2-aminoquinolines

1. A compound of formula (I)

wherein

Z is a bond, —CH 2 —, or —CHCH 3 —;

R 1 is alkyl, hydroxyalkyl, haloalkyl, aminoalkyl, cyanoalkyl, cycloalkyl, allyl, -alkylene-C(O)Oalkyl, -alkylene-C(O)NR i R ii , —C(N—R iii )NR iv R v , —C(═N—R iii )-cycloalkyl, —C(═N—R iii )-alkyl, —O-alkyl, —O-cycloalkyl,

—O-alkylene-O-alkyl, —O-alkylene-S(O) x -alkyl, or —NR a R b , wherein R a and R b are each independently H, alkyl, cycloalkyl, -alkylene-cycloalkyl, allyl, -alkylene-S(O) x -alkyl, —S(O) 2 NR vi R vii , —S(O) 2 -alkyl, —S(O) 2 -cycloalkyl, -alkylene-NR viii R ix , -alkylene-O-alkyl, —C(O)-cycloalkyl, —C(O)alkyl, —C(O)-alkylene-heterocycloalkyl, —C(O)-heterocycloalkyl, —C(O)NR vi R vii , —C(O)-alkylene-NR viii R ix , —C(O)-alkylene-O-alkyl, or heterocycloalkyl;

Ar 1 is phenyl or 5- to 10-membered mono- or bicyclic heteroaryl, each unsubstituted or substituted with one or more alkyl, cycloalkyl, alkoxy, haloalkoxy, haloalkyl, halo, OH, CN, NH 2 , NO 2 , or having two substituents in the ortho-position that form a bridge anellated to the aromatic ring, wherein the bridge is selected from —O—CH 2 CH 2 O—, —O—CHCH 3 CH 2 —, and —O—C(CH 3 ) 2 CH 2 —, and wherein phenyl is not substituted with halo in para-position;

R i , R ii , R vi , R vii , R viii and R ix are each independently H, alkyl, cycloalkyl, or -alkylene-N(alkyl) 2 ;

R iii , R iv , and R v are each independently H, OH or alkoxy;

x is 0, 1 or 2; and

heterocycloalkyl is unsubstituted or substituted with one or more oxo, alkyl, halo, haloalkyl, haloalkoxy, alkoxy, hydroxy, hydroxyalkyl, or CN,

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein

R 1 is alkyl, hydroxyalkyl, haloalkyl, aminoalkyl, cyanoalkyl, cycloalkyl, allyl, -alkylene-C(O)Oalkyl, -alkylene-C(O)NR i R ii , —C(N—R iii )NR iv R v ,

—O-alkyl, —O-cycloalkyl, —O-alkylene-O-alkyl, —O-alkylene-S(O) x -alkyl, or —NR a R b , wherein R a and R b are each independently H, alkyl, cycloalkyl, -alkylene-cycloalkyl, allyl, -alkylene-S(O) x -alkyl, —S(O) 2 NR vi R vii , —S(O) 2 -alkyl, —S(O) 2 -cycloalkyl, -alkylene-NR viii R ix , -alkylene-O-alkyl, or heterocycloalkyl;

R i , R ii , R vi , R vii , R viii and R ix are each independently H, alkyl, cycloalkyl, or -alkylene-N(alkyl) 2 ;

R iii , R iv , and R v are each independently H, OH or alkoxy; and

x is 0, 1 or 2, wherein

heterocycloalkyl is unsubstituted or substituted with one or more oxo, alkyl, halo, haloalkyl, haloalkoxy, alkoxy, hydroxy, hydroxyalkyl, or CN.

3. The compound of claim 2 , wherein

R 1 is alkyl, hydroxyalkyl, allyl, -alkylene-C(O)Oalkyl, -alkylene-C(O)NR i R ii , —C(N—R iii )NR iv R v , —O-alkyl, —O-alkylene-O-alkyl, —O-alkylene-S(O) x -alkyl,

or —NR a R b , wherein R a and R b are each independently H, alkyl, allyl, -alkylene-S(O) x -alkyl, —S(O) 2 NR vi R vii , —S(O) 2 -cycloalkyl, -alkylene-O-alkyl, or heterocycloalkyl;

R i , R ii , R vi and R vii are each independently H, alkyl, cycloalkyl, or alkylene-N(alkyl) 2 ;

R iii , R iv , and R v are each independently H, OH or alkoxy;and

x is 0, 1 or 2, wherein

heterocycloalkyl is unsubstituted or substituted with one or more oxo, alkyl, halo, haloalkyl, haloalkoxy, alkoxy, hydroxy, hydroxyalkyl, or CN.

4. The compound of claim 1 , wherein

R i , R ii , R vi , R vii , R viii and R ix are each independently H, alkyl, cycloalkyl, or -alkylene-N(alkyl) 2 .

5. The compound of claim 4 , wherein R i , R ii , R vi , R vii , R viii and R ix are alkyl.

6. The compound of claim 1 , wherein R iii , R iv , and R v are each independently H, OH or alkoxy.

7. The compound of claim 6 , wherein, R iii , R iv , and R v are each independently H or OH.

8. The compound of claim 1 , wherein heterocycloalkyl is unsubstituted or substituted with one or more oxo, alkyl, halo, haloalkyl, haloalkoxy, alkoxy, hydroxy, hydroxyalkyl, or CN.

9. The compound of claim 8 , wherein the substitutents are oxo or alkyl.

10. The compound of claim 1 , wherein heterocycloalkyl is selected from the group consisting of pyrrolidinyl, tetrahydrothiophenyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, piperazinyl, morpholinyl, and thiomorpholinyl.

11. The compound of claim 10 , wherein heterocycloalkyl is selected from the group consisting of tetrahydropyranyl, tetrahydrothiopyranyl and piperidinyl.

12. The compound of claim 1 , wherein Z is a bond or —CH 2 —.

13. The compound of claim 1 , wherein

Ar 1 is phenyl or a 5- to 10-membered mono- or bicyclic heteroaryl, each unsubstituted or substituted with one or more alkyl, cycloalkyl, alkoxy, haloalkoxy, haloalkyl, OH, CN, NH 2 , NO 2 , or having two substituents in the ortho-position that form a bridge anellated to the aromatic ring, wherein the bridge is selected from —O—CH 2 CH 2 O—, —O—CHCH 3 CH 2 —, and —O—C(CH 3 ) 2 CH 2 —.

14. The compound of claim 1 wherein

Ar 1 is phenyl or a 5- to 10-membered mono- or bicyclic heteroaryl, each unsubstituted or substituted with one or more alkyl, cycloalkyl, alkoxy, haloalkoxy, or having two substituents in the ortho-position that form a bridge anellated to the aromatic ring, wherein the bridge is selected from —O—CH 2 CH 2 O—, —O—CHCH 3 CH 2 —, and —O—C(CH 3 ) 2 CH 2 —.

15. The compound of claim 1 , wherein

Ar 1 is phenyl or a 5- to 10-membered mono- or bicyclic heteroaryl,

wherein phenyl is unsubstituted or substituted with one or more alkyl, cycloalkyl, alkoxy, haloalkoxy, haloalkyl, OH, CN, NH 2 , NO 2 , or having two substituents in the ortho-position that form a bridge anellated to the aromatic ring, wherein the bridge is selected from —O—CH 2 CH 2 O—, —O—CHCH 3 CH 2 —, and —O—C(CH 3 ) 2 CH 2 —, and

wherein the 5- to 10-membered mono- or bicyclic heteroaryl is unsubstituted or substituted with one or more alkyl, cycloalkyl, alkoxy, haloalkoxy, halo, haloalkyl, OH, CN, NH 2 , or NO 2 .

16. The compound of claim 1 , wherein

Ar 1 is phenyl or a 5- to 10-membered mono- or bicyclic heteroaryl,

wherein phenyl is unsubstituted or substituted with one or more alkyl, cycloalkyl, alkoxy, haloalkoxy, or having two substituents in the ortho-position that form a bridge anellated to the aromatic ring, wherein the bridge is selected from —O—CH 2 CH 2 O—, —O—CHCH 3 CH 2 —, and —O—C(CH 3 ) 2 CH 2 —, and

wherein the 5- to 10-membered mono- or bicyclic heteroaryl is unsubstituted or substituted with one or more alkyl, cycloalkyl, alkoxy, or haloalkoxy.

17. The compound of claim 16 , wherein the 5- to 10-membered mono- or bicyclic heteroaryl is selected from the group consisting of thiophenyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, [1,2,4]oxadiazolyl, [1,3,4]oxadiazolyl, [1,2,4]triazolyl, [1,2,3]triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, indolyl, benzofuranyl and benzothiofuranyl.

18. The compound of claim 17 , wherein heteroaryl is selected from the group consisting of furanyl and benzofuranyl.

19. The compound of claim 1 , wherein Ar 1 is selected from the group consisting of 5-methyl-furan-2-yl, 2-methoxy-phenyl, 2-methyl-benzofuran-7-yl, 2-trifluoromethoxy-phenyl, 2-methyl-2,3-dihydro-benzofuran-7-yl, 2,2-dimethyl-2,3-dihydro-benzofuran-7-yl, and 3-cyclopropyl-phenyl.

20. The compound of claim 1 , selected from the group consisting of

N 2 -(2-Methoxy-benzyl)-quinoline-2,5-diamine;

N 2 -(5-Methyl-furan-2-ylmethyl)-quinoline-2,5-diamine;

N 2 -(5-Methyl-furan-2-ylmethyl)-N 5 -(1-methyl-piperidin-4-yl)-quinoline-2,5-diamine;

N 5 -(2-Methoxy-ethyl)-N 2 -(5-methyl-furan-2-ylmethyl)-quinoline-2,5-diamine;

N 5 -Methyl-N 2 -(5-methyl-furan-2-ylmethyl)-quinoline-2,5-diamine;

N 5 -Allyl-N 2 -(5-methyl-furan-2-ylmethyl)-quinoline-2,5-diamine;

N 2 -(5-Methyl-furan-2-ylmethyl)-N 5 -(tetrahydro-pyran-4-yl)-quinoline-2,5-diamine;

N 5 -(3-Methoxy-propyl)-N 2 -(5-methyl-furan-2-ylmethyl)-quinoline-2,5-diamine;

N 2 -(5-Methyl-furan-2-ylmethyl)-N 5 -(2-methylsulfanyl-ethyl)-quinoline-2,5-diamine; and

N 5 -(2-Methanesulfinyl-ethyl)-N 2 -(5-methyl-furan-2-ylmethyl)-quinoline-2,5-diamine.

21. The compound of claim 1 , selected from the group consisting of

N 5 -(2-Methanesulfonyl-ethyl)-N 2 -(5-methyl-furan-2-ylmethyl)-quinoline-2,5-diamine;

N 2 -(2-Methyl-benzofuran-7-yl)-N 5 -(2-methylsulfanyl-ethyl)-quinoline-2,5-diamine;

N 2 -(2-Trifluoromethoxy-benzyl)-quinoline-2,5-diamine;

N 2 -(2-Methyl-benzofuran-7-yl)-quinoline-2,5-diamine;

N 2 -(2-Methyl-2,3-dihydro-benzofuran-7-yl)-quinoline-2,5-diamine;

N 2 -(2,2-Dimethyl-2,3-dihydro-benzofuran-7-yl)-quinoline-2,5-diamine;

N 2 -(2,2-Dimethyl-2,3-dihydro-benzofuran-7-yl)-N 5 -(1,1-dioxo-hexahydro-1λ 6 -thiopyran-4-yl)-quinoline-2,5-diamine;

N 2 -(3-Cyclopropyl-phenyl)-quinoline-2,5-diamine;

Cyclopropanesulfonic acid {2-[(5-methyl-furan-2-ylmethyl)-amino]-quinolin-5-yl}-amide;

N,N-dimethyl-N′-(2-{[(5-methyl-2-furyl)methyl]amino}quinolin-5-yl)sulfamide; and

N,N-dimethyl-N′-{2-[(2-methyl-2,3-dihydro-1-benzofuran-7-yl)amino]quinolin-5-yl}sulfamide.

22. The compound of claim 1 , selected from the group consisting of

(2-Methoxy-benzyl)-(5-vinyl-quinolin-2-yl)-amine;

(5-Methyl-furan-2-ylmethyl)-(5-vinyl-quinolin-2-yl)-amine;

{2-[(5-Methyl-furan-2-ylmethyl)-amino]-quinolin-5-yl}-methanol;

4-{2-[(5-Methyl-furan-2-ylmethyl)-amino]-quinolin-5-yl}-butyric acid methyl ester;

4-{2-[(5-Methyl-furan-2-ylmethyl)-amino]-quinolin-5-yl}-butan-1-ol;

N,N-Diethyl-4-{2-[(5-methyl-furan-2-ylmethyl)-amino]-quinolin-5-yl}-butyramide;

(2-Methoxy-benzyl)-[5-(2-methoxy-ethoxy)-quinolin-2-yl]-amine;

(2-Methoxy-benzyl)-(5-methoxy-quinolin-2-yl)-amine;

(2-Methoxy-benzyl)-[5-(2-methylsulfanyl-ethoxy)-quinolin-2-yl]-amine;

N-Hydroxy-2-[(5-methyl-furan-2-ylmethyl)-amino]-quinoline-carboxamidine; and

N-Hydroxy-2-(2-methoxy-benzylamino)-quinoline-5-carboxamidine.

23. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula I

wherein

Z is a bond, —CH 2 —, or —CHCH 3 —;

R 1 is alkyl, hydroxyalkyl, haloalkyl, aminoalkyl, cyanoalkyl, cycloalkyl, allyl, -alkylene-C(O)Oalkyl, -alkylene-C(O)NR i R ii , —C(N—R iii )NR iv R v , —C(═N—R iii )-cycloalkyl, —C(═N—R iii )-alkyl, —O-alkyl, —O-cycloalkyl,

—O-alkylene-O-alkyl, —O-alkylene-S(O) x -alkyl, or —NR a R b , wherein R a and R b are each independently H, alkyl, cycloalkyl, -alkylene-cycloalkyl, allyl, -alkylene-S(O) x -alkyl, —S(O) 2 NR vi R vii , —S(O) 2 -alkyl, —S(O) 2 -cycloalkyl, -alkylene-NR viii R ix , -alkylene-O-alkyl, —C(O)-cycloalkyl, —C(O)alkyl, —C(O)-alkylene-heterocycloalkyl, —C(O)-heterocycloalkyl, —C(O)NR vi R vii , —C(O)-alkylene-NR viii R ix , —C(O)-alkylene-O-alkyl, or heterocycloalkyl;

Ar 1 is phenyl or 5- to 10-membered mono- or bicyclic heteroaryl, each unsubstituted or substituted with one or more alkyl, cycloalkyl, alkoxy, haloalkoxy, haloalkyl, halo, OH, CN, NH 2 , NO 2 , or having two substituents in the ortho-position that form a bridge anellated to the aromatic ring, wherein the bridge is selected from —O—CH 2 CH 2 O—, —O—CHCH 3 CH 2 —, and —O—C(CH 3 ) 2 CH 2 —, and wherein phenyl is not substituted with halo in para-position;

R i , R ii , R vi , R vii , R viii and R ix are each independently H, alkyl, cycloalkyl, or -alkylene-N(alkyl) 2 ;

R iii , R iv , and R v are each independently H, OH or alkoxy;

x is 0, 1 or 2; and

heterocycloalkyl is unsubstituted or substituted with one or more oxo, alkyl, halo, haloalkyl, haloalkoxy, alkoxy, hydroxy, hydroxyalkyl, or CN,

or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.