Pyridin-3-yl derivatives as immunomodulating agents

1. A compound of the Formula (I),

wherein

A represents

wherein the asterisks indicate the bond that is linked to the pyridine group of Formula (I);

R 1 represents hydrogen, C 1-4 -alkyl, or chloro;

R 2 represents C 1-5 -alkyl or C 1-4 -alkoxy;

R 3 represents hydrogen, C 1-4 -alkyl, C 1-4 -alkoxy, or halogen;

R 4 represents hydrogen, C 1-4 -alkyl, C 1-4 -alkoxy, halogen, trifluoromethyl or trifluoromethoxy;

R 5 represents 2,3-dihydroxypropyl, di-(hydroxy-C 1-4 -alkyl)-C 1-4 -alkyl, —CH 2 —(CH 2 ) k —NHSO 2 R 53 , —(CH 2 )—CH(OH)—CH 2 —NHSO 2 R 53 , —CH 2 —(CH 2 ) k —NHCOR 54 , —(CH 2 ) n CH(OH)—CH 2 —NHCOR 54 , —CH 2 —(CH 2 ) n —CONR 51 R 52 , —(CH 2 ) n —CH(OH)—CH 2 —NR 51 R 52 , hydroxy, hydroxy-C 2-5 -alkoxy, di-(hydroxy-C 1-4 -alkyl)-C 1-4 -alkoxy, 2,3-dihydroxy-propoxy, 2-hydroxy-3-methoxy-propoxy, —OCH 2 —(CH 2 ) m —NR 51 R 52 , —OCH 2 —CH(OH)—CH 2 —NR 51 R 52 , —OCH 2 —(CH 2 ) m —NHSO 2 R 53 , —OCH 2 —CH(OH)—CH 2 —NHSO 2 R 53 , —OCH 2 —(CH 2 ) m —NHCOR 54 , —OCH 2 —CH(OH)—CH 2 —NHCOR 54 ;

R 51 represents hydrogen, 2-hydroxyethyl, 2-hydroxy-1-hydroxymethyl-ethyl, 2,3-dihydroxypropyl, carboxymethyl, 1-(C 1-5 -alkylcarboxy)methyl, 2-carboxyethyl, or 2-(C 1-5 -alkylcarboxy)ethyl;

R 52 represents hydrogen;

R 53 represents C 1-3 -alkyl, methylamino, ethylamino, or dimethylamino;

R 54 represents hydroxymethyl, hydroxyethyl, aminomethyl, methylaminomethyl, dimethylaminomethyl, aminoethyl, 2-methylamino-ethyl, or 2-dimethylamino-ethyl;

k represents the integer 1, 2, or 3;

m represents the integer 1 or 2;

n represents 0, 1, or 2; and

R 6 represents hydrogen, C 1-4 -alkyl or halogen;

in free or salt form.

2. The compound according to claim 1 , wherein A represents

wherein the asterisks indicate the bond that is linked to the pyridine group of Formula (I), in free or salt form.

3. The compound according to claim 1 , wherein A represents

in free or salt form.

4. The compound according to claim 1 , wherein R 1 represents C 1-4 -alkyl or chloro, in free or salt form.

5. The compound according to claim 1 , wherein R 1 represents C 1-4 -alkyl, in free or salt form.

6. The compound according to claim 1 , wherein R 2 represents C 1-5 -alkyl, in free or salt form.

7. The compound according to claim 1 , wherein R 2 represents n-propyl, or iso-butyl, in free or salt form.

8. The compound according to claim 1 , wherein R 2 represents C 1-4 -alkoxy, in free or salt form.

9. The compound according to claim 1 , wherein R 3 represents hydrogen, in free or salt form.

10. The compound according to claim 1 , wherein R 3 represents hydrogen; and R 4 represents C 1-4 -alkyl, or C 1-4 -alkoxy; and R 6 represents C 1-4 -alkyl, or halogen, in free or salt form.

11. The compound according to claim 1 , wherein R 3 represents hydrogen, R 4 represents C 1-3 -alkyl, or methoxy, and R 6 represents methyl, ethyl, or halogen, in free or salt form.

12. The compound according to claim 1 , wherein R 5 represents 2,3-dihydroxypropyl, di-(hydroxy-C 1-4 -alkyl)-C 1-4 -alkyl, —CH 2 —(CH 2 ) k —NHSO 2 R 53 , —(CH 2 )—CH(OH)—CH 2 —NHSO 2 R 53 , —CH 2 —(CH 2 ) k —NHCOR 54 , —(CH 2 ) n CH(OH)—CH 2 —NHCOR 54 , —CH 2 —(CH 2 ) n —CONR 51 R 52 , —(CH 2 ) n CH(OH)—CH 2 —NR 51 R 52 , hydroxy, hydroxy-C 2-5 -alkoxy, di-(hydroxy-C 1-4 -alkyl)-C 1-4 -alkoxy, 2,3-dihydroxy-propoxy, 2-hydroxy-3-methoxy-propoxy, —OCH 2 —(CH 2 ) m —NR 51 R 52 , —OCH 2 —CH(OH)—CH 2 —NR 51 R 52 , —OCH 2 —(CH 2 ) m —NHSO 2 R 53 , —OCH 2 —CH(OH)—CH 2 —NHSO 2 R 53 , —OCH 2 —(CH 2 ) m —NHCOR 54 , or —OCH 2 —CH(OH)—CH 2 —NHCOR 54 , in free or salt form.

13. The compound according to claim 1 , wherein R 5 represents 2,3-dihydroxypropyl, —CH 2 —(CH 2 ) k —NR 51 R 52 , —CH 2 —(CH 2 ) k —NHCOR 54 , —(CH 2 ) n CH(OH)—CH 2 —NHCOR 54 , —CH 2 —(CH 2 ) n —CONR 51 R 52 , —(CH 2 ) n CH(OH)—CH 2 —NR 51 R 52 , hydroxy-C 2-5 -alkoxy, di-(hydroxy-C 1-4 -alkyl)-C 1-4 -alkoxy, 2,3-dihydroxy-propoxy, 2-hydroxy-3-methoxy-propoxy, —OCH 2 —(CH 2 ) m —NR 51 R 52 , —OCH 2 —CH(OH)—CH 2 —NR 51 R 52 , —OCH 2 —(CH 2 ) m —NHCOR 54 , or —OCH 2 —CH(OH)—CH 2 —NHCOR 54 , in free or salt form.

14. The compound according to claim 1 , wherein R 5 represents hydroxy-C 2-5 -alkoxy, di-(hydroxy-C 1-4 -alkoxy, 2,3-dihydroxy-propoxy, —OCH 2 —(CH 2 ) m —NR 51 R 52 , —OCH 2 —CH(OH)—CH 2 —NR 51 R 52 , —OCH 2 —(CH 2 ) m —NHCOR 54 , or —OCH 2 —CH(OH)—CH 2 —NHCOR 54 , in free or salt form.

15. The compound according to claim 1 , wherein R 5 represents 3-hydroxy-2-hydroxymethyl-propoxy, 2,3-dihydroxy-propoxy, or —OCH 2 —CH(OH)—CH 2 —NHCOR 54 , in free or salt form.

16. The compound according to claim 1 selected from the group consisting of:

3-{4-[5-(5-Chloro-6-isopropoxy-pyridin-3-yl)-[2,4]oxadiazol-3-yl]-2,6-dimethyl-phenoxy}-propane-1,2-diol;

N-(3-{4-[5-(5-Chloro-6-isopropoxy-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide;

3-{4-[5-(6-Isobutyl-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl-phenoxy}-propane-1,2-diol;

2-Hydroxy-N-(2-hydroxy-3-{4-[5-(6-isobutyl-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl-phenoxy}-propyl)-acetamide;

N-(3-{2-Ethyl-4-[5-(6-isobutyl-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide;

3-{4-[5-(5,6-Diisobutyl-pyridin-3-yl)-[2,4]oxadiazol-3-yl]-2,6-dimethyl-phenoxy}-propane-1,2-diol;

N-(3-{4-[5-(5,6-Diethyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide;

2-Hydroxy-N-(2-hydroxy-3-{4-[5-(6-isobutyl-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-3-methyl-phenoxy}-propyl)-acetamide;

N-(3-{2-Chloro-4-[5-(6-isobutyl-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide;

N-(3-{2-Chloro-4-[5-(6-isobutyl-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methoxy-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide;

N—((R)-3-{2-Ethyl-4-[5-(6-isobutyl-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide;

N—((S)-3-{2-Ethyl-4-[3-(6-isobutyl-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide;

N—((S)-3-{2-Ethyl-4-[5-(6-isobutyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide;

(S)-3-{2-Ethyl-4-[5-(5-ethyl-6-isobutyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-propane-1,2-diol;

N-(3-{2-Ethyl-4-[5-(5-ethyl-6-isobutyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide;

(R)-3-{2-Ethyl-4-[5-(6-isopropoxy-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-propane-1,2-diol;

(S)-3-{2-Ethyl-4-[5-(6-isopropoxy-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-propane-1,2-diol;

N—((R)-3-{2-Ethyl-4-[5-(6-isopropoxy-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide;

N—((S)-3-{2-Ethyl-4-[5-(6-isopropoxy-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-2-hydroxy-propyl)-2-hydroxy-acetamide;

3-{2-Ethyl-4-[5-(6-isopropoxy-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-N-(2-hydroxy-ethyl)-propionamide;

(R)-3-{2-Ethyl-4-[3-(6-isopropoxy-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-6-methyl-phenoxy}-propane-1,2-diol;

(S)-3-{2-Ethyl-4-[3-(6-isopropoxy-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-6-methyl-phenoxy}-propane-1,2-diol; and

3-{2-Ethyl-4-[5-(6-isopropoxy-5-methyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-propionic acid,

in free or salt form.

17. A pharmaceutical composition comprising a compound according to claim 1 , in free or pharmaceutically acceptable salt form, and a pharmaceutically acceptable carrier.