5-[[4-[[morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2 Pyridyl]Amino]Pyrazine-2-carbonitrile and therapeutic uses thereof
The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to 5-[[4-[[morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2-pyridyl]amino]pyrazine-2-carbonitrile compounds (referred to herein as “TFM compounds”) which, inter alia, inhibit Checkpoint Kinase 1 (CHK1) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1, that are ameliorated by the inhibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or a thymidylate synthase (TS) inhibitor; (d) a microtubule targeted agent; (e) ionising radiation; (f) an inhibitor of a mitosis regulator or a mitotic checkpoint regulator; (g) an inhibitor of a DNA damage signal transducer; or (h) an inhibitor of a DNA damage repair enzyme.
1. A kit comprising
(a) a therapeutically-effective amount of a TFM compound in a suitable container, wherein the TFM compound is a compound of the following formula, or a pharmaceutically acceptable salt thereof:
and
(b) instructions for use.
2. The kit of claim 1 , wherein the instructions comprise written instructions on how to administer the TFM compound.
3. The kit of claim 1 , wherein the TFM compound is a compound of the following formula, or a pharmaceutically acceptable salt thereof:
4. The kit of claim 1 , wherein the TFM compound is a compound of the following formula, or a pharmaceutically acceptable salt thereof:
5. The kit of claim 1 , wherein the TFM compound is provided in a pharmaceutical composition comprising the TFM compound and a pharmaceutically acceptable carrier or diluent.
6. The kit of claim 5 , wherein the pharmaceutical composition is suitable for oral administration to a subject.
7. The kit of claim 1 , further comprising a therapeutically-effective amount of one or more other agents provided in suitable containers, wherein the agents are chosen from: (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or a thymidylate synthase (TS) inhibitor; (d) a microtubule targeted agent; (e) a systemic radiopharmaceutical; (f) an inhibitor of a mitosis regulator or a mitotic checkpoint regulator; (g) an inhibitor of a DNA damage signal transducer; and (h) an inhibitor of a DNA damage repair enzyme.
8. The kit of claim 1 , wherein the kit comprises instructions for treating a disease or condition that is mediated by CHK1.
9. The kit of claim 1 , wherein the kit comprises instructions for treating a disease or condition that is ameliorated by the inhibition of CHK1 kinase function.
10. The kit of claim 1 , wherein the kit comprises instructions for treating a proliferative condition.
11. The kit of claim 1 , wherein the kit comprises instructions for treating cancer.
12. The kit of claim 1 , wherein the kit comprises instructions for treating head cancer; neck cancer; nervous system cancer; brain cancer; neuroblastoma; lung/mediastinum cancer; breast cancer; oesophagus cancer; stomach cancer; liver cancer; biliary tract cancer; pancreatic cancer; small bowel cancer; large bowel cancer; colorectal cancer; gynaecological cancer; genito-urinary cancer; ovarian cancer; thyroid gland cancer; adrenal gland cancer; skin cancer; melanoma; bone sarcoma; soft tissue sarcoma; paediatric malignancy; Hodgkin's disease; non-Hodgkin's lymphoma; myeloma; leukaemia; or metastasis from an unknown primary site.
13. The kit of claim 1 , wherein the kit comprises instructions for treating lung cancer, breast cancer, ovarian cancer, pancreatic cancer, colorectal cancer, melanoma, glioma, or neuroblastoma.
14. The kit of claim 1 , wherein the kit comprises instructions for treating MYC-amplified cancer.
15. The kit of claim 1 , wherein the kit comprises instructions for treating c-MYC-amplified cancer.
16. The kit of claim 1 , wherein the kit comprises instructions for treating MYCN-amplified cancer.
17. The kit of claim 1 , wherein the kit comprises instructions for treating cancer characterised by overexpression of MYC.
18. The kit of claim 1 , wherein the kit comprises instructions for treating cancer characterised by overexpression of MYCN.
19. The kit of claim 1 , wherein the kit comprises instructions for treating cancer characterised by overexpression of c-MYC.
20. The kit of claim 1 , wherein the kit comprises instructions for treating MYCN-amplified neuroblastoma.
21. The kit of claim 1 , wherein the kit comprises instructions for treating c-MYC-amplified B cell lymphoma.