2,4-pyrimidinediamine compounds and prodrugs and their uses
View Patent ↗The present disclosure provides biologically active 2,4-pyrimidinediamine compounds of formulae (I)-(III): and salts thereof, compositions comprising these compounds, and methods of using these compounds in a variety of applications.
1. A method of treating a disease in a subject, where the disease is selected from an allergic disease, low grade scarring and scarring, comprising administering to the subject a pharmaceutically effective amount of a compound of any of formulae (I)-(III):
or a pharmaceutically acceptable salt thereof, effective to inhibit the Fc receptor signal transduction cascade.
2. The method according to claim 1 , comprising administering to the subject a pharmaceutically effective amount of the compound of formula (I):
or a pharmaceutically acceptable salt thereof.
3. The method according to claim 1 , comprising administering to the subject a pharmaceutically effective amount of the compound of formula (II):
or a pharmaceutically acceptable salt thereof.
4. The method according to claim 1 , comprising administering to the subject a pharmaceutically effective amount of the compound of formula (III):
or a pharmaceutically acceptable salt thereof.
5. A method according to claim 1 , comprising administering to the subject a pharmaceutically effective amount of a pharmaceutically acceptable salt of a compound of any of formulae (I)-(III).
6. A method according to claim 1 , comprising administering to the subject a pharmaceutically effective amount of a mono- or di-sodium salt, a mono- or di-potassium salt, a mono- or di-lithium salt, a calcium salt, a magnesium salt, or an ammonium salt of a compound of any of formulae (I)-(III).
7. A method according to claim 1 , comprising administering to the subject a pharmaceutically effective amount of a mono- or di-trifluoroacetic acid salt, a p-toluenesulfonic acid salt, a hydrochloride salt, a benzenesulfonic acid salt, or an ethanesulfonic acid salt of a compound of any of formulae (I)-(III).
8. A method according to claim 1 , comprising administering to the subject a pharmaceutically effective amount of a pharmaceutical composition comprising a compound of any of formulae (I)-(III) or a pharmaceutically acceptable salt thereof, and an acceptable carrier, excipient and/or diluent.
9. A method of treating an autoimmune disease in a subject, the autoimmune disease being selected from Hashimoto's thyroiditis, autoimmune hemolytic anemia, autoimmune atrophic gastritis of pernicious anemia, autoimmune encephalomyelitis, autoimmune orchitis, Goodpasture's disease, autoimmune thrombocytopenia, sympathetic ophthalmia, myasthenia gravis, Graves' disease, primary biliary cirrhosis, chronic aggressive hepatitis, ulcerative colitis, membranous glomerulopathy, systemic lupus erythematosis, rheumatoid arthritis, Sjogren's syndrome, Reiter's syndrome, polymyositis-dermatomyositis, systemic sclerosis, polyarteritis nodosa, multiple sclerosis and bullous pemphigoid, the method comprising administering to the subject a pharmaceutically effective amount of a compound of any of formulae (I)-(III):
or a pharmaceutically acceptable salt thereof, effective to treat the autoimmune disease.
10. The method according to claim 9 , comprising administering to the subject a pharmaceutically effective amount of the compound of formula (I):
or a pharmaceutically acceptable salt thereof.
11. The method according to claim 9 , comprising administering to the subject a pharmaceutically effective amount of the compound of formula (II):
or a pharmaceutically acceptable salt thereof.
12. The method according to claim 9 , comprising administering to the subject a pharmaceutically effective amount of the compound of formula (III):
or a pharmaceutically acceptable salt thereof.
13. A method of treating rheumatoid arthritis in a subject, comprising administering to a subject suffering from rheumatoid arthritis a pharmaceutically effective amount of a compound of any of formulae (I)-(III):
or a pharmaceutically acceptable salt thereof.
14. The method according to claim 13 , comprising administering to the subject a pharmaceutically effective amount of the compound of formula (I):
or a pharmaceutically acceptable salt thereof.
15. The method according to claim 13 , comprising administering to the subject a pharmaceutically effective amount of the compound of formula (II):
or a pharmaceutically acceptable salt thereof.
16. The method according to claim 13 , comprising administering to the subject a pharmaceutically effective amount of the compound of formula (III):
or a pharmaceutically acceptable salt thereof.
17. The method according to claim 13 in which the amount of the compound or salt administered is effective to achieve a serum concentration of the corresponding drug that is at or above the IC 50 of Syk inhibition of the drug, as measured in an in vitro assay.