6-cycloamino-3-(pyridazin-4-yl)imidazo[1,2-b]pyridazine and derivatives and pharmaceutical compositions comprising the same

1. A compound of formula (I):

in which:

R 2 represents an aryl group optionally substituted with one or more substituents chosen from halogen atoms and the groups C 1-6 alkyl, C 1-6 alkyloxy, C 1-6 alkylthio, C 1-6 fluoroalkyl, C 1-6 -fluoroalkyloxy and —CN;

A represents a group C 1-7 -alkylene optionally substituted with one or two groups R a ;

B represents a group C 1-7 -alkylene optionally substituted with a group R b ;

L represents either a nitrogen atom substituted with a group R c or R d , or a carbon atom substituted with a group R e1 and a group R d or two groups R e2 ;

the carbon atoms of A and B being optionally substituted with one or more groups R f , which may be identical to or different from one another;

R a , R b and R c are defined such that:

two groups R a may together form a group C 1-6 -alkylene;

R a and R b may together form a bond or a group C 1-6 -alkylene;

R a and R c may together form a bond or a group C 1-6 -alkylene;

R b and R c may together form a bond or a group C 1-6 -alkylene;

R d represents a group chosen from a hydrogen atom and the groups C 1-6 -alkyl, C 3-7 -cycloalkyl, C 3-7 -cycloalkyl-C 1-6 alkyl, hydroxy-C 1-6 -alkyl, C 1-6 -alkyloxy-C 1-6 -alkyl, C 1-6 -alkylthio-C 1-6 -alkyl, C 1-6 -fluoroalkyl and benzyl;

R e1 represents a group —NR 4 R 5 or a cyclic monoamine which is pyrrolidinyl optionally substituted with one or more substituents chosen from a fluorine atom and the groups C 1-6 -alkyl, C 1-6 -alkyloxy and hydroxyl;

two groups R e2 form, with the carbon atom that bears them, a cyclic monoamine optionally having an oxygen ring atom thereon selected from azetidine, pyrrolidine, piperidine and morpholine group, this cyclic monoamine being optionally substituted with one or more groups R f , which may be identical to or different from one another;

R f represents a group C 1-6 -alkyl, C 3-7 -cycloalkyl, C 3-7 -cycloalkyl-C 1-6 -alkyl, C 1-6 -alkyloxy-C 1-6 -alkyl, hydroxy-C 1-6 -alkyl, C 1-6 -fluoroalkyl or benzyl;

R 4 and R 5 represent, independently of each other, a hydrogen atom or a group C 1-6 -alkyl, C 3-7 -cycloalkyl or C 3-7 -cycloalkyl-C 1-6 -alkyl; and

R 7 and R 8 represent, independently of each other, a hydrogen atom or a group C 1-6 -alkyl;

or a salt thereof.

2. The compound of formula (I) according to claim 1 , wherein R 2 represents a phenyl optionally substituted with one or more halogen atoms or groups C 1-6 alkyl or C 1-6 fluoroalkyl.

3. The compound of formula (I) according to claim 1 , wherein R 2 represents a phenyl, 3-fluorophenyl, 4-fluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 3,5-dichlorophenyl, 3,5-dimethylphenyl or 3,5-di(trifluoromethyl)phenyl.

4. The compound of formula (I) according to claim 1 , wherein R 7 and R 8 represent, independently of each other, a hydrogen atom or a methyl group.

5. The compound of formula (I) according to claim 1 , wherein:

A represents a group C 1-7 -alkylene optionally substituted with one or two groups R a ;

B represents a group C 1-7 -alkylene optionally substituted with a group R b ;

L represents a nitrogen atom substituted with a group R c or R d ;

the carbon atoms of A and of B being optionally substituted with one or more groups R f , which may be identical to or different from each other;

R a and R b may together form a bond or a group C 1-6 -alkylene,

R a and R c may together form a bond or a group C 1-6 -alkylene;

R b and R c may together form a bond or a group C 1-6 -alkylene,

R d represents a substituent chosen from a group C 1-6 -alkyl, C 3-7 -cycloalkyl, C 3-7 -cycloalkyl-C 1-6 -alkyl, hydroxy-C 1-6 -alkyl, C 1-6 -alkyloxy-C 1-6 -alkyl, C 1-6 -fluoroalkyl or benzyl; and

R f represents a group C 1-6 -alkyl, hydroxy-C 1-6 -alkyl, C 1-6 -alkyloxy-C 1-6 -alkyl or C 1-6 -fluoroalkyl.

6. The compound of formula (I) according to claim 1 , wherein:

the cyclic amine formed by —N-A-L-B— represents a piperazin-1-yl, 3-(R)-methylpiperazin-1-yl, 3,3-dimethylpiperazin-1-yl, cis-3,5-dimethylpiperazin-1-yl, 4-methylpiperazin-1-yl, 4-(2-hydroxyethyl)piperazin-1-yl, 4-(2-fluoroethyl)piperazin-1-yl, 4-isopropylpiperazin-1-yl, 4-cyclopropylpiperazin-1-yl, 4-benzylpiperazin-1-yl, 4-(2-hydroxy-2-methylpropyl)piperazin-1-yl, 4-(3-hydroxy-3-methylbutyl)piperazin-1-yl, (S)-octahydropyrrolo[1,2-a]pyrazin-2-yl, (1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl, 5-(2-hydroxyethyl)-(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl, 5-isopropyl-(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl, hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl, 5-methyl-hexahydropyrrolo[3,4-c]pyrrol-2-(1H)-yl, 5-(2-isopropyl)hexahydropyrrolo[3,4-c]pyrrol-2-(1H)-yl, 5-(2-hydroxyethyl)hexahydropyrrolo[3,4-c]pyrrol-2-(1H)-yl, 5-(benzyl)hexahydro-pyrrolo[3,4-c]pyrrol-2-(1H)-yl, 3-(hydroxymethyl)piperazin-1-yl or 3-fluoromethylpiperazin-1-yl group.

7. The compound of formula (I) according to claim 1 , wherein:

A represents a group C 1-7 -alkylene;

B represents a group C 1-7 -alkylene;

L represents a carbon atom substituted with two groups R e2 ;

the carbon atoms of A and of B being optionally substituted with one or more groups R f , which may be identical to or different from each other;

R f represents a group C 1-6 -alkyl; and

two R e2 groups form, with the carbon atom which bears them, an azetidine, pyrrolidine, piperidine or morpholine group.

8. The compound of formula (I) according to claim 1 , wherein the cyclic amine formed by N-A-L-B— represents a 2,9-diazaspiro[5.5]undec-3-yl or 1-oxa-4,9-diazaspiro[5.5]undec-9-yl group.

9. The compound of formula (I) according to claim 1 , wherein:

A represents a group C 1-7 -alkylene;

B represents a group C 1-7 -alkylene;

L represents a carbon atom substituted with a group R e1 and a group R d ;

R d represents a hydrogen atom;

R e1 represents a group —NR 4 R 5 or pyrrolidinyl; and

R 4 and R 5 represent, independently of each other, a hydrogen atom or a group C 1-6 -alkyl, C 3-7 -cycloalkyl or C 3-7 -cycloalkyl-C 1-6 -alkyl.

10. The compound of formula (I) according to claim 1 , wherein:

the cyclic amine formed by —N-A-L-B— represents a (R,S)-3-[pyrrolidin-1-yl]-pyrrolidin-1-yl or 4-(pyrrolidin-1-yl)piperidin-1-yl group.

11. The compound of formula (I) according to claim 1 , wherein:

R 2 represents a phenyl, 3-fluorophenyl, 4-fluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 3,5-dichlorophenyl, 3,5-dimethylphenyl or 3,5-di(trifluoromethyl)phenyl group; the cyclic amine formed by —N-A-L-B— represents a piperazin-1-yl, 3-(R)-methylpiperazin-1-yl, 3,3-dimethylpiperazin-1-yl, cis-3,5-dimethylpiperazin-1-yl, 4-methylpiperazin-1-yl, 4-(2-hydroxyethyl)piperazin-1-yl, 4-(2-fluoroethyl)piperazin-1-yl, 4-isopropylpiperazin-1-yl, 4-cyclopropylpiperazin-1-yl, 4-benzylpiperazin-1-yl, 4-(2-hydroxy-2-methylpropyl)piperazin-1-yl, 4-(3-hydroxy-3-methylbutyl)piperazin-1-yl, (S)-octahydropyrrolo[1,2-c]pyrazin-2-yl, (1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl, 5-(2-hydroxyethyl)-(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl, 5-isopropyl-(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl, hexahydropyrrolo[3,4-c]pyrrol-2-(1H)-yl, 5-methyl-hexahydropyrrolo[3,4-c]pyrrol-2-(1H)-yl, 5-(2-isopropyl)hexahydropyrrolo-[3,4-c]pyrrol-2-(1H)-yl, 5-(2-hydroxyethyl)hexahydropyrrolo[3,4-c]pyrrol-2-(1H)-yl, 5-(benz-yl)hexahydro-pyrrolo[3,4-c]pyrrol-2-(1H)-yl, 3-(hydroxymethyl)piperazin-1-yl or 3-fluoromethylpiperazin-1-yl group; and

R 7 and R 8 represent, independently of each other, a hydrogen atom or a methyl group.

12. The compound of formula (I) according to claim 1 , wherein:

R 2 represents a 4-fluorophenyl, 3,5-difluorophenyl, 3,5-dichlorophenyl, 3,5-dimethylphenyl or 3,5-di(trifluoromethyl)phenyl group;

the cyclic amine formed by —N-A-L-B— represents a (R,S)-3-[pyrrolidin-1-yl]pyrrolidin-1-yl or 4-(pyrrolidin-1-yl)piperidin-1-yl group; and

R 7 and R 8 represent a hydrogen atom.

13. The compound of formula (I) according to claim 1 , which is selected from the group consisting of:

2-(4-fluorophenyl)-6-piperazin-1-yl-3-pyridazin-4-yl-imidazo[1,2-b]pyridazine;

2-(4-fluorophenyl)-6-((R)-3-methylpiperazin-1-yl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazine;

6-(3,3-dimethylpiperazin-1-yl)-2-(4-fluorophenyl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazine;

6-(cis-3,5-dimethylpiperazin-1-yl)-2-(4-fluorophenyl)-3-pyridazin-4-yl-imidazo-[1,2-b]pyridazine;

2-(4-fluorophenyl)-6-(4-methylpiperazin-1-yl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazine;

2-{4-[2-(4-fluorophenyl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazin-6-yl]piperazin-1-yl}-ethanol;

6-[4-(2-fluoroethyl)piperazin-1-yl]-2-phenyl-3-pyridazin-4-yl-imidazo[1,2-b]pyridazine;

6-[4-(2-fluoroethyl)piperazin-1-yl]-2-(4-fluorophenyl)-3-pyridazin-4-yl-imidazo-[1,2-b]pyridazine;

6-(4-isopropylpiperazin-1-yl)-2-phenyl-3-pyridazin-4-yl-imidazo[1,2-b]pyridazine;

2-(3-fluorophenyl)-6-(4-isopropylpiperazin-1-yl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazine;

2-(4-fluorophenyl)-6-(4-isopropylpiperazin-1-yl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazine;

2-(4-fluorophenyl)-6-(4-isopropylpiperazin-1-yl)-7,8-dimethyl-3-pyridazin-4-yl-imidazo-[1,2-b]pyridazine;

2-(3,5-dimethylphenyl)-6-(4-isopropylpiperazin-1-yl)-3-pyridazin-4-yl-imidazo-[1,2-b]pyridazine;

2-(3,4-difluorophenyl)-6-(4-isopropylpiperazin-1-yl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazine,

2-(3,5-difluorophenyl)-6-(4-isopropylpiperazin-1-yl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazine;

2-(3,5-dichlorophenyl)-6-(4-isopropylpiperazin-1-yl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazine;

2-(3,5-di(trifluoromethyl)phenyl)-6-(4-isopropylpiperazin-1-yl)-3-pyridazin-4-yl-imidazo-[1,2-b]pyridazine;

6-(4-cyclopropylpiperazin-1-yl)-2-(4-fluorophenyl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazine;

6-(4-benzylpiperazin-1-yl)-2-(4-fluorophenyl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazine;

1-{4-[2-(4-fluorophenyl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazin-6-yl]piperazin-1-yl}-2-methylpropan-2-ol;

4-{4-[2-(4-fluorophenyl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazin-6-yl]piperazin-1-yl}-2-methylbutan-2-ol;

2-(4-fluorophenyl)-6-(S)-hexahydropyrrolo[1,2-a]pyrazin-2-yl-3-pyridazin-4-yl-imidazo-[1,2-b]pyridazine;

6-((1S,4S)-2,5-diazabicyclo[2.2. 1]kept-2-yl)-2-(4-fluorophenyl)-3-pyridazin-4-yl-imidazo-[1,2-b]pyridazine;

2-{5-[2-(4-fluorophenyl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazin-6-yl]-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl}-ethanol;

2-(4-fluorophenyl)-6-(5-isopropyl-(1S,4S)-2,5-diazabicyclo[2.2.1]kept-2-yl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazine;

2-(4-fluorophenyl)-6-hexahydropyrrolo[3,4-c]pyrrol-2-(1H)-yl-3-pyridazin-4-yl-imidazo-[1,2-b]pyridazine;

2-(4-fluorophenyl)-6-(5-methylhexahydropyrrolo[3,4-c]pyrrol-2-(1H)-yl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazine;

2-(4-fluorophenyl)-6-(5-isopropylhexahydropyrrolo[3,4-c]pyrrol-2-(1H)-yl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazine;

2-{(5-[2-(4-fluorophenyl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazin-6-yl]-hexahydropyrrolo-[3,4-c]pyrrol-2-(1H)-yl}-ethanol;

2-(4-fluorophenyl)-6-(5-benzylhexahydropyrrolo[3,4-c]pyrrol-2-(1H)-yl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazine;

9-[2-(4-fluorophenyl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazin-6-yl]-2,9-diaza-spiro[5.5]undecane;

9-[2-(4-fluorophenyl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazin-6-yl]-1-oxa-4,9-diaza-spiro[5.5]undecane;

6-[1,3′]bipyrrolidinyl-1′-yl-2-(4-fluorophenyl)-3-pyridazin-4-yl-imidazo[1,2-b]pyridazine;

2-(4-fluorophenyl)-3-pyridazin-4-yl-6-(4-pyrrolidin-1-yl-piperidin-1-yl)-imidazo-[1,2-b]pyridazine;

2-(3,5-dimethylphenyl)-3-pyridazin-4-yl-6-(4-pyrrolidin-1-yl-piperidin-1-yl)-imidazo-[1,2-b]pyridazine;

2-(3,5-difluorophenyl)-3-pyridazin-4-yl-6-(4-pyrrolidin-1-yl-piperidin-1-yl)-imidazo-[1,2-b]pyridazine;

2-(3,5-dichlorophenyl)-3-pyridazin-4-yl-6-(4-pyrrolidin-1-yl-piperidin-1-yl)-imidazo-[1,2-b]pyridazine;

2-(3,5-di(trifluoromethyl)phenyl)-3-pyridazin-4-yl-6-(4-pyrrolidin-1-yl-piperidin-1-yl)-imidazo[1,2-b]pyridazine;

(+/−)-{4-[2-(4-fluorophenyl)-3-pyridazin-4-ylimidazo[1,2-b]pyridazin-6-yl]piperazin-2-yl}methanol;

(+/−)-6-(3-fluoromethylpiperazin-1-yl)-2-(4-fluorophenyl)-3-pyridazin-4-ylimidazo-[1,2-b]pyridazine;

6-(5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-2-phenyl-3-pyridazin-4-ylimidazo-[1,2-b]pyridazine;

2-(3-fluorophenyl)-6-(5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-3-pyridazin-4-ylimidazo[1,2-b]pyridazine;

2-(4-fluorophenyl)-7-methyl-6-(5-methylhexahydropyrrolo[3,4-c]pyrrol-2-(1H)-yl)-3-pyridazin-4-ylimidazo[1,2-b]pyridazine;

2-(4-fluorophenyl)-8-methyl-6-(5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-3-pyridazin-4-ylimidazo[1,2-b]pyridazine; and

2-(3,4-difluorophenyl)-6-(5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-3-pyridazin-4-ylimidazo[1,2-b]pyridazine:

or a pharmaceutically acceptable salt thereof.

14. A pharmaceutical composition comprising a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient.

15. A pharmaceutical composition comprising a compound of formula (I) according to claim 13 or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient.