4-Phenlthiazole and 4-phenylimidizole derivatives and their use as medicaments for the treatment of neurodegenerative diseases, pain and epilepsy

Abstract

The invention relates to novel derivatives of 4-phenylthiazoles and 4-phenylimidazoles and the use thereof medicament. The invention especially relates to the following compounds: butyl-2-[4-(4-(aminophenyl)-1<i>H</i>-imidazol-2-yl]ethyl-carbamate, and 4-[2-(1-aminocyclopentyl)-1,3-thiazol-4-yl]-2,6-di-tert-butylphenol, and the salts of the same.

1 . A compound: 
 butyl 2-[4-(4-aminophenyl)-1H-imidazol-2-yl]ethylcarbamate;    N,2-dimethyl-1-[4-(10H-phenothiazin-2-yl)-1,3-thiazol-2-yl]propan-1-amine;    N,2-dimethyl-1-[4-(10H-phenoxazin-2-yl)-1,3-thiazol-2-yl]propan-1-amine;    N,3-dimethyl-1-[4-(10H-phenoxazin-2-yl)-1,3-thiazol-2-yl]butan-1-amine;    N,3-dimethyl-1-[4-(10H-phenothiazin-2-yl)-1,3-thiazol-2-yl]butan-1-amine;    2,6-di-tert-butyl-4-{2-[3-methyl-1-(methylamino)butyl]-1,3-thiazol-4-yl}phenol;    [4-(3,5-di-tert-butylphenyl)-1,3-thiazol-2-yl]methylamine;    2,6-di-tert-butyl-4-{2-[(1S)-1-(methylamino)ethyl]-1,3-thiazol-4-yl}phenol;    2,6-di-tert-butyl-4-{2-[(1R)-1-(methylamino)ethyl]-1,3-thiazol-4-yl}phenol;    N-{[4-(3,5-di-tert-butylphenyl)-1,3-thiazol-2-yl]methyl}-N-methylamine;    N-methyl-N-{[4-(3,4,5-trimethoxyphenyl)-1,3-thiazol-2-yl]methyl}amine;    ethyl N-{[4-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3-thiazol-2-yl]methyl}glycinate;    N-{[4-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3-thiazol-2-yl]methyl}glycine;    2,6-di-tert-butyl-4-{2-[(4-methoxypiperidin-1-yl)methyl]-1,3-thiazol-4-yl}phenol;    N-methyl-N-{(1S)-2-methyl-1-[4-(10H-phenothiazin-2-yl)-1,3-thiazol-2-yl]propyl}amine;    N,2-dimethyl-1-[4-(10-methyl-10H-phenothiazin-2-yl)-1,3-thiazol-2-yl]propan-1-amine;    N-methyl-N-{(1S)-2-methyl-1-[4-(10H-phenoxazin-2-yl)-1,3-thiazol-2-yl]propyl}amine;    4-{2-[(1R)-1-aminoethyl]-1,3-thiazol-4-yl}-2,6-di-tert-butylphenol;    4-{2-[(1S)-1-aminoethyl]-1,3-thiazol-4-yl}-2,6-di-tert-butylphenol;    4-[2-(1-aminocyclopropyl)-1,3-thiazol-4-yl]-2,6-di-tert-butylphenol;    4-(2-[(methylamino)methyl]-1,3-thiazol-4-yl)benzene-1,2-diol;    N-methyl-N-{(1R)-2-methyl-1-[4-(10H-phenothiazin-2-yl)-1,3-thiazol-2-yl]propyl}amine;    (1R)-2-methyl-1-[4-(10H-phenothiazin-2-y 1)-1,3-thiazol-2-yl]propan-1-amine;    N-methyl-N-{(1R)-2-methyl-1-[4-(10H-phenoxazin-2-yl)-1,3-thiazol-2-yl]propyl}amine;    N 2 -{[4-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3-thiazol-2-yl]methyl}glycinamide;    ethyl N-{[4-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3-thiazol-2-yl]methyl}-N-(2-ethoxy-2-oxoethyl)glycinate;    4-(3,5-di-tert-butyl-4-methoxyphenyl)-2-(methoxymethyl)-1,3-thiazole;    4-[2-(1-aminocyclopentyl)-1,3-thiazol-4-yl]-2,6-di-tert-butylphenol;    or salts or combinations thereof.    
     
     
         2 . A compound according to  claim 1 , wherein the compound is butyl 2-[4-(4-aminophenyl)-1H-imidazol-2-yl]ethylcarbamate or a salt thereof.  
     
     
         3 . A compound or salt according to  claim 1 , wherein the compound is 4-[2-(1-aminocyclopentyl)-1,3-thiazol-4-yl]-2,6-di-tert-butylphenol or a salt thereof.  
     
     
         4 . A medicament, comprising a compound: 
 butyl 2-[4-(4-aminophenyl)-1H-imidazol-2-yl]ethylcarbamate;    N,2-dimethyl-1-[4-(10H-phenothiazin-2-yl)-1,3-thiazol-2-yl]propan-1-amine;    N,2-dimethyl-1-[4-(10H-phenoxazin-2-yl)-1,3-thiazol-2-yl]propan-1-amine;    N,3-dimethyl-1-[4-(10H-phenoxazin-2-yl)-1,3-thiazol-2-yl]butan-1-amine;    N,3-dimethyl-1-[4-(10H-phenothiazin-2-yl)-1,3-thiazol-2-yl]butan-1-amine;    2,6-di-tert-butyl-4-{2-[3-methyl-1-(methylamino)butyl]-1,3-thiazol-4-yl}phenol;    [4-(3,5-di-tert-butylphenyl)-1,3-thiazol-2-yl]methylamine;    2,6-di-tert-butyl-4-{2-[(1S)-1-(methylamino)ethyl]-1,3-thiazol-4-yl}phenol;    2,6-di-tert-butyl-4-{2-[(1R)-1-(methylamriino)ethyl]-1,3-thiazol-4-y 1}phenol;    N-{[4-(3,5-di-tert-butylphenyl)-1,3-thiazol-2-yl]methyl}-N-methylamine;    N-methyl-N-{[4-(3,4,5-trimethoxyphenyl)-1,3-thiazol-2-yl]methyl}amine;    ethyl N-{[4-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3-thiazol-2-yl]methyl}glycinate;    N-{[4-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3-thiazol-2-yl]methyl}glycine;    2,6-di-tert-butyl-4-{2-[(4-methoxypiperidin-1-yl)methyl]-1,3-thiazol-4-yl}phenol;    N-methyl-N-{(1S)-2-methyl-1-(4-(10H-phenothiazin-2-yl)-1,3-thiazol-2-yl]propyl}amine;    N,2-dimethyl-1-[4-(10-methyl-10H-phenothiazin-2-yl)-1,3-thiazol-2-yl]propan-1-amine;    N-methyl-N-{(1S)-2-methyl-1-[4-(10H-phenoxazin-2-yl)-1,3-thiazol-2-yl]propyl}amine;    4-{2-[(1R)-1-aminoethyl]-1,3-thiazol-4-yl}-2,6-di-tert-butylphenol;    4-{2-[(1S)-1-aminoethyl]-1,3-thiazol-4-yl}-2,6-di-tert-butylphenol;    4-[2-(1-aminocyclopropyl)-1,3-thiazol-4-yl]-2,6-di-tert-butylphenol;    4-{2-[(methylamino)methyl]-1,3-thiazol-4-yl}benzene-1,2-diol;    N-methyl-N-{(1R)-2-methyl-1-[4-(10H-phenothiazin-2-yl)-1,3-thiazol-2-yl]propyl}amine;    (1R)-2-methyl-1-(4-(10H-phenothiazin-2-yl)-1,3-thiazol-2-yl]propan-1-amine;    N-methyl-N-{(1R)-2-methyl-1-[4-(10H-phenoxazin-2-yl)-1,3-thiazol-2-yl]propyl}amine;    N 2 -{[4-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3-thiazol-2-yl]methyl}glycinamide;    ethyl N-{[4-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3-thiazol-2-yl]methyl}-N-(2-ethoxy-2-oxoethyl)glycinate;    4-(3,5-di-tert-butyl-4-methoxyphenyl)-2-(methoxymethyl)-1,3-thiazole;    4-(2-(1-aminocyclopentyl)-1,3-thiazol-4-yl]-2,6-di-tert-butylphenol;    or pharmaceutically acceptable salts or combinations thereof.    
     
     
         5 . A pharmaceutical composition comprising, as an active ingredient, at least one of the compounds or pharmaceutically acceptable salts of  claim 4 .  
     
     
         6 . A method of treating disorders/pathologies selected from neurodegenerative diseases, pain, or epilepsy comprising administering a medicament to a patient, wherein the medicament comprises one of the compounds or pharmaceutically acceptable salts of  claim 4 .  
     
     
         7 . The method of  claim 6 , wherein the disorders/pathologies treated are neurodegenerative diseases.  
     
     
         8 . The method of  claim 7 , wherein the compound or pharmaceutically acceptable salt is 4-[2-(1-aminocyclopentyl)-1,3-thiazol-4-yl)-2,6-di-tert-butylphenol or pharmaceutically acceptable salts thereof.  
     
     
         9 . The method of  claim 6  comprising treating pain.  
     
     
         10 . The method of  claim 9 , wherein the compound or pharmaceutically acceptable salt is butyl 2-[4-(4-aminophenyl)-1H-imidazol-2-yl)ethylcarbamate or pharmaceutically acceptable salts thereof