Short-acting benzodiazepines
The present invention provides a compound of formula (I): wherein all variables are as defined herein, pharmaceutical formulations containing the same, processes for preparing the same and their use therapy.
1. A compound of formula (I):
wherein
W is H, a C 1 -C 4 branched alkyl, or straight chained alkyl;
X is CH 2 or NCH 3 ; n is 1 or 2;
Y is O or CH 2 ; m is 0 or 1, provided that if X is CH 2 , n is 1 and m is 0, then R 1 is not CH 2 CH 3 ;
R 1 is H, a C 1 -C 7 straight chain alkyl, a C 3 -C 7 branched chain alkyl, a C 1-4 haloalkyl, a C 3 -C 7 cycloalkyl, an aryl, a heteroaryl, an aralkyl, or a heteroaralkyl;
R 2 is phenyl, 2-halophenyl or 2-pyridyl,
R 3 is H, Cl, Br, F, I, CF 3 or NO 2 ;
R 8 is hydrogen, C 1-4 alkyl or C 1-3 hydroxyalkyl;
and U and V are each N;
or a pharmaceutically acceptable salt or solvate thereof,
with the exclusion of a compound where R 1 is H, R 2 is phenyl, R 3 is Cl, R 8 is CH 3 , X is CH 2 , n is 1, Y is CH 2 and m is 1; and
with the exclusion of a compound where R 1 is H, R 2 is phenyl, R 3 is Cl, R 8 is CH 3 , X is CH 2 , and m is 0.
2. A compound of claim 1 wherein
W is H;
X is CH 2 , n is 1;
Y is CH 2 , m is 1;
R 1 is CH 3 or CH 2 CH(CH 3 ) 2 ;
R 2 is 2-fluorophenyl, 2-chlorophenyl or 2-pyridyl;
R 3 is Cl or Br; and
R 8 is H, CH 3 or CH 2 OH.
3. A compound of claim 1 wherein
W is H;
X is CH 2 , n is 1;
Y is CH 2 , m is 1;
R 1 is CH 3 or CH 2 CH(CH 3 ) 2 ;
R 2 is 2-fluorophenyl, 2-chlorophenyl or 2-pyridyl;
R 3 is Cl or Br; and
R 8 is H, CH 3 or CH 2 OH,
provided that when R 1 is CH 2 CH(CH 3 ) 2 , then X is CH 2 , n is 1, R 2 is 2-fluorophenyl, R 3 is Cl, and R 8 is CH 3 .
4. A compound of claim 1 wherein W is H; X is CH 2 ; n is 1; Y is CH 2 ; m is 1; R 1 is CH 3 ; R 2 is 2-chlorophenyl; R 3 is Cl; and R 8 is CH 3 .
5. A compound of claim 1 wherein W is H; X is CH 2 ; n is 1; Y is CH 2 ; m is 1; R 1 is CH 3 ; R 2 is 2-fluorophenyl; R 3 is Cl; and R 8 is CH 3 .
6. A compound of claim 1 wherein W is H; X is CH 2 ; n is 1; Y is CH 2 ; m is 1; R 1 is CH 2 CH(CH 3 ) 2 ; R 2 is 2-fluorophenyl; R 3 is Cl; and R 8 is CH 3 .
7. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound of claim 1 .
8. A pharmaceutical formulation comprising a pharmaceutically acceptable carrier and an effective amount of a compound of claim 2 .
9. A pharmaceutical formulation comprising a pharmaceutically acceptable carrier and an effective amount of a compound of claim 3 .
10. A pharmaceutical formulation comprising a pharmaceutically acceptable carrier and an effective amount of a compound of claim 4 .
11. A pharmaceutical formulation comprising a pharmaceutically acceptable carrier and an effective amount of a compound of claim 5 .
12. A pharmaceutical formulation comprising a pharmaceutically acceptable carrier and an effective amount of a compound of claim 6 .
13. A method of providing sedation or hypnosis, inducing anxiolysis, inducing muscle relaxation in a mammal, or treating convulsions in a mammal, comprising:
administering to the mammal an effective amount of a compound of claim 1 .
14. The method of claim 13 wherein the mammal is in need of sedation.
15. The method of claim 13 wherein the mammal is in need of hypnosis.
16. The method of claim 13 wherein the mammal is in need of muscle relaxation.
17. The method of claim 13 wherein the mammal suffers from convulsions.
18. A method of providing sedation or hypnosis, inducing anxiolysis, inducing muscle relaxation in a mammal, or treating convulsions in a mammal, comprising:
administering to the mammal an effective amount of a compound of claim 2 .
19. A method of producing sedation or hypnosis, inducing anxiolysis, inducing muscle relaxation in a mammal, or treating convulsions in a mammal, comprising:
administering to the mammal an effective amount of a compound of claim 3 .
20. A method of providing sedation or hypnosis, inducing anxiolysis, inducing muscle relaxation in a mammal, or treating convulsions in a mammal, comprising:
administering to the mammal an effective amount of a compound of claim 4 .
21. A method of providing sedation or hypnosis, inducing anxiolysis, inducing muscle relaxation in a mammal, or treating convulsions in a mammal, comprising:
administering to the mammal an effective amount of a compound of claim 5 .
22. A method of providing sedation or hypnosis, inducing anxiolysis, inducing muscle relaxation in a mammal, or treating convulsions in a mammal, comprising:
administering to the mammal an effective amount of a compound of claim 6 .