Triazine derivatives as kinase inhibitors

1. A compound of formula (I) or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof:

wherein

E represents an optionally substituted straight or branched C 1-3 alkylene chain;

Q represents oxygen, sulfur, N—R 6 or a covalent bond;

the ring comprising M represents an optionally substituted saturated five-, six- or seven-membered monocyclic ring containing one nitrogen atom and 0, 1, 2 or 3 additional heteroatoms independently selected from N, O and S, but containing no more than one O or S atom;

W represents C—R 7 or N;

R 1 , R 2 and R 3 independently represent hydrogen, halogen, cyano, nitro, C 1-6 alkyl, trifluoromethyl, aryl(C 1-6 )alkyl, hydroxy, C 1-6 alkoxy, difluoromethoxy, trifluoromethoxy, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, amino, C 1-6 alkylamino, di(C 1-6 )alkyl-amino, C 2-6 alkylcarbonylamino, C 2-6 alkoxycarbonylamino, C 1-6 alkylsulfonylamino, formyl, C 2-6 alkylcarbonyl, carboxy, C 2-6 alkoxycarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl, di(C 1-6 )alkylaminocarbonyl, aminosulfonyl, C 1-6 alkylaminosulfonyl or di(C 1-6 )alkylaminosulfonyl;

R 4 and R 5 independently represent C 1-6 alkyl, aryl, aryl(C 1-6 )alkyl, heteroaryl or heteroaryl(C 1-6 )alkyl, any of which groups may be optionally substituted by one or more substituents; or hydrogen, halogen, trifluoromethyl, —OR a , —SR a , —SOR a , —SO 2 R a , —NR b R c , —NR c COR d , —NR c CO 2 R d , —NR c SO 2 R e , —COR d , —CO 2 R d , —CONR b R c or —SO 2 NR b R c ;

R 6 represents hydrogen or C 1-6 alkyl;

R 7 represents hydrogen, halogen, C 1-6 alkyl or C 1-6 alkoxy;

R a represents C 1-6 alkyl, difluoromethyl or trifluoromethyl;

R b represents hydrogen or trifluoromethyl; or C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl(C 1-6 )alkyl, aryl, aryl(C 1-6 )alkyl, C 3-7 heterocycloalkyl, C 3-7 heterocycloalkyl-(C 1-6 )alkyl, heteroaryl or heteroaryl(C 1-6 )alkyl, any of which groups may be optionally substituted by one or more substituents;

R c represents hydrogen, C 1-6 alkyl or C 3-7 cycloalkyl;

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

R e represents C 1-6 alkyl.

2. A compound as claimed in claim 1 represented by formula (IIA) or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof:

wherein E, Q, M, R 1 , R 2 , R 4 and R 5 are as defined in claim 1 .

3. A compound as claimed in claim 1 wherein the ring comprising M represents a monocyclic ring selected from pyrrolidin-1-yl, imidazolidin-1-yl, piperidin-1-yl, morpholin-4-yl, [1,4]oxazepan-4-yl, thiomorpholin-4-yl, piperazin-l-yl and [1,4]diazepan-1-yl, any of which rings may be optionally substituted by one or more substituents independently selected from halogen, C 1-6 alkyl, C 1-6 alkoxy(C 1-6 )alkyl, C 1-6 alkylsulphonyl, hydroxy, hydroxy(C 1-6 )alkyl, trifluoroethyl, oxo, C 2-6 alkylcarbonyl, hydroxy(C 2-6 )alkylcarbonyl, (C 3-7 )cycloalkylcarbonyl, carboxy(C 1-6 )alkyl, C 2-6 alkoxycarbonyl, C 2-6 alkoxycarbonyl(C 1-6 )alkyl, C 2-6 alkylcarbonylamino, (C 2-6 )alkylcarbonylamino(C 1-6 )alkyl, C 1-6 alkylsulphonylamino, aminocarbonyl, di(C 1-6 )alkylaminocarbonyl, di(C 1-6 )alkylaminocarbonyl(C 1-6 )alkyl and (C 3-7 )heterocycloalkylcarbonyl(C 1-6 )alkyl.

4. A compound as claimed in claim 1 wherein R 5 represents —NR b R c , in which R b and R c are as defined in claim 1 .

5. A compound as claimed in claim 2 represented by formula (IIB) or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof:

6. A compound as claimed in claim 1 wherein E represents methylene or (methyl)methylene.

7. A compound as claimed in claim 1 wherein Q represents oxygen or N—R 6 , in which R 6 is as defined in claim 1 .

8. A compound as claimed in claim 1 wherein R 1 represents hydrogen, halogen or C 1-6 alkyl.

9. A compound as claimed in claim 1 wherein R 2 represents hydrogen or halogen.

10. A compound as claimed in claim 1 wherein R 4 represents hydrogen or C 1-6 alkyl.

11. A compound selected from the group consisting of

6-Methyl-N-{(S)-1-[8-methyl-2-(morpholin-4-yl)quinolin-3-yl]ethyl}1-[1,3,5]triazine-2,4-diamine,

6-Methyl-N-{(S)-1-[8-methyl-2-(pyrrolidin-1-yl)quinolin-3-yl]ethyl}1-[1,3,5]triazine-2,4-diamine,

4-{3-[(S)-1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-methylquinolin-2-yl}-piperazin-2-one,

N 2 -[(S)-1-{8-Chloro-2-[(S)-3-methylmorpholin-4-yl]quinolin-3-yl}ethyl]-[1,3,5]triazine-2,4-diamine,

N 2 -[(S)-1-{8-Chloro-2-[(S)-3-methylmorpholin-4-yl]quinolin-3-yl}ethyl]-6-methyl-[1,3,5]triazine-2,4-diamine,

N-[(S)-1-{3-[(S)-1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-methylquinolin-2-yl}pyrrolidin-3-yl]acetamide,

(S)-6-Methyl-N 2 -{1[-8-methyl-2-(thiomorpholin-4-yl)quinolin-3-yl]ethyl}-[1,3,5]triazine-2,4-diamine,

(S)-6-Methyl-N 2 -{1-1-[8-chloro-2-(1,1-dioxothiomorpholin-4-yl)quinolin-3-yl]ethyl}-[1,3,5]triazine-2,4-diamine,

(S)-N-(1-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperidin-4-yl)methanesulfonamide,

(S)-N-(1-{3-[1-(4Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}-piperidin-4-yl)methanesulfonamide,

(S)-1(4-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)ethanone,

(S)-1-(4-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)ethanone,

(S)-4-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-methylquinolin-2-yl}piperazin-2-one,

(S)-4-{3-[1-(4-Amino[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-2-one,

(S)-4-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-2-one,

(S)-4-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-7-fluoro-8-methylquinolin-2-yl}piperazin-2-one,

(S)-4-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-7-fluoro-8-methyl-quinolin-2-yl}piperazin-2-one,

N-{(1S)-1-[8-Chloro-2-(pyrrolidin-1-yl)quinolin-3-yl]ethyl}-[1,3,5]triazine-2,4-diamine,

N-{(1S)-1-[8-Chloro-2-(morpholin-4-yl)quinolin-3-yl]ethyl}-6-methyl-[1,3,5]triazine-2,4-diamine,

(3R)-1-(3-{(1S)-1-[(4-Amino-[1,3,5 ]triazin-2-yl)amino]ethyl}-8-chloroquinolin-2-yl)pyrrolidin-3-ol,

(3R)-1-(3-{(1S)-1-[(4-Amino-6-methyl-[1,3,5]triazin-2-yl)aminol]ethyl}-8-chloro-quinolin-2-yl)pyrrolidin-3-ol,

(3S)-1-(3-{(1S)-1-[(4-Amino-[1,3,5]triazin-2-yl)amino]ethyl}-8-chloroquinolin-2-yl)pyrrolidin-3-ol,

(3S)-1-(3-{(1S)-1-[(4-Amino-6-methyl-[1,3,5]triazin-2-yl)amino]ethyl}-8-chloroquinolin-2-yl)pyrrolidin-3-ol,

1-(3-{(1S)-1-1-[(4-Amino-[1,3,5]triazin-2-yl)aminol]ethyl}-8-chloroquinolin-2-yl)-[1,4]-diazepan-5-one,

1-(3-{(1S)-1-[(4-Amino-6-methyl-[1,3,5]triazin-2-yl)amino]ethyl}-8-chloroquinolin-2-yl)-[1,4]diazepan-5-one,

4-(3-{(1S)-1-[(4-Amino-[1,3,5]triazin-2-yl)amino]ethyl}-8-chloroquinolin-2-yl)-1-methylpiperazin-2-one,

4-(3-{(1S)-1-[(4-Amino-6-methyl-[1,3,5]triazin-2-yl)amino]ethyl}-8-chloroquinolin-2-yl)-1-methylpiperazin-2-one,

1-(3-{(1S)-1-[(4-Amino-[1,3,5]triazin-2-yl)amino]ethyl}-8-chloroquinolin-2-yl)-imidazolidin-2-one,

(S)-(4-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-methylquinolin-2-yl}piperazin-1-yl)(cyclopropyl)methanone,

(S)-4-(8-Chloro-3-{1-[4-(methylamino)-[1,3,5]triazin-2-ylamino]ethyl}quinolin-2-yl)piperazin-2-one,

1-(3-{(1S)-1-[(4-Amino-6-methyl-[1,3,5]triazin-2-yl)amino]ethyl}-8-methylquinolin-2-yl)-[1,4]diazepan-5-one,

1-(3-{(1S)-1-[(4-Amino-[1,3,5]triazin-2-yl)amino]ethyl}-8-methylquinolin-2-yl)-[1,4]-diazepan-5-one,

6-Methyl-N-{(1S)-1-[8-methyl-2-(piperazin-1-yl)quinolin-3-yl]ethyl}-[1,3,5]triazine-2,4-diamine,

(S)-(4-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)(cyclopropyl)methanone,

(S)-(4-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)(cyclopropyl)methanone,

(S)-2-(4-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-methylquinolin-2-yl}piperazin-1-yl)-N,N-dimethylacetamide,

(S)-2(4-{3-[1-(4Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-methylquinolin-2-yl}piperazin-1-yl)-1-(morpholin-4-yl)ethanone,

(S)-N 2 -(1-{8-Chloro-2-[4-(methylsulfonyl)piperazin-1-yl]quinolin-3-yl}ethyl)-6-methyl-[1,3,5]triazine-2,4-diamine,

(S)-Ethyl 2-(4-{3-[1-(4-amino-6-methyl-[1,3 ,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)acetate,

(S)-2(4-{3-[1-(4Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)-N,N-dimethylacetamide,

(S)-N 2 -(4-Methoxybenzyl)-6-methyl-N 4 -{1-[8-methyl-2-(pyrrolidin-1-yl)quinolin-3-yl]-ethyl}-[1,3,5]triazine-2,4-diamine,

(S)-4-(3-{1-[4-(4-Methoxybenzylamino)-6-methyl-[1,3,5]triazin-2-ylamino]ethyl}-8-methylquinolin-2-yl)piperazin-2-one,

N-{(1S)-1-[7-Fluoro-2-(pyrrolidin-1-yl)quinolin-3-yl]ethyl}-[1,3,5]triazine-2,4-diamine

N-[1-(3-{(1S)-1-[-(4-Amino-[1,3,5]triazin-2-yl)amino]ethyl}-7-fluoroquinolin-2-yl)-piperidin-4-yl]-acetamide,

N-{(1S)-1-[7-Fluoro-2-(pyrrolidin-1-yl)quinolin-3-yl]ethyl}-6-methyl-[1,3,5]triazine-2,4-diamine,

N-[-1-(3-{(1S)-1-[(4-Amino-6-methyl-[1,3,5]triazin-2-yl)amino]ethyl}-7-fluoroquinolin-2-yl)piperidin-4-yl]acetamide,

1-[4-(3-{(1S)-1-[(4-Amino-6-methyl-[1,3,5]triazin-2-yl)amino]ethyl}-7-fluoroquinolin-2-yl)piperazin-1-yl]ethanone,

1-[4-(3-{(1S)-1-[(4-Amino-[1,3,5]triazin-2-yl)amino]ethyl}-7-fluoroquinolin-2-yl-piperazin-l-yl-]ethanone,

4-{[8-Methyl-2-(pyrrolidin-1-yl)quinolin-3-yl]methoxy}-[1,3,5]triazin-2-amine,

4-{[8-Methyl-2-(morpholin-4-yl)quinolin-3-yl]methoxy}-[1,3,5]triazin-2-amine,

4-{3-[(4-Amino-[1,3,5]triazin-2-ylamino)methyl]-8-methylquinolin-2-yl}piperazin-2-one,

4-{3-[(4-Amino-6-methyl-[-1,3,5]triazin-2-ylamino)methyl]-8-methylquinolin-2-yl}-piperazin-2-one,

(S)-1-(4-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-methylquinolin-2-yl}-piperazin-1-yl)ethanone,

4-{3-[(4-Amino-[1,3,5]triazin-2-yloxy)methyl]-8-methylquinolin-2yl}piperazin-2-one

4-{3-[(4-Amino-6-methyl-[1,3,5]-triazin-2-yloxy)methyl]-8-methylquinolin-2-yl}-piperazin-2-one,

(S)-4-(8-Chloro-3-{1-[4-(dimethylamino)-[1,3,5]triazin-2-ylamino]ethyl}quinolin-2-yl)piperazin-2-one,

(S)-N 2 -{1-[8-Chloro-2-(3,3-difluoropyrrolidin-1-yl)quinolin-3-yl]-lethyl}-[1,3,5]-1triazine-2,4-diamine,

(S)-N 2 -{1-[8-Chloro-2-(3 ,3-difluoropyrrolidin-1-yl)quinolin-3-yl]ethyl}-6-methyl-[1,3,5]triazine-2,4-diamine,

N 2 -[(S)-1-{8-Chloro-2-[(R)-3-fluoropyrrolidin-1-yl]quinolin-3-yl}ethyl]-[1,3,5]triazine-2,4-diamine,

N 2 -[(S)-1-{8-Chloro-2-[(R)-3-fluoropyrrolidin-1-yl]quinolin-3-yl}ethyl]-6-methyl-[1,3,5]1triazine-2,4-diamine,

N 2 -[(S)-1-{8-Chloro-2-[(S)-3-fluoropyrrolidin-1-yl]quinolin-3-yl}ethyl]-6-methyl-[1,3,5]triazine-2,4-diamine,

(S)-Ethyl 2(4-{3-[-1-(4amino-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)acetate,

(S)-4-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}-N,N-dimethylpiperazine-1-carboxamide,

(S)-1-(4-{3-[1-(4Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}-[1,4]diazepan-1-yl)ethanone,

(S)-4-(7-Fluoro-8-methyl-3-{1-[4-(methylamino)-[1,3,5]triazin-2-ylamino]ethyl}-quinolin-2-yl)piperazin-2-one,

(S)-N 2 -{1-[7-Fluoro-8-methyl-2-(pyrrolidin-1-yl)quinolin-3-yl]ethyl}-6-methyl-[1,3,5]triazine-2,4-diamine,

(S)-2-[4-(8-Chloro-3-{1-[4-(methylamino)-[1,3,5]triazin-2-ylamino]ethyl}quinolin-2-yl)piperazin-1-yl]ethanol,

(S)-2-(4-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)ethanol,

(S)-2-(4-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)ethanol,

(S)-1-(4-{3-[1-(4Amino-[1,3,5]triazin-2-ylamino)ethyl]-7-fluoro-8-methylquinolin-2-yl}piperazin-1-yl)-2-hydroxyethanone,

(S)-Ethyl 2-[4-(8-chloro-3-{1-[4-(methylamino)-[1,3,5]triazin-2-ylamino]ethyl}quinolin-2-yl)piperazin-1-yl]acetate,

(S)-2-(4-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperazin-1-yl)acetic acid,

(S)-2-[4-(8-Chloro-3-{1-[4-(methylamino)-[1,3,5]triazin-2-ylamino]ethyl}quinolin-2-yl)piperazin-1-yl]acetic acid,

N-{[(R)-1-{3-[(S)-1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-chloro-quinolin-2-yl}pyrrolidin-3-yl]methyl}acetamide,

(S)-1-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-7-fluoro-8-methyl-quinolin-2-yl}piperidine-4-carboxamide,

(S)-1-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-7-fluoro-8-methylquinolin-2-yl}piperidine-4-carboxamide,

(S)-N 2 -(1-{7-Fluoro-8-methyl-2-[4-(2,2,2-trifluoroethyl)piperazin-1-yl]quinolin-3-yl}ethyl)-6-methyl-[1,3,5]triazine-2,4-diamine,

N 2 -[(S)-1-{2-[(3S,5R)-3,5-Dimethylpiperazin-1-yl]-7-fluoro-8-methylquinolin-3-yl}ethyl]-6-methyl-[1,3,5]triazine-2,4-diamine,

(S)-N 2 -{1-[7-Fluoro-2-(4-isopropylpiperazin-1-yl)-8-methylquinolin-3-yl]ethyl}-6-methyl-[1,3,5]triazine-2,4-diamine,

(S)-1-(4-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-7-fluoro-8-methylquinolin-2-yl}piperazin-1-yl)-2,2-dimethylpropan-1-one,

(S)-4-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-bromoquinolin-2-yl}piperazin-2-one,

(S)-4-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-5-fluoro-8-methyl-quinolin-2-yl}piperazin-2-one,

N-[(R)-1-{3-[(S)-1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-7-fluoro-8-methylquinolin-2-yl}pyrrolidin-3-yl]acetamide,

N-[(R)-1-{3-[(S)-1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-7-fluoro-8-methylquinolin-2-yl}pyrrolidin-3-yl]acetamide,

(S)-N -(1-{3-[1-(4-Amino-6-methyl-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}piperidin-4-yl)acetamide,

(S)-N-(1-{3-[1-(4-Amino-[1,3,5]triazin-2-ylamino)ethyl]-8-chloroquinolin-2-yl}-piperidin-4-yl)acetamide,

(S)-N 2 -{1-[8-chloro-2-([1,4]oxazepan-4-yl)quinolin-3-yl]ethyl}-6-methyl-[1,3,5]triazine-2,4-diamine,

(S)-Methyl 4-{3-[1-(4-amino-[1,3,5]triazin-2-ylamino)ethyl]-7-fluoro-8-methylquinolin-2-yl}piperazine-1-carboxylate,

N 2 -[(S)-1-{8-chloro-2-[(R)-2-(methoxymethyl)pyrrolidin-1-yl]quinolin-3-yl}ethyl]-6-methyl-[1,3,5]triazine-2,4-diamine,

N 2 -[(S)-1-{8-Chloro-2-[(S)-2-(methoxymethyl)pyrrolidin-1-yl]quinolin-3-yl}ethyl]-[1,3,5]triazine-2,4-diamine,

N 2 -[(S)-1-{8-Chloro-2-[(R)-2-(methoxymethyl)pyrrolidin-1-yl]quinolin-3-yl}ethyl]-[1,3,5]triazine-2,4-diamine,

N 2 -[(S)-1-{8-Chloro-2-[(S)-2-(methoxymethyl)pyrrolidin-1-yl]quinolin-3-yl}ethyl]-6-methyl-[1,3,5]triazine-2,4-diamine,

4-{3-[(4-Amino-[1,3,5]triazin-2-ylamino)methyl]-8-chloroquinolin-2-yl}piperazin-2-one,

and N-oxides, and pharmaceutically acceptable salts and solvates of any of the above compounds.

12. A pharmaceutical composition comprising a compound of formula (I) as defined in claim 1 or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof, in association with a pharmaceutically acceptable carrier.