The compound 2,7-diamino-5-methylmercapto-thiazolo 4,5-d pyrimidine is known from J. Amer. Chem. Soc., 73,4226-4227 (1951).

Chemokines play an important role in immune and inflammatory responses in various diseases and disorders, including asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis. These small secreted molecules are a growing superfamily of 8-14 kDa proteins characterised by a conserved four cysteine motif. The chemokine superfamily can be divided into two main groups exhibiting characteristic structural motifs, the Cys-X-Cys (C-X-C) and Cys-Cys (C-C) families. These are distinguished on the basis of a single amino acid insertion between the NH-proximal pair of cysteine residues and sequence similarity.

The C-X-C chemokines include several potent chemoattractants and activators of neutrophils such as interleukin-8 (IL-8) and neutrophil-activating peptide 2 (NAP-2).

The C-C chemokines include potent chemoattractants of monocytes and lymphocytes but not neutrophils such as human monocyte chemotactic proteins 1-3 (MCP-1, MCP-2 and MCP-3), RANTES (Regulated on Activation, Normal T Expressed and Secreted), eotaxin and the macrophage inflammatory proteins l oc and 1 (3 (MIP-1 oc and MIP-15).

Studies have demonstrated that the actions of the chemokines are mediated by subfamilies of G protein-coupled receptors, among which are the receptors designated CCR1, CCR2, CCR2A, CCR2B, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CCR10, CXCR1, CXCR2, CXCR3 and CXCR4. These receptors represent good targets for drug

development since agents which modulate these receptors would be useful in the treatment of disorders and diseases such as those mentioned above.

In accordance with the present invention, there is therefore provided a compound of general formula <BR> wherein R¹ represents a hydrogen atom, or a group-NR³R4;<BR> <BR> <BR> <BR> R³ and R4 each independently represent a hydrogen atom, or a 4-piperidinyl, C3-C6 cycloalkyl or Ci-Cg alkyi group, which latter two groups may be optionally substituted by one or more substituent groups independently selected from halogen atoms and-NR R -CONRSR6,-OR,-COOR,-NRgCOR9,-SR1,-S02R1,-S02NRSR6,-NR S02R morpholinyl, Cl-C4 alkyl, C3-C6 cycloalkyl, tetrahydrofuranyl and aryl groups, wherein an aryl substituent group may be a phenyl, naphthyl, thienyl, pyridinyl, imidazolyl or indolyl group, each of which may be optionally substituted by one or more substituents independently selected from halogen atoms and cyano, nitro,-NR R,-CONR R -oR7,-NR8COR,-SO2NR R,-NR SO2R, Cl-C6 alkyl and trifluoromethyl groups, or R3 and R together with the nitrogen atom to which they are attached form a 4-to 7-membered saturated heterocyclic ring system, which ring system may be optionally substituted by one or more substituent groups independently selected from

-NR5R6,-CoNR5R6,-oR7,-COOR10,-NR COR, and Cl-C6 alkyl optionally substituted by one or more substituents independently selected from halogen atoms and -NR11R12 and-OR groups; <BR> <BR> <BR> <BR> <BR> X represents a group-OH or-NR¹³R14;<BR> <BR> <BR> <BR> <BR> <BR> <BR> R¹³ and R14 each independently represent a hydrogen atom, a 4-piperidinyl group optionally substituted by a Cl-C4 alkylphenyl substituent group, or a C3-C7 carbocyclic, C l-Cg alkyl, C2-C6 alkenyl or C2-C6 alkynyl group, which latter four groups may be optionally substituted by one or more substituent groups independently selected from halogen atoms and -NR5R6, -CONR5R6, -OR7, -COOR7,-NR8COR9, -SR10, -SO2Rl07-So2NR5R6,-NR8SO2R, morpholinyl, Cl-C4 alkyl, C3-C6 cycloalkyl and aryl groups, wherein an aryl substituent group may be a phenyl, naphthyl, thienyl, pyridinyl, imidazolyl or indolyl group, each of which may be optionally substituted by one or more substituents independently selected from halogen atoms and cyano, nitro, -NRSR6,-CONR5R6,-OR,-NR8COR9,-S02NRSR6, NRgS02R9, Cl-C6alkyl and trifluoromethyl groups, <BR> <BR> <BR> <BR> <BR> or R¹³ and R14 together with the nitrogen atom to which they are attached form a 4-to 7-membered saturated heterocyclic ring system, which ring system may be optionally substituted by one or more substituent groups independently selected from-NR R, -CONRSR6,-OR,-COOR,-NRgCOR9, and C I-C6 alkyl optionally substituted by one or more substituents independently selected from halogen atoms and phenyl,-NR R 2 and-OR groups; <BR> <BR> <BR> <BR> <BR> R² represents a Cl-C6 alkyl or C2-C6 alkenyl group optionally substituted by a phenyl or phenoxy group, wherein the phenyl or phenoxy group may itself be optionally substituted by one or more substituents independently selected from halogen atoms and nitro, Cl-C6 alkyl, trifluoromethyl,-OR,-C (O) R,-SR,-NR 5R16 and phenyl groups; R and R each independently represent a hydrogen atom or a C l-C6 alkyl or phenyl group, each of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, phenyl,-OR and-NR R, or R and R together with the nitrogen atom to which they are attached form a 4-to 7-membered saturated heterocyclic ring system optionally comprising a further heteroatom

selected from oxygen and nitrogen atoms, which ring system may be optionally substituted by one or more substituent groups independently selected from phenyl,-OR 1, -COOR, NR R, CONR R, NR COR, SONR R, and C I-C6 alkyl optionally substituted by one or more substituents independently selected from halogen atoms and-NR R and-OR groups; <BR> <BR> <BR> <BR> R7 and R9 each independently represent a hydrogen atom or a C1-C6, particularly C l-C4, alkyl (e. g. methyl, ethyl, propyl, butyl, pentyl or hexyl) or phenyl group, each of which may be optionally substituted by one or more (e. g. one, two, three or four) substituent groups independently selected from halogen atoms (e. g. fluorine, chlorine, bromine or iodine), phenyl,-OR and-NR R; and each of R, R, R, R, R, R and R independently represents a hydrogen atom or a Cl-C6, particularly Cl-C4, alkyl (e. g. methyl, ethyl, propyl, butyl, pentyl or hexyl) or <BR> <BR> <BR> <BR> <BR> phenyl group; with the proviso that when R¹ and X both represent-NH2, then R² does not represent a methyl group; or a pharmaceutically acceptable salt or solvate thereof.

In the context of the present specification, unless otherwise indicated, an alkyl or alkenyl group or an alkyl or alkenyl moiety in a substituent group may be linear or branched.

Where a substituent in an alkenyl group is a phenoxy group, the phenoxy group is not attached to an unsaturated carbon atom. A carbocyclic group is a saturated hydrocarbyl group that may be monocyclic or polycyclic (e. g. bicyclic). Similarly, a saturated heterocyclic ring system may be monocyclic or polycyclic (e. g. bicyclic). <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <P>In formula (I) above, the group R¹ represents a hydrogen atom, or a group-NR³R4.

Particularly advantageous compounds of formula (1) are those in which R represents a group-NR R. <BR> <BR> <BR> <BR> <BR> <BR> <BR> <P> Preferably, R³ and R4 each independently represent a hydrogen atom, or a 4-piperidinyl, C3-C6 cycloalkyl (i. e. cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl) or Cl-Cg, particularly Ci-C6, alkyl group (e. g. methyl, ethyl, propyl, isopropyl, butyl, isobutyl,

t-butyl, pentyl, hexyl, heptyl or octyl), which latter two groups may be optionally substituted by one, two, three or four substituent groups independently selected from halogen atoms (e. g. fluorine, chlorine, bromine or iodine) and-NRSR,-CONR R6, -OR,-COOR,-NR8COR9,-SR,-S02R,-S02NRSR6,-NRgS02R morpholinyl, C1-C4 alkyl (e. g. methyl, ethyl, propyl, isopropyl, butyl or t-butyl), C3-C6 cycloalkyl (i. e. cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl), tetrahydrofuranyl and aryl groups, wherein an aryl substituent group may be a phenyl, naphthyl, thienyl, pyridinyl, imidazolyl or indolyl group, each of which may be optionally substituted by one, two, three or four substituents independently selected from halogen atoms (e. g. fluorine, chlorine, bromine or iodine) and cyano, nitro,-NR R,-CONR R,-OR, -NR8COR9,-SO2NR R,-NR S02R, C1-C6, particularly Cl-C4, alkyl (e. g. methyl, ethyl, propyl, butyl, pentyl or hexyl) and trifluoromethyl groups, <BR> <BR> <BR> or R³ and R4 together with the nitrogen atom to which they are attached form a 4-to 7-membered saturated heterocyclic ring system, which ring system may be optionally substituted by one, two or three substituent groups independently selected from -NR5R6,-CONR5R6,-oR7,-COOR,-NR8COR, and Cl-C6, particularly C1-C4, alkyl (e. g. methyl, ethyl, propyl, butyl, pentyl or hexyl) optionally substituted by one, two or three substituents independently selected from halogen atoms (e. g. fluorine, chlorine, bromineoriodine) and-NR R and-OR groups. <BR> <BR> <BR> <BR> <BR> <BR> <P>Particularly advantageous compounds of formula (I) are those in which R³ and R4 each independently represent a hydrogen atom, or a C í-C6 alkyl group substituted by a -CONR5R6 or imidazolyl (e. g. lH-imidazol-4-yl) group.

Preferably, R represents a C1-C6 alkyl or C2-C6 alkenyl group optionally substituted by a phenyl or phenoxy group, wherein the phenyl or phenoxy group may itself be optionally

substituted by one, two, three or four substituents independently selected from halogen atoms (e. g. fluorine, chlorine, bromine or iodine) and nitro, Cl-C6, particularly Cl-C4, alkyl (e. g. methyl, ethyl, propyl, butyl, pentyl or hexyl), trifluoromethyl,-OR,-C (o) R7, -SR10,-NR R and phenyl groups.

Particularly advantageous compounds of formula (I) are those in which R represents a Cl-C6 alkyl group optionally substituted by a phenyl, halophenyl (e. g. 2,3-difluorophenyl) or-OR (e. g. phenoxy) group.

Preferably, R and R each independently represent a hydrogen atom or a Cl-C6, particularly Cl-C4, alkyl or phenyl group, each of which may be optionally substituted by one, two, three or four substituent groups independently selected from halogen atoms (e. g. fluorine, chlorine, bromine or iodine), phenyl,-OR and-NR R, or R and R together with the nitrogen atom to which they are attached form a 4-to 7-membered saturated heterocyclic ring system optionally comprising a further heteroatom selected from oxygen and nitrogen atoms (e. g. one or two oxygen and/or nitrogen atoms), which ring system may be optionally substituted by one, two or three substituent groups independently selected from phenyl,-OR,-COOR,-NR R,-CONR R -NR15COR16,-SONR15R16, and C1-C6, particularly Cl-C4, alkyl (e. g. methyl, ethyl, propyl, butyl, pentyl or hexyl) optionally substituted by one, two or three substituents independently selected from halogen atoms (e. g. fluorine, chlorine, bromine or iodine) and -NR15Rl6 and-oR17 groups. <BR> <BR> <BR> <BR> <BR> <BR> <BR> <P> Preferably, R¹³ and R14 each independently represent a hydrogen atom, a 4-piperidinyl group optionally substituted by a Cl-C4 alkylphenyl substituent group, or a C3-C7 carbocyclic, C1-Cg, particularly C1-C6, alkyl (e. g. methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, heptyl or octyl), C2-C6 alkenyl (ethenyl, propenyl, butenyl, pentenyl or hexenyl) or C2-C6 alkynyl (ethynyl, propynyl, butynyl, pentynyl or hexynyl) group, which latter four groups may be optionally substituted by one, two, three or four substituent groups independently selected from halogen atoms (e. g. fluorine, chlorine,

bromine or iodine) and-NR R CONR R OR COOR NR COR SR -S02R1,-S02NRSR6,-NRgS02R9, morpholinyl, C1-C4 alkyl (e. g. methyl, ethyl, propyl, isopropyl, butyl or t-butyl), C3-C6 cycloalkyl (i. e. cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl), and aryl groups, wherein an aryl substituent group may be a phenyl, naphthyl, thienyl, pyridinyl, imidazolyl or indolyl group, each of which may be optionally substituted by one, two, three or four substituents independently selected from halogen atoms (e. g. fluorine, chlorine, bromine or iodine) and cyano, nitro,-NR R -CONRSR6,-OR,-NR8COR9,-S02NRSR6, NR8S02R9) Cl-C6, particularly Cl-C4, alkyl (e. g. methyl, ethyl, propyl, butyl, pentyl or hexyl) and trifluoromethyl groups, <BR> <BR> <BR> or R¹³ and R14 together with the nitrogen atom to which they are attached form a 4-to 7-membered saturated heterocyclic ring system, which ring system may be optionally substituted by one, two or three substituent groups independently selected from-NR R, -CoNR5R6,-OR,-COOR,-NR COR, and Ci-Ce, particularly Cl-C4, alKyl (e. g. methyl, ethyl, propyl, butyl, pentyl or hexyl) optionally substituted by one, two or three substituents independently selected from halogen atoms (e. g. fluorine, chlorine, bromine or iodine) and phenyl,-NR R and-OR groups; <BR> <BR> <BR> <BR> <BR> <BR> <BR> Particularly advantageous compounds of formula (1) are those in which one of R¹³ and R14 represents a hydrogen atom and the other of R and R represents a C I-C6 alkyl group substituted by an-OR group, e. g.-CII (CH2CH3) CH20H,-C (CH3) 2CH20H or CH (CH2CH (CH3) 2) CH20H.

Particularly preferred compounds of the invention include: (2R)-2-2-Amino-5-(phenylmethyl) thio thiazolo [4,5-d] pyrimidin-7-yl] amino]-1-butanol, (S)-2-2-Amino-5-(phenylmethyl) thio] thiazolo [4,5-dlpyrimidin-7-yl] amino]-l-butanol, 2-Amino-5- (2,3-difluorophenyl) methyl thio thiazolo [4,5-d] pyrimidin-7 (4H)-one, 5-[[(3-Phenoxyphenyl)methyl]thio]thiazolo[4, 5-dlpyrimidin-7 (4H)-one, 2-Amino-5- (3-phenoxyphenyl) methyl] thio] thiazolo 4, 5-dlpyrimidin-7 (4H)-one, ()-2- 2-Amino-5- (pentylthio) thiazolo [4,5-dl pyrimidin-7-yl] amino]-1-butanol, 2- 2-Amino-5- (pentylthio) thiazolo 4, 5-dl pyrimidin-7-yl amino] ethanol,

5- (Pentylthio) thiazolo [4,5-dlpyrimidin-7 (4H)-one, 2-Amino-5-[(phenylmethyl)thio]thiazolo[4, 5-d pyrimidin-7 (4H)-one, 2-Amino-5-(pentylthio)thiazolo[4, 5-dlpyrimidin-7 (4H)-one, 2-[[3-(Dimethylamino) propyl] amino]-5-(pentylthio) thiazolo [4, 5-dlpyrimidin-7 (4H)-one, 2-[[2-(Diethylamino) ethyl] amino]-5-(pentylthio) thiazolo[[2-(Diethylamino) ethyl] amino]-5-(pentylthio) thiazolo [4,5-dlpyrimidin-7 (4H)-one, 2-[[2-(Dimethylamino) ethyl] amino]-5-(pentylthio) thiazolo[[2-(Dimethylamino) ethyl] amino]-5-(pentylthio) thiazolo [4,5-d] pyrimidin-7 (4H)-one, 2- (3-Hydroxypropyl) amino-5- (pentylthio) thiazolo [4,5-dlpyrimidin-7 (4H)-one, 2-[[2-(Acetylamino)ethyl] amino)-5- (pentylthio) thiazolo [4,5-d]pyrimidin-7(4H)-one, (+)-2-(2, 3-Dihydoxypropyl) amino-5-(pentylthio) thiazolo 4,5-d pyrimidin-7 (4H)-one, 2-[[2-(4-Morpholinyl)ethyl]amino]-5-(pentylthio)thiazolo [4,5-d] pyrimidin-7 (4H)-one, 2-[(2-Methoxyethyl)amino]-5-(pentylthio)thiazolo [4,5-dlpyrimidin-7 (4H)-one, 2- (l-Methylethyl) amino-5- (pentylthio) thiazolo [4,5-J) pynmidin-7 (4)-one, 2- (Cyclopropylamino)-5- (pentylthio) thiazolo 4, 5-dlpyrimidin-7 (4H)-one, (#)-2-[(2-Hydoxypropyl)amino]-5-(pentylthio)thiazolo[4,5-d] pyrimidin-7 (41)-one, 2- 2- (2-Hydroxyethoxy) ethyl amino-5- (pentylthio) thiazolo [4,5-dlpyrimidin-7 (4H)-one, 2-[(2-Hydroxy-2-methylpropyl) amino]-5-(pentylthio)[(2-Hydroxy-2-methylpropyl) amino]-5-(pentylthio) thiazolo [4,5-dlpyrimidin-7 (4H)-one, 2-[(2-Hydroxyethyl)amino]-5-(pentylthio)thiazolo[4,5-d]pyrim idin-7(4H)-one, (2S, 3R)-3-Hydroxy-2- (7-oxo-5- (pentylthio)-4H-thiazolo [4,5-dlpyrimidin-2-yl]- amino) butanamide, N7- 3- (Dimethylamino) propyll-5- (pentylthio) thiazolo [4,5-dlpyrimidine-2,7-diamine, N7-[2-(Diethylamino) ethyl]-5-(pentylthio) thiazolof4, 5-dlpyrimidine-2,[2-(Diethylamino) ethyl]-5-(pentylthio) thiazolof4, 5-dlpyrimidine-2, 7-diamine, N7-[2-(Dimethylamino) ethyl]-5-(pentylthio)[2-(Dimethylamino) ethyl]-5-(pentylthio) thiazolo [4,5-d] pyrimidine-2,7-diamine, 3-[(2-Amino-5-(pentylthio)thiazolo[4,5-d]pyrimidin-7-yl)amin o]-1-propanol, N7-CycloheXyl-5-(pentylthio) thiazolo(pentylthio) thiazolo [4,5-d] pyrimidine-2, 7-diamine, (#)-3-[(2-Amino-5-((phenylmethyl)thio) thiazolo [4,5-d]pyrimidin-7-yl)amino]-1,2- propanediol, N7-(2-Methoxyethyl)-5-(pentylthio)thiazolo [4,5-dlpyrimidine-2,7-diamine, 5-(Pentylthio)-N7-propylthiazolo[4, 5-dlpyrimidine-2,7-diamine, N7-Cyclopentyl-5-(pentylthio)(pentylthio) thiazolo [4,5-d]pyrimidine-2,7-diamine, N7-Cyclopropyl-5-(pentylthio)thiazolo [4,5-d]pyrimidine-2,7-diamine,

N7- (2-Methylpropyl)-5- (pentylthio) thiazolo [4,5-dlpyrimidine-2,7-diamine, (_)-1-(2-Amino-5-(pentylthio) thiazolo [4,5-d] pyrimidin-7-yl) amino]-2-propanol, (exo)-N7-Bicyclo [2.2.1] hept-2-yl-5- (pentylthio) thiazolo [4,5-d] pyrimidine-2,7-diamine, 2-[2-[[2-Amino-5-(pentylthio) thiazolo [4, 5-dupyrimidin-7-yl][2-[[2-Amino-5-(pentylthio) thiazolo [4, 5-dupyrimidin-7-yl] amino] ethoxy] ethanol, ()-N7- (2-Methylbutyl)-5- (pentylthio) thiazolo [4,5-dlpyrimidine-2,7-diamine, 1- 2-Amino-5- (pentylthio) thiazolo [4,5-d] pyrimidin-7-yl] amino]-2-methyl-2-propanol, N7-[(2-Aminophenyl) methyl]-5-(pentylthio) thiazolo [47s-dlpyrimidine-2,[(2-Aminophenyl) methyl]-5-(pentylthio) thiazolo [47s-dlpyrimidine-2, 7-diamine, 2-Amino-5-[(2-phenoxyethyl) thio] thiazolo[(2-phenoxyethyl) thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one, (E)-2-Amino-5- (3-phenyl-2-propenyl) thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one, 2-Amino-5-[[3-[2,4-bis(1,1-dimethylethyl)phenoxy]propyl]thio ] thiazolo [4,5-d] pyrimidin- 7 (4H)-one, 2-Amino-5-[[[(4-trifluoromethyl)phenyl]methyl]thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one, 2-Amino-5-[[(3,5-dichlorophenyl)methyl]thio] thiazolo 4,5-d pyrimidin-7 (4H)-one, 2-Amino-5-[[(2, 4-dichlorophenyl) methyl][[(2, 4-dichlorophenyl) methyl] thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one, 2-Amino-5-[[(3,4-dichlorophenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one, 2-Amino-5-[[(3,5-dibromophenyl)methyl] thio thiazolo [4,5-d] pyrimidin-7 (4H)-one, 2-Amino-5-[[(2-nitrophenyl) methyl] thio] thiazolo[[(2-nitrophenyl) methyl] thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one, 2-Amino-5-[[(2-fluorophenyl) methyl] thio] thiazolo[[(2-fluorophenyl) methyl] thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one, 2-Amino-5-[[(2-iodophenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one, 2-Amino-5-[[(3-chlorophenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one, 2-Amino-5-[[(2-chlorophenyl) methyl][[(2-chlorophenyl) methyl] thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one, 2-Amino-5- (4-chloro-2-nitrophenyl) methyl thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one, 2-Amino-5-[[(3-chloro-4-methoxyphenyl)methyl]thio] thiazolo [4,5-dlpyrimidin-7 (4hO-one, 2-Amino-5- (2,3-dichlorophenyl) methyl thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one, 2-Amino-5-[[(3,5-difluorophenyl)methyl]thio] thiazolo [4,5-d]pyrimidin-7(4H)-one, 2-Amino-5- (2,4-bis (trifluoromethyl) phenyl methyl thio] thiazolo [4,5-d] pyrimidin-7 (4H)- one, 2-Amino-5-[[(2-bromophenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one, 2-Amino-5- (2,3,4-trifluorophenyl) methyl thio thiazolo [4,5-d] pyrimidin-7 (4H)-one, 2-Amino-5-[[(3-bromophenyl)methyl]thio] thiazolo [4,5-d]pyrimidin-7(4H)-one,

2-Amino-5-[[(2-fluoro-3-methylphenyl) methyl] thio] thiazolo[[(2-fluoro-3-methylphenyl) methyl] thio] thiazolo [4,5-dlpyrimidin-7 (4H)-one, 3-[[2-Amino-5-[(phenylmethyl)thio] thiazolo 4,5-d pyrimidin-7-yl amino]-2,2-dimethyl-1- propanol, (#)-α-[[[2-Amino-5-[(phenylmethyl)thio] thiazolo [4,5-d] pyrimidin-7- yl amino] methyl benzenemethanol, (R)-ß-2-Amino-5-(phenylmethyl) thio] thiazolo [4,5-d]pyrimidin-7- yl amino benzenepropanol, 2-[[2-Amino-5-[(phenylmethyl) thio] thiazolo[[2-Amino-5-[(phenylmethyl) thio] thiazolo [4,5-dlpyrimidin-7-yl] amino] ethanol, (2R)-2-[[2-Amino-5-[(phenylmethyl)thio] thiazolo [4,5-dupyrimidin-7-yl] amino] 4- methylpentanol, ()-1- 2-Amino-5- (phenylmethyl) thiol thiazolo [4,5-d] pyrimidin-7-yl] amino]-2-propanol, (#)-ß-[[2-Amino-5-[(phenylmethyl)thio] thiazolo [4,5-d]pyrimidin-7-yl]amino]-4- chlorobenzenepropanol, (+)-3-2-Amino-5-(phenylmethyl) thio thiazolo [4,5-d]pyrimidin-7-yl]amino]-1,2- propanediol, 2-[[2-Amino-5-[(phenylmethyl) thio][[2-Amino-5-[(phenylmethyl) thio] thiazolo [4,5-d]pyrimidin-7-yl]propylamino]ethanol, (+)-1-2-Amino-5-(phenylmethyl) thio] thiazolo 4, 5-d pyrimidin-7-yl-3-pyrrolidinol, (+)-1-2-Amino-5-(phenylmethyl) thio thiazolo [4,5-d] pyrimidin-7-yl]-3-piperidinol, 1-[2-Amino-5-[(phenylmethyl) thio] thiazolo[2-Amino-5-[(phenylmethyl) thio] thiazolo [4,5-dlpyrimidin-7-yl]-4-piperidinol, 3-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]-2,2- dimethyl-1-propanol, (#)-2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]- 1-butanol, (+)-a-2-Amino-5-(3-phenoxyphenyl) methyl thiolthiazolo [4,5-d] pyrimidin-7-yl]- amino] methyl benzenemethanol, 4-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]-1- butanol, 6-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-dlpyrimidin-7-yl] amino]-1- hexanol,

4- 2-Amino-5- (3-phenoxyphenyl) methyl thio] thiazolo [4,5-d] pyrimidin-7-yl]- amino cyclohexanol, (R)-ß-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4 , 5-dlpyrimidin-7-yl- amino benzenepropanol, (#)-2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-dlpyrimidin-7-yl] amino]- 1-propanol, 2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7-yl]- amino] ethanol, (2R)-2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-dlpyrimidin-7-yl]- amino-4-methylpentanol, (#)-1-Amino-3-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7- yl amino]-2-propanol, (#)-1-[[2-Amino-5-[[(3-phenoxyphenyl)methyl] thio thiazolo [4,5-dlpyrimidin-7-yl] amino]- 2-propanol, 2-[[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo 4,5-d pyrimidin-7- yl amino methyl-2-ethyl-1, 3-propanediol, (#)-ß-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]- 4-chlorobenzenepropanol, (#)-3-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4, 5-d pyrimidin-7-yl amino]- 1,2-propanediol, 2-[[2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-dlpyrimidin-7- yl amino] ethyl amino] ethanol, 3-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7-yl amino-1- propanol, (#)-α-[[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[ 4,5-d pyrimidin-7- yl amino] methyl-3,4-dichlorobenzenepropanol, 1-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]-2- methyl-2-propanol, 2-[2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl] thio thiazolo [4,5-d] pyrimidin-7- yl amino ethoxy ethanol,

5-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4,5-d] pyrimidin-7-yl]amino]-1- pentanol, (2S)-2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl] thio thiazolo [4,5-dlpyrimidin-7- yl]amino]-4-(methylthio)-1-butanol, 2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo 4, 5-d pyrimidin-7- yl butylamino ethanol, 2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo 4, 5-d pyrimidin-7- yl propylamino ethanol, 2,2'-[[2-Amino-5-[[(3-phenoxyphenyl)methyl] thio thiazolo [4,5-d] pyrimidin-7- yl imino bisethanol, 2-[[[2-Amino-5-[[(3-phenoxyphenyl) methyl] thio] thiazolo[[[2-Amino-5-[[(3-phenoxyphenyl) methyl] thio] thiazolo [4,5-d] pyrimidin-7-yl]- (2- hydroxyethyl) amino methyl phenol, 3-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d]pyrimidin-7-yl]-(2- hydroxyethyl) amino-1-propanol, (#)-1-[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7-yl]-3- pyrrolidinol, (trans)-1-[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d]pyrimidin-7-yl]-4- hydroxy-L-proline phenylmethyl ester, (#)-1-[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4,5 -dlpyrimidin-7-yl-3- piperidinemethanol, (#)-1-[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4,5 -d]pyrimidin-7-yl]-3- piperidinol, (25)-1-2-Amino-5-(3-phenoxyphenyl) methyl thio thiazolo [4,5-d] pyrimidin-7-yl]-2- pyrrolidinemethanol, 1-[2-Amino-5-[[(3-phenoxyphenyl)methyl] thio] thiazolo [4,5-d]pyrimidin-7-yl]-4- piperidinol, (2R)-2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4 , 5-dlpyrimidin-7- yl amino-I-butanol, (2S)-2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4 , 5-dlpyrimidin-7- yl] amino-1-butanol,

(2R)-2-[[2-Amino-5-[[(2,3-difluorophenyl)methyl] thio thiazolo [4,5-dlpyrimidin-7- yl amino-1-butanol, 2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4, 5-d pyrimidin-7-yl amino-1,3- propanediol, 2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]-2- methyl-1-propanol, 2-[[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo[[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]-2- methyl-1-propanol, I-[[2-Amino-5-[[(2, 3-difluorophenyl) methyl][[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]-2- methyl-2-propanol, 5-[[(2, 3-Difluorophenyl) methyl] thio]-N7-(2-fluoroethyl) thiazolo[[(2, 3-Difluorophenyl) methyl] thio]-N7-(2-fluoroethyl) thiazolo [4,5-d] pyrimidine-2,7- diamine, (IR-trans) 2-2-Amino-5-(2, 3-difluorophenyl) methyl thio] thiazolo [4,5-d] pyrimidin-7- yl amino]-cyclopentanol, (l S-trans) 2-2-Amino-5-(2, 3-difluorophenyl) methyl thio thiazolo [4,5-d] pyrimidin-7- yl amino]-cyclopentanol, 2- 2-Amino-5- (phenylmethyl) thio] thiazolo [4,5-d]pyrimidin-7-yl]amino]-2-methyl-1- propanol, 2-Methyl-2-[[2-(methylamino)-5-[(phenylmethyl)thio] thiazolo [4,5-d] pyrimidin-7- yl amino-1-propanol, 2-[[2-[[5-[[(2,3-Difluorophenyl)methyl]thio]-2-[(phenylmethy l)amino] thiazolo 4,5- d pyrimidin-7-yl amino-2-methyl-1-propanol, 5-[[(2, 3-Difluorophenyl) methyl] thio] thiazolo[[(2, 3-Difluorophenyl) methyl] thio] thiazolo [4,5-d]pyrimidin-7(4H)-one, (+)-2-2-Amino-5-(2, 3-difluorophenyl) methyl thio thiazolo [4,5-d] pyrimidin-7- yl] amino-I-butanol, (I S, 2S)-2-2-Amino-5-(2, 3-difluorophenyl) methyl thio thiazolo [4,5-d] pyrimidin-7- yl] amino-cyclohexanol, (+)-2-2-Amino-5-(2, 3-difluorophenyl) methyl thio thiazolo [4,5-d] pyrimidin-7- yl amino-I-propanol,

2-[[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo[[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo [4,5-dlpyrimidin-7-yl] amino]-1- ethanol, (2R)-2-[[2-Amino-5-[[(2,3-difluorophenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7- yl amino-4-methyl-1-pentanol, (+)-1-2-Amino-5-(2, 3-difluorophenyl) methyl thio thiazolo [4,5-dlpyrimidin-7- yl amino]-2-propanol, 2-[[2-Amino-5-[[(2,3-difluorophenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]-2- methyl-1,3-propanediol, 1-[[[2-Amino-5-[[(2,3-difluorophenyl)methyl]thio] thiazolo [4,5-dlpyrimidin-7- yl]amino] methyl]-cyclohexanol, (2R)-2-[[2-Amino-5-[[(2,3-difluorophenyl)methyl]thio] thiazolo [4,5-dlpyrimidin-7- yl] amino-1-butanol, 2-[[2-Amino-5-[[(2,3-difluorophenyl)methyl]thio]thiazolo [4,5-d] pyrimidin-7-yl]- (2- aminoethyl) amino-1-ethanol, 2-[2-[[2-Amino-5-[[(2,3-difluorophenyl)methyl]thio] thiazolo [4,5-dlpyrimidin-7- yl amino] ethoxy-1-ethanol, (aS)-a-(1R)-1-2-Amino-5-(2, 3-difluorophenyl) methyl thio] thiazolo [4,5-d] pyrimidin- 7-yl methylamino ethyl-benzenemethanol, 1-[2-Amino-5-[[(2, 3-difluorophenyl) methyl][2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo [4,5-d] pyrimidin-7-yl]-4- piperidinol, 5-[[(2, 3-Difluorophenyl)[[(2, 3-Difluorophenyl) methyl] thio-N7-ethyl-thiazolo [4,5-d] pyrimidine-2,7-diamine, 5-[[(2, 3-Difluorophenyl) methyl] thio]-N7-(2-propenyl)-thiazolo[[(2, 3-Difluorophenyl) methyl] thio]-N7-(2-propenyl)-thiazolo [4,5-d] pyrimidine-2,7- diamine, (1 S, 2S)-2-2-Amino-5-(2,3-difluorophenyl) methyl] thio] thiazolo [4,5-d] pyrimidin-7- yl] amino-1-phenyl-1,3-propanediol, 2-[[2-Amino-5-[[(2, 3-difluorophenyl) methyl][[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo 4,5-d pyrimidin-7-yl amino- 1,3-propanediol, 2-[[2-Amino-5-[[(2, 3-difluorophenyl) methyl][[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo [4,5-dlpyrimidin-7-yl] amino]-1- ethanol,

(_)-5-(2, 3-Difluorophenyl) methyl thio-N7-(2-methoxy-1-methylethyl)-thiazolo [4,5- dJpyrimidine-2,7-diamine, N7-Cyclopropyl-5-[[(2,3-difluorophenyl) methyl thio-thiazolo [4,5-d] pyrimidine-2,7- diamine, (i)-2-2-Amino-5-(2, 3-difluorophenyl) methyl thio-thiazolo [4,5-d] pyrimidin-7- yl amino-I-propanol, 4-[[2-Amino-5-[[(2,3-difluorophenyl)methyl] thio-thiazolo [4,5-dlpyrimidin-7-yl] amino]-1- butanol, 5-[[(2, 3-Difluorophenyl) methyl] thio]-N7-[2-(lH-imidazol-4-yl) ethyl]-thiazolo[[(2, 3-Difluorophenyl) methyl] thio]-N7-[2-(lH-imidazol-4-yl) ethyl]-thiazolo [4,5- d pyrimidine-2,7-diamine, (+)-N-5-(2, 3-Difluorophenyl) methyl thio-7-(2-hydroxy-1, 1- dimethylethyl) amino] thiazolo [4,5-d] pyrimidin-2-yl]-serine, methyl ester, 2- 5- (2,3-Difluorophenyl) methyl thio-2- (I-methylethyl) amino] thiazolo [4,5- d pyrimidin-7-yl amino-2-methyl-1-propanol, 2-[[5-[[(2,3-Difluorophenyl)methyl] thio-2- (ethylamino) thiazolo(ethylamino) thiazolo [4,5-d] pyrimidin-7- yl] amino-2-methyl-1-propanol, 2-[[5-[[(2,3-Difluorophenyl)methyl]thio]-2-[[2-(1H-indol-3-y l)ethyl]amino]thiazolo[4,5- d pyrimidin-7-yl amino-2-methyl-1-propanol, 2-[[5-[[(2,3-Difluorophenyl)methyl]thio]-2-[(1-naphthalenylm ethyl)amino]thiazolo[4, 5- d pyrimidin-7-yl amino-2-methyl-1-propanol, 2- 5- (2,3-Difluorophenyl) methyl thio-2- (1,2-diphenylethyl) amino] thiazolo [4,5- d pyrimidin-7-yl amino-2-methyl-1-propanol, 2- 5- (2,3-Difluorophenyl) methyl thio-2- [(2, 2,2-trifluoroethyl) amino] thiazolo [4,5- d pyrimidin-7-yl amino-2-methyl-1-propanol, 2-[[5-[[(2,3-Difluorophenyl)methyl]thio]-2-[[(3,4, 5- trimethoxyphenyl) methyl] amino] thiazolo [4,5-dlpyrimidin-7-yl] amino]-2-methyl-1- propanol, 2-[[5-[[(2,3-Difluorophenyl)methyl]thio]-2-[(1,1-dimethyleth yl)amino] thiazolo [4,5- d pyrimidin-7-yl amino-2-methyl-1-propanol,

2-[[5-[[(2,3-Difluorophenyl)methyl]thio]-2-[[2-(2-thienyl)et hyl]amino] thiazolo [4,5- d pyrimidin-7-yl amino-2-methyl-1-propanol, 2- 5- (2,3-Difluorophenyl) methyl thio-2- (4-methylcyclohexyl) amino thiazolo [4,5- d pyrimidin-7-yl amino-2-methyl-1-propanol, 2- 5- (2, 3-Difluorophenyl)methyl]thio]-7-[(2-hydroxy-1,1- dimethylethyl) amino thiazolo [4,5-d]pyrimidin-2-yl]amino]-acetamide, 2-[[2-[[2-(4-Aminophenyl) ethyl] amino]-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo[[2-[[2-(4-Aminophenyl) ethyl] amino]-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo [4,5- d pyrimidin-7-yl amino-2-methyl-l-propanol, 2- 5- (2, 3-Difluorophenyl)methyl]thio]-2-[(2-fluoroethyl)amino] thiazolo [4,5- d pyrimidin-7-yl amino-2-methyl-1-propanol, 2-[[2-(Cyclopropylamino)-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo[[2-(Cyclopropylamino)-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo [4,5-d]pyrimidin-7- yl] amino-2-methyl-1-propanol, (#)-2-[[5-[[(2,3-Difluorophenyl)methyl]thio]-7-[(2-hydroxy-1 ,1- dimethylethyl) amino thiazolo [4,5-d]pyrimidin-2-yl]amino]-1-pentanol, 2- 5- (2, 3-Difluorophenyl) methyl thio-2- 2- (2- hydroxyethoxy) ethyl amino thiazolo [4,5-d] pyrimidin-7-yl] amino]-2-methyl-1-propanol, N-[5-[[(2,3-Difluorophenyl) methyl thio-6, 7-dihydro-7-oxo-thiazolo [4,5-d]pyrimidin-2- yl]-DL-serine, methyl ester, 5-[[(2, 3-Difluorophenyl) methyl] thio]-2-[(1-methylethyl) amino]-thiazolo[[(2, 3-Difluorophenyl) methyl] thio]-2-[(1-methylethyl) amino]-thiazolo [4,5-d] pyrimidin- 7(4H)-one, 5-[[(2, 3-Difluorophenyl) methyl] thio]-2-[[2-(IH-indol-3-yl) ethyl] amino]-thiazolo[[(2, 3-Difluorophenyl) methyl] thio]-2-[[2-(IH-indol-3-yl) ethyl] amino]-thiazolo [4,5- d pyrimidin-7(4H)-one, 2-[[5-[[(2,3-Difluorophenyl)methyl]thio]-6,7-dihydro-7-oxo-t hiazolo[4,5-d]pyrimidin-2- yl amino]-acetamide, 2-[[2-(4-Aminophenyl)ethyl]amino]-5-[[(2,3-difluorophenyl)me thyl]thio]-thiazolo[4, 5- d pyrimidin-7(4H)-one, 5-[[(2, 3-Difluorophenyl) methyl] thio]-2-[(2-fluoroethyl) amino]-thiazolo[[(2, 3-Difluorophenyl) methyl] thio]-2-[(2-fluoroethyl) amino]-thiazolo [4,5-d] pyrimidin- 7(4H)-one, 5-[[(2, 3-Difluorophenyl) methyl] thio]-2-[[2-(2-hydroxyethoxy) ethyl] amino]-thiazolo[[(2, 3-Difluorophenyl) methyl] thio]-2-[[2-(2-hydroxyethoxy) ethyl] amino]-thiazolo [4,5- dlpyrimidin-7 (4H)-one,

2-[[2-(Cyclohexylamino)-5-[(phenylmethyl)thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]-2- methyl-1-propanol, 2-[[2-[(1, 1-Dimethylethyl) amino]-5-[(phenylmethyl)[[2-[(1, 1-Dimethylethyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5-dlpyrimidin-7- yl amino-2-methyl-1-propanol, N-[7-[(2-Hydroxy-l, l-dimethylethyl) amino]-5-[(phenylmethyl) thio] thiazolo [4, 5 d pyrimidin-2-yl-DL-alanine, methyl ester, 4-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5-[(phenylmethyl) thio]thiazolo[4, 5- d pyrimidin-2-yl amino-cyclohexanol, 2-Methyl-2-[[2-[(4-phenylbutyl)amino]-5-[(phenylmethyl)thio] thiazolo [4,5-d] pyrimidin-7- yl amino-1-propanol, 2-Methyl-2-[[5-[(phenylmethyl)thio]-2-[[(tetrahydro-2-furany l)methyl]amino] thiazolo [4,5- d pyrimidin-7-yl amino-1-propanol, 2-Methyl-2-[[2-[(1-methylethyl) amino]-5-[(phenylmethyl)[[2-[(1-methylethyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7- yl amino-1-propanol, 2-[[2-[[2-(4-Aminophenyl) ethyl] amino]-5-[(phenylmethyl)[[2-[[2-(4-Aminophenyl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7- yl amino-2-methyl-1-propanol, N-[7-[(2-Hydroxy-1, 1-dimethylethyl) amino]-5-[(phenylmethyl) thio][7-[(2-Hydroxy-1, 1-dimethylethyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-2-yl-L-valine, ethyl ester, (2S)-2-7-(2-Hydroxy-1, 1-dimethylethyl) amino-5-(phenylmethyl) thio] thiazolo [4,5- c pyrimidin-2-yl amino-4-methyl-pentanamide, 2-Methyl-2-[[2-[(2-phenylethyl) amino]-5-[(phenylmethyl)[[2-[(2-phenylethyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7- yl] amino-I-propanol, 2-[[2-[[(4-Aminophenyl)methyl]amino]-5-[(phenylmethyl)thio] thiazolo [4,5-d] pyrimidin-7- yl amino-2-methyl-1-propanol, 2-Methyl-2-[[5-[(phenylmethyl)thio]-2-[[2-(2-thienyl)ethyl]a mino]thiazolo[4, 5- d pyrimidin-7-yl amino-1-propanol, 2-[[2-[(2-Fluoroethyl)amino]-5-[(phenylmethyl)thio] thiazolo [4,5-d]pyrimidin-7-yl]amino]- 2-methyl-1-propanol, 2-Methyl-2-[[2-[[(3-nitrophenyl)methyl]amino]-5-[(phenylmeth yl)thio] thiazolo [4,5- d pyrimidin-7-yll amino-I-propanol,

(αR)-α-[(1S)-1-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5- [(phenylmethyl)thio] thiazolo [4,5-dupyrimidin-2-yl] amino] ethyl-benzenemethanol, 2-Methyl-2-[[5-[(phenylmethyl)thio]-2-[[(3,4, 5- trimethoxyphenyl) methyl amino thiazolo [4,5-d] pyrimidin-7-yl] amino]-1-propanol, 2-Methyl-2-[[2-[(lR-trans)-(2-phenylcyclopropyl)[[2-[(lR-tra ns)-(2-phenylcyclopropyl) amino]-5- (phenylmethyl) thio] thiazolo [4,5-pyrimidin-7-yl] amino]-1-propanol, 2-[[2-[[2-(lH-Indol-3-yl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo[[2-[[2-(lH-Indol-3-yl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7- yl amino-2-methyl-1-propanol, 2-[[2-[(1, 1-Dimethylpropyl) amino]-5-[(phenylmethyl) thio] thiazolo[[2-[(1, 1-Dimethylpropyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7- yl amino-2-methyl-l-propanol, (+)-2-Methyl-2-2-(l-methylbutyl) amino-5-(phenylmethyl) thio thiazolo [4,5- dlpyrimidin-7-yl amino-1-propanol, (+)-2-Methyl-2-2-(l-methylhexyl) amino-5-(phenylmethyl) thio thiazolo [4,5- dlpyrimidin-7-yl amino-1-propanol, 2-[[2-[[(2-Aminophenyl) methyl] amino]-5-[(phenylmethyl)[[2-[[(2-Aminophenyl) methyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7- yl] amino-2-methyl-1-propanol, 2-[[7-[(2-Hydroxy-1,1-dimethylethyl) amino-5- [(phenylmethyl) thio][(phenylmethyl) thio] thiazolo [4,5- d]pyrimidin-2-yl]amino]-1,3-propanediol, 2-[[2-[[2-(Ethylthio) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo[[2-[[2-(Ethylthio) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5-dlpyrimidin-7- yl amino-2-methyl-1-propanol, (2S)-2-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5-[(phenylme thyl)thio] thiazolo [4,5- d pyrimidin-2-yl amino]-3,3-dimethyl-1-butanol, (aS)-a-(lR)-1-7-(2-Hydroxy-1, 1-dimethylethyl) amino]-5- (phenylmethyl) thio thiazolo [4,5-dlpyrimidin-2-yl] amino]-2-methoxyethyl]- benzenemethanol, 2-[[2-(Ethylamino)-5-[(phenylmethyl)thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]-2-methyl- 1-propanol, 2-[[2-[[[3-Fluoro-5-(trifluoromethyl)phenyl]methyl]amino]-5- (phenylmethyl) thio thiazolo [4,5-d] pyrimidin-7-yl] amino]-2-methyl-l-propanol,

(i)-2-Methyl-2-2-(1-methylpropyl) amino-5-(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-1-propanol, 2-[[2-[[(4-Methoxyphenyl)methyl]amino]-5-[(phenylmethyl)thio ]thiazolo[4, 5-d pyrimidin- 7-yl amino-2-methyl-1-propanol, 2-[[2-[(2-Hydroxyethyl) amino]-5-[(phenylmethyl) thio] thiazolo[[2-[(2-Hydroxyethyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5-dlpyrimidin-7- yl] amino-2-methyl-1-propanol, 2-[[2-[[2-(lH-Imidazol-4-yl) ethyl] amino]-5-[(phenylmethyl)[[2-[[2-(lH-Imidazol-4-yl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo 4, 5-d pyrimidin- 7-yl amino-2-methyl-l-propanol, 2-[[2-[(Diphenylmethyl)amino]-5-[(phenylmethyl)thio] thiazolo [4,5-dlpyrimidin-7- yl amino-2-methyl-l-propanol, (2S)-2-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5-[(phenylme thyl)thio] thiazolo [4,5- d pyrimidin-2-yl amino-1-butanol, 2-[[2-[(2,2-Diethoxyethyl)amino]-5-[(phenylmethyl)thio] thiazolo [4,5-d] pyrimidin-7- yl] amino-2-methyl-1-propanol, 4-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d amino-1-butanol, (1S,2S)-2-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5-[(pheny lmethyl)thio] thiazolo [4,5- d amino-cyclohexanol, (_)-2-2-(2-Hydroxy-1-methylethyl) amino-5-(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-2-methyl-1-propanol, 2-[[2-[[2-(2-Hydroxyethoxy) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo[[2-[[2-(2-Hydroxyethoxy) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin- 7-yl] amino-2-methyl-1-propanol, (#)-2-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5-[(phenylmet hyl)thio] thiazolo [4,5- d pyrimidin-2-yl amino-l-pentanol, 2-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d]pyrimidin-2-yl]amino]-acetamide, ()-2- 2- 1- (4-Fluorophenyl) ethyll amino-5- (phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-2-methyl-propanol, (lR,2S)-2-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5-[(pheny lmethyl)thio] thiazolo [4,5- d pyrimidin-2-yl amino]-cyclohexanol,

(αS)-α-[(1R)-1-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5- (phenylmethyl) thio] thiazolo [4,5-dJpyrimidin-2-yl] amino] ethyl]-benzenemethanol, (#)-2-[[2-(Methylamino)-5-[(phenylmethyl)thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]-I- propanol, (2R)-4-Methyl-2-2-(methylamino)-5-(phenylmethyl) thio thiazolo [4,5-d] pyrimidin-7- yl]amino]-1-pentanol, N-[2-(Methylamino)-5-[(phenylmethyl)[2-(Methylamino)-5-[(phe nylmethyl) thio] thiazolo [4,5-d3pyrimidin-7-yl]-L-serine, ethyl ester, (+)-2-5-(Phenylmethyl) thio-2-(tetrahydro-2-furanyl) methyl amino thiazolo [4,5- c pyrimidin-7-yl amino-1-butanol, (#)-2-[[5-[(Phenylmethyl)thio]-2-[[(tetrahydro-2-furanyl)met hyl]amino] thiazolo [4,5- d pyrimidin-7-yl amino-I-propanol, (2R)-4-Methyl-2-[[5-[(phenylmethyl)thio]-2-[[(tetrahydro-2- furanyl) methyl] amino] thiazolo [4,5-d]pyrimidin-7-yl]amino]-1-pentanol, N-[5-[(Phenylmethyl)thio]-2-[[(tetrahydro-2-furanyl)methyl]a mino] thiazolo [4,5- d pyrimidin-7-yl-L-serine, ethyl ester, (+)-2-2-2-(2-Hydroxyethoxy) ethyl amino-5-(phenylmethyl) thio thiazolo [4,5- d]pyrimidin-7-yl]amino]-1-propanol, (#)-4-[2-[[7-[[1-(Hydroxymethyl)propyl]amino]-5-[(phenylmeth yl)thio]thiazolo[4,5- d pyrimidin-2-yl amino ethyl-benzenesulfonamide, (#)-4-[2-[[7-[(2-Hydroxy-1-methylethyl)amino]-5-[(phenylmeth yl)thio] thiazolo [4,5- d pyrimidin-2-yl amino] ethyl-benzenesulfonamide, 4-[2-[[7-[[(1R)-1-(Hydroxymethyl)-3-methylbutyl]amino]-5- (phenylmethyl) thio thiazolo [4,5-d] pyrimidin-2-yl] amino] ethyl]-benzenesulfonamide, ()-4- 4-2-7-(2-Hydroxypropyl) amino-5-(phenylmethyl) thio thiazolo [4,5-d]pyrimidin-2- yl] amino ethyl-benzenesulfonamide, N'-Ethyl-N2- 2- (IH-imidazol-4-yl) ethyl-5- (phenylmethyl) thiothiazolo [4,5-d] pyrimidine- 2,7-diamine, N2-[2-(lH-Imidazol-4-yl) ethyl]-5-[(phenylmethyl) thio]-N7-(3-pyridinylmethyl)- thiazolo [4,5-d] pyrimidine-2,7-diamine,

(i)-2-2-2-(lH-Imidazol-4-yl) ethyl] amino-5- [(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino- 1-butanol, (i)-2-2-2-(lH-Imidazol-4-yl) ethyl amino-5-(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino- 1-propanol, (2R)-2-2-2-(lH-Imidazol-4-yl) ethyl amino-5-(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-4-methyl-1-pentanol, (i)-1-2-2-(lH-Imidazol-4-yl) ethyl] amino-5- [(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino]-2-propanol, 5-[[2-[[2-(lH-Imidazol-4-yl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolor4, 5-d3pyrimidin- 7-yl] amino-1-pentanol, 1-[2-[[2-(lH-Imidazol-4-yl) ethyl] amino]-5-[(phenylmethyl)[2-[[2-(lH-Imidazol-4-yl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5-d3pyrimidin- 7-yl-4- (phenylmethyl)-4-piperidinol, (+)-l-2-2-(lH-Imidazol-4-yl) ethyl amino-5-(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl-3-piperidinecarboxamide, 2-[Ethyl [2-[[2-(lH-imidazol-4-yl)[Ethyl [2-[[2-(lH-imidazol-4-yl) ethyl] amino-5- [(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-1-ethanol, N2-[2-(lH-Imidazol-4-yl) ethyl]-N7, N7-dimethyl-5-[(phenylmethyl) thio]-thiazolo[2-(lH-Imidazol-4-yl) ethyl]-N7, N7-dimethyl-5-[(phenylmethyl) thio]-thiazolo [4,5- d3pyrimidine-2,7-diamine, N7- 2- (Diethylamino) ethyl-N-ethyl-N2- 2- (lH-imidazol-4-yl) ethyl-5- [(phenylmethyl)thio]-thiazolo [4,5-d3pyrimidine-2,7-diamine, N2- (2-Phenoxyethyl)-5- (phenylmethyl) thio-N7- (3-pyridinylmethyl)-thiazolo [4,5- d]pyrimidine-2,7-diamine, N2-(2-Phenoxyethyl)-N7-[1-(phenylmethyl)-4-piperidinyl]-5-[( phenylmethyl)(2-Phenoxyethyl)-N7-[1-(phenylmethyl)-4-piperid inyl]-5-[(phenylmethyl) thio]- thiazolo [4,5-d] pyrimidine-2,7-diamine, 2-Methyl-2-[[2-[(2-phenoxyethyl) amino]-5-[(phenylmethyl)[[2-[(2-phenoxyethyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5-d3pyrimidin- 7-yl amino-1-propanol, (#)-2-[[2-[(2-Phenoxyethyl)amino]-5-[(phenylmethyl)thio] thiazolo [4,5-dlpyrimidin-7- yl] amino-1-propanol, (#)-4-Methyl-2-[[2-[(2-phenoxyethyl)amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-1-pentanol,

1-[2-[(2-Phenoxyethyl)amino]-5-[(phenylmethyl)thio] thiazolo [4,5-d] pyrimidin-7-yl]-4- (phenylmethyl)-4-piperidinol, 2-[[2-(Cyclopropylamino)-5-[(phenylmethyl)thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]-1- butanol, 2-[[2-(Cyclopropylamino)-5-[(phenylmethyl)thio] thiazolo [4,5-dlpyrimidin-7-yl] amino]-1- propanol, (2R)-2-2-(Cyclopropylamino)-5-(phenylmethyl) thio] thiazolo [4,5-dlpyrimidin-7- yl] amino-4-methyl-1-pentanol, N-[2-(Cyclopropylamino)-5-[(phenylmethyl)thio] thiazolo [4,5-d] pyrimidin-7-yl]-L-serine, ethyl ester, (2R)-2-2-1-(Hydroxymethyl) butyl amino-5-(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-4-methyl-l-pentanol, N-[2-[[l-(Hydroxymethyl) butyl] amino]-5-[(phenylmethyl) thio] thiazolo[2-[[l-(Hydroxymethyl) butyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7- yl-L-serine, ethyl ester, (#)-2-[[7-[Cyclohexyl(2-hydroxyethyl)amino-5- [(phenylmethyl)[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-2-yl amino-1-pentanol, 2-[2-[[7-(Ethylamino)-5-[(phenylmethyl)thio] thiazolo [4,5-dl pyrimidin-2-yl] amino] ethoxy- 1-ethanol, 2-[2-[[7-[(1-Methylethyl)amino]-5-[(phenylmethyl)thio] thiazolo [4,5-dlpyrimidin-2- yl amino] ethoxy-1-ethanol, ()-2- 2- 2- (2-Hydroxyethoxy) ethyl amino-5- (phenylmethyl) thio thiazolo 4,5- d pyrimidin-7-yl amino-1-butanol, 2-[[2-[[2-(2-Hydroxyethoxy)ethyl]amino]-5-[(phenylmethyl)thi o] thiazolo [4,5-d] pyrimidin- 7-yl amino-2-methyl-1-propanol, (2R)-2-[[2-[[2-(2-Hydroxyethoxy)ethyl]amino]-5-[(phenylmethy l)thio] thiazolo [4,5- dlpyrimidin-7-yl amino-4-methyl-1-pentanol, 2-[Cyclohexyl-[2-[[2-(2-hydroxyethoxy)ethyl] amino-5- [(phenylmethyl) thio] thiazolo[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-1-ethanol, ()-2- thio-2- (4-piperidinylamino) thiazolo [4,5-d] pyrimidin-7- yl amino-1-propanol,

(#)-N-[2-[[7-[[1-(Hydroxymethyl)propyl]amino]-5-[(phenylmeth yl)thio] thiazolo [4,5- d pyrimidin-2-yl amino ethyl-acetamide, (i)-N-2-7-(2-Hydroxy-l-methylethyl) amino-5-(phenylmethyl) thio thiazolo [4,5- d pyrimidin-2-yl amino ethyl-acetamide, N-[2-[[7-[(2-Hydroxyethyl)amino]-5-[(phenylmethyl)thio] thiazolo [4,5-dlpyrimidin-2- yl amino ethyl]-acetamide, N-[2-[[7-[[(1R)-1-(Hydroxymethyl)-3-methylbutyl]amino]-5- [(phenylmethyl)thio] thiazolo [4,5-d] pyrimidin-2-yl] amino] ethyl]-acetamide, N7-(2-Methoxyethyl)-5-[(phenylmethyl) thio]-N2-[2-(2-thienyl)(2-Methoxyethyl)-5-[(phenylmethyl) thio]-N2-[2-(2-thienyl) ethyl] thiazolo [4,5- dlpyrimidine-2,7-diamine, N7- (2-Ethoxyethyl)-5- (phenylmethyl) thio-N2- 2- (2-thienyl) ethyl] thiazolo [4,5- d pyrimidine-2,7-diamine, N7-(2, 2-Dimethylpropyl)-S-[(phenylmethyl) thio]-N2-[2-(2-thienyl) ethyl] thiazolo(2, 2-Dimethylpropyl)-S-[(phenylmethyl) thio]-N2-[2-(2-thienyl) ethyl] thiazolo [4,5- d pyrimidine-2, 7-diamine, (2R)-4-Methyl-2-[[5-[(phenylmethyl)thio]-2-[[2-(2-thienyl)et hyl] amino thiazolo [4,5- d pyrimidin-7-yl amino-1-pentanol, (#)-1-[[5-[(Phenylmethyl)thio]-2-[[2-(2-thienyl)ethyl]amino] thiazolo [4,5-d] pyrimidin-7- yl] amino- 2-propanol, (#)-2-[[5-[(Phenylmethyl)thio]-2-[[2-(2-thienyl)ethyl]amino] thiazolo 4,5-d pyrimidin-7- yl amino- 1-butanol, (#)-2-[[5-[(Phenylmethyl)thio]-2-[[2-(2-thienyl)ethyl]amino] thiazolo [4,5-d] pyrimidin-7- yl] amino-1-propanol, (2R)-2-[[2-[(2-Hydroxyethyl)amino]-5-[(phenylmethyl)thio] thiazolo [4,5-dlpyrimidin-7- yl amino-4-methyl-1-pentanol, (#)-N,N-Diethyl-1-[2-[(2-hydroxyethyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl-3-piperidinecarboxamide, (2R)-2-[[2-[(3-Hydroxypropyl)amino]-5-[(phenylmethyl)thio] thiazolo [4,5-d] pyrimidin-7- yl amino-4-methyl-l-pentanol, ()-2- 2- (3-Hydroxypropyl) aminol-5- (phenylmethyl) thio thiazolo [4,5-d] pyrimidin-7- yl amino-l-butanol,

()-2- 2- (3-Hydroxypropyl) aminol-5- (phenylmethyl) thiojthiazolo [4,5-d] pyrimidin-7- yl amino-1-propanol, 2-[[7-[(2-Hydroxy-1-methylethyl)amino]-5-[(phenylmethyl)thio ] thiazolo 4, 5-d pyrimidin- 2-yl amino-acetamide, 4- I- 7- (4-Methylcyclohexyl) amino-5- (phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-2- yl-3-azetidinyl-1-piperazinesulfonamide, 3-[[2-[[2-(4-Morpholinyl) ethyl] amino]-5-[(phenylmethyl)[[2-[[2-(4-Morpholinyl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7- yl] amino-1-propanol, 2-Methyl-2-[[2-[[2-(4-morpholinyl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo[[2-[[2-(4-morpholinyl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-1-propanol, (#)-2-[[2-[[2-(4-Morpholinyl)ethyl]amino-5- [(phenylmethyl)[(phenylmethyl) thio] thiazolo 4,5- d pyrimidin-7-yl amino-1-propanol, (2R)-4-Methyl-2-[[2-[[2-(4-morpholinyl)ethyl]amino]-5-[(phen ylmethyl)thio] thiazolo [4,5- dlpyrimidin-7-yl amino-l-pentanol, 2-[[2-(3, 4-Dihydroxyphenyl) ethyl] amino]-5-[(phenylmethyl) thio]-thiazolo[[2-(3, 4-Dihydroxyphenyl) ethyl] amino]-5-[(phenylmethyl) thio]-thiazolo [4,5- dupyrimidin-7 (4H)-one, (+)-2-(2-Hydroxy-1-methylethyl) amino-5-(phenylmethyl) thio-thiazolo [4,5-dlpyrimidin- 7 (4H)-one, and their pharmaceutically acceptable salts and solvates.

According to the invention there is also provided a process for the preparation of a compound of formula (I) which comprises: (a) when X represents-OH and R is NH2, heating a compound of general formula <BR> wherein R² is as defined in formula (1); or (b) when X represents-OH and R is NH2, reacting a compound of formula

with a compound of general formula (IV), R-L, wherein L represents a leaving group <BR> <BR> <BR> such as a halogen atom (e. g. chlorine) and R² is as defined in formula (I); or (c) when X represents-OH or-NR R and R is a hydrogen atom, reacting a corresponding compound of formula (I) in which R is NH2, with a diazotizing agent; or <BR> <BR> <BR> (d) when X represents-OH and R¹ is a group -NR³R4, reacting a compound of general formula <BR> <BR> wherein L² represents a leaving group such as a halogen atom (e. g. bromine) and R² is as<BR> <BR> <BR> <BR> <BR> <BR> <BR> defined in formula (I), with a compound of general formula (VI), R³R4NH, wherein R³ and R4 are as defined in formula (1); or <BR> <BR> <BR> <BR> (e) when X represents-NR¹³R14 and R¹ represents-NR³R4, reacting a compound of general formula wherein L represents a leaving group such as a halogen atom (e. g. chlorine) and R, R and R4 are as defined in formula (I), with a compound of general formula (VE), NHR R, wherein R andR are as defined in formula (I) ; or <BR> <BR> <BR> (f) when X represents-NR¹³R14 and R¹ represents -NR³R4, reacting a compound of general formula

wherein L4 is a leaving group (e. g. bromine), L5 is a leaving group (e. g. chlorine) and R is as defined in formula (I), initially with a compound of formula (VI) as defined in (d) above followed by reaction with a compound of formula (VII) as defined in (e) above; and optionally after (a), (b), (c), (d), (e) or (f) forming a pharmaceutically acceptable salt or solvate of the compound of formula (I).

Process (a) is conveniently carried out in the presence of a solvent or solvent mixture such as dimethylformamide/water at a temperature in the range from e. g. 50 to 150°C.

Process (b) is conveniently carried out in an organic solvent such as tetrahydrofuran or dimethyl sulphoxide/dimethylformamide mixture, optionally in the presence of a base such as potassium tert-butoxide or diisopropylamide.

Process (c) is conveniently carried out in an organic solvent such as tetrahydrofuran.

Examples of suitable diazotizing agents to use include tert-butyl nitrite.

Process (d) is conveniently carried out in an organic solvent such as tetrahydrofuran, e. g. at a temperature of 50°C for 5 hours.

Process (e) is conveniently carried out in an organic solvent such as tetrahydrofuran with heating for a period in the range from 1 day to 3 weeks.

Process (f) is conveniently carried out in an organic solvent such as tetrahydrofuran or N-methylpyrrolidine at a temperature between 0° and 130°C, with a reaction time of 1 hour to 3 weeks.

Compounds of formula (In may be readily prepared by reacting a compound of general formula wherein R is as defined above, with potassium thiocyanate and bromine in dimethylformamide/pyridine.

Compounds of formula (X) are suitably prepared by reacting a compound of formula with a compound of formula (IV) as defined above.

Compounds of formula (V) may be prepared by reacting a compound of formula (I) in which R is NH2, with a diazotizing agent and a halogenating agent. The reaction is conveniently carried out in an organic solvent such as acetonitrile in the presence of a diazotizing agent such as tert-butyl nitrite and a halogenating agent such as a trimethylsilyl halide. <BR> <BR> <BR> <BR> <BR> <BR> <BR> <P>Compounds of formula (VIt) in which L³ is a chlorine atom may be prepared by reacting a compound of formula (I) in which X is-OH with phosphorus oxychloride in dimethylaniline under reflux conditions. <BR> <BR> <BR> <BR> <BR> <BR> <BR> <P>Compounds of formula (IX) in which L4 represents a bromine atom and L5 represents a chlorine atom may be prepared by reacting a compound of formula (I) in which X is-OH and R is NH2 with phosphorus oxychloride in dimethylaniline under reflux conditions, followed by reaction with tert-butyl nitrite and bromoform.

Compounds of formulae (hui), (IV), (VI), (VU and (XI) are either commercially available, are well known in the literature or may be prepared easily using known techniques.

The compounds of formulae (V), (VII) and (EX) are novel intermediates and therefore form <BR> <BR> <BR> <BR> a further aspect of the present invention. In formula (V), L² is preferably a bromine atom.<BR> <BR> <BR> <BR> <BR> <P>In formula (VI1), R³ and R4 preferably both represent a hydrogen atom. In formula (IX),<BR> <BR> <BR> <BR> <BR> L³ is preferably a bromine atom and L4 is preferably a chlorine atom.

It will be appreciated by those skilled in the art that in the processes of the present invention certain functional groups such as hydroxyl or amino groups in the starting reagents or intermediate compounds may need to be protected by protecting groups. Thus, the preparation of the compounds of formula (I) may involve, at an appropriate stage, the removal of one or more protecting groups.

The protection and deprotection of functional groups is fully 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 & P. G. M. Wuts, Wiley-Interscience (1991).

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, fumarate, maleate, tartrate, citrate, oxalate, methanesulphonate or p-toluenesulphonate.

Certain compounds of formula (I) are capable of existing in stereoisomeric forms. It will be understood that the invention encompasses all geometric and optical isomers of the compounds of formula (1) and mixtures thereof including racemates. Tautomers and mixtures thereof also form an aspect of the present invention, for example tautomers of general formula <BR> <BR> <BR> <BR> <BR> <BR> wherein R¹ and R² are as defined in formula (I), or of general formula

<BR> <BR> <BR> <BR> <BR> <BR> wherein R¹ and R² are as defined in formula (I).

Similarly, it will be understood that in the above processes tautomeric forms of the compounds of formulae (II), (III), (IX) and (X) may also be used, for example, and

The compounds of formula (I) have activity as pharmaceuticals, in particular as modulators of chemokine receptor (especially CXCR2) activity, and may be used in the treatment (therapeutic or prophylactic) of conditions/diseases in human and non-human animals which are exacerbated or caused by excessive or unregulated production of chemokines.

Examples of such conditions/diseases include: (1) (the respiratory tract) obstructive airways diseases including chronic obstructive pulmonary disease (COPD) such as irreversible COPD; asthma, such as bronchial, allergic, intrinsic, extrinsic and dust asthma, particularly chronic or inveterate asthma (e. g. late asthma and airways hyper-responsiveness); bronchitis; acute, allergic, atrophic rhinitis and chronic rhinitis including rhinitis caseosa, hypertrophic rhinitis, rhinitis purulenta, rhinitis sicca and rhinitis medicamentosa; membranous rhinitis including croupous, fibrinous and pseudomembranous rhinitis and scrofoulous rhinitis; seasonal rhinitis including rhinitis nervosa (hay fever) and vasomotor rhinitis; sarcoidosis, farmer's lung and related diseases, fibroid lung and idiopathic interstitial pneumonia; (2) (bone and joints) rheumatoid arthritis, seronegative spondyloarthropathies (including ankylosing spondylitis, psoriatic arthritis and Reiter's disease), Behcet's disease, Sjogren's syndrome and systemic sclerosis; (3) (skin) psoriasis, atopical dermatitis, contact dermatitis and other eczmatous dermitides, seborrhoetic dermatitis, Lichen planus, Pemphigus, bullous Pemphigus, Epidermolysis bullosa, urticaria, angiodermas, vasculitides, erythemas, cutaneous eosinophilias, uveitis, Alopecia areata and vernal conjunctivitis;

(4) (gastrointestinal tract) Coeliac disease, proctitis, eosinopilic gastro-enteritis, mastocytosis, Crohn's disease, ulcerative colitis, food-related allergies which have effects remote from the gut, e. g., migraine, rhinitis and eczema; (5) (other tissues and systemic disease) multiple sclerosis, atherosclerosis, Acquired Immunodeficiency Syndrome (AIDS), lupus erythematosus, systemic lupus, erythematosus, Hashimoto's thyroiditis, myasthenia gravis, type I diabetes, nephrotic syndrome, eosinophilia fascitis, hyper IgE syndrome, lepromatous leprosy, sezary syndrome and idiopathic thrombocytopenia pupura; (6) (allograft rejection) acute and chronic following, for example, transplantation of kidney, heart, liver, lung, bone marrow, skin and cornea; and chronic graft versus host disease; (7) cancers, especially non-small cell lung cancer (NSCLC) and squamous sarcoma; (8) diseases in which angiogenesis is associated with raised CXCR2 chemokine levels (e. g. NSCLC); and (9) cystic fibrosis, stroke, re-perfusion injury in the heart, brain, peripheral limbs and sepsis.

Thus, 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 a further aspect, the present 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 a still further aspect, the present invention provides the use of a compound of formula (1), or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore defined in the manufacture of a medicament for the treatment of human diseases or conditions in which modulation of chemokine receptor activity is beneficial.

In the context of the present specification, the term"therapy"also includes"prophylaxis" unless there are specific indications to the contrary. The terms"therapeutic"and "therapeutically"should be construed accordingly.

The invention still further provides a method of treating a chemokine mediated disease wherein the chemokine binds to a CXCR2 receptor, which comprises administering to a patient a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore defined.

The invention also provides a method of treating an inflammatory disease, especially psoriasis, in a patient suffering from, or at risk of, said disease, which comprises administering to the patient a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore defined.

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 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 0.05 to 80 % w,

still more preferably from 0.10 to 70 % w, and even more preferably from 0.10 to 50 % w, of active ingredient, all percentages by weight being based on total composition.

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 (1), or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore defined, with a pharmaceutically acceptable adjuvant, diluent or carrier.

The pharmaceutical compositions 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 invention will now be further illustrated by reference to the following examples. In the examples the Nuclear Magnetic Resonance (NMR) spectra were measured on a Varian Unity Inova 300 or 400 MHz spectrometer and the Mass Spectrometry (MS) spectra measured on a Finnigan Mat SSQ7000 or Micromass Platform spectrometer. Where necessary, the reactions were performed under an inert atmosphere of either nitrogen or argon. Chromatography was generally performed using Matrex Silica 60 (35-70 micron) or Prolabo Silica gel 60 (35-70 micron) suitable for flash silica gel chromatography.

High pressure liquid chromatography purification was performed using either a Waters Micromass LCZ with a Waters 600 pump controller, Waters 2487 detector and Gilson FC024 fraction collector or a Waters Delta Prep 4000. The abbreviations m. p. and DMSO used in the examples stand for melting point and dimethyl sulphoxide respectively.

Example 1 (2R)-2-2-Amino-5-(phenylmethyl) thio thiazolo [4,5-dlpyrimidin-7-yl] amino]-1- butanol

(a) 7-Chloro-5- [(phenylmethyl) thio] thiazolo [4,5Zdlpyrimidin-2-amine 2-Amino-5-[(phenylmethyl)[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one (0.89g) (prepared as described in Example 9), phosphorus oxychloride (12mL) and N, N-dimethylaniline (1.2mL) were heated at reflux for 2 hours. The cooled reaction mixture was poured onto ice and water and stirred for 2 hours. Chromatography on silica eluting with methanol/dichloromethane mixtures gave the sub-title chloride. m. p. 217-218.5°C MS: APCI (+ve) 309/11 (M+1) H NMR: 8 (DMSO) 4.38 (s, 2H), 7.20-7.48 (m, 5H) and 8.95 (br s, 2H).

(b) (2R)-2-2-Amino-5-(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]-l- butanol The chloro compound from step (a) (0.12g) in tetrahydrofuran (3 mL) was treated with (R)-2-amino-1-butanol (0.56g) and the reaction mixture was heated at reflux for 5 days.

Dichloromethane and dilute hydrochloric acid were added. The resulting solid was filtered off, washed with water and ether to give the title compound which was obtained containing 0.23 moles of hydrogen chloride and 0.93 moles of water. Yield 0.045g. m. p. 118-121°C

MS: APCI (+ve) 362 (M+1) H NMR: 8 (DMSO) 0.83 (t, 3H), 1.45 (m, 2H), 1.65 (m, 2H), 3.39 (m, 2H), 4.31 (q, 2H), 4.65 (t, lH), 6.91 (d, lH), 7.17-7.44 (m, SH) and 8.00 (s, 2H).

Example 2 (S)-2-2-Aniino-S-(phenylmethyl) thio thiazolo [4,5-d] pyrimidin-7-yl] amino]-1- butanol Prepared by the method of Example 1 (b) from the chloro compound of Example 1 (a) and (S)-2-amino-1-butanol. Obtained as a solid containing 0.7 moles of hydrogen chloride. mp 204-208°C MS: APCI (+ve) 362 (M+1) H NMR: 8 (DMSO) 0.82 (t, 3H), 1.37-1.74 (m, 2H), 3.36-3.52 (m, 2H), 4.10 (br s, lH), 4.41 (q, 2H), 7.20-7.46 (m, 5H), 7.63 (br s, lH) and 8.42 (s, 2H).

Example 3 2-Amino-5-[[(2, 3-difluorophenyl) methyl][[(2, 3-difluorophenyl) methyl] thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one a) 2-Amino-5-mercapto-thiazolo [4,5-d] pyrimidin-7 (4H)-one Aluminium tribromide (1 M in CH2Br2,15.2ml) was added to a solution of the product of Example 9 (2.0g) in toluene (25ml) and the reaction mixture heated at 60°C for 6 hours.

On cooling to room temperature, water (40ml) was added and the resulting solid isolated by filtration then triturated with hot ethanol to afford the sub-title compound (0.8g).

MS: (APCI) 201 (M+H+, 100%) b) 2-Amino-5- [[(2, 3-difluorophenyl) methyl] thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one Potassium t-butoxide solution (0.45mL of 1M in tetrahydrofuran) was added to a stirred solution of the product of step a) (0.09g) and 2,3-difluorobenzyl bromide in dimethyl sulphoxide (2mL). After stirring for 3 days, the reaction mixture was poured onto water.

The title compound was obtained. Yield 0.065g. m. p. 310-313°C MS: APCI (+ve) 327 (M+1) H NMR: 8 (DMSO) 4.48 (s, 2H), 7.18-7.45 (m, 3H), 8.20 (s, 2H) and 12.62 (s, lH).

Example 4 5- (3-Phenoxyphenyl) methyl thio] thiazolo [4,5 dlpyrimidin-7 (4N)-one 2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one (0.3g) (product of Example 5) was added over 90 minutes to a solution of t-butyl nitrite (0.17mL) in tetrahydrofuran (3mL) at 65°C. After a further 3.5 hours at 65°C, the solvent was evaporated and the residue chromatographed on silica eluting with methanol/dichloromethane mixtures to give the title compound. Yield 0.071g. m. p. 197-198°C MS: APCI (+ve) 368 (M+1) IH NMR: 8 (DMSO) 4.49 (s, 2H), 6.86-7. 38 (m, 9H), 9.58 (s, lH) and 13.11 (s, lH).

Example 5 2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one

Prepared by the method of Example 3 using 3-phenoxybenzyl chloride. m. p. 266-269°C MS: APCI (+ve) 383 (M+1) H NMR: 8 (DMSO) 4.40 (s, 2H), 6.81-7.41 (m, 9H), 8.15 (s, 2H) and 12.55 (s, lH).

Example 6 ()-2- 2-Amino-5- (pentylthio) thiazolo [4,5-d]pyrimidin-7-yl] amino]-1-butanol (a) 7-Chloro-5- (pentylthio) thiazolo [4,5-pyhmidin-2-amine Prepared by the method of Example l (a) from 2-amino-5- (pentylthio) thiazolo [4,5- d pyrimidin-7 (4H)-one (product of Example 10). m. p. 176.5-177.5°C MS: APCI (+ve) 289 (M+1) H NMR: 8 (DMSO) 0.88 (t, 3H), 1.22-1.42 (m, 4H), 1.60-1.74 (m, 2H), 3.08 (t, 2H) and 8.90 (s, 2H).

(b) ()-2- 2-Aniino-5- (pentylthio) thiazolo [4,5-d] pyrimidin-7-yl] amino]-1-butanol

Prepared by the method of Example 1 (b) from the chloro compound of Example 6 (a) and the appropriate amine. m. p. 151-154°C MS: APCI (+ve) 342 (M+1) 1H NMR: 8 (DMSO) 0.82-0.95 (m, 6H), 1.22-1.72 (m, 8H), 3.04 (m, 2H), 3.39-3.56 (m, 2H), 4.07 (m, lH), 4.64 (t, lH), 6 88 (d, lH), 7.44 (br s, lH) and 7.96 (s, 2H).

Example 7 2-rr2-Amino-5- (pentylthio) thiazolof4, 5-dlpyrimidin-7-vllaminolethanol Prepared by the method of Example 6 (b). m. p. 192-195°C MS: APCI (+ve) 314 (M+1) 1H NMR: 8 (DMSO) 0.87 (t, 3H), 1.21-1.42 (m, 4H), (m, 2H), 2.99 (t, 2H), 3.37-3.46 (m, 2H), 3.46-3.58 (m, 2H), 4.71 (t, lH), 7.22 (t, lH) and 7.97 (s, 2H).

Example 8 5- (Pentylthio) thiazolo [4,5-d] pyrimidin-7 (4H)-one Prepared by the method of Example 4. m. p. 208-209°C MS: APCI (+ve) 256 (M+1) 1H NMR: 8 (DMSO) 0.88 (t, 3H), 1.22-1.44 (m, 4H), 1.63-1.75 (m, 2H), 3.20 (t, 2H), 9.57 (s, 1 H) and 13.06 (s, lH).

Example 9

2-Amino-5-[(phenylmethyl) thio] thiazolo[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one (a) 6-Amino-2- [(phenylmethyl) thio]-5-thiocyanato-4 (1)-pyrimidinone 6-Amino-2- (phenylmethyl) thio]-4 (1H)-pyrimidinone (10. Sg) (prepared as described in WO 96/35678) and potassium thiocyanate (25g) in dimethylformamide (200mL) were heated together at 65°C. Pyridine (6.3mL) was added and the solution cooled to 5°C.

Bromine (2.2mL) was added slowly and the reaction mixture stirred for 2 hours at 5-10°C.

The reaction mixture was poured onto ice and water, stirred for 1 hour and the solid was filtered off. After washing with water and ether a pure sample was obtained after tituration with hot methanol. m. p. 260-262°C MS: APCI (+ve) 291 (M+1) H NMR: 5 (DMSO) 4.38 (s, 2H), 7.21-7.51 (m, 5H), 7.70 (br s, 2H) and 12.35 (s, lH).

(b) 2-Amino-5- [(phenylmethyl) thio] thiazolo [4,5 dlpyrimidin-7 (4H)-one The product of step (a) (7. 35g) was heated at 120°C in dimethylformamide (40mL) and water (l OmL) for 10 hours. After cooling, the resulting solid was filtered off, washed with water, ether and ethyl acetate to give the title compound containing 0.4 moles of dimethylformamide. m. p.-325° MS: APCI (+ve) 291 (M+ 1) 1H NMR: 8 (DMSO) 4.41 (s, 2H), 7.21-7.50 (m, 5H), 8.17 (s, 2H) and 12.53 (br s, lH).

Example 10

2-Amino-5-(PentYlthio) thiazolof4z5-dlpyrimidin-7 (4H)-one (a) 6-Amino-2-(pentylthio)-5-thiocyanato-4 (1H)-pyrimidinone Prepared by the method of Example 9 (a). m. p. 260-262°C MS: APCI (+ve) 214 (M+1) IH NMR: 8 (DMSO) 0.86 (t, 3H), 1.22-1.40 (m, 4H), 1.56-1. 68 (m, 2H), 3.10 (t, 2H), 7.58 (br s, 2H) and 12.30 (s, lH).

(b) 2-Amino-5- (pentylthio) thiazolo [4,5 dlpyrimidin-7 (4H)-one Prepared by the method of Example 9 (b).

MS: APCI (+ve) 271 (M+1) 1H NMR: S (DMSO) 0.86 (t, 3H), 1.24-1.40 (m, 4H), 1.58-1.70 (m, 2H), 3.12 (t, 2H), 8.12 (br s, 2H) and 12.49 (s, 1H).

Example 11 2-Bromo-5- (pentylthio) thiazolo [4,5-dlpyrimidin-7 (4H)-one Trimethylsilyl bromide (0.44mL) was added slowly to a solution at 0°C under nitrogen of t-butyl nitrite (0.42mL) in acetonitrile (2mL). After 30 minute at 0°C, 2-amino-5- (pentylthio) thiazolo [4,5-d] pyrimidin-7 (4H)-one (0. 5g) (product of Example 10) was added.

The reaction mixture was stirred at room temperature for 16 hours and the solvent was evaporated. Chromatography on silica eluting with dichloromethane/methanol mixtures gave the title bromide. m. p. 189-191°C MS: APCI (+ve) 336/7 (M+1) H NMR: 8 (DMSO) 0.88 (t, 3H), 1.26-1.41 (m, 4H), 1.64-1.75 (m, 2H), 3.18 (t, 2H) and 13.22 (s, lH).

Examples 12-26 The compounds of Examples 12 to 26 were prepared by heating 2-bromo-5- (pentylthio) thiazolo [4,5-d] pyrimidin-7 (4H)-one (product of Example 11) with 5 equivalents of the appropriate amine in tetrahydrofuran at 45°C for 5 hours.

Example 12 2- 3- (Dimethylamino) propyl] amino-5- (pentylthio) thiazolo [4,5 dlpyrimidin-7 (4H)- one MS: APCI (+ve) 356 (M+1) Example 13 2-[[2-(Diethylamino) ethyl] amino]-5-(pentylthio) thiazolo[[2-(Diethylamino) ethyl] amino]-5-(pentylthio) thiazolo [4,5-d] pyrimidin-7 (4H)-one MS: APCI (+ve) 370 (M+1)

Example 14 2-[[2-(Dimethylamino) ethyl] amino]-5-(pentylthio) thiazolo[[2-(Dimethylamino) ethyl] amino]-5-(pentylthio) thiazolo [4,5-d] pyrimidin-7 (4H)-one MS: APCI (+ve) 342 (M+l) Example 15 2-[(3-Hydroxypropyl) amino]-5-(pentylthio) thiazolo [4, 5-dlpyrimidin-7 (4H)-one MS: APCI (+ve) 329 (M+1) Example 16 2-[[2-(Acetylamino) ethyl] amino]-5-(pentylthio) thiazolo[[2-(Acetylamino) ethyl] amino]-5-(pentylthio) thiazolo [4,5 dlpyrimidin-7 (4H)-one MS: APCI (+ve) 356 (M+l) Example 17 ()-2- (2, 3-Dihydoxypropyl) amino-5- (pentylthio) thiazolo [4,5-dlpyrimidin-7 (4N)-one MS: APCI (+ve) 345 (M+l)

Example 18 2-rr2- (4-Morpholinyl) ethylaminol-5- (pentylthio) thiazolof 4. 5-dlpvrimidin-7f(4H)-one MS: APCI (+ve) 384 (M+1) Example 19 2- (2-Methoxyethyl) amino-5- (pentylthio) thiazolo[4,5-dlpyrimidin-7 (4H)-one MS: APCI (+ve) 329 (M+1) Example 20 2-r (l-Methylethyl) amino-5- (pentylthio) thiazolo 4, 5-dlpyrimidin-7 (4I)-one MS: APCI (+ve) 313 (M+1) Example 21 2-(Cyclopropylamino)-5-(pentylthio)thiazolo[4,5-d]pyrimidin- 7(4H)-one MS: APCI (+ve) 311 (M+1)

Example 22 (+)-2-(2-Hydoxypropyl) amino-5-(pentylthio) thiazolo [4,5-d] pyrimidin-7 (4H)-one MS: APCI (+ve) 329 (M+1) Example 23 2-[[2-(2-Hydroxyethoxy) ethyl] amino]-5-(pentylthio) thiazolo[[2-(2-Hydroxyethoxy) ethyl] amino]-5-(pentylthio) thiazolo [4,5-dlpyrimidin-7 (4H)- one MS: APCI (+ve) 359 (M+1) Example 24 2-[2-Hydroxy-2-methylpropyl)amino]-5-(pentylthio)thiazolo[4, 5-d pyrimidin-7 (4H)- one MS: APCI (+ve) 343 (M+1) Example 25 2-[(2-Hydroxyethyl) amino]-5-(pentylthio) thiazolo [4, 5-dlpyrimidin-7 (4H)-one MS: APCI (+ve) 315 (M+1)

Example 26 (2S, 3R)-3-Hydroxy-2- (7-oxo-5- (pentylthio)-4H-thiazolo [4,5-dlpyrimidin-2-yl]- amino) butanamide MS: APCI (+ve) 372 (M+1) Examples 27-43 The compounds of Examples 27 to 43 were prepared by heating 7-chloro-5- (pentylthio) thiazolo [4,5-d] pyrimidin-2-amine (product of Example 6, step a) with 5 equivalents of the appropriate amine in tetrahydrofuran at 45°C for 5 hours.

Example 27 N7- 3- (Dimethylamino) propyl-5- (pentylthio) thiazolo[4,5-dlpyrimidine-2, 7-diamine MS: APCI (+ve) 355 (M+l) Example 28- N7-[2-(Diethylamino) ethyl]-5-(pentylthio) thiazolo[2-(Diethylamino) ethyl]-5-(pentylthio) thiazolo [4,5-d] pyrimidine-2,7-diamine MS: APCI (+ve) 369 (M+1) Example 29 N'-[2-(Dimethylåmino) ethyl]-5-(pentylthio) thiazolo[2-(Dimethylåmino) ethyl]-5-(pentylthio) thiazolo [4,5-dlpyrimidine-2,7-diamine MS: APCI (+ve) 341 (M+1) Example 30 3-[(2-Amino-5-(pentylthio) thiazolo[(2-Amino-5-(pentylthio) thiazolo [4,5-d]pyrimidin-7-yl)amino]-1-propanol MS: APCI (+ve) 328 (M+l) Example 31 N7-Cyclohexyl-5- (pentylthio) thiazolo [4,5-d] pyrimidine-2, 7-diamine MS: APCI (+ve) 352 (M+1) Example 32 ()-3- (2-Amino-5- ( (phenylmethyl) thio) thiazolo [4,5-d] pyrimidin-7-yl) amino]-1,2- propanediol MS: APCI (+ve) 344 (M+1)

Example 33 N7- (2-Methoxyethyl)-5- (pentylthio) thiazolor4, 5-dlpyrimidine-2,7-diamine MS: APCI (+ve) 328 (M+l) Example 34 5-(Pentylthio)-N7-propylthiazolo[4,5-d]pyrimidine-2,7-diamin e MS: APCI (+ve) 312 (M+1) Example 35 N7-Cyclopentyl-5- (pentylthio) thiazolo 4, 5-d pyrimidine-2,7-diamine MS: APCI (+ve) 338 (M+l) Example 36 N7-Cyclopropyl-5-(pentylthio) thiazolo(pentylthio) thiazolo [4,5-d] pyrimidine-2, 7-diamine MS: APCI (+ve) 310 (M+l)

Example 37 N7- (2-Methylpropyl)-5- (pentylthio) thiazolo [4,5-d] pyrimidine-2,7-diamine MS: APCI (+ve) 326 (M+l) Example 38 (+)-1-(2-Amino-5-(pentylthio) thiazolo [4,5-d]pyrimidin-7-yl) amino-2-propanol MS: APCI (+ve) 328 (M+1) Example 39 (exo)-N7-Bicyclo [2. 2.1]hept-2-yl-5-(pentylthio)thiazolo[4, 5 dlpyrimidine-2,7-diamine MS: APCI (+ve) 364 (M+l) Example 40 2-[2-[[2-Amino-5-(pentylthio)thiazolo[4, 5 dlpyrimidin-7-yl amino ethoxy ethanol MS: APCI (+ve) 358 (M+I)

Example 41 ()-N7- (2-Methylbutyl)-5- (pentylthio) thiazolo[4,5-dlpyrimidine-2,7-diamine MS: APCI (+ve) 340 (M+1) Example 42 1-[[2-Amino-5-(pentylthio) thiazolo[[2-Amino-5-(pentylthio) thiazolo [4,5-d] pyrimidin-7-yl] amino]-2-methyl-2-propanol MS: APCI (+ve) 342 (M+l) Example 43 N7-r (2-Aminophenyl) methyl-5-(pentylthio) thiazolo 4 ! 5 alpyrimidine-2,7-diamine MS: APCI (+ve) 375 (M+l) Examples 44-47 The compounds of Examples 44 to 47 were prepared from 2-amino-5,6-dihydro-5- thioxothiazolo [4,5-d] pyrimidin-7 (4H)-one, diisopropylethylamine and the appropriate alkyl halide in dimethyl sulphoxide/dimethylformamide at 60°C. A total of 5 equivalents of base and alkyl halide were added over 3 days.

Example 44 2-Amino-5-[(2-phenoxyethyl)thio] thiazolo [4,5-dlpyrimidin-7 (4H)-one MS: APCI (+ve) 321 (M+1) Example 45 (E)-2-Amino-5-[(3-phenyl-2-propenyl)thio]thiazolo[4,5-d]pyri midin-7(4H)-one MS: APCI (+ve) 317 (M+l) Example 46 2-Amino-5- 3- 2,4-bis (1,1-dimethylethyl) phenoxy] propyl thio thiazolo [4,5-d]- pyrimidin-7 (4H)-one MS: APCI (+ve) 447 (M+1) Example 47 2-Amino-5- (4-trifluoromethyl) phenyllmethyl thiolthiazolo 4, 5-d pyrin-iidin-7 (4H)- one

MS: APCI (+ve) 359 (M+1) Examples 48-65 The compounds of Examples 48 to 65 were prepared from 2-amino-5,6-dihydro-5- thioxothiazolo [4,5-d] pyrimidin-7 (4H)-one (product of Example 3, step a), potassium t-butoxide and the appropriate benzyl halide in dimethyl sulphoxide at room temperature.

A total of 1.2 equivalents of base and alkyl halide were used and a reaction time of 24 hours.

Example 48 2-Amino-5-[[(3,5-dichlorophenyl)methyl]thio]thiazolo[4, 5-dlpyrimidin-7 (4H)-one MS: APCI (+ve) 359 (M+1) Example 49 2-Amino-5-[[(2,4-dichlorophenyl)methyl]thio]thiazolo[4,5-d]p yrimidin-7(4H)-one

MS: APCI (+ve) 359 (M+1) Example 50 2-Amino-5-[[(3,4-dichlorophenyl)methyl]thio]thiazolo[4,5-d]p yrimidin-7(4H)-one MS: APCI (+ve) 359 (M+l) Example 51 2-Amino-5-[[(3,5-dibromophenyl)methyl]thio]thiazolo[4, 5-d pyrimidin-7 (4H)-one MS: APCI (+ve) 449 (M+1) Example 52 2-Amino-5-[[(2-r. itrophenyl) methyl] thio] thiazolo[[(2-r. itrophenyl) methyl] thio] thiazolo [4,5-dlpyrimidin-7 (4H)-one MS: APCI (+ve) 336 (M+1)

Example 53 2-Amino-5- ( (2-fluorophenyl) methyl thio) thiazolo [4,5-d]pyrimidin-7(4H)-one MS: APCI (+ve) 309 (M+1) Example 54 2-Amino-5-[[(2-iodophenyl) methyl] thio] thiazolo[[(2-iodophenyl) methyl] thio] thiazolo [4,5-dapyrimidin-7 (4H)-one MS: APCI (+ve) 417 (M+1) Example 55 2-Amino-5-[[(3-chlorophenyl)methyl]thio]thiazolo[4, 5 dlpyrimidin-7 (4H)-one MS: APCI (+ve) 325 (M+1) Example 56 2-Amino-5-[[(2-chlorophenyl)methyl]thio] thiazolo [4,5-d]pyrimidin-7(4H)-one MS: APCI (+ve) 325 (M+1)

Example 57 2-Amino-5-[[(4-chloro-2-nitrophenyl)methyl]thio]thiazolo[4,5 -d] pyrimidin-7 (4H)-one MS: APCI (+ve) 370 (M+1) Example 58 2-Amino-5-[[(3-chloro-4-methoxyphenyl)methyl]thio]thiazolo[4 , 5-d pyrimidin-7 (4H)- one MS: APCI (+ve) 355 (M+1) Example 59 2-Amino-5-[[(2, 3-dichlorophenyl) methyl] thio] thiazolor4, 5 dlpyrimidin-7 (4H)-one MS: APCI (+ve) 359 (M+1) Example 60 2-Amino-5-[[(3,5-difluorophenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one

MS: APCI (+ve) 327 (M+1) Example 61 2-Amino-5-[[[(2,4-bis (trifluoromethyl) phenyl methyl thio] thiazolo [4,5 dlpyrimidin- 7(4H)-one MS: APCI (+ve) 427 (M+1) Example 62 2-Amino-5-[[(2-bromophenyl) methyl] thio] thiazolo [4, 5-dlpyrimidin-7 (4H)-one MS: APCI (+ve) 371 (M+1) Example 63 2-Amino-5- (2,3,4-trifluorophenyl) methyl thio] thiazolo [4,5-dlpyrimidin-7 (4H)-one MS: APCI (+ve) 345 (M+1)

Example 64 2-Amino-5-[[(3-bromophenyl)methyl]thio]thiazolo[4,5-d]pyrimi din-7(4H)-one MS: APCI (+ve) 369 (M+1) Example 65 2-Amino-5- ( (2-fluoro-3-methylphenyl) methyl thioJthiazolo [4,5-d] pyrimidin-7 (4H)- one MS: APCI (+ve) 323 (M+1) Examples 66-77 The compounds of Examples 66 to 77 were prepared from 7-chloro-5- (phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-2-amine and the appropriate hydroxyamine in dimethyl sulphoxide at 45°C. A total of 6 equivalents of amine were added and the reaction time was 2 days.

Example 66 3-[[2-Amino-5-[(phenylmethyl) thio] thiazolo[[2-Amino-5-[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]-2,2- dimethyl-1-propanol MS: APCI (+ve) 376 (M+1)

Example 67 (#)-α-[[[2-Amino-5-[(phenylmethyl)thio]thiazolo[4,5-d]pyrim idin-7- yl amino] methyl benzenemethanol MS: APCI (+ve) 410 (M+1) Example 68 (R)-ß-2-Amino-5-(phenylmethyl) thio] thiazolo [4,5-d]pyrimidin-7- yl amino benzenepropanol MS: APCI (+ve) 424 (M+1) Example 69 2-[[2-Amino-5-[(phenylmethyl)[[2-Amino-5-[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7-yl] aminolethanol MS: APCI (+ve) 334 (M+1)

Example 70 (2R)-2-2-Amino-5-(phenylmethyl) thio thiazolo [4,5-dlpyrimidin-7-yl] amino] 4- methylpentanol MS: APCI (+ve) 390 (M+1) Example 71 (#)-1-[[2-Amino-5-[(phenylmethyl)thio]thiazolo[4,5-d]pyrimid in-7-yl]amino]-2- propanol MS: APCI (+ve) 348 (M+1) Example 72 (#)-ß-[[2-Amino-5-[(phenylmethyl)thio]thiazolo[4, 5-d pyrimidin-7-yl amino]-4- chlorobenzenepropanol

MS: APCI (+ve) 458 (M+1) Example 73 (#)-3-[[2-Amino-5-[(phenylmethyl)thio]thiazolo[4,5-d pyrimidin-7-yl amino-1,2- propanediol MS: APCI (+ve) 364 (M+1) Example 74 2-[[2-Amino-5-[(phenylmethyl)thio] thiazolo [4,5-d] pyrimidin-7-yl]- propylamino ethanol MS: APCI (+ve) 376 (M+1) Example 75 ()-1-2-Amino-5-(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7-yl]-3-pyrrolidinol MS: APCI (+ve) 360 (M+1)

Example 76 ()-l-r2-Amino-5- (phenylmethyl) thio thiazolo[4,5-dlpyrimidin-7-yl]-3-piperidinol MS: APCI (+ve) 374 (M+1) Example 77 1-[2-Amino-5-[(phenylmethyl)[2-Amino-5-[(phenylmethyl) thio] thiazolo [4,5-dlpyrimidin-7-yl]-4-piperidinol MS: APCI (+ve) 374 (M+1) Examples 78-110 The compounds of Examples 78 to 110 were prepared from 7-chloro-5- 3- phenoxyphenyl) methyl thio] thiazolo [4,5-d] pyrimidin-2-amine (prepared by the method of Example 1, step a) using the product of Example 5) and the appropriate hydroxyamine in tetrahydrofuran at 45°C. A total of 6 equivalents of amine were added and the reaction time was 2 days.

Example 78 3-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]- 2,2-dimethyl-1-propanol MS: APCI (+ve) 468 (M+l) Example 79 (#)-2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7-yl]- amino-1-butanol MS: APCI (+ve) 454 (M+1) Example 80 (#)-α-[[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[ 4,5-dlpyrimidin-7-yl- amino methyl benzenemethanol MS: APCI (+ve) 502 (M+1) Example 81 4- [[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]- 1-butanol 5 10 15 MS: APCI (+ve) 454 (M+1) Example 82 6-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-dJpyrimidin-7-yl] amino]- 1-hexanol MS: APCI (+ve) 482 (M+1) Example 83 4-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7-yl]- amino] cyclohexanol MS: APCI (+ve) 480 (M+1)

Example 84 (R)-ß-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4 , 5-d pyrimidin-7-yl- amino benzenepropanol MS: APCI (+ve) 516 (M+1) Example 85 (#)-2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5 dlpyrimidin-7-yl]- amino-1-propanol MS: APCI (+ve) 440 (M+l) Example 86 2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7-yl]- amino] ethanol MS: APCI (+ve) 426 (M+1)

Example 87 (2R)-2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-dJpyrimidin-7-yl]- amino-4-methylpentanol MS: APCI (+ve) 482 (M+l) Example 88 (#)-1-Amino-3-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thi azolo[4,5-d pyrimidin- 7-yl amino-2-propanol MS: APCI (+ve) 455 (M+l) Example 89 (#)-1-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7- yl amino-2-propanol MS: APCI (+ve) 440 (M+l)

Example 90 2-[[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4, 5-dlpyrimidin-7- vllaminolmethyll-2-ethyl-1, 3-propanediol MS: APCI (+ve) 498 (M+l) Example 91 (#)-ß-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-dlpyrimidin-7- yllaminol-4-chlorobenzenepropanol MS: APCI (+ve) 550 (M+1) Example 92 (#)-3-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7- yl amino-1, 2-propanediol MS: APCI (+ve) 456 (M+1)

Example 93 2-[[2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4, 5-d pyrimidin-7- yl amino ethyl amino ethanol MS: APCI (+ve) 469 (M+1) Example 94 3-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4, 5-d pyrimidin-7-yl amino]- 1-propanol MS: APCI (+ve) 440 (M+1) Example 95 (#)-α-[[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[ 4, 5-d pyrimidin-7- yl amino methyl-3, 4-dichlorobenzenepropanol MS: APCI (+ve) 598 (M+1)

Example 96 1-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4, 5-dlpyrimidin-7-yl amino- 2-methyl-2-propanol MS: APCI (+ve) 454 (M+1) Example 97 2-[2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4, 5-dlpyrimidin-7- yl amino] ethoxy ethanol MS: APCI (+ve) 470 (M+1) Example 98 5-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,541pyrimidin-7-yl] amino]- 1-pentanol MS: APCI (+ve) 468 (M+1)

Example 99 (2S)-2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-dlpyrimidin-7- yl amino-4-(methylthio)-1-butanol MS: APCI (+ve) 500 (M+1) Example 100 2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl] thio] thiazolo [4,5-dpyrimidin-7- yl]butylamino]ethanol MS: APCI (+ve) 482 (M+1) Example 101 2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4, 5-d pyrimidin-7- yl propylamino ethanol MS: APCI (+ve) 468 (M+1)

Example 102 2,2'-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4, 5-dlpyrimidin-7- yl imino bisethanol MS: APCI (+ve) 470 (M+1) Example 103 2-[[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4, 5-d pyrimidin-7-yl- (2- hydroxyethyl) amino methyl phenol MS: APCI (+ve) 532 (M+1) Example 104 3-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7-yl]- (2- hydroxyethyl) amino-l-propanol MS: APCI (+ve) 484 (M+1)

Example 105 (#)-1-[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4,5 -dlpyrimidin-7-yl-3- pyrrolidino MS: APCI (+ve) 452 (M+1) Example 106 (trans)-1-[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-dlpyrimidin-7-yl]- 4-hydroxy-L-proline phenylmethyl ester MS: APCI (+ve) 586 (M+1) Example 107 (#)-1-[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5 dlpyrimidin-7-yl]-3- piperidinemethanol MS: APCI (+ve) 480 (M+1)

Example 108 (#)-1-[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7-yl]-3- piperidinol MS: APCI (+ve) 466 (M+1) Example 109 (2S)-1-[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4, 5 dlpyrimidin-7-yl-2- pyrrolidinemethanol MS: APCI (+ve) 466 (M+1) Example 110 1-[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo 4,5-d pyrimidin-7-yl-4- piperidinol MS: APCI (+ve) 466 (M+1) Example 111 (2R)-2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4 , 5-d pyrimidin-7- yl amino-1-butanol

(a) 7-chloro-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-2-amine Prepared by the method of Example 1 (a). m. p. 178-180°C MS: APCI (+ve) 401 (M+1) H NMR: 8 (DMSO) 4.37 (s, 2H), 6.83-7.39 (m, 9H) and 8.95 (s, 2H).

(b) (2R)-2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4 , 5-dlpyrimidin-7- yl]amino-1-butanol Prepared by the method of Example 1 (b). m. p. 108-111°C MS: APCI (+ve) 454 (M+1) H NMR: 8 (DMSO) 0.81 (t, 3H), 1.41 (m, 2H), 1.62 (m, 2H), 3.36 (m, 2H), 4.03 (m, lH), 4.31 (q, 2H), 4.62 (s, lH), 6.78-7.38 (m, 9H) and 8.00 (s, 2H).

Example 112 (2S)-2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4 , 5-dlpyrimidin-7- yl amino-l-butanol

Prepared by the method of Example l (b). m. p. 111-114°C MS: APCI (+ve) 454 (M+1) 1H NMR: 8 (DMSO) 0.81 (t, 3H), 1.41 (m, 2H), 1.62 (m, 2H), 3.36 (m, 2H), 4.02 (br d, lH), 4.32 (q, 2H), 4.60 (s, lH), 6.79-7.40 (m, 9H) and 8.04 (s, 2H).

Example 113 (2R)-2-2-Amino-5-(2, 3-difluorophenyl) methyl thio thiazolo [4,5 dlpyrimidin-7- yl amino-1-butanol (a) 7-Chloro-5-[[(3,4-difluorophenyl)methyl]thio]thiazolo[4, 5-d pyrimidin-2-amine Prepared by the method of Example 1 (a) using the product of Example 3. m. p. 209-210°C MS: APCI (+ve) 345/6 (M+1) 1H NMR: 8 (DMSO) 4.45 (s, 2H), 7.10-7.42 (m, 3H) and 8.90 (br s, 2H).

(b) (2R)-2-2-Amino-5-(3, 4-difluorophenyl) methyl thio] thiazolo [4,5-d] pyrimidin-7- yl]amino]-1-butanol Prepared by the method of Example l (b) using the product of step a) above.

MS: APCI (+ve) 398 (M+1) H NMR: 8 (DMSO) 0.82 (t, 3H), 1.34-1.71 (m, 4H), 3.37 (m, 2H), 4.03 (br d, lH), 4.38 (q, 2H), 4.62 (t, lH), 6.96 (d, lH), 7.06-7.40 (m, 3H) and 8.02 (s, 2H).

Example 114 2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio]thiazolo[4, 5-d pyrimidin-7-yl amino]- 1,3-propanediol Prepared by the method of Example 1 (b). m. p. 220-222°C MS: APCI (+ve) 456 (M+1) 1H NMR: 8 (DMSO) 3.50 (t, 4H), 4.13 (m, lH), 4.32 (s, 2H), 4.60 (t, 2H), 6.78-7.40 (m, IOH) and 8.01 (s, 2H).

Example 115 2-[[2-Amino-5-[[(3-phenoxyphenyl)methyl]thio] thiazolo 4, 5-d pyrimidin-7-yl amino]- 2-methyl-1-propanol

Prepared by the method of Example l (b) with 10 equivalents of amine, 45-65°C and reaction time of 3 weeks. Purification by chromatography on silica eluting with methanol/dichloromethane mixtures gave the title compound. m. p. 126-130°C MS: APCI (+ve) 454 (M+l) H NMR: 8 (DMSO) 1.30 (s, 6H), 3.53 (d, 2H), 4.33 (s, 2H), 4.86 (t, lH), 6.28 (s, lH), 6.80-7.40 (m, 9H) and 8.00 (s, 2H).

Example 116 2-[[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo[[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo [4,5-d] pyrimidin-7- yl amino-2-methyl-1-propanol Prepared by the method of Example l (b) using the product of Example 113, step a), 10 equivalents of amine, 45-65°C and reaction time of 3 weeks. Purification by chromatography on silica eluting with methanol/dichloromethane mixtures gave the title compound. m. p. 231-234°C MS: APCI (+ve) 398 (M+1) H NMR: 8 (DMSO) 1.30 (s, 6H), 3.53 (d, 2H), 4.40 (s, 2H), 4.84 (t, lH), 6.32 (s, lH), 7.10-7.40 (m, 3H) and 8.03 (s, 2H).

Example 117 1-[[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo[[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo [4,5-d] pyrimidin-7- yl amino-2-methyl-2-propanol The product from Example 113, step a) (0.1 g) and 1-amino-2-methyl-propan-2-ol (0. 5g) in tetrahydrofuran (10ml) was heated in a sealed vessel at 100 °C for 18 hours. The mixture was evaporated to dryness and purified (HPLC, Novapake C 18 column, 0.1 % aqueous ammonium acetate: acetonitrile, gradient elution 70: 30 to 0: 100 over 15 minutes) to afford the title compound (0.051 g).

MS (APCI) 398 (M+H+, 100%).

NMR 8H (d6-DMSO) 8.05 (2H, s), 7.39-7.17 (2H, m), 7.16-7.05 (2H, m), 4.51 (1H, s), 5.23 (1H, d), 4.39 (2H, s), 3.37 (2H, d), 1.06 (6H, s).

Example 118 5-[[(2, 3-Difluorophenyl) methyl] thio]-N7-(2-fluoroethyl) thiazolo[[(2, 3-Difluorophenyl) methyl] thio]-N7-(2-fluoroethyl) thiazolo [4,5-d] pyrimidine-2,7- diamine The product from Example 113, step a) (0.1 g), 2-fluoroethylamine hydrochloride (0.5g) and N, N-ethyldiisopropylamine (0.4ml) in tetrahydrofuran: water (7ml, 5: 2) was heated in a sealed vessel at 100 °C for 18 hours. The mixture was evaporated to dryness and purified (HPLC, Novapake C 18 column, 0.1% aqueous ammonium acetate: acetonitrile, gradient elution 70: 30 to 0: 100 over 15 minutes) to afford the title compound (0.027g).

MS (APCI) 372 (M+H+, 100%).

NMR 8H (d6-DMSO) 8.09 (2H, s), 7.36 (1H, t), 7.38-7.10 (3H, m), 4.57 (1H, t), 4.21 (3H, m), 3.71 (1 H, q), 4.39 (2H, s), 3.63 (1H, q).

Example 119 (IR-trans) 2-2-Amino-5-(2, 3-difluorophenyl) methyl thio thiazolo [4,5-d] pyrimidin- 7-yl amino-cyclopentanol The product from example 113 step a) (0.2g), (IR, 2R) 2-aminocyclopentanol hydrochloride (1. Og) and N-ethyldiisopropylamine (1.2ml) in methanol (lSml) was heated in a sealed vessel at 120 °C for 90 mins. The mixture was evaporated to dryness and purified (HPLC, Novapak° C 18 column, 0.1% aqueous ammonium acetate: acetonitrile, gradient elution 70: 30 to 0: 100 over 15 minutes) to afford the title compound (0.098g).

MS (APCI) 410 (M+H+, 100%).

NMR 8H (d6-DMSO) 8.04 (2H, s), 7.41-7.27 (2H, m), 7. 20 (1H, d), 7.16-7.11 (1H, m), 4.76 (1H, d), 4.41 (2H, dd), 4.09 (IH, m), 3.95 (IH, m), 1.99 (1H, m), 1.89 (1H, m), 1.62 (2H, m), 1.49-1. 36 (2H, m).

Example 120 (15-trans) 2-2-Amino-5-(2, 3-difluorophenyl) methyl thio thiazolo [4,5-d] pyrimidin- 7-yl amino-cyclopentanol Prepared by the method of Example 119 using the product from Example 113, step a) and (lys, 2S)-2-aminocyclopentanol hydrochloride.

MS (APCI) 410 (M+H+, 100%).

NMR 8H (d6-DMSO) 8.03 (2H, s), 7.41-7.27 (2H, m), 7.20 (1H, d), 7.16-7.11 (1H, m), 4.76 (1H, d), 4.41 (2H, dd), 4.09 (1H, m), 3.96 (1H, m), 1.99 (1H, m), 1.89 (1H, m), 1.62 (2H, m), 1.49-1.36 (2H, m).

Example 121 2-[[2-Amino-5-[(phenylmethyl)[[2-Amino-5-[(phenylmethyl) thio] thiazolo [4,5-dlpyrimidin-7-yl] amino]-2-methyl-1- propanol Prepared by the method of Example 117 using the product of Example 1, step a) (0.6g) and 2-amino-2-methyl-propanol. Purification (Si02, ethyl acetate as eluant) gave the title compound (0.46g).

MS (APCI) 362 (M+H+, 100%).

NMR 8H (d6-DMSO) 8.00 (2H, s), 7.42-7.20 (SH, m), 6.29 (1H, s), 4.86 (1H, s), 4.35 (2H, s), 3.56 (2H, d), 1.32 (6H, s).

Example 122 2-Methyl-2-[[2-(methylamino)-5-[(phenylmethyl) thio] thiazolo[[2-(methylamino)-5-[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7- yl] amino-1-propanol a) 2- [[2-Bromo-5-[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]-2-methyl- 1-propanol To a solution of the product from Example 121 (0.1 g) in bromoform (5 ml) was added isoamylnitrite (0.13 ml) and the mixture heated at 60°C for 10 mins. The mixture was s evaporated to dryness then purified (Si02, ethyl acetate: dichloromethane 1 : 9 as eluant) to give the subtitle compound (0.043g).

MS (APCI) 426 (M+H+, 100%). b) 2-Methyl-2- [[2-(methylamino)-5-[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7- yl amino-l-propanol

To a solution of the product from step a) (0.043g) in methanol (Sml) was added a saturated solution of methanolic methylamine (20ml) and the mixture strirred for 30 mins. The mixture was evaporated to dryness and purified (HPLC, Novapak''C 18 column, 0.1 % aqueous ammonium acetate: acetonitrile, isocratic elution 70: 30 over 15 minutes) to afford the title compound (0.026g).

MS (APCI) 376 (M+H+, 100%).

NMR 8H (d6-DMSO) 8.49 (1H, d), 7.42-7.21 (5H, m), 6.34 (1H, s), 4.87 (1H, s), 4.35 (2H, s), 3.56 (2H, d), 2.94 (3H, d), 1.33 (6H, s).

Example 123 2-[[2-[[5-[[(2, 3-Difluorophenyl) methyl] thio]-2-[(phenylmethyl) amino] thiazolo[[2-[[5-[[(2, 3-Difluorophenyl) methyl] thio]-2-[(phenylmethyl) amino] thiazolo [4,5- cpyrimidin-7-yl amino-2-methyl-1-propanol a) 2-[[2-Bromo-5-[[(2,3-difluorophenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7- yl] amino-2-methyl-1-propanol The sub-title compound was prepared by the method of Example 122, step a) using the product from Example 116. Purification (Si02, ethyl acetate: dichloromethane 1: 9 as eluant) gave the subtitle compound (0.16g).

MS (APCI) 461 (M+H+, 100%). b) 2- [[2-[[5-[[(2, 3-Difluorophenyl) methyl] thio]-2-[(phenylmethyl) amino] thiazolo 4,5- d pyrimidin-7-yl amino-2-methyl-l-propanol Prepared by the method of Example 122, step b) using the product from step a).

Purification (SiO2, ethyl acetate: dichloromethane 1: 9 as eluant) gave the title compound (0.051 g).

MS (APCI) 488 (M+H+, 100%).

NMR 8H (d6-DMSO) 9.08 (1H, d), 7.38-7.12 (8H, m), 6.42 (1H, s), 4.82 (1H, t), 4.59 (2H, s), 4.42 (2H, s), 3.54 (2H, d), 1.29 (6H, s).

Example 124 5-[[(2, 3-Difluorophenyl) methyl] thio] thiazolo[[(2, 3-Difluorophenyl) methyl] thio] thiazolo [4,5-dlpyrimidin-7 (4H)-one To a solution of the product from Example 3 (1.0g) in tetrahydrofuran (50ml) was added isoamyl nitrite (3ml) and the mixture heated at 70°C for 2 hours. The mixture was evaporated to dryness and purified (SiO2, ethyl acetate: chloroform 1: 9 as eluant) to give the title compound (0.61g).

MS (APCI) 512 (M+H+, 100%).

NMR 8H (d6-DMSO) 13.19 (1H, s), 9.61 (1H, d), (2H, m), 7.22-15 (1H, m), 4.59 (2H, s).

Example 125-148 Example 125 to 148 were prepared by heating, the product of Example 113, step a) (Sx10-6 moles) with the appropriate amine (10 equivalents) and N-ethyldiisopropylamine (20 equivalents) in N-methylpyrrolidinone (0.3 ml) in a sealed vessel at 120°C for 16 hours.

Example 125 (+)-2-2-Amino-5-(2, 3-difluorophenyl) methyl thio thiazolo [4,5-d] pyrimidin-7- yl amino-1-butanol MS (APCI) 398 (M+H+, 100%).

Example 126 (lS, 2S)-2- [[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo [4,5-d] pyrimidin-7- yl amino-cyclohexanol MS (APCI) 424 (M+H+, 100%).

Example 127 (#)-2-[[2-Amino-5-[[(2,3-difluorophenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7- yl amino-1-propanol MS (APCI) 384 (M+H+, 100%) Example 128 2-[[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo[[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo [4,5-d] pyrimidin-7- yl amino-1-ethanol MS (APCI) 370 (M+H+, 100%).

Example 129 (w)-2-2-Amino-5-(2, 3-difluorophenyl) methyl thio] thiazolo [4,5-dlpyrimidin-7- yl amino-4-methyl-1-pentanol MS (APCI) 426 (M+H+, 100%).

Example 130 (_)-1-2-Amino-5-(2, 3-difluorophenyl) methyl thio] thiazolo [4,5-dlpyrimidin-7- yl amino-2-propanol MS (APCI) 384 (M+H+, 100%).

Example 131 2-[[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo[[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo [4,5-d] pyrimidin-7- yl amino-2-methyl-1, 3-propanediol MS (APCI) 414 (M+H+, 100%).

Example 132 1-[[[2-Amino-5-[[(2,3-difluorophenyl)methyl]thio]thiazolo[4, 5-d pyrimidin-7- yl amino methyl-cyclohexanol MS (APCI) 438 (M+H+, 100%).

Example 133 (2R)-2-2-Amino-5-(2, 3-difluorophenyl) methyl thio thiazolo [4,5-dlpyrimidin-7- yl amino-1-butanol MS (APCI) 398 (M+H+, 100%).

Example 134 2-[[2-Amino-5-[[(2, 3-difluorophenyl) methyl][[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo [4,5-illpyrimidin-7-yl]-(2- aminoethyl) amino-1-ethanol MS (APCI) 413 (M+H+, 100%).

Example 135 2-[2-[[2-Amino-5-[[(2,3-difluorophenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7- yl amino ethoxy-1-ethanol MS (APCI) 414 (M+H+, 100%).

Example 136 (osS)-a-(lR)-1-2-Amino-5-(2, 3-difluorophenyl) methyl thio] thiazolo [4,5- d pyrimidin-7-yl methylamino ethyl-benzenemethanol MS (APCI) 474 (M+H+, 100%).

Example 137 1-[2-Amino-5-[[(2, 3-difluorophenyl) methyl][2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo [4,5-d] pyrimidin-7-yl]-4- piperidinol MS (APCI) 410 (M+H+, 100%).

Example 138 5-[[(2, 3-Difluorophenyl) methyl] thio]-N7-ethyl-thiazolo[[(2, 3-Difluorophenyl) methyl] thio]-N7-ethyl-thiazolo [4,5-dlpyrimidine-2, 7-diamine MS (APCI) 354 (M+H+, 100%).

Example 139 5-[[(2, 3-Difluorophenyl) methyl] thio]-N7-(2-propenyl)-thiazolo[[(2, 3-Difluorophenyl) methyl] thio]-N7-(2-propenyl)-thiazolo [4,5-dlpyrimidine-2,7- diamine MS (APCI) 366 (M+H+, 100%).

Example 140 2-Bromo-5-[(phenylmethyl) thio] thiazolo[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7 (4H)-one To a solution of the product from Example 9 (2g) in bromoform (100ml) was added isoamyl nitrite (2ml) and the mixture heated at 80°C for 2 hour. The mixture was evaporated to dryness and purified (Si02, dichloromethane as eluant) to give the title compound (0. 76g).

MS (APCI) 355,354 (M+H+), 354 (100%).

Example 141 (lS,2S)-2-[[2-Amino-5-[[(2,3-difluorophenyl)methyl]thio] thiazolo 4, 5-dlpyrimidin-7- yl] amino-1-phenyl-1, 3-propanediol MS (APCI) 476 (M+H+, 100%).

Example 142 2-[[2-Amino-5-[[(2, 3-difluorophenyl) methyl][[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo [4,5-dlpyrimidin-7- yl amino-1,3-propanediol MS (APCI) 400 (M+H+, 100%).

Example 143 2-[[2-Amino-5-[[(2,3-difluorophenyl)methyl]thio] thiazolo [4,5-d] pyrimidin-7- yl amino-1-ethanol MS (APCI) 370 (M+H+, 100%).

Example 144 ()-5- (2,3-Difluorophenyl) methyl]thio]-N7-(2-methoxy-1-methylethyl)-thiazolo[4, 5- dlpyrimidine-2,7-diamine MS (APCI) 398 (M+H+, 100%).

Example 145 N7-Cyclopropyl-5-[[(2, 3-difluorophenyl) methyl] thio]-thiazolo[[(2, 3-difluorophenyl) methyl] thio]-thiazolo [4,5-d] pyrimidine-2,7- diamine

MS (APCI) 366 (M+H+, 100%).

Example 146 (_)-2-2-Amino-5-(2, 3-difluorophenyl) methyl thio-thiazolo [4,5-d] pyrimidin-7- yllaminol-l-propanol MS (APCI) 384 (M+H+, 100%).

Example 147 4-[[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio]-thiazolo[[2-Amino-5-[[(2, 3-difluorophenyl) methyl] thio]-thiazolo [4,5-d] pyrimidin-7- yl amino-1-butanol MS (APCI) 398 (M+H+, 100%).

Example 148 5- (2, 3-Difluorophenyl) methyl thio-N7- 2- (1H-imidazol-4-yl) ethyl-thiazolo 4,5- dlpyrimidine-2,7-diamine MS (APCI) 420 (M+H+, 100%).

Example 149-165 The compounds of Example 149 to 165 were prepared by heating 2- 2-bromo-5- (2,3- difluorophenyl) methyl] thio thiazolo [4,5-dlpyrimidin-7-yl] amino]-2-methyl-1-propanol (prepared according to the method of Example 122, step a) using the product of Example 116) (six 10-6 moles) with the appropriate amine (2 equivalents) and N-ethyldiisopropylamine (2 equivalents) in tetrahydrofuran (0.5 ml) at 50-60°C for 16 hours.

Example 149 N-[5-[[(2,3-Difluorophenyl)methyl]thio]-7-[(2-hydroxy-1,1- dimethylethyl) amino] thiazolo [4,5-dlpyrimidin-2-yl]-serine, methyl ester MS (APCI) 500 (M+H+, 100%).

Example 150 2-[[5-[[(2,3-Difluorophenyl)methyl]thio]-2-[(1-methylethyl)a mino]thiazolo [4,5- dlpyrimidin-7-yl amino-2-methyl-1-propanol MS (APCI) 440 (M+H+, 100%).

Example 151 2-[[5-[[(2, 3-Difluorophenyl) methyl] thio]-2-(ethylamino) thiazolo[[5-[[(2, 3-Difluorophenyl) methyl] thio]-2-(ethylamino) thiazolo [4,5-dlpyrimidin-7- yl amino-2-methyl-1-propanol MS (APCI) 426 (M+H+, 100%).

Example 152 2-[t5-[[(2, 3-Difluorophenyl) methyl] thio]-2-[[2-(lH-indol-3- yl) ethyl amino thiazolo [4,5-d] pyrimidin-7-yl] amino]-2-methyl-1-propanol MS (APCI) 541 (M+H+, 100%).

Example 153 2-[[5-[[(2,3-Difluorophenyl)methyl]thio]-2-[(1- naphthalenylmethyl) amino thiazolo [4,5-d] pyrimidin-7-yl] amino]-2-methyl-1- propanol MS (APCI) 538 (M+H+, 100%).

Example 154 2-[[5-[[(2, 3-Difluorophenyl) methyl] thio]-2-[(1, 2-diphenylethyl) amino] thiazolo[[5-[[(2, 3-Difluorophenyl) methyl] thio]-2-[(1, 2-diphenylethyl) amino] thiazolo [4,5- dlpyrimidin-7-yl amino-2-methyl-1-propanol MS (APCI) 578 (M+H+, 100%).

Example 155 2-[[5-[[(2,3-Difluorophenyl)methyl]thio]-2-[(2,2, 2-trifluoroethyl) amino thiazolo [4,5- d pyrimidin-7-yl amino-2-methyl-1-propanol MS (APCI) 480 (M+H+, 100%).

Example 156 2-[[5-[[(2,3-Difluorophenyl)methyl]thio]-2-[[(3,4, 5- trimethoxyphenyl) methyl amino] thiazolo [4,5-d] pyrimidin-7-yl] amino]-2-methyl-1- propanol MS (APCI) 578 (M+H+, 100%).

Example 157 2-[[5-[[(2,3-Difluorophenyl)methyl]thio]-2-[(1,1-dimethyleth yl)amino]thiazolo[4,5- d pyrimidin-7-yl amino-2-methyl-1-propanol MS (APCI) 454 (M+H+, 100%).

Example 158 2-[[5-[[(2,3-Difluorophenyl)methyl]thio]-2-[[2-(2-thienyl)et hyl]amino] thiazolo [4,5- dlpyrimidin-7-yl amino-2-methyl-1-propanol

MS (APCI) 508 (M+H+, 100%).

Example 159 2-[[5-[[(2,3-Difluorophenyl)methyl]thio]-2-[(4-methylcyclohe xyl)amino]thiazolo[4, 5- dlpyrimidin-7-yl amino-2-methyl-1-propanol MS (APCI) 494 (M+H+, 100%).

Example 160 2-[[5-[[(2, 3-Difluorophenyl) methyl] thio]-7-[(2-hydroxy-1, 1- dimethylethyl) amino] thiazolo [4,5-dlpyrimidin-2-yl] amino]-acetamide MS (APCI) 455 (M+H+, 100%).

Example 161 2-[[2-[[2-(4-Aminophenyl) ethyl] amino]-5-[[(2,[[2-[[2-(4-Aminophenyl) ethyl] amino]-5-[[(2, 3- difluorophenyl) methyl thio thiazolo [4,5-d] pyrimidin-7-yl] amino]-2-methyl-1- propanol MS (APCI) 517 (M+H+, 100%).

Example 162 2-[[5-[[(2,3-Difluorophenyl)methyl]thio]-2-[(2-fluoroethyl)a mino] thiazolo [4,5- dJpyrimidin-7-yl amino-2-methyl-1-propanol MS (APCI) 444 (M+H+, 100%).

Example 163 2-[[2-(Cyclopropylamino)-5-[[(2, 3-difluorophenyl) methyl][[2-(Cyclopropylamino)-5-[[(2, 3-difluorophenyl) methyl] thio] thiazolo [4,5- d pyrimidin-7-yl amino-2-methyl-1-propanol

MS (APCI) 438 (M+H+, 100%).

Example 164 (#)-2-[[5-[[(2,3-Difluorophenyl)methyl]thio]-7-[(2-hydroxy-1 ,1- dimethylethyl) amino] thiazolo [4,5-d] pyrimidin-2-yl] amino]-1-pentanol MS (APCI) 484 (M+H+, 100%).

Example 165 2-[[5-[[(2, 3-Difluorophenyl) methyl] thio]-2-[[2-(2- hydroxyethoxy) ethyl amino thiazolo [4,5-d] pyrimidin-7-yl] amino]-2-methyl-1- propanol MS (APCI) 486 (M+HF, 100%).

Example 166 2-Bromo-5-[[(2S3-difluorophenyl) methyl] thio]-thiazolo[[(2S3-difluorophenyl) methyl] thio]-thiazolo [4,5-d] pyrimidin-7 (4H)-one To a solution of the product from Example 3 (0.2g) in bromoform (5ml) was added isoamyl nitrite (0.25ml) and the mixture heated at 70°C for 1 hour. The mixture was evaporated to dryness and purified (Si02, dichloromethane as eluant) to give the title compound (0.08g).

NMR oH (d6-DMSO) 7.42-7.14 (3H, m), 4.55 (2H, s).

Example 167-173 The compounds of Example 167 to 173 were prepared by heating, the product of Example 166 with the appropriate amine (1.2 equivalents) and N-ethyldiisopropylamine (0. lml) in tetrahydrofuran (0.2 ml) at 40°C for 16 hours.

Example 167 N-[5-([(2,3-Difluorophenyl)methyl]thio]-6,7-dihydro-7-oxo-th iazolo[4, 5-d pyrimidin- 2-yl-DL-serine, methyl ester MS (APCI) 429 (M+H+, 100%).

Example 168 5-[[(2, 3-Difluorophenyl) methyl] thio]-2-[(1-methylethyl) amino]-thiazolo[[(2, 3-Difluorophenyl) methyl] thio]-2-[(1-methylethyl) amino]-thiazolo [4,5- d pyrimidin-7 (4H)-one MS (APCI) 369 (M+H+, 100%).

Example 169 5-[[(2, 3-Difluorophenyl) methyl] thio]-2-[[2-(1H-indol-3-yl) ethyl] amino]-thiazolo[[(2, 3-Difluorophenyl) methyl] thio]-2-[[2-(1H-indol-3-yl) ethyl] amino]-thiazolo [4,5- dlpyrimidin-7 (4H)-one.

MS (APCI) 470 (M+H+, 100%).

Example 170 2-[[5-[[(2, 3-Difluorophenyl) methyl][[5-[[(2, 3-Difluorophenyl) methyl] thio]-6,7-dihydro-7-oxo-thiazolo [4,5-d] pyrimidin- 2-yl amino-acetamide MS (APCI) 384 (M+H+, 100%).

Example 171 2-[[2-(4-Aminophenyl) ethyl] amino]-5-[[(2, 3-difluorophenyl) methyl] thio]-thiazolo[[2-(4-Aminophenyl) ethyl] amino]-5-[[(2, 3-difluorophenyl) methyl] thio]-thiazolo [4,5- dJpyrimidin-7 (4H)-one MS (APCI) 446 (M+H+, 100%).

Example 172 5-[[(2, 3-Difluorophenyl) methyl] thio]-2-[(2-fluoroethyl) amino]-thiazolo[[(2, 3-Difluorophenyl) methyl] thio]-2-[(2-fluoroethyl) amino]-thiazolo [4,5- d pyrimidin-7 (4H)-one MS (APCI) 373 (M+H+, 100%).

Example 173 5-[[(2, 3-Difluorophenyl) methyl] thio]-2-[[2-(2-hydroxyethoxy) ethyl] amino]- thiazolo [4,5-dlpyrimidin-7 (4H)-one MS (APCI) 415 (M+H+, 100%).

Example 174-218 Example 174 to 218 were prepared by heating the product of Example 122, step a) (5x 10-6 moles) with the appropriate amine (2 equivalents) and N-ethyldiisopropylamine (2 equivalents) in N-methylpyrrolidinone (0.1 ml) in a sealed vessel at 60°C for 5 hours.

Example 174 2- 2- (Cyclohexylamino)-5- (phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]- 2-methyl-1-propanol MS (APCI) 444 (M+H+, 100%).

Example 175 2-[[2-[(1, 1-Dimethylethyl) amino]-5-[(phenylmethyl) thio] thiazolo[[2-[(1, 1-Dimethylethyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5-dlpyrimidin-7- yl amino-2-methyl-1-propanol MS (APCI) 418 (M+H+, 100%).

Example 176 N- 7- (2-Hydroxy-1, 1-dimethylethyl) amino-5- (phenylmethyl) thio] thiazolo [4,5- d pyrimidin-2-yl-DL-alanine, methyl ester MS (APCI) 448 (M+H+, 100%).

Example 177 4-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5-[(phenylmethyl) thio]thiazolo[4, 5- d pyrimidin-2-yl amino-cyclohexanol MS (APCI) 460 (M+H+, 100%).

Example 178 2-Methyl-2-[[2-[(4-phenylbutyl) amino]-5-[(phenylmethyl) thio] thiazolo[[2-[(4-phenylbutyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-1-propanol MS (APCI) 494 (M+H+, 100%).

Example 179 2-Methyl-2-[[5-[(phenylmethyl)thio]-2-[[(tetrahydro-2- furanyl) methyl amino thiazolo [4,5-d] pyrimidin-7-yl] amino]-1-propanol MS (APCI) 446 (M+H+, 100%).

Example 180 2-Methyl-2-[[2-[(1-methylethyl) amino]-5-[(phenylmethyl)[[2-[(1-methylethyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-1-propanol MS (APCI) 404 (M+H+, 100%).

Example 181 2-[[2-[[2-(4-Aminophenyl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo[[2-[[2-(4-Aminophenyl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5- dupyrimidin-7-yl amino-2-methyl-1-propanol MS (APCI) 481 (M+H+, 100%).

Example 182 N- 7- (2-Hydroxy-1, 1-dimethylethyl) amino-5- (phenylmethyl) thio] thiazolo [4,5- zpyrimidin-2-yl-L-valine, ethyl ester MS (APCI) 490 (M+H+, 100%).

Example 183 (2S)-2-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5-[(phenylme thyl)thio]thiazolo[4, 5- d pyrimidin-2-yl amino-4-methyl-pentanamide.

MS (APCI) 475 (M+H+, 100%).

Example 184 2-Methyl-2-[[2-[(2-phenylethyl) amino]-5-[(phenylmethyl)[[2-[(2-phenylethyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-1-propanol MS (APCI) 466 (M+H+, 100%).

Example 185 2-[[2-[[(4-Aminophenyl) methyl] amino]-5-[(phenylmethyl)[[2-[[(4-Aminophenyl) methyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-2-methyl-1-propanol MS (APCI) 467 (M+H+, 100%).

Example 186 2-Methyl-2-[[5-[(phenylmethyl)thio]-2-[[2-(2-thienyl)ethyl]a mino]thiazolo[4, 5- d pyrimidin-7-yl amino-1-propanol MS (APCI) 472 (M+H+, 100%).

Example 187 2-[[2-[(2-Fluoroethyl) amino]-5-[(phenylmethyl) thio] thiazolo[[2-[(2-Fluoroethyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5-d]pyrimidin-7- yl amino-2-methyl-1-propanol MS (APCI) 408 (M+H+, 100%).

Example 188 2-Methyl-2-[[2-[[(3-nitrophenyl)methyl]amino]-5-[(phenylmeth yl)thio]thiazolo[4, 5- d pyrimidin-7-yl amino-1-propanol MS (APCI) 497 (M+H+, 100%).

Example 189 (αR)-α-[(1S)-1-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5- (phenylmethyl) thio thiazolo [4,5-d] pyrimidin-2-yl] amino] ethyl]-benzenemethanol MS (APCI) 496 (M+H+, 100%).

Example 190 2-Methyl-2-[[5-[(phenylmethyl)thio]-2-[[(3,4, 5- trimethoxyphenyl) methyl amino thiazolo [4,5-d] pyrimidin-7-yl] amino]-1-propanol MS (APCI) 542 (M+H+, 100%).

Example 191 2-Methyl-2-[[2-[(lR-trans)-(2-phenylcyclopropyl) amino]-5- (phenylmethyl) thio thiazolo [4,5-dlpyrimidin-7-yl] amino]-1-propanol MS (APCI) 478 (M+H+, 100%).

Example 192 2-[[2-[[2-(lH-Indol-3-yl) ethyl] amino]-5-[(phenylmethyl)[[2-[[2-(lH-Indol-3-yl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin- 7-yl amino-2-methyl-1-propanol MS (APCI) 505 (M+H+, 100%).

Example 193 2-[[2-[(1, 1-Izimethylpropyl) amino]-5-[(phenylmethyl)[[2-[(1, 1-Izimethylpropyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7- yl amino-2-methyl-1-propanol MS (APCI) 432 (M+H+, 100%).

Example 194 (+)-2-Methyl-2-2-(1-methylbutyl) amino-5-(phenylmethyl) thio thiazolo [4,5- dlpyrimidin-7-yl amino-1-propanol MS (APCI) 432 (M+H+, 100%).

Example 195 (_)-2-Methyl-2-2-(1-methylhexyl) amino-5-(phenylmethyl) thio thiazolo [4,5- d]pyrimidin-7-yl]amino]-1-propanol MS (APCI) 460 (M+H+, 100%).

Example 196 2-[[2-[[(2-Aminophenyl) methyl] amino]-5-[(phenylmethyl)[[2-[[(2-Aminophenyl) methyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-2-methyl-1-propanol MS (APCI) 467 (M+H+, 100%).

Example 197 2-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5-[(phenylmethyl) thio]thiazolo[4, 5- d pyrimidin-2-yl amino-1, 3-propanediol MS (APCI) 436 (M+H+, 100%).

Example 198 2-[[2-[[2-(Ethylthio)ethyl]amino]-5-[(phenylmethyl)thio] thiazolo [4,5-dlpyrimidin-7- yl amino-2-methyl-1-propanol MS (APCI) 450 (M+H+, 100%).

Example 199 (2S)-2-7-(2-Hydroxy-1, 1-dimethylethyl) amino-5-(phenylmethyl) thio thiazolo [4,5- d pyrimidin-2-yl amino-3, 3-dimethyl-1-butanol MS (APCI) 462 (M+H+, 100%).

Example 200 (αS)-α-[(1R)-1-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5- (phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-2-yl] amino]-2-methoxyethyl]- benzenemethanol MS (APCI) 526 (M+H+, 100%).

Example 201 2-[[2-(Ethylamino)-5-[(phenylmethyl)thio] thiazolo [4,5-d]pyrimidin-7-yl]amino]-2- methyl-1-propanol MS (APCI) 390 (M+H+, 100%).

Example 202 2-[[2-[[[3-Fluoro-5-(trifluoromethyl) phenyl] methyl][[2-[[[3-Fluoro-5-(trifluoromethyl) phenyl] methyl] amino]-5- [(phenylmethyl)thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]-2-methyl-1-propanol MS (APCI) 538 (M+H+, 100%).

Exainple 203 (+)-2-Methyl-2-2-(1-methylpropyl) amino-5-(phenylmethyl) thio thiazolo [4,5- d pyrimidin-7-yl amino-1-propanol MS (APCI) 418 (M+H+, 100%).

Example 204 2-[[2-[[(4-Methoxyphenyl)methyl]amino]-5-[(phenylmethyl)thio ]thiazolo[4, 5- d pyrimidin-7-yl amino-2-methyl-1-propanol MS (APCI) 482 (M+H+, 100%).

Example 205 2-[[2-[(2-Hydroxyethyl) amino]-5-[(phenylmethyl)[[2-[(2-Hydroxyethyl) amino]-5-[(phenylmethyl) thio] thiazolo 4, 5-d pyrimidin-7- yl amino-2-methyl-1-propanol MS (APCI) 406 (M+H+, 100%).

Example 206 2-[[2-[[2-(lH-Imidazol-4-yl) ethyl] amino]-5-[(phenylmethyl)[[2-[[2-(lH-Imidazol-4-yl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-2-methyl-1-propanol MS (APCI) 456 (M+H+, 100%).

Example 207 2-[[2-[(Diphenylmethyl) amino]-5-[(phenylmethyl) thio] thiazolo[[2-[(Diphenylmethyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7- yl amino-2-methyl-1-propanol MS (APCI) 528 (M+H+, 100%).

Example 208 (2S)-2-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5- [(phenylmethyl)thio] thiazolo [4,5- d pyrimidin-2-yl amino-1-butanol MS (APCI) 434 (M+H+, 100%).

Example 209 2-[[2-[(2, 2-Diethoxyethyl) amino]-5-[(phenylmethyl)[[2-[(2, 2-Diethoxyethyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7- yl amino-2-methyl-1-propanol MS (APCI) 478 (M+H+, 100%).

Example 210 4-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-2-yl amino-1-butanol MS (APCI) 434 (M+H+, 100%).

Example 211 (lS, 2S)-2-7-(2-Hydroxy-1, 1-dimethylethyl) amino]-5- (phenylmethyl) thio thiazolo [4,5-d] pyrimidin-2-yl] amino]-cyclohexanol.

MS (APCI) 460 (M+H+, 100%).

Example 212 (_)-2-2-(2-Hydroxy-1-methylethyl) amino-5-(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-2-methyl-1-propanol MS (APCI) 420 (M+H+, 100%).

Example 213 2-[[2-[[2-(2-Hydroxyethoxy) ethyl] amino]-5-[(phenylmethyl)[[2-[[2-(2-Hydroxyethoxy) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-2-methyl-1-propanol MS (APCI) 450 (M+H+, 100%).

Example 214 (#)-2-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5-[(phenylmet hyl)thio] thiazolo [4,5- d]pyrimidin-2-yl]amino]-1-pentanol MS (APCI) 448 (M+H+, 100%).

Example 215 2-[[7-[(2-Hydroxy-1, 1-dimethylethyl) amino]-5-[(phenylmethyl) thio] thiazolo[[7-[(2-Hydroxy-1, 1-dimethylethyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-2-yl amino-acetamide MS (APCI) 419 (M+H+, 100%).

Example 216 (#)-2-[[2-[[1-(4-Fluorophenyl)ethyl]amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-2-methyl-propanol MS (APCI) 484 (M+H+, 100%).

Example 217 (lR,2S)-2-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5- (phenylmethyl) thio thiazolo [4,5-dlpyrimidin-2-yl] amino]-cyclohexanol MS (APCI) 460 (M+H+, 100%).

Example 218 (αS)-α-[(1R)-1-[[7-[(2-Hydroxy-1,1-dimethylethyl)amino]-5- [(phenylmethyl)thio] thiazolo [4,5-alpyrimidin-2-yl] amino] ethyl]-benzenemethanol MS (APCI) 496 (M+H+, 100%).

Example 219 2-Bromo-7-chloro-5-[(phenylmethyl)thio]-thiazolo[4, 5-d pyrimidine To a solution of the product from Example 1, step a) (lOg) in bromoform (300mol3 was added t-butylnitrite (10ml) and the mixture heated at 60°C for 30 mins. The mixture was

evaporated to dryness then purified (Si02, isohexane: dichloromethane 1: 1 as eluant) to give the title compound (7.5g).

MS (APCI) 373 (M+H+, 100%).

NMR oH (d6-DMSO) 7.47-7.24 (SH, m), 4.49 (2H, s).

Example 220 7-Chloro-N-methyl-5-[(phenylmethyl) thio]-thiazolo[(phenylmethyl) thio]-thiazolo [4,5-pyrimidin-2-amine A solution of the product from Example 219 (0.3g) in tetrahydrofuran (2ml) containing methylamine (2. 0 molar in THF: 0.81ml) was stirred for 16 hours. The mixture was evaporated to dryness then purified (Si02, ethyl acetate: dichloromethane 1: 9 as eluant) to give the title compound (295mg).

MS (APCI) 323 (M+H+, 100%).

NMR AH (d6-DMSO) 9.30 (1H, s), 7.46-7.22 (SH, m), 4.40 (2H, s), 3.05 (3H, s).

Example 221-223 Examples 221 to 223 were prepared by heating the product of Example 220 (2.5x 10-6 moles) with the appropriate amine (2 equivalents) and N-ethyldiisopropylamine (3 equivalents) in N-methylpyrrolidinone (0.1 ml) in a sealed vessel at 100°C for 10 hours.

Example 221 ()-2- 2- (Methylamino)-5- (phenylmethyl) thio] thiazolo 4,5-d pyrimidin-7-yl amino]- 1-propanol MS (APCI) 362 (M+H+, 100%).

Example 222 (2R)-4-Methyl-2-2-(methylamino)-5-(phenylmethyl) thio thiazolo [4,5-d] pyrimidin-7- yl amino-1-pentanol MS (APCI) 404 (M+H+, 100%).

Example 223 N-[2-(Methylamino)-5-[(phenylmethyl)[2-(Methylamino)-5-[(phe nylmethyl) thio] thiazolo [4,5-dlpyrimidin-7-yl]-L-serine, ethyl ester MS (APCI) 420 (M+H+, 100%).

Example 224 7-Chloro-5- (phenylmethyl) thio-N- (tetrahydro-2-furanyl) methyl-thiazolo [4,5- d pyrimidin-2-amine Prepared according to the method of Example 220 using the product of Example 219 and tetrahydrofurfurylamine.

MS (APCI) 393 (M+H+, 100%).

NMR 8H (d6-DMSO) 9.50 (1H, s), 7.47-7.19 (SH, m), 4.39 (2H, s), 4.06 (1H, m) 3.82 (1H, m), 3.66 (2H, m), 3.50 (1H, m), 2.00-1.53 (4H, m).

Examples 225-228 Examples 225-228 were prepared by the method of Example 221, using the product of Example 224.

Examples 225 <BR> <BR> <BR> <BR> (#)-2-[[5-[(Phenylmethyl)thio]-2-[[(tetrahydro-2-furanyl)met hyl]amino]thiazolo[4,5- d pyrimidin-7-yl amino-1-butanol MS (APCI) 446 (M+H+, 100%).

Examples 226 (#)-2-[[5-[(Phenylmethyl)thio]-2-[[(tetrahydro-2-furanyl)met hyl]amino]thiazolo[4,5- d pyrimidin-7-yl amino-1-propanol MS (APCI) 432 (M+H+, 100%).

Examples 227 (2R)-4-Methyl-2-[[5-[(phenylmethyl)thio]-2-[[(tetrahydro-2- furanyl) methyl amino thiazolo [4,5-d] pyrimidin-7-yl] amino]-1-pentanol MS (APCI) 474 (M+H+, 100%).

Examples 228 N-[5-[(Phenylmethyl)thio]-2-[[(tetrahydro-2-furanyl)methyl]a mino]thiazolo[4, 5- d pyrimidin-7-yl-L-serine, ethyl ester MS (APCI) 490 (M+H+, 100%).

Example 229 2- 2- 7-Chloro-5- (phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-2-yl] amino] ethoxy]-1- ethanol Prepared according to the method of Example 220 using the product of Example 219 (0.3g) and 2- (2-aminoethoxy) ethanol.

MS (APCI) 397 (M+H+, 100%).

Example 230 (+)-2-l2-2-(2-Hydroxyethoxy) ethyl amino-5-(phenylmethyl) thiolthiazolo [4,5- d pyrimidin-7-yl amino-1-propanol Prepared by the method of Example 221, using the product of Example 229.

MS (APCI) 436 (M+H+, 100%).

Example 231 4-[2-[[7-Chloro-5-[(phenylmethyl) thio] thiazolo[2-[[7-Chloro-5-[(phenylmethyl) thio] thiazolo [4,5-dlpyrimidin-2-yleamino] ethyl]- benzenesulfonamide A solution of the product from Example 219 (0.3g) in tetrahydrofuran (2ml) containing 4- (2-aminoethyl) benzenesulfonamide (0.161 g) and N-ethyldiisopropylamine (0.5 ml) was stirred for 16 hours. The mixture was evaporated to dryness then purified (SiO2, ethyl acetate: dichloromethane 4: 6 as eluant) to give the title compound (310mg).

MS (APCI) 492 (M+H+, 100%).

NMR 8H (d6-DMSO) 9.45 (1H, s), 7.78-7.23 (9H, m), 4.41 (2H, s), 3.77 (2H, s) 3.02 (2H, t).

Examples 232-235 Examples 232-235 were prepared by the method of Example 221, using the product of Example 231.

Example 232 (#)-4-[2-[[7-[[1-(Hydroxymethyl)propyl]amino]-5-[(phenylmeth yl)thio] thiazolo [4,5- d pyrimidin-2-yl amino ethyl-benzenesulfonamide MS (APCI) 545 (M+H+, 100%).

Example 233 ()-4- 2- 7- (2-Hydroxy-1-methylethyl) amino-5- (phenylmethyl) thio thiazolo [4,5- d pyrimidin-2-yl amino ethyl-benzenesulfonamide MS (APCI) 531 (M+H+, 100%).

Example 234 4-[2-[[7-[[(lR)-1-(Hydroxymethyl)-3-methylbutyl] amino]-5- (phenylmethyl) thio thiazolo [4,5-dlpyrimidin-2-yl] amino] ethyl]-benzenesulfonamide.

MS (APCI) 573 (M+H+, 100%).

Example 235 (#)-4-[2-[[7-[(2-Hydroxypropyl)amino]-5-[(phenylmethyl)thio] thiazolo[4,5- d pyrimidin-2-yl amino ethyl-benzenesulfonamide MS (APCI) 531 (M+H+, 100%).

Example 236 7-Chloro-N-[2-(lH-imidazol-4-yl) ethyl]-5-[(phenylmethyl) thio]-thiazolo[2-(lH-imidazol-4-yl) ethyl]-5-[(phenylmethyl) thio]-thiazolo [4,5- d pyrimidin-2-amine Prepared according to the method of Example 231 using the product of Example 219 and histamine.

MS (APCI) 403 (M+H+, 100%).

NMR 8H (d6-DMSO) 11.86 (IH, s), 9.42 (IH, s), 7.56 (1H, s), 7.56-7.23 (SH, m), 6.87 (IH, s), 4.41 (2H, s) 3.73 (2H, m), 2.85 (2H, t).

Examples 237-248 Examples 237-248 were prepared by the method of Example 221, using the product of Example 236.

Example 237 N7-Ethyl-N2- 2- (lH-imidazol-4-yl) ethyl-5- (phenylmethyl) thiothiazolo [4,5- d pyrimidine-2, 7-diamine MS (APCI) 412 (M+H+, 100%).

Example 238 N2- 2- (lH-Imidazol-4-yl) ethyl-5- (phenylmethyl) thio-N7- (3-pyridinylmethyl)- thiazolo [4,5-dlpyrimidine-2, 7-diamine MS (APCI) 475 (M+H+, 100%).

Example 239 (_)-2-2-2-(lH-Imidazol-4-yl) ethyl amino-5-(phenylmethyl) thio thiazolo [4,5- dlpyrimidin-7-yl amino-1-butanol MS (APCI) 456 (M+H+, 100%).

Example 240 (+)-2-2-2-(lH-Imidazol-4-yl) ethyl amino-5-(phenylmethyl) thio thiazolo [4,5- d pyrimidin-7-yl amino- 1-propanol MS (APCI) 442 (M+H+, 100%).

Example 241 (2R)-2-2-2-(lH-Imidazol-4-yl) ethyl amino-s-(phenylmethyl) thio] thiazolo 4, 5- dlpyrimidin-7-yl amino-4-methyl-1-pentanol MS (APCI) 484 (M+H+, 100%).

Example 242 ()-1- 2- 2- (lH-Imidazol-4-yl) ethyl amino-5- (phenylmethyl) thio thiazolo [4,5- d pyrimidin-7-yl amino-2-propanol MS (APCI) 442 (M+H+, 100%).

Example 243 5-[[2-[[2-(lH-Imidazol-4-yl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo[[2-[[2-(lH-Imidazol-4-yl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-1-pentanol MS (APCI) 470 (M+H+, 100%).

Example 244 1- 2- 2- (lH-Imidazol-4-yl) ethylamino-5- (phenylmethyl) thio thiazolo [4,5- d pyrimidin-7-yl-4- (phenylmethyl)-4-piperidinol MS (APCI) 558 (M+H+, 100%).

Example 245 ()-1- 2- 2- (lH-Imidazol-4-yl) ethylamino-5- (phenylmethyl) thio thiazolo [4,5- d pyrimidin-7-yl-3-piperidinecarboxamide MS (APCI) 495 (M+H+, 100%).

Example 246 2-[Ethyl [2-[[2-(lH-imidazol-4-yl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo[Ethyl [2-[[2-(lH-imidazol-4-yl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-1-ethanol MS (APCI) 456 (M+H+, 100%).

Example 247 N2- 2- (lH-Imidazol-4-yl) ethylJ-N7, N'-dimethyl-5- (phenylmethyl) thio- thiazolo 4,5- d pyrimidine-2,7-diamine MS (APCI) 412 (M+H+, 100%).

Example 248 N7-[2-(Diethylamino) ethyl]-N7-ethyl-N2-[2-(lH-imidazol-4-yl) ethyl]-5- [(phenylmethyl)thio]-thiazolo[4, 5 dlpyrimidine-2, 7-diamine MS (APCI) 511 (M+H+, 100%).

Example 249 7-Chloro-N-(2-phenoxyethyl)-5-[(phenylmethyl)thio]-thiazolo[ 4, 5-d pyrimidin-2- amine Prepared by the method of Example 231, using the product of Example 219 and 2-phenoxyethylamine.

MS (APCI) 429 (M+H+, 100%).

NMR 8H (d6-DMSO) 9.65 (1H, s), 7.46-6.93 (1OH, m), 4.41 (2H, s), 4.20 (2H, t), 3.87 (2H, m).

Examples 250-255 Examples 250-255 were prepared by the method of Example 221, using the product of Example 249.

Example 250 N2-(2-Phenoxyethyl)-5-[(phenylmethyl) thio]-N7-(3-pyridinylmethyl)-thiazolo(2-Phenoxyethyl)-5-[(ph enylmethyl) thio]-N7-(3-pyridinylmethyl)-thiazolo [4,5- dlpyrimidine-2, 7-diamine MS (APCI) 501 (M+H+, 100%).

Example 251 N2- (2-Phenoxyethyl)-N7- l- (phenylmethyl)-4-piperidinyl-5- (phenylmethyl) thio]- thiazolo 4,5 dlpyrimidine-2, 7-diamine MS (APCI) 583 (M+H+, 100%).

Example 252 2-Methyl-2-[[2-[(2-phenoxyethyl) amino]-5-[(phenylmethyl)[[2-[(2-phenoxyethyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5- dlpyrimidin-7-yl amino-1-propanol.

MS (APCI) 482 (M+H+, 100%).

Example 253 (+)-2-2-(2-Phenoxyethyl) amino-5-(phenylmethyl) thio thiazolo [4,5-d] pyrimidin-7- yl amino-l-propanol MS (APCI) 468 (M+H+, 100%).

Example 254 (2R)-4-Methyl-2-2-(2-phenoxyethyl) amino-5-(phenylmethyl) thio thiazolo [4,5- d pyrimidin-7-yl amino-1-pentanol MS (APCI) 510 (M+H+, 100%).

Example 255 1-[2-[(2-Phenoxyethyl) amino]-5-[(phenylmethyl) thio] thiazolo[2-[(2-Phenoxyethyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5 dlpyrimidin-7-yl]-4- (phenylmethyl)-4-piperidinol.

MS (APCI) 584 (M+H+, 100%).

Example 256 7-Chloro-N-cyclopropyl-S-[(phenylmethyl) thio]-thiazoloC4, 5 dlpyrimidin-2-amine, Prepared by the method of Example 220, using the product of Example 219 and cyclopropanamine.

MS (APCI) 351,349 (M+H+, 100%).

NMR 8H (d6-DMSO) 7.46-7.22 (5H, m), 4.41 (2H, s), 2.85-2.80 (1H, m), 0.90-0.84 (2H, m), 0.71-0.66 (2H, m).

Examples 257-260 Example 257 to 260 were prepared by the method of Example 221 using the product of Example 256.

Example 257 2-[[2-(Cyclopropylamino)-5-[(phenylmethyl)thio] thiazolo [4,5-d] pyrimidin-7- yl amino-l-butanol MS (APCI) 402 (M+H+, 100%).

Example 258 2-[[2-(Cyclopropylamino)-5-[(phenylmethyl)thio] thiazolo [4,5-d] pyrimidin-7- yl amino-l-propanol MS (APCI) 388 (M+H+, 100%).

Example 259 (2R)-2- 2- (Cyclopropylamino)-5- (phenylmethyl) thio] thiazolo [4,5-d]pyrimidin-7-yl]amino]-4-methyl-1-pentanol MS (APCI) 430 (M+H+, 100%).

Example 260 N-[2-(Cyclopropylamino)-5-[(phenylmethyl)thio] thiazolo [4,5 dlpyrimidin-7-yl]-L- serine, ethyl ester MS (APCI) 446 (M+H+, 100%).

Example 261 2-[[7-Chloro-5-[(phenylmethyl) thio] thiazolo[[7-Chloro-5-[(phenylmethyl) thio] thiazolo [4,5-d]pyrimidin-2-yl]amino]-1-pentanol Prepared by the method of Example 231, using the product of Example 219 and 2-amino-1-pentanol.

MS (APCI) 397,395 (M+H+, 100%).

IH NMR (d6-DMSO) 8 9.29 (1H, s), 7.46-7.22 (5H, m), 4.93 (1H, t), 4.39 (2H, s), 4.07- 4.00 (1H, m), 3.50 (2H, t), 1.63-1.43 (2H, m), 1.38-1.32 (2H, m), 0.89 (3H, t).

Examples 262-264 Example 262 to 264 were prepared by the method of Example 221 using the product of Example 261.

Example 262 (2R)-2-[[2-[[1-(Hydroxymethyl)butyl]amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-4-methyl-l-pentanol MS (APCI) 476 (M+H+, 100%).

Example 263 N-[2-[[1-(Hydroxymethyl)butyl]amino]-5-[(phenylmethyl)thio] thiazolo [4,5- d pyrimidin-7-yl-L-serine, ethyl ester MS (APCI) 492 (M+H+, 100%).

Example 264 (_)-2-7-Cyclohexyl (2-hydroxyethyl) amino-5-(phenylmethyl) thio thiazolo [4,5- dlpyrimidin-2-yl amino-1-pentanol

MS (APCI) 502 (M+H+, 100%).

Examples 265-270 The following examples were prepared by the method of Example 221, using the product of Example 229.

Examples 265 2-[2-[[7-(Ethylamino)-5-[(phenylmethyl)[2-[[7-(Ethylamino)-5 -[(phenylmethyl) thio] thiazolo [4,5-d]pyrimidin-2- yl amino] ethoxy-1-ethanol MS (APCI) 406 (M+H+, 100%).

Examples 266 2-[2-[[7-[(1-Methylethyl)amino]-5-[(phenylmethyl)thio]thiazo lo[4, 5<pyrimidin-2- yl amino] ethoxy-1-ethanol MS (APCI) 420 (M+H+, 100%).

Examples 267 (_)-2-2-2-(2-Hydroxyethoxy) ethyl amino-5-(phenylmethyl) thio] thiazolo [4,5- dlpyrimidin-7-yl amino-1-butanol, MS (APCI) 450 (M+H+, 100%).

Examples 268 2-[[2-[[2-(2-Hydroxyethoxy)ethyl]amino]-5-[(phenylmethyl)thi o]thiazolo[4, 5- d pyrimidin-7-yl amino-2-methyl-1-propanol MS (APCI) 450 (M+H+, 100%).

Examples 269 (2R)-2-2-2-(2-Hydroxyethoxy) ethyl amino-5-(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-4-methyl-1-pentanol, MS (APCI) 478 (M+H+, 100%).

Examples 270 2-[Cyclohexyl-[2-[[2-(2-hydroxyethoxy) ethyl] amino]-5- (phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]-1-ethanol MS (APCI) 504 (M+H+, 100%).

Examples 271 ()-2- 5- (Phenylmethyl) thio-2- (4-piperidinylamino) thiazolo [4,5-d] pyrimidin-7- yl amino-1-propanol a) 7-Chloro-5- [(phenylmethyl) thio]-N-(4-piperidinyl)-thiazolo [4,5-d] pyrimidin-2- amine A solution of the product from Example 219 (0.3g) in tetrahydrofuran (2ml) containing 4- amino-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester (0.161 g) and N-ethyldiisopropylamine (0.5 ml) was stirred for 16 hours before evaporating to dryness.

The residue was taken into dichloromethane (30ml) and trifluoroacetic acid (3ml) added.

The solution was stirred for 30 minutes then concentrated to give the title compound (310mg).

MS (APCI) 392 (M+H+, 100%).

NMR 8H (d6-DMSO) 9.47 (1H, s), 8.64-8.48 (2H, s), 7.46-7.23 (SH, s), 4.41 (2H, s) 4. 21 (1H, s), 3. 34 (2H, m), 3.09 (2H, m), 2.18 (2H, m), 1.69 (2H, m).

b) (#)-2-[[5-[(Phenylmethyl)thio]-2-(4-piperidinylamino)thiazol o[4, 5-d pyrimidin-7- yl amino-1-propanol Prepared by the method of Example 221, using the product of step a).

MS (APCI) 431 (M+H+, 100%).

Example 272 N-[2-[[7-Chloro-5-[(phenylmethyl)thio]thiazolo[4, 5 d pyrimidin-2-yl amino] ethyl]- acetamide Prepared according to the method of Example 231 using the product of Example 219.

MS (APCI) 396,394 (M+H+), 394 (100%).

Examples 273-276 Examples 273-276 were prepared by the method of Example 221 using the product of Example 272.

Example 273 (#)-N-[2-[[7-[[1-(Hydroxymethyl)propyl]amino]-5-[(phenylmeth yl)thio] thiazolo [4,5- d pyrimidin-2-yl amino ethyl-acetamide MS (APCI) 447 (M+H+, 100%) Examples 274 (+)-N-2-7-(2-Hydroxy-1-methylethyl) amino-5-(phenylmethyl) thio] thiazolo [4,5- d pyriniidin-2-yllamino ethyl-acetamide,

MS (APCI) 433 (M+H+, 100%) Examples 275 N- 2- 7- (2-Hydroxyethyl) amino-5- (phenylmethyl) thio] thiazolo [4,5-dlpyrimidin-2- yl amino ethyl-acetamide MS (APCI) 419 (M+H+, 100%) Example 276 N-[2-[[7-[[(1R)-1-(Hydroxymethyl)-3-methylbutyl]amino]-5- (phenylmethyl) thio thiazolo [4,5-d]pyrimidin-2-yl]amino]ethyl]-acetamide, MS (APCI) 475 (M+H+, 100%) Example 277 7-Chloro-5-[(phenylmethyl) thio]-N-[2-(2-thienyl) ethyl]-thiazolo[(phenylmethyl) thio]-N-[2-(2-thienyl) ethyl]-thiazolo [4,5-d] pyrimidin-2- amine Prepared by the method of Example 231, using the product of Example 219 and 2- (2-thienyl) ethylamine.

MS (APCI), 420,418 (M+H+), 418 (100%).

NMR 8H (d6-DMSO) 7.45-7.32 (5H, m), 6.96 (2H, m), 4.40 (2H, s), 3.78 (2H, s), 3.16 (2H, t).

Examples 278-284 Examples 276 to 284 were prepared by the method of Example 221 using the product of Example 277.

Example 278 N7-(2-Methoxyethyl)-5-[(phenylmethyl) thio]-N2-[2-(2-thienyl) ethyl] thiazolo(2-Methoxyethyl)-5-[(phenylmethyl) thio]-N2-[2-(2-thienyl) ethyl] thiazolo [4,5- d pyrimidine-2, 7-diamine MS (APCI) 457 (M+H+, 100%).

Example 279 N7-(2-Ethoxyethyl)-5-[(phenylmethyl) thio]-N2-[2-(2-thienyl) ethyl] thiazolo(2-Ethoxyethyl)-5-[(phenylmethyl) thio]-N2-[2-(2-thienyl) ethyl] thiazolo [4,5- d pyrimidine-2, 7-diamine MS (APCI) 471 (M+H+, 100%).

Example 280 N7-(2,2-Dimethylpropyl)-5-[(phenylmethyl)thio]-N²-[2-(2-thi enyl)ethyl]thiazolo[4, 5- d pyrimidine-2,7-diamine MS (APCI) 469 (M+H+, 100%).

Example 281 (2R)-4-Methyl-2-[[5-[(phenylmethyl)thio]-2-[[2-(2-thienyl)et hyl]amino]thiazolo[4, 5- dlpyrimidin-7-yl amino-l-pentanol MS (APCI) 499 (M+H+, 100%).

Example 282 (_)-1-5-(Phenylmethyl) thio-2-2-(2-thienyl) ethyl amino] thiazolo [4,5-d) pyrimidin- 7-yl]amino]-2-propanol MS (APCI) 457 (M+H+, 100%).

Example 283 (#)-2-[[5-[(Phenylmethyl)thio]-2-[[2-(2-thienyl)ethyl]amino] thiazolo [4,5-d] pyrimidin- 7-yl amino-1-butanol MS (APCI) 471 (M+H+, 100%).

Example 284 (#)-2-[[5-[(Phenylmethyl)thio]-2-[[2-(2-thienyl)ethyl]amino] thiazolo[4,5-dJpyrimidin- 7-yl amino-l-propanol MS (APCI) 457 (M+H+, 100%).

Example 285 2- 7-Chloro-5- (phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-2-yl] amino]-1-ethanol Prepared by the method of Example 231, using the product of Example 219 and 2-aminoethanol.

MS (APCI) 355,353 (M+H+), 353 (100%).

NMR 8H (d6-DMSO) 9.48 (1H, s), 7.45-7.30 (5H, m), 4.95 (1H, t), 4.40 (2H, s), 3.60 (4H, m).

Examples 286-287 Examples 286 to 287 were prepared by the method of Example 221 using the product of Example 285.

Example 286 (2R)-2-[[2-[(2-Hydroxyethyl)amino]-5-[(phenylmethyl)thio] thiazolo [4,5-d] pyrimidin- 7-yl amino-4-methyl-1-pentanol

MS (APCI) 433 (M+H+, 100%).

Example 287 (_)-N, N-Diethyl-1-2-(2-hydroxyethyl) amino-5-(phenylmethyl) thio thiazolo [4,5- dlpyrimidin-7-yl-3-piperidinecarboxamide MS (APCI) 500 (M+H+, 100%).

Example 288 3- 7-Chloro-5- (phenylmethyl) thio] thiazolo [4,5 dlpyrimidin-2-yl] amino]-1-propanol Prepared by the method of Example 231, using the product of Example 219 and 3- aminopropanol.

MS (APCI) 369,367 (M+H+), 367 (100%).

NMR #H (d6-DMSO) 9.36 (1H, s), 7.43-7.27 (5H, m), 4.57 (1H, t), 4.40 (2H, s), 3.49 (4H, m), 1.75 (2H, m).

Examples 289-291 Examples 289-291 were prepared by the method of Example 221 using the product of Example 288.

Example 289 (2R)-2-2-(3-Hydroxypropyl) amino-5-(phenylmethyl) thio thiazolo [4,5- d pyrimidin-7-yl amino-4-methyl-1-pentanol MS (APCI) 447 (M+H+, 100%).

Example 290 (_)-2-2-(3-Hydroxypropyl) amino-5-(phenylmethyl) thio thiazolo [4,5-dlpyrimidin- 7-yl] amino-1-butanol MS (APCI) 419 (M+H+, 100%).

Example 291 ()-2- 2- (3-Hydroxypropyl) amino-5- (phenylmethyl) thio] thiazolo [4,5-d]pyrimidin- 7-yl] amino-1-propanol MS (APCI) 405 (M+H+, 100%) Example 292 2-[[7-Chloro-5-[(phenylmethyl)thio] thiazolo [4,5-dlpyrimidin-2-yl] amino]-acetamide Prepared by the method of Example 231, using the product of Example 219 and glycinamide hydrochloride.

MS (APCI) 368,66 (M+H+), 366 (100%).

NMR 8H (d6-DMSO) 7.61 (1H, s), 7.45-7.24 (6H, m), 4.40 (2H, s), 4.14-4.12 (2H, m), 9.57 (1H, s).

Example 293 2-[[7-[(2-Hydroxy-l-methylethyl) amino]-5-[(phenylmethyl)[[7-[(2-Hydroxy-l-methylethyl) amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-2-yl amino-acetamide Prepared according to the method of Example 221 using the product of Example 292.

MS (APCI) 404 (M+H+, 100%).

Example 294 4-[[7-Chloro-5-[(phenylmethyl) thio] thiazolo[[7-Chloro-5-[(phenylmethyl) thio] thiazolo [4,5 dlpyrimidin-2-yl]-3-azetidinyl]-1- piperazinesulfonamide Prepared by the method of Example 231, using the product of Example 219 and 3-azetidinyl-1-piperazinesulfonamide.

MS (APCI), 512,514 (M+H+), 512 (100%).

NMR 8H (d6-DMSO) 7.69-7.22 (5H, m), 6.80 (2H, s), 4.40 (2H, s), 4.34-4.12 (4H, m), 3.56-3.50 (1H, m), 3.40 (4H, s), 3.00 (4H, s).

Example 295 4- l- 7- (4-Methylcyclohexyl) amino-5- (phenylmethyl) thio thiazolo [4,5-dlpyrimidin- 2-yl-3-azetidinyl-1-piperazinesulfonamide, Prepared by the method of Example 221, using the product of Example 294.

MS (APCI) 588 (M+H+, 100%).

Example 296 7-Chloro-N- 2- (4-morpholinyl) ethyl-5- (phenylmethyl) thio-thiazolo [4,5- d pyrimidin-2-amine Prepared by the method of Example 231, using the product of Example 219 and 2- (4-morpholinyl) ethyl) amine.

MS (APCI) 424,422 (M+H+), 422 (100%).

NMR 8H (d6-DMSO) 9.34 (1H, s), 7.68-7.23 (5H, m), 4.40 (2H, s), 3.59-3.56 (6H, m), 2.54 (2H, t), 2.44-2.41 (4H, m).

Examples 297-300 Examples 297-300 were prepared according to the method of Example 221 using the product of Example 296.

Example 297 3-[[2-[[2-(4-Morpholinyl) ethyl] amino]-5-[(phenylmethyl)[[2-[[2-(4-Morpholinyl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5- d pyrimidin-7-yl amino-1-propanol MS (APCI) 460 (M+H+, 100%).

Example 298 2-Methyl-2-[[2-[[2-(4-morpholinyl) ethyl] amino]-5-[(phenylmethyl)[[2-[[2-(4-morpholinyl) ethyl] amino]-5-[(phenylmethyl) thio] thiazolo [4,5- dlpyrimidin-7-yllaminol-l-propanol MS (APCI) 464 (M+H+, 100%).

Example 299 (_)-2-2-2-(4-Morpholinyl) ethyl amino-5-(phenylmethyl) thio] thiazolo 4,5- d pyrimidin-7-yl amino-1-propanol MS (APCI) 460 (M+H+, 100%).

Example 300 (2R)-4-Methyl-2-2-2-(4-morpholinyl) ethyl amino-5- (phenylmethyl) thio] thiazolo [4,5-d] pyrimidin-7-yl] amino]-1-pentanol MS (APCI) 502 (M+H+, 100%).

Examples 301-302 Examples 301-302 were prepared by the method of Example 12 using the product of Example 140.

Example 301 2-[[2-(3, 4-Dihydroxyphenyl) ethyl] amino]-5-[(phenylmethyl) thio]-thiazolo[[2-(3, 4-Dihydroxyphenyl) ethyl] amino]-5-[(phenylmethyl) thio]-thiazolo [4,5- d pyrimidin-7 (4H)-one MS (APCI) 427 (M+H+, 100%).

Example 302 (+)-2-(2-Hydroxy-1-methylethyl) amino-5-(phenylmethyl) thio-thiazolo [4,5- d pyrimidin-7 (4H)-one MS (APCI) 349 (M+H+, 100%).

Pharmacological Data Ligand Binding Assay 125I1IL-8 (human, recombinant) was purchased from Amersharn, U. K. with a specific activity of 2, OOOCi/mmol. All other chemicals were of analytical grade. High levels of hrCXCR2 were expressed in HEK 293 cells (human embryo kidney 293 cells ECACC No.

85120602) (Lee et al. (1992) J. Biol. Chem. 267 ppl6283-16291). hrCXCR2 cDNA was amplified and cloned from human neutrophil mRNA. The DNA was cloned into PCRScript (Stratagene) and clones were identified using DNA. The coding sequence was sub-cloned into the eukaryotic expression vector RcCMV (Invitrogen). Plasmid DNA was prepared using Quiagen Megaprep 2500 and transfected into HEK 293 cells using Lipofectamine reagent (Gibco BRL). Cells of the highest expressing clone were harvested in phosphate- buffered saline containing 0.2% (w/v) ethylenediaminetetraacetic acid (EDTA) and centrifuged (200g, 5min.). The cell pellet was resuspended in ice cold homogenisation

buffer 1 OmM HEPES (pH 7.4), 1 mM dithiothreitol, 1 mM EDTA and a panel of protase inhibitors (1mM phenyl methyl sulphonyl fluoride, 2pg/ml soybean trypsin inhibitor, 3mM benzamidine, 0.5pg/ml leupeptin and 100pg/ml bacitracin)] and the cells left to swell for 10 minutes. The cell preparation was disrupted using a hand held glass mortar/PTFE pestle homogeniser and cell membranes harvested by centrifugation (45 minutes, 100,000g, 4°C).

The membrane preparation was stored at-70°C in homogenisation buffer supplemented with Tyrode's salt solution (137mM NaCI, 2.7mM KCI, 0.4mM NaH2P04), 0. 1% (w/v) gelatin and 10% (v/v) glycerol.

All assays were performed in a 96-well MultiScreen 0.45pm filtration plates (Millipore, U. K.). Each assay contained ~50pM 125I1IL-8 and membranes (equivalent to-200,000 cells) in assay buffer Tyrode's salt solution supplemented with l OmM HEPES (pH 7.4), 1.8mM CaC12, ImM MgCl2,0.125mg/ml bacitracin and 0.1% (w/v) gelatin]. In addition, a compound of formula (1) according to the Examples was pre-dissolved in DMSO and added to reach a final concentration of 1 % (v/v) DMSO. The assay was initiated with the addition of membranes and after 1.5 hours at room temperature the membranes were harvested by filtration using a Millipore MultiScreen vacuum manifold and washed twice with assay buffer (without bacitracin). The backing plate was removed from the MultiScreen plate assembly, the filters dried at room temperature, punched out and then counted on a Cobra y-counter.

The compounds of formula (1) according to the Examples were found to have In50 values of less than (<) 10, ohm.

Intracellular Calcium Mobilisation Assay Human neutrophils were prepared from EDTA-treated peripheral blood, as previously described (Baly et al. (1997) Methods in Enzymology 287 pp70-72), in storage buffer [Tyrode's salt solution (137mM NaCI, 2.7mM KCI, 0.4mM NaH2PO4) supplemented with 5.7mM glucose and lOmM HEPES (pH 7.4)].

The chemokine GROa (human, recombinant) was purchased from R&D Systems (Abingdon, U. K.). All other chemicals were of analytical grade. Changes in intracellular free calcium were measured fluorometrically by loading neutrophils with the calcium sensitive fluorescent dye, fluo-3, as described previously (Merritt et al. (1990) Biochem. J.

269, pp513-519). Cells were loaded for 1 hour at 37°C in loading buffer (storage buffer with 0.1 % (w/v) gelatin) containing 5uM fluo-3 AM ester, washed with loading buffer and then resuspended in Tyrode's salt solution supplemented with 5.7mM glucose, 0.1% (w/v) bovine serum albumin (BSA), l. 8mM CaCI2 and 1mM MgCl2. The cells were pipetted into black walled, clear bottom, 96 well micro plates (Costar, Boston, U. S. A.) and centrifuged (200g, 5 minutes, room temperature).

A compound of formula (1) according to the Examples was pre-dissolved in DMSO and added to a final concentration of 0.1% (v/v) DMSO. Assays were initiated by the addition of an Aso concentration of GROa and the transient increase in fluo-3 fluorescence (Ex =490nm and XEm = 520nm) monitored using a FLIPR (Fluorometric Imaging Plate Reader, Molecular Devices, Sunnyvale, U. S. A.).

The compounds of formula (1) according to the Examples were tested and found to be antagonists of the CXCR2 receptor in human neutrophils.