Heterocyclic Compounds as CCR2 Antagonists

Abstract

Compounds of formula (I) Q-L-W—C(═X)—Z—P wherein Q is an amine of the formula —N(R 1 )(R 2 ); L is an alkyl or heterocyclyl-alkyl linker; W is a 6- or 7-membered aliphatic ring comprising ring atoms Y 1 and Y 2 which are linked to groups L and C(X) respectively and Y 1 and Y 2 are independently selected from N and C; X is O, N, N—CN or S; Z is NR 3 ; P is an optionally substituted monocyclic or bicyclic aryl or heteroaryl group; and pharmaceutically acceptable salts or solvates thereof, are useful in the treatment of C—C chemokine mediated conditions.

1 - 12 . (canceled) 
     
     
         13 . A method comprising treating human diseases or conditions in which modulating chemokine receptor activity is beneficial by administering to a human in need thereof. The use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
       
       wherein
 R 2  is selected from hydrogen, C 1-6  alkyl, C 3-7  cycloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, cycloalkyl-alkyl of up to 14 ring and chain atoms, heterocyclyl of up to 7 ring atoms, heterocyclyl-alkyl of up to 14 ring and chain atoms, heterocyclyl-cycloalkyl of up to 14 ring atoms, heterocyclyl-heterocyclyl-alkyl of up to 20 ring and chain atoms, heterocyclyl-aryl-alkyl of up to 20 ring and chain atoms, heterocyclyl-aryl of up to 20 ring atoms; aryl-alkyl of up to 14 ring and chain atoms, aryl-heterocyclyl-alkyl of up to 20 ring and chain atoms, aryl-oxy-alkyl of up to 14 ring and chain atoms, aryl-cycloalkyl of up to 14 ring atoms, and aryl-aryl-alkyl of up to 20 ring and chain atoms; 
 and wherein each chain or ring is independently optionally substituted by up to 3 substituents each independently selected from halogen, hydroxy, C 1-6  alkyl, C 1-4 alkoxy optionally substituted by C 1-4  alkoxy, cyano, C 1-4  alkylsulfonyl, trifluoromethyl, carboxy, C 1-4  alkoxycarbonyl, C 1-2 alkyloxycarbonylphenyl, phenyl, NH 2 , NO 2 , ═O C 1-4  alkylcarbonyl, C 3-7  cycloalkyl-heteroaryl of up to 10 ring atoms, and a nitrogen atom of a heteroaromatic ring may be substituted by an oxide group; and 
 P is a phenyl optionally substituted by 1 or 2 substituents independently selected from halogen, C 1-4 alkyl, cyano, trifluoromethyl, C 1-4 alkoxy, and trifluoromethylthio. 
 
     
     
         14 - 26 . (canceled) 
     
     
         27 . A method comprising treating human diseases or conditions in which modulating chemokine receptor activity is beneficial by administering to a human in need thereof a pharmaceutical composition comprising (i) a compound of formula (I), or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
       
       wherein
 R 2  is selected from hydrogen, C 1-6  alkyl, C 3-7  cycloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, cycloalkyl-alkyl of up to 14 ring and chain atoms, heterocyclyl of up to 7 ring atoms, heterocyclyl-alkyl of up to 14 ring and chain atoms, heterocyclyl-cycloalkyl of up to 14 ring atoms, heterocyclyl-heterocyclyl-alkyl of up to 20 ring and chain atoms, heterocyclyl-aryl-alkyl of up to 20 ring and chain atoms, heterocyclyl-aryl of up to 20 ring atoms; aryl-alkyl of up to 14 ring and chain atoms, aryl-heterocyclyl-alkyl of up to 20 ring and chain atoms, aryl-oxy-alkyl of up to 14 ring and chain atoms, aryl-cycloalkyl of up to 14 ring atoms, and aryl-aryl-alkyl of up to 20 ring and chain atoms; 
 and wherein each chain or ring is independently optionally substituted by up to 3 substituents each independently selected from halogen, hydroxy, C 1-6  alkyl, C 1-4  alkoxy optionally substituted by C 1-4  alkoxy, cyano, C 1-4  alkylsulfonyl, trifluoromethyl, carboxy, C 1-4  alkoxycarbonyl, C 1-2 alkyloxycarbonylphenyl, phenyl, NH 2 , NO 2 , ═O, C 1-4  alkylcarbonyl, C 3-7  cycloalkyl-heteroaryl of up to 10 ring atoms, and a nitrogen atom of a heteroaromatic ring may be substituted by an oxide group; and 
 
       P is a phenyl optionally substituted by 1 or 2 substituents independently selected from halogen, C 1-4  alkyl, cyano, trifluoromethyl, C 1-4  alkoxy, and trifluoromethylthio; and 
       (ii) a pharmaceutically-acceptable diluent or carrier.