Therapeutically active pyrazolo-pyrimidine derivatives

1. A compound represented by formula (IA), or a pharmaceutically acceptable salt or solvate thereof:

wherein R 12 represents hydrogen, trifluoromethyl or C 1-6 alkyl;

Q is

in which the asterisk (*) represents the point of attachment to the remainder of the molecule;

Y represents —C(O)—, —C(O)N(R 4 )— or —C(O)C(O)—;

Z represents C 3-7 cycloalkyl, C 3-7 heterocycloalkyl, aryl, or heteroaryl any of which groups is optionally substituted by one or more substituents independently selected from halogen, cyano, C 1-6 alkyl, trifluoromethyl, (C 3-7 )-heterocycloalkyl, dihalo(C 3-7 )heterocycloalkyl, hydroxy, oxo, C 1-6 alkoxy, difluoromethoxy, trifluoromethoxy, trifluoroethoxy, C 1-6 alkylsulfonyl, C 1-6 alkylamino and di(C 1-6 )alkylamino;

A 1 represents hydrogen, methyl, ethyl, isopropyl, isobutyl, trifluoromethyl, trifluoroethyl, —CH 2 OR a or —CH 2 CH 2 OR a ;

A 2 represents hydrogen or C 1-6 alkyl;

R 4 represents hydrogen or C 1-6 alkyl;

R a represents hydrogen or C 1-6 alkyl; and

R 13 represents C 1-6 alkyl.

2. A compound as claimed in claim 1 wherein Q represents a group of formula (Qa-1), (Qa-2) or (Qa-3):

in which the asterisk (*) represents the point of attachment to the remainder of the molecule.

3. A compound as claimed in claim 1 represented by formula (IIA), or a pharmaceutically acceptable salt or solvate thereof:

wherein

A 11 represents hydrogen, methyl, ethyl, isopropyl, isobutyl, trifluoromethyl, —CH 2 CF 3 , hydroxymethyl, or hydroxyethyl; and

R 12 represents hydrogen, trifluoromethyl or C 1-6 alkyl.

4. A compound as claimed in claim 1 represented by formula (IIB), or a pharmaceutically acceptable salt or solvate thereof:

wherein

R 12 represents hydrogen, trifluoromethyl or C 1-6 alkyl; and

A 11 represents hydrogen, methyl, ethyl, isopropyl, isobutyl, trifluoromethyl, —CH 2 CF 3 , hydroxymethyl, or hydroxyethyl.

5. A compound as claimed in claim 3 wherein A 11 represents methyl, ethyl, hydroxymethyl or hydroxyethyl.

6. A compound as claimed in claim 1 wherein Z represents C 3-7 cycloalkyl, C 3-7 heterocycloalkyl, aryl or heteroaryl, any of which groups is optionally substituted by one, two or three substituents independently selected from halogen, cyano, C 1-6 alkyl, trifluoromethyl, (C 3-7 )heterocycloalkyl, dihalo(C 3-7 )-heterocycloalkyl, hydroxy, oxo, C 1-6 alkoxy, difluoromethoxy, trifluoromethoxy, trifluoroethoxy, C 1-6 alkylsulfonyl, C 1-6 alkylamino and di(C 1-6 )alkylamino.

7. A compound as claimed in claim 6 wherein Z represents (methoxy)(methyl)-phenyl, (methyl)(trifluoromethoxy)phenyl, (methoxy)(methyl)pyridinyl, (ethyl)-(methoxy)pyridinyl, (ethoxy)(methyl)pyridinyl or dimethoxypyridinyl.

8. A compound as claimed in claim 1 wherein R 12 represents hydrogen or methyl.

9. A compound as claimed in claim 1 wherein R 13 represents methyl.

10. A compound of formula (IA) as claimed in claim 1 which is

6-Amino-4-{4-[(4-methoxy-2-methylphenyl)carbamyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine;

6-Amino-4-{4-[(4-methoxyphenyl)carbamyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]-pyrimdine;

6-Amino-4-{4-[(4-methoxy-2-methylphenyl)carbamyl]-2-(S)-methylpiperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine;

6-Amino-4-{4-[(4-methoxyphenyl)carbamyl]-2-(S)-methylpiperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine;

6-Amino-4-{4-[(4-methoxy-2-methylphenyl)carbamyl]-2-(S)-methylpiperazin-1-yl}-1-methylpyrazolo[3,4-d]pyrimidine;

6-Amino-4-{4-[(4-methoxyphenyl)carbamyl]-2-(S)-methylpiperazin-1-yl}-1-methylpyrazolo[3,4-d]pyrimidine;

6-Amino-4-[4-(indan-5-ylcarbamyl)-2-(S)-methylpiperazin-1-yl]-1-methylpyrazolo[3,4-d]pyrimidine;

6-Amino-4-(4-{[4-(dimethylamino)phenyl]carbamyl}-2-(S)-methylpiperazin-1-yl)-1-methylpyrazolo[3,4-d]pyrimidine;

(3S)-4-(6-Amino-1,3-dimethylpyrazolo[3,4-d]pyrimidin-4-yl)-N-[6-(3,3-difluoroazetidin-1-yl)-2-methylpyridin-3-yl]-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1,3-dimethylpyrazolo[3,4-d]pyrimidin-4-yl)-N-(4-methoxy-2-methyl-phenyl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1,3-dimethylpyrazolo[3,4-d]pyrimidin-4-yl)-N-(6-methoxy-2-methyl-pyridin-3-yl)-3-methylpiperazine-1-carboxamide;

(3R)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-N-[6-(3,3-difluoroazetidin-1-yl)-2-methylpyridin-3-yl]-3-(hydroxymethyl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-N-[6-(3,3-difluoroazetidin-1-yl)-2-methylpyridin-3-yl]-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-N-(6-methoxy-2-methyl-pyridin-3-yl)-3-methylpiperazine-1-carboxamide;

(3R)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-N-(4-methoxy-2-methyl-phenyl)-3-methylpiperazine-1-carboxamide;

(3S)-4-[6-Amino-1-methyl-3-(trifluoromethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-N-[6-(3,3-difluoroazetidin-1-yl)-2-methylpyridin-3-yl]-3-methylpiperazine-1-carboxamide;

(3S)-4-[6-Amino-1-methyl-3-(trifluoromethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-N-(6-methoxy-2-methylpyridin-3-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-[6-Amino-1-methyl-3-(trifluoromethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-N-(4-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-N-(2, 1,3-benzothiadiazol-4-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-N-(1H-indazol-7-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-N-(2, 1,3-benzothiadiazol-5-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-N-(1H-indol-7-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-N-(1H-indol-4-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-3-methyl-N-(2-methyl-1H-benzimidazol-4-yl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-3-methyl-N-(1-methylindazol-7-yl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-3-methyl-N-(4-methyl-1H-indazol-7-yl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-N-(6-hydroxy-2-methylpyridin-3-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-3-methyl-N-[2-methyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-N-(1,2-dimethyl-6-oxopyridin-3-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-3-methyl-N-[2-methyl-6-(methylamino)pyridin-3-yl]-piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo-[3,4-d]pyrimidin-4-yl)-N-[2-(3,3-difluoroazetidin-1-yl)-4-methyl-pyrimidin-5-yl]-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo-[3,4-d]pyrimidin-4-yl)-N-[4-(difluoro-methoxy)-2-methylphenyl]-3-methyl-piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo-[3,4-d]pyrimidin-4-yl)-N-[2-(dimethyl-amino)-4-methylpyrimidin-5-yl]-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo-[3,4-d]pyrimidin-4-yl)-N-[6-(azetidin-1-yl)-2-methylpyridin-3-yl]-3-methyl-piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo-[3,4-d]pyrimidin-4-yl)-N-[6-(3,3-difluoroazetidin-1-yl)-4-methylpyridin-3-yl]-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo-[3,4-d]pyrimidin-4-yl)-N-[6-(dimethyl-amino)-2-methylpyridin-3-yl]-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo-[3,4-d]pyrimidin-4-yl)-N-[6-(dimethyl-amino)-methylpyridin-3-yl]-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1,3-dimethyl-pyrazolo[3,4-d]pyrimidin-4-yl)-N-[6-(azetidin-1-yl)-2-methylpyridin-3-yl]-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1,3-dimethyl-pyrazolo[3,4-d]pyrimidin-4-yl)-N-[6-(dimethylamino)-4-methylpyridin-3-yl]-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1,3-dimethyl-pyrazolo[3,4-d]pyrimidin-4-yl)-N-[6-(dimethylamino)-2-methylpyridin-3-yl]-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1,3-dimethylpyrazolo[3,4-d]pyrimidin-4-yl)-N-(4-methoxyphenyl)-3-methylpiperazine-1-carboxamide;

[(3S)-4-(6-Amino-1-methylpyrazolo-[3,4-d]pyrimidin-4-yl)-3-methyl-piperazin-1-yl](2,3-dihydrobenzo-furan-2-yl)methanone;

1-[(3S)-4-(6-Amino-1-methylpyrazolo-[3,4-d]pyrimidin-4-yl)-3-methyl-piperazin-1-yl]-2-phenylethane-1,2-dione;

[(3S)-4-(6-Amino-1-methylpyrazolo-[3,4-d]pyrimidin-4-yl)-3-methyl-piperazin-1-yl](5-methoxybenzofuran-2-yl)methanone;

(3S)-N-(4-Methoxy-2-methylphenyl)-3-methyl-4-[1-methyl-6-(methylsulfanyl)-pyrazolo[3,4-d]pyrimidin-4-yl]piperazine-1-carboxamide;

(3S)-N-(Indan-5-yl)-3-methyl-4-[1-methyl-6-(methylsulfonyl)pyrazolo[3,4-d]pyrimidin-4-yl]piperazine-1-carboxamide;

(3S)-N-(Indan-5-yl)-4-(6-methoxy-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-3-methyl-piperazine-1-carboxamide;

(3S)-4-(6-Cyano-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-N-(indan-5-yl)-3-methyl-piperazine-1-carboxamide;

(3S)-4-[6-(2-Hydroxyethylamino)-1-methylpyrazolo[3,4-d]pyrimidin-4-yl]-N-(4-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-3-methyl-N-[2-methyl-4-(trifluoromethoxy)phenyl]piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-[2-fluoro-4-(trifluoromethoxy)-phenyl]-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-[2-chloro-4-(trifluoromethoxy)-phenyl]-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-[3-methoxy-5-(trifluoromethyl)-phenyl]-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(1-ethyl-1H-indazol-3-yl)-3-methyl-piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-[6-(difluoromethoxy)-2-methyl-pyridin-3-yl]-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(6-ethoxy-5-fluoropyridin-3-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(2-chloro-4-fluoro-5-methylphenyl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(5-fluoro-6-methoxypyridin-3-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(6-ethoxy-2-methylpyridin-3-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3-methyl-N-[1-methyl-5-(trifluoro-methyl)-1H-indazol-3-yl]piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(6-fluoro-1-methyl-1H-indazol-3-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(5-fluoro-1-methyl-1H-indazol-3-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(imidazo[1,2-a]pyridin-8-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3-methyl-N-(5-methyl-1,2-oxazol-3-yl)-piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(1,2-benzoxazol-3-yl)-3-methyl-piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3-methyl-N-(1-methyl-1H-indazol-3-yl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(6-cyano-2-methylpyridin-3-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3-methyl-N-[2-methyl-4-(methyl-sulfonyl)phenyl]piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-[6-(difluoromethoxy)-4-methyl-pyridin-3-yl]-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(6-methoxy-5-methylpyridin-3-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(6-methoxy-4-methylpyridin-3-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(5-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(3-chloro-4-methylphenyl)-3-methyl-piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(2,5-dichlorophenyl)-3-methyl-piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(4-cyano-2-methylphenyl)-3-methyl-piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-3-ethyl-N-(6-methoxy-2-methylpyridin-3-yl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-N-(6-ethoxy-2-methylpyridin-3-yl)-3-ethylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-N-(2,6-dimethoxypyridin-3-yl)-3-ethylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-3-ethyl-N-(4-methoxy-2-methylphenyl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-N-[6-(3,3-difluoroazetidin-1-yl)-2-methylpyridin-3-yl]-3-ethylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-3-ethyl-N-[2-methyl-4-(trifluoromethoxy)phenyl]piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-3-ethyl-N-(4-methoxy-3-methylphenyl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(1,2-benzoxazol-3-yl)-3-ethyl-piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3-ethyl-N-(1-methyl-1H-indazol-3-yl)-piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-[6-(difluoromethoxy)-4-methyl-pyridin-3-yl]-3-ethylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3-ethyl-N-(6-methoxy-5-methyl-pyridin-3-yl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3-ethyl-N-[2-methyl-4-(methyl-sulfonyl)phenyl]piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3-ethyl-N-(6-methoxy-4-methyl-pyridin-3-yl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3-ethyl-N-[1-methyl-5-(trifluoro-methyl)-1H-indazol-3-yl]piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3-ethyl-N-(6-fluoro-1-methyl-1H-indazol-3-yl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3-ethyl-N-(5-fluoro-1-methyl-1H-indazol-3-yl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-[6-(difluoromethoxy)-2-methyl-pyridin-3-yl]-3-ethylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3-ethyl-N-(imidazo[1,2-a]pyridin-8-yl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(6-ethoxy-5-fluoropyridin-3-yl)-3-ethylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(2-chloro-4-fluoro-5-methyl-phenyl)-3-ethylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3-ethyl-N-(5-fluoro-6-methoxy-pyridin-3-yl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(6-cyano-2-methylpyridin-3-yl)-3-ethylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(4-cyano-2-methylphenyl)-3-ethyl-piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-[4-(difluoromethoxy)-2-methyl-phenyl]-3-ethylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-[5-(dimethylamino)-3-methyl-pyrazin-2-yl]-3-ethylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-3-methyl-N-(1-methyl-1H-indazol-4-yl)-piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-(2-methoxy-6-methylpyridin-3-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-3-methyl-N-(1-methyl-1H-indol-4-yl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-3-methyl-N-(1-methyl-1H-benzotriazol-4-yl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-(imidazo[1,2-a]pyridin-5-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-(imidazo[1,2-a]pyridin-3-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3-methyl-N-(1-methyl-1H-pyrazolo-[4,3-c]pyridin-4-yl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(3-chloro-5-methoxypyridin-2-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(2-chloro-4-methoxyphenyl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-[6-methoxy-2-(trifluoromethyl)-pyridin-3-yl]-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(6-fluoro-1-methyl-1H-indazol-4-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(2-ethyl-6-methoxypyridin-3-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-[5-(dimethylamino)-3-methyl-pyrazin-2-yl]-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3-ethyl-N-(1-methyl-1H-pyrazolo[4,3-c]pyridin-4-yl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(2-chloro-4-methoxyphenyl)-3-ethylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3-ethyl-N-(6-fluoro-1-methyl-1H-indazol-4-yl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3-ethyl-N-[6-methoxy-2-(trifluoro-methyl)pyridin-3-yl]piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3-ethyl-N-(2-ethyl-6-methoxypyridin-3-yl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1,3-dimethyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-[2-(dimethylamino)-4-methyl-pyrimidin-5-yl]-3-methylpiperazine-1-carboxamide;

4-(6-Amino-1-methylpyrazolo[3,4-d]pyrimidin-4-yl)-3-(2-hydroxyethyl)-N-[2-methyl-4-(trifluoromethoxy)phenyl]piperazine-1-carboxamide;

(3R)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-3-(hydroxymethyl)-N-[2-methyl-4-(trifluoromethoxy)phenyl]piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(6-methoxy-2-methylpyridin-3-yl)-3-(propan-2-yl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(6-methoxy-2-methylpyridin-3-yl)-3-(2-methylpropyl)piperazine-1-carboxamide;

4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(6-methoxy-2-methylpyridin-3-yl)-3-(2,2,2-trifluoroethyl)piperazine-1-carboxamide;

4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(imidazo[1,2-a]pyridin-8-yl)-3-(2,2,2-trifluoroethyl)piperazine-1-carboxamide;

(3S,5S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(1-ethyl-1H-indazol-3-yl)-3,5-dimethylpiperazine-1-carboxamide;

(3S,5S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3,5-dimethyl-N-(1-methyl-1H-indazol-3-yl)piperazine-1-carboxamide;

(3S,5S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-[5-(dimethylamino)-3-methyl-pyrazin-2-yl]-3,5-dimethylpiperazine-1-carboxamide;

(3S,5S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(imidazo[1,2-a]pyridin-8-yl)-3, 5-dimethylpiperazine-1-carboxamide;

(3S,5S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-3,5-dimethyl-N-[2-methyl-4-(trifluoromethoxy)phenyl]piperazine-1-carboxamide;

(3S,5S)-4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(6-methoxy-2-methylpyridin-3-yl)-3,5-dimethylpiperazine-1-carboxamide;

4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(6-methoxy-2-methylpyridin-3-yl)-3-(trifluoromethyl)piperazine-1-carboxamide;

4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(4-methoxy-2-methylphenyl)-3-(trifluoromethyl)piperazine-1-carboxamide;

(3S)-4-(6-Amino-1,3-dimethyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(6-fluoro-1-methyl-1H-indazol-3-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1,3-dimethyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-(5-fluoro-1-methyl-1H-indazol-3-yl)-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1,3-dimethyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-[6-(difluoromethoxy)-2-methyl-pyridin-3-yl]-3-methylpiperazine-1-carboxamide;

(3S)-4-(6-Amino-1,3-dimethyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-[5-(dimethylamino)-3-methyl-pyrazin-2-yl]-3-methylpiperazine-1-carboxamide; or

(3S)-4-(6-Amino-1,3-dimethyl-1H-pyrazolo[3,4-d]-pyrimidin-4-yl)-N-[4-(difluoromethoxy)-2-methyl-phenyl]-3-methylpiperazine-1-carboxamide;

(3S)-4-[6-Amino-3-(4-fluorophenyl)-1-methylpyrazolo[3,4-d]pyrimidin-4-yl]-N-(4-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide; or

(3S)-4-[6-Amino-1-methyl-3-(pyridin-3-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-N-(4-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide;

or a pharmaceutically acceptable salt of one of the foregoing.

11. A pharmaceutical composition comprising a compound of formula (IA) as defined in claim 1 , or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier.

12. A method for the treatment of organ or cell transplant rejection, which comprises administering to a patient in need of such treatment an effective amount of a compound of formula (IA) as defined in claim 1 , or a pharmaceutically acceptable salt or solvate thereof.