Thiazole compounds, compositions and methods for treatment of degenerative diseases and disorders

Abstract

Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of degenerative diseases and disorders.

What is claimed is: 
     
         1 . The compound according to formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is pyridinyl or phenyl; 
         R 2  is pyridinyl, unsubstituted phenyl or phenyl substituted with alkoxy; 
         R 3  is —OR 4  or —NR 5 R 6 ; 
         R 4  is hydrogen or lower alkyl; and 
         one of R 5  or R 6  is hydrogen or methyl and the other is unsubstituted lower alkyl, unsubstituted phenyl, lower alkyl substituted with alkoxy or phenyl substituted with halogen, alkoxy or —NH-phenyl; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The compound according to  claim 1 , wherein R 1  is pyridinyl. 
     
     
         3 . The compound according to  claim 1 , wherein R 1  is or phenyl. 
     
     
         4 . The compound according to  claim 1 , wherein R 2  is pyridinyl. 
     
     
         5 . The compound according to  claim 1 , wherein R 2  is unsubstituted phenyl or phenyl substituted with alkoxy. 
     
     
         6 . The compound according to  claim 1 , wherein R 3  is —OR 4 . 
     
     
         7 . The compound according to  claim 1 , wherein R 3  is —NR 5 R 6 . 
     
     
         8 . The compound according to  claim 1 , wherein R 4  is hydrogen or ethyl. 
     
     
         9 . The compound according to  claim 1 , wherein one of R 5  or R 6  is hydrogen and the other is unsubstituted lower alkyl, unsubstituted phenyl, lower alkyl substituted with alkoxy or phenyl substituted with halogen, alkoxy or —NH-phenyl. 
     
     
         10 . The compound according to  claim 1 , wherein one of R 5  or R 6  is lower alkyl and the other is unsubstituted lower alkyl, unsubstituted phenyl, lower alkyl substituted with alkoxy or phenyl substituted with halogen, alkoxy or —NH-phenyl. 
     
     
         11 . The compound according to  claim 1 , wherein R 3  is hydroxy or alkoxy. 
     
     
         12 . The compound according to  claim 1 , wherein R 3  is —NH-phenyl, —NH-halophenyl, —N(CH 3 )CH 2 CH 2 OCH 3 , —NH-phenylalkoxy or —NH-phenylaminophenyl. 
     
     
         13 . The compound according to  claim 1 , wherein said compound is:
 Ethyl 2,4-diphenylthiazole-5-carboxylate;   2,4-diphenylthiazole-5-carboxylic acid;   N,2,4-triphenylthiazole-5-carboxamide;   N-(4-fluorophenyl)-2,4-diphenylthiazole-5-carboxamide;   Ethyl 2-(4-methoxyphenyl)-4-phenylthiazole-5-carboxylate;   N-(2-methoxyethyl)-N-methyl-2,4-diphenylthiazole-5-carboxamide;   Ethyl 4-phenyl-2-(pyridin-2-yl)thiazole-5-carboxylate;   N-(4-methoxyphenyl)-2,4-diphenylthiazole-5-carboxamide;   Ethyl 2-phenyl-4-(pyridin-2-yl)thiazole-5-carboxylate;   Ethyl 4-phenyl-2-(pyridin-4-yl)thiazole-5-carboxylate;   4-Phenyl-2-(pyridin-2-yl)thiazole-5-carboxylic acid; or   4-Phenyl-N-(2-(phenylamino)phenyl)-2-(pyridin-2-yl)thiazole-5-carboxamide.   
     
     
         14 . A pharmaceutical composition, comprising a therapeutically effective amount of a compound according to  claim 1  or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. 
     
     
         15 . A method for treating a degenerative disease or disorder, comprising the step of administering a therapeutically effective amount of a compound according to  claim 1  or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier to a patient in need thereof. 
     
     
         16 . The method according to  claim 15 , wherein said degenerative disease or disorder is retinitis pigmentosa. 
     
     
         17 . A method of treating a retinal degenerative disease in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof according to  claim 1 . 
     
     
         18 . A method for preventing calcium-induced or oxidant-induced mitochondrial damage preventing or loss of mitochondrial respiratory capacity in a cell susceptible thereof wherein the calcium-induced or oxidant-induced mitochondrial damage or loss of mitochondrial respiratory capacity comprises excess of cGMP that increases the number of cGMP-gated cation channels in an open configuration, allowing an influx of Ca2+ into the cell, said method comprising contacting the cell with an effective amount of a compound or a pharmaceutically acceptable salt thereof according to  claim 1 .