2,4-PYRIMIDINEDIAMINE COMPOUNDS AND THEIR USES
The present invention provides 2,4-pyrimidinediamine compounds that inhibit the IgE and/or IgG receptor signaling cascades that lead to the release of chemical mediators, intermediates and methods of synthesizing the compounds and methods of using the compounds in a variety of contexts, including in the treatment and prevention of diseases characterized by, caused by or associated with the release of chemical mediators via degranulation and other processes effected by activation of the IgE and/or IgG receptor signaling cascades.
1 . A pharmaceutical composition, comprising:
a means for inhibiting an Fc receptor signal cascade; and
a pharmaceutically acceptable excipient.
2 . The pharmaceutical composition of claim 1 , wherein the Fc receptor signal cascade is an FcεRI signal cascade.
3 . The pharmaceutical composition of claim 1 , wherein the Fc receptor signal cascade is an FcγRI signal cascade.
4 . The pharmaceutical composition of claim 1 , wherein the means is a means for reducing or preventing degranulation of immune cells.
5 . The pharmaceutical composition of claim 1 , wherein the means is a means for ameliorating or preventing Type I hypersensitivity reactions.
6 . The pharmaceutical composition of claim 1 , wherein the means is a means for inhibiting Syk kinase activity.
7 . The pharmaceutical composition of claim 6 , wherein inhibiting Syk kinase activity comprises inhibiting phosphorylation of one or more Syk kinase substrates.
8 . The pharmaceutical composition of claim 1 , wherein the means is a means for reducing inflammation.
9 . The pharmaceutical composition of claim 1 , wherein reducing inflammation comprises inhibiting a pro-inflammatory activation pathway.
10 . The pharmaceutical composition of claim 1 , wherein the means is a means for selectively inhibiting Fc-mediated cell degranulation without inhibiting other degranulation mechanisms.
11 . The pharmaceutical composition of claim 10 , wherein the means for selectively inhibiting Fc-mediated cell degranulation is a means for selectively inhibiting FcεRI-mediated cell degranulation.
12 . The pharmaceutical composition of claim 10 , wherein the means for selectively inhibiting Fc-mediated cell degranulation is a means for selectively inhibiting FcγRI-mediated cell degranulation.
13 . The pharmaceutical composition of claim 10 , wherein the means for selectively inhibiting Fc-mediated cell degranulation is about 10-fold or more selective for Fc-mediated degranulation over ionophore-induced degranulation.
14 . The pharmaceutical composition of claim 1 , wherein the means is a means for inhibiting IgG-induced or IgE-induced degranulation of a cell.
15 . The pharmaceutical composition of claim 14 , wherein the cell is a mast, basophil, neutrophil, or eosinophil cell.
16 . The pharmaceutical composition of claim 1 , wherein the means comprises a pyrimidine diamine compound.
17 . A method for inhibiting an Fc receptor signal cascade in a subject, comprising administering to the subject a pharmaceutical composition according to claim 1 .
18 . A method, comprising contacting a cell that degranulates with an amount of a the pharmaceutical composition according to claim 1 effective to inhibit degranulation of the cell.
19 . A method for inhibiting a Syk kinase, comprising contacting the Syk kinase with a pharmaceutical composition according to claim 1 .
20 . The method of claim 19 , wherein the Syk kinase is in a subject.
21 . The method of claim 20 , wherein the method is a method for treating a disease or condition for which a Syk inhibitor is indicated.