Compounds with tubulin polymerisation inhibitory activity and immunomodulatory properties
The present invention relates to the Compound of following formula (I): or a pharmaceutically acceptable salt thereof. The present invention also relates to a pharmaceutical composition containing such a compound and a method for preparing such a compound.
1. A compound of following formula (I):
in which:
X represents a —CH— group or a nitrogen atom,
R 1 represents a hydrogen atom, a halogen atom, a (C 1 -C 6 )alkyl group, a —CN group or a —CF 3 group,
R 2 represents a hydrogen atom, a (C 1 -C 6 )alkyl group, an aryl-(C 1 -C 6 )alkyl group, or a —COR 21 group with R 21 representing a (C 1 -C 6 )alkyl group or an aryl group,
R 3 represents a (C 1 -C 6 )alkyl group, an aryl-(C 1 -C 6 )alkyl group or a —COR 31 group with R 31 representing a (C 1 -C 6 )alkyl group or an aryl group,
R 41 , R 42 , R 43 and R 44 represent independently of each other a hydrogen atom; a halogen atom; —OR 45 ; —SR 45 ; —NR 45 R 46 ; —NO 2 ; or a (C 1 -C 6 )alkyl group optionally substituted by one or more substituents selected from among a halogen atom, —OR 45 , —SR 45 , —NR 45 R 46 and —NO 2 , with R 45 and R 46 representing independently of each other a hydrogen atom, a (C 1 -C 6 )alkyl group, a —CF 3 group or a —COR 47 group with R 47 representing a (C 1 -C 6 )alkyl group or an aryl group,
R 5 and R 6 represent a hydrogen atom or form together a —CR 51 ═CR 52 —CR 53 ═CR 54 — chain with R 51 , R 52 , R 53 and R 54 representing independently of each other a hydrogen atom; a halogen atom; —OR 55 ; —SR 55 ; —NR 55 R 56 ; —NO 2 ; or a (C 1 -C 6 )alkyl group optionally substituted by one or more substituents selected from among a halogen atom, —OR 55 , —SR 55 , —NR 55 R 56 and —NO 2 , with R 55 and R 56 representing independently of each other a hydrogen atom, a (C 1 -C 6 )alkyl group, a —CF 3 group or a —COR 57 group with R 57 representing a (C 1 -C 6 )alkyl group or an aryl group,
wherein, when X represents a nitrogen atom, R 1 represents a chlorine atom, a —CN group or a —CF 3 group, or R 5 and R 6 form together a —CR 51 ═CR 52 —CR 53 ═CR 54 — chain,
or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 , wherein R 1 represents a chlorine atom, a —CN group or a —CF 3 group.
3. The compound according to claim 1 , wherein R 1 represents a chlorine atom.
4. The compound according to claim 1 , wherein R 3 represents a (C 1 -C 6 )alkyl group and/or R 2 represents a (C 1 -C 6 )alkyl group, or an aryl-(C 1 -C 6 )alkyl group.
5. The compound according to claim 4 , wherein R 3 represents a methyl group.
6. The compound according to claim 4 , wherein R 2 represents a methyl group or a benzyl group.
7. The compound according to claim 4 , wherein R 2 represents a methyl group.
8. The compound according to claim 1 , wherein R 41 , R 42 , R 43 and R 44 represent independently of each other a hydrogen atom, a halogen atom, —OR 45 , —SR 45 , —NR 45 R 46 or —NO 2 with R 45 and R 46 representing independently of each other a hydrogen atom, a CF 3 group or a (C 1 -C 6 )alkyl group.
9. The compound according to claim 8 , wherein R 41 , R 42 , R 43 and R 44 represent independently of each other a hydrogen atom, —OR 45 , —NR 45 R 46 or —NO 2 with R 45 and R 46 representing independently of each other a hydrogen atom, or a (C 1 -C 6 )alkyl group.
10. The compound according to claim 8 , wherein R 41 , R 42 , R 43 and R 44 represent a hydrogen atom.
11. The compound according to claim 1 , having following formula (Ia):
in which X, R 1 , R 2 , R 3 , R 41 , R 42 , R 43 , R 44 , R 51 , R 52 , R 53 and R 54 are as defined in claim 1 ,
or a pharmaceutically acceptable salt thereof.
12. The compound according to claim 1 , wherein R 51 , R 52 , R 53 and R 54 represent independently of each other a hydrogen atom, —OR′, —NR 55 R 56 , —NO 2 or a (C 1 -C 6 )alkyl group optionally substituted by one or more substituents selected from among a halogen atom, a —OR 55 , —SR 55 , —NR 55 R 56 and —NO 2 group, with R 55 and R 56 representing independently of each other a hydrogen atom or a (C 1 -C 6 )alkyl group.
13. The compound according to claim 1 , wherein R 51 , R 52 , R 53 and R 54 represent independently of each other a hydrogen atom, a halogen atom, —OR 55 , —NR 55 R 56 , —NO 2 or a (C 1 -C 6 )alkyl group optionally substituted by a —OR 55 group, with R 55 and R 56 representing independently of each other a hydrogen atom, a CF 3 group or a (C 1 -C 6 )alkyl group.
14. The compound according to claim 1 , wherein R 5 and R 6 represent a hydrogen atom.
15. The compound according to claim 1 , having the following formula (Ib):
16. The compound according to claim 1 , selected from among:
and pharmaceutically acceptable salts thereof.
17. A pharmaceutical composition comprising at least one compound as defined in claim 1 and a pharmaceutically acceptable excipient.