Benzimidazole derivatives and pharmaceutical compositions comprising these compounds

1. A benzimidazole derivative represented by the general Formula I,

or a pharmaceutically acceptable salt thereof, wherein,

R′ represents a group of the formula -(alk) q -R 1 , wherein (alk) represents alkyl, alkenyl or alkynyl, q is 0 or 1, R 1 represents a group of the formula —CO 2 R 2 , wherein R 2 represents hydrogen, alkyl, hydroxy-alkyl, alkoxy-alkyl, thioalkoxy-alkyl, alkyl-“Heterocycle”, or -alkyl-NR 3 R 4 , wherein “Heterocycle” represents a mono- or polycyclic heterocyclic group, which heterocyclic group is optionally substituted one or more times with substituents selected from the group consisting of halogen, alkyl, hydroxy, oxo, cyano, hydroxy-alkyl, alkoxy-alkyl, carboxyl and acyl, and a group of the formula -(alkyl) p -CN, -(alkyl) p -aryl, -(alkyl) p -“Heterocycle”, -(alkyl) p -CO 2 -“Heterocycle” or -(alkyl-CO 2 ) s -(alkyl) t -COR 5 , in which formulas p, s and t independently of each another is 0 or 1, “Heterocycle” represents a mono- or polycyclic heterocyclic group, which heterocyclic group is optionally substituted one or more times with substituents selected from the group consisting of halogen, alkyl, hydroxy, oxo, cyano, hydroxy-alkyl, alkoxy-alkyl, carboxyl and acyl, R 5 represents hydroxy, alkoxy, hydroxy-alkoxy, alkoxy-alkoxy, thioalkoxy-alkoxy, or a group of the formula —NR 6 R 7 or —O-alkyl-NR 6 R 7 , in which formulas R 6 and R 7 independently of each another represent hydrogen, alkyl, cycloalkyl or a mono- or polycyclic heterocyclic group, which heterocyclic group is optionally substituted one or more times with substituents selected from the group consisting of halogen, alkyl, hydroxy, oxo, hydroxy-alkyl, alkoxy-alkyl, carboxyl and acyl, or R 6 and R 7 together with the nitrogen to which they are attached form a mono- or polycyclic heterocyclic group, which heterocyclic group may be substituted one or more times with substituents selected from the group consisting of halogen, alkyl, hydroxy, oxo, hydroxy-alkyl, alkoxy-alkyl, carboxyl and acyl; and R 3 and R 4 independently of each another represent hydrogen, alkyl or cycloalkyl, or R 3 and R 4 together with the nitrogen to which they are attached form a mono- or poly-cyclic heterocyclic group, which heterocyclic group is optionally substituted one or more times with substituents selected from the group consisting of halogen, alkyl, hydroxy, oxo, hydroxy-alkyl, alkoxy-alkyl, carboxyl and acyl;

R″ represents -(alkyl) o -“Heterocycle” wherein o is 1 and “Heterocycle” represents a monocyclic heterocyclic group selected from a thienyl group, a pyrrolyl group, an imidazolyl group, an oxazolyl group, and isoxazolyl group, an oxadiazolyl group, a pyridinyl group, or a tetrazolyl group, which heterocyclic group is optionally substituted one or more times with substituents selected from the group consisting of halogen, alkyl, hydroxy, oxo, cyano, hydroxy-alkyl, alkoxy-alkyl, carboxyl, and acyl, and a group of the formula -(alkyl) p -CN, -(alkyl) p -aryl, -(alkyl) p -aralkyl, -(alkyl) p -O-aryl, -(alkyl) p -O-aralky, -(alkyl) p -CO 2 -aryl, -(alkyl) p -CO 2 -aralkyl, -(alkyl) p -“Heterocycle”, -(alkyl) p -CO 2 -“Heterocycle” or -(alkyl-CO 2 ) s -(alkyl) t -COR 5 , in which formulas p, s and t independently of each another is 0 or 1, “Heterocycle” represents a mono- or polycyclic heterocyclic group, which heterocyclic group is optionally substituted one or more times with substituents selected from the group consisting of halogen, alkyl, hydroxy, oxo, cyano, hydroxy-alkyl, alkoxy-alkyl, carboxyl and acyl, R 5 represents hydrogen, hydroxy, alkyl, alkoxy, hydroxy-alkyl, hydroxy-alkoxy, alkoxy-alkyl, alkoxy-alkoxy, thioalkoxy-alkyl, thioalkoxy-alkoxy, or a group of the formula —NR 6 R 7 or —O-alkyl-NR 6 R 7 , in which formulas R 6 and R 7 independently of each another represent hydrogen, alkyl, cycloalkyl or a mono- or polycyclic heterocyclic group, which heterocyclic group is optionally substituted one or more times with substituents selected from the group consisting of halogen, alkyl, hydroxy, oxo, hydroxy-alkyl, alkoxy-alkyl, carboxyl and acyl, or R 6 and R 7 together with the nitrogen to which they are attached form a mono- or polycyclic heterocyclic group, which heterocyclic group is optionally substituted one or more times with substituents selected from the group consisting of halogen, alkyl, hydroxy, oxo, hydroxy-alkyl, alkoxy-alkyl, carboxyl and acyl.

2. The benzimidazole derivative of claim 1 , wherein R 1 represents a group of the formula —CO 2 R 2 , wherein R 2 represents alkyl, hydroxy-alkyl, alkoxy-alkyl, thioalkoxy-alkyl, or alkyl-N (alkyl) 2 .

3. The benzimidazole derivative of claim 2 , wherein R 1 represents a group of the formula —COOH, —CO 2 —CH 3 , —CO 2 —C 2 H 5 , —CO 2 —CH 2 —CH(OH), —CO 2 (CH 2 ) 2 OCH 3 , —CO 2 (CH 2 ) 2 SCH 3 , —CO 2 (CH 2 ) 2 SC 2 H 5 , or —CO 2 (CH 2 ) 2 N(CH 3 ).

4. The benzimidazole derivative of either of claims 2 - 3 , wherein R″ represents a group of the formula -(alkyl) o -“Heterocycle”, wherein o is 1, and “Heterocycle” represents a furanyl group, a thienyl group, a pyrrolyl group, an imidazolyl group, an oxazolyl group, an isoxazolyl group, an oxadiazolyl group, a pyridinyl group, or a tetrazolyl group, which heterocyclic groups may be substituted one or more times with substituents selected from the group consisting of halogen, alkyl, oxo, acyl, alkyl-CO 2 H, alkyl-CO 2 -alkyl -(alkyl) p -CO 2 -aryl, -(alkyl) p -CO 2 -aralkyl and alkyl-CO 2 -alkyl-CONR 6 R 7 , wherein R 6 and R 7 independently of each another represent hydrogen or alkyl.

5. The benzimidazole derivative of claim 4 , wherein “Heterocycle” represents an imidazol-1-yl; a pyridin-4-yl; or a piperidin-4-yl group.

6. The benzimidazole derivative of claim 5 , wherein R″ represents 1-imidazolylmethyl.

7. The benziznidazole derivative of claim 6 , which is

Methyl 1-(3-(1-imidazolylmethyl)-phenyl)-benzimidazole-5-carboxylate;

2-(Methylthio)-ethyl 1-(3-(1-imidazolylmethyl)-phenyl)-benzimidazole-5-carboxylate;

or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition containing a therapeutically effective amount of a benzimidazole derivative according to claim 1 , or a pharmaceutically acceptable addition salt thereof, together with at least one pharmaceutically acceptable carrier, excipient or diluent.

9. A method for treatment or alleviation of fever cramps or status epilepticus of a living animal body, including a human, wherein said fever cramps or status epilepticus is responsive to modulation of the GABA receptor complex, which method comprises the step of administering to such a living animal body in need thereof a therapeutically effective amount of a benzimidazole derivative according to claim 1 .

10. A method for the induction or maintenance of anaesthesia or pre-anaesthesia in a living animal body, including a human, which method comprises the step of administering to such a living animal an amount of a benzimidazole derivative according to claim 1 effective to induce or maintain anaesthesia or pre-anaesthesia.