Chemokine receptor antagonists and methods of use therefor

The method of claim 13 wherein said phenyl group bears a meta substituent, R40, and the antagonist of chemokine receptor function is represented by the following structural formula:

• 24
• wherein R40 is -OH, -COOH, -NO, halogen, aliphatic group, substituted aliphatic group, an aromatic group, a substituted aromatic group, -NR24R25, -CONR24R25, Q-(aliphatic group), Q-(substituted aliphatic group), -O-(aliphatic group), -O-(substituted aliphatic group), -O-(aromatic group), -O-(substituted aromatic group), an electron withdrawing group,
• -(O)u-(CH2)t-C(O)OR20, -(O)u-(CH2)t-OC(O)R20,
• -(O)u-(CH2)t-C(O)-NR21R22 or -(O)u-(CH2)t-NHC(O)O-R20;
• R20, R21 or R22 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group;
• or
• R21 and R22, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring;
• Q is -NR24C(O)- or -NR24S(O)2-;
• R24 and R25 are independently -H, -OH, an aliphatic group or a substituted aliphatic group;
• u is zero or one;
• and
• t is an integer from zero to about 3.

A method of treating a disease associated with aberrant leukocyte recruitment and/or activation comprising administering to a subject in need thereof an effective amount of a compound represented by the following structural formula:

• 25
• and physiologically acceptable salts thereof, wherein:
• Ar1 is a substituted or unsubstituted heteroaryl group;
• Ar2 is a substituted or unsubstituted aromatic carbocyclic or heteroaryl group;
• n is an integer from one to about four;
• M is >NR2, >CR1R2, -O-CR1R2-O- or -CH2-CR1R2-O-;
• The ring containing M is substituted or unsubstituted;
• R1 is -H, -OH, -N3, a halogen, an aliphatic group, a substituted aliphatic group, an aminoalkyl group, -O-(aliphatic group), -O-(substituted aliphatic group),-SH, -S-(aliphatic group), -S-(substituted aliphatic group), -OC(O)-(aliphatic group), -O-C(O)-(substituted aliphatic group), -C(O)O-(aliphatic group), -C(O)O-(substituted aliphatic group), -COOH, -CN, -CO-NR3R4, -NR3R4 or R1 is a covalent bond between the ring atom at M and an adjacent carbon atom in the ring which contains M;
• R2 is -H, -OH, an acyl group, a substituted acyl group, -NR5R6, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group, a substituted non-aromatic heterocyclic group, -O-(substituted or unsubstituted aromatic group) or -O-(substituted or unsubstituted aliphatic group);
• R3, R4, R5 and R6 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group;
• or
• R1 and R2, R3 and R4, or R5 and R6 taken together with the atom to which they are bonded, form a substituted or unsubstituted non-aromatic heterocyclic ring.

A method of treating a disease associated with aberrant leukocyte recruitment and/or activation comprising administering to a subject in need thereof an effective amount of a compound represented by the following structural formula:

• 27
• and physiologically acceptable salts thereof, wherein:
• Ar1 is a substituted or unsubstituted heteroaryl group;
• Ar2 is a substituted or unsubstituted aromatic carbocyclic or heteroaryl group;
• n is an integer from one to about four;
• n is an integer from one to about four;
• R50 and R51 are each, independently, -H,R50 and R51 are each independently -H, an aliphatic group, a substituted aliphatic group, an aminoalkyl group, -NR3R4, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group, a substituted non-aromatic heterocyclic group, or a covalent bond between the nitrogen atom an adjacent carbon atom;
• R3 and R4 are independently -H, an acyl group, a substituted acyl group, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group.

A compound represented by the following structural formula:

• 29
• and physiologically acceptable salts thereof, wherein:
• Ar1 is a substituted or unsubstituted heteroaryl group;
• Ar1 is a substituted or unsubstituted aromatic carbocyclic or heteroaryl group;
• n is an integer from one to about four;
• M is >NR2, >CR1R2-O-CR1R2-O- or -CH2-CR1R2-O-;
• The ring containing M is substituted or unsubstituted;
• q1 is an integer, such as an integer from zero to about three;
• q2 is an integer from zero to about one;
• R1 is -H, -OH, -N3, a halogen, an aliphatic group, a substituted aliphatic group, an aminoalkyl group, -O-(aliphatic group), -O-(substituted aliphatic group),-SH, -S-(aliphatic group), -S-(substituted aliphatic group), -OC(O)-(aliphatic group), -O-C(O)-(substituted aliphatic group), -C(O)O-(aliphatic group), -C(O)O-(substituted aliphatic group), -COOH, -CN, -CO-NR3R4, -NR3R4 or R1 is a covalent bond between the ring atom at M and an adjacent carbon atom in the ring which contains M;
• R2 is -H, -OH, an acyl group, a substituted acyl group, -NR5R6, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group, a substituted non-aromatic heterocyclic group, -O-(substituted or unsubstituted aromatic group) or -O-(substituted or unsubstituted aliphatic group);
• R3, R4, R5 and R6 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group;
• or
• R1 and R2, R3 and R4, or R5 and R6 taken together with the atom to which they are bonded, form a substituted or unsubstituted non-aromatic heterocyclic ring.

A compound represented by the following structural formula:

• 35
• and physiologically acceptable salts thereof, wherein:
• Ar1 is a substituted or unsubstituted heteroaryl group;
• Ar2 is a substituted or unsubstituted aromatic carbocyclic or heteroaryl group;
• n is an integer from one to about four;
• M is >NR2, >CR1R2 -O-CR1R2-O- or -CH2-CR1R2-O-;
• The ring containing M is substituted or unsubstituted;
• R1 is -H, -OH, -N3, a halogen, an aliphatic group, a substituted aliphatic group, an aminoalkyl group, -O-(aliphatic group), -O-(substituted aliphatic group),-SH, -S-(aliphatic group), -S-(substituted aliphatic group), -OC(O)-(aliphatic group), -O-C(O)-(substituted aliphatic group), -C(O)O-(aliphatic group), -C(O)O-(substituted aliphatic group), -COOH, -CN, -CO-NR3R4, -NR3R4 or R1 is a covalent bond between the ring atom at M and an adjacent carbon atom in the ring which contains M;
• R2 is -H, -OH, an acyl group, a substituted acyl group, -NR5R6, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group, a substituted non-aromatic heterocyclic group, -O-(substituted or unsubstituted aromatic group) or -O-(substituted or unsubstituted aliphatic group);
• R3, R4, R5 and R6 are independently -H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group;
• or
• R1 and R2, R3 and R4, or R5 and R6 taken together with the atom to which they are bonded, form a substituted or unsubstituted non-aromatic heterocyclic ring.

A compound represented by the following structural formula:

• 37
• and physiologically acceptable salts thereof, wherein:
• Ar1 is a substituted or unsubstituted heteroaryl group;
• Ar2 is a substituted or unsubstituted aromatic carbocyclic or heteroaryl group;
• n is an integer from one to about four;
• n is an integer from one to about four;
• R50 and R51 are each, independently, -H,R50 and R51 are each independently -H, an aliphatic group, a substituted aliphatic group, an aminoalkyl group,
• NR3R4, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group, a substituted non-aromatic heterocyclic group, or a covalent bond between the nitrogen atom an adjacent carbon atom;
• R3 and R4are independently -H, an acyl group, a substituted acyl group, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group, a substituted benzyl group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group.