Chemokine receptor antagonists and methods of use therefor

A compound represented by the following structural formula:

• or physiologically acceptable salt thereof, wherein:
• n is an integer from one to five;
• M is >NR2 or >CR1R2;
• R1 is —H, —OH, a halogen, an aliphatic 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), —CN, —COOH, —CO—NR3R4 or —NR3R4;
• R2 is —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 or a substituted non-aromatic heterocyclic group;
• wherein:
• R3, R4, R5 and R6 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;
• 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 carbocyclic or heterocyclic ring;
• Z is represented by the following structural formula:
• Rc is a C10-C20 aliphatic group, a substituted C1-C20 aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group or a substituted benzyl group;
• and
• Ring A and Ring B are independently substituted or unsubstituted;
• said substituted aliphatic group, substituted acyl group, substituted aromatic group, substituted benzyl group, substituted non-aromatic heterocyclic group, substituted non-aromatic carbocyclic group, Ring A when substituted and Ring B when substituted, are substituted with one or more substituents independently selected from the group consisting of an aliphatic group, electron withdrawing group, a halogen, azido, —OH, —SH, —CN, —COOH, —CONH2, —NO2, —NH(benzyl), —O— (aliphatic group), —O— (aromatic group), —O— (benzyl group), —N— (benzyl group)2, —COO(aliphatic group), —COO(aromatic group), —COO(benzyl group), —CONH(benzyl group), —CON(benzyl)2, —SOk(aromatic group), —SOk(benzyl group), —SOk(aliphatic group), —CO—NR21R22, —NR21R22, —NH—C(═NH)—NH2, —(O)u—(CH2)t—COOR20, —(O)u—(CH2)t—OC(O)R20, —(O)u—(CH2)t—C(O)—NR21R22 and —(O)u—(CH2)t—NHC(O)—O—R20;
• wherein:
• k is 0, 1 or 2;
• u is zero or one;
• t is an integer from zero to 3;
• R20, R21 and R22 are independently —H, an aliphatic group, an 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;
• and
• said non-aromatic heterocyclic group and said non-aromatic heterocyclic ring are a 5- to 8-membered ring comprising one or two heteroatoms independently selected from the group consisting of nitrogen, oxygen or sulfur, optionally fused to a cycloalkyl or aromatic ring.

A compound represented by the following structural formula:

• or physiologically acceptable salt thereof, wherein:
• n is an integer from one to five;
• M is >NR2 or >CR1R2;
• R1 is —OH, a halogen, —O— (substituted aliphatic group), —S— (substituted aliphatic group), —OC(O)— (aliphatic group), —O—C(O)— (substituted aliphatic group), —CN, —COOH, —CO—NR3R4 or —NR3R4;
• R2 is —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 or a substituted non-aromatic heterocyclic group;
• wherein:
• R3, R4, R5 and R6 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;
• 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 carbocyclic or heterocyclic ring;
• Z is represented by a structural formula selected from:
• wherein:
• Q is —CO—NRc—;
• Wb is —CH═NH, —CN, —CH2—NR11R12, —CH2—OR11, —CH2—NH—CO—NR11R12, —CH2—O—CO—NR11R12 or —CH2—NHC(O)—O—R11;
• R11 and R12 are independently —H, an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group or a non-aromatic heterocyclic group;
• or
• R11 and R12, taken together with the nitrogen atom to which they are bonded, form a non-aromatic heterocyclic ring;
• Rc is hydrogen a C10-C20 aliphatic group, a substituted C1-C20 aliphatic group, an aromatic group, a substituted aromatic group, a benzyl group or a substituted benzyl group;
• and
• Ring A and Ring B are independently substituted or unsubstituted;
• said substituted aliphatic group, substituted acyl group, substituted aromatic group, substituted benzyl group, substituted non-aromatic heterocyclic group, substituted non-aromatic carbocyclic group, Ring A when substituted and Ring B when substituted, are substituted with one or more substituents independently selected from the group consisting of an aliphatic group, electron withdrawing group, a halogen, azido, —OH, —SH, —CN, —COOH, —CONH2, —NO2, —NH(benzyl), —O— (aliphatic group), —O— (aromatic group), —O— (benzyl group), —N— (benzyl group)2, —COO(aliphatic group), —COO(aromatic group), —COO(benzyl group), —CONH(benzyl group), —CON(benzyl)2, —SOk(aromatic group), —SOk(benzyl group), —SOk(aliphatic group), —CO—NR21R22, —NR21R22, —NH—C(═NH)—NH2, —(O)u—(CH2)t—COOR20, —(O)u—(CH2)t—OC(O)R20, —(O)u—(CH2)t—C(O)—NR21R22 and —(O)u—(CH2)t—NHC(O)—O—R20;
• wherein:
• k is 0, 1 or 2;
• u is zero or one;
• t is an integer from zero to 3;
• R20, R21 and R22 are independently —H, an aliphatic group, an 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;
• and
• said non-aromatic heterocyclic group and said non-aromatic heterocyclic ring are a 5- to 8-membered ring comprising one or two heteroatoms independently selected from the group consisting of nitrogen, oxygen or sulfur, optionally fused to a cycloalkyl or aromatic ring.