Pharmaceutical compounds

1. A method for the treatment of:

A. a disease state or condition mediated by a kinase which is BCR-abl, VEGFR, PDGFR, EGFR, Flt3, JAK, C-abl, PDK1, Chk, FGFR, Ret, Eph, or Src; or

B. a cancer in which the cancer cells thereof contain a drug resistant kinase mutation which is:

(a) a threonine gatekeeper mutation; or

(b) a drug-resistant gatekeeper mutation; or

(c) an imatinib resistant mutation; or

(d) a nilotinib resistant mutation; or

(e) a dasatinib resistant mutation; or

(f) a T670I mutation in KIT; or

(g) a T674I mutation in PDGFR; or

(h) T790M mutation in EGFR; or

(i) a T315I mutation in abl; or

C. a cancer which expresses a mutated molecular target which is a mutated form of BCRabl , c-kit, PDGF, EGF receptor or ErbB2;

which method comprises administering to a patient in need thereof a therapeutically effective amount of a compound of the formula:

or a salt, solvate, tautomer, or N-oxide thereof.

2. A method according to claim 1 comprising administering 1-cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-urea or a salt thereof.

3. A method according to claim 2 wherein the salt is an L-lactate, D-lactate or citric acid salt.

4. A method as defined in claim 1 , wherein said method is for the treatment of any one or more (in any combination) of diseases and conditions selected from ocular diseases or conditions; myeloproliferative disorders (MPD); juvenile myelomonocytic leukemia (JMML); Chronic Myelomonocytic Leukemias (CMML); megakaryocytic leukaemia (including megakaryocytic AML (AML M7)); Philadelphia chromosome-negative CML; imatinib resistant CML; nilotinib-resistant CML; dasatinib-resistant CML; gastrointestinal stromal tumours (GISTs); chronic myelomonocytic leukemia (CMML); the hypereosinophilic syndrome; dermatofibrosarcoma protuberans; Philadelphia chromosome positive malignancies; myeloproliferative syndrome; multiple myelomas, epithelial cancers, head and neck cancers, abnormalities in human skeletal development; thyroid cancers; and Hirschsprung's disease.

5. A method according to claim 1 wherein diseases or conditions (in any combination) are selected from myeloproliferative disorders (MPD); juvenile myelomonocytic leukemia (JMML); Chronic Myelomonocytic Leukemias (CMML); megakaryocytic leukaemia including megakaryocytic AML (AML M7); Philadelphia chromosome-negative CML; and imatinib resistant CML.

6. A method according to claim 1 wherein the disease state or condition is myelofibrosis with myeloid metaplasia (MMM).

7. A method for the diagnosis and treatment of a disease state or condition mediated by a kinase as defined in claim 1 ; which method comprises (i) screening a patient to determine whether a disease or condition from which the patient is or may be suffering is one which would be susceptible to treatment with a compound having activity against the kinase; and (ii) where it is indicated that the disease or condition is one from which the patient is thus susceptible, thereafter administering to the patient a compound as defined in claim 1 or a salt, solvate, tautomer, or N-oxide thereof.

8. A method for the diagnosis and treatment of a cancer in which the cancer cells thereof contain a drug resistant kinase mutation as defined in claim 1 , which method comprises (i) screening a patient to determine whether a cancer from which the patient is or may be suffering is one in which the cancer cells thereof contain the drug resistant kinase mutation; and (ii) where it is indicated that the cancer cells do contain the drug resistant mutation, thereafter administering to the patient a compound as defined in claim 1 or a salt, solvate, tautomer, or N-oxide thereof.

9. A method for the diagnosis and treatment of a cancer which expresses a mutated molecular target which is a mutated form of BCRabl , c-kit, PDGF, EGF receptor or ErbB2; which method comprises (i) screening a patient to determine whether a cancer from which the patient is or may be suffering is one which expresses the said mutated molecular target; and (ii) where it is indicated that the cancer cells do express the said mutated molecular target, thereafter administering to the patient a compound as defined in claim 1 or a salt, solvate, tautomer, or N-oxide thereof.

10. A method according to claim 1 wherein the disease state or condition is a cancer selected from multiple myeloma, bladder, hepatocellular, oral squamous cell carcinoma, cervical, prostate and thyroid carcinomas, lung, breast, and colon cancers.

11. A method of modulating a cellular process by modulating the activity of a kinase selected from BCR-abl, VEGFR, PDGFR, EGFR, Flt3, JAK, C-abl, PDK1, Chk, FGFR, Ret, Eph, and Src using a compound as defined in claim 1 or a salt, solvate, tautomer, or N-oxide thereof.

12. A method for alleviating or reducing the incidence of a disease state or condition as defined in claim 1 , which method comprises administering to a patient in need thereof a compound, in a therapeutically effective amount, as defined in claim 1 or a salt, solvate, tautomer, or N-oxide thereof.

13. A method according to claim 1 wherein the disease or condition is a myeloproliferative disorder (MPD) and the myeloproliferative disorder is polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis.

14. A method according to claim 1 wherein the disease or condition is a Philadelphia chromosome positive malignancy and the Philadelphia chromosome positive malignancy is Philadelphia chromosome positive leukemia.

15. A method according to claim 3 wherein the salt is an L-lactate salt.

16. A method according to claim 2 wherein the salt is an L-lactate or citrate salt, or a mixture thereof.

17. A method according to claim 1 wherein the disease state or condition is multiple myeloma.

18. A method according to claim 17 comprising administering 1-cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H -pyrazol-4-yl]-urea or a salt thereof.

19. A method according to claim 18 wherein the salt is an L-lactate, D-lactate or citric acid salt.

20. A method according to claim 19 wherein the salt is an L-lactate salt.

21. A method according to claim 18 wherein the salt is an L-lactate or citrate salt, or a mixture thereof.

22. A method of treating multiple myeloma comprising administering a therapeutically effective amount of 1-cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H -benzoimidazol-2-yl)-1H-pyrazol-4-yl]-urea or a salt, solvate, tautomer, or N-oxide thereof.

23. A method according to claim 22 comprising administering 1-cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H -pyrazol-4-yl]-urea or a salt thereof.

24. A method according to claim 23 wherein the salt is an L-lactate, D-lactate or citric acid salt.

25. A method according to claim 24 wherein the salt is an L-lactate salt.

26. A method according to claim 23 wherein the salt is an L-lactate or citrate salt, or a mixture thereof.