Derivatives of indole for the treatment of cancer, viral infections and lung diseases

1. A compound of formula (I):

wherein:

X is a C—CN unit;

R 1 and R 1 ′ are selected such that one is H and the other is halogen or (C 1 -C 6 )alkoxy optionally substituted with a carboxylic group or one —NR 11 R 12 unit, wherein R 11 and R 12 are independently H or (C 1 -C 6 )alkyl;

R 2 is:

a radical (C 1 -C 6 )alkoxy, (C 3 -C 6 )cycloalkoxy, aryloxy, (C 1 -C 6 )alkyl-aryloxy, said radical being optionally substituted with halogen, or a radical thio-(C 1 -C 6 )alkyl, thio-aryl, or thio-(C 1 -C 6 )alkyl-aryl, said radical being optionally substituted with halogen or (C 1 -C 6 )alkoxy, or

a —NR 4 R 5 unit, a O—(C 1 -C 6 )alkyl-NR 4 R 5 unit or a S—(C 1 -C 6 )alkyl-NR 4 R 5 unit wherein R 4 and R 5 are independently H or (C 1 -C 6 )alkyl, with the proviso that at least one of R 4 and R 5 is not H, or

a NHCOR 6 unit wherein R 6 is a (C 1 -C 6 )alkyl group,

an aryl optionally substituted with halogen, trifluoromethyl, or (C 1 -C 3 )alkoxy, or

a halogen,

with the proviso that if R 1 or R 1 ′ is (C 1 -C 3 )alkoxy, then R 2 is not a halogen; and

R 3 is hydrogen, (C 1 -C 3 )alkyl, (C i -C 3 )alkoxy or halogen;

or a pharmaceutically acceptable salt.

2. The compound according to claim 1 , wherein the compound has the formula (Ia):

wherein X, R 1 , R 1′ , R 2 , and R 3 , are defined in claim 1 .

3. The compound according to claim 1 , wherein the compound has the formula (Ib):

wherein X, R 1 , R 1′ , R 2 , and R 3 are defined in claim 1 .

4. The compound according to claim 1 , wherein R 1 ′ is H.

5. The compound according to claim 1 , wherein R 1 is a halogen selected from the group consisting of bromine and chlorine.

6. The compound according to claim 1 , wherein R 1 is H.

7. The compound according to claim 1 , wherein R 1 ′ is a halogen selected from the group consisting of bromine, chlorine and fluorine.

8. The compound according to claim 1 , wherein R 2 is:

a radical (C 1 -C 6 )alkoxy, or phenoxy, said radical being optionally substituted with halogen; or

a halogen; or

a R 4 —N—R 5 unit or a S—(C 1 -C 6 )alkyl-NR 4 R 5 unit, wherein R 4 and R 5 are independently H or (C 1 -C 6 )alkyl, with the proviso that at least one of R 4 and R 5 is not H; or

a NHCOR 6 unit wherein R 6 is (C 1 -C 6 )alkyl; or

a radical thio-(C 1 -C 6 )alkyl, thio-aryl, or thio-(C 1 -C 6 )alkyl-aryl, said radical being optionally substituted with halogen or (C 1 -C 6 )alkoxy; or

an aryl group optionally substituted with halogen or trifluoromethyl.

9. The compound according to claim 1 wherein R 2 is:

a radical (C 1 -C 6 )alkoxy selected from the group consisting of methoxy, ethoxy, isopropoxy, and phenoxy, optionally substituted with fluorine or trifluoromethyl; or

a halogen selected from the group consisting of fluorine and chlorine; or

a R 4 —N—R 5 unit or a S—(C 1 -C 6 )alkyl-NR 4 R 5 unit wherein R 4 and R 5 are independently methyl or ethyl; or

a NHCOR 6 unit wherein R 6 is a tent-butyl group; or

a radical selected from the group consisting of thio-methyl, thio-ethyl, thio-benzyl, and thio-phenyl, optionally substituted with fluorine or trifluoromethyl; or

a phenyl group optionally substituted with bromine or trifluoromethvi.

10. The compound according to claim 1 wherein said compound is selected from the group consisting of:

(Z)-3-(2-(5-bromo-1H-indol-3-yl)-2-cyanovinyl)-4-(4-fluorophenoxy)benzonitrile;

(Z)-3-(2-(5-bromo- 1H-indol-3-yl)-2-cyanovinyl)-4-methoxybenzonitrile;

(E)-3-(2-(5-bromo-1H-indol-3-yl)-2-cyanovinyl)-4-methoxybenzonitrile;

(Z)-3-(2-5-bromo- 1H-indol-3-yl)-2-cyanovinyl)-4-(dimethylamino)benzonitrile;

(Z)-3-(2-(5-chloro-1H-indol-3-yl)-2-cyanovinyl)-4-methoxybenzonitrile;

(Z)-3-(2-(5-chloro-1H-indol-3-yl)-2-cyanovinyl)-4-(dimethylamino)benzonitrile;

(Z)-3-(2-(5-chloro-1H-indol-3-yl)-2-cyanovinyl)-4-(ethylthio)benzonitrile;

(Z)-3-(2-(5-chloro-1H-indol-3-yl)-2-cyanovinyl)-4-(trifluoromethoxy)benzonitrile;

(Z)-3-(2-(5-bromo-1H-indol-3-yl)-2-cyanovinyl)-4-(trifluoromethoxy)benzonitrile;

(Z)-3-(2-cyano-2-(6-methoxy-1H-indol-3-yl)vinyl)-4-methoxybenzonitrile;

and their pharmaceutically acceptable salt.

11. The compound according to claim 1 wherein said compound is selected from the group consisting of:

(Z)-3-(2-(5-bromo- 1H-indol-3-yl)-2-cyanovinyl)-4-methoxybenzonitrile;

(E)-3-(2-(5-bromo-1H-indol-3-yl)-2-cyanovinyl)-4-methoxybenzonitrile;

(Z)-3-(2-(5-bromo- 1H-indol-3-yl)-2-cyanovinyl)-4-(dimethylamino)benzonitrile;

(Z)-3-(2-(5-chloro-1H-indol-3-yl)-2-cyanovinyl)-4-(trifluoromethoxy)benzonitrile;

(Z)-3-(2-(5-bromo-1H-indol-3-yl)-2-cyanovinyl)-4-(trifluoromethoxy)benzonitrile;

and their pharmaceutically acceptable salt.

12. A pharmaceutical composition comprising as an active ingredient a compound according to claim 1 and at least one pharmaceutically acceptable vehicle, carrier or auxiliary agent.