Castration-resistant prostate cancer
This invention relates to inhibitors of UDP-glucose dehydrogenase, and more particularly to UDP-glucose dehydrogenase inhibitors that are useful in the treatment of prostate cancer. Methods of inhibiting UDP-glucose dehydrogenase and improving the efficacy of additional prostate cancer therapies are also provided.
1. A method of treating prostate cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the compound is administered in combination with one or more additional therapies comprising administration of a chemotherapeutic agent, androgen deprivation therapy, or a combination thereof.
3. The method of claim 1 , wherein the compound is selected from the group consisting of 2,2′-[1-(4-amino-1,2,5-oxadiazol-3-yl)-1H-1,2,3-triazole-4,5-diyl]di(2-butanol) (1), or a pharmaceutically acceptable salt thereof, and 3-[5-(2-thienyl)-2-furyl]propanoic acid (31), or a pharmaceutically acceptable salt thereof.
4. The method of claim 1 , wherein the prostate cancer is mediated by UDP-glucose dehydrogenase (UGDH).
5. The method of claim 4 , wherein the compound is selected from the group consisting of 2,2′-[1-(4-amino-1,2,5-oxadiazol-3-yl)-1H-1,2,3-triazole-4,5-diyl]di(2-butanol) (1), or a pharmaceutically acceptable salt thereof, and 3-[5-(2-thienyl)-2-furyl]propanoic acid (31), or a pharmaceutically acceptable salt thereof.
6. The method of claim 1 , wherein the prostate cancer is castration resistant prostate cancer (CRPC).
7. The method of claim 1 , wherein the compound is 2,2′-[1-(4-amino-1,2,5-oxadiazol-3-yl)-1H-1,2,3-triazole-4,5-diyl]di(2-butanol) (1), or a pharmaceutically acceptable salt thereof.
8. The method of claim 1 , wherein the compound is 3-[5-(2-thienyl)-2-furyl]propanoic acid (31), or a pharmaceutically acceptable salt thereof.
9. The method of claim 2 , wherein the compound is 2,2′-[1-(4-amino-1,2,5-oxadiazol-3-yl)-1H-1,2,3-triazole-4,5-diyl]di(2-butanol) (1), or a pharmaceutically acceptable salt thereof.
10. The method of claim 2 , wherein the compound is 3-[5-(2-thienyl)-2-furyl]propanoic acid (31), or a pharmaceutically acceptable salt thereof.
11. The method of claim 4 , wherein the compound is 2,2′-[1-(4-amino-1,2,5-oxadiazol-3-yl)-1H-1,2,3-triazole-4,5-diyl]di(2-butanol) (1), or a pharmaceutically acceptable salt thereof.
12. The method of claim 4 , wherein the compound is 3-[5-(2-thienyl)-2-furyl]propanoic acid (31), or a pharmaceutically acceptable salt thereof.
13. A method of treating castration resistant prostate cancer (CRPC), comprising administering to a patient in need thereof a therapeutically effective amount a compound which is 2,2′-[1-(4-amino-1,2,5-oxadiazol-3-yl)-1H-1,2,3-triazole-4,5-diyl]di(2-butanol) (1), or a pharmaceutically acceptable salt thereof.
14. The method of claim 13 , wherein the compound is administered in combination with one or more additional therapies comprising administration of a chemotherapeutic agent, androgen deprivation therapy, or a combination thereof.
15. A method of treating castration resistant prostate cancer (CRPC), comprising administering to a patient in need thereof a therapeutically effective amount a compound which is 345-(2-thienyl)-2-furyl]propanoic acid (31), or a pharmaceutically acceptable salt thereof.
16. The method of claim 15 , wherein the compound is administered in combination with one or more additional therapies comprising administration of a chemotherapeutic agent, androgen deprivation therapy, or a combination thereof.
17. A method of treating castration resistant prostate cancer (CRPC) mediated by UDP-glucose dehydrogenase (UGDH), comprising administering to a patient in need thereof a therapeutically effective amount a compound selected from the group consisting of 2,2′-[1-(4-amino-1,2,5-oxadiazol-3-yl)-1H-1,2,3-triazole-4,5-diyl]di(2-butanol) (1), or a pharmaceutically acceptable salt thereof, and 3-[5-(2-thienyl)-2-furyl]propanoic acid (31), or a pharmaceutically acceptable salt thereof.
18. The method of claim 17 , wherein the compound is administered in combination with one or more additional therapies comprising administration of a chemotherapeutic agent, androgen deprivation therapy, or a combination thereof.