Method of inhibiting the expression and/or the activity of JNK

1. A method for treating rheumatoid arthritis, comprising administering to a patient in need thereof a benzothiazole compound according to formula I

as well as its automats, its geometrical isomers, its optically active forms as enantiomers, diastereomers and its racemate forms, or pharmaceutically acceptable salts thereof, wherein:

G is an unsubstantiated or substituted pyrimidinyl group;

R 1 is selected from the group consisting of hydrogen, C 1 -C 6 -alkyl, optionally substituted by halogen; and

R 2 is hydrogen.

2. The method of claim 1 , wherein the benzothiazole compound is a benzothiazole compound according to formula I, as well as its automats according to formula II below,

its geometrical isomers, its optically active forms as enantiomers, diastereomers and their racemate forms, or pharmaceutically acceptable salts thereof.

3. The method of claim 1 , wherein, in the benzothiazole compound, G is a pyrimidinyl group

L is selected from the group consisting of hydrogen, unsubstantiated or substituted C 1 -C 6 alkyl, unsubstantiated or substituted C 1 -C 6 alkoxy, unsubstantiated or substituted C 1 -C 6 thioalkoxy, unsubstantiated or substituted C 2 -C 6 alkenyl, unsubstantiated or substituted C 2 -C 6 alkynyl, primary, secondary or tertiary amino groups, aminoacyl, aminocarbonyl, amino -(C 1 -C 10 ) alkyl, amino -unsubstantiated or substituted (C 1 -C 10 ) -alkyl -aryl, amino -unsubstantiated or substituted (C 1 -C 10 )alkyl -heteroaryl, unsubstantiated or substituted C 1 -C 6 alkoxycarbonyl, carboxyl, cyano, halogen, hydroxyl, nitro, sulfoxy, sulfonyl, unsubstantiated or substituted aryl, unsubstantiated or substituted heteroaryl, unsubstantiated or substituted 3-8 membered cyclically, optionally containing at least one heteroatom selected from N, O, S, and unsubstantiated or substituted hydracids groups, wherein the term “substituted” means that said groups can be substituted with from 1 to 5 substituents selected from the group consisting of C 1 -C 6 -alkyl, C 1 -C 6 -alkyl aryl, C 1 -C 6 -alkyl heteroaryl, C 2 -C 6 -alkenyl, C2-C6-alkynyl, primary, secondary or tertiary amino groups or quarternary ammonium moieties, acryl, acyloxy, calamine, aminocarbonyl, alkoxycarbonyl, aryl, heteroaryl, carboxyl, cyano, halogen, hydroxyl, mercapto, nitro, sulfoxy, sulfonyl, alkoxy, thioalkoxy, and trihalomethyl; and

said substitution may optionally include situations where neighboring substituents have undergone ring closure wherein said substituents form lactase, lactones, cyclic anhydrides, acetyls, thioacetals, or ammonals formed by ring closure.

4. The method of claim 3 , wherein, in the benzothiazole compound, L is a group —N(R a , R b ) or —OR a , with R a and R b being each independently selected from the group consisting of H, unsubstantiated or substituted (C 1 -C 10 ) -alkyl, unsubstantiated or substituted C 1 -C 6 alkyl -aryl, unsubstantiated or substituted C 1 -C 6 -alkyl -heteroaryl, unsubstantiated or substituted aryl, heteroaryl and unsubstantiated or substituted 4-8 membered saturated or unsaturated cycloalkyl.

5. The method of claim 4 , wherein, in the benzothiazole compound, L is selected from

where n is 1 to 10, and

R 5 and R 5 ′ are independently selected from each other from the group consisting of H, substituted or unsubstantiated C 1 -C 10 alkyl, substituted or unsubstantiated aryl or heteroaryl, substituted or unsubstantiated C 1 -C 6 alkyl -aryl and substituted or unsubstantiated C 1 -C 6 -alkyl -heteroaryl.

6. The method of claim 5 , wherein, in the benzothiazole compound, n is 1 to 6.

7. The method of claim 5 , wherein, in the benzothiazole compound, R 1 is H.

8. The method of claim 1 , wherein, in the benzothiazole compound, R 1 is hydrogen, G is a pyrimidinyl group

with L being either

where n is 0, 1 or 2 and R 5 is an aryl or heteroaryl.

9. The method of claim 8 , wherein, in the benzothiazole compound, R 5 is phenyl, pyridyl, or imidazolyl.

10. The method of claim 1 , wherein the benzothiazole compound is selected from the following group:

1,3-benzothiazol-2-yl (2-chloral -4-pyrimidinyl)acetonitrile;

1,3-benzothiazol-2-yl (2, 6-dimethoxy -4 pyrimidinyl) acetonitrile;

1,3-benzothiazol-2-yl (2-chloral -6-methyl -4 -pyrimidinyl) acetonitrile;

1,3-benzothiazol-2-yl [2 -(methylsulfanyl) - 4 -pyrimidinyl] acetonitrile;

1,3-benzothiazol-2-yl{6-chloral -5-nitro -4 -pyrimidinyl }acetonitrile;

1,3-benzothiazol-2-yl(2-hydroxyl -pyrimidinyl -4-yl) acetonitrile;

(2-chloropyrimidin-4-yl)[5-(trifluoromethyl) -1, 3-benzothiazol-2-yl]acetonitrile;

(2E) -(2-chloral -4-pyrimidinyl)(3-methyl -1, 3-benzothiazol-2(3H) -ylidene)ethanenitrile;

1,3-benzothiazol-2-yl(2-{[2-(1H -imidazol -5-yl)ethyl]amino}-4-pyrimidinyl) -acetonitrile;

1,3-benzothiazol-2-yl[2 -(1-piperazinyl) -4 -pyrimidinyl]acetonitrile;

1, 3-benzothiazol-2-yl[2-(4-benzyl -1-piperidinyl) -4-pyrimidinyl]acetonitrile;

1,3-benzothiazol-2-yl[2 -(4-methyl -1-piperazinyl) -4 -pyrimidinyl ]acetonitrile;

1,3-benzothiazol-2-yl[2 -(4-morpholinyl) -4 -pyrimidinyl]acetonitrile;

1,3-benzothiazol-2-yl[2-(methylamine) -4 -pyrimidinyl ]acetonitrile;

1,3- benzothiazol-2-yl(2-{4-[2-(4-morpholinyl) ethyl]-1 -piperazinyl}-4-pyrimidinyl)acetonitrile;

1,3-benzothiazol-2-yl{2-[4 -(benzyloxy) -1-piperidinyl ]-4-pyrimidinyl }acetonitrile;

1,3-benzothiazol-2-yl[2-(4-hydroxyl -1-piperidinyl) -4-pyrimidinyl]acetonitrile;

1,3-benzothiazol-2-yl(2-hydrazine -4-pyrimidinyl) acetonitrile;

1,3-benzothiazol-2-yl(2-{[2-(dimethylamino)ethyl ]amino}-4-pyrimidinyl)acetonitrile;

1,3-benzothiazol-2-yl[2-(dimethylamino) - 4-pyrimidinyl]acetonitrile;

1,3-benzothiazol-2-yl{2-[(2-methoxyethyl) amino ]-4-pyrimidinyl}acetonitrile;

1,3-benzothiazol-2-yl{2-[(2-hydroxyethyl) amino]4 -pyrimidinyl}acetonitrile;

1,3-benzothiazol-2-yl[2-(propylamino) -4 -pyrimidinyl]acetonitrile;

1,3-benzothiazol-2-yl(2-{[3-(1H -imidazol -1-yl)propyl ]amino}-4-pyrimidinyl)acetonitrile;

1,3-benzothiazol-2-yl[2-(1-pyrrolidinyl) - 4 -pyrimidinyl]acetonitrile;

1,3-benzothiazol-2-yl{2-[(2-phenylethyl) amino]-4-pyrimidinyl-}acetonitrile;

1,3-benzothiazol-2-yl(2-{[2-(2-pyridinyl) ethyl]amino}-4-pyrimidinyl)acetonitrile;

1,3-benzothiazol-2-yl{2-[(2-pyridinylmethyl)amino]-4-pyrimidinyl}acetonitrile;

1,3-benzothiazol-2-yl{2 -[4-(1H -1,2,3-benzotriazol -1-yl) -1-piperidinyl]-4-pyrimidinyl}acetonitrile;

1,3-benzothiazol-2-yl{2-[4-(2-pyrazinyl) -1-piperazinyl]-4-pyrimidinyl}acetonitrile;

1,3-benzothiazol-2-yl{2 -[4 -(2-pyrimidinyl) -1piperazinyl]-4-pyrimidinyl}acetonitrile;

1,3-benzothiazol-2-yl(2-{[2-(3-pyridinyl)ethyl]amino}-4-pyrimidinyl)acetonitrile;

1,3-benzothiazol-2-yl(5-bromo -2{[2-(dimethylamino) ethyl]amino}-4-pyrimidinyl)acetonitrile;

1,3-benzothiazol-2-yl{2-[(2-morpholin -4-ylethyl) amino]pyrimidin-4-yl}acetonitrile;

1,3-benzothiazol-2-yl[2-(4-{3-[(trifluoromethyl) sulfonyl]anilino}piperidin -1-yl)pyrimidin-4-yl]acetonitrile;

1,3-benzothiazol-2-yl(2-{[3-(2-oxopyrrolidin -1-yl) propyl]amino}pyrimidin-4-yl)acetonitrile;

1,3-benzothiazol-2-yl(2-{methyl[3-(methylamino) propyl]amino}pyrimidin-4-yl)acetonitrile;

1,3-benzothiazol-2-yl(2-{[3-(4-methylpiperazin1 -yl) propyl]amino}pyrimidin-4-yl) acetonitrile;

1,3-benzothiazol-2-yl{2-[(3-morpholin -4-ylpropyl) amino]pyrimidin-4-yl}acetonitrile;

1,3-benzothiazol-2-yl(2-{[2-(1-methyl -1H -imidazol -4 -yl) ethyl]amino}pyrimidin-4-yl) acetonitrile;

1,3-benzothiazol-2-yl(2-{[2-(1H -indol -3 -yl) ethyl]amino }pyrimidin-4-yl)acetonitrile;

1,3-benzothiazol-2-yl(2-{[2-(4 -hydroxyphenyl) ethyl]amino}pyrimidin-4-yl) acetonitrile;

tert -butyl({4-[1,3-benzothiazol-2-yl (cyano)methyl]pyrimidin-2-yl}amino)acetate {2-[(3-aminopropyl)amino]pyrimidin-4-yl}(1,3-benzothiazol-2 -yl) acetonitrile;

{-2[(2-aminoethyl)amino]pyrimidin-4-yl}(1,3-benzothiazol-2 -yl)acetonitrile;

1,3-benzothiazol-2-yl(2-{[3 -(dimethylamino) propyl]amino}pyrimidin-4-yl)acetonitrile;

1,3-benzothiazol-2-yl{2-[(2-piperidin -1 -ylethyl) amino]pyrimidin-4-yl}acetonitrile;

1,3-benzothiazol-2-yl(2-{[2-(1-methyl -1H -imidazol -5 -yl) ethyl]amino}pyrimidin-4-yl)acetonitrile;

1,3-benzothiazol-2-yl[2-(benzylamino) pyrimidin-4-yl]acetonitrile; isopropyl3-({4-[1,3-benzothiazol-2 -yl (cyano)methyl]pyrimidin-2-yl}amino)propionate

1,3-benzothiazol-2-yl{2-[(3-hydroxypropyl)amino]pyrimidin-4-yl}acetonitrile;

1,3-benzothiazol-2-yl{2-[(pyridine-3 -ylmethyl) amino]pyrimidin-4-yl}acetonitrile; (2-aminopyrimidin-4-yl)(1,3-benzothiazol-2-yl)acetonitrile;

1,3-benzothiazol-2-yl{2-[(pyridine-4-ylmethyl) amino]pyrimidin-4-yl}acetonitrile;

tert -butyl4-[2-({4-[1,3-benzothiazol-2-yl (cyano)methyl]pyrimidin-2-yl}amino)ethyl]phenylcarbamate (2-{[2-(4-aminophenyl)ethyl]amino}pyrimidin-4-yl) (1,3-benzothiazol-2-yl)acetonitrile;

1,3-benzothiazol-2-yl(2-{[2-(3,4-dimethoxyphenyl) ethyl]amino}pyrimidin-4-yl)acetonitrile;

1,3-benzothiazol-2-yl(2-{[2-(3 methoxyphenyl) ethyl]amino}pyrimidin-4-yl)acetonitrile;

1,3-benzothiazol-2-yl(2-{[2-(2 -fluorophenyl) ethyl]amino}pyrimidin-4-yl)acetonitrile;

1,3-benzothiazol-2-yl[2-({2-[3-(trifluoromethyl) phenyl]ethyl}amino)pyrimidin-4-yl]acetonitrile;

1,3-benzothiazol-2-yl{2-[(2-hydroxyl -2phenylethyl) amino]pyrimidin-4-yl}acetonitrile;

1,3-benzothiazol2-yl{2[(2{[3 (trifluoromethyl)pyridin2 yl]amino}ethyl)amino]pyrimidin-4-yl}acetonitrile;

1,3-benzothiazol-2-yl(2{[2(3 chiorophenyl) ethyl]amino }pyrimidin-4-yl) acetonitrile;

1,3-benzothiazol-2-yl(2{[2(3,4 dichlorophenyl) ethyl]amino }pyrimidin-4-yl) acetonitrile; 1,3-benzothiazol-2-yl(2{[2(4 methoxyphenyl) ethyl]amino }pyrimidin-4-yl) acetonitrile;

1,3-benzothiazol-2-yl(2{[2(4 methylphenyl) ethyl]amino }pyrimidin-4-yl) acetonitrile;

1,3-benzothiazol-2-yl(2{[2(3 fluorophenyl) ethyl]amino }pyrimidin-4-yl) acetonitrile;

1,3-benzothiazol-2-yl(2-{[2-(4 -phenoxyphenyl) ethyl]amino}pyrimidin-4-yl)acetonitrile;

1,3-benzothiazol-2-yl(2-{[2-(2 -phenoxyphenyl) ethyl]amino}pyrimidin-4-yl)acetonitrile;

l,3-benzothiazol-2-yl(2-{[2-(4 -bromophenyl) ethyl]amino}pyrimidin-4-yl)acetonitrile;

1,3-benzothiazol-2-yl(2-{[2-(4 -fluorophenyl) ethyl]amino}pyrimidin-4-yl)acetonitrile;

1,3-benzothiazol-2-yl{2-[(2-[1,1′-biphenyl]-4-ylethyl) amino]pyrimidin-4-yl}acetonitrile;

1,3-benzothiazol-2-yl{2[(2{4 [hydroxyl(oxide)amino]phenyl}ethyl)amino]pyrimidin-4- yl }acetonitrile;

1,3-benzothiazol-2-yl(2-{[2-(1H -1,2,4-triazol -1-yl) ethyl]amino}pyrimidin-4-yl)acetonitrile;

1,3-benzothiazol-2-yl(2-{[3-(1H -pyrazol1-yl) propyl]amino}pyrimidin-4-yl)acetonitrile;

4[2-({4-[1,3-benzothiazol-2-yl(cyano)methyl]pyrimidin-2-yl}amino)ethyl]benzene sulfonamide {2-[(2-pyridin-3-ylethyl)amino]pyrimidin-4-yl}[5-(trifluoromethyl) -1,3-benzothiazol-2-yl]acetonitrile;

1,3-benzothiazol-2-yl{2-[(1H -tetraazol -5 -ylmethyl) amino]pyrimidin-4-yl}acetonitrile;

1,3-benzothiazol-2-yl[2-(benzyloxy)pyrimidin-4-yl]acetonitrile;

1,3-benzothiazol-2-yl{2-[(4-pyridin-3-ylbenzyl) oxy]pyrimidin-4-yl}acetonitrile;

1,3-benzothiazol-2-yl[2-(pyridin-4-ylmethoxy) pyrimidin-4-yl]acetonitrile;

1,3-benzothiazol-2-yl[2-(pyridin-2-ylmethoxy) pyrimidin-4-yl]acetonitrile;

1,3-benzothiazol-2-yl[2-(3-pyridin-2-ylpropoxy) pyrimidin-4-yl]acetonitrile;

1,3-benzothiazol-2-yl{2-[(4-methoxybenzyl)oxy]pyrimidin-4-yl }acetonitrile;

1,3-benzothiazol-2-yl[2-(pyridin-3-ylmethoxy)pyrimidin-4-yl]acetonitrile;

1, 3-benzothiazol-2-yl{2-[2-(4-methoxyphenyl)ethoxy]pyrimidin-4-yl}acetonitrile;

1,3-benzothiazol-2-yl[2-([1,1′-biphenyl]-3-ylmethoxy) pyrimidin-4-yl]acetonitrile;

1,3-benzothiazol-2-yl{2-[(3,4,5-trimethoxybenzyl) oxy]pyrimidin-4-yl}acetonitrile;

1,3-benzothiazol-2-yl{2-[(3,4-dichlorobenzyl)oxy]pyrimidin-4-yl}acetonitrile;

1,3-benzothiazol-2-yl[2-({3-[(dimethylamino)methyl]benzyl}oxy)pyrimidin-4-yl]acetonitrile;

1,3-benzothiazol-2-yl{2-[(1-oxidopyridin-3-yl) methoxy]pyrimidin-4-yl}acetonitrile;

1,3-benzothiazol-2-yl(2-{[4-(morpholin -4-ylmethyl) benzyl]oxy}pyrimidin-4-yl)acetonitrile;

1,3-benzothiazol-2-yl{2-[(4-pyridin-2-ylbenzyl) oxy]pyrimidin-4-yl}acetonitrile;

1,3-benzothiazol-2-yl(2-{[4-(piperidin -1-ylmethyl) benzyl]oxy}pyrimidin-4-yl)acetonitrile;

1,3-benzothiazol-2-yl [2-(4-methoxyphenoxy) pyrimidin-4-yl]acetonitrile;

1,3-benzothiazol-2-yl[2-(4-butoxyphenoxy) pyrimidin-4-yl]acetonitrile;

{2-[4-(4-acetylpiperazin -1-yl)phenoxy]pyrimidin-4-yl}(1,3-benzothiazol-2-yl)acetonitrile;

[2-(4-methoxyphenoxy)pyrimidin-4-yl][5-(trifluoromethyl) -1,3-benzothiazol-2-yl]acetonitrile;

1,3-benzothiazol-2-yl(pyrimidin-4-yl)acetonitrile; and N -[2-({4-[1,3-benzothiazol-2-yl(cyano)methyl]pyrimidin-2-yl}amino)ethyl]-4-chlorobenzamidel,3-benzothiazol-2-yl (2-methoxy -4-pyrimidinyl)acetonitrile.

11. The method of claim 10 , wherein the benzothiazole compound is selected from the group consisting of:

1,3-benzothiazol-2-yl(2-chloro -4-pyrimidinyl)acetonitrile;

1,3-benzothiazol-2-yl[2-(methylsulfanyl) -4-pyrimidinyl]acetonitrile;

1,3-benzothiazol-2-yl(2-{[2-(1H -imidazol -5-yl)ethyl]amino}-4-pyrimidinyl)acetonitrile;

1,3-benzothiazol-2-yl[2-(methylamino) -4 pyrimidinyl]acetonitrile;

1,3-benzothiazol-2-yl{2-[(2-hydroxyethyl) amino]4-pyrimidinyl}acetonitrile;

1,3-benzothiazol-2-yl[2-(benzyloxy)pyrimidin-4-yl]acetonitrile;

1,3-benzothiazol-2-yl[2-(4-methoxyphenoxy) pyrimidin-4-yl]acetonitrile;

1,3-benzothiazol-2-yl (2-methoxy -4-pyrimidinyl)acetonitrile; and

1,3-benzothiazol-2-yl(2-{[2-(3-pyridinyl)ethyl]amino}-4-pyrimidinyl)acetonitrile.

12. The method of claim 1 , wherein the benzothiazole compound is 1,3-benzothiazol-2-yl ([2-{[4-(morpholin -4-ylmethyl)benzyl]oxy}-pyrimidin-4-yl) acetonitrile.