Thiazole Inner Salt Compounds, and Preparation Methods and Uses Thereof

Abstract

The present invention pertains to field of pharmaceutical chemicals, and relates to thiazole inner salt compounds, preparation methods and uses thereof. Specifically, the present invention relates to a compound of Formula I, hydrates or pharmaceutically acceptable salts thereof. The compound of Formula I of the present invention is a potent cross-linking protein cleavage agent, has a stable structure, good physical and chemical properties, and good pharmacological activities, and is suitable for large scale production to obtain samples with stable, controllable and reliable quality, thereby being suitable for pharmaceutical development.

1 . A compound of Formula I or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
         wherein: 
         n is 0, 1, 2 or 3. 
       
     
     
         2 . The compound of Formula I or the pharmaceutically acceptable salt thereof according to  claim 1 , wherein said compound of Formula I is selected from:
 3-methylcarbonyloxy-4-methyl-thiazole inner salt, and   3-methylcarbonyloxy-4-methyl-thiazole inner salt monohydrate.   
     
     
         3 . A method for preparing the compound of Formula I according to  claim 1 , comprising the following steps:
 Compound A is reacted with 1,2-epoxypropane to obtain Compound B,   
       
         
           
           
               
               
           
         
         wherein, in the structure of Compound A, X is chlorine, bromine or iodine. 
       
     
     
         4 . The method according to  claim 3 , wherein Compound A is prepared via the following steps:
 4-methylthiazole is reacted with chloroacetic acid, bromoacetic acid or iodoacetic acid to obtain Compound A,   
       
         
           
           
               
               
           
         
       
     
     
         5 . The method according to  claim 4 , wherein Compound A and/or Compound B is separated and purified via recrystallization; preferably, the solvent used for recrystallization is any one independently selected from the group consisting of acetone, methanol, ethanol, ethyl ether, petroleum ether, and n-hexane, or any mixture thereof. 
     
     
         6 . A method for preparing monocrystals of the compound of Formula I according to  claim 1 , comprising the following steps:
 3-methylcarbonyloxy-4-methyl-thiazole inner salt is dissolved in methanol, then is added with ethyl acetate drop-wisely and is left to stand to obtain monocrystals; preferably, for 1 mg of 3-methylcarbonyloxy-4-methyl-thiazole inner salt, 0.05 mL methanol and 0.3 mL ethyl acetate are used.   
     
     
         7 . A composition, comprising one or more of the compounds of Formula I or the pharmaceutically acceptable salt thereof according to  claim 1 , and optionally one or more pharmaceutically or cosmetically acceptable excipients; optionally, the composition further comprises one or more antihypertensive drugs; preferably, said antihypertensive drug is Nifedipine; preferably, said composition is an oral cavity cleaning preparation. 
     
     
         8 .- 9 . (canceled) 
     
     
         10 . A method selected from any one of the following items (1) to (9), characterized in that said method comprises a step of using or administering an effective amount of the compound of Formula I or the pharmaceutically acceptable salt thereof according to  claim 1 , or composition comprising the compound of Formula I or the pharmaceutically acceptable salt thereof:
 (1) a method for breaking advanced glycation end products (AGEs) in vivo or in vitro;   (2) a method for improving cardiovascular system sclerosis;   (3) a method for enhancing sensitivity of diabetes or cardiovascular disease for drug therapy;   (4) a method for treatment and/or prophylaxis and/or adjuvant therapy of chronic heart failure;   (5) a method for preventing or reversing tooth-staining;   (6) a method for preservation of plant protein or animal protein; and   (7) a method for treatment and/or relief and/or prophylaxis and/or adjuvant therapy of protein aging associated diseases or disorders; preferably, said protein aging associated diseases or disorders are any one or more selected from:   i) skin elasticity decrease or skin wrinkles increase; ii) diabetes; iii) sequelae of diabetes; iv) kidney injury; v) vascular injury; vi) hypertension; vii) retinopathy; viii) lensprotein injury; ix) cataract; x) peripheral neuropathy; xi) osteoarthritis; xii) diabetes associated hypertension;   (8) a method for breaking cross-linked proteins;   (9) a method for reducing plasma BNP content and/or plasma MCP-1 content.