Modulators of chemokine receptor activity

Abstract

Chemokine receptor antagonists, in particular, bicyclic diamine compounds of Formula (I) that act as antagonists of chemokine CCR2 and CCR3 receptors including pharmaceutical compositions and uses thereof to treat or prevent diseases associated with monocyte accumulation, lymphocyte accumulation or leucocyte accumulation are described herein.

1 . A compound having the formula (I)  
     
       
         
         
             
             
         
       
     
     wherein 
 A is a substituted or unsubstituted (C 1 -C 6 )alkyl, substituted or unsubstituted (C 2 -C 6 )alkenyl, substituted or unsubstituted partially saturated or fully saturated (C 3 -C 6 )cycloalkyl, substituted or unsubstituted partially saturated or fully saturated 5 to 6 membered heterocyclic ring, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl group;  
 a is 0, 1, 2 or 3;  
 w, x, y and z are each independently 0, 1, 2, 3 or 4, with the proviso that (i) w is not 0 when x is 0; (ii) y is not 0 when z is 0; (iii) x is not 0 when w is 1, y is 0 and z is 1; (iv) x is not 0 when w is 1, z is 0 and y is 1; (v) x is not 0 when y is 0; (vi) w is not 0 when z is 0; (vii) w+x is less than 8; and (viii) y+z is less than 8;  
 p is 0 or 1;  
 L is a linking group selected from the group consisting of —(CH 2 ) q —X—, where X is NH, O, or oxo and q is an integer from 1 to 4 , —S(O) r —(CH 2 ) t —NH—, where r is 0, 1 or 2 and t is integer from 1 to 4, -(aryl)-NH—, -(heteroaryl)-NH—, and an amino acid residue where the amino nitrogen of said amino acid residue is attached to B and the carbonyl of said amino acid residue is attached to the ring nitrogen; and  
 B is a substituted or unsubstituted (C 1 -C 6 )alkylcarbonyl, substituted or unsubstituted arylcarbonyl, substituted or unsubstituted (C 1 -C 6 )alkoxy-carbonyl, substituted or unsubstituted aryloxycarbonyl, substituted or unsubstituted (C 1 -C 6 )alkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted (C 1 -C 6 ) alkylthiocarbonyl, substituted or unsubstituted arylthiocarbonyl, substituted or unsubstituted (C 1 -C 6 )alkyl-carbamoyl, substituted or unsubstituted arylcarbamoyl, substituted or unsubstituted (C 1 -C 6 )alkyl-C(═NH)—, substituted or unsubstituted aryl-C(═NH)—, or a protecting group;  
 a prodrug thereof, or a pharmaceutically acceptable salt, hydrate, or solvate of the compound or the prodrug.  
 
   
   
       2 - 28 . (canceled)