 'H NMR δ (CDCI 3 ) 8.58(bs, IH), 8.25(bs, IH), 7.63(4 IH), 7.20(m, 2H), 6.95(t, IH), 6.50(d, IH), 6.35(d, IH), 3.60(bs, 2H), 2.80(s, IH), 2.60(s, IH), 2.30(bs, 3H), 2.20(d, IH), 2.0(m, IH), 1.90(bs, 2H), 1.70(s, 2H), 1.30(bd, 6H) Example 54 Cs-2-(3,5-Dimethyl-4-(4-qumazolinyl)piperazin-l-yl)-N-(2-methyl-5-(2-(N- methylamino)ethoxy)phenyl)acetamide i) Cis-2-(3,5-Dimethyl-4-(4-quiιιazolinyl)piperazin-l-yl)-N-(2-methyl-5-(2-(l,l- dimethylethyloxycarbonyI-N-methylaminoethoxy)phenyl)acetamide The subtitle compound was prepared from the product of Example 52 step (ii) (0.64g) and the product from Example 33 step (iii) (0.59g) by the method of Example 33 step (iv). Yield. 0.45g MS: APCI(+ve) 563 (M+l), APCI(-ve) 561 (M-1) H) Cz5-2-(3,5-Dimethyl-4-(4-quinazolinyl)piperazin-l-yl)-N-(2-methyl-5-(2-(N- methylamino)ethoxy)phenyl)acetamide The title compound was prepared from the product of step (i) (0.4g) by the method of Example 27 step (iv). Purification was by reverse phase HPLC eluting with 1% aq. ammonium acetate/acetonitrile (99% to 50%) to give the title compound as a white solid. Yield: 0.25g MS: APCI(+ve) 463 (M+l) 'H NMR δ (CDC1 3 ) 9.30(bs, IH), 9.12(bs, IH), 8.39(, IH), 8.05(d, IH), 7.95(m, 2H), 7.60(t, IH), 7.10(4 IH), 6.70(d, IH), 4.20(m, 2H), 4.0(bs, 2H), 3.30(s, 2H), 3.20(m, 2H), 2.90(m, 2H), 2.60(m+s, 5H), 2.35(s, 3H), 1.0(bs, 6H) Example 55 c s-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide i) cts-2-(3,5-Dimethylpiperazin-l-yl-N-(2-methylphenyl)acetamide A mixture of 2-chloro-N-(2-methylphenyl)acetamide (1.83g), N,N-disopropylethylamine (5.0ml), sodium iodide (0.020g) and ets-2,6-dimethylpiperazine 1.14g) in ethanol (50ml) was heated at reflux for 2.5 hours. The solvent was removed and the residue was crystallised from ethanol as white needles. It was dissolved in water and the solution was made basic with 2N aqueous NaOH, extracted with dichloromethane and the extracts were dried (MgSO 4 ), filtered and evaporated to dryness, leaving an oil which crystallised on standing. Yield l.lg. H NMR: δ (CDCI 3 ) 1.08(6H, d), 1.40(1H br s) 1.94(2H, t), 2.27(3H, s), 2.83(2H, m), 2.98(2H, m) 3.14(2H, s), 7.03(1H, m), 7.20(2H, m), 8.18(1H, d), 9.32(1H, br s) MP: 105-6 °C ii) c s-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide The product of step (i) (0.60g), 4-dimethylaminopyridine (0.14g) in pyridine (2.0ml) was stirred while 3-cyanobenzenesulphonyl chloride (0.46g) was added. The mixture was stirred for 10 minutes after which it solidified. After 1 hour the solid was triturated with water and filtered off. It was purified by chromatography on silica eluting with ethyl acetate/iso-hexane (1:1) to give the title compound as a pale yellow solid. Yield: 0.22g. MS: APCI(+ve) 427 (M+l, 100%) H NMR: δ (CDCI 3 ) 1.55(6H, d), 2.17(2H, d of d), 2.32(3H, s), 2.73(2H, d), 3.10(2H, s), 4.13(2H, m), 7.10(1H, m), 7.20(2H, m), 7.67(1H, m), 7.85(1H, m), 7.95(1H, m), 8.05(1H, m), 8.12(1H, m), 8.67(1H, br s). MP: 152-3 °C Example 56 c s-N-(2-Methylphenyl)-2-[4-(3-nitrobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]- acetamide The title compound was prepared from the product of Example 55 step (i) and 3- nitrobenzenesulphonyl chloride by the method of Example 55 step (ii) as an off white solid. Yield: 3.06g MS: APCI(+ve) 447 (M+l, 100%) ! H NMR: δ (CDC1 3 ) 1.59(6H, d), 2.20(2H, d of d), 2.30(3H, s), 2.74(2H, d), 3.10(2H, s), 4.16(2H, m), 7.05(1H, m), 7.20(2H, m), 7.75(1H, t), 7.96(1H, d), 8.16(1H, d of d), 8.43(1H, d of d), 8.67(2H, br s). MP: 163-4 °C Example 57 c s-2-[4-(3-Aminobenzenesulphonyl)-3,5-dimethylpiperazύι-l-yl]-N-(2- methylphenyl)acetamide To a stirred solution ofthe product of Example 56 (3.0g) in ethanol (1500ml) was added 5%,palladium on charcoal (1.5g) followed by dropwise addition of hydrazine hydrate (20ml). The mixture was stirred for 1 hour, filtered through 'hyflo' and the filtrate was evaporated to dryness. The solid residue was crystallised from ethanol to give the title compound as a white solid. Yield 1.6g. MS: APCI(+ve) 417 (M+l, 100%) ^ NMR: δ (CDCI 3 ) 1.54(6H, d), 2.18(2H, d of d), 2.30(3H, s), 2.65(2H, d), 3.07(2H, s), 3.90(2H, s), 4.15(2H, m), 6.82(1H, d of d), 7.05-7.20(6H, m), 7.99(1H, d), 8.75(1H, s). MP: 202-3 °C Example 58 C5-2-(3,5-Dimethyl-4-(3-cyanobeιιzenesulphonyl)piperazm-l-yl)-N-(qumolin-5- yl)acetamide i) C/5-2-(3,5-Dimethyl-piperazm-l-yl)-N-(quinolin-5-yl)acetamide A mixture of 2-chloro-N-(quinolin-5-yl)acetamide (7.76g) (J. Indian Chem Soc, 1940, 17, 619-621), cis-2,6-dimethylpiperazine (4.42g), sodium bicarbonate (8.9g) in ethanol (100ml) was heated at reflux for 4h. The solvent was removed under reduced pressure, The residue was partitioned between chloroform and brine. The organic phase collected and the aqeuous phase further extracted (x6 ) with chloroform. The combined extracts dried (MgSO 4 ) and solvent removed under reduced pressure. Yield: 6.8g MS: APCI(+ve) 299 (M+l) ii) Ct 2-(3,5-Dimethyl-4-(3-cyanobenzenesulphonyl)piperazm-l-yl)-N-(quinolin-5- yl)acetamide The product from step (i) (150mg), 4-N,N-dimethylaminopyridine (31mg) in pyridine (0.5ml) was treated in one portion with 3-cyanobenzenesuphonyl chloride (leq) and then immediately heated for 30 minutes. The mixture was partitioned between dichloromethane and water. The organic phase collected, dried (MgSO 4 ) and solvent removed under reduced pressure. The reisdue was purified by reverse phase HPLC eluting with 0.1% aq. ammonium acetate/acetontrile (95%> to 50%) as eluant to give the title compound as a white solid. Yield: 8mg MS: APCI(+ve) 464 (M+l) 'HNMR δ (CD 3 OD) 9.87(d, IH), 8.4(4 IH), 8.3(4 IH), 8.2(m, 2H), 8.0(m 2H), 7.78(m, 2H), 7.6(m, IH), 4.2(m, 2H), 3.24(s, 2H), 2.82(d, 2H), 2.1(dd, 2H), 1.57(d, 6H) Example 59 C/5-2-(3,5-Dimethyl-4-(4-cyanobenzenesulphonyl)piperazin-l-yl)-N-(quinolm-5- yl)acetamide The title compound was prepared from the product of Example 58 step (i) (0.503 mmol) and 4-cyanobenzenesulphonyl chloride (0.503mmol) by the method of Example 58 step (ii) as a white solid. Yield: 4mg MS: APCI(+ve) 464 (M+l) 'HNMR δ (CD 3 OD) 8.9(d, IH), 8.4(d, IH), 8.1(d, 2H), 7.93-7.96(m, 2H), 7.8(m, 2H), 7.6(m, IH), 4.2(m, 2H), 3.24(s, 2H), 2.81(d, 2H), 2.1(dd, 2H), 1.57(d, 6H) Example 60 Cw-2-(4-(3-cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl)-N-(3-fluoro-2- methylphenyl)acetamide i) c s-(3,5-Dimethylpiperazin-l-yl)-N-(2-methyl-3-fluorophenyl)acetamide The subtitle compound was prepared from the product of Example 36 step (i) (14.5g) and cz ' s-2,6-dimethylpiperazine (9.0g) by the method of Example 58 step (i) as cream solid. Yield: 11.48g MS: APCI(+ve) 280 (M+l) ii) C/s-2-(4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazm-l-yl)-N-(3-fluoro-2- methylphenyl)acetamide The title compound was prepared from the product of step (i) (0.503mmol) and 3- cyanobenzenesulphonyl chloride (0.503mmol) by the method of Example 58 step (ii) as a white solid. Yield: 44mg MS: APCI(+ve) 445 (M+l) 'H NMR δ (CD 3 OD) 8.24(d, IH), 8.14(4 IH), 7.98(4 IH), 7.76(t, IH), 7.36(4 IH), 7.1(q, IH), 6.93(t, IH), 4.14-4.16(m, 2H), 3.10(s, 2H), 2.73(4 2H), 2.16(d, 3H), 2.04(dd, 2H), 1.53(4 6H) Example 61 Cis-2-(4-(4-Cyanobenzenesulphonyl)-3,5-dimethyipiperazin-l-yl)-N-(3-fluoro-2- methylphenyl)acetamide The title compound was prepared from the product of Example 60 step (i) (0.503mmol) and 4-cyanobenzenesulphonyl chloride (0.503mmol) by the method of Example 58 step (ii) as a white solid. Yield: 4mg MS: APCI(+ve) 445 (M+l) 'H NNMR δ (CD 3 OD) 8.24(d, IH), 8.14(4 IH), 7.98(4 IH), 7.76(t, IH), 7.36(4 IH), 7.1 (q, IH), 6.93(t, IH), 4.14-4.16(m, 2H), 3.10(s, 2H), 2.73(4 2H), 2.16(d, 3H), 2.04(dd, 2H), 1.53(d, 6H) Example 62 c/s-2-[4-(3-Acetylaminobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide A solution ofthe product from Example 57 (0.2g) and N,N-diisopropylethylamine (0.3ml) in dichloromethane (10ml) was rapidly stirred whilst a solution of acetyl chloride (0.055g) in dichloromethane (2.0ml) was added. After 3 hours a further amount of acetyl chloride (0.022g) was added, the mixture was stirred 3 hours more then evaporated to dryness. The residue was triturated with water, filtered and dried in vacuo, to give the title compound as a white solid. Yield 0.17g. MS: APCI(+ve) 459 (M+l, 100%) H NMR: δ (CDCI 3 +DMSO) 1.53(6H, d), 2.17(3H, s), 2.26(2H, m), 2.30(3H, s), 2.66 * (2H,d), 3.08(2H, s), 4.14(2H, m), 7.07(113, m), 7.20(2H, m), 7.42(1H, m), 7.48(1H, m), 7.82(1H, d), 7.95(1H, d), 8.16(1H, s), 8.77(1H, s), 9.49(1H, s) MP: 236-8 °C Example 63 c 5-2-[4-(3-Am ocarbonylbeιιzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide Hydrgen chloride gas was bubbled through a solution ofthe product of Example 55 step (ii) (0.2 lg), in methanol (50ml) at 0 °C for 4 hours. The mixture was evaporated to dryness, the residue was dissolved in methanol and ethylenediamine (0.18g) was added. After 3 hours LC/MS indicated mainly amide. After 18 hours the mixture was evaporated to dryness, the residue was triturated with ether/ethanol, filtered and the solid was purified by chromatography on silica gel eluting with dichloromethane containing ethanol (2.5-5%) to give the title compound as a white solid. Yield 0.08g. MS: APCI(+ve) 445 (M+l, 100%) H NMR: δ (CDCI 3 +DMSO) 1.54(6H, d), 2.13(2H, ), 2.29(3H, s), 2.70(2H,d), 3.06(2H, s), 4.14(2H, ), 6.24(1H, br s), 7.07(1H, m), 7.21(2H, m), 7.60(1H, t), 7.68(lH, br s), 7.93(2H, d), 8.15(1H, d), 8.41(1H, s), 8.74(1H, s) MP: 124-5 °C Example 64 c 5-2-[4-(3-Methanesulphonylanιinobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N- (2-methylphenyl)acetamide The title compound was prepared from the product of Example 57 and methane sulphonyl chloride by the method of Example 62. The solid obtained at the end ofthe reaction was suspended in ethanol (50ml) to which a solution of K 2 CO 3 (0.2g) in water (10ml) was added, and stirred for 18 hours, in order to hydrolyse any bis-sulphonamide. The ethanol was removed, water (50ml) was added and the pH was adjusted to 5.0. The solid was filtered off, washed with water and ether and dried in vacuo to give the title compound as a white solid. Yield 0.13g. MS : APCI(+ve) 495 (M+ 1 , 100%) ! H NMR: δ (CDC1 3 ) 1.54(6H, d), 2.20(2H, m), 2.30(3H, s), 2.68(2H,d), 3.06(3H, s), 3.09(2H, s), 4.13(2H, m), 7.07(1H, m), 7.20(2H, m), 7.25(1H, s), 7.40(1H, d of d), 7.48(1H, t), 7.60(1H, d), 7.68(1H, m), 7.95(1H, d), 8.73(1H, s) MP: 102-3 °C Example 65 cis-2-[4-(2-Methanesulphonylbenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(3- methoxy-2-methylphenyl)acetamide i) c s-[3,5-Dimethylpiperazm-l-yl]-N-(3-methoxy-2-methylphenyl)acetamide The subtitle compound was prepared from 2-chloro-N-(3-methoxy-2- methylphenyl)acetamide (10.72g) and cts-2,6-dimethylpiperazine (6.29g) by the method of Example 58 step (i) as a tan solid. Yield: 13.13g 'H NMR δ (CDCI 3 ) 9.32(bs, IH), 7.79(d, IH), 7.18(t, IH), 6.68(d, IH), 3.83(s, 3H), 3.14(s, 2H), 2.93-3.04(m, 2H), 2.81-2.85(m, 2H), 2.14(s, 3H), 1.92(t, 2H), 1.10(d, 6H) ϋ) cw-2-[4-(2-Methanesulphonylbenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(3- methoxy-2-methylphenyl)acetamide The title compound was prepared from the product of step (i) (0.503mmol) and 2- methanesulphonylbenzenesulphonyl chloride (0.503mmol) by the method of Example 58 step (ii) as a white solid. Yield: 6mg MS: APCI(+ve) 510(M+1) 'H NMR δ (CD 3 OD) 8.4(m, IH), 8.3(m, IH), 7.91-7.89(m, 2H), 7.16-7.18(m, 2H), 6.8(t, IH), 4.2(m, 2H), 3.84(s, 3H), 3.43(s, 3H), 3.14(s, 2H), 2.74(d, 2H), 2.33(dd, 2H), 2.14(s, 3H), 1.61(d, 6H) Example 66 cfs-2-[4-(2-Methanesulphonylbenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(3- fluoro-2-methylphenyi)acetamide The title compound was prepared from the product of Example 60 step (i) (0.503mmol) and 2-methanesulphonylbenzenesulphonyl chloride (0.503mmol) by the method of Example 58 step (ii) as a white solid. Yield: 17mg MS: APCI(+ve) 498 (M+l) 'H NMR δ (CD 3 OD) 8.4(m, IH), 8.3(m, IH), 7.89-7.91(m, 2H), 7.4(d, IH), 7.1(q, IH), 6. ' 9(t, IH), 4.2(m, 2H), 3.44(s, 3H), 3.16(s, 2H), 2.74(4 2H), 2.3(dd, IH), 2.20(d, 2H), 1.62(d, 6H) Example 67 cw-2-[4-(l-MethyUjmidazol-4-sulphonyl-4-yl)-3,5-dimethylpiperazm-l-yl]-N-(qumojlin- 5-yl)acetamide The title compond was prepared from the product of Example 58 step (i) (0.503mmol) and l-methylimidazole-4-sulphonyl chloride (0.503mmol) by the method of Example 58 step (ii) as a white solid. Yield: 16mg MS: APCI(+ve) 443 (M+l) Η NMR δ (CD 3 OD) 8.90(d, IH), 4.45(d, IH), 7.97(t, IH), 7.82(s, IH), 7.80(4 IH), 7.68(s, IH), 7.58-7.63(m, IH), 4.17-2.21(m, 2H), 3.79(s, 3H), 3.26(s, 2H), 2.80(4 2H), 2.25(dd, 2H), 1.58(d, 6H) Example 68 s-2-[4-(l-MethyUmidazol-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-l-yl]-N-(3- methoxy-2-methylphenyl)acetamide The title compound was prepared from the product of Example 65 step (i) (0.503mmol) and l-methylimidazol-4-sulphonyl chloride (0.503mmol) by the method of Example 58 step (ii) as a white solid. Yield: 3 lmg MS APCI(+ve) 436 (M+l) 'H NMR δ (CD 3 OD) 7.77 (s, IH), 7.67(s, IH), 7.16-7.18(m, 2H), 6.82-6.85(m, IH), 4.14- 4.18(m, 2H), 3.84(s, 3H), 3.79(s, 3H), 3.10(s, 2H), 2.72(d, 2H), 2.20(dd, 2H), 2.13(s, 3H), 1.53(d, 6H) Example 69 c/s-2-[4-(l-MethyUιmdazoϊ-4-sulphonyl-4-yl)-3,5-dimethyIpiperazin-l-yl]-N-(3-fluoro- 2-methylphenyl)acetamide The title compound was prepared from the product of Example 60 step (i) (0.503mmol) and l-methylimidazol-4-sulphonyl chloride (0.503mmol) by the method of Example 58 step (ii) as a white solid. Yield: 21mg MS: APCI(+ve) 424 (M+l) 'H NMR δ (CD 3 OD) 7.77 (s, IH), 7.67 (s, IH), 7.43 (d, IH), 7.20(q, IH), 6.95(t, IH), 4.12- 4.20(m, 2H), 3.79(s, 3H), 3.12(s, 2H), 2.72(d, 2H), 2.17-2.23(m, 5H), 1.54(d, 6H) Example 70 c/s-2-[4-(3-Methanesulphonylbenzeuesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- trifluoromethylphenyl)acetamide i) 2-Chloro-N-(2-trifluoromethylphenyl)acetamide The subtitle compound was prepared from 2-trifluoromethylaniline(10.5g) and chloroacetyl chloride (6.8ml) by the method of Example 33 step (iii) as a white solid. Yield: 13.7g MS: APCI(-ve) 236 (M-1) ii) cw-3,5-Dimethylpiperazm-l-yl]-N-(2-trifluoromethylphenyl)acetamide The subtitle compound was prepared from the product of step (i) (7.6g ) and cis-2,6- dimethylpiperazine (3.53g) by the method of Example 58 step (i) as a white solid. Yield: 8.57g MS: APCI(+ve) 316 (M+l) iii) cts-2-[4-(3-MethanesuIphonylbenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- trifluoromethylphenyl)acetamide The product of step (iii) (0.25g) and 3-methanesulphonylbenzenesulphonyl chloride (0.606g), potassium carbonate (0.275g) in 2,6-lutidine(0.5ml) were heated in a lOOWatt microwave oven at 120 °C for lOmin. The mixture was then partitioned between dichloromethane and water. The organic phase collected, dried (MgSO 4 ), and the solvent evaporated under reduced pressure. Purification was by revese phase HPLC eluting with l%tøq. ammonium acetate/acetonitrile (95% to 60%) to give the title compound as a white solid. Yield: O.lg MS: APCI(+ve) 534 (M+l) 'H NMR δ (CDC1 3 ) 9.16(bs, IH), 8.41 (s, IH), 8.30(4 IH), 8.20(d, IH), 7.58(t, IH), 7.26(d, IH), 4.15(m, 2H) Example 71 ew-2-[4-(2-AniinoethylammocarbouyIbenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]- N-(2-methylphenyl)acetamide The title compound was prepared from the product of Example 55 by the method of Example 63 followed by addition of ethylenediamine, the mixture was heated at reflux for 5 hours, evaporated to dryness and the residue was crystallised from ethanol to give the title compound as a white solid. Yield 0.15g MS: APCI(+ve) 488 (M+l, 100%) lH NMR: δ (CDC1 3 ) 1.56(8H, m), 2.17(2H, m), 2.29(3H, s), 2.68(2H, d), 2.98(2H, t), 3.06(2H, s), 3.51(2H, m), 4.14(2H, m), 6.97(1H, br t), 7.07(1H, m), 7.20(2H, m), 7.60(1H, t), 7.9(3H, m), 8.25(1H, m), 8.71 (IH, br s) MP: 90-2 °C Example 72 c/5-2-[4-(l,l,2,2-Tetrahydroisoqumj in-7-sulphonyl-7-yl)-3,5-dimethylpiperazm-l-yl]- N-(2,6-dimethylphenyl)acetamide i) cw-3,5-Dimethylpiperazin-l-yl]-N-(2,6-dimethylphenyl)acetamide The subtitle compound was prepared from 2-chloro-N-(2,6-dimethylphenyl)acetamide (6.54g) and cz -2,6-dimethylpiperazine (3.78 ' g) by the method of Example 58 step (i) as a white solid. Yield:7.85g MS: APCI(+ve): 276(M+1) ϋ) c s-2-[4-(N-Trifluoroacetyl(l,l,2,2-tetrahydroisoqumilin)-7-sulphonyl-7-yl)-3,5- dimethylpiperazin-l-yl]-N-(2,6-dimethylphenyl)acetamide The subtitle compound was prepared from the product of step (i) (0.165g) and N-trifluoroacetyl(l,l,2,2-tetrahydroisoquinolin)-7-sulphonyl chloride (0.39g) by the method of Example 58 step (ii) as a white solid. Yield: 96mg MS: APCI(+ve) 567 (M+l) iu) α5-2-[4-(l,l,2,2-Tetrahydroisoqumilm-7-sulphonyl-7-yl)-3,5-dimethylpiperazin-l- yl]-N-(2,6-dimethylphenyl)acetamide The product from step (ii) (90mg), potassium carbonate (200mg) in water (10ml) and methanol (15ml) were heated at reflux for 2h. Water (50ml) was added and the mixture extracted with ethyl acetate. The organic phase collected, dried (MgSO 4 ) and solvent evaporated under reduced pressure to give the title compound as a white solid. Yield: 55mg MS: APCI(+ve) 471 (M+l) 'H NMR δ (CDC1 3 ) 8.29(s, IH), 7.55(d, IH), 7.50(s, IH), 7.17(d, IH), 7.1 l(m, 3H), 4.14(m, 2H), 4.06(s, 2H), 3.48(q, IH), 3.17(t, IH), 3.12(s, 2H), 2.87(t, 2H), 2.72(d, 2H), 2.25(d, IH), 2.22(s, 6H), 2.05(s, IH), 1.69(bs, IH), 1.51(4 6H), 1.19-1.28(m, 4H) Example 73 c/5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2,6- dimethylphenyl)acetamide The title compound was prepared from the product of Example 72 step (i) (0.165g) and 3- cyanobenzenesulphonyl chloride (0.15g) by the method of Example 58 step (ii) as a white solid. Yield: 40mg MS: APCI(+ve) 441 (M+l) 'H NMR δ (CDC1 3 ) 8.22 (s, IH), 8.13(s, IH), 8.05(4 IH), 7.86(4 IH), 7.67(t, IH), 7.12(m, 3H), 4.15(m, 2H), 3.14(s, 2H), 2.78(4 2H), 2.22(s, 8H), 1.54(4 6H) Example 74 c/s-2-[4-(4-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide 4-Cyanobenzenesulphonyl chloride (0.36g) was added to a stirred mixture ofthe product of Example 55 step (i) (0.5g) and potassium carbonate (0.62g) in l-methyl-2-pyrrolidinone (3ml). After 20 min the reaction mixture was partitioned between ethyl acetate and water. The organic phase was washed with water and brine, dried (MgSO 4 ) and evaporated under reduced pressure. Purification was by flash chromatography eluting with 1% ethanol in dichloromethane followed by trituration with methanol to givethe title compound as a white crystalline solid. Yield 55mg. MS: ES (+ve) 427 (M+l) H NMR: δ (CDCI 3 ) 8.67 (lH,brs), 7.99-7.93 (3H,m), 7.83 (2H,d), 7.21 (2H,m), 7.08 (lH,m), 4.14 (2H,m), 3.10 (2H,s), 2.73 (2H,d), 2.30 (3H,s), 2.18 (2H,dd), 1.57 (3H,s), 1.54 (3H,s). Example 75 cis-2-[4-(2-Cyanobenzenesulphonyl)-3,5-dimethylpiperazm-l-yl]-N-(2,6- dimethylphenyl)acetamide, hydrochloride salt The free base ofthe title compound was prepared from the product of Example 72 step (i) (0.165g) and 2-cyanobenzenesulphonyl chloride (0.15g) by the method of Example 58 step (ii). The title compound was prepared by adding IM hydrogen chloride in diethyl ether to a solution ofthe free base to produce a white precipitate. This was filtered and further washed with diethyl ether to give the title compound as a white solid. Yield: 20mg MS: APCI(+ve) 441 (M+l) 'H NMR δ (CDCI 3 ) 8.19(bs, IH), 7.91(bs, IH), 7.78(bs, 2H), 7.10(m, 3H), 4.40(bs, 2H), 4.20(bs, 2H), 3.50(m, 3H), 2.20(s, 6H), 2.00-1.40(m, 6H) Example 76 cis-2-[4-(3-CyanobenzenesuIphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- chlorophenyl)acetamide The title compound was prepared from the product of Example 15 step (ii) (0.2g) and 3- cyanobenzenesulphonyl chloride (0.28g) by the method of Example 74 as a white solid. Yield 8mg. MS: APCI (+ve) 447 (M+l) H NMR: δ (CDC1 3 ) 9.45 (lH,brs), 8.49 (lH,dd), 8.13 (lH,s), 8.05 (lH,d), 7.87 (lH,d), 7.68 (lH,t), 7.38 (lH,d), 7.29 (lH,m), 7.06 (lH,t), 4.14 (2H,m), 3.11 (2H,s), 2.72 (2H,d), 2.18 (lH,dd), 1.60 (3H,s), 1.58 (3H,s). Example 77 2-[8-(Isqumolin-l-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2-methylphenyl)acetamide The title compound was prepared from the product Example 20 step (iv) (0.32g) and 1- chloroisoquinoline (0.14g) by the method of Example 52 step (i) as a beige solid. Yield: 40mg MS: ESI(+ve) 387 (M+l) 'H NMR δ (DMSO) 9.21(bs, IH), 8.20(4 IH), 8.00(4 IH), 7.93(d, 2H), 7.70(t, IH), 7.60(t, IH), 7.35(d, IH), 7.20(m, 2H), 7.06(t, IH), 4.40(bs, 2H), 2.98(4 2H), 2.85(4 2H), 2.30(s, 3H), 2.00(d, 2H), 1.90(m, 2H) Example 78 α5-2-[4-(4-Acetamidobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide 2,6-Lutidine (0.3ml) was added to a mixture of 4-acetamidobenzenesulphonyl chloride (0.25g), potassium carbonate (0.18g) and the product of Example 55 step (i) (0.14g). The reaction mixture was heated at 100°C for 5 minutes in a 100 Watt microwave oven, allowed to cool and partitioned between dichloromethane and water. The organic phase was washed with brine, dried (MgSO 4 ) and evaporated under reduced pressure. Purification was by reverse phase HPLC (acetonitrile/ 1% aq.ammonium acetate). Yield 15mg. MS: AP (+ve) 459 (M+l) H NMR: δ (DMSO) 10.35 (lH,s), 7.76 (4H,q), 7.55 (lH,d), 7.22-7.14 (2H,m), 7.07 (lH,m), 4.00 (2H,m), 3.02 (2H,s), 2.64 (2H,d), 2.20 (3H,s), 2.09 (3H,s), 1.92 (2H,dd), 1.42 (3H,s), 1.40 (3H,s) Example 79 cts-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- trifluoromethylphenyl)acetamide The title compound was prepared from the product of Example 70 step (i) (0.189g) and 3- cyanobenzenesulphonyl chloride (0.15g) by the method of Example 58 step (ii) as a white solid. Yield: 17mg MS: APCI(+ve) 481 (M+l) 'H NMR δ (DMSO) 8.98(bs, IH), 8.1 l(m, 2H), 7.93(m, 2H), 7.05(m, 4H), 4.10(m, 2H), 3.30(s, 2H), 2.90(d, 2H), 2.40(bd, 2H), 1.50(d, 6H) Example 80 c/5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5- methauesuIphonamidophenyl)acetamide i) c 5-l-(3-Cyanobenzenesulphonyl)-2,6-dimethyl-4-phenyhτιethylpiperazme A solution of cz5-4-benzyl-2,6-dimethylpiperazine (lg), 4-N,N- dimethylaminopyridine(0.54g), 3 -cyanobenzenesulphonyl chloride (2.13g) in pyridine (3ml) were stirred at ambient temperature. After lh the mixture was partitioned between dichloromethane and water. The organic phase further washed with brine, collected, dried, (MgSO 4 ) and solvent evaporated under reduced pressure to leave the subtitle compound as an orange gum. Yield: lg MS: APCI(+ve) 370 (M+l) ii) c s-l-(3-Cyanobenzenesulphonyl)-2,6-dimethylpiperazine A solution ofthe product from step (i) (lg) in 1,2-dichloroethane (10ml) was treated with 1-chloroethyl chlorofoimate (0.44ml). The mixture was heated at 80 °C for 16h. The solvents were then evaporated under reduced pressure and the residue dissolved in methanol (50ml). The mixture then heated at 50 °C for lh. The solvents were then evaporated under reduced pressure. Purification was by trituration with ethyl acetate and filtration to give the subtitle compound as a white solid. Yield: 0.85g MS: APCI(+ve) 279 (M+l) iii) c/s-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5- bis(methanesulphonyl)amidophenyl)acetamide A solution ofthe product from step (ii) (0.5g) and the product of Example 24 step (i) (0.8g), N,N-diisopropylethylamine (0.6ml), potassium iodide (2mg) in l-methyl-2- pyrrolidinone (10ml) were heated at 90 °C for 3h. The mixture was then partitioned dichloromethane and water. The organic phase collected, further washed with brine, dried (MgSO 4 ) and solvent evaporated under reduced pressure to give the subtitle compound as a brown foam. Yield: 1.04g MS: APCI(+ve) 597 (M+l) iv) c s-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5- methanesuIphonamidophenyl)acetamide The product from step (iii) (lg), potassium carbonate (lg), water (10ml) and tetrahydrofuran (20ml) were stirred at ambient temperamre for 16h then heated at 90 °C for 6h. The mixture partitioned between dichloromethane and water. The organic phase collected, dried (MgSO 4 ) and solvent evaporated under reduced pressure. Purification was by silica gel chromatography eluting with iso-hexane/ethyl acetate (1 :9) to give the title compound as a white solid. Yield: 0.5g MS: APCI(+ve) 520(M+1), APCI(-ve) 518 (M-1) 'HNMR δ (CDC1 3 ) 8.9(bs, IH), 8.13(2xs, 2H), 8.05(d, IH), 7.90(d, IH), 7.70(t, IH), 7.40(bs, IH), 7.10(m, 2H), 4.10(m, 2H), 3.10(s, 2H), 2.95(s, 3H), 2.70(d, 2H), 2.30(s, 3H), 2.20(m, 2H), 1.60(d, 6H) Example 81 2-[8-(4-Benzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2- methylphenyl)acetamide The title compound was prepared from the product of Example 20 step (iv) (0.34mmol) and 4-cyanobenzenesulphonyl chloride (0.34mmol) by the method of Example 58 step (ii) as a white solid. Yield: lOmg MS: ESI(+ve) 425 (M+l) 'H NMR δ (CDC1 3 ) 8.68(bs, IH), 8.05(m, 3H), 7.83(4 2H), 7.23-7.17(m, 2H), 7.07(m, IH), 4.26(m, 2H), 3.19(s, 2H), 2.86(dd, 2H), 2.65(4 2H), 2.27(s, 3H), 1.94(m, 2H), 1.74(m, 2H) Example 82 2-[8-(2-Benzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2- methylphenyl)acetamide The title compound was prepared from the product of Example 20 step (iv) (0.34mmol) and 2-cyanobenzenesulphonyl chloride (0.34mmol) by the method of Example 58 step (ii) as a white solid. Yield: 8mg MS: APCI(+ve) 425 (M+l) 'H NMR δ (CDC1 3 ) 8.77(bs, IH), 8.15(dd, IH), 8.03(4 IH), 7.88(ss, IH), 7.78-7.69(m, 2H), 7.25-7.18(m, 2H), 7.07(t, IH), 4.36(m, 2H), 3.20(s, 3H), 2.85(dd, IH), 2.74(d, IH), 2.30(s, 3H), 2.07-1.99 (m, 4H) Example 83 c s-2-[4-(l,2-DimethyIimidazol-4-suIphonyl-4-yl)-3,5-dimethylpiperazin-l-yl]-N- (quinolin-5-yl)acetamide The title compound was prepared from the product of Example 58 step (i) (0.503mmol) and l,2-dimethylimidazole-4-sulphonyl chloride (0.503mmol) by the method of Example 58 step (ii) as a white solid. Yield: 20mg MS: APCI(+ve) 457 (M+l) Η NMR δ (CD 3 OD) 8.88-8.89(m, IH), 8.44(4 IH), 7.97-7.94(m, IH), 7.76-7.81(m, 2H), 7.56-7.60(m, 2H), 4.19-4.13(m, 2H), 3.65(s, 3H), 3.25(s, 2H), 2.79(4 2H), 2.38(s, 3H), 2.54(dd, 2H), 1.55(d, 6H) Example 84 c 5-2-[4-(5-Chloro-l,3-dimethylpyrazole-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-l- yl]-N-(3-methoxy-2-methylphenyl)acetamide The title compound was prepared from the product of Example 65 step (i) (0.503mmol) and 5-chloro-l,3-dimethyl-4-sulphonyl chloride (0.503mmol) by the method of Example 58 step (ii) as a white solid. Yield: 6mg MS: APCI(+ve) 485 (M+l) 'H NMR δ (CD 3 OD) 7.15-7.16(m, 2H), 6.81-6.84(m, IH), 4.07-4.10(m ,2H), 3.83(s, 3H), 3.82(s, 3H), 3.15(s, 2H), 2.79(4 2H), 2.37(s, 3H), 2.56(dd, 2H), 2.12(s, 3H), 1.54(4 6H) Example 85 2-[8-(2-(Isoxazol-3-yl)thiophen-5-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N- (2- methylphenyl)acetamide The title compound was prepared from the product of Example 20 step (iv) (0.34mmol) and 2-(isoxazol-3-yl)thiophenesulphonyl chloride (0.34mmol) as a white solid. Yield: lOmg MS: ESI(+ve) 473 (M+l) Η NMR δ (CDCI 3 ) 8.72(bs, IH), 8.05(4 IH), 7.61(4 IH), 7.46(4 IH), 7.23(4 2H), 7.06(t, IH), 6.53(d, IH), 4.33(m, 2H), 3.22(s, 2H), 2.89(dd, 2H), 2.73(4 2H), 2.28(s, 3H), 1.94(m, 2H), 1.87(m, 2H) Example 86 2-[8-(l,l,2,2-Tetrahydroisoqumilin-7-suIphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2- methylphenyl)acetamide The title compound was prepared from the product of Example 20 step (iv) (0.34mmol) and N-trifluoroacetyl-l,l,2,2-tetrahydroisoquinoline-7-sulphonyl chloride (0.34mmol) by the method of Example 58 step (ii) followed by the method of Example 72 step (iii) as a white solid. Yield: 26mg MS: ESI(+ve) 551 (M+l) Η NMR δ (CDCI 3 ) 8.73(bs, IH), 8.04(4 IH), 7.77-7.68(m, 2H), 7.33(t, IH), 7.25-7.17(m, 2H), 7.06(t, IH), 4.83(d, 2H), 4.24(m, 2H), 3.92(dt, 2H), 3.19(s, 2H), 3.05(m, 2H), 2.85"(dd, 2H), 2.66(4 2H), 2.27(s, 3H), 1.90(m, 2H), 1.76(4 2H) Example 87 c 5-2-[4-(5-Chloro-l,3-dimethylpyrazole-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-l- yl] -N-(2-methylphenyl)acetamide The title compound was prepared from the product of Example 20 step (iv) (0.34mmol) and 5-chloro-l,3-dimethylpyrazole-4-sulphonyl chloride (0.34mmol) by the method of Example 58 step (ii) as a white solid. Yield: 12mg MS: ESI (+ve) 452 (M+l) 'H NMR δ (CDC1 3 ) 8.77(bs, IH), 8.04(d, IH), 7.23-7.18(m, 2H), 7.07(t, IH), 4.25(m, 2H), 3.83(s, 3H), 3.19(s, 2H), 2.85(dd, 2H), 2.65(d, 2H), 2.43(s, 3H), 2.30(s, 3H), 1.95(s, 4H) Example 88 c s-2-[4-(3,5-Dimethylisoxazole-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide The title compound was prepared from the product of Example 20 step (iv) (0.34mmol) and 3,5-dimethylisoxazol-4-sulphonyl chloride (0.34mmol) by the method of Example 58 step (ii) as a white solid. Yield: 5.6mg MS; ESI (+ve) 419 (M+l) Η NMR δ (CDCI 3 ) 8.72(bs, IH), 8.04(4 IH), 7.21(t, 2H), 7.08(t, IH), 4.18(m, 2H), 3.20(s, 2H), 2.88(dd, 2H), 2.66(s, 3H), 2.61(4 2H), 2.44(s, 3H), 2.3 l(s, 3H), 2.03(m, 4H) Example 89 c 5-2-[4-(2-Methanesulphonylbenzenesulphonyl)-3,5-dimethylpiperazm-l-yl]-N-(2- methylphenyl)acetamide The title compound was prepared from the product of Example 20 step (iv) (0.34mmol) and 2-methanesulphonylbenzenesulphonyl chloride (0.34mmol) by the method of Example 58 step (ii) as a white solid. Yield: 13mg MS: ESI (+ve) 478 (M+l) 'H NMR δ (CDC1 3 ) 8.81(bs, IH), 8.40(m, IH), 8.28(m, IH), 8.03(4 IH), 7.80(m, 2H), 7.25-7.17(m, 2H), 7.06(t, IH), 4.48(m, 2H), 3.46(s, 3H), 3.16(s, 2H), 2.82(dd, 2H), 2.68(d, 2H), 2.29(s, 3H), 1.95(d, 4H) Example 90 c/5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(3-methoxy-2- methylphenyl)acetamide T ie title compound was prepared from the product of Example 65 step (i) (0.503mmol) and 3-cyanobenzenesulphonyl chloride (0.503mmol) by the method of Example 58 step (ii) as a white solid. Yield: 21mg MS: ESI (+ve) 424 (M+l) 'H NMR δ (CD 3 OD) 7.77(s, IH), 7.67(s, IH), 7.43(4 IH), 7.20(q, IH), 6.95(t, IH), 4.12- 4.20(m, 2H), 3.78(s, 3H), 3.12(s, 2H), 2.72(4 2H), 2.17-2.23(m, 5H), 1.54(4 6H) Example 91 '5-2-[4-(4-Methanesulphonylbenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide The title compound was prepared from the product of Example 20 step (iv) (0.34mmol) and 4-methanesulphonylbenzenesulphonyl chloride (0.34mmol) by the method of Example 58 step (ii) as a white solid. Yield: 25mg MS: ESI (+ve) 478 (M+l) 'H NMR δ (CDC1 3 ) 8.69(bs, IH), 8.10(q, 4H), 8.04(4 IH), 7.25-7.17(m, 2H), 7.07(t, IH), 4.28(m, 2H), 3.20(s, 2H), 3.1 l(s, 3H), 2.87(dd, 2H), 2.67(4 2H), 2.27(s, 3H), 1.93(m, 2H), 1.74(m, 2H) Example 92 ct5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(5-cyano-2- methylphenyl)acetamide i) 2-Chloro-N-(5-cyano-2-methylphenyl)acetamide The subtitle compound was prepared from 5-cyano-2-methylaniline (1.6g) and chloroacetyl chloride (1.1ml) by the method of Example 33 step (iii) as a white solid. Yield: 1.85g MS: APCI (-ve) 207 (M-1) ii) cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(5-cyano-2- methylphenyl)acetamide The title compound was prepared from the product of step (i) (0.19g) and the product from Example 80 step (ii) (0.2g) by the method of Example 80 step (iii) as a white solid. Yield: 0.25g MS: APCI(+ve) 452 (M+l) 'H NMR δ (CDC1 3 ) 8.81(bs, IH), 8.49(s, IH), 8.13(s, IH), 8.05(4 IH), 7.90(4 IH), 7.70(t, IH), 7.29(d, IH), 7.27(d. IH), 4.20(m, 2H), 3.10(s, 2H), 2.70(4 2H), 2.36(s, 3H), 2.20(m, 2H), 1.60(d, 6H) Example 93 c s-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(5-acetamido-2- methylphenyl)acetamide i) ct * 5-2-Chloro-N-(5-acetamido-2-methylphenyl)acetamide Ther subtitle compound was prepared from 5-acetamido-2-methylaniline (0.5g) and chloroacetyl chloride (0.27ml) by the method of Example 33 step (iii) as a beige solid. Yield: 0.55g MS: APCI(+ve) 241 (M+l) ii) c 5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(5-acetamido-2- methylphenyl)acetamide The title compound was prepared from the product of step (i) (0.22g) and the product of Example 80 step (ii) (0.2g) by the method of Example 80 step (iii) as a white solid. Yield: 0.1 lg MS: APCI(+ve) 468 (M+l) 'H NMR δ (CDC1 3 ) 9.60(bs, IH), 8.78(bs, IH), 8.19(s, IH), 8.17(d, IH), 8.05(s, IH), 7.98(d, IH), 8.77(t, IH), 7.75(s, IH), 7.50(4 IH), 7.10(4 IH), 4.10(m, 2H), 2.75(4 2H), 2.25(s, 3H), 2.16(m, 2H), 2.10(s, 3H), 1.50(4 6H) Example 94 (R)-2-[4-(4-Cyanobenzenesulphonyl)-3-methyIpiperazm-l-yl]-N-(qumolin-5- yl)acetamide i) (R)-2-(3-Methylpiperazin-l-yl)-N-(quinolin-5-yl)acetamide The subtitle compound was prepared from 2-chloro-N-(quinolin-5-yl)acetamide (lg) (J Indian Chem Soc, 1940, 17, 619-621) and (R)-2-methylpiperazine (0.5g) by the method of Example 58 step (i) as a white solid. Yield: 1.4g MS; APCI(+ve) 285 (M+l) ii) (R)-2- [4-(4-Cy anobenzenesulphonyl)-3-methylpiperazin-l -yl] -N-(quinolin-5- yl)acetamide The title compound was prepared from the product of step (i) (1.4g) and 4- cyanobenzenesulphonyl chloride (lg) by the method of Example 58 step (ii) as a white solid. Yield: 0.4 lg MS: APCI(+ve) 450 (M+l) 'H NMR δ (CDCI 3 ) 9.30(s, IH), 8.95(4 IH), 8.09(m, 2H), 7.99-7.94(m, 3H), 7.86-7.82(4 2H), 7.73(m, IH), 7.43(m, IH), 4.27(m, IH), 3.78(4 IH), 3.42(m, IH), 3.26(q, 2H), 2.98(d, IH), 2.82(d, IH), 2.55(dd, IH), 2.39(m, IH), 1.35(4 3H) Example 95 (S)-2-[4-(4-Cyanobenzenesulphonyl)-3-methylpiperazm-l-yl]-N-(qumolin-5- yl)acetamide i) (S)-2-(3-Methylpiperazm-l-yl)-N-(qumolin-5-yl)acetamide The subtitle compound was prepared from 2-chloro-N-(quinolin~5-yl)acetamide (lg) (J Indian Chem Soc, 1940, 17, 619-621) and (S)-2-methylpiperazine (0.5g) by the method of Example 58 step (i) as a white solid. Yield: 1.4g MS: APCI(+ve) 285 (M+l) ii) (S)-2-[4-(4-Cyanobenzenesulphonyl)-3-methylpiperazin-l-yl]-N-(quinolin-5- yl)acetamide The title compound was prepared from the product of step (i) (1.4g) and 4- cyanobenzenesulphonyl chloride (lg) by the method of Example 58 step (ii) as a white solid. Yield: 0.53g MS: APCI(+ve) 450 (M+l) 'H NMR δ (CDCI 3 ) 9.30(s, IH), 8.95(d, IH), 8.09(m, 2H), 7.99-7.94(m, 3H), 7.86-7.82(4 2H), 7.73(m, IH), 7.43(m, IH), 4.27(m, IH), 3.78(d, IH), 3.42(m, IH), 3.26(q, 2H), 2.98(d, IH), 2.82(d, IH), 2.55(dd, IH), 2.39(m, IH), 1.35(d, 3H) Example 96 cis-2-[4-(3-CyanobenzenesuIphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5- methanesulphonylphenyl)acetamide i) 2-Chloro-N-(2-methyl-5-methanesulphonylphenyl)acetamide The subtitle compound was prepared from 5-methanesulphonyl-2-methylaniline (0.82g) and chloroacetyl chloride (0.72ml) by the method of Example 33 step (iii) as a beige solid. Yield: 0.6 lg MS: APCI -ve) 260 (M-1) ii) cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazm-l-yl]-N-(2-methyl-5- methanesulphonylphenyl)acetamide The title compound was prepared from the product of step (i) (0.14g) and the product of Example 80 step (ii) by the method of Example 80 step (iii) as a white solid. Yield: 0.03g MS: APCI(+ve) 505 (M+l) 'H NMR δ (CDC1 3 ) 8.84(bs, IH), 8.63(s, IH), 8.10(s, IH), 8.06(d, IH), 7.90(4 IH), 7:65(d, IH), 7.64(d, IH), 7.40(4 IH), 4.25(m, 2H), 3.14(s, 2H), 3.07(s, 3H), 2.74(4 2H), 2.40(s, 3H), 2.20(m, 2H), 1.60(4 6H) Example 97 c/5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5-(4- amino-l-piperidinyl)methyl)phenyl] acetamide i) 2-Methyl-5-((l,l-dimethyl)-l-dimethylethyl)silyloxymethyl-aniline A mixture of 2-methyl-5-hydoxymethylaniline (lOg), tert-butyldimethylsilyl chloride (10.84g), imidazole (12.24g) in dry N,N-dimethylformamide (80ml) were stirred at ambient temperature for 18h. The mixture was partitioned between ethyl acetate and saturated brine. The organic phase washed with water, collected, dried (MgSO 4 ) and solvent evaporated under reduced pressure to leave a brown gum which slowly crystalised on standing. Yield: 19.2g MS:APCI(+ve) 252 (M+l) ii) 2-Chloro-N-(2-methyl-5-((l,l-dimethyl)-l-dimethylethyl)silyloxymethyl)acetamide The subtitle compound was prepared from the product of step (i) (18.3g) and chloroacetyl chloride (17.5ml) by the method of Example 33 step (iii) as a beige solid. Yield: 23g MS: APCI(-ve) 326(M-1) iii) cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5- C(l,l-dimethyl)-l-dimethyl)silyloxymethyl)phenyl] acetamide The subtitle compound was prepared from the product of step (ii) (1.25g) and the product of Example 80 step (ii) (lg) by the method of Example 80 step (iii) as a beige foam. Yield: 1.3g MS: APCI(+ve) 571 (M+l) iv) c/5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5- hydroxymethyl)phenyl] acetamide A solution ofthe product of step (iii) (1.3g) in tetrahydrofuran (9ml) was treated with IM tetrabutylammonium fluoride in tetrahydrofuran (2.6ml) at ambient temperature. After stirring for 1.5h the solvent was evaporated under reduced pressure to leave a brown gum. Purification was by silica gel chromatography eluting with ethyl acetate/ iso-hexane (9:1) to give the subtitle compound as a white solid. Yield: 0.93g MS: APCI(+ve) 457 (M+l) v) α5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5- iodomethyl)phenyl] acetamide The product from step (iv) (O.lg) in tetrahydrofuran (2ml), N,N-diisopropylethylamine (0.15ml), potassium iodide (2mg) was treated with methanesulphonyl chloride (0.34ml). After stirring at ambient temperature for 40h. The solvent was evaporated under reduced pressure to leave a beige gum. This was used directly in the next step. vi) cw-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5-(4- amino-l-piperidinyl)methyl)phenyl]acetamide The crude product from step (v) (0.2g) was treated with 1,1-dimethylethyl, 4- aminopiperidinyl-4-carboxylate (0.13g) in tetrahydrofuran (2ml) at 55 °C for 24h. The solvent was evaporated under reduced pressure. The residue was then treated with 4M hydrogen chloride in 1,4-dioxane (3ml) for 5h. The solvents were then evaporated under reduced pressure. Purification was by reverse phase HPLC to give the title compound as a white solid. Yield. 0.1 g MS: APCI(+ve) 539 (M+l) Η NMR δ (DMSO) 9.84(bs, IH), 9.19(s, IH), 8.33(s, IH), 8.16(m, 4H), 7.82(t, IH), 7.76(s, IH), 7.32(d, IH), 7.19(d, IH), 4.22(s, 2H), 4.1 l(m, 2H), 3.41(d, 2H), 3.25(bs, 2H), 3.10(s, 2H), 3.01(m, 2H), 2.70(4 2H), 2.40(m, 2H), 2.34(s, 3H), 2.08(4 2H), 1.96(dd, 2H), 1.75(q, 2H), 1.45(d, 6H) Example 98 (R)-2-[4-(4-Methanesulphonylbenzenesulphonyl)-3-methylpiperazin-l-yl]-N- (quinolin-5-yl)acetamide i) (R )-l,l-Dimethylethyl, (4-Methanesulphonylbenzenesulphonyl-3-methylpiperazm- 1-yl-l-carboxylate The subtitle compound was prepared from (R)- 1 , 1 -dimethylethyl, 3-methylpiperazin- 1 -yl- 1 -carboxylate (0.75g) (J. Med. Chem, 1993, 36(6), 690)and 4-methanesulphonyl- benzenesulphonyl chloride (0.96g) by the method of Example 58 step (ii) as white solid. Yield: 0.9g 'H NMR δ (DMSO) 8.15(d, 2H), 8.07(4 2H), 4.08(bs, IH), 3.85(bs, IH), 3.65(bs, IH), 3.33(s, 2H), 3.32(s, 3H), 3.09(t, IH), 1.36(s, 9H), 0.93(4 3H) ii) (R )- l-(4-Methanesulphonylbenzenesulphonyl-3-methylpiperazine, hydrochloride salt The subtitle compound was prepared from the product of step (i) (0.209g) by the method of Example 27 step (iv) as a white solid. Yield: 0.15g MS:APCI(+ve) 319(M+l) iii) (R)-2-[4-(4-Methanesulphonylbenzenesulphonyl)-3-methylpiperazin-l-yl]-N- (quinolin-5-yl)acetamide The title compound was prepared from the product of step (ii) (0.14g) and 2-chloro-N- (quinolin-5-yl)acetamide (0.97g) (J Indian Chem Soc, 1940, 17, 619-621) by the method of Example 33 step (iv) as a white solid. Yield: 0.135g MS: APCI(+ve) 503(M+1) 'H NMR δ (DMSO) 9.88(s, IH), 8.91(d, IH), 8.32(d, IH), 8.16(d, 2H), 8.09(d, 2H), 7.88(dd, IH), 7.73(m, 2H), 7.55(q, IH), 4.09(d, IH), 3.66(d, IH), 3.38(d, IH), 3.3 l(s, 3H), 3.22(s, 2H), 2.91(d, IH), 2.73(d, IH), 2.31(m, 2H), 2.15(t, IH), 1.21(4 3H) Example 99 (R)-2-[4-(4-Acetanύdobenzenesulphonyl)-3-methylpiperazm-l-yl]-N-(quinolin-5- yl)acetamide i) (R)-l,l-Dimethylethyl, (4-Acetamidobenzenesulphonyl-3-methylpiperazin-l-yI-l- carboxylate The subtitle compound was prepared from (R)- 1,1 -dimethylethyl, 3-methylpiperazin- 1-yl- 1 -carboxylate (4g) (J. Med. Chem, 1993, 36(6), 690) and 4-acetamidobenzenesulphonyl chloride (4.68g) by the method of Example 58 step (ii) as white solid. Yield: 4.9g MS: APCI(+ve) 398(M+1) ii) (R)-l-(4-Acetamidobenzenesulphonyl)-3-methylpiperazine, hydrochloride salt The subtitle compound was prepared from the product of step (i) (4.9g) by the method of Example 27 step (iv) as a white solid. Yield: 4.38g 'H NMR δ (DMSO) 10.60(s, IH), 8.92(bs, IH), 8.91(4 2H), 8.04(t, IH), 7.85(4 2H), 7.78(d, 2H), 7.45(d, IH), 6.66(4 IH), 3.27(t, 2H), 3.06(m, 2H), 2.87(m, 2H), 2.73(m, 3H), 2.10(s, 3H), 1.30(d, 2H), 1.16(4 3H) iii) (R)-2-[4-(4-AcetylammobenzenesuIphonyI)-3-methyIpiperazin-l-yl]-N-(qumolin- 5-yl)acetamide The title compound was prepared from the product of step (ii) (0.65g) and 2-chloro-N- (quinolin-5-yl)acetamide (0.39g) (J Indian Chem Soc, 1940, 17, 619-621) by the method of Example 33 step (iv) as a white solid. Yield: 0.064g MS: APCI(+ve) 439(M-42(+H,-Ac)) 'HNMR δ (DMSO) 9.89(s, IH), 8.91(s, IH), 8.31(4 IH), 7.87(m, IH), 7.75(s, 2H), 7.50(m, IH), 7.43(d, 2H), 6.63(4 2H), 6.01(s, 2H), 3.90(s, IH), 3.42(4 IH), 3.42(d, IH), 3.24(s, IH), 3.20(d, 2H), 2.86(4 IH), 2.68(4 IH), 2.31(4 IH), 2.18(t, IH), 1.18(4 3H) Example 100 c s-2-[4-(3-CyanobenzenesuIphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5-(l- piperazinylmethyl)phenyl)acetamide The title compound was prepared from the product of Example 97 step (v) (0.2g) and 1,1- dimethylethyl, piperazine- 1 -carboxylate (0.12g) by the method of Example 97 step (vi) to give the title compound as a white solid. Yield: 74mg MS: APCI(+ve) 525 (M+l) 'H NMR δ (DMSO) 9.21 (s, IH), 9.0(bs, 2H), 8.33(s, IH), 8.17(4 2H), 7.82(t, IH), 7.69(s, IH), 7.28(d, IH), 7.16(d, IH), 4.14(m, 2H), 3.27(bs, 4H), 3.15(s, 2H), 3.05(bs, 2H), 2.69(d, 2H), 2.2 l(s, 3H), 2.0(4 2H), 1.44(4 6H) Example 101 s-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5-(4- piperidinylamino)methyl)phenyl)acetamide The title compound was prepared from the product of Example 97 step (v) (0.2g) and 1,1- dimethylethyl, 4-aminopiperidinyl-l -carboxylate (0.12g) by the method of Example 97 step (vi) as a white solid. Yield: 34mg MS: APCI(+ve) 539(M+1) 'H NMR δ (DMSO) 9.18(s, IH), 9.09(s, 2H), 8.81(m, IH), 8.60(m, IH), 8.33(s, IH), 8.15(d, 2H), 7.82(t, IH), 7.75(s, IH), 7.30(4 IH), 7.21(4 IH), 4.10(m, 4H), 3.40(4 2H), 3.32(s, 2H), 2.92(q, 2H), 2.68(4 2H), 2.23(s, 3H), 1.94(dd, 2H), 1.73(q, 2H), 1.43(4 6H) Example 102 c s-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5-(l- morpholinyl)methyl)phenyl)acetamide The title compound was prepared from the product of Example 97 step (v) (0.2g) and morpholine (0.058g) by the method of Example_97 step (vi). The solvents evaporated under reduced pressure and the residue purified by reverse phase HPLC to give the title compound as a white solid. Yield: 97mg MS: APCI(+ve) 526 (M+l) 'H NMR δ (DMSO) 10.1 l(bs, IH), 9.22(s, IH), 8.34(s, IH), 8.16(d, 2H), 7.83(d, IH), 7.78(d, IH), 7.33(d, IH), 7.21(d, IH), 4.31(s, 2H), 4.12(t, 4H), 3.63(m, 2H), 3.3(m, 4H), 2.70(4 2H), 2.23(s, 3H), 1.97(dd, 2H), 1.43(d, 6H) Example 103 c s-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5-(2- hydroxyethylamino)methyl)phenyl)acetamide The title compound was prepared from the product of Example 97 step (v) (0.2g) and ethanolamine (0.04 lg) by the method of Example 97 step (vi). The solvents evaporated under reduced pressure and the residue purified by reverse phase HPLC to give the title compound as a white solid. Yield: 37mg MS: APCI(+ve) 500(M+1) 'HNMR δ (DMSO) 8.27(s, IH), 8.18(4 IH), 8.02(4 IH), 7.74-7.82(m, 3H), 7.35(d, 2H), 7:25(d, IH), 4.27(t, 2H), 4.20(s, 2H), 3.83(t, 2H), 3.40(s, 2H), 3.25(s, IH), 3.14(t, 2H), 2.97(d, 2H), 2.33(s, 5H), 1.56(d, 6H) Example 104 c s-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5-(S,S)- (2,5-diazabicy clo [2.2.1 ] hept-2-yl)methy l)phenyl)acetamide The title compound was prepared from the product of Example 97 step (v) (0.2g) and 1,1- dimethylethyl, (S,S)-2,5-diazabicyclo[2.2.1]heptane-5-carboxylate (0.13g) by the method of Example 97 step (vi) as a white solid. Yield: 107mg MS: APCI(+ve) 537 (M+l) • 'H NMR δ (DMSO) 9.2(s, IH), 8.34(s, IH), 8.16(d, 2H), 7.83(d, IH), 7.79(s, IH), 7.31(d, IH), 7.24(d, IH), 4.46(s, IH), 4.32(m, 2H), 4.12(s, 2H), 3.35(d, 2H), 3.1 l(s, 2H), 2.68(d, 2H), 2.23(s, 3H), 1.98(t, 3H), 1.44(d, 6H) Example 105 (R)-2-[4-(2-Pyridmesulphonyl)-3-methylpiperazm-l-yl]-N-(quinojl -5-yl)acetamide i) (R )-l,l-Dimethylethyl, (2-Pyridinesulphonyl-3-methylpiperazin-l-yl-l-carboxylate A solution of 1,1-dimethylethyl, 3 -(R)-methylpiperazine-l -carboxylate (2g) (J. Med. Chem, 1993, 36(6), 690), 4-N,N'-dimethylaminopyridine (1.22g) in pyridine (10ml) was treated with 2-pyridinesulphonyl chloride (2.7g) at 0 °C. The ice bath was removed and the mixture further stirred for lh at ambient temperature. The mixmre was partitioned between dichloromethane and water. The organic phase further washed with brine, collected, dried (MgSO 4 ) and solvent evaporated under reduced pressure. Purification was by silica gel chromatography eluting with ethyl acetate/dichloromethane mixtures to give the subtitle compound as white solid. Yield: 3.3g MS: ESI(+ve) 342(M+1) ii) (R )-l-(2-Pyridinesulphonyl-3-methyIpiperazme, hydrochloride salt The subtitle compound was prepared from the product of step (i) (2.5g) by the method of Example 27 step (iv) as a white solid. Yield: 2.5g MS: ESI(+ve) 242 (M+l) iii) (R)-2-[4-(2-Pyridmesulphonyl)-3-methylpiperazm-l-yl]-N-(quinolin-5- yl)acetamide The title compound was prepared from the product of step (ii) (0.6g) and 2-chloro-N- (quinolin-5-yl)acetamide (0.39g) (J Indian Chem Soc, 1940, 17, 619-621) by the method of Example 80 step (iii). Purification was by silica gel chromatography eluting with ethyl acetate to give a white solid. Yield: 0.41 g MS: ESI(+ve) 424(M+1) 'H NMR δ (DMSO) 8.8(4 IH), 8.35(4 IH), 8.10(t, IH), 7.97(4 IH), 7.90(4 IH), 7.7(m, 3H), 7.55(m, IH), 4.10(m, IH), 3.7(m, IH) 3.5(t, IH), 3.3(m, 2H), 3.2(m, IH), 2.95(4 IH), 2.7(d, IH), 2.4-2.1(m, 2H), 1.2(4 3H) Example 106 αs-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazm-l-yl]-N-(2-methyl-3-(4- amino-l-piperidinyl)methyl)phenyl]acetamide i) 2-Methyl-3-((l,l-dimethyl)-l-dimethylethyl)silyloxymethylaniline The subtitle compound was prepared from 2-methyl-3-hydoxymethylaniline (5g) and tert- butyldimethylsilyl chloride (5.42g) by the method of Example 97 step (i) as an oil which crystalised on standing. Yield: 9.12g MS: APCI(+ve) 252(M+1) u) 2-Chloro-N-(2-methyl-3-((l,l-dimethyl)-l-dimethylethyl)silyloxymethyl)acetamide The subtitle compound was prepared from the product of step (i) (4.13g) and chloroacetyl chloride (1.5ml) by the method of Example 33 step (iii) as a beige solid. Yield: 3.12g MS:APCI(+ve) 328(M+1) iii) cw-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5- ((l,l-dimethyl)-l-dimethylethyl)silyloxymethyl)phenyl]acetamide The subtitle compound was prepared from the product of step (ii) (1.25g) and the product of Example 80 step (ii) (lg) by the method of Example 80 step (iii) as a cream solid. Yield: 1.5g MS: APCI(+ve) 571 (M+l) iv) c 5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5- hydroxymethyl)pheny 1] acetamide The subtitle compound was prepared from the product of step (iii) (1.4g) and IM tetrabutylammonium fluoride in tetrahydrofuran (2.7ml) by the method of Example 97 step (iv) as a white solid. Yield: lg MS:APCI(+ve) 457(M+1) v) cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazm-l-yl]-N-(2-methyl-3- iodomethyl)phenyl] acetamide The product from step (iv) (O.lg) in tetrahydrofuran (2ml), N,N-diisopropylethylamine (0.15ml), potassium iodide (2mg) was treated with methanesulphonyl chloride (0.34ml). After stirring at ambient temperature for 40h. The solvent was evaporated under reduced pressure to leave a beige gum. This was used directly in the next step. vi) cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5-(4- amino-l-piperidinyl)methyl)phenyl] acetamide The crude product from step (v) (0.2g) was treated with 1,1-dimethylethyl, 4- aminopiperidinyl-4-carboxylate (0.13g) in tetrahydrofuran (2ml) at 55 °C for 24h. The solvent was evaporated under reduced pressure. . The residue was then treated with 4M hydrogen chloride in 1 ,4-dioxane (3ml) for 5h. The solvents were then evaporated under reduced pressure. Purification was by reverse phase HPLC to give the title compound as a white solid. Yield. 0.068g MS: APCI(+ve) 539 (M+l) 'H NMR δ (CDCVDMSO) 8.87(bs, IH), 8.67(bs, IH), 8.14(s, IH), 8.10(4 IH), 7.95(4 IH), 7.80(d, IH), 7.75(t, IH), 7.30(m, 2H), 4.30(bs, IH), 4.20(m, 2H), 3.10(s, 2H), 2.80(4 2H), 2.30(s, 3H), 2.20(m, 4H), 1.60(4 6H) Example 107 c s-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-3-(4- piperidinylamino)methyl)phenyl)acetamide The title compound was prepared from the product of Example 106 step (v) (0.2g) and 1,1- dimethylethyl, 4-aminopiperidinyl-l -carboxylate (0.12g) by the method of Example 106 step (vi) as a white solid. Yield: 38mg MS: APCI(+ve) 539(M+1) 'H NMR δ (DMSO) 9.33(bs, IH), 9.10(bs, IH), 8.8(bd, IH), 8.60(bd, IH), 8.37(s, IH), 8.20(m, IH), 7.90(t, IH), 7.40(d, IH), 7.30(m, 2H), 4.20(bs, 2H), 4.10(m, 2H), 3.10(s, 2H), 3.00(m, 2H), 2.7(m, 2H), 2.30(m, 2H), 2.20(s, 3H), 2.00-1.80(m, 4H), 1.40(s, 6H) Example 108 c s-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazm-l-yl]-N-(2-methyl-3-(l- piperazinylmethyl)phenyl)acetamide The title compound was prepared from the product of Example 106 step (v) (0.2g) and 1,1- dimethylethyl, piperazine- 1 -carboxylate (0.12g) by the method of Example 106 step (vi) as a white solid. Yield: 74mg MS : APCI(+ve) 525 (M+l ) 'H NMR δ (DMSO) 8.34(s, IH), 8.20(m, 2H), 7.80(t, IH), 7.40(t, IH), 7.20(2xd, 2H), 4.20(m, 2H), 3.90(bs, 2H), 3.20(m, 6H), 3.00-2.60(m, 6H), 2.20(s, 3H), 2.00(m, 2H), 1.5Q(d, 6H) Example 109 c 5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-3-(S,S)- (2,5-diazabicyclo[2.2.1]hept-2-yl)methyl)phenyl)acetamide The title compound was prepared from the product of Example 106 step (v) (0.2g) and 1,1- dimethylethyl, (S,S)-2,5-diazabicyclo[2.2.1]heptane-5-carboxylate (0.13g) by the method of Example 106 step (vi) as a white solid. Yield: 82mg s MS: APCI(+ve) 537 (M+l) Η NMR δ (DMSO) 8.38(s, IH), 8.20(m, 2H), 7.80(t, IH), 7.50(4 IH), 7.30(m, 2H), 4.40(s, IH), 4.30(m, 2H), 4.10(m, 2H), 3.30(m, 2H), 3.10(s, 2H), 2.80(m, 2H), 2.22(s, 3H), 2.00(m, 4H), 1.50(d, 6H) o Example 110 c 5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl-3-(l- morpholinyl)methyl)phenyl)acetamide The title compound was prepare from the product of Example 106 step (v) (0.2g) and morpholine (0.058g) by the method of Example 106 step (vi) as a white solid. Yield: 69mg MS: APCI(+ve) 526 (M+l) 'H NMR δ (DMSO) 8.34(s, IH), 8.20(m, 2H), 7.80(t, IH), 7.60(d, IH), 7.40(m, 2H), 4.40(s, 2H), 4.20(m, 2H), 4.00(bs, 2H), 3.70(bs, 2H), 3.30(bs+s, 6H), 2.80(d, 2H), 2.30(s, 3H), 2.00(m, 2H), 1.50(4 6H) Example 111 C/5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl-3-(2- (l-pyrroIidinyl)ethoxy)phenyl)acetamide i) 2-Methyl-3-((l,l-dimethyl)-l-dimethylethyl)silyloxyaniIine The subtitle compound was prepared from 3-amino-2-methylphenol (lOg) and tert- butyldimethylsilyl chloride(12.22g) by the method of Example 97 step (i) as a brown oil. Yield: 15g 'H NMR δ (CDC1 3 ) 6.86(t, IH), 6.33(4 IH), 6.27(4 IH), 3.58(bs, 2H), 2.04(s, 3H), 1.01(s, 9H), 0.20(s, 6H) ii) 2-Chloro-N-(2-methyl-3-((l,l-dimethyl)-l-dimethylethyl)silyloxy)phenyl)acetamide The product from step (i) (5g), PyBrop (9.82g), chloroacetic acid (1.99g), N,N- diisopropylethylamine (11ml) in dichloromethane (100ml) were stirred at ambient temperature for 16h. The mixture was partitioned between water and dichloromethane, the organic phase collected, dried (MgSO 4 ) and solvent evaporated under reduced pressure. Purification was by silica gel chromatography eluting with 10% diethyl ether in iso-hexane containing 1% triethylamine to give the subtitle compound as a pale yellow oil. Yield: 3.5g 'H NMR δ (CDCI 3 ) 8.21(bs, IH), 7.48(4 IH), 7.09(t, IH), 6.68(d, IH), 4.23(s, 2H), 2.16(s, 3H), 1.02(s, 9H), 0.22(s, 6H) iii) C s-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl-3- ((l,l-dimethyl)-l-dimethylethyl)silyloxy)phenyl)acetamide The subtitle compound was prepared from the product of step (ii) (lg) and the product of Example 80 step (ii) (0.89g) by the method of Example 80 step (iii) as a beige solid. Yield: 1.6g 'H NMR δ (CDCI 3 ) 8.67(s, IH), 8.12(s, IH), 8.03(4 IH), 7.85(4 IH), 7.67(t, IH), 7.59(4 IH), 7.07(t, IH), 6.64(d, IH), 4.05-4.10(m, 2H), 3.10(s, 2H), 2.73(d, 2H), 2.19(4 2H), 2.10(s, 3H), 1.54(s, 6H), 1.01(s, 9H), 0.22(s, 6H) iv) C5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl-3- hydroxy)phenyl)acetamide The subtitle compound was prepared from the product of step (iii) (1.6g) and tetrabutylammonium fluoride (3.18ml) by the method of Example 97 step (iv) as a white solid Yield: 0.5g MS APCI(+ve) 443 (M+l) v) Cis-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazm-l-yl]-N-((2-methyl-3- (2-(l-pyrrolidmyl)ethoxy)phenyl)acetamide The product from step (iv) (0. lg), l-(2-chloroethyl)pyrrolidine hydrochloride (76mg), ceasium carbonate (0.36g) in l-methyl-2-pyrrolidinone (2ml) were stirred at 70 °C for 16h. The mixture was partitioned between ethyl acetate and water, the organic phase collected, dried (MgSO 4 ) and solvent evaporated under reduced pressure. Purification was by reverse phase HPLC eluting with 5 to 90% methanol in 0.1% aqueous trifluoroacetic acid to give the the title compound as a white solid. Yield: 7mg MS: APCI(+ve) 540(M+1) 'H NMR δ (CD 3 OD) 8.15(s, IH), 8.05(4 IH), 7.89(4 IH), 7.67(t, IH), 7.06(s, IH), 7.04(s, IH), 6.74(t, IH), 4.01-4.09(m, 4H), 2.99(s, 2H), 2.88(t, 2H), 2.61-2.66(m, 6H), 2.05(s, 3H), 1.95(dd, 2H), 1.71-1.77(m, 4H), 1.44(4 6H) Example 112 (+) C/5-2-[4-(3-CyanobenzenesuIphonyl)-3,5-dimethyIpiperazm-l-yI]-N-((2-methyl-3- (l-methylpiperidin-3-yI)methoxy)phenyl)acetamide The title compound was prepared from the product of Example 111 step (iv) (O.lg) and (±) l-methyl-3-chloromethylpiperidine (83mg) by the method of Example 111 step (v) as a white solid. Yield: 19mg MS: APCI(+ve) 554 (M+l) 'H NMR δ (CD 3 OD) 8.24(s, IH), 8.14(4 IH), 7.98(4 IH), 7.77(t, IH), 7.10-7.15(m, 2H), 6.78-6.81(m, IH), 4.12-4.18(m, 2H), 3.80-3.92(m, 2H), 3.09(s, 3H), 2.75-2.85(m, IH), 2.74(d, 2H), 2.3 l(s, 3H), 2.12(s, 3H), 1.64-2.17(m, 8H), 1.53(4 6H), 1.15-1.19(m, 2H) Example 113 CXs-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl-4-(2- (l-pyrrolidinyl)ethoxy)phenyl)acetamide i) 2-Methyl-4-((l,l-dimethyl)-l-dimethylethyl)silyloxyaniline The subtitle compound was prepared from 4-amino-3-methylphenol (lOg) and tert- butyldimethylsilyl chloride(12.22g) by the method of Example 97 step (i) as a brown oil. Yield: 14g 'H NMR δ (CDC1 3 ) 6.53-6.58(m, 3H), 3.33(bs, 2H), 2.12(s, 3H), 0.98(s, 9H), 0.15(s, 6H) ii) 2-Chloro-N-(2-methyl-3-((l,l-dimethyl)-l-dimethylethyl)silyloxy)phenyl)acetamide The subtitle compound was prepared from the product of step (i) (5g) by the method of Example 111 step (ii) as pale yellow oil. Yield: 5g 'H NMR δ (CDCI 3 ) 8.06(bs, IH), 7.57-7.60(m, IH), 6.53-6.58(m, 3H), 3.33(bs, 2H), 2.12(s, 3H), 0.98(s, 9H), 0.15(s, 6H) iii) C y -2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethyIpiperazin-l-yl]-N-((2-methyl-4- ((l,l-dimethyl)-l-dimethylethyl)silyloxy)phenyl)phenyl)acetamide The subitle compound was prepared from the product of step (ii) (lg) and the product of Example 80 step (ii) (0.89g) by the method of Example 80 step (iii) as a white solid. Yield: 1.6g 'H NMR δ (CDCI 3 ) 8.48(s, IH), 8.12(s, IH), 8.04(d, IH), 7.86(d, IH), 7.64-7.70(m, 2H), 6.67-6.70(m, 2H), 4.11-4.15(m, 2H), 3.08(s, 2H), 2.73(d, 2H), 2.22(s, 3H), 2.16(dd, 2H), 1.55(d, 6H), 0.97(s, 9H), 0.18(s, 6H) iv) C75-2-[4-(3-CyanobenzenesuIphonyl)-3,5-dimethyIpiperazin-l-yl]-N-((2-methyl-4- hydroxy)phenyl)acetamide The subtitle compound was prepared from the product of step (iii) (1.6g) and tetrabutylammonium fluoride (3.21ml) by the method of Example 97 step (iv) as a white solid Yield: 0.4g MS APCI(+ve) 443 (M+l) v) Cs-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl-4- (2-(l-pyrrolidinyl)ethoxy)phenyl)acetamide The title compound was prepared from the product of step (iv) (O.lg) and l-(2- chloroethyl)pyrrolidine hydrochloride (76mg) by the method of Example 111 step (v) as a white solid. Yield: lOmg MS: APCI(+ve) 540 (M+l) 'H NMR δ (CD 3 OD) 8.24(s, IH), 8.15(d, IH), 7.98(d, IH), 7.77(t, IH), 7.30(d, IH), 6.83(d, IH), 6.77(dd, IH), 4.13-4.18(m, 2H), 4.10(t, 2H), 3.07(s, 2H), 2.91(t, 2H), 2.73(d, 2H), 2.65-2.69(m, 4H), 2.25(s, 3H), 2.04(dd, 2H), 1.79-1.86(m, 4H), 1.53-1.54(4 6H), Example 114 (+) C 5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazm-l-yl]-N-((2-methyl-4- (l-methylpiperidin-3-yl)methoxy)phenyl)acetamide The title compound was prepared from the product of Example 113 step (iv) (O.lg) and (±) l-methyl-3-chloromethylpiperidine (83mg) by the method of Example 111 step (v) as a white solid. Yield: 19mg MS: APCI(+ve) 554 (M+l) 'H NMR δ (CD 3 OD) 8.24(s, IH), 8.15(d, IH), 7.98(d, IH), 7.77(t, IH), 7.29(d, IH), 6.79(d, IH), 6.74(dd, IH), 4.13-4.16(m, 2H), 3.75-3.88(m, 2H), 3.08(s, 2H), 3.02-3.04(m, IH), 2.82-2.85(m, IH), 2.73(d, 2H), 2.29(s, 3H), 2.21(s, 3H), 1.62-2.10(m, 8H), 1.53(d, 6H), 1.09-1.13(m, IH), Example 115 (+) C/ 2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl-5- (l-methylpiperidin-3-yl)methoxy)phenyl)acetamide i) 2-Methyl-5-((l,l-dimethyl)-l-dimethylethyl)silyloxyaniline The subtitle compound was prepared from 3-amino-4-methylphenol (lOg) and tert- butyldimethylsilyl chloride(12.22g) by the method of Example 97 step (i) as a brown oil. Yield: 15g Η NMR δ (CDC1 3 ) 6.84-6.88(m, IH), 6.18-6.22(m, 2H), 3.52(bs, 2H), 2.08(s, 3H), 0.97(s, 9H), 0.17(s, 6H) ii) 2-Chloro-N-(2-methyl-5-((l,l-dimethyl)-l-dimethylethyl)silyloxy)phenyl)acetamide The subtitle compound was prepared from the product of step (i) (5g) by the method of Example 111 step (ii) as pale yellow oil. Yield: 5.3g 'H NMR δ (CDCI 3 ) 8.19(bs, IH), 7.57(4 IH), 7.03(4 IH), 6.61(dd, IH), 4.22(s, 2H), 2.23(s, 3H), 0.98(s, 9H), 0.21(s, 6H) iii) Cs-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl-5- ((l,l-dimethyl)-l-dimethylethyl)silyloxy)phenyl)phenyl)acetamide The subtitle compound was prepared from the product of step (ii) (lg) and the product of Example 80 step (ii) (0.89g) by the method of Example 80 step (iii) as a white solid. Yield: l. ' 8g 'H NM δ (CDCI 3 ) 8.64(s, IH), 8.12(s, IH), 8.04(d, IH), 7.87(4 IH), 7.68-7.70(m, 2H), 7.01(d, IH), 6.56(dd, IH), 4.09-4.16(m, 2H), 3.08(s, 2H), 2.72(4 2H), 2.22(s, 3H), 2.16(dd, 2H), 1.55(4 6H), 0.97(s, 9H), 0.19(s, 6H) iv) Cts-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperaziu-l-yl]-N-((2-methyl-5- hydroxy)phenyl)acetamide The subtitle compound was prepared from the product of step (iii) (1.81g) and tetrabutylammonium fluoride (3.24ml) by the method of Example 97 step (iv) as a white solid Yield: 0.8g MS APCI(+ve) 443 (M+l) v) (+) Cis-2- [4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl] -N-((2-methyl- 5-(l-methylpiperidin-3-yl)methoxy)phenyl)acetamide The title compound was prepared from the product of step (iv) (O.lg) and (±) l-methyl-3- chloromethylpiperidine (76mg) by the method of Example 111 step (v) as a white solid. Yield: 5mg MS: APCI(+ve) 540 (M+l) 'H NMR δ (CD 3 OD) 8.24(s, IH), 8.14(d, IH), 7.98(d, IH), 7.77(t, IH), 7.32(d, IH), 7.10(d, IH), 6.67(dd, IH), 4.12-4.18(m, 2H), 3.73-3.86(m, 2H), 3.09(s, 2H), 3.02-3.05(m, IH), 2.83-2.86(m, IH), 2.74(d, 2H), 2.29(s, 3H), 2.24(s, 3H), 1.58-2.1 l(m, 9H), 1.54(d, 6H), 1.09-1.13(m, IH), Example 116 (+) C/5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl-6- (J-methylpiperidm-3-yl)methoxy)phenyl)acetamide i) 2-Methyl-6-((l,l-dimethyl)-l-dimethylethyl)silyIoxyaniline The subtitle compound was prepared from 2-amino-3-methylphenol (lOg) and tert- butyldimethylsilyl chloride(12.22g) by the method of Example 97 step (i) as a brown oil. Yield: 14g 'H NMR δ (CDC1 3 ) 6.53-6.70(m, 3H), 3.66(bs, 2H), 2.17(s, 3H), 1.02(s, 9H), 0.24(s, 6H) ii) 2-Chloro-N-(2-methyl-6-((l,l-dimethyl)-l-dimethylethyl)silyloxy)phenyl)acetamide The subtitle compound was prepared from the product of step (i) (5g) by the method of Example 111 step (ii) as pale yellow oil. Yield: 4.6g 'H NMR δ (CDCI 3 ) 7.97(bs, IH), 7.07(t, IH), 6.86(d, IH), 6.72(d, IH), 4.22(s, 2H), 2.23(s, 3H), 1.00(s, 9H), 0.22(s, 6H) iii) Cts-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl-6- ((l,l-dimethyl)-l-dimethylethyl)silyloxy)phenyl)acetamide The subitle compound was prepared from the product of step (ii) (lg) and the product of Example 80 step (ii) (0.89g) by the method of Example 80 step (iii) as a white solid. This product was used directly in the next step iv) Cw-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl-6- hydroxy)phenyl)acetamide The subtitle compound was prepared from the product of step (iii) (2g) and tetrabutylammonium fluoride (3.18ml) by the method of Example 97 step (iv) as a white solid Yield: 0.8g MS APCI(+ve) 441 (M-l) v) (±) Os-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl- 6-(l-methylpiperidm-3-yl)methoxy)phenyl)acetamide The title compound was prepared from the product of step (iv) (O.lg) and (+) l-methyl-3- chloromethylpiperidine (76mg) by the method of Example 111 step (v) as a white solid. Yield: 26mg MS: APCI(+ve) 540 (M+l) 'H NM δ (CD 3 OD) 8.29(s, IH), 8.17(4 IH), 7.98(4 IH), 7.78(t, IH), 7.17(t, IH), 6.87(s, IH), 6.84(s, IH), 4.19-4.20(m, 2H), 3.83-3.88(m, 2H), 3.12(s, 2H), 2.80-3.0(m, 3H), 2.28(s, 3H), 2.20(s, 3H), 1.6-2.1(m, 9H), 1.55(4 6H), 1.0-1.2(m,lH) Example 117 C5-2-[4-(l-MethyUmidazol-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-l-yl]-N-((2- methyl-3-(2-(l-pyrrolidinyl)ethoxy)phenyl)acetamide i) C 5-l-(l-Methylimidazol-4-sulphonyl-4-yl)-2,6-dimethyl-4-phenylmethylpiperazine l-methylimidazol-4-sulphonyl chloride (19.45g) was added in small portions to a solution of cz ' 5'-4-benzyl-2,6-dimethylpiperazine (20g) in pyridine (53ml) at 120 °C. After heating for a further lOmin at reflux the solvent was evaporated under reduced pressure. The mixture was partitioned between dichloromethane and dilute sodium hydroxide solution. The organic phase collected, dried (MgSO 4 ) and solvent evaporated under reduced pressure. Purification was by silica gel chromatography eluting with 0 to 5% methanol in dichloromethane to give the subtitle compound as pale yellow solid. Yield: 14.2g 'H NMR δ (CDC1 3 ) 7.22-7.46(m, 7H), 4.07-4.15(m, 2H), 3.73(s, 3H), 3.42(4 2H), 2.53(d, 2H), 2.08(dd, 2H), 1.46(4 6H) ii) C5-l-(l-Methylimidazol-4-sulphonyl-4-yl)-2,6-dimethylpiperazine The subtitle compound was prepared from the product of step (i) (14.07g) by the method of Example 80 step (ii) as tan solid. Yield: 12.16g MS: APCI (+ve) 259(M+1) iu) C5-2-[4-(l-MethyUmidazol-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-l-yl]-N-((2- methyl-3-((l,l-dj ιethyl)-l-dimethylethyl)silyloxy)phenyl)acetamide The subtitle compound was prepared from the product of step (ii) (0.82g) and the product of Example 111 step (ii) (lg) by the method of Example 80 step (iii) as a white solid. Yield: 1.6g 'H NMR δ (CDC1 3 ) 8.83(s, IH), 7.61(4 IH), 7.47(s, IH), 7.40(s, IH), 7.07(t, IH), 6.63(4 IH), 4.21-4.24(m, 2H), 3.75(s, 3H), 3.10(s, 2H), 2.65(d, 2H), 2.17(s, 3H), 1.56(d, 6H), 1.02(s, 9H), 0.22(s, 6H) iv) Crø-2-[4-(l-Methylimidazol-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-l-yl]-N-((2- methyl-3-hydroxy)phenyl)acetamide The subtitle compound was prepared from the product of step (iii) (1.51g) by the method of Example 111 step (iv) as a white solid. Yield: 0.4g MS» APCI(+ve) 422 (M+l) y) C/s-2-[4-(l-Methyhmidazol-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-l-yl]-N-((2- methyl-3-(2-(l-pyrrolidinyl)ethoxy)phenyl)acetamide The title compound was prepared from the product of step (iv) (95mg) and l-(2- chloroethyl)pyrrolidine (83mg) by the method of Example 111 step (v) as a white solid. Yield: 19mg MS: APCI(+ve) 519 (M+l) 'H NMR δ (CD 3 OD) 7.76(s, IH), 7.67(s, IH), 7.13-7.24(m, 2H), 6.84(d, IH), 4.12-4.19(m, 4H), 3.78(s, 3H), 3.1 l(s, 2H), 3.01(t, 2H), 2.67-2.76(m, 6H), 2.18-2.28(m, 5H), 1.54(d, 6H) Pharmacological Analysis Certain compounds such as benzoylbenzoyl adenosine triphosphate (bbATP) are known to be agonists ofthe P2X 7 receptor, effecting the formation of pores in the plasma membrane (Drug Development Research (1996), 37(3), p.126). Consequently, when the receptor is activated using bbATP in the presence of ethidium bromide (a fluorescent DNA probe), an increase in the fluorescence of intracellular DNA-bound ethidium bromide is observed. The increase in fluorescence can be used as a measure of P2X 7 receptor activation and therefore to quantify the effect of a compound on the P2X 7 receptor. In this manner, each ofthe title compounds ofthe Examples was tested for antagonist activity at the P2X 7 receptor. Thus, the test was performed in 96-well flat bottomed microtitre plates, the wells being filled with 250 μl of test solution comprising 200 μl of a 6 -4 suspension of THP-1 cells (2.5 x 10 cells/ml) containing 10 M ethidium bromide, 25 μl of a high potassium buffer solution containing 10 " M bbATP, and 25 μl ofthe high potassium buffer solution containing 3 x 10 " M test compound. The plate was covered with a plastics sheet and incubated at 37 °C for one hour. The plate was then read in a Perkin-Elmer fluorescent plate reader, excitation 520 nm, emission 595 nm, slit widths: Ex 15 nm, Em 20 nm. For the purposes of comparison, bbATP (a P2X 7 receptor agonist) and rjyridoxal 5-phosphate (a P2X 7 receptor antagonist) were used separately in the test as controls. From the readings obtained, a pIC 50 figure was calculated for each test compound, this figure being the negative logarithm ofthe concentration of test compound necessary to reduce the bbATP agonist activity by 50%. Each ofthe compounds ofthe Examples demonstrated antagonist activity, having a PIC 5 0 figure > 5.0.

Claims: C L A I M S 1. A compound of general formula wherein, X represents a nitrogen atom or a group C(R ); Y represents an oxygen or sulphur atom or a group NR ; 1 2 either R and R each independently represent a hydrogen atom or a C 1 -C alkyl 1 2 group but do not both simultaneously represent a hydrogen atom, or R and R together represent a group -CH 2 ZCH 2 -; 7 Z represents a bond, an oxygen or sulphur atom or a group CH 2 or NR ; m is 0 or 1 ; 3 R 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 substimted by one or more substituents independently selected from halogen, nitro, cyano, NR 8 R 9 , C r C 4 alkyl-C(O)NH-, NHR 12 C(O)-, C r C 4 alkyl-SO 2 -, C r C 4 alkyl-SO 2 NH-, C r C 4 alkyl-NHSO 2 -, C r C 4 alkoxy, and C r C 4 alkyl optionally substimted by one or more fluorine atoms; 4 R represents a phenyl or pyridinyl group, each of which is substituted in an ortho position with a substiment selected from halogen, C r C 4 alkoxy, C r C 4 alkylthio, and C C^. alkyl optionally substimted 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 r C 4 alkylthio, C r C 4 alkyl-NH-, NHR 13 -C r C 4 alkyl-, C r C 4 alkyl-SO 2 -, C r C 4 alkyl-SO 2 NH-, C r C 4 alkyl-NHSO 2 -, C r C 4 alkyl-C(O)NH-, C r C 4 alkyl-NHC(O)-, -D-G, C r C 4 alkoxy optionally substimted by -NR R or by R , and C 1 -C4 alkyl optionally substituted by one or more fluorine atoms or by one or more hydroxyl groups, 4 or R 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 substimted by one or more substituents independently selected from halogen, oxo, C 1 -C alkyl, C 1 -C 4 alkoxy, C r C 4 alkylthio and -NR 10 R U ; 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 represents a hydrogen atom, or a hydroxyl or C j - alkoxy group; R represents a hydrogen atom, or a cyano, nitro, hydroxyl, C ] _ -C 4 alkyl or C r C 4 alkoxy group; 7 8 9 R , R and R each independently represent a hydrogen atom or a C j -C 4 alkyl group; R and R each independently represent a hydrogen atom or a C^C^. alkyl group, or R and R 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; 12 R represents a hydrogen atom, or a C O^ alkyl group optionally substituted by ammo; 13 R represents a hydrogen atom, or a C r C 4 alkyl group optionally substituted by hydroxyl; R and R each independently represent a hydrogen atom or a C 1 -C 4 alkyl group 14 15 optionally substituted by hydroxyl, or R and R 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 represents a l-(C 1 -C -alkyl)-piperidinyl group; 4 with the proviso that when m is 0, X is N and Y is O, then R 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. 3 4. A compound according to any one of claims 1 to 3, wherein, in R , the 5- to 10- membered unsaturated ring system is selected from phenyl, pyridinyl, pyrimidinyl, naphthyl, furanyl, pyrryl, thienyl, isothiazolyl, imidazolyl, benzimidazolyl, tefrazolyl, 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 tWenopyrimidinyl. 5. A compound according to any one ofthe preceding claims, wherein, in R , 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 ofthe preceding claims, wherein, in R , an ortho substituent in the phenyl or pyridinyl group is halogen or C r C 4 alkyl optionally substituted by one or more fluorine atoms. 7. A compound according to any one of claims 1 to 5, wherein, in R , 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-βT]pyrimidin-4-yl)piperazin-l- yl)acetamide, 5 cz5-[2-(3,5-Dimethyl-4-(thieno[2,3-<5T]pyrimidin-4-yl)piperazin-l-yl)]-N-(2,6- dimethylphenyl)acetamide, (+)-2-[3-Methyl-4-(4-methylphenyl)piperazin-l-yl]-N-(2,6-dimethylphenyl) acetamide, cz5-N-[3-Hydroxymethyl-2-methylphenyl]-2-(3,5-dimethyl-4-(thieno[2,3- (R)-2-[4-(l-Methylimidazol-4-sulphonyl-4-yl)-3-ethylpiperazin-l-yl]-N-(quinolin-5- yl)acetamide, cz * 5-2-[3,5-Dimethyl-4-(tMeno[2,3-(i]pyrimidin-4-yl)piperazin-l-yl]-N-(2- methylphenyl)acetamide, is cz ' 5'-N-(2-Chlorophenyl)-2-[3,5-dimethyl-4-(tMeno[2,3-^pyrimidin-4-yl)piperazin-l- yl] acetamide, ct5-N-(2-Chlorophenyl)-2-[3,5-dimethyl-4-(9-methyl-9H-purin-6yl)piperazin-l- yl] acetamide, cz5-2-(3,5-Dimethyl-4-(tMeno[2,3-(i]pyrimidin-4-yl)piperazin-l-yl)-N-(isoquinolin-0 5-yl)acetamide, cis-2-(3 ,5-Dimethyl-4-thieno [2,3 -< ]pyrimidin-4-yl)piperazin- 1 -yl)-N-(quinolin-5- yl)acetamide, cz ' j-2-(3,5-Dimethyl-4-(thieno[2,3-(f]pyrimidin-4-yl)piperazin-l-yl)-N-(2-methyl-5- methylsulphonamidophenyl)acetamide, 5 cw-2-(3,5-Dimethyl-4-(thieno[2,3-(/]pyrimidin-4-yl)piperazin-l-yl]-N-(2- trifluoromethylphenyl)acetamide, cz ' _f-2-(3,5-Dimethyl-4-(thieno[2,3-fiTlpyrimidm-4-yl)piperazm-l-yl)-N-(3- methylpyridin-2-yl)acetamide, cz * 5-2-(3,5-Dimethyl-4-(tln^no[2,3-rf]pyrimidin-4-yl)piperazin-l-yl)-N-(isoquinolin-0 l-yl)acetamide, ew-4-(4-Amino-5-cyanopyrimidin-2-yl)-3,5-dimethylpiperazin-l-yl)-N-(2- chlorophenyl)acetamide, cz5-2-(4-Benzenesulphonyl-3,5-dimethylpiperazin-l-yl)-N-(2-chloro- phenyl)acetamide, (+)-N-(2, 6-Dimethylphenyl)-2- [(3 -methyl-4-thiazolo(5 ,4- >yrimidin-7-yl)piperazin- l-yl]acetamide, cw-N-(2-Chlorophenyl)-2-[(3 ,5-dimethyl-4-quinazolin-4-yl)piperazin- 1 - yl] acetamide, N-(2-Chlorophenyl)-2-[(8-(thieno[2,3-< ]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-^]pyrimidin-7-yl)-3,8-diazabicyclo[3.2.1]oct-3- yl] acetamide, N-(2-Methylphenyl)-2-[(8-thiazolo[5,4-(i]pyrimidin-7-yl)-3,8-diazabicyclo[3.2.1 ]oct- 3 -yl] acetamide, N-(2-Methyl-5-(methylsulphonyl)amidoρhenyl)-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-< ]pyrimidin-7-yl)- 3 , 8 -diazabicyclo [3.2.1 ] oct-3 -yl] acetamide, N-[2-Methyl-5-(me1hylsulphonyl)amidophenyl]-2-[4-(thieno[2,3- ( ]pyrimidin-4-yl)- 3,8-diazabicyclo[3.2.1]oct-3-yl]acetamide, cz5-2-(3,5-Dimethyl-4-(thieno[2,3-d]pyrimidin-4-yl)piperazin-l-yl)-N-(2-methyl-5- (l-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. l]oct-3-yl]acetamide, N-(2-Methyl-5-(l-piperazinylmethyl)phenyl)-2-[(8-(thieno[2,3-d]pyrimidin-4-yl)-3,8- diazabicyclo[3.2. l]oct-3-yl]acetamide, cz5-N-(5-(2-Aminoethoxy)-2-methyl-phenyl)-2-(3,5-dimethyl-4-(thieno[2,3- d]pyrimidin-4-yl)piperazin-l-yl)acetamide, hydrochloride salt, cw-N-(5-(2-(N-Methylamino)ethoxy)-2-methyl-phenyl)-2-(3,5-dimethyl-4-(thieno[2,3- d]pyrimidin-4-yl)piperazin-l-yl)acetamide, hydrochloride salt, cz5 , -N-(5-(2-(N-Methylamino)ethoxy)-2-methyl-phenyl)-2-(4-benzenesulphonyl)-3,5- dimethyl)piperazin- 1 -yl)acetamide, cz ' i'-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-lH-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, cz5-N-(3-Fluoro-2-methyl-phenyl)-2-(4-benzenesulphonyl)-3,5-dimefhyl)piperazin-l- 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[l,2,5]oxadiazole-4-sulρhonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2- methylphenyl)acetamide, 2-[8-(Benzo[l,2,5]thiadiazole-4-sulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N-(2- methylphenyl)acetamide, 2-[8-(5-Chlorothieno-2-yl)sulphonyl)-3,8-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-[8-(4-Acetylaminomethoxybenzenesulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N- (2-methylphenyl)acetamide, N-(2-Methylphenyl)-2-[(8-(3-methyltMeno[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- 1 H- benzoimidazol-2-yl)acetamide, cw-2-(3,5-Dimethyl-4-(thieno[2,3-d]pyrimidin-4-yl)piperazin-l-yl)-N-(2-methyl-5- (4-piperidinyloxy)phenyl)acetamide, hydrochloride salt, cz-f-2-(3,5-Dimethyl-4-benzenesulphonyl)piperazin-l-yl)-N-(2-methyl-5-(4- piperidinyloxy)phenyl)acetamide, cz ' 5'-2-(3,5-Dimethyl-4-(quinazolin-4-yl)piperazin-l-yl)-N-(2-methyl-5-(4- piperidinyloxy)phenyl)acetamide, ct5-2-(3,5-Dimethyl-4-(4-quinazolinyl)piperazin-l-yl)-N-(2-methyl-5-(piperazin-4- yl-methyl)phenyl)acetamide, cis-2-(3 ,5-Dimethyl-4-(4-quinazolinyl)piperazin- 1 -yl)-N-(2-methyl-5-(2-(N- methylamino)ethoxy)phenyl)acetamide, '"Cz * -f-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide, cz ' i'-N-(2-Methylphenyl)-2-[4-(3-nitrobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]- acetamide, cz5-2-[4-(3-Aminobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide, cw-2-(3,5-Dimethyl-4-(3-cyanobenzenesulphonyl)piperazin-l-yl)-N-(quinolin-5- yl)acetamide, cis-2-(3 ,5-Dimethyl-4-(4-cyanobenzenesulphonyl)piperazin- 1 -yl)-N-(quinolin-5- yl)acetamide, cz5-2-(4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl)-N-(3-fluoro-2- methylphenyl)acetamide, ew-2-(4-(4-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl)-N-(3-fluoro-2- methylphenyl)acetamide, cz ' '-2-[4-(3-Acetylaminobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide, cz5 , -2-[4-(3-Aminocarbonylbenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide, cw-2-[4-(3-Methanesulphonylaminobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]- N-(2-methylphenyl)acetamide, cis -2-[4-(2-Methanesulphonylbenzenesulphonyl)-3 ,5-dimethylpiperazin- 1 -yl]-N-(3- methoxy-2-methylphenyl)acetamide, cz>s-2-[4-(2-Methanesulphonylbenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(3- fluoro-2-methylphenyl)acetamide, cz ' 5-2-[4-(l-Methylimidazol-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-l-yl]-N- (quinolin-5-yl)acetamide, cz_'-2-[4-(l-Methylimidazol-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-l-yl]-N-(3- methoxy-2-methylphenyl)acetamide, cz ' -?-2-[4-( 1 -Methylimidazol-4-sulphonyl-4-yl)-3 ,5-dimethylpiperazin- 1 -yl]-N-(3 - fluoro-2-methylphenyl)acetamide, ' " cz ' 1 s , -2-[4-(l-Methanesulphonylbenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- trifluoromethylphenyl)acetamide, , cw-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, cz ' 5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2,6- dimethylphenyl)acetamide, cz5-2-[4-(4-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide, cz ' -r-2-[4-(2-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2,6- dimethylphenyl)acetamide, hydrochloride salt, cz5 , -2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- chlorophenyl)acetamide, 2-[8-(Isquinolin-l-yl)-3,8-diazabicyclo[3.2. l]oct-3-yl]-N-(2- methylphenyl)acetamide, cz * 5-2-[4-(4-Acetamidobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide, cz5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- trifluoromethylphenyl)acetamide, ct5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-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, cz ' 5'-2-[4-(l,2-Dimethylimidazol-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-l-yl]-N- (quinolin-5-yl)acetamide, cz_7-2-[4-(5-Chloro-l,3-dimethylpyrazole-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-l- 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-(l,l,2,2-Tetrahydroisoquinilin-7-sulphonyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-N- (2-methylphenyl)acetamide, ez 2-[4-(5-Chloro-l,3-dimethylpyrazole-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-l- yl] -N-(2-methylphenyl)acetamide, cz5-2-[4-(3,5-Dimethylisoxazole-4-sulphonyl-4-yl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide, cz ' 5'-2-[4-(2-Methanesulphonylbenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2- methylphenyl)acetamide, cis-2-[4-(3 -Cyanobenzenesulphonyl)-3 ,5-dimethylpiperazin- 1 -yl]-N-(3-methoxy-2- methylphenyl)acetamide, eti , -2-[4-(4-Methanesulphonylbenzenesulphonyl)-3 ,5-dimethylpiperazin- 1 -yl]-N-(2- methylphenyl)acetamide, cz5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiρerazin-l-yl]-N-(5-cyano-2- methylphenyl)acetamide, ct-?-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiρerazin-l-yl]-N-(5-acetamido-2- methylphenyl)acetamide, (R)-2-[4-(4-Cyanobenzenesulphonyl)-3-methylpiperazin-l-yl]-N-(quinolin-5- yl)acetamide, (S)-2-[4-(4-Cyanobenzenesulphonyl)-3-methylpiperazin-l-yl]-N-(quinolin-5- yl)acetamide, cw-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5- methanesulphonylphenyl)acetamide, cz-f-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5-(4- amino-l-piperidinyl)methyl)phenyl]acetamide, (R)-2-[4-(4-Methanesulphonylbenzenesulphonyl)-3-methylpiperazin-l-yl]-N- (quinolin-5-yl)acetamide, (R)-2-[4-(4-Acetamidobenzenesulphonyl)-3-methylpiperazin-l-yl]-N-(quinolin-5- yl)acetamide, cz ' -5 , -2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5-(l- piperazinylmethyl)phenyl)acetamide, cw-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiρerazin-l-yl]-N-(2-methyl-5-(4- piperidinylamino)methyl)phenyl)acetamide, cw-2-[4-(3-Cyanobenzenesulρhonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5-(l- morpholinyl)methyl)phenyl)acetamide, c/5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-5-(2- hydroxyethylamino)methyl)phenyl)acetamide, cw-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylρiperazin-l-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-l-yl]-N-(quinolin-5-yl)acetamide, cz5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-3-(4- amino- 1 -piperidinyl)methyl)phenyl] acetamide, cz5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-3-(4- piperidinylamino)methyl)phenyl)acetamide, ct5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-3-(l- piperazinylmethyl)phenyl)acetamide, ct5 , -2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-(2-methyl-3- (S,S)-(2,5-diazabicyclo[2.2.1 ]hept-2-yl)methyl)phenyl)acetamide, c/5-2-[4-(3-CyanobenzenesuIphonyl)-3,5-dimethylpiperazin- 1 -yl]-N-((2-methyl-3-(l - morpholinyl)methyl)phenyl)acetamide, ct5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl-3-(2- ( 1 -pyrrolidinyl)ethoxy)phenyl)acetamide, (±) cz5 , -2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl- 3 -(1 -methylpiperidin-3 -yl)methoxy)phenyl)acetamide, cz5-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl-4-(2- ( 1 -pyrrolidiny I)ethoxy)phenyl)acetamide, (±) cz ' 5'-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl- 4-( 1 -methylpiperidin-3 -yl)methoxy)phenyl)acetamide, (±) cz -2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin- 1 -yl]-N-((2-methyl- 5-(l-methylpiperidin-3-yl)methoxy)phenyl)acetamide, (+) cw-2-[4-(3-Cyanobenzenesulphonyl)-3,5-dimethylpiperazin-l-yl]-N-((2-methyl- 6-(l -methylpiperidin-3-yl)methoxy)phenyl)acetamide, and cis-2-[4-(l -Methylimidazol-4-sulphonyl-4-yl)-3,5-dimethylpiperazin- 1 -yl]-N-((2- methyl-3-(2-(l-pyrrolidinyl)ethoxy)phenyl)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 , R and R are as defined in formula (I), with a compound of general formula (III), R 3 -(SO 2 ) m -L 1 , wherein L1 represents a leaving group and m and R 3 are as defined in formula (I); or (b) when X represents a nitrogen atom and Y represents an oxygen atom, reacting a compound of general formula wherein m, R 1 , R2 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 , R2 and R 3 are as defined in formula (I), with a compound of general formula (Nil), H 2 Ν - 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 treating 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 treating 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 admimstering 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.

Inventors: BENNION COLIN, MEGHANI PREMJI, BENNION, COLIN, MEGHANI, PREMJI
Applicants: ASTRAZENECA AB, BENNION COLIN, MEGHANI PREMJI, BENNION, COLIN, MEGHANI, PREMJI
Application year: 2000
Main classification: C07D513
IPC codes: A61K31, A61P11, A61P19, A61P29, A61P31, A61P37, C07D211, C07D215, C07D217, C07D231, C07D233, C07D239, C07D241, C07D261, C07D295, C07D401, C07D403, C07D473, C07D487, C07D495, C07D513, C07D519