Composition Comprising a Jnk Inhibitor and Cyclosporin

1 : A pharmaceutical composition comprising a JNK inhibitor and a cyclosporin.

2 : Pharmaceutical composition according to claim 1 , wherein the JNK inhibitor is a JNK3 inhibitor.

3 : Pharmaceutical composition according to claim 2 , wherein the JNK inhibitor is a benzothiazole derivative according to formula I

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

G is a pyrimidinyl group.

L is an C 1 -C 6 -alkoxy, or an amino group, or an 3-8 membered heterocycloalkyl, containing at least one heteroatom selected from N, O, S;

R 1 is selected from the group comprising or consisting of hydrogen, sulfonyl, amino, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl or C 1 -C 6 -alkoxy, aryl, halogen, cyano or hydroxy.

4 : Pharmaceutical composition according to claim 3 , wherein R 1 is H or C 1 -C 3 alkyl.

5 : Pharmaceutical composition according to claim 3 , wherein the JNK inhibitor has any of formulae (Ia), (Ia′) or (Ia″):

wherein R 1 is selected from the group comprising or consisting of hydrogen, sulfonyl, amino, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl or C 1 -C 6 -alkoxy, aryl, halogen, cyano or hydroxy;

L is an amino group of the formula —NR 3 R 4 wherein R 3 and R 4 are each independently from each other H, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkoxy, aryl, heteroaryl, saturated or unsaturated 3-8-membered cycloalkyl, 3-8-membered heterocycloalkyl, (wherein said cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups may be fused with 1-2 further cycloalkyl, heterocycloalkyl, aryl or heteroaryl group), C 1 -C 6 -alkyl aryl, C 1 -C 6 -alkyl heteroaryl, C 2 -C 6 -alkenyl aryl, C 2 -C 6 -alkenyl heteroaryl, C 2 -C 6 -alkynyl aryl, C 2 -C 6 -alkynyl heteroaryl, C 1 -C 6 -alkyl cycloalkyl, C 1 -C 6 -alkyl heterocycloalkyl, C 2 -C 6 -alkenyl cycloalkyl, C 2 -C 6 -alkenyl heterocycloalkyl, C 2 -C 6 -alkynyl cycloalkyl, C 2 -C 6 -alkynyl heterocycloalkyl, or

R 3 and R 4 may form a ring together with the nitrogen to which they are bound.

6 : Pharmaceutical composition according to claim 5 , wherein R 3 is hydrogen or a methyl or ethyl or propyl group and R 4 is selected from the group consisting of (C 1 -C 6 )-alkyl, C 1 -C 6 alkyl-aryl, C 1 -C 6 -alkyl-heteroaryl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl and 4-8 membered saturated or unsaturated cycloalkyl.

7 : Pharmaceutical composition according to claim 5 , wherein R 3 and R 4 form an optionally substituted piperazine or a piperidine or a morpholine or a pyrrolidine ring together with the nitrogen to which they are bound, whereby said optional substituent is selected from the group consisting of C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkoxy, aryl, heteroaryl, saturated or unsaturated 3-8-membered cycloalkyl, 3-8-membered heterocycloalkyl, (wherein said cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups may be fused with 1-2 further cycloalkyl, heterocycloalkyl, aryl or heteroaryl group), C 1 -C 6 -alkyl aryl, C 1 -C 6 -alkyl heteroaryl, C 2 -C 6 -alkenyl aryl, C 2 -C 6 -alkenyl heteroaryl, C 2 -C 6 -alkynyl aryl, C 2 -C 6 -alkynyl heteroaryl, C 1 -C 6 -alkyl cycloalkyl, C 1 -C 6 -alkyl heterocycloalkyl, C 2 -C 6 -alkenyl cycloalkyl, C 2 -C 6 -alkenyl heterocycloalkyl, C 2 -C 6 -alkynyl cycloalkyl, C 2 -C 6 -alkynyl heterocycloalkyl.

8 : Pharmaceutical composition according to claim 5 wherein L is selected from:

wherein n is 1 to 10, preferably 1 to 6,

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

9 : Pharmaceutical composition according to claim 5 wherein L is selected from:

wherein n is 1 to 10, preferably 1 to 6,

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

10 : Pharmaceutical composition according to claim 1 wherein the JNK inhibitor is selected from the group consisting of:

1,3-benzothiazol-2-yl(2,6-dimethoxy-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-(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-(methylamino)-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-hydroxy-1-piperidinyl)-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)-1-piperazinyl]-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-methylpiperazin-1-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 isopropyl 3-({4-[1,3-benzothiazol-2-yl(cyano)methyl]pyrimidin-2-yl}amino)propanoate

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

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

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

tert-butyl 4-[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-hydroxy-2-phenylethyl)amino]pyrimidin-4-yl}acetonitrile

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

1,3-benzothiazol-2-yl(2-{[2-(3-chlorophenyl)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

1,3-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-[hydroxy(oxido)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-pyrazol-1-yl)propyl]amino}pyrimidin-4-yl)acetonitrile

4-[2-({4-[1,3-benzothiazol-2-yl(cyano)methyl]pyrimidin-2-yl}amino)ethyl]benzenesulfonamide

{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

N-[2-({4-[1,3-benzothiazol-2-yl(cyano)methyl]pyrimidin-2-yl}amino)ethyl]-4-chlorobenzamide

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

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

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

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

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

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

(3H-Benzothiazol-2-ylidene)-{2-[4-(4-[1,2,4]oxadiazol-3-ylmethyl-piperazin-1-ylmethyl)-benzyloxy]-pyrimidin-4-yl}-acetonitrile

4-(4-{4-[(3H-Benzothiazol-2-ylidene)-cyano-methyl]-pyrimidin-2-yloxymethyl}-benzyl)-piperazine-1-carboxylic acid methyl ester

2-[4-(4-{4-[(3H-Benzothiazol-2-ylidene)-cyano-methyl]-pyrimidin-2-yloxymethyl}-benzyl)-piperazin-1-yl]-acetamide

(2-{4-[4-(2-Amino-acetyl)-piperazin-1-ylmethyl]-benzyloxy}-pyrimidin-4-yl)-(3H-benzothiazol-2-ylidene)-acetonitrile

[4-(4-{4-[(3H-Benzothiazol-2-ylidene)-cyano-methyl]-pyrimidin-2-yloxymethyl}-benzyl)-piperazin-1-yl]-acetic acid methyl ester

(3H-Benzothiazol-2-ylidene)-(2-{4-[4-(2-methoxy-ethyl)-piperazin-1-ylmethyl]-benzyloxy}-pyrimidin-4-yl)-acetonitrile

4-(4-{4-[(3H-Benzothiazol-2-ylidene)-cyano-methyl]-pyrimidin-2-yloxymethyl}-benzyl)-piperazine-1-carboxylic acid dimethylamide

(3H-Benzothiazol-2-ylidene)-{2-[4-(4-ethyl-piperazin-1-ylmethyl)-benzyloxy]-pyrimidin-4-yl}-acetonitrile

(3H-Benzothiazol-2-ylidene)-(2-{4-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzyloxy}-pyrimidin-4-yl)-acetonitrile

11 : Pharmaceutical composition according to claim 1 , wherein the JNK inhibitor is a compound of formula II

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

Y is an 4-12-membered saturated cyclic or bicyclic alkyl containing at least one nitrogen atom, whereby one nitrogen atom within said ring is forming a bond with the sulfonyl group of formula I thus providing the sulfonamide;

R 1 is selected from the group comprising or consisting of hydrogen, C 1 -C 6 -alkoxy, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, amino, sulfanyl, sulfinyl, sulfonyl, sulfonyloxy, sulfonamide, acylamino, aminocarbonyl, C 1 -C 6 alkoxycarbonyl, aryl, heteroaryl, carboxy, cyano, halogen, hydroxy, nitro, hydrazides;

R 2 is selected from the group comprising or consisting of hydrogen, COOR 3 , CONR 3 R 3′ , OH, a C 1 -C 4 alkyl substituted with an OH or amino group, a hydrazido carbonyl group, a sulfate, a sulfonate, an amine or an ammonium salt;

with R 3 , R 3′ being substituents independently selected from the group consisting of H, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, aryl, heteroaryl, aryl-C 1 -C 6 -alkyl, heteroaryl-C 1 -C 6 -alkyl

12 : Pharmaceutical composition according to claim 11 , wherein R 1 is selected from the group consisting of hydrogen, halogen, C 1 -C 6 alkyl or C 1 -C 6 alkoxy.

13 : Pharmaceutical composition according to claim 11 , wherein Y is either of the cyclic amines having the general formulae

whereby, L 1 and L 2 are independently selected from each other from the group consisting of C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 4 -C 8 -cycloalkyl optionally containing 1-3 heteroatoms and optionally fused with aryl or heteroaryl; or L 1 and L 2 are independently selected from the group consisting of aryl, heteroaryl, aryl-C 1 -C 6 -alkyl, heteroaryl-C 1 -C 6 -alkyl, —C(O)—OR 3 , —C(O)—R 3 , —C(O)—NR 3′ R 3 , —NR 3′ R 3 , —NR 3′ C(O)R 3 , —NR 3′ C(O)NR 3′ R 3 , —(SO)R 3 , —(SO 2 )R 3 , —NSO 2 R 3 , —SO 2 NR 3′ R 3 ,

with R 3 , R 3′ being substituents independently selected from the group consisting of H, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, aryl, heteroaryl, aryl-C 1 -C 6 -alkyl, heteroaryl-C 1 -C 6 -alkyl;

or L 1 and L 2 taken together form a 4-8-membered, saturated cyclic alkyl or heteroalkyl group; and

R 6 is selected from the group consisting of hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, OH, halogen, nitro, cyano, sulfonyl, oxo (═O), and

n′ is an integer from 0 to 4, preferably 1 or 2.

14 : Pharmaceutical composition according to claim 13 , wherein R 6 is H, L 2 is H, L 1 is —NR 3′ R 3 ; where at least one of R 3′ and R 3 is not hydrogen, but a substituent selected from the group consisting of straight or branched C 4 -C 18 -alkyl, aryl-C 1 -C 18 -alkyl, heteroaryl-C 2 -C 18 -alkyl, C 1 -C 14 -alkyl substituted with a C 3 -C 12 -cycloalkyl or -bicyclo or -tricyloalkyl, and whereby said alkyl chain may contain 1-3 O or S atoms.

15 : Pharmaceutical composition according to claim 14 , wherein L 1 is —NHR 3 ; where R 3 is a straight or branched C 4 -C 12 -alkyl, preferably a C 6 -C 12 -alkyl, optionally substituted with a cyclohexyl group or a benzyl group.

16 : Pharmaceutical composition according to claim 15 , wherein Y is a piperidine group

L 1 is —NHR 3 ; where R 3 is a straight or branched C 4 -C 12 -alkyl, preferably a C 8 -C 12 -alkyl, or a benzyl group.

17 : Pharmaceutical composition according to claim 11 wherein the JNK inhibitor is selected from the group consisting of:

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

4-chloro-N-[(5-{[4-(butylamino)piperidin-1-yl]sulfonyl}thien-2-yl)methyl]benzamide acetonitrile

18 : Pharmaceutical composition according to any of claim 1 , wherein the cyclosporin is cyclosporin A.

19 : Pharmaceutical composition according to claim 1 , wherein the molar ratio of the cyclosporin and the JNK inhibitor is 1/1 to 1/100.

20 : Pharmaceutical composition according to claim 1 , wherein the dose of cyclosporin is between 1 and 100 mg/kg.

21 : Pharmaceutical composition according to claim 1 , further comprising a pharmaceutically acceptable excipient.

22 : A composition according to any of claim 1 , for use as a medicament.

23 : A method of using the composition according to claim 1 , for the manufacture of a medicament for the treatment of a neuronal disorder, an autoimmune disease, an inflammatory disorder, cancer or a cardiovascular disease.