Arylimidazole derivatives, preparation and therapeutic used thereof

1. A compound of the formula

in the form of racemic, enantiomeric mixture of any combination of these forms, wherein

R 1 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl and aralkyl, the aromatic ring of which is optionally substituted from one to 3 times by a member chosen independently selected from the group consisting of halogen, alkyl and alkoxy;

R 2 is selected from the group consisting of hydrogen and alkyl;

X is selected from the group consisting of a bond and, alkylene of 1 to 5 carbon atoms;

Y is selected from the group consisting of hydrogen, cycloalkyl, NR 4 R 5 , OR 14 , SR 15 and

or Y is selected from the group consisting of aryl optionally substituted from one to 3 times by a member independently selected from the group consisting of halogen, alkyl and alkoxy;

A is selected from the group consisting of a bond or phenylene;

B and B′ are independently selected from the group consisting of alkyl, cycloalkyl, —NR 6 R 7 , —SR 8 , carbocyclic aryl and heterocyclic aryl with 5 to 6 ring members having 1 to 4 heteroatoms selected from the group consisting of O, S and N, said carbocyclic and heterocyclic aryl being optionally substituted by one to three members independently selected from the group consisting of alkyl, alkenyl and alkoxy,

R 3 is selected from the group selected from the group consisting of hydrogen, alkyl and aralkyl;

R 4 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, —C(O)—R 9 , —C(O)OR 9 , —C(O)NHR 9 , —SO 2 R 9 and aralkyl, the aromatic ring of which is optionally substituted one to 3 times by a member independently selected from the group consisting of hydrogen, alkyl and alkoxy, or R 4 is bis-phenylalkyl,

R 5 is selected from the group consisting of hydrogen, alkyl, aryl and aralkyl, or R 4 and R 5 form with the nitrogen atom which carries them a non-aromatic heterocyclic of five to seven ring members having 1 to 2 heteroatoms, the elements for completing the heterocycle being independently selected from the group consisting of —CHR 10 —, —NR 11 —, —O— and —S—;

R 6 and R 7 are selected from the group consisting of hydrogen, alkyl, alkenyl and alkynyl;

or R 6 is —NO 2 and R 7 is hydrogen,

or R 6 and R 7 form with the nitrogen atom which carries them a non-aromatic heterocyclic with five to six ring members, the elements for completing the heterocycle being independently selected from the group consisting of —CH 2 —, —NR 12 —, —O— and —S—;

R 8 is alkyl of 1 to 6 carbon atoms optionally substituted from one to 3 times by a member independently selected from the group consisting of halogen, —OH, amino, cyano and aryl;

R 9 is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, carbocyclic and heterocyclic aralkyl and aryl, the aromatic ring of which is optionally substituted from one to 3 times by a member independently selected from the group consisting of halogen, alkyl and alkoxy;

R 10 is selected from a group consisting of hydrogen, alkyl and aryl optionally substituted from one to 3 times by a member independently selected from the group consisting of halogen, alkyl and alkoxy,

R 11 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, —C(O)R 13 , —C(O)OR 13 , —SO 2 R 13 , —C(O)NHR 13 and the aryl and aralkyl, the aromatic ring of which is optionally substituted from one to 3 times by a member independently selected from the group consisting of halogen, alkyl and alkoxy;

R 12 is selected from the group consisting of hydrogen and alkyl;

R 13 is selected from the group consisting of alkyl, haloalkyl and carbocyclic and heterocyclic aralkyl or aryl, the aromatic ring of which is optionally substituted one to 3 times by a member independently selected from the group consisting of halogen, alkyl and alkoxy;

R 14 is selected from the group consisting of alkyl, phenyl and aralkyl; and

R 15 is selected from the group consisting of alkyl, phenyl and aralkyl;

it being understood:

that alkyl or alkoxy, unless otherwise specified, has 1 to 12 carbon atoms;

that alkenyl or alkynyl, unless otherwise specified, has 2 to 6 carbon atoms;

that cycloalkyl, unless otherwise specified, has 3 to 7 carbon atoms;

and a salt of a compound of formula (I).

2. A compound of claim 1 , wherein X is a bond or alkylene of 1 to 5 carbon atoms and Y is —NR 4 R 5 ; and a salt thereof.

3. A compound of claim 1 , wherein X is a bond or alkylene of 1 to 5 carbon atoms and Y is

and a salt thereof.

4. A compound of claim 1 , wherein X is a bond or alkylene of 1 to 5 carbon atoms and Y is cycloalkyl or aryl optionally substituted one to 3 times by a member independently selected from the group consisting of halogen, alkyl and alkoxy; and a salt thereof.

5. A compound of claim 1 , selected from the group consisting of

butyl-2-[4-(4-{[(1Z)-amino(thien-2-yl)methylene]amino}phenyl)-1H-imidazol-2-yl]ethylcarbamate;

butyl-2-[4-(3-{[(1E)-amino(thien-2-yl)methylene]-amino}phenyl)-1H-imidazol-2-yl]ethylcarbamate;

butyl-2-[4-(4′-{[(1Z)amino(thien-2-yl)methylene]amino}-1,1′-biphenyl-4-yl)-1H-imidazol-2-yl]ethylcarbamate;

N′-(4-{2-[(cyclohexylamino)methyl]-1H-imidazol-4-yl}phenyl)thiophene-2-carboximidamide;

N′-(4-{2-[2-(cyclohexylamino)ethyl]-1H-imidazol-4-yl}phenyl)thiophene-2-carboximidamide;

N′-(3-{2-[(cyclohexylamino)methyl]-1H-imidazol-4-yl}phenyl)thiophene-2-carboximidamide;

N′-[4-(2-{[cyclohexyl(methyl)amino]methyl}-1H-imidazol-4-yl)phenyl]thiophene-2-carboximidamide;

N′-(4-{2-[(dibenzylamino)methyl]-1H-imidazol-4-yl}phenyl)thiophene-2-carboximidamide;

N′(4-{2-[(benzylamino)methyl]-1H-imidazol-4-yl}phenyl)thiophene-2-carboximidamide;

N′-{3-[2-(aminoethyl)-1H-imidazol-4-yl]phenyl}thiophene-2-carboximidamide;

N′-{3-[2-({[(1E)-amino(thien-2-yl)methylene]-amino}methyl)-1H-imidazol-4-yl]phenyl}thiophene-2-carboximidamide;

N′-{4-[2-({[(1E)-amino(thien-2-yl)methylene]amino}methyl)-1H-imidazol-4-yl]phenyl}thiophene-2-carboximidamide;

N-{3-[-2-(2-cyclohexylethyl)-1H-imidazol-4-yl]phenyl}thiophene-2-carboximidamide;

N′-{3-[2-(1-pentylhexyl)-1H-imidazol-4-yl]phenyl}thiophene-2-carboximidamide;

N′-{4-[2-(2-cyclohexylethyl)-1H-imidazol-4-yl]phenyl}thiophene-2-carboximidamide;

N′-{3-[2-(cyclohexylmethyl)-1H-imidazol-4-yl]phenyl}thiophene-2-carboximidamide;

N′-{3-[2-(3-cyclohexylpropyl)-1H-imidazol-4-yl]phenyl}thiophene-2-carboximidamide;

N′-[3-(2-hexyl-1H-imidazol-4-yl)phenyl]thiophene-2-carboximidamide;

N-{4-[2-(2-cyclohexylethyl)-1H-imidazol-4-yl]phenyl}-N″-nitroguanidine;

N′-(4-{2-[(cycloheptylamino)methyl]-1H-imidazol-4-yl}phenyl)thiophene-2-carboximidamide;

N′-(4-{2-[(methylamino)methyl]-1H-imidazol-4-yl}phenyl)thiophene-2-carboximidamide;

N′-(4-{2-[(cyclobutylamino)methyl]-1H-imidazol-4-yl}phenyl)thiophene-2-carboximidamide;

N′-[4-(2-{[(2,2-diphenylethyl)amino]methyl}-1H-imidazol-4-yl)phenyl]thiophene-2-carboximidamide;

N′-{3-[2-(2-{[(1E)-amino(thien-2-yl)methylene]amino}ethyl)-1H-imidazol-4-yl]phenyl}thiophene-2-carboximidamide;

N′-(3-{2-[(phenylthio)methyl]-1H-imidazol-4-yl}phenyl)thiophene-2-carboximidamide;

N′-(4-{2-[(phenylthio)methyl]-1H-imidazol-4-yl}phenyl)thiophene-2-carboximidamide and;

N′-{3-[2-(4-isobutylbenzyl)-1H-imidazol-4-yl]phenyl}thiophene-2-carboximidamide;

and a salt thereof.

6. A pharmaceutical composition containing, as active ingredient, a compound of claim 1 and an inert pharmaceutical acceptable excipient.

7. A method of treating pain in warm-blooded animals comprising administering to warm-blooded animals in need thereof an effective amount of a compound of claim 1 .