Phenyl amino pyrimidine compounds and uses thereof
The present invention relates to phenyl amino pyrimidine compounds which are inhibitors of protein kinases including JAK kinases. In particular the compounds are selective for JAK2 kinases. The kinase inhibitors can be used in the treatment of kinase associated diseases such as immunological and inflammatory diseases including organ transplants; hyperproliferative diseases including cancer and myeloproliferative diseases; viral diseases; metabolic diseases; and vascular diseases.
1. The compound N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide having the structure
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 which is a hydrochloride salt of N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide.
3. The compound of claim 1 which is N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide.
4. The compound N-(cyanomethyl)-4-(2-(4-(4-hydroxypiperidin-1-yl)phenylamino)-5-methylpyrimidin-4-yl)benzamide or a pharmaceutically acceptable salt thereof.
5. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
6. An implant which comprises the compound of claim 1 .
7. A pharmaceutical composition comprising the compound of claim 4 in a pharmaceutically acceptable carrier.
8. An implant which comprises the compound of claim 4 .
9. A method for the treatment of a disease associated with Janus Kinase (JAK) which comprises administering to a subject in need an effective amount of the compound of claim 1 or a pharmaceutical composition thereof, wherein the disease is a myeloproliferative disease.
10. The method of claim 9 wherein the myeloproliferative disease is myelofibrosis, polycythemia vera (PV) and essential thrombocythemia (ET).
11. The method of claim 10 wherein the myeloproliferative disease is myelofibrosis.
12. A method for the treatment of a disease associated with Janus Kinase (JAK) which comprises administering to a subject in need an effective amount of the compound of claim 4 or a pharmaceutical composition thereof, wherein the disease is a myeloproliferative disease.
13. The method of claim 12 wherein the myeloproliferative disease is selected from the group consisting of polycythemia vera (PV), myelofibrosis, thrombocythemia, essential thrombocythemia (ET), idiopathic myelofibrosis, chronic myelogenous leukemia, systemic mastocystosis (SM), chronic neutrophilic leukemia (CNL), myelodisplastic syndrome (MDS) and systemic mast cell disease (SMCD).
14. The method of claim 13 wherein the myeloproliferative disease is myelofibrosis, polycythemia vera (PV) and essential thrombocythemia (ET).
15. The method of claim 13 wherein the myeloproliferative disease is myelofibrosis.
16. A method of inhibiting a JAK in a cell comprising contacting the cell with the compound of claim 1 .
17. A method of inhibiting a JAK in a cell comprising contacting the cell with the compound of claim 4 .