Phosphoramidate derivatives of 5-fluoro-2′-deoxyuridine for use in the treatment of cancer
Phosphoramidate derivatives of 5-fluoro-2′-deoxyuridine are disclosed for use in the treatment of cancer, especially in the treatment of cancer where the patient shows resistance, for example, in a patient with cells with a lowered level of nucleoside transporter proteins and/or with nucleoside kinase-deficient cells and/or with mycoplasma-infected cells and/or with cells with a raised level of thymidylate synthase.
1. A compound which is 5-fluoro-2′-deoxyuridine-5′-O-[1-naphthyl(benzoxy-L-alaninyl)]phosphate (CPF373), or a pharmaceutically acceptable salt or metabolite thereof.
2. A compound which is 5-fluoro-2′-deoxyuridine-5′-O-[1-naphthyl(benzoxy-L-alaninyl)]phosphate (CPF373), or a pharmaceutically acceptable salt thereof.
3. A compound which is 5-fluoro-2′-deoxyuridine-5′-O-[1-naphthyl(benzoxy-L-alaninyl)]phosphate (CPF373), or a metabolite thereof.
4. A compound which is 5-fluoro-2′-deoxyuridine-5′-O-[1-naphthyl(benzoxy-L-alaninyl)]phosphate (CPF373).
5. A pharmaceutical composition comprising the compound according to claim 1 , or a pharmaceutically acceptable salt or metabolite thereof, in combination with a pharmaceutically acceptable carrier, diluent or excipient.
6. A pharmaceutical composition comprising the compound according to claim 2 , or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, diluent or excipient.
7. A pharmaceutical composition comprising the compound according to claim 3 , or a metabolite thereof, in combination with a pharmaceutically acceptable carrier, diluent or excipient.
8. A pharmaceutical composition comprising the compound according to claim 4 in combination with a pharmaceutically acceptable carrier, diluent or excipient.
9. A method of treating a cancer selected from leukemia, pancreatic cancer, prostate cancer, lung cancer, breast cancer, and cervical cancer, comprising administering to a Homo sapiens patient in need of such treatment an effective dose of the compound according to claim 1 , or a pharmaceutically acceptable salt or metabolite thereof.
10. The method of claim 9 wherein said cancer is breast cancer.
11. The method of claim 9 wherein said cancer is lung cancer.
12. A method of treating a cancer selected from oesophageal cancer, gastrointestinal cancer, head and neck cancer, and ovarian cancer, comprising administering to a Homo sapiens patient in need of such treatment an effective dose of the compound according to claim 1 , or a pharmaceutically acceptable salt or metabolite thereof.
13. The method of claim 12 wherein said gastrointestinal cancer is selected from gastric cancer, small intestine cancer, and colon and rectum cancer.
14. The method of claim 12 wherein said cancer is colon and rectum cancer.
15. A method of treating a cancer selected from leukemia, pancreatic cancer, prostate cancer, lung cancer, breast cancer, and cervical cancer, comprising administering to a Homo sapiens patient in need of such treatment an effective dose of the compound according to claim 2 , or a pharmaceutically acceptable salt thereof.
16. The method of claim 15 wherein said cancer is breast cancer.
17. The method of claim 15 wherein said cancer is lung cancer.
18. A method of treating a cancer selected from oesophageal cancer, gastrointestinal cancer, head and neck cancer, and ovarian cancer, comprising administering to a Homo sapiens patient in need of such treatment an effective dose of the compound according to claim 2 , or a pharmaceutically acceptable salt thereof.
19. The method of claim 18 wherein said gastrointestinal cancer is selected from gastric cancer, small intestine cancer, and colon and rectum cancer.
20. The method of claim 18 wherein said cancer is colon and rectum cancer.
21. A method of treating a cancer selected from leukemia, pancreatic cancer, prostate cancer, lung cancer, breast cancer, and cervical cancer, comprising administering to a Homo sapiens patient in need of such treatment an effective dose of the compound according to claim 3 , or a metabolite thereof.
22. The method of claim 21 wherein said cancer is breast cancer.
23. The method of claim 21 wherein said cancer is lung cancer.
24. A method of treating a cancer selected from oesophageal cancer, gastrointestinal cancer, head and neck cancer, and ovarian cancer, comprising administering to a Homo sapiens patient in need of such treatment an effective dose of the compound according to claim 3 , or a metabolite thereof.
25. The method of claim 24 wherein said gastrointestinal cancer is selected from gastric cancer, small intestine cancer, and colon and rectum cancer.
26. The method of claim 24 wherein said cancer is colon and rectum cancer.
27. A method of treating a cancer selected from leukemia, pancreatic cancer, prostate cancer, lung cancer, breast cancer, and cervical cancer, comprising administering to a Homo sapiens patient in need of such treatment an effective dose of the compound according to claim 4 .
28. The method of claim 27 wherein said cancer is breast cancer.
29. The method of claim 27 wherein said cancer is lung cancer.
30. A method of treating a cancer selected from oesophageal cancer, gastrointestinal cancer, head and neck cancer, and ovarian cancer, comprising administering to a Homo sapiens patient in need of such treatment an effective dose of the compound according to claim 4 .
31. The method of claim 30 wherein said gastrointestinal cancer is selected from gastric cancer, small intestine cancer, and colon and rectum cancer.
32. The method of claim 30 wherein said cancer is colon and rectum cancer.