Compounds and methods for treating cancer

• US 10,301,273 B2
• Filed: 08/07/2015
• Issued: 05/28/2019
• Est. Priority Date: 08/07/2014
• Status: Active Grant

• Current Assignee: Mayo Foundation For Medical Education And Research (Mayo Clinic)
• Original Assignee: Mayo Foundation For Medical Education And Research (Mayo Clinic)
• Inventors: Copland, III, John A., Tun, Han W., Caulfield, Thomas R., Von Roemeling, Christina, Marlow, Laura Ann
• Primary Examiner(s): Rao, Deepak R
• Assistant Examiner(s): Daniel, Laura M
• Application Number:
  US15/502,301
• Publication Number:
  US 20170226073A1
• Time in Patent Office: 1,390 Days
• Field of Search: None
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 211/64 having an aryl radical as the second substituent in position 4
• CPC Class Codes: C07D 211/66 having a hetero atom as the second substituent in position 4
• CPC Class Codes: C07D 213/64 attached in position 2 or 6
• CPC Class Codes: C07D 213/75 Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 295/192 from aromatic carboxylic acids

Abstract

This document provides compounds, compositions, and methods for treating cancers including renal cancer (e.g., renal cell carcinoma) as well as ovarian, breast, prostate, colon, pancreatic, bladder, liver, lung, and thyroid cancers and melanoma. For example, compounds, compositions, and methods for using one or more inhibitors of SCD1 to treat renal cell carcinoma (e.g., clear cell renal cell carcinoma (ccRCC)), thyroid cancer, or liver cancer; or to increase the efficacy of treatment for the same.

Claims

1. A method for treating a cancer in a human subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound according to Formula (II):

6. The method of claim 1 or 2, wherein the compound according to Formula (II) has the structure of Formula (IIa):

7. The method of claim 1 or 1, wherein the compound according to Formula (II) has the structure of Formula (IIa):

8. The method of claim 1, wherein the compound according to Formula (II) is

13. The method of claim 1, wherein the cancer is clear cell renal cell carcinoma.

14. The method of claim 1, wherein the cancer is bladder cancer selected from transitional cell carcinoma, urothelial carcinoma, papillary carcinoma, flat carcinoma, squamous cell carcinoma, adenocarcinoma, small-cell carcinoma, and sarcoma.

2. A method of treating a cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound according to Formula (II):

3. The method of claim 2, wherein the mode of administration of the compound and the mTor inhibitor is selected from the group consisting of:

i) the compound and the mTor inhibitor are admixed prior to administration;

ii) the compound and the mTor inhibitor are administered concurrently;

iii) the compound and the mTor inhibitor are administered sequentially;

iv) the compound is administered prior to the administration of the mTor inhibitor; and

v) the mTor inhibitor is administered prior to the administration of the compound.

4. The method of claim 2 or 3, wherein the mTOR inhibitor is selected from sirolimus, temsirolimus, everolimus, and ridaforolimus, or a pharmaceutically acceptable salt thereof.

5. The method of claim 4, wherein the mTOR inhibitor is temsirolimus, or a pharmaceutically acceptable salt thereof.

9. The method of claim 2, wherein the compound according to Formula (II) is

10. The method of claim 9, wherein the mode of administration of the compound and the mTor inhibitor is selected from the group consisting of:

i) the compound and the mTor inhibitor are admixed prior to administration;

ii) the compound and the mTor inhibitor are administered concurrently;

iii) the compound and the mTor inhibitor are administered sequentially;

iv) the compound is administered prior to the administration of the mTor inhibitor; and

v) the mTor inhibitor is administered prior to the administration of the compound.

11. The method of claim 9 or 10, wherein the mTOR inhibitor is selected from sirolimus, temsirolimus, everolimus, and ridaforolimus, or a pharmaceutically acceptable salt thereof.

12. The method of claim 11, wherein the mTOR inhibitor is temsirolimus, or a pharmaceutically acceptable salt thereof.