IP Library › Granted Patent US 8,614,218

Granted Patent B2

US 8,614,218 · App. 12/731,880 · Granted Dec 24, 2013

Fused bicyclic pyrimidines

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Quick Facts

Patent No.: US 8,614,218
App. No.: 12/731,880
Granted: Dec 24, 2013
Kind: B2

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Abstract

Compounds of formula (I) a tautomer or stereoisomer thereof, or a salt thereof, wherein ring B and the pyrimidine to which it is fused, R4, R5, R6 and R7 have the meanings as given in the description and the claims, are effective inhibitors of the Pi3K/Akt pathway.

Claims (241)

1. A method for the treatment or amelioration of a cancer selected from breast, ovarian, lung, and colon cancers comprising administering to a subject in need thereof an effective amount of a compound of formula (I)

wherein ring B and the pyrimidine to which it is fused form a ring system selected from the group consisting of

wherein

R1 is hydrogen, 1-4C-alkyl, halogen, amino, 1-4C-alkoxy, cyano, 3-7C-cycloalkyl, 2-4C-alkenyl, 2-4C-alkynyl, 3-7C-cycloalkoxy, mono- or di-1-4C-alkylamino, mono- or di-1-4C-alkylaminocarbonyl, —C(O)NH2, —C(O)OR2 or trifluoromethyl,

R2 is hydrogen or 1-4C-alkyl,

R3 is hydrogen, 1-4C-alkyl or halogen,

R4 is phenyl or thienyl,

R5 is hydrogen, 1-4C-alkoxy, amino, mono- or di-1-4C-alkylamino, 1-4C-alkyl or 3-7C-cycloalkyl,

R6 is hydrogen or 1-4C-alkyl,

R7 is —W—Y,

W is a monocyclic 5-membered heteroarylene comprising 1 nitrogen atom and optionally 1 or 2 further heteroatoms independently selected from consisting of oxygen, nitrogen and sulphur,

and wherein the heteroarylene is optionally substituted by R8,

R8 is 1-4C-alkyl or 3-7C-cycloalkyl,

Y is phenyl or a monocyclic 5 or 6 membered heteroaryl comprising 1 nitrogen, oxygen or sulfur atom and optionally 1 or 2 further heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulphur,

and wherein the heteroaryl is optionally substituted by R9,

R9 is 1-4C-alkyl, 1-4C-alkoxy or halogen,

or a salt, a tautomer, or a stereoisomer thereof, or a salt of said tautomer or said stereoisomer.

2. A method according to claim 1 , wherein in the compound of formula (I) ring B and the pyrimidine to which it is fused form a ring system selected from the group consisting of

wherein

R2 is hydrogen or 1-4C-alkyl,

R3 is hydrogen,

R4 is phenyl or thienyl,

R5 is hydrogen, 1-4C-alkoxy, amino, mono- or di-1-4C-alkylamino, 1-4C-alkyl or 3-7C-cycloalkyl,

R6 is hydrogen or 1-4-C-alkyl,

R7 is —W—Y,

W is triazolylene, pyrazolylene or imidazolylene,

each of which is optionally substituted by R8,

R8 is 1-4C-alkyl or 3-7C-cycloalkyl,

Y is phenyl, pyrrolyl, furanyl, thienyl, thiazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, wherein each of pyrrolyl, furanyl, thienyl, thiazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl is optionally substituted by R9,

R9 is 1-4C-alkyl, 1-4C-alkoxy or halogen,

or a salt, a tautomer, or a stereoisomer thereof, or a salt of said tautomer or said stereoisomer.

3. A method according to claim 1 , wherein in the compound of formula (I) ring B and the pyrimidine to which it is fused form a ring system selected from the group consisting of

wherein

R2 is hydrogen or 1-4C-alkyl,

R3 is hydrogen,

R4 is phenyl or thienyl,

R5 is hydrogen, 1-4C-alkoxy, amino, mono- or di-1-4C-alkylamino, 1-4C-alkyl or 3-7C-cycloalkyl,

R6 is hydrogen or methyl,

R7 is —W—Y,

W is 1,2,4-triazolylene, pyrazolylene or imidazolylene,

Y is phenyl, furan-2-yl, pyrrol-2-yl, thien-2-yl, thiazol-2-yl, thiazol-4-yl, oxazol-2-yl, oxazol-4-yl, 1,3,4-thiadiazol-2-yl, 1,3,4-oxadiazol-2-yl, pyridin-2-yl, pyridin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-2-yl or pyridazin-3-yl, wherein each of furan-2-yl, pyrrol-2-yl, thien-2-yl, thiazol-2-yl, thiazol-4-yl, oxazol-2-yl, oxazol-4-yl, 1,3,4-thiadiazol-2-yl, 1,3,4-oxadiazol-2-yl, pyridin-2-yl, pyridin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-2-yl or pyridazin-3-yl is optionally substituted by R9,

R9 is 1-4C-alkyl, 1-4C-alkoxy or halogen,

or a salt, a tautomer, or a stereoisomer thereof, or a salt of said tautomer or said stereoisomer.

4. A method according to claim 1 , wherein in the compound of formula (I) ring B and the pyrimidine to which it is fused form a ring system selected from the group consisting of

wherein

R1 is hydrogen, 1-4C-alkyl, halogen, amino, 1-4C-alkoxy, cyano, 3-7C-cycloalkyl, 2-4C-alkenyl, 2-4C-alkynyl, mono- or di-1-4C-alkylamino, —C(O)OR2 or trifluoromethyl,

R2 is 1-4C-alkyl,

R3 is hydrogen,

R4 is phenyl or thienyl,

R5 is hydrogen, 1-4C-alkoxy, mono- or di-1-4C-alkylamino or 1-4C-alkyl,

R6 is hydrogen or methyl,

R7 is —W—Y,

W is 1,2,4-triazolylene or pyrazolylene,

Y is phenyl, furan-2-yl, pyrrol-2-yl, pyridin-4-yl, thiazol-2-yl, pyridin-2-yl, pyrimidin-2-yl, pyrazin-2-yl, pyrimidin-4-yl or pyridazin-3-yl, wherein each of furan-2-yl, pyrrol-2-yl, pyridin-4-yl, thiazol-2-yl, pyridin-2-yl, pyrimidin-2-yl, pyrazin-2-yl, pyrimidin-4-yl or pyridazin-3-yl is optionally substituted by R9,

R9 is 1-4C-alkyl, 1-4C-alkoxy or halogen,

or a salt, a tautomer, or a stereoisomer thereof, or a salt of said tautomer or said stereoisomer.

5. A method according to claim 1 , wherein the compound of formula (I) is selected from

6-phenyl-7-(4-{[4-(3-pyridin-2-yl-1,2,4-triazol-5-yl)piperidin-1-yl]methyl}phenyl)imidazo[1,2a]-pyrimidine;

6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]triazolo[1,5-a]-pyrimidine;

2-methyl-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]-triazolo[1,5-a]pyrimidine;

2-cyclopropyl-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]-triazolo[1,5-a]pyrimidine;

6-phenyl-7-(4-{[4-(3-pyridin-2-yl-pyrazol-5-yl)piperidin-1-yl]methyl}phenyl)imidazo[1,2-a]pyrimidine;

6-phenyl-7-(4-{[4-(5-pyridin-4-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)imidazo[1,2-a]-pyrimidine;

2-cyclobutyl-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]-triazolo[1,5-a]pyrimidine;

6-phenyl-7-(4-{[4-(5-pyridin-2-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)imidazo[1,2-a]-pyrimidine-3-carbonitrile;

3-fluoro-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)-imidazo[1,2-a]pyrimidine;

N-methyl-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)-imidazo[1,2-a]pyrimidin-5-amine;

3-bromo-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)imidazo[1,2-a]pyrimidine;

3-chloro-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)imidazo[1,2-a]pyrimidine;

3-ethynyl-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}-phenyl)imidazo[1,2-a]pyrimidine;

3-methyl-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)imidazo[1,2-a]pyrimidine;

6-phenyl-7-(4-{[4-(5-pyridin-2-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)-3-vinylimidazo[1,2-a]pyrimidine;

Ethyl-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)imidazo[1,2-a]pyrimidine-2-carboxylate;

2-ethyl-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)imidazo[1,2-a]pyrimidine;

6-phenyl-7-(4-{[4-(5-pyrimidin-2-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)imidazo[1,2-a]pyrimidine;

6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrazolo[1,5-a]pyrimidine;

6-phenyl-7-(4-{[4-(4-pyridin-2-yl-imidazol-1-yl)piperidin-1-yl]methyl}phenyl)imidazo[1,2-a]pyrimidine;

6-phenyl-7-(4-{[4-(5-pyrazin-2-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)imidazo[1,2-a]pyrimidine;

3-ethyl-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)imidazo[1,2-a]pyrimidine;

6-phenyl-7-(4-{1-[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]ethyl}phenyl)imidazo[1,2-a]pyrimidine;

3-fluoro-6-phenyl-7-(4-{[4-(5-pyrazin-2-yl-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)imidazo[1,2-a]pyrimidine;

3-fluoro-6-phenyl-7-(4-{[4-(5-pyrimidin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)-imidazo[1,2-a]pyrimidine;

6-phenyl-7-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)-2-(trifluoromethyl)imidazo[1,2-a]pyrimidine;

5-methyl-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)-imidazo[1,2-a]pyrimidine;

2-Isopropyl-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]triazolo[1,5-a]pyrimidine;

7-Methoxy-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrazolo[1,5-a]pyrimidine;

3-Chloro-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrazolo[1,5-a]pyrimidine;

3-Bromo-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrazolo[1,5-a]pyrimidine;

6-Phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile;

3-Ethynyl-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrazolo[1,5-a]pyrimidine;

3-Ethyl-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrazolo[1,5-a]pyrimidine;

7-[4-({4-[5-(4-Methylpyridin-2-yl)-1H-1,2,4-triazol-3-yl]piperidin-1-yl}methyl)phenyl]-6-phenylimidazo[1,2-a]pyrimidine;

7-[4-({4-[5-(6-Methylpyridin-2-yl)-1H-1,2,4-triazol-3-yl]piperidin-1-yl}methyl)phenyl]-6-phenylimidazo[1,2-a]pyrimidine;

3-Methyl-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrazolo[1,5-a]pyrimidine;

2,7-Dimethyl-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]triazolo[1,5-a]pyrimidine;

2-Ethyl-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]triazolo[1,5-a]pyrimidine;

2-Methyl-6-phenyl-5-[4-({4-[5-(1,3-thiazol-2-yl)-1H-1,2,4-triazol-3-yl]piperidin-1-yl}methyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidine;

2-Methyl-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrazolo[1,5-a]pyrimidine;

2-Methyl-6-phenyl-5-(4-{[4-(5-pyrimidin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]triazolo[1,5-a]pyrimidine;

2-Methyl-6-phenyl-5-(4-{[4-(3-pyridin-2-yl-1H-pyrazol-5-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]triazolo[1,5-a]pyrimidine;

2-Methyl-6-phenyl-5-(4-{[4-(5-pyridin-4-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]triazolo[1,5-a]pyrimidine;

2-Cyclopropyl-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrazolo[1,5-a]pyrimidine;

2,7-Dimethyl-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrazolo[1,5-a]pyrimidine;

5-(4-{[4-(5-Pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)-6-(3-thienyl)pyrazolo[1,5-a]pyrimidine;

7-(4-{[4-(5-Pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)-6-(3-thienyl)imidazo[1,2-a]pyrimidine;

2-Bromo-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]triazolo[1,5-a]pyrimidine;

2-Ethynyl-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]triazolo[1,5-a]pyrimidine;

2-Methyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)-6-(3-thienyl)[1,2,4]triazolo[1,5-a]pyrimidine;

N,N-Dimethyl-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]triazolo[1,5-a]pyrimidin-2-amine;

6-Phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidine;

N,N,2-Trimethyl-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl) [1,2,4]triazolo[1,5-a]pyrimidin-7-amine;

N-Methyl-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]triazolo[1,5-a]pyrimidin-2-amine;

2-Methoxy-6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]triazolo[1,5-a]pyrimidine;

6-Phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]triazolo[1,5-a]pyrimidin-2-amine;

6-Phenyl-7-[4-({4-[3-(1H-pyrrol-2-yl)-1H-1,2,4-triazol-5-yl]piperidin-1-yl}methyl)phenyl]imidazo[1,2-a]pyrimidine;

6-Phenyl-5-(4-{[4-(3-pyrimidin-2-yl-1H-1,2,4-triazol-5-yl)piperidin-1-yl]methyl}phenyl)pyrazolo[1,5-a]pyrimidine;

6-Phenyl-5-[4-({4-[3-(1,3-thiazol-2-yl)-1H-1,2,4-triazol-5-yl]piperidin-1-yl}methyl)phenyl]pyrazolo[1,5-a]pyrimidine;

6-Phenyl-5-(4-{[4-(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)piperidin-1-yl]methyl}phenyl)pyrazolo[1,5-a]pyrimidine;

6-Phenyl-5-[4-({4-[3-(1H-pyrrol-2-yl)-1H-1,2,4-triazol-5-yl]piperidin-1-yl}methyl)phenyl]pyrazolo[1,5-a]pyrimidine;

2-Methyl-6-phenyl-5-[4-({4-[3-(1H-pyrrol-2-yl)-1H-1,2,4-triazol-5-yl]piperidin-1-yl}methyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidine;

2-Methyl-5-[4-({4-[3-(6-methylpyridin-2-yl)-1H-1,2,4-triazol-5-yl]piperidin-1-yl}methyl)phenyl]-6-phenyl[1,2,4]triazolo[1,5-a]pyrimidine;

5-[4-({4-[3-(6-Methylpyridin-2-yl)-1H-1,2,4-triazol-5-yl]piperidin-1-yl}methyl)phenyl]-6-phenylpyrazolo[1,5-a]pyrimidine;

6-Phenyl-5-(4-{[4-(3-pyridin-2-yl-1H-pyrazol-5-yl)piperidin-1-yl]methyl}phenyl)pyrazolo[1,5-a]pyrimidine;

Methyl 6-phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrazolo[1,5-a]pyrimidine-2-carboxylate;

6-Phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;

6-Phenyl-5-(4-{[4-(5-pyridin-2-yl-1H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrazolo[1,5-a]pyrimidine-2-carboxylic acid;

5-[4-({4-[3-(2-furyl)-1H-1,2,4-triazol-5-yl]piperidin-1-yl}methyl)phenyl]-2-methyl-6-phenyl[1,2,4]triazolo[1,5-a]pyrimidine;

5-[4-({4-[3-(2-furyl)-1H-1,2,4-triazol-5-yl]piperidin-1-yl}methyl)phenyl]-6-phenylpyrazolo[1,5-a]pyrimidine;

7-[4-({4-[3-(2-furyl)-1H-1,2,4-triazol-5-yl]piperidin-1-yl}methyl)phenyl]-6-phenylimidazo[1,2-a]pyrimidine;

2-methyl-6-phenyl-5-(4-{[4-(3-phenyl-1H-1,2,4-triazol-5-yl)piperidin-1-yl]methyl}phenyl)[1,2,4]triazolo[1,5-a]pyrimidine;

7-[4-({4-[5-(4-methoxypyridin-2-yl)-1H-1,2,4-triazol-3-yl]piperidin-1-yl}methyl)phenyl]-6-phenylimidazo[1,2-a]pyrimidine; and

6-phenyl-7-{4-[4-(5-pyridin-2-yl-1H-[1,2,4]triazol-3-yl)-piperidin-1-ylmethyl]-phenyl}-imidazo[1,2-a]pyrimidine;

or a salt, a tautomer, or a stereoisomer thereof, or a salt of said tautomer or said stereoisomer.

6. A method according to claim 1 , further comprising administering one or more additional chemotherapeutic anti-cancer agents or target-specific anti-cancer agents.

7. A method according to claim 1 , wherein the cancer is breast cancer.

8. A method of claim 1 , wherein the cancer is ovarian cancer.

9. A method of claim 1 , wherein the cancer is lung cancer.

10. A method according to claim 1 , wherein a compound of formula (I) or a pharmaceutically acceptable salt thereof is administered.

11. A method according to claim 5 , wherein a compound of formula (I) or a pharmaceutically acceptable salt thereof is administered.

12. A method according to claim 1 , wherein the cancer is colon cancer.

13. A method according to claim 1 , wherein

Y is phenyl or a monocyclic 5 or 6 membered heteroaryl comprising 1 nitrogen atom and optionally 1 or 2 further heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulphur, and wherein the heteroaryl is optionally substituted by R9.

14. A method for mediating a dysregulated function of a single protein kinase or multiple protein kinases and/or induction of apoptosis comprising administering to a subject in need thereof an effective amount of a compound of formula (I)

wherein ring B and the pyrimidine to which it is fused form a ring system selected from the group consisting of

wherein

R2 is hydrogen or 1-4C-alkyl,

R3 is hydrogen, 1-4C-alkyl or halogen,

R4 is phenyl or thienyl,

R5 is hydrogen, 1-4C-alkoxy, amino, mono- or di-1-4C-alkylamino, 1-4C-alkyl or 3-7C-cycloalkyl,

R6 is hydrogen or 1-4C-alkyl,

R7 is —W—Y,

W is a monocyclic 5-membered heteroarylene comprising 1 nitrogen atom and optionally 1 or 2 further heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulphur,

and wherein the heteroarylene is optionally substituted by R8,

R8 is 1-4C-alkyl or 3-7C-cycloalkyl,

Y is phenyl or a monocyclic 5 or 6 membered heteroaryl comprising 1 nitrogen, oxygen or sulphur atom and optionally 1 or 2 further heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulphur,

and wherein the heteroaryl is optionally substituted by R9,

R9 is 1-4C-alkyl, 1-4C-alkoxy or halogen,

or a salt, a tautomer, or a stereoisomer thereof, or a salt of said tautomer or said stereoisomer.

15. A method according to claim 14 , wherein the compound of formula (I) is selected from