QUINOLINE CONTAINING COMPOUNDS AND THEIR USE FOR TREATING ENDOPLASMIC RETICULUM STRESS-RELATED DISEASES

• US 20170231973A1
• Filed: 11/27/2016
• Published: 08/17/2017
• Est. Priority Date: 11/28/2015
• Status: Active Grant

• Current Assignee: Neurodon Corp.
• Original Assignee: Russell Dahl
• Inventors: Dahl, Russell
• Granted Patent: US 10,383,868 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings

Abstract

Provided herein are quinoline, pharmaceutical compositions thereof, and methods of their use for treating, preventing, or ameliorating one or more symptoms of an endoplasmic reticulum stress-caused disease. Also provided herein are methods of their use for reducing endoplasmic reticulum stress and modulating the activity of a sarcoplasmic/endoplasmic reticulum Ca²⁺ATPase.

Claims

1. A method for treating, preventing, or ameliorating one or more symptoms of an endoplasmic reticulum stress-caused disease in a subject, comprising administering to the subject a compound of Formula I:

2. The method of claim 1, wherein the endoplasmic reticulum stress-caused disease is a cardiovascular disease, cancer, diabetes, an inflammatory disease, a metabolic disease, or a neurological disease.

3. The method of claim 1, wherein the endoplasmic reticulum stress-caused disease is Alzheimer'"'"'s disease, Parkinson'"'"'s disease, Huntington'"'"'s disease, amyotrophic lateral sclerosis, muscular dystrophy, polyglutamine disease, prion disease, stroke, bipolar disorder, heart disease, atherosclerosis, cancer, diabetes, obesity, muscle degeneration, an inflammatory disease, an ischemic disease, or an autoimmune disease.

4. The method of claim 1, wherein the endoplasmic reticulum stress-caused disease is diabetes.

5. The method of claim 1, wherein the endoplasmic reticulum stress-caused disease is Alzheimer'"'"'s disease.

6. The method of claim 1, wherein the endoplasmic reticulum stress-caused disease is cancer.

16. The method of any one of claims 1 to 15, wherein the method comprises administering to the subject a second therapeutic agent, in combination or alternation.

17. The method of any one of claims 1 to 16, wherein the subject is a human.

19. The method of claims 1 to 17, wherein the compound has the structure of Formula VII:

20. The method of claim 1, wherein the compound is:

7. A method for treating, preventing, or ameliorating one or more symptoms of a disorder, disease, or condition mediated by a sarcoplasmic/endoplasmic reticulum calcium ATP-ase (SERCA, including isoforms 1a, 1b, 2a, 2b, 3a, 3b, and 3c) in a subject, comprising administering to the subject a compound of Formula I:

8. The method of claim 7, wherein the disorder, disease, or condition mediated by a sarcoplasmic/endoplasmic reticulum calcium ATP-ase is a cardiovascular disease, cancer, diabetes, an inflammatory disease, a metabolic disease, or a neurological disease.

9. The method of claim 7, wherein the disorder, disease, or condition mediated by a sarcoplasmic/endoplasmic reticulum calcium ATP-ase is Alzheimer'"'"'s disease, Parkinson'"'"'s disease, Huntington'"'"'s disease, amyotrophic lateral sclerosis, muscular dystrophy, polyglutamine disease, prion disease, stroke, bipolar disorder, heart disease, atherosclerosis, cancer, diabetes, obesity, muscle degeneration, an inflammatory disease, an ischemic disease, or an autoimmune disease.

10. The method of claim 7, wherein the disorder, disease, or condition mediated by a sarcoplasmic/endoplasmic reticulum calcium ATP-ase is diabetes.

11. The method of claim 7, wherein the disorder, disease, or condition mediated by a sarcoplasmic/endoplasmic reticulum calcium ATP-ase is Alzheimer'"'"'s disease.

12. The method of claim 7, wherein the disorder, disease, or condition mediated by a sarcoplasmic/endoplasmic reticulum calcium ATP-ase is cancer.

13. The method of any one of claims 4 and 10 wherein the diabetes is type 1.

14. The method of any one of claims 4 and 10 wherein the diabetes is type 2.

15. The method of claim 6 or 12 wherein the cancer is breast cancer.

18. The method of claim 18, wherein the compound has the structure of Formula III: