IP Library › Granted Patent US 9,108,971

Granted Patent B2

US 9,108,971 · App. 13/887,845 · Granted Aug 18, 2015

6-cycloamino-3-(pyridazin-4-yl)imidazo[1,2-b]-pyridazine and derivatives thereof preparation and therapeutic application thereof

Inventors: Frederic Puech (Gif sur Yvette, FR); Yulin Chiang (Convent Station, NJ); Sylvain Cote des Combes (Ballancourt-surEssonne, FR); Adrien Tak Li (Fontenay aux Roses, FR); Philippe Burnier (Maisons-Laffitte, FR)

Assignee: SANOFI

C07D487/04 A61K31/5025 C07D519/00

View Patent ↗

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US 9,108,971
App. No.: 13/887,845
Granted: Aug 18, 2015
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

The invention relates to the 6-cycloamino-3-(pyridazin-4-yl)imidazo[1,2-b]pyridazine derivatives corresponding to general formula (I): Wherein R 2 , R 7 , R 8 , A, L and B are as defined herein. Also disclosed are the preparative methods and therapeutic use thereof.

Claims (199)

1. A method for treating a sleep disorder or a circadian rhythm disorder comprising administering to a patient in need of said treatment a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, said compound of formula (I) having the formula

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

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

L represents either a nitrogen atom optionally 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 C 1-6 -alkylene;

R d represents a group chosen from hydrogen atom, 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 —NR 4 R 5 or pyrrolidinyl, said pyrrolidinyl being optionally substituted with one or more substituents chosen from fluorine atom, 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 azetidinyl, pyrrolidinyl, piperidinyl, and morpholinyl, 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 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, hydrogen atom or 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, hydrogen atom or C 1-6 -alkyl;

or a salt thereof, wherein the sleep disorder is selected from primary sleep disorders, sleep disorders related to sleep apnea, sleep disorders related to the circadian rhythm, unspecified dyssomnias and sleep disorders related to medical/psychiatric disorders.

2. The method according to claim 1 , wherein R 2 represents phenyl optionally substituted with one or more halogen atoms or C 1-6 alkyl or C 1-6 fluoroalkyl.

3. The method according to claim 1 , wherein R 2 represents 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 method according to claim 1 , wherein R 7 and R 8 represent, independently of each other, hydrogen or methyl group.

5. The method according to claim 1 , wherein:

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

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

L represents a nitrogen atom substituted with 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 C 1-6 -alkylene;

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

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

R d represents a substituent chosen from 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 and benzyl; and

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

6. The method according to claim 1 , wherein:

the cyclic amine formed by —N-A-L-B— represents 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-diaza-bicyclo[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 method according to claim 1 , wherein:

A represents C 1-7 -alkylene;

B represents C 1-7 -alkylene;

L represents 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 C 1-6 -alkyl; and

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

8. The method according to claim 1 , wherein:

A represents C 1-7 -alkylene;

B represents C 1-7 -alkylene;

L represents a carbon atom substituted with group R e1 and 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, hydrogen atom or a group C 1-6 -alkyl, C 3-7 -cycloalkyl or C 3-7 -cycloalkyl-C 1-6 -alkyl.

9. The method according to claim 1 , wherein:

R 2 represents 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 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-diaza-bicyclo[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; and

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

10. The method according to claim 1 , wherein the compound of Formula (I) is a compound selected from the following group or is a pharmaceutically acceptable salt thereof:

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]hept-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-diazabicyclo[2.2.1]hept-2-yl}-ethanol;

2-(4-fluorophenyl)-6-(5-isopropyl-(1S,4S)-2,5-diazabicyclo[2.2.1]hept-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]-hexahydro-pyrrolo[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.

11. A method for treating a disease related to dependency on cocaine, morphine, nicotine, ethanol and cannabis comprising administering to a patient in need of said treatment a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, said compound of formula (I) having the formula:

in which:

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

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

L represents either a nitrogen atom optionally 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 C 1-6 -alkylene;

R e1 represents —NR 4 R 5 or pyrrolidinyl, said pyrrolidinyl being optionally substituted with one or more substituents chosen from fluorine atom, C 1-6 -alkyl, C 1-6 -alkyloxy and hydroxyl;

R f represents C 1-6 -alkyl, C 3-7 -cycloalkyl, 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, hydrogen atom or 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, hydrogen atom or C 1-6 -alkyl;

or salt thereof.

12. The method according to claim 11 wherein R 2 represents phenyl optionally substituted with one or more halogen atoms or C 1-6 alkyl or C 1-6 fluoroalkyl.

13. The method according to claim 11 wherein R 2 represents phenyl, 3-fluorophenyl, 4-fluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 3,5-dichlorophenyl, 3,5-dimethylphenyl or 3,5-di(trifluoromethyl)phenyl.

14. The method according to claim 11 wherein R 7 and R 8 represent, independently of each other, hydrogen or methyl group.

15. The method according to claim 11 wherein

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

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

L represents a nitrogen atom optionally 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 C 1-6 -alkylene;

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

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

R d represents a substituent chosen from 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 and benzyl; and

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

16. The method according to claim 11 wherein the cyclic amine formed by —N-A-L-B— represents 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-iso-propyl)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.

17. The method according to claim 11 wherein

A represents C 1-7 -alkylene;

B represents 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 C 1-6 -alkyl; and

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

18. The method according to claim 11 wherein

A represents group C 1-7 -alkylene;

B represents group C 1-7 -alkylene;

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

R d represents hydrogen atom;

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

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

19. The method according to claim 11 wherein

R 2 represents 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 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-diaza-bicyclo[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; and

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

20. The method according to claim 11 wherein the compound of Formula I is a compound selected from the following group or is a pharmaceutically acceptable salt thereof: