Inhibitors of alpha4 mediated cell adhesion

Abstract

The present invention relates to a phenylalanine derivative of Formula (I) wherein X 1 is a halogen atom, X 2 is a halogen atom, Q is a CH 2 R— is a carboxyl group which may be esterified; or a pharmaceutically acceptable salt thereof.

1 . A method for treating a condition caused by α 4  integrin-mediated cell adhesion selected from the group consisting of allergic condition, adult respiratory distress syndrome, cardiovascular diseases, thrombosis or harmful platelet aggregation, reocclusion following thrombolysis, reperfusion injury, psoriasis, eczema, diabetes, systemic lupus erythematosus, pancreatitis, mastitis, hepatitis, cholecystitis, cholangitis, pericholangitis, bronchitis, sinusitis, collagen disease, sarcoidosis, osteoporosis, osteoarthritis, atherosclerosis, wound, eye diseases, Sjogren's syndrome, intimal hyperplasia, arteriosclerosis, reinfarction or restenosis after surgery, and central nervous system injury, in a patient comprising administering to said patient an effective amount of a compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein X 1  is a halogen atom, X 2  is a halogen atom, Q is a —CH 2 — group or a —(CH 2 ) 2 — group, Y is a C 1-6  alkyl group, CO 2 R is a carboxyl group or a C 2-7  alkoxycarbonyl group, or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The method according to  claim 1 , wherein said condition is allergic condition or rejection after transplantation. 
     
     
         3 . The method according to  claim 2 , wherein allergic condition is rhinitis. 
     
     
         4 . The method according to  claim 1 , wherein the compound is represented by the following chemical formula [I-1]: 
       
         
           
           
               
               
           
         
         wherein the symbols are the same as defined in  claim 1 . 
       
     
     
         5 . The method according to  claim 4 , wherein X 1  is chlorine atom or fluorine atom, X 2  is chlorine atom or fluorine atom, and Y is a C 1-4  alkyl group. 
     
     
         6 . The method according to  claim 5 , wherein X 1  is chlorine atom or fluorine atom, X 2  is chlorine atom or fluorine atom, Q is a —CH 2 — group, Y is methyl group, ethyl group, or n-propyl group, and CO 2 R is a carboxyl group, methoxycarbonyl group, ethoxycarbonyl group or tert-butoxycarbonyl group. 
     
     
         7 . The method according to  claim 5 , wherein X 1  is fluorine atom, X 2  is chlorine atom or fluorine atom, Q is a —CH 2 — group, and Y is methyl group or ethyl group. 
     
     
         8 . The method according to  claim 1 , wherein the compound is selected from the group consisting of N-(2,6-difluorobenzoyl)-4-(2,6-dimethoxy-4-ethoxymethylphenyl)-L-phenylalanine, N-(2-chloro-6-fluorobenzoyl)-4-(2,6-dimethoxy-4-ethoxymethylphenyl)-L-phenylalanine, N-(2-chloro-6-fluorobenzoyl)-4-(2,6-dimethoxy-4-methoxymethylphenyl)-L-phenylalanine, and N-(2,6-difluorobenzoyl)-4-(2,6-dimethoxy-4-methoxymethylphenyl)-L-phenylalanine. 
     
     
         9 . The method according to  claim 1 , wherein the compound is N-(2,6-difluorobenzoyl)-4-(2,6-dimethoxy-4-ethoxymethylphenyl)-L-phenylalanine.