Inhibitors of protein kinases

1. A compound according to the general Formula I

wherein

R 1 is —XSO 2 NR 5 R 6 or —XSO 2 R 8 ;

X is methylene;

R 5 and R 6 independently of each other are selected from the group consisting of hydrogen, C 1-4 alkyl, hydroxy-C 1-4 alkyl, C 3-4 alkenyl, C 3-8 -cycloalkyl, C 3-8 -cycloalkyl-C 1-4 alkyl, C 4-7 -heterocycloalkyl-C 0-4 alkyl, C 4-7 -aryl-C 0-4 alkyl, and C 4-7 -heteroaryl-C 0-4 alkyl, or

wherein R 5 and R 6 together with the N-atom to which they are bound form a 5- to 8-membered heterocycloalkyl,

wherein said cycloalkyl, heterocycloalkyl, aryl, heteroaryl or alkyl is further optionally substituted by up to 2 radicals selected from the group consisting of halo, hydroxy, aminocarbonyl, C 1-4 alkyl, hydroxy-C 1-4 alkyl, C 1-4 alkyl-O—C 1-4 alkyl, C 1-4 alkyl-O—, and —NR 5 R 6 ;

R 8 is C 1-4 alkyl, hydroxy-C 2-4 alkyl or C 3-4 alkenyl, C 3-8 -cycloalkyl, C 3-8 -cycloalkyl-C 1-4 alkyl, or C 4-7 -heterocycloalkyl-C 0-4 alkyl;

wherein said cycloalkyl, heterocycloalkyl or alkyl is further optionally substituted by up to 2 radicals selected from the group consisting of halo, hydroxy, C 1-4 alkyl, hydroxy-C 1-14 alkyl, C 1-4 alkyl-O—C 1-4 alkyl, C 1-4 alkyl-O, and —NR 5 R 6 ;

R 2 is one or two substituents independently selected from halogen and hydrogen;

R 3 can be 1 to 3 substituents each independently selected from the group consisting of hydrogen, halo, hydroxy, C 1-4 alkyl, C 3-7 cycloalkyl, C 1-4 alkyl-cycloalkyl, C 1-4 alkyl-heterocycloalkyl, —O-heterocycloalkyl, C 1-4 alkoxy, C 2-4 alkenyloxy, —OCF 3 , C 2-4 alkanoyl, C 1-4 alkylsulfonyl, mono- and di-(C 1 -C 4 alkyl)sulfonamido, aminocarbonyl, mono- and di-(C 1 -C 4 alkyl)aminocarbonyl, aryl-C 1-4 alkoxy, heteroaryl-C 1-4 alkoxy, heterocycloalkyl-C 1-4 -alkoxy, heterocycloalkyl-C 1-4 -alkyl, heteroaryl-C 1-4 -alkyl, C 1-4 alkyloxymethyl, hydroxy-C 1-4 alkyloxymethyl, cyano, —COOH, and C 1 -C 4 alkoxycarbonyl, wherein the above mentioned substituents can be further substituted by radicals selected from the group consisting of C 1-4 -alkyl, hydroxyl-C 0-4 -alkyl, C 1-4 -alkoxy, aminocarbonyl, halo, and NR 5 R 6 ;

R 4a and R 4b are the same or different and each is independently hydrogen, C 1-4 alkyl, or —NR′R″, wherein R′ and R″ are each independently hydrogen or C 1-4 alkyl;

and N-oxides of such compounds.

2. The compound of claim 1 , wherein R 3 is 1 to 3 substituents independently selected from the group consisting of methyl, ethyl, hydroxymethyl, hydroxy, methoxy, ethoxy, isopropoxy, benzyloxy, hydrogen, fluoro, chloro, trifluoromethyl, 2-methoxy-ethoxy, methoxymethyl, 2-methoxy-ethyl, tetrahydro-furan-3-yloxy, tetrahydro-furan-2-yl-methoxy, —N(CH 3 )SO 2 CH 3 , piperidin-1-yl-methyl, 2-hydroxymethyl-piperidin-1-yl-methyl, 3-hydroxymethyl-piperidin-1-yl-methyl, 3-(2-hydroxy-ethyl)-piperidin-1-yl-methyl, 3-aminocarbonyl-piperidin-1-yl-methyl, dimethylaminomethyl, diethylaminomethyl, (ethyl-isopropyl-amino)-methyl, morpholin-4-ylmethyl, 4-methyl-piperazin-1-yl-methyl, [1,2,4]triazol-1-yl-methyl, pyridine-3-yl-methoxy, and pyridine-4-yl-methoxy.

3. The compound of claim 1 , wherein R 1 is —XSO 2 NR 5 R 6 , and R 5 and R 6 are each independently selected from the group consisting of hydrogen, methyl, cyclopropyl, 2-dimethylaminoethyl, 3-dimethylaminopropyl, and 2-hydroxyethyl.

4. The compound of claim 1 , wherein R 1 is —XSO 2 R 8 and R 8 is C 1-4 alkyl or hydroxy-C 2-4- alkyl.

5. The compound of claim 1 , wherein the compound has a structure according to Formula Ia

wherein

R 9 is —NR 5 R 6 or R 8 ,

R 2 is hydrogen or halogen,

R 3a is hydrogen, halogen or C 1-4 -alkoxy,

R 3b is hydrogen,

R 3c is hydrogen or halogen,

R 4a and R 4b are each independently hydrogen or C 1-4 alkyl,

R 5 and R 6 are each independently hydrogen, cycloalkyl, or C 1-4 alkyl optionally substituted by hydroxyl or dialkylamino,

R 8 is hydroxy-C 2-4 -alkyl,

and N-oxides of such compounds.

6. The compound of claim 1 , which is selected from the group consisting of:

{3-[4-(2-Methoxy-phenyl)-pyrimidin-2-ylamino]-phenyl}-methanesulfonamide (Compound 1);

{3-[4-(2-Isopropoxy-phenyl)-pyrimidin-2-ylamino]-phenyl}-methanesulfonamide (Compound 2);

C-{3-[4-(2-Methoxy-phenyl)-pyrimidin-2-ylamino]-phenyl}-N,N-dimethyl-methanesulfonamide (Compound 3);

C-{3-[4-(2-Methoxy-phenyl)-pyrimidin-2-ylamino]-phenyl}-N-methyl-methanesulfonamide (Compound 4);

{3-[4-(4-Fluoro-2-methoxy-phenyl)-pyrimidin-2-ylamino]-phenyl}-methanesulfonamide (Compound 5);

N-Cyclopropyl-C-{3-[4-(2-methoxy-phenyl)-pyrimidin-2-ylamino]-phenyl}-methanesulfonamide (Compound 6);

N-(2-Hydroxy-ethyl)-C-{3-[4-(2-methoxy-phenyl)-pyrimidin-2-ylamino]-phenyl}-methanesulfonamide (Compound 7);

N-(2-Hydroxy-ethyl)-C-{3-[4-(2-methoxy-phenyl)-pyrimidin-2-ylamino]-phenyl}-N-methyl-methanesulfonamide (Compound 8);

2-{3-[4-(2-Methoxy-phenyl)-pyrimidin-2-ylamino]-phenylmethanesulfonyl}-ethanol (Compound 9);

{3-[4-(2-Methoxy-phenyl)-6-methyl-pyrimidin-2-ylamino]-phenyl}-methanesulfonamide (Compound 10);

-(2-Hydroxy-ethyl)-C-{3-[4-(2-methoxy-phenyl)-6-methyl-pyrimidin-2-ylamino]-phenyl}-N-methyl-methanesulfonamide (Compound 11);

2-{3-[4-(2-Methoxy-phenyl)-6-methyl-pyrimidin-2-ylamino]-phenylmethanesulfonyl}-ethanol (Compound 12);

{3-[4-(2-Methoxy-phenyl)-5-methyl-pyrimidin-2-ylamino]-phenyl}-methanesulfonamide (Compound 13);

N-(2-Hydroxy-ethyl)-C-{3-[4-(2-methoxy-phenyl)-5-methyl-pyrimidin-2-ylamino]-phenyl}-N-methyl-methanesulfonamide (Compound 14); and

2-{3-[4-(2-Methoxy-phenyl)-5-methyl-pyrimidin-2-ylamino]-phenylmethanesulfonyl}-ethanol (Compound 15).

7. A pharmaceutical composition containing the compound of claim 1 , together with a pharmaceutically acceptable carrier.

8. A method for the treatment of neuropathic pain, comprising administering a therapeutically effective amount of at least one of the compounds of claim 1 to a patient suffering from neuropathic pain.

9. A pharmaceutical composition containing the compound of claim 2 , together with a pharmaceutically acceptable carrier.

10. A method for the treatment of neuropathic pain, comprising administering a therapeutically effective amount of at least one compound of claim 2 to a patient suffering from neuropathic pain.

11. A pharmaceutical composition containing the compound of claim 5 , together with a pharmaceutically acceptable carrier.

12. A method for the treatment of neuropathic pain a disease diseases, comprising administering a therapeutically effective amount of at least one compound of claim 5 to a patient suffering from neuropathic pain.

13. A pharmaceutical composition containing the compound of claim 6 , together with a pharmaceutically acceptable carrier.

14. A method for the treatment of neuropathic pain, comprising administering a therapeutically effective amount of at least one compound of claim 6 to a patient suffering from neuropathic pain.