Compounds and methods for treating cancer

Patent metadata

Field	Value
Publication number	US-12286413-B2
Application number	US-202217713949-A
Country	US
Kind code	B2
Filing date	Apr 5, 2022
Priority date	Aug 7, 2014
Publication date	Apr 29, 2025
Grant date	Apr 29, 2025

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.

First claim

What is claimed is:

1. A compound according to Formula (I):

or a pharmaceutically acceptable salt thereof,
wherein:
R 1 is an unsubstituted C 1-6 alkyl or C 1-6 haloalkyl;
X is

Y is selected from the group consisting of:

m is 0 or 1;
n is 0, 1, or 2;
V is NR 4 or O;
R 2 , R 3 , and R 4 are each independently H or an unsubstituted C 1-6 alkyl; and
Z is an unsubstituted aryl.

2. The compound of claim 1 , wherein the compound according to Formula (I) has the structure of Formula (Ia):

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , wherein R 1 is CF 3 .

4. The compound of claim 1 , wherein m is 0.

5. The compound of claim 1 , wherein Vis NH.

6. The compound of claim 1 , wherein Y is

7. The compound of claim 1 , wherein Y is

8. The compound of claim 1 , wherein m is 1.

9. The compound of claim 1 , wherein Vis O.

10. The compound of claim 9 , wherein Y is

11. The compound of claim 1 , wherein R 2 is H; and R 3 is CH 3 .

12. The compound of claim 11 , wherein Y is

13. The compound of claim 1 , wherein n is 1.

14. The compound of claim 1 , wherein Z is phenyl.

15. The compound of claim 1 , wherein the compound according to Formula (I) is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

16. A pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt thereof, according to claim 1 , and a pharmaceutically acceptable carrier.

17. A method for inhibiting SCD1 in a cancer cell, the method comprising contacting the cancer cell with an effective amount of a compound, or a pharmaceutically acceptable salt thereof, according to claim 1 .

18. The method of claim 17 , wherein the cancer cell is selected from a kidney cancer cell, a liver cancer cell, a breast cancer cell, a lung cancer cell, a pancreatic cancer cell, a bladder cancer cell, a colon cancer cell, a melanoma cell, a thyroid cancer cell, an ovarian cancer cell, and a prostate cancer cell.

19. A method for treating a cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, according to claim 1 .

20. The method of claim 19 , wherein the cancer is selected from a kidney cancer, a liver cancer, a breast cancer, a lung cancer, a pancreatic cancer, a bladder cancer, a colon cancer, a melanoma, a thyroid cancer, an ovarian cancer, and a prostate cancer.

Assignees

• Mayo Found Medical Education & Res

Inventors

• Copland Iii John A
• Tun Han W
• Caulfield Thomas R
• Von Roemeling Christina
• Marlow Laura Ann

Classifications

• C07D211/66

  having a hetero atom as the second substituent in position 4 · CPC title

• A61K31/495

  having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) · CPC title

• A61K31/44

  Non condensed pyridines; Hydrogenated derivatives thereof · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• C07D213/64

  attached in position 2 or 6 · CPC title