Fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives

Abstract

The invention relates to fluorinated compounds and their use as integrin receptor antagonists. Novel fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives and pharmaceutically acceptable salts or solvates thereof and their use are described.

1 . A compound of formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or solvate thereof, wherein 
         X is selected from CH and N; 
         Y is selected from CH and N; 
         R 1  is C 1 -C 6  alkoxy wherein said C 1 -C 6  alkoxy is substituted with 0, 1, 2, 3, 4, or 5 fluorine atoms; 
         and 
         R 2  and R 3  are each independently selected from H and F, 
         or R 2  and R 3  taken together with the carbon atom to which they are attached form a 3- or 4-membered carbocyclic or heterocyclic ring, 
         provided that the compound of formula I contains at least one fluorine atom. 
       
     
     
         2 . The compound of  claim 1 , wherein the compound is of formula II: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or solvate thereof, wherein 
         X is selected from CH and N; 
         Y is selected from CH and N; 
         R 1  is C 1 -C 6  alkoxy wherein said C 1 -C 6  alkoxy is substituted with 0, 1, 2, 3, 4, or 5 fluorine atoms; 
         and 
         R 2  and R 3  are each independently selected from H and F, 
         or R 2  and R 3  taken together with the carbon atom to which they are attached form a 3- or 4-membered carbocyclic or heterocyclic ring, 
         provided that the compound of formula II contains at least one fluorine atom. 
       
     
     
         3 . The compound of  claim 1 , wherein the compound is of formula III: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or solvate thereof, wherein 
         R 1  is C 1 -C 6  alkoxy wherein said C 1 -C 6  alkoxy is substituted with 0, 1, 2, 3, 4, or 5 fluorine atoms; 
         and 
         R 2  and R 3  are each independently selected from H and F, 
         or R 2  and R 3  taken together with the carbon atom to which they are attached form a 3- or 4-membered carbocyclic or heterocyclic ring, 
         provided that the compound of formula III contains at least one fluorine atom. 
       
     
     
         4 . The compound of  claim 1 , wherein the compound is of formula IV: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or solvate thereof, wherein 
         R 1  is C 1 -C 6  alkoxy wherein said C 1 -C 6  alkoxy is substituted with 0, 1, 2, 3, 4, or 5 fluorine atoms; 
         and 
         R 2  and R 3  are each independently selected from H and F, 
         or R 2  and R 3  taken together with the carbon atom to which they are attached form a 3- or 4-membered carbocyclic or heterocyclic ring, 
         provided that the compound of formula IV contains at least one fluorine atom. 
       
     
     
         5 . The compound of  claim 1 , wherein the compound is of formula V: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or solvate thereof, wherein 
         R 1  is C 1 -C 6  alkoxy wherein said C 1 -C 6  alkoxy is substituted with 0, 1, 2, 3, 4, or 5 fluorine atoms; 
         and 
         R 2  and R 3  are each independently selected from H and F, 
         or R 2  and R 3  taken together with the carbon atom to which they are attached form a 3- or 4-membered carbocyclic or heterocyclic ring, 
         provided that the compound of formula V contains at least one fluorine atom. 
       
     
     
         6 . A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of  claim 1  and a pharmaceutical carrier, diluent, or excipient. 
     
     
         7 . A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of  claim 2  and a pharmaceutical carrier, diluent, or excipient. 
     
     
         8 . A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of  claim 3  and a pharmaceutical carrier, diluent, or excipient. 
     
     
         9 . A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of  claim 4  and a pharmaceutical carrier, diluent, or excipient. 
     
     
         10 . A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or solvate thereof as in one of  claim 5  and a pharmaceutical carrier, diluent, or excipient. 
     
     
         11 . A method of treating and/or preventing a condition, eliciting an integrin receptor antagonizing effect, inhibiting bone resorption, or treating tumor growth in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or solvate as in one of  claim 1 . 
     
     
         12 . A method of treating and/or preventing a condition, eliciting an integrin receptor antagonizing effect, inhibiting bone resorption, or treating tumor growth in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or solvate as in one of  claim 2 . 
     
     
         13 . A method of treating and/or preventing a condition, eliciting an integrin receptor antagonizing effect, inhibiting bone resorption, or treating tumor growth in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or solvate as in one of  claim 3 . 
     
     
         14 . A method of treating and/or preventing a condition, eliciting an integrin receptor antagonizing effect, inhibiting bone resorption, or treating tumor growth in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or solvate as in one of  claim 4 . 
     
     
         15 . A method of treating and/or preventing a condition, eliciting an integrin receptor antagonizing effect, inhibiting bone resorption, or treating tumor growth in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt or solvate as in one of  claim 5 . 
     
     
         16 . A method of synthesizing a compound or a pharmaceutically acceptable salt or solvate thereof as in one of  claim 1 . 
     
     
         17 . A method of synthesizing a compound or a pharmaceutically acceptable salt or solvate thereof as in one of  claim 2 . 
     
     
         18 . A method of synthesizing a compound or a pharmaceutically acceptable salt or solvate thereof as in one of  claim 3 . 
     
     
         19 . A method of synthesizing a compound or a pharmaceutically acceptable salt or solvate thereof as in one of  claim 4 . 
     
     
         20 . A method of synthesizing a compound or a pharmaceutically acceptable salt or solvate thereof as in one of  claim 5 .