4-methyldihydropyrimidinone compounds and pharmaceutical use thereof

Abstract

The present invention relates to 4-methyldihydropyrimidinone compounds, or pharmaceutically acceptable salts thereof, having RORγ antagonist activity, pharmaceutical compositions comprising the same, and pharmaceutical use thereof. A compound of Formula (1) or (2) or a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising the same, and pharmaceutical use thereof are provided.

1 - 12 . (canceled) 
     
     
         13 . A method of preparing a compound of Formula (1): 
       
         
           
           
               
               
           
         
       
       the method comprising reacting a compound of the following formula: 
       
         
           
           
               
               
           
         
       
       with sodium hydroxide. 
     
     
         14 . The method of  claim 13 , wherein the reacting is carried out at room temperature in the presence of isopropanol. 
     
     
         15 . A method of preparing a compound of the following formula: 
       
         
           
           
               
               
           
         
       
       the method comprising reacting a compound of the following formula: 
       
         
           
           
               
               
           
         
       
       with (diacetoxyiodo)benzene in the presence of 2,2,6,6-tetramethylpiperidine-1-oxyl radical. 
     
     
         16 . The method of  claim 15 , wherein the reacting is carried out at room temperature in the presence of acetic acid and cyclopentyl methyl ester. 
     
     
         17 . A compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         18 . The compound of  claim 17 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         19 . The compound of  claim 17 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         20 . The compound of  claim 17 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         21 . The compound of  claim 17 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         22 . The compound of  claim 17 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         23 . The compound of  claim 17 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         24 . The compound of  claim 17 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         25 . The compound of  claim 17 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         26 . The compound of  claim 17 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         27 . The compound of  claim 17 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         28 . The compound of  claim 17 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         29 . The compound of  claim 17 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         30 . A compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         31 . The compound of  claim 30 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         32 . The compound of  claim 30 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         33 . The compound of  claim 30 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         34 . The compound of  claim 30 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         35 . The compound of  claim 30 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         36 . The compound of  claim 30 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         37 . A crystalline form of a compound of Formula (1): 
       
         
           
           
               
               
           
         
       
       showing a powder X-ray diffraction pattern having three or more peaks selected from the group consisting of 7.4±0.2°, 9.9±0.2°, 10.5±0.2°, 11.4±0.2°, 11.6±0.2°, 13.4±0.2°, 14.2±0.2°, 17.4±0.2°, 18.3±0.2°, 18.7±0.2°, and 19.4±0.2° of the diffraction angle (2θ) measured with CuKα radiation.