Methods to inhibit or augment an inflammatory response
Isolated and purified chemokine peptides, variants, and derivatives thereof, as well as chemokine peptide analogs, are provided.
1. A method of inhibiting a respiratory disease associated with a chemokine-induced activity, comprising: administering to a human afflicted with, the respiratory disease, or a human in need thereof, an amount of:
a compound of formula (XIV);
or a pharmaceutically acceptable salt thereof;
effective to inhibit said respiratory disease, wherein the respiratory disease is asthma and wherein formula (XIV) is:
wherein R 1 is N(Rb)(Rc) wherein each Rb and Rc is independently H or (C 1 -C 6 )alkyl; R 2 is OH; R 3 is H; R 4 is H; and n is 0 or 1; wherein any (C 1 -C 6 )alkyl or the benzo ring in formula (XIV) is optionally substituted with at least one substituent selected from the group consisting of halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkanoyloxy, (C 1 -C 6 )alkoxycarbonyl, methoxydioxy, hydroxy, C(═O), SO 2 H, SO 3 H, and N(Rb)(Rc).
2. A method of treating a human afflicted with, a respiratory disease, or human in need thereof associated with chemokine-induced activity, comprising: administering to a human afflicted with, the respiratory disease, or a human in need thereof, an amount of:
a compound of formula (XIV);
or a pharmaceutically acceptable salt thereof;
effective to treat said respiratory disease, wherein the respiratory disease is asthma and wherein formula (XIV) is:
wherein R 1 is N(Rb)(Rc) wherein each Rb and Rc is independently H or (C 1 -C 6 )alkyl; R 2 is OH; R 3 is H; R 4 is H; and n is 0 or 1; wherein any (C 1 -C 6 )alkyl or the benzo ring in formula (XIV) is optionally substituted with at least one substituent selected from the group consisting of halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkanoyloxy, (C 1 -C 6 )alkoxycarbonyl, methoxydioxy, hydroxy, C(═O), SO 2 H, SO 3 H, and N(Rb)(Rc).
3. A method of inhibiting a respiratory disease associated with a chemokine-induced activity, comprising: administering to a human afflicted with, the respiratory disease, or a human in need thereof, an amount of a compound of formula (XIV);
or a pharmaceutically acceptable salt thereof;
effective to inhibit said respiratory disease, wherein the respiratory disease is chronic obstructive pulmonary disease (COPD) and wherein formula (XIV) is:
wherein R 1 is N(Rb)(Rc) wherein each Rb and Rc is independently H or (C 1 -C 6 )alkyl; R 7 is OH; R 3 is H; R 4 is H; and n is 0 or 1; wherein any (C 1 -C 6 )alkyl or the benzo ring in formula (XIV) is optionally substituted with at least one substituent selected from the group consisting of halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkanoyloxy, (C 1 -C 6 )alkoxycarbonyl, methoxydioxy, hydroxy, C(═O), SO 2 H, SO 3 H, and N(Rb)(Rc).
4. A method of inhibiting a respiratory disease associated with a chemokine-induced activity, comprising: administering to a human afflicted with, the respiratory disease, or a human in need thereof, an amount of a compound of formula (XIV);
or a pharmaceutically acceptable salt thereof;
effective to inhibit said respiratory disease, wherein the respiratory disease is allergic rhinitis and wherein formula (XIV) is:
wherein R 1 is N(Rb)(Rc) wherein each Rb and Rc is independently H or (C 1 -C 6 )alkyl; R 9 is OH; R 3 is H, R 4 is H; and n is 0 or 1; wherein any (C 1 -C 6 )alkyl or the benzo ring in formula (XIV) is optionally substituted with at least one substituent selected from the group consisting of halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkanoyloxy, (C 1 -C 6 )alkoxycarbonyl, methoxydioxy, hydroxy, C(═O), SO 2 H, SO 3 H, and N(Rb)(Rc).
5. A method of treating a human afflicted with, a respiratory disease, or human in need thereof associated with chemokine-induced activity, comprising: administering to a human afflicted with, the respiratory disease, or a human in need thereof, an amount of:
a compound of formula (XIV);
or a pharmaceutically acceptable salt thereof;
effective to treat said respiratory disease, wherein the respiratory disease is chronic obstructive pulmonary disease (COPD) and wherein formula (XIV) is:
wherein R 1 is N(Rb)(Rc) wherein each Rb and Rc is independently H or (C 1 -C 6 )alkyl; R 2 is OH; R 3 is H; R 4 is H; and n is 0 or 1; wherein any (C 1 -C 6 )alkyl or the benzo ring in formula (XIV) is optionally substituted with at least one substituent selected from the group consisting of halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkanoyloxy, (C 1 -C 6 )alkoxycarbonyl, methoxydioxy, hydroxy, C(═O), SO 2 H, SO 3 H, and N(Rb)(Rc).
6. A method of treating a human afflicted with, a respiratory disease, or human in need thereof associated with chemokine-induced activity, comprising: administering to a human afflicted with, the respiratory disease, or a human in need thereof, an amount of:
a compound of formula (XIV);
or a pharmaceutically acceptable salt thereof; effective to treat said respiratory disease, wherein the respiratory disease is allergic rhinitis and wherein formula (XIV) is:
wherein R 1 is N(Rb)(Rc) wherein each Rb and Rc is independently H or (C 1 -C 6 )alkyl; R 2 is OH; R 3 is H; R 4 is H; and n is 0 or 1; wherein any (C 1 -C 6 )alkyl or the benzo ring in formula (XIV) is optionally substituted with at least one substituent selected from the group consisting of halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 1 -C 6 )alkyl, (C 1 -C o )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkanoyloxy, (C 1 -C 6 )alkoxycarbonyl, methoxydioxy, hydroxy, C(═O), SO 2 H, SO 3 H, and N(Rb)(Rc).