Chemokine receptor antagonists and methods of use therefor

A method of treating a subject having a disease associated with aberrant leukocyte recruitment and/or activation, said disease being selected from the group consisting of arthritis, psoriasis, multiple sclerosis, ulcerative colitis, Crolin's disease, allergy, asthma, AIDS associated encephalitis, AIDS related maculopapular skin eruption, AIDS related interstitial pneumonia, AIDS related enteropathy, AIDS related periportal hepatic inflammation and AIDS related glomerulo nepliritis, comprising administering to the individual a therapeutically effective amount of a compound represented by the following structural formula:

• and physiologically acceptable salts thereof, wherein:
• M is >NR2, >CR1R2 or —CO—;
• R1 is —H, —OH, an aliphatic group, —O-(aliphatic group), —SH or —S-(aliphatic group);
• and
• R2 is an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzylic group, a substituted benzylic group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group;
• and
• Z is represented by a structural formula selected from:
• wherein:
• X1 is a chemical bond, —S—, —CH2— or —CH2S—;
• W is —H or an electron withdrawing group;
• and
• wherein Ring A and Ring B are substituted or un substituted.

A method of treating a subject having a disease associated with aberrant leukocyte recruitment and/or activation, comprising administering to the individual a therapeutically effective amount of a compound represented by the following structural formula:

• and physiologically acceptable salts thereof, wherein:
• Ring A and Ring B are each, independently, substituted or unsubstituted;
• X1 is —CH2CH2—, —CH2S— or —S—;
• W is —H or an electron withdrawing group;
• Y is a covalent bond, —O— or —CO—;
• n is an integer from one to about five;
• X is a covalent bond or —CO—,
• M is >NR2, >CR1R2 or >C═O;
• R1 is —H, —OH, an aliphatic group, —O-(aliphatic group), —SH or —S-(aliphatic group);
• and
• R2 is an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzylic group, a substituted benzylic group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group.

A method of treating a subject having a disease associated with aberrant leukocyte recruitment and/or activation, comprising administering to the individual a therapeutically effective amount of a compound that can inhibit the binding of a chemokine to a chemokine receptor, wherein the compound is represented by the following structural formula:

• and physiologically acceptable salts thereof, wherein:
• M is >NR2, >CR1R2 or >C═O;
• Y is a covalent bond, —O— or —CO—;
• n is an integer from one to about five;
• X is a covalent bond or —CO—;
• R1 is —H, —OH, an aliphatic group, —O-(aliphatic group), —SH or —S-(aliphatic group);
• R2 is an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzylic group, a substituted benzylic group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group;
• and
• Z is represented by a structural formula selected from:
• wherein:
• X1 is a chemical bond, —S—, —CH2— or —CH2S—;
• W is —H or an electron withdrawing group;
• and
• wherein ring A and ring B are substituted or unsubstituted.

A method of treating a subject having a disease associated with aberrant leukocyte recruitment and/or activation, comprising administering to the individual a therapeutically effective amount of a compound that can inhibit the binding of a chemokine to a chemokine receptor, wherein the compound is represented by the following structural formula:

• and physiologically acceptable salts thereof, wherein:
• Ring A and Ring B are each, independently, substituted or unsubstituted,
• X1 is —CH2CH2—, —CH2S— or —S—;
• W is —H or an electron withdrawing group;
• Y is a covalent bond, —O— or —CO—;
• n is an integer from one to about five;
• X is a covalent bond or —CO—;
• M is >NR2, >CR1R2or >C═O;
• R1 is —H, —OH, an aliphatic group, —O-(aliphatic group), —SH or —S-(aliphatic group);
• and
• R2 is an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzylic group, a substituted benzylic group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group.