Inhibitors of the Wnt/beta-catenin pathway

Patent metadata

Field	Value
Publication number	US-12404243-B2
Application number	US-202318125961-A
Country	US
Kind code	B2
Filing date	Mar 24, 2023
Priority date	Jan 30, 2018
Publication date	Sep 2, 2025
Grant date	Sep 2, 2025

Abstract

The present disclosure relates to compounds that are capable of modulating the WNT/Beta-Catenin pathway. The disclosure further relates to methods of treating colorectal cancer and other WNT/Beta-Catenin mediated cancers.

First claim

We claim:

1. A compound having a structure represented by Formula Ib or a pharmaceutically acceptable salt thereof:

wherein
R 4 is substituted alkenyl, substituted acyl, substituted C(O)alkyl, substituted C(O)Oalkyl, substituted C(O)Oaryl, substituted C(O)Oheteroaryl, substituted C(O)N(R 5a R 5b ), or substituted alkylsulfonyl, further wherein each substituted alkenyl, substituted acyl, substituted C(O)alkyl, substituted C(O)Oalkyl, substituted C(O)Oaryl, substituted C(O)Oheteroaryl, substituted C(O)N(R 5a R 5b ), or substituted alkylsulfonyl is substituted with at least one basic nitrogen; and
R 5a and R 5b are each independently hydrogen, alkyl, or aryl.

2. The compound of claim 1 , wherein R 4 is substituted C(O)alkyl.

3. The compound of claim 1 , wherein the basic nitrogen is NH 2 .

4. The compound of claim 1 , wherein the basic nitrogen is alkylamino.

5. The compound of claim 1 , wherein the basic nitrogen is dialkylamino.

6. The compound of claim 1 , wherein the basic nitrogen is methylamino, diethylamino, or di(methoxyethyl)amino.

7. The compound of claim 1 , wherein the basic nitrogen is a basic nitrogen-containing heterocycle.

8. The compound of claim 1 , wherein the basic nitrogen is azepanyl, pyrrolidinyl, piperidyl, morpholinyl, piperazinyl, piperidonyl, or thiomorpholinyl.

9. The compound of claim 1 , wherein the basic nitrogen is pyrrolidine, N-methyl pyrrolidine, N-methylpiperazine, or 1-(4-fluorophenyl)piperazine.

10. A compound selected from:

or a pharmaceutically acceptable salt thereof.

11. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

12. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.

14. A method of inhibiting β-catenin, comprising administering to a subject in need thereof a compound of claim 1 .

15. A method of treating cancer, comprising administering to a subject in need thereof a compound of claim 1 , wherein the cancer is bladder cancer, bone cancer, brain cancer, breast cancer, cardiac cancer, cervical cancer, colon cancer, colorectal cancer, esophageal cancer, fibrosarcoma, gastric cancer, gastrointestinal cancer, head, spine and neck cancer, Kaposi's sarcoma, kidney cancer, leukemia, liver cancer, lymphoma, melanoma, multiple myeloma, pancreatic cancer, penile cancer, testicular germ cell cancer, thymoma and thymic carcinoma, lung cancer, ovarian cancer, and prostate cancer.

16. A method of treating cancer, comprising administering to a subject in need thereof the compound of claim 10 , wherein the cancer is bladder cancer, bone cancer, brain cancer, breast cancer, cardiac cancer, cervical cancer, colon cancer, colorectal cancer, esophageal cancer, fibrosarcoma, gastric cancer, gastrointestinal cancer, head, spine and neck cancer, Kaposi's sarcoma, kidney cancer, leukemia, liver cancer, lymphoma, melanoma, multiple myeloma, pancreatic cancer, penile cancer, testicular germ cell cancer, thymoma and thymic carcinoma, lung cancer, ovarian cancer, and prostate cancer.

Assignees

• Univ California

Inventors

• Jung Michael E
• Chen Xiaohong
• Wang Cun-Yu
• Li Jiong
• Zheng Jie

Classifications

• C07D295/135

  with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings · CPC title

• C07D295/16

  acylated on ring nitrogen atoms · CPC title

• C07D213/38

  having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom · CPC title

• C07D213/06

  containing only hydrogen and carbon atoms in addition to the ring nitrogen atom · CPC title

• C07D213/40

  Acylated substituent nitrogen atom · CPC title