Quinolines that modulate SERCA and their use for treating disease
View Patent ↗Provided herein are quinolines, e.g., a compound of Formula I, pharmaceutical compositions thereof, and methods of their use for treating, preventing, or ameliorating one or more symptoms of a neurological disease, neurodegenerative disorder, or diabetes. Also provided herein are methods of their use for modulating the activity of a sarcoplasmic/endoplasmic reticulum C 2+ ATPase.
1. A method for activating the sarcoplasmic/endoplasmic reticulum calcium ATP-ase (SERCA) in a subject with Alzheimer's disease or Parkinson's disease comprising administering to the subject an effective amount of the compound selected from the group consisting of:
and isotopic variants thereof; and pharmaceutically acceptable salts, solvates, and hydrates thereof.
2. A method for treating, or ameliorating one or more symptoms of diabetes in a subject in need thereof comprising administering to the subject an effective amount of the compound selected from the group consisting of:
and isotopic variants thereof; and pharmaceutically acceptable salts, solvates, and hydrates thereof.
3. The method of claim 2 , wherein the diabetes is type 1.
4. The method of claim 2 , wherein the diabetes is type 2.
5. The method of claim 1 , wherein the C 2+ concentration of an ER is increased.
6. The method of claim 1 , wherein the C 2+ dyshomeostasis is corrected.
7. The method of claim 1 , wherein endoplasmic reticulum stress is reduced.
8. The method of any one of claims 1 , 2 , and 3 - 7 , wherein the subject is a human.