Propanolaminotetralines, preparation thereof and compositions containing same

1. A compound of formula (I):

in which:

R 1 and R 2 are independently a hydrogen atom, a benzyl group, a benzoyl group, a —CO(C 1 –C 4 )Alk group, a —CH 2 OCH 3 group, a —COO(C 1 –C 4 )Alk group or a benzyloxycarbonyl group; or

R 1 and R 2 together form a carbonyl, methylene or di(C 1 –C 4 )Alk-methylene group so that R 1 and R 2 taken together with the oxygen and nitrogen atoms to which they are attached and the carbon atoms of the phenyl moiety to which the O and N atoms are attached form heterocyclyl;

R 3 is a hydrogen atom or a (C 1 –C 4 )Alk group;

R 4 is a hydroxyl group, a (C 1 –C 4 )alkoxy group or an —NR 5 R 6 group;

R 5 and R 6 are independently a hydrogen atom; a (C 1 –C 4 )Alk group; an aryl or heteroaryl group, each of which is optionally substituted with an R 7 group; an aralkyl or heteroaralkyl group, each of which is optionally substituted with an R 7 group; or R 5 and R 6 taken together with the nitrogen atom to which they are attached form a saturated or unsaturated 5 to 7 atom cycle;

R 7 is a hydrogen atom, a halogen atom, a hydroxyl group, a (C 1 –C 4 )Alk group, a (C 1 –C 4 )alkoxy group, a —COOH group, a —COO(C 1 –C 4 )Alk group, a —CN group, an —NH(C 1 –C 4 )Alk group or an —N(C 1 –C 4 )Alk 2 group; and

X is O or CH 2 ;

or a salt or solvate thereof.

2. The compound as claimed m claim 1 , in which the tetralin is attached to the amino group at the beta position.

3. The compounds as claimed in claim 2 , in which the two asymmetric carbon atoms marked with an asterisk “*” have the (S) configuration.

4. The compounds as claimed in claim 3 , in which R 5 and R 6 taken together with the nitrogen atom to which they are attached form a piperidino, pyrrolidino, morpholino or thiomorpholino group.

5. The compounds as claimed in claim 4 , in which the substituent —X—CH 2 —CO—R 4 is connected to the 7 position of the tetralin.

6. The compounds as claimed in claim 5 , in which R 5 is a hydrogen atom and R 6 is an aryl or heteroaryl group selected from phenyl, naphthyl and pyridyl.

7. The compounds as claimed in claim 5 , in which R 5 is a hydrogen atom and R 6 is an aralkyl or heteroaralkyl group selected from benzyl, naphthylmethyl and pyridylmethyl.

8. The compound as claimed in claim 1 , selected from:

1-3-methylsulfonylamino-4-hydroxyphenoxy)-3(7-ethoxycarbonylmethoxy-tetralin-2-yl-amino)-2-propanol;

1-(3-methylsulfonylamino-4-hydroxyphenoxy)-3-(7-ethoxycarbonylmethoxy-tetralin-(2S)-2-yl-amino)-(2S)-2-propanol;

1-(3-methylsulfonylamino-4-hydroxyphenoxy)-3-(7-piperidinocarbonylmethoxy-tetralin-2-yl-amino)-2-propanol;

1-(3-methylsulfonylamino-4-hydroxyphenoxy)-3-(7-piperidinocarbonylmethoxy-tetralin-(2S)-2-yl-amino)-(2S)-2-propanol;

1-(3-methylsulfonylamino-4-hydroxyphenoxy)-3-(7-aminocarbonylmethoxy-tetralin-(2S)-2-yl-amino)-(2S)-2-propanol;

1-(3-methylsulfonylamino-4-hydroxyphenoxy)-3-[7-(N,N-diethylaminocarbonylmethoxy)-tetralin-(2S)-2-yl-amino]-(2S)-2-propanol;

1-(3-methylsulfonylamino-4-hydroxyphenoxy)-3-[7-(n-butylaminocarbonylmethoxy)-tetralin-(2S)-2-yl-amino]-(2S)-2-propanol;

1-(3-methylsulfonylamino-4-hydroxyphenoxy)-3-(7-benzylaminocarbonylmethoxy-tetralin-(2S)-2-yl-amino)-(2S)-2-propanol;

1-(3-propylsulfonylamino-4-hydroxyphenoxy)-3-(7-ethoxycarbonylmethoxy-tetralin-(2S)-2-yl-amino)-(2S)-2-propanol;

1-(3-methylsulfonylamino-4-hydroxyphenoxy)-3-[7-(2-(piperidinocarbonyl)-ethyl)-tetralin-(2S)-2-yl-amino]-(2S)-2-propanol;

1-(3-methylsulfonylamino-4-hydroxyphenoxy)-3-[7-(2-(ethoxycarbonyl)-ethyl)-tetralin-(2S)-2-yl-amino)-(2S)-2-propanol;

1-(3-methylsulfonylamino-4-benzyloxyphenoxy)-3-(7-hydroxycarbonylmethoxy-tetralin-(2S)-2-yl-amino)-(2S)-2-propanol;

or a salt or solvate thereof.

9. A process for preparing a compound of formula (I) according to claim 1 comprising reacting a compound of formula (II):

in which R 1 , R 2 and R 3 are as defined in claim 1 , with an amine of formula (III):

in which X and R 4 are as defined in claim 1 to form the compound of formula (I) corresponding thereto.

10. A pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (I) as claimed in claim 1 or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutical excipient.

11. A pharmaceutical composition comprising a therapeutically effective amount of the compound of fornmla (I) as claimed in claim 2 or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutical excipient.

12. A pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (I) as claimed in claim 3 or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutical excipient.

13. A pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (I) as claimed in claim 4 or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutical excipient.

14. A pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (I) as claimed in claim 5 or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutical excipient.

15. A pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (I) as claimed in claim 6 or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutical excipient.

16. A pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (I) as claimed in claim 7 or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutical exipient.

17. A pharmaceutical composition comprising a therapeutically effective amount of the compound of formula (I) as claimed in claim 8 or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutical excipient.

18. A method for treating urniary incontinence, in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof.

19. A method for treating irritable bowel syndrome, in a petient in need thereof, comprising administering to the patient a therapeutically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof.

20. A method for treating depression, in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof.