Adamantane derivatives are known in the art, e. g. from US-A-3,789,072 as serotonin inhibitors, from Chem. Abs. (1974), Vol. 80, No. S (26871 m) as inflammation and edema inhibitors or analgesics, from Chem. Abs. (1975), Vol. 82, No. l (3853j) and Chem. Abs.

(1977), Vol. 86, No. 17 (120855e) as antiviral agents, and also from Chem. Abs. (1968), Vol. 69, No. 1 (2562h), Chem. Abs. (1975), Vol. 82, No. 3 (165 1 Ov) and Tetrahedron (1988), 44, No. 23,7234-7242.

The P2X7 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 inflammatory/immune process, specifically, macrophages, mast cells and lymphocytes (T and B). Activation of the P2X7 receptor by extracellular nucleotides, in particular adenosine triphosphate, leads to the release of interleukin-1ß (IL-1ß) and giant cell formation (macrophages/microglial cells), degranulation (mast cells) and L-selectin shedding (lymphocytes). P2X7 receptors are also located on antigen-presenting cells (APC), keratinocytes, salivary acinar cells (parotid cells) and hepatocytes.

It would be desirable to make compound effective as P2X7 receptor antagonists for use in the treatment of inflammatory, immune or cardiovascular diseases, in the aetiologies of which the P2X7 receptor may play a role.

In accordance with the present invention, there is therefore provided a compound of general formula

wherein A represents a group CH2 or an oxygen atom; B represents a hydrogen or halogen atom (e. g. fluorine, chlorine, iodine and especially bromine); D represents a group CH2, OCH2, NHCH2 or CH2CH2, in particular a group CH2, OCH2 or NHCH2; R represents a phenyl, benzothiazolyl, indolyl, indazolyl, purinyl, pyridyl, pyrimidinyl or thiophenyl group, each of which may be optionally substituted by one or more substituents independently selected from a halogen atom or a cyano, carboxyl, hydroxyl, nitro, halo-C1-C6-alkyl,halo-C1-C6-alkyl,-N(R1)-C(=O)-R2, C3-C8-cycloalkyl,-NR5R6, 3-to 8-memberedheterocyclyl, C3-Cg-cycloalkyloxy, Cl-C6-alkylcarbonyl, phenoxy, benzyl, Cl-C6-alkylthio, phenylthio, C1-C6-alkoxycarbonyl, Cl-C6-alkylsulphinyl or Cl-C6-alkylsulphonyl group, or a Cl-C6-alkyl or Cl-C6-alkoxy group optionally substituted by one or more substituents independently selected from a halogen atom or an amino, carboxyl, hydroxyl, Cl-C6-alkoxy, (di) Cl-C6-alkylamino, Cl-C6-alkoxycarbonyl, imidazolyl, morpholinyl, piperidinyl or pyrrolidinyl group; R1 represents a hydrogen atom or a Cl-C6-alkyl or C3-Cg-cycloalkyl group; R2 represents a Cl-C6-alkyl or C3-Cg-cycloalkyl group; and R3, R4,R5 and R6 each independently represent a hydrogen atom or a Cl-C6-alkyl or C3-Cg-cycloalkyl group; with the provisos that when A is CH2, B is H and D is CH2, then R does not represent a phenyl, ortho-carboxyphenyl, methylphenyl or para-phenoxyphenyl group, and that when A is. CH2, D is CH2 or CH2CH2 and R represents a substituted phenyl group, the substituent or substituents present do not comprise, in an ortho position, a C l-C6-alkoxy

group substituted by an amino, (di) Cl-C6-alkylamino7 imidazolyl, morpholinyl, piperidinyl or pyrrolidinyl group; or a pharmaceutically acceptable salt or solvate thereof.

In the context of the present specification, unless otherwise indicated, an alkyl substituent or alkyl moiety in a substituent group may be linear or branche. Furthermore, the (cyclo) alkyl moities in a dialkylamino, dicycloalkylamino, dialkylamido or dicycloalkylamido substituent group may be the same or different. When D represents a goup OCH2 0£iCH2, the group is orientated such that the oxygen or nitrogen atom is directly attache to the adamantyl group. A 3-to 8-membered heterocyclyl group should be understood to mean an aliphatic heterocyclic ring system containing a single heteroatom selected from nitrogen, oxygen or sulphur. The term"in an ortho position"defines the ring position on the phenyl ring of R which is adjacent to the point of attachment of the amide linking group to R, e. g., as illustrated in the formula below where the asterisks devine the "ortho position" : Similarly, meta and para positions in the phenyl group R are defined relative to the point of attachment of the amide linking group to R and are indicated in the above formula by the symbols + and # respectively.

Preferably, R represents a phenyl, benzothiazolyl, indolyl, indazolyl, purinyl, pyridyl, pyrimidinyl or thiophenyl group, each of which may be optionally substituted by one, two, three or four substituents independently selected from a halogen atom (e. g. fluorine, chlorine, bromine or iodine) or a cyano, carboxyl, hydroxyl, nitro, halo-C l-C6-alkyl (e. g.

-C(O)NR3R4,-NR5R6,C3-C8-cycloalkyl(e.g.trifluoromethyl),- N(R1)-C(=O)-R2, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl), 3-to 8-membered heterocyclyl (e. g.

aziridinyl, pyrrolidinyl, piperidinyl), C3-C8-cycloalkyloxy (e. g. cyclopropyloxy, cyclobutyloxy, cyclopentyloxy or cyclohexyloxy), Cl-C6-alkylcarbonyl (e. g. methyl-, ethyl-, propyl-, butyl-, pentyl-or hexylcarbonyl), phenoxy, benzyl, C1-C6-alkylthio (e. g. methyl-, ethyl-, propyl-, butyl-, pentyl-orhexylthio), phenylthio, C1-C6-alkoxycarbonyl (e. g. methoxy-, ethoxy-, propoxy-, butoxy-, pentoxy-or hexoxycarbonyl), Cl-C6- alkylsulphinyl (e. g. methyl-, ethyl-, propyl-, butyl-, pentyl- orhexylsulphinyl), or Cl-C6- alkylsulphonyl (e. g. methyl-, ethyl-, propyl-, butyl-, pentyl- or hexylsulphonyl) group, or a C1-C6-alkyl (e. g. methyl, ethyl, propyl, butyl, pentyl or hexyl) or C1-C6-alkoxy (e. g. methoxy-, ethoxy-, propoxy-, butoxy-, pentoxy-or hexoxy) group optionally substituted by one, two, three or four substituents independently selected from a halogen atom (e. g. fluorine, chlorine, bromine or iodine) or an amino, carboxyl, hydroxyl) Cl-C6-alkoxy (e. g. methoxy, ethoxy, propoxy, butoxy, pentoxy or hexoxy), (di) C1-C6-alkylamino (e. g. (di) methylamino or (di) ethylamino), C1-C6-alkoxycarbonyl (e. g. methoxy-, ethoxy-, propoxy-, butoxy-, tert-butoxy-, pentoxy-or hexoxycarbonyl),, imidazolyl, morpholinyl, piperidinyl or pyrrolidinyl group.

More preferably, R represents a phenyl, benzothiazolyl, indolyl, indazolyl, purinyl, pyridyl or thiophenyl group, each of which may be optionally substituted by one, two or three substituents independently selected from a halogen atom (especially chlorine) or a hydroxyl, nitro or C1-C4-alkoxycarbonyl (in particular methoxycarbonyl) group, or a C1-C4-alkyl (most preferably Cl-C2-alkyl) or Cl-C4-alkoxy (most preferably Ci-C3-alkoxy) group optionally substituted by one or two substituents independently selected from a halogen atom or an amino, carboxyl, hydroxyl, Cl-C4-alkoxy (especially methoxy), (di) C I-C4-alkylamino (in particular methylamino or dimethylamino), Cl-C4-alkoxycarbonyl (especiallytert-butoxycarbonyl), imidazolyl, morpholinyl, piperidinyl or pyrrolidinyl group.

It is preferred that R1 represents a hydrogen atom or a Cl-C4-alkyl (e. g. methyl, ethyl, propyl or butyl) or C3-C6-cycloalkyl (e. g. cyclopentyl or cyclohexyl) group.

Preferably R represents a Cl-C4-alkyl (e. g. methyl, ethyl, propyl or butyl) or C3-C6-cycloalkyl (e. g. cyclopentyl or cyclohexyl) group.

Preferably, R3,R4,R5 and R6 each independently represent a hydrogen atom or a C1-C4-alkyl (e. g. methyl, ethyl, propyl or butyl) or C3-C6-cycloalkyl (e. g. cyclopentyl or cyclohexyl) group.

Preferred compound of the invention include: N-(2-Methyl-6-benzothiæolyl)-tricyclo(2-Methyl-6-benzothiæ olyl)-tricyclo [3.3.1.13 7] decane-1-acetamide, N-(3-(3-(Aminopropyloxy)-2-methylphenyl)-tricyclo(3-(3-(Amin opropyloxy)-2-methylphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, hydrochloride, N- (2-Chlorophenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, N-(2,4,5-Trimethylphenyl)-tricyclo[3.3.1.13,7]decane-1-aceta mide, N-(5-Methoxy-2-methylphenyl)-tricyclo[3.3.1.13,7]decane-1-ac etamide, N-(2,3-Dimethylphenyl)-tricyclo[3.3.1.13,7]decane-1-acetamid e, N-(5-Indolyl)-tricyclo[3.3.1.13,7]decane-1-acetamide, N-(2,3-Dimethyl-5-indolyl)-tricyclo[3.3.1.13,7]decane-1-acet amide, N-[5-(3-N,N-Dimethylaminopropoxy)-2-methylphenyl]-tricyclo[3 .3.1.13,7]decane-1- acetamide, hydrochloride, N-(5-Indæolyl)-tricyclo(5-Indæolyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, N-(6-Indæolyl)-tricyclo(6-Indæolyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, N-(5-Hydroxy-2-methylphenyl)-tricyclo[3.3.1.13,7]decane-1-ac etamide, N-(lH-Indol-4-yl)-tricyclo(lH-Indol-4-yl)-tricyclo [3.3.1.13, 7 Idecane-l-acetamide, 4-Methyl-3-[[1-oxo-2-(tricyclo[3.3.1.13,7]dec-1-yl)ethyl]ami no[phenoxy-aceticacid, hydrochloride salt, N-(1-Methyl-1H-indol-5-yl)tricyclo[3.3.1.13,7]decane-1-aceta mide, N-(1-(N, N-Dimethylamino) ethyl-lH-indo-5-yl)-tricyclo(1-(N, N-Dimethylamino) ethyl-lH-indo-5-yl)-tricyclo [3.3. 13,7]decane-1-acetamide, 5-[[1-Oxo-2-(tricyclo[3.3.1.13,7]dec-1-yl)ethyl]amino]-1H-in dole-1-aceticacid, 1,1-dimethylethyl ester, N-(3-(2-Chloropyridyl))-tricyclo(3-(2-Chloropyridyl))-tricyc lo [3.3.1. 13,7]decane-1-acetamide, N-(3-(N,(3-(N, N-Dimethylamino) methyl-lH-indo-5-yl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, N-(4-methoxy-2-methylphenyl)-tricyclo[3.3.1.13,7]decane-1-ac etamide, N- (2-Chloro-5-methoxyphenyl)-fficyclo [3.3.1. 13,7]decane-1-acetamide, N-(4-Hydroxy-2-methylphenyl)-tricyclo[3.3.1.13,7]decane-1-ac etamide,

N-(3-Hydroxymethyl-2-methylphenyl)-tricyclo[3.3.1.13,7]decan e-1-acetamide, N-(5-Methoxy-2-methyl-3-nitrophenyl)-tricyclo[3.3.1.13,7]dec ane-1-acetamide, N-(5-Hydroxymethyl-2-methylphenyl)-tricyclo(5-Hydroxymethyl- 2-methylphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, N-(3-Hydroxy-2-methylphenyl)-tricyclo[3.3.1.13,7]decane-1-ac etamide, N-(2-Methyl-5-(1-pyrrolidinemethyl)(2-Methyl-5-(1-pyrrolidin emethyl) phenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, hydrochloride, N-(2-Chloro-5-hydroxyphenyl)-tricyclo(2-Chloro-5-hydroxyphen yl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, lY (2-Chloro-4-hydroxyphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, N-(2-Methyl-3-(2-(1-pyrrolidino)ethyloxy)phenyl)-tricyclo [3.3.1.13 7] decane-1-acetamide, hydrochloride, N-(5-Methoxymethyl-2-methylphenyl)-tricyclo[3.3.1.13,7]decan e-1-acetamide, N-(2-Methyl-3-(2-(1-morpholino)ethyloxy)phenyl)-tricyclo[3.3 .1.13,7]decane-1-acetamide, hydrochloride, N-(2-Methyl-3-(2-(1-piperidino)ethyloxy)phenyl)-tricyclo[3.3 .1.13,7]decane-1-acetamide, hydrochloride, N-(2-Methyl-5-(1-morpholinomethyl)phenyl)-tricyclo [3.3.1.13 7] decane-l-acetamide, hydrochloride, N-(5-(3-(2-N, N-dimethylaminoethyl)(5-(3-(2-N, N-dimethylaminoethyl) indolyl))-tricyclo [3.3.1. 13,7]decane-1-acetamide, hydrochloride, Methyl 4-methyl-3-[[1-oxo-2-(tricyclo [3.3.1. 13,7]dec-1-yl) ethyl] amino] thiophene-2- carboxylate, N-(3-Methoxy-2-methylphenyl)-tricyclo[3.3.1.13,7]decane-1-ac etamide, N-(2-Methyl-3-(2-(1-imidazolo)ethyloxy)phenyl)-tricyclo[3.3. 1.13,7]decane-1-acetamide, N-(2,4,6-Trimethylphenyl)-tricyclo[3.3.1.13,7]decane-1-aceta mide, N-(5-(3-Aminopropyloxy)-2-methylphenyl)-tricyclo[3.3.1.13,7] decane-1-acetamide, hydrochloride, N-(5-(3-(N-Methylamino)propyloxy)-2-methylphenyl)-tricyclo[3 .3.1.13,7]decane-1- acetamide, hydrochloride, N6- (Tricyclo [3.3.1.13, 7 Idecane-I-acetyl) adenine, N-(3,5-Dimethoxy-2-methylphenyl)-tricyclo[3.3.1.13,7]decane- 1-acetamide,

N-(3-(3-(N-Methylamino)propyloxy)-2-methylphenyl)-tricyclo[3 .3.1.13,7]decane-1- acetamide, hydrochloride, N- (5- (3- (N, N-Dimethylamino) propyloxy)-2-methylphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, acetamide, hydrochloride, N- (5-Methoxy-2-methylphenyl)-tricyclo [3.3.1. 13,7]decanyloxy-1-acetamide, N-(5-Methoxy-2-methylphenyl)-(3-bromo-tricyclo(5-Methoxy-2-m ethylphenyl)-(3-bromo-tricyclo [3.3.1. 13,7]decane-1-acetamide, N-(5-Methoxy-2-methylphenyl)-(2-oxa-tricyclo(5-Methoxy-2-met hylphenyl)-(2-oxa-tricyclo [3.3.1. 13,7]decane-1-acetamide, N-(5-Methoxy-2-methylphenyl)-2-(tricyclo[3.3.1.13,7]decan-1- amino)acetamide, N (3,5-Dimethoxyphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, N (3,5-Dihydroxyphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, N (3,5-Dimethoxyphenyl)-tricyclo [3.3.1. 13,7]decanyloxy-1-acetamide, N-(3, 5-Bis-(3-aminopropyloxy)(3, 5-Bis-(3-aminopropyloxy) phenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, N-(2,4,5-Trimethylphenyl)-tricyclo [3.3.1. 13,7]decanyloxy-1-acetamide, N- (5-Hydroxy-2-methylphenyl)-tricyclo [3.3.1. 13,7]decanyloxy-1-acetamide, N-(5-(2-(N-Methylaminokthyloxy)-2-methylphenyl)-tricyclo(5-( 2-(N-Methylaminokthyloxy)-2-methylphenyl)-tricyclo [3.3.1.13 7] decane-1- acetamide, hydrochloride, N-(5-(2-(N-Methylaminokthyloxy)-2-methylphenyl)-tricyclo(5-( 2-(N-Methylaminokthyloxy)-2-methylphenyl)-tricyclo [3.3.1.13 7] decanyloxy-1- acetamide, N-(5-(3-(N-Methylamino) propyloxy)-2-methylphenyl)-tricyclo(5-(3-(N-Methylamino) propyloxy)-2-methylphenyl)-tricyclo [3.3.1. 13,7]decanyloxy-1- acetamide, and N (3,5-Dihydroxy-2-methylphenyl)-tricyclo [3.3.1. 13,7]decane-acetamide, The present invention further provides a process for the preparation of a compound of formula (I) as defined above which comprises reacting a compound of general formula

wherein L represents a leaving group (e. g. a halogen atom such as chlorine or an imidazole group) and A, B and D are as defined in formula (I), with a compound of general formula (III), R-NH2, wherein R is as defined in formula (I); and optionally forming a pharmaceutically acceptable salt or solvate thereof.

The process may conveniently be carried out in a solvent (e. g. acetonitrile, N, N-dimethylformamide or dichloromethane) and optionally in the presence of a base (e. g. triethylamine, 4-dimethylaminopyridine or diisopropylethylamine). The process is conveniently operated at a temperature in the range from 0 to 100 °C, preferably in the range from 10 to 80 °C, and especially at ambient temperature (20 °C).

The compound of formula (ici) and (III) are known compound or may be prepared by processes analogous to those known in the art.

It will be appreciated by those skilled in the art that in the process of the present invention certain functional groups such as hydroxyl or amino groups in the intermediate compound may need to be protected by protecting groups. Thus, the final stage in the preparation of the compound of formula (I) may involve 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).

The compound 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, fumarate, maleate, tartrate, citrate, oxalate, methanesulphonate or p-toluenesulphonate, or an alkali metal salt such as a sodium or potassium salt.

Certain compound of formula (I) are capable of existing in stereoisomeric forms. It will be understood that the invention encompasses all geometric and optical isorners of the compound of formula (I) and mixtures thereof including racemates. Tautomers and mixtures thereof also form an aspect of the present invention.

The compound of the present invention are advantageous in that they possess pharmacological activity. They are therefore indicated as pharmaceuticals for use in the treatment or prevention of rheumatoid arthritis, osteoarthritis, psoriasis, allergic dermatitis, asthma, hyperresponsiveness of the airway, septic shock, glomerulonephritis, irritable bowel disease, Crohn's disease, ulcerative colitis, atherosclerosis, growth and metastases of alignant cells, myocardial ischaemia, myoblastic leukaemia, diabetes, Alzheimer's disease, osteoporosis, burn injury, stroke, varicose veins and meningitis.

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.

The invention further provides a method of effecting immunosuppression (e. g. in the treatment of rheumatoid arthritis, irritable bowel disease, atherosclerosis or psoriasis) 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 disorder indicated.

The compound 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 of the 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 of the 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 tables, 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 be further understood by reference to the following illustrative examples in which the terms MS, NMR, CDC13 and DMSO denote respectively mass spectrometry, nuclear magnetic resonance, chloroformd and dimethylsulphoxide.

Example 1 N-(2-Methyl-6-benzothiazolyl)-tricyclo(2-Methyl-6-benzothiaz olyl)-tricyclo [3.3.1.13'7] decane-l-acetamide a) 1-Adamantaneacetyl chloride A solution of 1-adamantaneacetic acid (4.5 g) in thionyl chloride (20 ml) was heated at reflux temperature for 24 hours and then allowed to cool to ambient temperature. The excess thionyl chloride was removed under reduced pressure to leave the sub-title compound as a syrup (4.9 g).

b) N-(2-Methyl-6-benzothiazolyl)-tricyclo [3.3.1.13o7] decane-1-acetamide To a solution of 1-adamantaneacetyl chloride (0.5 g) prepared as described in a) above in acetonitrile (10 ml) was added triethylamine (0.38 ml) and 6-amino-2- methylbenzothiazole (0.39 g). The rection mixture was stirred at ambient temperature for 1 hour before being diluted with ethyl acetate. The organic phase was then washed with dilute hydrochloric acid and water, dried over magnesium sulphate (MgSO4) and finally concentrated under reduced pressure to give the title compound as a white solid (0.12 g).

Melting point: 172 °C MS (APCI +ve) 341 (M+H) + <BR> <BR> <BR> H NMR (CDCl3) 6 458. (1H, d), 7.84 (1 H, d), 7.19 (2H, m), 2.81 (3H, s), 2.13 (2H, s), 2.00 (3H, s), 1.75 (12H, m) Example 2 N-(3-(3-(Aminopropyloxy)-2-methylphenyl)-tricyclo(3-(3-(Amin opropyloxy)-2-methylphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, hydrochloride Diethyl azodicarboxylate (1.0 ml) was added to a solution of N-(3-hydroxy-2- methylphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, (0.408 g, Example 26), tert-butyl N- (3-hydroxypropyl) carbamate (1.11 g) and triphenylphosphine (1.74 g) in tetrahydrofuran (5 ml). After stirring overnight at room temperature the rection mixture was concentrated under reduced pressure. The residue was purifie by column chromatography over silica eluting with dichloromethane: ethyl acetate (9: 1) and then further purifie by HPLC over a Dynamax# column using a Waters Prep 4000 eluting with iso-hexane: ethyl acetate (7: 3) to give the Mitsunobu rection product (0.34 g) which was dissolve in methanol (10 mol).

A solution of hydrogen chloride (generated by slow addition of acetyl chloride (12 ml) to

methanol (10 ml) at 0°C CARE-Very Exothermic) was then added to the latter solution and the rection stirred at room temperature for 2 hours. The rection was partitioned between saturated aqueous sodium hydrogen carbonate (100 ml) and extracted with ethyl acetate (100 ml). The organic extract was dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The residue was purifie by silica gel chromatography eluting with dichloromethane: ethanol: triethylamine (18: 2: 1) to give a yellow oil. The latter was dissolve in methanol (10 ml) and dichloromethane (2 ml) and reaed with an ethereal solution of hydrogen chloride (1M, 5 ml). After 2 minutes the solvents were removed under reduced pressure. The residual gum was stirred in ether: iso- hexane (1: 1) overnight, the solvent removed by filtration to leave the title compound as a solid (0.186 g) which was isolated by decanting the solvent then drying the residue.

MS (APCI +ve) 357 (M-HCl+H) + IH NMR (DMSO-d6) õ 9.20 (1H, s), 7.97 (3H, bs), 7.10 (1H, t), 6.94 (1H, d), 6.77 (1H, d), 4.05 (2H, t), 3.05-2.9 (2H, m), 2.1-2.0 (7H, ion), 1.94 (3H, s), 1.75-1.55 (12H, ion).

Example 3 N-(2-Chlorophenyl)-tricyclo(2-Chlorophenyl)-tricyclo [3.3.1.13h7] decane-1-acetamide Prepared according to the method of Example 1 b) from 1-adamantaneacetyl chloride (0.2 g) and 2-chlorolaniline (0.12 g) to give the title compound as a white solid (0.05 g).

Melting point: 122-124 °C MS (APCI +ve) 304/306 (M+H) + EI NMR (CDC13) 8 8.40 (1H, d), 7. 55 (1H, s), 7.40 (1H, dd), 7.3 (1H, m), 7.05 (1H, m), 2.16 (2H, s), 2.00 (3H, s), 1.75 (12H, m)

Example 4 N-(2, 4,5-Trimethylphenyl)-tricyclo [3.3.1.13'7] decane-1-acetamide Prepared according to the method of Example lb) from 1-adamantaneacetyl chloride (0.2 g) and 2,4,5-trimethylaniline (0.13 g) to give the title compound as a white solid (0.042 g).

Melting point: 158 °C MS (APCI +ve) 312 (M+H) + 1H NMR (DMSO-d6) õ 9.00 (1H, s), 7.08 (1H, s), 6.94 (1H, s), 2.14 (6H, s), 2.10 (3H, s), 2.04 (2H, s), 1.98 (3H, s), 1.75 (12H, m) Example.5 N-(5-Methoxy-2-methylphenyl)-tricyclo[3.3.1.13,7]decane-1-ac etamide, Prepared according to the method of Example lb) from 1-adamantaneacetyl chloride (0.2 g) and 5-methoxy-2-methylaniline (0.13 g) to give the title compound as a white solid (0.043 g).

Melting point: 147 °C MS (APCI +ve) 314 (M+H)+

1H NMR (DMSO-d6) 9.00 (1H, s), 7.07 (1H, d), 7.04 (1H, d), 6.65 (1H, dd), 3.69 (3H, s), 2.13 (3H, s), 2.09 (2H, s), 1.95 (3H, s), 1.75 (12H, m) Example 6 N-(2,3-Dimethylphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, Prepared according to the method of Example lb) from 1-adamantaneacetyl chloride (0.2 g) and 2,3-dimethylaniline (0.11 g) to give the tille compound as a white solid (0.034 g).

Melting point: 170 °C +ve)298(M+H)+MS(APCl 1H NMR (DMSO-d6) 8 209. (1H, s), 7.20-6.95 (3H, m), 2.23 (3H, s), 2.07 (5H, s), 1.95 (3H, s), 1.75 (12H, m) Example 7 N-(5-Indolyl)-tricyclo[3.3.1.13,7]decane-1-acetamide, Prepared according to the method of Example I b) from 1-adamantaneacetyl chloride (0.076 g) and 5-aminoindole (0.05 g) to give the title compound as a white solid (0.05 g).

Melting point: 184-185 °C

MS (APCI +ve) 309 (M+H) + H NMR (DMSO-d6) õ 10.95 (1H, s), 9.51 (1H, s), 7.85 (1H, s), 7.28 (2H, m), 7.16 (1H, dd), 6.35 (1H, t), 2.04 (2H, s), 1.94 (3H, s), 1.70-1.50 (12H, m) Example 8 N-(2, 3-Dimethyl-5-indolyl)-tricyclo [3.3.1.13, 7 Idecane-l-acetamide To a solution of 1-adamantaneacetic acid (0.30 g) in dichloromethane (10 ml) were added 4-dimethylaminopyridine (0.19 g) and 1- (3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride (0.30 g). The rection mixture was stirred for 0.5 hour before addition of 5-amino-2,3-dimethylindole (0.25 g). Stirring was then continue overnight at ambient temperature. The next day the rection mixture was washed with dilute hydrochloric acid, water and brine, dried over sodium sulphate (Na2SO4) and finally concentrated under reduced pressure to leave a residue. Purification of the residue by silica gel chromatography, eluting with 40% ethyl acetate in isohexanes, gave the title compound as a white solid (0.14 g).

Melting point: 234-235 °C MS (APCI +ve) 337 (M+H) + 1H NMR (DMSO-d6) õ 10.50 (1H, s), 9.46 (1H, s), 7.67 (1H, s), 7.08 (2H, m), 2.28 (3H, s), 2.03 (3H, s), 1.99 (2H, s), 1.94 (3H, s), 1.70-1.50 (12H, m)

Example 9 N [5- (3-N, N Dimethylaminopropoxy)-2-methylphenyl]-tricyclo [3.3.1. 13,7]decane-1- acetamide, hydrochloride To a solution of N-(5-methoxy-2-methylphenyl)-tricycol [3.3.1. 13,7]decane-1- acetamide prepared as described in Example 5 (1.00 g) in dichloromethane (20 ml) was added borontribromide (4 ml of a 1. OM solution in dichloromethane) ay -78ïC under an inert atmosphere. The rection mixture was stirred for 24 hours and then warmed to ambient temperature and washed with brine. The organic layer was then dried over magnesium sulphate (MgS04) and concentrated under reduced pressure to yield a residue.

To a solution of the residue (200 mg) in N, N dimethylformamide (10 ml) were added . potassium carbonate (0.185 g) andN, N-dimethyl-3-chloropropylamine hydrochloride (0.11 g) and the rection mixture was heated, with stirring, to 80°C for 4 hours. Once cooled, the rection mixture was diluted with ethyl acetate and washed with saturated brine. The organic phase was separated, dried over magnesium sulphate (MgSO4) and then passed through an"ISOLUTE" (trade mark) NH2 solid phase extraction cartridge, eluting with ethyl acetate. Evaporation of the eluant, followed by treatment with 1. 0M hydrogen chloride in ether and finally concentration under reduced pressure gave the title compound as a white solid (0.02 g).

Melting point: 139-140 °C MS (APCI +ve) 385 (M+H) + (for free base) IH NMR (DMSO-d6) 8 3810. (1H, s), 9.05 (1H, s), 7.08 (2H, d+s), 3.95 (4H, m), 3.2 (2H, m), 2.78 (6H, 2s), 2.13 (3H, s), 2.10 (2H, s), 1.95 (3H, s), 1.6 (12H, m)

Example 10 N-(5-Indazolyl)-tricyclof3.(5-Indazolyl)-tricyclof3. 3.1. 13,7]decane-1-acetamide, Prepared according to the method of Example lb) from 1-adamantaneacetyl chloride (0.1 g) and 5-aminoindazole (0.067 g) to give the title compound as a white solid (0.12 g).

Melting point: 265 °C MS (APCI +ve) 310 (M+H) + 1H NMR (DMSO-d6) 8 12.93 (1H, s), 9.73 (1H, s), 8.12 (1H, s), 7.99 (1H, s), 7.40 (2H, m), 2.04 (2H, s), 1.94 (3H, s), 1.70-1.50 (12H, m) Example 11 N-(6-Indazolyl)-tricyclo(6-Indazolyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, Prepared according to the method of Example lb) from l-adamantaneacetyl chloride (0.2 g) and 6-aminoindazole (0.13 g) to give the title compound as a white solid (0.064 g).

Melting point: 245 °C MS (APCI +ve) 310 (M+H) + lHNMR (DMSO-d6) o 12.84 (1H, s), 9.87 (1H, s), 8.16 (1H, s), 7.94 (1H, s), 7.62 (1H, d), 7.05 (1H dd), 2.04 (2H, s), 1.94 (3H, s), 1.70-1.50 (12H, m)

Example 12 N-(5-Hydroxy-2-methylphenyl)-tricyclo[3.3.1.13,7]decane-1-ac etamide, To a solution of N (5-methoxy-2-methylphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, prepared as described in Example 5 (1.00 g) in dichloromethane (20 ml), was added boron tribromide (4 ml of a 1. 0M solution in dichloromethane) at -78°C under an inert atmosphere. The rection mixture was stirred for 24 hours and then warmed to ambient temperature and washed with brine. The organic layer was dried over magnesium sulphate (MgSO4) and concentrated under reduced pressure to yield a residue. Trituration with diethyl ether gave a solid (0.335g). A portion of this material (0. 050g) was further purifie by Supercritical Fluid chromatography using a Cyano column, eluting with a gradient of methanol in supercritical carbon dioxide to give the title compound as a white solid.

(0.030g) Melting point: 255-256 °C MS (APCI +ve) 300 (M+H) 1H NMR (DMSO-d6) 8 9.11 (1H, s), 8.92 (1H, s), 6.92 (1H, m), 6.45 (lH, dd), 2.04 (5H, s), 1.94 (3H, s), 1.70-1.50 (12H, m)

Example 13 N-(1H-Indol-4-yl)-tricyclo[3.3.1.13'7] decane-l-acetamide Prepared according to the method of Example 1b) from 1-adamantaneacetyl chloride (0.074 g) and 4-aminoindole hydrochloride (0.059 g) to give the title compound as a white solid (0.068 g).

Melting point: 211-213 °C MS (APCI +ve) 309 (M+H) + H NMR (DMSO-d6) õ 11.07 (1H, s), 9.35 (1H, s), 7. 53 (1H, d), 7.27 (1H, t), 7.12 (1H, d), 6.99 (1H, t), 6.66 (1H, s), 2.19 (2H, s), 1.94 (3H, s), 1.68 (6H, d), 1.68-1.58 (6H, m).

Example 14 4-Methyl-3-[[1-oxo-2-(tricyclo[3.3.1.13,7]dec-1-yl]amino]phe noxy-aceticacid, hvdrochloride salt To a solution of N-(5-Hydroxy-2-methylphenyl)-tricyclo [3.3.1.137] decane-1-acetamide from Example 12 (0.20 g) was added potassium carbonate (0.106g) and ethyl bromoacetate (0. 3ml). The rection mixture was stirred and heated at 80°C for 24 hours. Once cooled, the rection mixture was diluted with ethyl acetate and washed with saturated brine. The organic phase was separated, dried over magnesium sulphate (MgSO4) and evaporated

under reduced pressure to leave a residue which was purifie by silica gel chromatography eluting with iso-hexane/diethyl ether (1: 1) to give a white solid. The solid was dissolve in dioxane (20mol) and the solution treated with 2M sodium hydroxide solution, the rection mixture was stirred at ambient temperature for 24 hours, acidifie (2M hydrochloric acid) and extracted into ethyl acetate. The organic phase was washed with brine, dried over magnesium sulphate (MgS04) and evaporated under reduced pressure. The residue was triturated with diethyl ether to leave the title compound as a white solid (0.070g).

Melting point: 204-205 °C MS (APCI +ve) 358 (M+H) + IH NMR (DMSO-d6) 6 9512. (1H, s), 9.03 (1H, s), 7.05 (2H, m), 6.60 (lH, dd), 4.58 (2H, s), 2.12 (3H, s), 2.090 (2H, s), 1.94 (3H, s), 1.70-1.50 (12H, m) Example 15 N-(1-Methyl-lH-indol-5-yl)-tricyclo(1-Methyl-lH-indol-5-yl)- tricyclo [3.3.1.13'7] decane-1-acetamide a) 1-Methyl-5-nitro-lH-indole To a solution of 5-nitroindole (0.20 g) in tetrahydrofuran (2 ml) was added sodium hydride (0.06 g of 60% dispersion in oil) and evolution of gas noted. After stirring for 30 min methyl iodide (0.086 ml) was added to the dark brown rection mixture and the rection mixture heated to 65 °C for 2 hr before cooling to room temperature and partitioning between dichloromethane and water. Organic phase separated, washed with sodium thiosulphate solution, dried (Na2SO4) and concentrated to leave sub-title compound as a yellow solid (0.20 g).

IH NMR (DMSO-d6) 8 8.58 (1H, d), 8.04 (1H, dd), 7.65 (1H, d), 7.61 (1H, d), 6.75 (1H, dd), 3.88 (3H, s). b) N-(1-Methyl-1H-indol-5-yl)-tricyclo[3.3.1.13,7]decane-1-acet amide, To a solution of 1-methyl-5-nitroindole from step a) (0.11 g) in ethanol (10 ml) was added 10% palladium on carbon (0.023 g) and resulting suspension stirred under 4 bar pressure of hydrogen for 0.75 h before filtering off the catalyst and concentration at reduced pressure. The resulting residue was condense with 1-adamantneacetyl chloride (0.10 g) according to the method of Example lb) to give the title compound as a white solid (0.11 g).

Melting point: 183-184 °C MS (APCI +ve) 323 (M+H) + 1H NMR (DMSO-d6) õ 9.55 (1H, s), 7.87 (1H, d), 7. 32 (1H, d), 7.26 (1H, d), <BR> <BR> <BR> <BR> <BR> 7.23 (1H, dd), 6.34 (1H, dd), 3.75 (3H, s), 2.04 (2H, s), 1.94 (3H, s), 1.75-1.50 (12H, m).

Example 16 N-(1-(N, N-Dimethylamino) ethyl-lH-indo-5-yl)-tricyclo(1-(N, N-Dimethylamino) ethyl-lH-indo-5-yl)-tricyclo [3.3.1.13'7] decane-1-acetamide a) 1- (N, N-Dimethylamino) ethyl-5-nitro-1H-indole Prepared according to the method of Example 15a) from 5-nitroindole (0.217 g) and dimethylaminoethyl chloride hydrochloride (0.21 g) to leave sub-title compound as an orange/brown solid (0.24 g).

H NMR (DMSO-d6) å 8.56 (1H, d), 8.02 (1H, dd), 7.71 (1H, d), 7.61 (1H, d), 6.74 (1H, dd), 4.35 (2H) t), 2.62 (2H, t), 2.17 (6H, s).

b) N-(1-N,N-Dimethylamino)ethyl-1H-indo-5-yl)-tricyclo[3.3.1.13 ,7]decane-1- acetamide Prepared according to the method of Example 15b) from 1- (N, N-dimethylamino) ethyl- 5-nitroindole (0.23 g) and 1-adamantaneacetyl chloride (0.21 g) to give the title compound as a white solid (0.22 g).

Melting point: 125-127 °C MS (APCI +ve) 380 (M+H) + 1H NMR (DMSO-d6) # 9.5 4 (1H, s), 7.85 (1H, d), 7.36 (1H, d), 7.32 (1H, d), 7.20 (1 H, dd), 6.33 (1H, d), 4,20 (2H, t), 2.58 (2H, t), 2.17 (6H, s), 2.04 (2H, s), 1.94 (3H, s), 1.65 (12H, m).

Example 17 5-[[1-Oxo-2-(tricyclo[3.3.1.13,7]dec-1-yl)ethyl]amino]-1H-in dole-1-aceticacid, 1,1-dimethylethylester a) 5-Nitro-1F1-indole-1-acetic acid, 1, 1-dimethylethyl ester Prepared according to the method of Example 15a) from 5-nitroindole (0.207 g) and 2- bromoaceticacid, 1,1-diemthylethyl ester (0.23 ml) to leave sub-title compound as a yellow oily solid (0.29 g).

H NMR (DMSO-d6) å 8. 58 (1H, d), 8.04 (1H, dd), 7.60 (2H, m), 6.77 (1H, dd), 3.15 (2H, s), 1.42 (9H, s)

b) 5- ( [1-Oxo-2- (tricyclo [3.3.1. 13,7]dec-1-yl) ethyl] amino]-1H-indole-1-acetic acid, 1,1-diinethylethyl ester Prepared according to the method of Example 15b) from 5-nitro-lH-indole-1-acetic acid, 1,1-dimethylethyl ester (0.29 g) and 1-adamantaneacetyl chloride (0.20 g) to give the title compound as a white solid (0.24 g).

Melting point: 199 °C MS (APCI +ve) 423 (M+H) + 1H NMR (DMSO-d6) 8 9.56 (1H, s), 7.86 (1H, d), 7.27 (1H, d), 7.22 (2H, m), 6.38 (1H, d), 4.94 (2H, s), 2.04 (2H, s), 1.94 (3H, s), 1.65 (12H, m), 1.41 (9H, s).

Example 18 N (3- (2-Chloropyridyl))-tricyclo [3.3.1. 13,7]decane-1-acetamide, Prepared according to the method of Example lb) from 1-adamantaneacetyl chloride (0. 5g) and 2-chloro-3-aminopyridine (0.31 g) to give the title compound as a white solid (0.27 g).

Melting point: 135-136 °C MS (APCI +ve) 305 (M+H) + IH NMR (DMSO-d6) å 9.51 (1 H, s), 8.22 (1 H, dd), 8.15 (1H, dd), 7.4 (1H, dd), 2.20 (2H, s), 1.98 (3H, s), 1.60 (12H, m) Example 19 N-(3-(N,N-Dimethylamino)methyl-1H-indo-5-yl)-tricyclo[3.3.1. 13,7]decane-1- acetamide

To a suspension of indole amide from Example 7 (0.163 g) in acetic acid (0.20 ml) was added aqueous dimethylamine (0.065 ml of a 40% solution), aqueous formaldehyde (0.043 ml of a 37% solution) and acetic acid (0.10 ml) and resulting rection mixture heated to 60 OC for 2 hr before cooling to 0-5 °C. Rection mixture made alkaline by addition of aqueous ammonia solution and partitioned between ethyl acetate and water.

Organic phase separated, washed with brine, dried (Na2S04) and concenetrated and residue <BR> <BR> <BR> purifie by chromatography on A1203 eluting with 0-10% methanol in dichloromethane to give the title compound as a brown solid (0.07 g).

Melting point: 194-213 °C (dec.) MS (APCI +ve) 366 (M+H) + H NMR (DMSO-d6) å 11.24 (1H, s), 9.62 (1H, s), 8.00 (1H, s), 7.46 (1H, d), 7.32 (1H, d), 7.21 (1H, dd), 4.12 (2H, br s), 2.55 (6H, s), 2.06 (2H, s), 1.94 (3H, s), 1.70-1.58 (12H, m).

Example 20 N (4-Methoxy-2-methylphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide Prepared according to the method of Example I b) from 1-adamantaneacetyl chloride (2.0g) and 4-methoxy-2-methylaniline (1.29 g) to give the title compound as a white solid (1.37 g).

Melting point: 156-157 °C MS (APCI +ve) 314 (M+H) + IH NMR (DMSO-d6) 8 9.01 (lH, s), 7.15 (1H, d), 6.80 (1H, d), 6.7 (1H, dd), 3.7 (3H, s), 2.20 (3H, s), 2.05 (2H, s), 1.95 (3H, s), 1.60 (12H, m) Example 21 N-(2-Chloro-5-methoxyphenyl)-tricyclo[3.3.1.13,7]decane-1-ac etamide, Prepared according to the method of Example lb) from 1-adamantaneacetyl chloride (2.0g) and 2-chloro-5-methoxyaniline (1.49 g) to give the title compound as a white solid (0.60 g).

Melting point: 122-123 °C MS (APCI +ve) 334 (M+H) +

IH NMR (DMSO-d6) õ 9.20 (1H, s), 7.36 (2H, m), 6.76 (1H, dd), 6.7 (1H, dd), 3.73 (3H, s), 2.20 (2H, s), 1.95 (3H, s), 1.60 (12H, m) Example22 N (4-Hydroxy-2-methylphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, To a solution of N- (4-Methoxy-2-methylphenyl)-tricyclo [3.3. 13,7]decane-1- acetamide from Example 20 (1.20 g) in dichloromethane (50 ml) at-78 °C was added boron tribromide (4 ml of a 1. OM solution in dichloromethane) under an inert atmosphere.

The rection mixture was stirred for 24 hours and then warmed to ambient temperature and washed with brine. The organic layer was then dried over magnesium sulphate (MgSO4) and concentrated vider reduced pressure to yield a residue which was purifie by silica gel chromatography eluting with iso-hexane/diethyl ether (1: 1) to give the title compound as a white solid. (0.54g) Melting point: 205-206 °C MS (APCI +ve) 300 (M+H) + 1H NMR (DMSO-d6) 8 9.15 (1H, s), 8.91 (1H, s), 7.00 (1H, d), 6.54 (2H, m), 2.53 (3H, s), 2.03 (2H, s), 1.94 (3H, s), 1.70-1.50 (12H, m)

Example 23 N-(3-Hydroxymethyl-2-methylphenyl)-tricyclo[3.3.1.13,7]decan e-1-acetamide, Prepared according to the method of Example lb) from 1-adamantaneacetyl chloride (2.0g) and 3-amino-2-methylbenzyl alcohol (1.29 g). Silica gel chromatography, eluting with 5% ethylacetate in dichloromethane gave the title compound as a white solid (0.80g).

Melting point: 205-206 °C MS (APCI +ve) 314 (M+H) + IH NMR (DMSO-d6) õ 9.16 (1H, s), 7.20-7.05 (3H, m), 5.07 (1H, bs), 4.47 (2H, s), 2.09 (2H, s), 2.08 (3H, s), 1.95 (3H, s), 1.60 (12H, m) Example 24 N (5-Methoxy-2-methyl-3-nitrophenyl)-tricyclo[3.3.1.13'7] decane 1 acetamide Prepared according to the method of Example lb) from 1-adamantaneacetyl chloride (2.0g) and 5-methoxy-2-methyl-4-nitroaniline (1.71 g). Silica gel chromatography, eluting with iso-hexane/diethyl ether (1: 1), gave the title compound as a yellow solid (1.10 g).

Melting point: 141-142 °C MS (APCI +ve) 359 (M+H) +

IH NMR (DMSO-d6) 6 269. (1H, s), 7.82 (1H, s), 7.76 (1H, s), 3.86 (3H, s), 2.23 (3H, s), 2.08 (2H, s), 1.95 (3H, s), 1.60 (12H, m) Example25 N (5-Hydroxymethyl-2-methylphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, Prepared according to the method of Example 1b) from 1-adamantaneacetyl chloride (2.0g) and 3-amino-4-methylbenzyl alcohol (1.29 g). Silica gel chromatography, eluting with 5% ethylacetate in dichloromethane gave the title compound as a white solid (1. 10 g).

Melting point: 190 °C MS (APCI +ve) 314 (M+H) + IH NMR (DMSO-d6) 8 8.54 (1H, bs), 7.46 (1H, s), 7.1 (2H, m), 4.70 (1H, bs), 4.54 (2H, d), 2.24 (3H, s), 2.15 (2H, s), 2.0 (3H, s), 1.70 (12H, m) Example 26 N (3 Hydroxy 2 methylphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, Prepared according to the method of Example lb) from 1-adamantaneacetyl chloride (0. 81) and 3-amino-2-methylphenol (0.5 g) to give the title compound as a white solid (0.5g).

Melting point: 211 °C MS (APCI +ve) 300 (M+H) + HNMR (DMSO-d6) 5 9.28 (1H, bs), 9. 04 (1H, bs), 6.91 (lH, t), 6.8 (1H, d), 6.6 (1H, d), 2.05 (2H, s), 1.98 (3H, S) 1.94 (3H, bs), 1.6 (12H, m) Example 27 N (2-Methyl-5- (1-pyrrolidinemethyl) phenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, hydrochloride To a solution of N-(5-Hydroxymethyl-2-methylphenyl)-tricyclo [3.3.1. 13,7]decane-1- acetamide from Example 25) (1.0 g) in acetonitrile was added triphenylphosphine (0.93g) and carbon tetrabromide (1.2g). The rection mixture was stirred at ambient temperature for 24 hours and evaporated under reduced pressure. The residue was purifie by silica gel chromatography eluting with iso-hexane/diethyl ether to give a white solid. A portion (O. lg) of the solid was dissolve in acetonitrile (3ml) and treated with pyrrolidine (0. 2ml).

The rection mixture was stirred and heated at 80°C for 24 hours. Once cooled, the rection mixture was diluted with ethyl acetate and washed with saturated brine. The organic phase was separated, dried over magnesium sulphate (MgSO4), treated with a solution of hydrogen chloride in diethyl ether (1ml of 1. OM) and evaporated under reduced pressure to leave a residue which was triturated with iso-hexane to give the title compound as an off-white solid. (0.030g) Melting point: 214-215 °C MS (APCI +ve) 367 (M+H) + for free base.

1H NMR (DMSO-d6) 6 229. (1H, s), 7.60 (1H, s), 7.27 (2H, s), 4.27 (2H, d), 3.35 (2H, m), 3.05 (2H, m), 2.21 (3H, s), 2.1 (2H, s), 2.0-1.8 (7H, m), 1.60 (12H, m) Example28 N-(2-Chloro-5-hydroxyphenyl)-tricyclo[3.3.1.13,7]decane-1-ac etamide, Prepared according to the method of Example I b) from 1-adamantaneacetyl chloride (2.9g) and 2-chloro-4-hydroxyaniline (2. 0 g). Silica gel chromatography, eluting with 30% diethyl ether in iso-hexane, followed by recrystallisation from acetonitrile gave the title compound as a white solid (0.15 g).

Melting point: 224-225 °C MS (APCI +ve) 320 (M+H) + <BR> <BR> 1H NMR (DMS O-ds) 8 769. (1H, s), 9.14 (1H, s), 7.26 (1H, d), 6.83 (1H, d), 6.69 (1H, dd), 2.05 (2H, s), 1.95 (3H, s), 1.60 (12H, m) Example 29 N-(2-Chloro-4-hydroxyphenyl)-tricyclo[3.3.1.13,7]decane-1-ac etamide, Prepared according to the method of Example lb) from 1-adamantaneacetyl chloride (2. 9 g) and 2-chloro-4-hydroxyaniline to give the title compound as a white solid. (0.15g).

Melting point: 224-225 °C MS (APCI +ve) 320 (M+H) + IH NMR (DMSO-d6) 8 659. (1H, s), 9.09 (1H, s), 7.23 (2H, m), 6.55 (1H, dd), 2.20 (2H, s), 1.95 (3H, s), 1.60 (12H, m) Example30 N"(2-Methyl-3-(2-(l-pyrrolidino)(2-Methyl-3-(2-(l-pyrrolidin o) ethyloxy) phenyl)-tricyclo [3.3.1.13w7] decane-l-<BR> <BR> <BR> <BR> scetamide,hydrochloride To a solution of N (3-Hydroxy-2-methylphenyl)-tricyclo [3.3.1.13 ;] decane-l-acetamide from Example 26 (0.060g), in acetonitrile (3mol), was added caesium carbonate (0.196g) and N- (2-chloroethyl)-pyrrolidine hydrochloride (0.068g). The rection mixture was stirred and heated at 80°C for 24 hours. After cooling, the rection mixture was diluted with ethyl acetate and washed with water. The organic phase was dried over magnesium sulphate and evaporated under reduced pressure to leave a residue which was purifie by Supercritical Fluid Chromatography using a gradient elution of 0.1 % v/v solution of diethylamine in methanol and supercritical carbon dioxide on a Cyano column. The pure product was dissolve in dichloromethane, treated with l. OM solution of hydrogen chloride in diethyl ether and evaporated under reduced pressure to leave the title compound as a white solid. (0.010g) Melting point: 105-106 OC MS (APCI +ve) 397 (M+H) for free base.

IH NMR (DMSO-d6) õ 9.22 (1H, s), 7.12 (1H, t), 6.97 (1H, d), 6.81 (1H, d), 4.30 (2H, t), 3.60 (4H, m), 3.10 (2H, m), 2.05 (6H, s), 1.95 (6H, m), 1.60 (12H, m)

Example 31 N-(S-Methoxymethyl-2-methylphenyl)-tricyclo(S-Methoxymethyl- 2-methylphenyl)-tricyclo [3.3.1.13'7] decane-l-acetamide To a solution of the benzyl bromide prepared in Example 27 (0.10 g) in methanol (5ml) and added sodium methoxide (0.020g). The rection mixture was stirred at ambient temperature for 2 hours then evaporated under reduced pressure to leave a residue which was dissolve in ethyl acetate and washed with 2M hydrochloric acid. The organic phase was dried over magnesium sulphate and evaporated under reduced pressure, the residue was triturated with diethyl ether to yield the title compound as a white solid. (0.015g) Melting point: 127-128 °C MS (APCI +ve) 328 (M+H) + 1H NMR (DMSO-d6) 8 9.10 (1H, s), 7.33 (lH, s), 7.15 (lH, d), 6.99 (1H, d), 4. 34 (2H, s), 2.20 (3H, s), 2.10 (2H, s), 1.95 (6H, m), 1.60 (12H, m)

Example 32 N (2-Methyl-3- (2- (1-morpholinothyloxy) phenyl)-tricyclo[3.3.1.13'7] decane-l- acetamide, hydrochloride Prepared according to the method of Example 30 from N-(3-Hydroxy-2- methylphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide (0.060g) and N-(2-chloroethyl)- morpholine hydrochloride (0.075g) to give the title compound as a white solid. (0.024g).

Melting point: 195-197 °C MS (APCI +ve) 413 (M+H) + for free base.

IH NMR (DMSO-d6) 8 3611. (1H, bs), 9.23 (1H, s), 7.15 (1H, t), 6.99 (1H, d), 6.83 (1H, d), 4.42 (2H, t), 4.10-3.0 (12H, m), 2.08 (2H, s), 2.07 (3H, s), 1.95 (3H, s), 1.60 (12H, m) Example 33 N-(2-Methyl-3-(2-(1-piperidino)(2-Methyl-3-(2-(1-piperidino) ethyloxy) phenyl)-tricyclo [3.3.1.13t7] decane-1- acetamide, hydrochloride Prepared according to the method of Example 30 from N-(3-Hydroxy-2- methylphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide (0.060g) and N- (2-chloroethyl)- piperidine hydrochloride (0.074g) to give the title compound as a white solid (0.036g).

Melting point: 105-106 °C MS (APCI +ve) 412 (M+H) + for free base.

IH NMR (DMSO-d6) 8 10.62 (1H, bs), 9.24 (1H, s), 7.12 (1H, t), 6.97 (1 H, d), 6.82 (1 H, d), 4.42 (2H, t), 3.50 (4H, m), 3.05 (2H, m), 2.10 (2H, s), 2.05 (3H, s), 2.0 (3H, s), 1.90-1.50 (18H, m) Example 34 N-(2-Methyl-5-(1-morpholinomethyl)(2-Methyl-5-(1-morpholinom ethyl) phenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide, hydrochloride Prepared according to the method of Example 27 from N-(5-Hydroxymethyl-2- methylphenyl)-tricyclo [3.3.1.13'7] decane-l-acetamide andmorpholine hydrochloride (0. 040ml). Purification by Supercritical Fluid chromatography using a gradient elution of 0.1 % v/v solution of diethylamine in methanol and supercritical carbon dioxide on a Cyano column gave the pure product which was dissolve in dichloromethane, treated with 1. OM solution of hydrogen chloride in diethyl ether and evaporated under reduced pressure to leave the title compound as a white solid (0.085g).

Melting point: 204-205 °C MS (APCI +ve) 384 (M+H) + for free base.

1H NMR (DMSO-d6) 8 9.22 (1H, s), 7.60 (1H, s), 7.27 (2H, s), 4.30 (2H, d), 4.0 (2H, m), 3.8-3.6 (4H, m), 3.40-2.8 (7H, m), 2.25 (3H, s), 2.15 (2H, s), 2.0 (3H, s), 1.60 (12H, m) Example 35 N-(5-(3-(2-N, N-dimethylaminoethyl)(5-(3-(2-N, N-dimethylaminoethyl) indolyl))-tricyclo [3.3.1. 13,7]decane-1-acetamide, hydrochloride

Prepared according to the method of Example lb) from 1-adamantaneacetyl chloride (0.040g) and 5-amino-3- (2-dimethylaminoethylhndole dihydrochloride (0.18 g).

Supercritical Fluid chromatography using a gradient elution of 0.1 % v/v solution of diethylamine in methanol and supercritical carbon dioxide on a Cyano column gave the pure product which was dissolve in dichloromethane, treated with 1. OM solution of hydrogen chloride in diethyl ether and evaporated under reduced pressure to leave the title compound as a pale yellow solid. (0.031g).

Melting point: 145-147 °C MS (APCI +ve) 380 (M+H) + for free base 1H NMR (DMS O-d6) 810.89 (1H, s), 9. 58 (1H, s), 7.95 (1H, d), 7.25 (1H, dd), 7.15 (1H, d), 7.12 (1H, dd), 3.33 (2H, m), 3.05 (2H, m), 2.85 (6H, 2s), 2.03 (2H, s), 1.95 (3H, s), 1.60 (12H, m) Example 36 Methyl 4-methyl-3-[[1-oxo-2-(tricyclo [3.3.1. 13,7]dec-1-yl) ethyl] amino] thiophene-2- carboxylate

A solution of l-adamantaneacetyl chloride (0.2 g) prepared as described in Example la) was added to a solution of methyl 3-amino-4-methylthiophene-2-carboxlate (0.16 g) in pyridine (2 ml) and dichloromethane (4 ml). The rection mixture was stirred at ambient temperature for 2 days before being diluted with ethyl acetate. The organic phase was then washed with dilute hydrochloric acid and water, dried over magnesium sulphate (MgSO4) and finally concentrated under reduced pressure to give an oil. Purification of the residue by silica gel chromatography, eluitng with 10% ethyl acetate in isohexanes, gave the title compound as a white solid (0.049 g).

Melting point: 124-124.5 °C MS (APCI +ve) 348 (M+H) + 1H NMR (CDC13) õ 8.76 (1H, s), 7.13 (1H, s), 3.86 (3H, s), 2.23 (3H, s), 2.18 (2H, s), 2.0 (3H, bs), 1.70 (12H, m).

Example 37 N-(3-Methoxy-2-methylphenyl)-tricyclo[3.3.1.13,7]decane-1-ac etamide, Diethyl azodicarboxylate (0.20 ml) was added to a solution of N- (3-hydroxy-2- methylphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide (0.20 g, Example 26), methanol (0.10 ml) and triphenylphosphine (0.41 g) in toluene (10 ml) and tetrahydrofuran (5 ml).

After 2 hours stirring at room temperature further triphenylphosphine (0.20 g) and diethyl azodicarboxylate (0.10 ml) were added and the solution stirred for 2 hours. The rection mixture was concentrated under reduced pressure and the residue purifie by silica gel chromatography eluting with dichloromethane: ethyl acetate (19: 1) to give the title compound as a colourless solid (0.20 g).

Melting point: 173-175 °C MS (APCI +ve) 314 (M+H) + H NMR (CDC13) 6 487. (1H, d), 7.16 (1H, t), 6.86 (1H, bs), 6.69 (1H, d), 3.82 (3H, s), 2.13 (5H, s), 2.00 (3H, s), 1.75-1.6 (12H, m).

Example 38 N- (2-Methyl-3- (2- (1-imidazolothyloxy) phenyl)-tricyclo[3.3.1.13'7] decane-1-acetamide Diethyl azodicarboxylate (0.060 ml) was added to a solution of N-(3-hydroxy-2- methylphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide (0.100 g, Example 26), 1- (2-

hydroxyetheyl) imidazole (0.048 g, J. Heterocyclic Chem., 1990,27,215) and triphenylphosphine (0.097 g) in tetrahydrofuran (4 ml). After 24 hours stirring at room temperature further triphenylphosphine (0.100 g) and diethyl azodicarboxylate (0.060 ml) were added and the solution stirred for 6 days. The rection mixture was concentrated under reduced pressure and the residue purifie by NPHPLC on a Novapak# column using a Gilson automate chromatography machine eluting with 0-10% ethanol in dichloromethane to give an oil which was triturated with ether to give the title compound as a colourless solid (0.041 g).

Melting point: 119.5-121 °C MS (APCI +ve) 394 (M+H) + HNMR (CDC13) o7.60 (1H. s). 7.51 (lH, d), 7.14 (1H, t), 7.08 (1H, s), 7.03 (1H, s), 6.85 (1H, bs), 6.61 (1H, d), 4.37 (2H, t), 4.21 (2H, t), 2.13 (2H, s), 2.09 (3H, s), 2.00 (3H, s), 1-8-1.6 (12H, m).

Example 39 N-(2,4,6-Trimethylphenyl)-tricyclo[3.3.1.13b7] decane-1-acetamide Thionyl chloride (3 ml) was added to l-adamantaneacetic acid (0.50 g) and the rection heated at reflux for 2 minutes. The excess thionyl chloride was removed by concentration under reduced pressure and the residue was dissolve in dichloromethane (5 ml). This solution was added to a solution of 2,4,6-trimethylaniline (0.72 ml) in dichloromethane (20 ml) and triethylamine (1 ml) at room temperature over 1 minute.

After 5 minutes the rection mixture was concentrated under reduced pressure and the residue added to a column of silica. The mixture was then chromatographed eluting with

dichloromethane then dichloromethane: ethyl acetate (9: 1) to give the title compound as a colourless solid (0.469 g).

Melting point: 212-215 °C MS (APCI +ve) 312 (M+H) + 1H NMR (DMSO-d6) 8 8.97 (1H, s), 6.85 (2H, s), 2.21 (3H, s), 2.10 (6H, s), 2.06 (2H, s), 1.95 (3H, s), 1.8-1.5 (12H, m).

Example 40 N-(5-(3-Aminopropyloxy)-2-methylphenyl)-tricyclo(5-(3-Aminop ropyloxy)-2-methylphenyl)-tricyclo [3.3.1.13'7] decane-1-acetamide, hydrochloride Prepared according to the method of Example 2 using diethyl azodicarboxylate (1.05 ml), N-(5-hydroxy-2-methylphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide (0.506 g, Example 12), tert-butylN-(3-hydroxypropyl) carbamate (1. 15 g) andtriphenylphosphine (1.75 g) to give the title compound as a yellow solid (0.21 g).

Melting point: 145 °C (dec.) MS (APCI +ve) 357 (M-HCl+H) + 1H NMR (DMSO-d6) 8 059. (1H, s), 7.91 (3H, bs), 7.15-7.05 (2H, m), 6.66 (1H, dd), 3.99 (2H, t), 2.94 (2H, t), 2.13 (3H, s), 2.10 (2H, s), 2.05-1.9 (5H, m), 1.75-1.55 (12H, m).

Example 41 N-(5-(3-(N-Methylamino)(5-(3-(N-Methylamino) propyloxy)-2-methylphenyl)-tricyclo [3.3.1. 13,7]decane-1- acetamide, hydrochloride Diethyl azodicarboxylate (0.50 ml) was added to a solution of N-(5-hydroxy-2- methylphenyl)-tricyclo [3.3.1.13'7] decane-l-acetamide (0.50 g, Example 12), tert-butyl N- (3-hydroxypropyl)-N-methylcarbamate (0.60 g, J. Org. Chem., 1988,53 (10), 2229) and triphenylphosphine (0.88 g) in tetrahydrofuran (5 ml). After stirring for 19 hours at room temperature further triphenylphosphine (0.90 g) and diethyl azodicarboxylate (0.50 ml) were added. After stirring for 4 hours at room temperature further triphenylphosphine (0. 90g) and diethyl azodicarboxylate (0.50 ml) were added and the rection mixture was stirred for 3 days. The rection was then concentrated under reduced pressure and the residue was purifie by silica gel chromatography eluting with dichloromethane: ethyl acetate (9: 1) to give material that was further purifie by chromatography over a Dynamax column using a Gilson automate chromatography machine eluting with iso- hexane: ethyl acetate (4: 1) to give the Mitsunobu rection product (0.29 g) which was dissolve in methanol (10 mol). A solution of hydrogen chloride (generated by slow addition of acetyl chloride (12 ml) to methanol (10 ml) at 0°C CARE-Very Exothermic) was then added to the latter solution and the rection stirred at room temperature for 1 hour. The rection was then concentrated under reduced pressure to give the title compound as a yellow solid (0.13 g).

MS (APCI +ve) 371 (M-HCI+H) + 1H NMR (DMSO-d6) 8 059. (1H, s), 8.76 (2H, bs), 7.15-7.05 (2H, m), 6.66 (1H, dd), 3.99 (2H, t), 3.1-2.95 (2H, m), 2.6-2.5 (3H, m), 2.13 (3H, s), 2.10 (2H, s), 2.1-2.0 (2H, m), 1.94 (3H, m), 1.75-1.55 (12H, m).

Example 42 N6- (Tricyclo [3.3.1. 13,7]decane-1-acetyl) adenine To a solution of 1-adamantaneacetyl chloride from Example la) (0.226 g) in dichloromethane (5 ml) was added 4-nitrophenol (0.149 g) and rection mixture stirred at room temperature for 1 hr before concentration at reduced pressure. The resulting 4-nitrophenol ester was used without further purification.

To a suspension of the 4-nitrophenol ester (0.209 g), adenine (0.09 g) in dimethylsulphoxide (1.4 ml) was added triethylamine (0.19 ml) and rection mixture heated to 90 °C for 2 days before cooling to room temperature. Rection mixture was poured into aqueous sodium hydrogencarbonate solution and extracted with ethyl acetate.

Organic extracts combine, washed with water (x 3), brine, dried (Na2S04) and concentrated at reduced pressure. Trituration of the residue with isohexane and ether left the product as a pale yellow solid (0.036 g).

Melting point: 309 °C (dec.) MS (APCI +ve) 312 (M+H) + 1H NMR (DMSO-d6) 8 12.10 (1H. s), 11.06 (1H, s), 8.61 (lH, s), 8.40 (1H, s), 2.29 (2H, s), 1.92 (3H, s), 1.66 (6H, d), 1.60 (6H, m).

Example 43 N-(3,5-Dimethoxy-2-methylphenyl)-tricyclo [3.3.1.13s7] decane-1-acetamide a) 3,5-Dimethoxy-2-methylbenzoic acid To a solution of methyl 3,5-dimethoxy-2-methylbenzoate (5.83 9, J CS. Perkin I, 1973,2853.) in methanol (80 ml) was added a solution of aqueous sodium hydroxide (10%, 80 ml) and rection mixture stirred at room temperature for 1 hour. The rection was then concentrated under reduced pressure to approximately half of the original volume before adding aqueous hydrochloric acid (200 ml). The white precipitate that formed was extracted with ethyl acetate (2 x 250 ml). The combine extracts were dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure to give the sub-title compound as a colourless solid (5.41 g).

1H NMR (CDC13) 8 107. (1H, d), 6.64 (1H, d), 3.84 (6H, s), 2.45 (3H, s). b) N-(3,5-Dimethoxy-2-methylphenyl)-tricyclo [3.3.1.1397] decane-1-acetamide Triethylamine (0.8 ml) followed by diphenylphosphoryl azide (1.2 MI) were added to a solution of 3,5-dimethoxy-2-methylbenzoic acid (1.0 g) in tert-butanol (30 ml) and the mixture was heated at reflux temperature for 12 hours. The rection was cooled and concentrated under reduced pressure. The residue was partitioned between aqueous sodium hydroxide (2M, 100 ml) and dichloromethane (300 ml). The organic phase was dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to give an oil (0.74 g) which was dissolve in methanol (10 ml). A solution of hydrogen chloride (generated by slow addition of acetyl chloride (12 ml) to methanol (10 ml) at 0°C CARE-Very Exothermic) was then added to the latter solution and the rection stirred at

room temperature for 1 hour. The rection was concentrated under reduced pressure and the residue partitioned between an aqueous solution of saturated sodium hydrogen carbonate (100 ml) and dichloromethane (100 ml). The organic phase was dried over magnesium sulphate, filtered and concentrated under reduced pressure to give an oil (0.5 g) which was dissolve in dichloromethane (10 ml) and triethylamine (2 ml). A solution of 1-adamantaneacetyl chloride (generated from 1-adamantaneacetic acid (0.50 g) andthionyl chloride) in dichloromethane (5 ml) was added to the latter solution and the mixture stirred <BR> <BR> <BR> at room temperature for 2 houris. The rection was diluted with dichloromethane (100 ml) and the solution washed with aqueous hydrochloric acid (2M, 50 ml) then an aqueous solution of saturated sodium hydrogen carbonate (50 ml). The organic phase was dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure.

The residue was purifie by column chromatography over silica eluting with dichloromethane then dichloromethane: ethyl acetate (19: 1) to give the title compound as a colourless solid (0.54 g).

Meeting point: 201-203 °C MS (APCI +ve) 344 (M+H) + H NMR (DMSO-d6) õ 9.08 (1H, s), 6.61 (1H, d), 6.38 (1H, d), 3.76 (3H, s), 3.70 (3H, t), 2.07 (2H, s), 1.94 (6H, s), 1.75-1.55 (12H, ion).

Example 44 N-(3-(3-(N-Methylammo)(3-(3-(N-Methylammo) propyloxy)-2-methylphenyl)-tricyclo [3.3.1.13o7] decane-l- acetamide, hydrochloride Dry dichloromethane (40 ml), triphenylphosphine (3.28 g), imidazole (1.05 g) and iodine (3.85 g) were combine in that order. A solution of tert-butyl N-(3-hydroxypropyl)-

N-methylcarbamate (1. 90 g, J. Org. Chem., 1988,53 (10), 2229) in dichloromethane (10 ml) was added and the resulting rection mixture stirred at room temperature for 1 hour. An aqueous solution of sodium hydrogen sulphite (6 g in 100 ml of water) was then added and the organic layer separated. The latter was dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure. The residue was purifie by column chromatography over silica eluting with iso-hexane: ether (7: 3) to give tert-butyl N-(3-iodopropyl)-N-methylcarbamate(3-iodopropyl)-N-methylcar bamate (2.54 g) which was used immediately.

Caesium carbonate (0.655 g) was added to a suspension of N- (3-hydroxy-2-methylphenyl)- tricyclo [3.3. l. l37] decane-l-acetamide (0.453 g, Example 26) in acetonitrile (35 ml) and the mixture heated at 100°C for 10 minutes. After cooling to room temperature a solution of tert-butyl N-(3-iodopropyl)-N-methylcarbamate (0.600 g) in acetonitrile (5 ml) was added and the rection heated at reflux for 90 minutes. The rection was concentrated under reduced pressure and the residue partitioned between dichloromethane (100 ml) and water (100 ml). The organic layer was dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure. The residue was purifie by silica gel chromatography eluting with dichloromethane: ethyl acetate (9: 1) to give a solid that was dissolve in methanol (10 ml). A solution of hydrogen chloride (generated by slow addition of acetyl chloride (12 ml) to methanol (15 ml) at 0°C CARE-Very Exothermic) was then added to the latter solution and the rection stirred at room temperature for 1 hour. The rection was concentrated under reduced pressure to give a gum that was scratche under ether: hexane (1: 1) (20 ml) to give the title compound as a pale yellow powder (0.477 g).

MS (APCI +ve) 371 (M-HCI+H) + <BR> <BR> <BR> IH NMR (DMSO-d6) 8 209. (1H, s), 8.82 (2H, bs), 7.10 (1H, t), 6.94 (1H, d), 6.78 (1H, d), 4.05 (2H, t), 3.15-3.0 (2H, m), 2.58 (3H, t), 2.15-2.0 (7H, m), 1.94 (3H, ion), 1.75-1.55 (12H, m).

Example 45 N-(5-(3-(N, N-Dimethylamino) Propyloxy)-2-methylphenyl)-tricyclo(5-(3-(N, N-Dimethylamino) Propyloxy)-2-methylphenyl)-tricyclo [3.3. 1.13,7]decane-1 acetamide, hydrochloride Caesium carbonate (1.31 g) was added to a suspension of N-(3-hydroxy-2- methylphenyl)-tricyclo [3.3.1.13'7] decane-1-acetamide (0.473 g, Example 26) in acetonitrile (35 ml) and the mixture heated at 80°C for 5 minutes. After cooling to room temperature solid N, N dimethyl-3-chloropropylamine (0.274 g) was added and the rection heated at reflux overnight. The rection was concentrated under reduced pressure and the residue partitioned between dichloromethane (100 ml) and water (100 ml). The organic layer was dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure.

The residue was purifie by column chromatography over silica eluting with dichloromethane: ethanol: triethylamine (95: 4: 1) to give a yellow gum. This was dissolve in methanol (10 ml) and treated with an excess of ethereal hydrogen chloride (1M, 5 equivalents). The solution was concentrated under reduced pressure to give a gum that was stirred for 2 days in ether (20 ml) to give a solid which was isolated by filtration (0.588 g).

MS (APCI +ve) 385 (M-HCI+H) + 1H NMR (DMSO-d6) qo 10.33 (1H, bs), 9.21 (1H, s), 7.10 (1H, t), 6.94 (1H, d), 6.78 (1H, d), 4.04 (2H, t), 3.3-3.1 (2H, m), 2.79 (6H, d), 2.2-2.1 (2H, ion), 2.08 (2H, s), 2.05 (3H, s), 1.95 (3H, s), 1.75-1.55 (12H, m).

Example 46 N-(5-Methoxy-2-methylphenyl)-tricyclo(5-Methoxy-2-methylphen yl)-tricyclo [3.3.1. 13,7]decanyloxy-1-acetamide

Thionyl chloride (3 ml) was added to l-adamantyloxyacetic acid (0.38 g, CA 1966,65, 2149a) and the rection heated at reflux for 2 minutes. The excess thionyl chloride was removed by concentration under reduced pressure and the residue was then dissolve in dichloromethane (2.5 ml). This solution was then added over 1 minute to a solution of 5- methoxy-2-methylaniline (0.37 g) in dichloromethane (20 ml) and triethylamine (1 ml) at room temperature. After 3 days the rection mixture was concentrated under reduced pressure and the residue added to a column of silica. The mixture was then chromatographed eluting with dichloromethane then dichloromethane: ethyl acetate (19: 1) to give a solid. This was dissolve in dichloromethane (75 ml) and the solution washed with aqueous hydrochloric acid (2M, 2 x 30 ml). The organic solution was dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure. The residue was washed with ether: hexane (1: 1) to give the title compound as a colourless solid (0.40 g).

Melting point: 128-130 °C MS (APCI +ve) 330 (M+H) + lHNMR (DMSO-d6) o8.81 (lH, s), 7.46 (1H, d), 7.12 (1H, d), 6.65 (1H, dd), 4.04 (2H, s), 3.71 (3H, s), 2.15-2.12 (6H, m), 1.78 (6H, d), 1.7-1.5 (6H, m).

Example 47 N-(5-Methoxy-2-methylphenyl)-(3-bromo-tricyclo(5-Methoxy-2-m ethylphenyl)-(3-bromo-tricyclo [3.3.1. 13,7]decane-1-acetamide To a solution of 3-bromoadamantane acetic acid (CN 17768-34-2) (0.123 g) in dichloromethane (5 ml) was added oxalyl chloride (0.5 ml) and resulting rection mixture heated to reflux temperature for 2 hr before concentration at reduced pressure. Residue was dissolve in dichloromethane (5 ml) and a mixture of 5-methoxy-2-methylaniline (0.062 g) and triethylamine (0.2 ml) in dichloromethane (2 ml) was added dropwise and rection mixture stirred at room temperature for 18 hr before being poured into dilute HCI and extracted with diethyl ether. Organic extracts combine, washed with water, 15% NaOH solution, brine, dried (Na2S04) and concentrated to leave a solid that was triturated with ether to leave the title compound as a white solid (0.07 g).

Melting point: 133 °C MS (APCI +ve) 392/394 (M+H) + IH NMR (DMSO-d6) õ 9.13 (1H, s), 7.09 (1H, d), 7.05 (1H, d), 6.66 (1H, dd), 3.70 (3H, s), 2.28-2.13 (11H, m), 2.18 (2H, s), 1.68-1.55 (6H, m).

Example 48 N-(5-Methoxy-2-methylphenyl)-(2-oxa-tricyclo(5-Methoxy-2-met hylphenyl)-(2-oxa-tricyclo [3.3.1.13'7] decane)-1-acetamide a) Ethyl (2-oxa-tricyclo [3.3.1. 13,7]decane)-1-acetate Sodium borohydride (0.093 g) was added to a solution of ethyl 7-oxobicyclo [3.3.1] non-3-ylideneacetate (0.113g, Chem. Phare. Bull., 1979,27,824) in ethanol (2 ml) and the rection left to stir at room temperature for 3 days. Rection was diluted with dichloromethane (60 ml) and washed with a saturated solution of aqueous ammonium chloride (20 ml). The organic phase was dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure. The residue was purifie by column chromatography over silica eluting with dichloromethane and then dichloromethane: ether (9: 1) to give the sub-title compound as an oil (0.078 g).

1H NMR (CDCl3) # 4.15 (2H, q), 4.09 (1H, bs), 2.37 (2H, s), 2.16 (2H, bs), 2.2-1.5 (1OH, m), 1.27 (3H, t). b) N- (5-Methoxy-2-methylphenyl)-(2-oxa-tricyclo [3.3.1.13') decane)-1-acetamide Aqueous sodium hydroxide (10%, 2 ml) was added to a solution of ethyl (2-oxa- tricyclo [3.3.1. 13,7]decane)-1-acetate (66 mg) in ethanol (2 ml). After stirring at room temperature for 1 hour the solvent was removed under reduced pressure. The residue was partitioned between aqueous hydrochloric acid (2M, 6 ml) and dichloromethane (2 x 20 ml). The organic extracts were dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure to give (2-oxa-tricyclo [3.3.1.137] decane)-l-acetic acid. Thionyl chloride (3 ml) was added to the acid and the rection heated at reflux for 2 minutes. The excess thionyl chloride was removed by concentration under reduced

pressure and the residue was then dissolve in dichloromethane (5 ml). This solution was then added over 1 minute to a solution of 5-methoxy-2-methylaniline (69 mg) in dichloromethane (5 ml) and triethylamine (1 ml) at room temperature for 20 minutes. The rection mixture was diluted with dichloromethane to 60 ml and then washed with aqueous hydrochloric acid (2M, 30 ml). The organic phase was dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure. The residue was purifie by column chromatography over silica eluting with dichloromethane then dichloromethane : ether (19: 1) to give, after trituration with iso-hexane, a colourless solid (0.05 g).

Melting point: 108-109.5 °C MS (APCI +ve) 316 (M+H) + 1H NMR (DMSO-d6) 5 9. 12 (lH, s), 7.39 (1H, d), 7.08 (1H, d), 6.61 (lH, dd), 4.09 (1H, bs), 3.69 3H, s), 2.37 (2H, s), 2.15-2.05 (2H, m), 2.13 (3H, s), 1-9-1.55 (l OH, m).

Example 49 N- (5-Methoxy-2-methylphenyl)-2- (tricyclo [3.3.1.13'7] decan-1-amino) acetamide a) N- (5-Methoxy-2-methylphenyl)-2-chloroacetamide To a solution of 5-methoxy-2-methylaniline (7.62 g) and triethylamine (15.5 ml) in dichloromethane (150 ml) at 0-5°C was added chloroacetyl chloride (5.0 ml) dropwise and the ice bath removed. The resulting rection mixture was stirred for 45 min before being poured into dil HUI and extracted with dichloromethane. Organic extracts were combine, washed with water, dried (Na2S04) and concentrated to give a brown solid that was triturated with diethyl ether to leave the sub-title compound as a beige solid (5.7 g).

Melting point: 89-91 °C

IH NMR (DMSO-d6) 8 9.58 (1H, s), 7.12 (1H, d), 7.05 (1H, d), 6.71 (lH, dd), 4.30 (2H, s), 3.71 (3H, s), 2.13 (3H, s). b) N- (5-Methoxy-2-methylphenyl)-2- (tricyclo [3.3.1. 13,7]decan-1-amino) acetamide A solution of chloroamide from step a) (0.092 g), adamantanamine (0.13g), diisopropylethylamine (0. 17ml) and tetrahydrofuran (1.5 ml) was heated in a sealed Wheaton vial to 100 °C for 18 hr. Rection mixture cooled to room temperature and poured into water and extracted with diethyl ether. Organic extracts combine, washed with brine, dried (Na2S04) and concentrated and residue purifie by column chromatography over silica eluting 0-2% methanol in dichloromethane to give the title compound as a white solid (0.034 g).

Melting point: 158 °C MS (APCI +ve) 329 (M+H) + IH NMR (DMSO-d6) 8 929. (1H, s), 7.76 (1H, d), 7.10 (1H, d), 6.57 (1H, dd), 3.69 (3H, s), 3.22 (2H, s), 2.27 (1H, br s), 2.18 (3H, s), 2.01 (3H, s), 1.58 (12H, s).

Example 50 N- (3,5-Dimethoxyphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide Prepared according to the method of Example 39 from 1-adamantaneacetic acid (3.0 g) and 3,5-dimethoxyaniline (3.0 g) to give the title compound as a white solid (4.2 g).

Melting point: 144-146 °C MS (APCI +ve) 330 (M+H) +

IH NMR (DMSO-d6) 6 699. (1H, S), 6.86 (2H, d), 6.18 (1H, t), 3.70 (6H, s), 2.02 (2H, s), 1.93 (3H, s), 1.68-1.57 (12H, m).

Example51 N- (3,5-Dihydroxyphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide To a solution of N (3,5-dimethoxyphenyl)-tricyclo [3.3.1.137] decane-l-acetamide (2.22 g) in dichloromethane (200 ml) at - 78°C was added boron tribromide (60 ml of a 1M solution in dichloromethane). Cooling bath was removed and rection stirred at room temperature for 3 days. Rection was quenched by addition of ice (230 g). After stirring vigorously for 30 min ethyl acetate (700 ml) added and the organic layer separated, dried (MgS04) anå concentrated. The residue was purifie by column chromatography over silica eluting 5% ethanol in dichloromethane to give the leave a white solid (1.95 g). A portion of this was recrystallised from hot ethyl acetate to leave the title compound as an off-white solid.

Melting point: 239-242 °C MS (APCI +ve) 302 (M+H) + H NMR (DMSO-d6) 8 9.42 (1H, s), 9.09 (2H, s), 6.55 (2H, d), 5.87 (1H, t), 1.99 (2H, s), 1.92 (3H, s), 1.69-1.56 (12H, m).

Example 52 N-(3,5-Dimethoxyphenyl)-tricyclo[3.3.1.13,7]decanyloxy-1-ace tamide Prepared according to the method of Example 46 using 1-adamantyloxyacetic acid (2.0 g) and 3,5-dimethoxyaniline (1.75 g) to leave the title compound as an oil (2.5 g).

MS (APCI +ve) 346 (M+H) + <BR> <BR> IH NMR (DMS O-db) 8 239. (1H, s), 6.94 (2H, s), 6.23 (1H, s), 3.98 (2H, s), 3.71 (6H, s), 2.12 (3H, s), 1.76 (6H, d), 1.59 (6H, m).

Example 53 N-(3,5-Bis-(3-aminopropyloxy)phenyl)-tricyclo[3.3.1.13,7]dec ane-1-acetamide Prepared according to the method of Example 2 using N (3,5-dihydroxyphenyl)- tricyclo [3.3.1. 13,7]decane-1-acetamide from Example 51 (0.60 g), tert-butyl N (3- hydroxypropyl) carbamate (1.43 g), tributylphosphite (2.0 ml) and 1, 1' (azodicarbonyl) dipiperidine (2.05 g) to leave the title compound as a fawn solid (0.12 g).

MS (APCI +ve) 416 (M+H)' H NMR (DMSO-d6) # 819. (1 H, s), 8.00 (6H, br s), 6.91 (2H, d), 6.22 (1H, t), 4.00 (4H, t), 2.93 (4H, t), 2.04-1.98 (9H, m), 1.69-1.56 (12H, m).

Example 54 N-(2,4,5-Trimethylphenyl)-tricyclo[3.3.1.13'7] decanyloxy-1-acetamide

The title compound was prepared as in Example 46 from 2,4,5-trimethylaniline (0.30 g) and 1-adamantyloxyacetic acid (0.38 g, CA 1966,65,2149a) as a colourless solid (0.41 g).

Melting point: 138-140 °C MS (APCI +ve) 328 (M+H) + 1H NMR (DMSO-d6) 6 768. (1H, s), 7.42 (1H, s), 6.98 (1H, s), 4.00 (2H, s), 2.2-2.1 (12H, m), 1.8-1.75 (6H, m), 1.65-1.55 (6H, m).

Example 55 N-(S-Hydroxy-2-methylphenyl)-tricyclo(S-Hydroxy-2-methylphen yl)-tricyclo [3.3.1. 13,7]decanyloxy-1-acetamide Thionyl chloride (5 ml) was added to l-adamantyloxyacetic acid (2.00 g, CA 1966,65, 2149a) and the rection heated at reflux for 5 minutes. The excess thionyl chloride was removed by concentration under reduced pressure and the residue was then dissolve in dichloromethane (10 ml). This solution was then added over 5 minutes to a solution of 2-methyl-5-hydroxyaniline hydrochloride (1.00 g J. Chem. Soc. Perkin Trans. 2, 539)1972, in dichloromethane (20 ml) and triethylamine (10 ml) at 0°C. The solution was then allowed to warm to room temperature and, after 30 minutes stirring, was concentrated

under reduced pressure. The residue was dissolve in methanol (20 ml) and tetrahydrofuran (10 ml) and was treated with a solution of sodium methoxide in methanol (25 wt. %, 10 ml). After 15 minutes stirring the rection was treated with formic acid (4 ml) and then concentrated under reduced pressure. The residue was partitioned between aqueous hydrochloric acid (2M, 90 ml), ethyl acetate (90 ml) and tetrahydrofuran (50 ml).

The organic phase was separated, washed with saturated aqueous sodium chloride (50 ml), dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure to give a solid (2.62 g). This was purifie by column chromatography over silica eluting with dichloromethane: ethyl acetate (4: 1) to give a colourless solid (1. 39 g).

Melting point: 258 °C (dec.) MS (APCI +ve) 316 (M+H) + 1H NMR (DMSO-d6) 5 9.22 (1H, s), 8.71 (lH, s), 7.37 (1H, d), 6.98 (1H, d), 6.45 (1H, dd), 4.02 (2H, s), 2.13 (3H, bs), 2.10 (3H, s), 2.15-2.12 (6H, m), 1.78 (6H, d), 1.7-1.5 (6H, m).

Example 56 N-(5-(2-(N-Methylamino)(5-(2-(N-Methylamino) ethyloxy)-2-methylphenyl)-tricyclo [3.3.1. 13,7]decane-1- acetamide, hydrochloride Tert-butyl-N-(2-hydroxyethyl)-N-methylcarbamate(2-hydroxyeth yl)-N-methylcarbamate (1.05 g, Synth. Commun., 1993, 23 (17), 2443), N- (5-hydroxy-2-methylphenyl)-tricyclo [3.3.1. 13,7]decane-1-acetamide (1.00 g, Example 12), tetrahydrofuran (40 ml) and tributylphosphine (1.35 MI) were combine, cooled in ice/water, before addition of 1, 1'- (azodicarbonyl) dipiperidine (1.39 g) and rection stirred for 10 minutes. After stirring at room temperature for 90 minutes further

tert-butyl N- (2-hydroxyethyl)-N-methylcarbamate (1.04 g) and tributylphosphine (1.35 ml) were added and the solution recooled in ice/water before addition of l, 1'- (azodicarbonyl) dipiperidine (1.39 g) and stir in ice/water for 10 minutes then at room temperature overnight. The rection mixture was diluted with iso-hexane (50 ml) and filtered. The residue was washed with ether (100 ml) and the combine organics concentrated under reduced pressure. The residue was purifie by column chromatography over silica eluting with iso-hexane: ethyl acetate (7: 3) and further purifie by column chromatography over silica eluting with dichloromethane: ethyl acetate (9: 1) to give the coupled product (0.57 g) which was dissolve in methanol (10 ml). A solution of hydrogen chloride (generated by slow addition of acetyl chloride (10 ml) to methanol (15 ml) at 0°C CARE-Very Exothermic) was then added to the latter solution and the rection stirred at room temperature for 2 hours. The rection was then concentrated under reduced pressure and then triturated with ether (100 ml) give the title compound as colourless solid (0.35 g).

Melting point: 193-195 °C MS (APCI +ve) 357 (M+H) + as free base 1H NMR (DMSO-d6) 6 069. (1H, s), 8.91 (2H, bs), 7.19 (1H, 6), 7.12 (1H, d), 6.70 (1H, dd), 4.17 (2H, t), 3.4-3.25 (2H, m), 2.61 (3H, s), 2.15 (3H, s), 2.11 (2H, s), 1.95 (3H, s), 1.75-1.55 (12H, m).

Example 57 N-(5-(2-(N-Methylamino)(5-(2-(N-Methylamino) ethyloxy)-2-methylphenyl)-tricyclo [3.3.1.13w7] decanyloxy-1- acetamide a) N- (5-Hydroxy-2-methylphenyl)-tricyclo [3.3.1. 13,7]decanyloxy-1-acetamide Thionyl chloride (5 ml) was added to l-adamantyloxyacetic acid (2.00 g, CA 1966,65, 2149a) and the rection heated at reflux for 5 minutes. The excess thionyl chloride was

removed by concentration under reduced pressure and the residue was dissolve in dichloromethane (10 ml). This solution was added over 5 minutes to a solution of 5- hydroxy-2-methylaniline, hydrochloride (1.00 g J. Chem. Soc. Perkin Trans. 2, 539)1972, in dichloromethane (20 ml) and triethylamine (10 ml) at O °C. The solution was allowed to warm to room temperature and, after 30 minutes stirring, was concentrated under reduced pressure. The residue was dissolve in methanol (20 ml) and tetrahydrofuran (10 ml) and was treated with a solution of sodium methoxide in methanol (25 wt. %, 10 ml). After 15 minutes stirring the rection was treated with formic acid (4 MI) and concentrated under reduced pressure. The residue was partitioned between aqueous hydrochloric acid (2M, 90 ml), ethyl acetate (90 ml) and tetrahydrofuran (50 ml). The organic phase was separated, washed with saturated aqueous sodium chloride (50 ml), dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure. The residue was purifie by column chromatography over silica eluting with dichloromethane: ethyl acetate (4: 1) to give the sub-title compound as a colourless solid (1.39 g).

258°C(dec.)Meltingpoint: MS (APCI +ve) 316 (M+H) + IH NMR (DMSO-d6) 5 9.22 (1H, s), 8.71 (lH, s), 7.37 (1H, d), 6.98 (1H, d), 6.45 (1H, dd), 4.02 (2H, s), 2.13 (3H, bs), 2.10 (3H, s), 2.15-2.12 (6H, m), 1.78 (6H, d), 1.7-1.5 (6H, m). b) N- (5-(2-(N-Methylamino) ethyloxy)-2-methylphenyl)-tricyclo [3.3.1.13, 7] _ decanyloxy-1-acetamide Prepared using the method described in Example 2 using tert-butyl N- (2- hydroxyethyl)-N-methylcarbamate (1.05 g, Synth. Commun., 1993,23 (17), 2443) and N- (5-hydroxy-2-methylphenyl)-tricyclo [3.3.1. 13,7]decanyloxy-1-acetamide (1.00 g, part a) to give the title compound as a colourless solid (0.54 g).

Melting point: 155-158 OC (dec.) MS (APCI +ve) 373 (M-HCI+H) +

IH NMR (DMSO-d6) 8 079. (2H, bs), 8.84 (1H, s), 7.57 (IH, d), 7.16 (1H, d), 6.71 (1H, dd), 4.20 (2H, t), 4.05 (2H, s), 3.30 (2H, t), 2.60 (3H, t), 2.17 (3H, s), 2.13 (3H, s), 1.78 (6H, d), 1.65-1.55 (6H, m).

Example58 <BR> <BR> N-(s-(3-(N-Methylamino)(s-(3-(N-Methylamino) propyloxy)-2-methylphenyl)-tricyclo [3.3. 1.13,7]decanhyloxy-1- acetamide Prepared using the method described in Example 56 from tert-butyl N (3- hydroxypropyl)-N-methylcarbamate (1.01 g, J. Org. Chem., 1988,53 (10), 2229) andN-(5- hydroxy-2-methylphenyl)-tricyclo [3.3.1. 13,7]decanyloxy-1-acetamide (1.00 g, Example 55) to give the title compound as a colourless solid (0.50 g).

Melting point: 151-154 °C (dec.) MS (APCI +ve) 387 (M-HCI+H) + 1H NMR (DMSO-d6) 5 918. (2H, bs), 8.82 (1H, s), 7.49 (1H, d), 7.13 (1H, d), 6.67 (1H, dd), 4.04 (2H, s), 4.01 (2H, t), 3.03 (2H, quinte), 2.55 (3H, t), 2.15 (3H, s), 2.13 (3H, s), 2.06 (2H, quinte), 1.78 (6H, d), 1.65-1.55 (6H, m).

Example 59 N- (3,5-Dihydroxy-2-methylphenyl)-tricyclo [3.3.1. 13,7] decane-acetamide

A solution of dimethoxy ether from Example 43 (2.0 g) in 50% hydrobromic acid in acetic acid was heated at 100 degrees for 12 hours. The solution was concentrated under vacuum, the residue taken in water and extracted with ethyl acetate. The organic layers were dried over magnesium sulfate, filtered, concentrated under vacuum. The crude material was purifie over silica eluting with dichloromethane'ethyl acetateto afford the title compound as a white solid.

Melting point: 270 °C (dec.) MS (APCI +ve) 316 (M+H) + 'H NMR (CDC13) 6 099. (1H, s); 8.91 (1H, s); 8.86 (1H, bs); 6.35 (1H, d); 6.11 (4H, d); 2.04 (2H, s); 1.94 (3H, bs); 1.87 (3H, s); 1.80-1.50 (12H, ion).

Example 60 Pharmacological Analysis Certain compound such as benzoylbenzoyl adenosine triphosphate (bbATP) are known to be aganists of the P2X7 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 observe. The increase in fluorescence can be used as a measure of P2X7 receptor activation and therefore to quantify the effect of a compound on the P2X7 receptor.

In this manner, each of the title compound of Examples 1 to 59 were tested for antagonist activity at the P2X7 receptor. Thus, the test was performed in 96-well flat bottomed microtitre plates, the wells being filled with 250 ri ouf test solution comprising 200 RI of a suspension of THP-1 cells (2.5 x 106cells/ml) containing 104M ethidium bromide, 25 RI of high potassium buffer solution containing 10 M bbATP, and 25, ul of 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, mission 595 nm, slit widths: Ex 15 nm, Em 20 nm. For the purposes of comparison, bbATP (a P2X7 receptor

agonist) and pyridoxal 5-phosphate (a P2X7 receptor antagonist) were used separately in the test as controls. From the readings obtained, a pIC50 figure was calculated for each test compound, this figure being the negative logarithm of the concentration of test compound necessary to reduce the bbATP agonist activity by 50%. Each of the compound of Examples 1 to 59 demonstrated antagonist activity, having a pIC50 figure > 4.50.