Chemical compounds

Abstract

The invention relates to piperazine derivatives, to processes for their preparation, to pharmaceutical compositions containing them, and to their medical use. The novel compounds are antagonists of tachykinins, including substance P and other neurokinins.

1 - 19 . (canceled)  
     
     
         20 . A method for the treatment of a condition mediated by a tachykinin, in a mammal, said method comprising administering an effective amount of a compound of formula (1):  
       
         
           
           
               
               
           
         
       
       wherein 
 R is a halogen atom or a C 1-4  alkyl group;  
 R 1  is hydrogen or a C 1-4  alkyl group;  
 R 2  is hydrogen, a C 1-4  alkyl, C 2-6  alkenyl or a C 3-7  cycloalkyl group; or R 1  and R 2  together with nitrogen and carbon atom to which they are attached respectively are a 5-6 membered heterocyclic group;  
 R 3  is a trifluoromethyl, a C 1-4  alkyl, a C 1-4  alkoxy, a trifluoromethoxy, or a halogen group;  
 R 4  is hydrogen, a (CH 2 ) q R 7  or a (CH 2 ) r CO(CH 2 ) p R 7  group;  
 R 5  is hydrogen, a C 1-4  alkyl or a COR 6  group;  
 R 6  is hydrogen, hydroxy, amino, methylamino, dimethylamino, a 5 membered heteroaryl group containing 1 to 3 heteroatoms selected from oxygen, sulphur and nitrogen or a 6 membered heteroaryl group containing 1 to 3 nitrogen atoms;  
 R 7  is hydrogen, hydroxy or NR 8 R 9  wherein R 8  and R 9  are independently hydrogen or C 1-4  alkyl optionally substituted by hydroxy, or by amino;  
 R 10  is hydrogen, a C 1-4  alkyl I group or  
 R 10  together with R 2  is a C 3-7  cycloalkyl group;  
 m is zero or an integer from 1 to 3; n is zero or an integer from 1 to 3; both p and r are independently zero or an integer from 1 to 4; q is an integer from 1 to 4; provided that, when R 1  and R 2  together with nitrogen and carbon atom to which they are attached respectively are a 5 to 6 membered heterocyclic group, i) m is 1 or 2; ii) when m is 1, R is not fluorine and iii) when m is 2, the two substituents R are not both fluorine,  
 or a pharmaceutically acceptable salt or solvate thereof.  
 
     
     
         21 . The method of  claim 20  wherein said tachykinin is substance P or other neurokinins.  
     
     
         22 . The method of  claim 20  wherein said mammal is man.