Compounds derived from indole and pharmaceutical compositions containing them
The present invention relates to a compound derived from indole corresponding to the following formula II: wherein X represents N, CR8 or N + R8, wherein R8 represents a hydrogen atom, a hydroxyl or alkyl or methoxy group optionally substituted with a phenyl group; R2, R3 and R4 independently represent a hydrogen atom or a halogen atom or an optionally substituted alkyl, amine, alkene, ester, sulfonamide, ether or benzyl group; R5 represents a hydrogen atom or an optionally substituted, saturated or unsaturated alkyl group, amine, benzyl group; R6 represents an optionally substituted C1-C3 alkyl group; R7 represents a hydrogen atom or an optionally substituted C1-C3 alkyl group and R7 is absent when the ring A is in the b position, and A represents a ring; R9 and R10 represent together a carbon bond or independently represent an R11 OR11, SR11 group; wherein R11 represents a hydrogen atom, an optionally substituted, saturated or unsaturated, C1-C3 alkyl group, which may contain one or more sulfur, oxygen or nitrogen atoms; pharmaceutically acceptable salts of said compounds, their isomers and/or a mixture thereof; pharmaceutical composition comprising such a compound; the use of such a compound for preparing a drug intended to treat a genetic disease resulting from at least one mutation causing the occurrence of an early termination codon.
1. A compound corresponding to the following formula II:
wherein:
X represents N or the anhydrobase N + R8, wherein R8 represents a hydrogen atom, a hydroxyl or alkyl or methoxy group optionally substituted with a phenyl group,
R2, R3, and R4 independently represent a hydrogen atom or a halogen atom or an optionally substituted alkyl, amino group, alkene, ester, sulfonamide, ether, or benzyl group,
R5 represents a hydrogen atom or an optionally substituted, saturated or unsaturated alkyl group, amino group, or benzyl group,
R6 represents an optionally substituted C1-C3 alkyl group,
R7 represents a hydrogen atom or an optionally substituted C1-C3 alkyl group, and R7 is absent when A is in position b, and
R9 and R10 independently represent a hydrogen atom, a R11, OR11, or SR11 group, wherein R11 independently represents a hydrogen atom, an optionally substituted, saturated or unsaturated, C1-C3 alkyl group, which may contain one or more sulfur, oxygen, or nitrogen atoms; and
A represents a ring group which, when A is in the a or b position, corresponds to:
wherein:
R1 represents a hydrogen, oxygen, or halogen atom, or an optionally substituted, linear or branched and/or unsaturated alkyl group,
R13 represents a hydrogen atom or C1-C4 alkyl group optionally substituted, and
Z represents a R1 group;
pharmaceutically acceptable salts of said compounds, their isomers and/or a mixture thereof.
2. The compound according to claim 1 , of the following formula Ia:
wherein R2, R3, R4, R5, R6, R7, X, and the ring A are as defined in claim 1 .
3. The compound according to claim 1 , wherein R2, R3, and R4 represent independently of each other, a hydrogen atom or a halogen atom or an optionally substituted alkyl, amino, alkene, or benzyl group.
4. The compound according to claim 1 , wherein R2, R3, and R4 represent independently of each other, a hydrogen atom or a halogen atom or a C1-C4 alkyl group.
5. The compound according to claim 4 , wherein R2, R3, and/or R4 represent independently of each other, a halogen atom selected from the group consisting of F, Cl, Br, and I.
6. The compound according to claim 1 , wherein R5 represents a hydrogen atom or a saturated or unsaturated alkyl group.
7. The compound according to claim 1 , wherein R7 represents a methyl or ethyl group.
8. The compound according to claim 1 , wherein R1 represents a hydrogen, oxygen, or halogen atom.
9. The compound according to claim 1 , wherein the ring A is in position a.
10. The compound according to claim 1 , wherein the ring A represents:
wherein R1 and R13 are as defined in claim 1 .
11. The compound according to claim 10 , wherein A is selected from the group consisting of:
12. The compound according to claim 1 , wherein the compound is selected from the group consisting of:
5,8-dimethyl-6-(pyridin-2-ylamino)-2H-isoquinolin-1-one;
5,8-dimethyl-6-(3-methoxy-pyridin-2-ylamino)-isoquinolin-1-one; and
5,8-dimethyl-6-(5-methyl-pyridin-2-ylamino)-isoquinoline.
13. The compound according to claim 12 , wherein the compound is 5,8-dimethyl-6-(pyridin-2-ylamino)-2H-isoquinolin-1-one.
14. A pharmaceutical composition comprising at least one indole derivative according to claim 1 and optionally a pharmaceutically acceptable support.
15. A method for treating Duchenne's muscular dystrophy (DMD) comprising the administration of an effective amount of a compound of claim 1 .
16. The method according to claim 15 , wherein said compound corresponds to the following formula I:
wherein:
R2, R3, R4, R5, R6, R7, X, and the ring A are as defined in claim 1 .
17. The method according to claim 15 , wherein R9 and R10 both represent a hydrogen atom.
18. The method according to claim 15 , wherein the ring A is in the a position.
19. The method according to claim 15 , wherein the compound is selected from the group consisting of:
5,8-dimethyl-6-(pyridin-2-ylamino)-2H-isoquinolin-1-one;
5,8-dimethyl-6-(3-methoxy-pyridin-2-ylamino)-isoquinolin-1-one; and
5,8-dimethyl-6-(5-methyl-pyridin-2-ylamino)-isoquinoline.