Alanine 2,6-dialkoxyphenyl ester derivatives as hypnotics

1. An alanine 2,6-dialkoxyphenyl ester derivative having the general formula I

wherein

R 1 is (C 1-3 )alkyloxy, (C 1-3 )alkyloxy(C 1-3 )alkyl, (C 1-3 )alkylthio, (C 1-3 )alkylthio(C 1-3 )alkyl, (C 1-3 )alkylsulfinyl, (C 1-3 )alkylsulfinyl(C 1-3 )alkyl, (C 1-3 )alkylsulfonyl, (C 1-3 )alkylsulfonyl(C 1-3 )alkyl, (C 1-3 )alkyloxycarbonyl, (CH 2 ) n —CO—NR 8 R 9 or (CH 2 ) n —NR 8 R 9 ;

n is 0, 1 or 2;

R 2 is hydrogen or (C 1-3 )alkyl;

R 3 is (C 1-3 )alkyl or (C 1-3 )alkyloxy(C 1-3 )alkyl;

R 4 is (C 1-3 )alkyloxy(C 1-3 )alkyl; or

R 3 and R 4 form together with the nitrogen atom to which they are bound a 5-, 6-, or 7-membered ring, optionally containing a further heteroatom selected from O and S, and which ring may optionally contain a double bond and be optionally substituted with (C 1-3 )alkyl or (C 1-3 )alkyloxy;

R 5 and R 6 are independently (C 1-3 )alkyl;

R 7 is hydrogen, (C 1-3 )alkyl, (C 1-3 )alkyloxy or (C 2-3 )alkenyl;

R 8 and R 9 are independently (C 1-3 )alkyl; or

R 8 and R 9 form together with the nitrogen atom to which they are bound a 5-, 6-, or 7-membered, optionally containing a further heteroatom selected from O and S, and which ring may optionally contain a double bond; or a pharmaceutically acceptable salt thereof.

2. The alanine 2,6-dialkoxyphenyl ester derivative of claim 1 , wherein R 5 and R 6 are methyl.

3. The alanine 2,6-dialkoxyphenyl ester derivative of claim 1 , wherein R 3 and R 4 form together with the nitrogen atom to which they are bound a 5-, 6- or 7-membered ring, optionally containing a further heteroatom selected from O and S, and which ring may optionally contain a double bond and be optionally substituted with (C 1-3 )alkyl or (C 1-3 )alkyloxy.

4. The alanine 2,6-dialkoxyphenyl ester derivative of claim 3 , wherein R 1 is (C 1-3 )alkyloxy or (C 1-3 )alkyloxy(C 1-3 )alkyl.

5. The alanine 2,6-dialkoxyphenyl ester derivative of claim 4 , wherein the α-carbon atom is that of the R-enantiomer.

6. A pharmaceutical composition, comprising:

an alanine 2,6-dialkoxyphenyl ester derivative according to claim 1 , or a pharmaceutically acceptable salt thereof, and

pharmaceutically acceptable auxiliaries.

7. A method of manufacturing a pharmaceutical composition, comprising:

admixing the alanine 2,6-dialkoxyphenyl ester derivative according to claim 1 , or a pharmaceutically acceptable salt thereof, and

pharmaceutically acceptable auxiliaries.

8. A method of treating GABA related diseases selected from the group consisting of anxiety, stress, sleep disorders, post natal depression, and premenstrual tension, in a patient in need thereof, comprising:

administering to a patient in the need thereof an effective amount of the alanine 2,6-dialkoxyphenyl ester derivative according to claim 1 , or a pharmaceutically acceptable salt.

9. The method according to claim 8 , wherein an administration route is selected from the group consisting of oral, sublingual, subcutaneous, intravenous, intramuscular, and rectal.

10. A method of inducing hypnotic activity in a patient, comprising:

administering to a patient an effective amount of the 2,6-dialkoxyphenyl ester derivative according to claim 1 , wherein the effective amount induces hypnotics.

11. The method according to claim 10 , wherein an administration route is selected from the group consisting of oral, sublingual, subcutaneous, intravenous, intramuscular, and rectal.

12. A method to induce analgesic activity in a patient in need thereof, comprising:

administering to a patient an effective amount of the 2,6- dialkoxyphenyl ester derivative according to claim 1 , wherein the effective amount induces analgesic activity in said patient.

13. The method according to claim 12 , wherein an administration route is selected from the group consisting of oral, sublingual, subcutaneous, intravenous, intramuscular, and rectal.

14. The method according to claim 12 , wherein the administration route is intravenous.