Quinoxalines useful as cytoprotective agents
View Patent ↗Provided herein are compounds 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.
1. A compound of Formula I:
or an enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt thereof; wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R Y are each as defined herein;
R 1 is phenyl or heteroaryl, each optionally substituted with one or more substituents selected from halo, nitro, cyano, —CF 3 , —O—(C 1 -C 4 alkyl), C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, hydroxyl, and —N(C 1 -C 4 alkyl) 2 , with the proviso that R 1 is not pyridone, substituted pyridone, 2-pyridyl, pyrazole, —(H 5 )Ph, or -(2,6-di-Cl)Ph; and
R 2 , R 3 , R 4 , R 5 , R 6 , are each independently hydrogen, halo, nitro, cyano, —CF 3 , —O—(C 1 -C 4 alkyl), C 1 -C 6 alkyl, and —N(C 1 -C 4 alkyl) 2 ; and
R Y is hydrogen or C 1 -C 4 alkyl.
2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is phenyl or thienyl, each optionally substituted with one to two substituents selected from halo, nitro, cyano, —CF 3 , —O—(C 1 -C 4 alkyl), C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, hydroxyl, and —N(C 1 -C 4 alkyl) 2 , with the proviso that R 1 is not —(H 5 )Ph or -(2,6-di-Cl)Ph.
3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 , R 3 , R 4 , R 5 , and R 6 are hydrogen.
4. The compound according to claim 1 selected from the group consisting of:
5. A method for treating a neurological or neurodegenerative disorder wherein the neurological or neurodegenerative disorder is Alzheimer's disease or Parkinson's disease in a subject comprising administering to the subject an effective amount of a compound of Formula I:
or an enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt thereof; wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R Y are each as defined herein;
R 1 is phenyl or heteroaryl, each optionally substituted with one or more substituents selected from halo, nitro, cyano, —CF 3 , —O—(C 1 -C 4 alkyl), C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, hydroxyl, and —N(C 1 -C 4 alkyl) 2 , with the proviso that R 1 is not pyridone, substituted pyridone, 2-pyridyl, pyrazole, —(H 5 )Ph, or -(2,6-di-Cl)Ph; and
R 2 , R 3 , R 4 , R 5 , R 6 , are each independently hydrogen, halo, nitro, cyano, —CF 3 , —O—(C 1 -C 4 alkyl), C 1 -C 6 alkyl, and —N(C 1 -C 4 alkyl) 2 ; and
R Y is hydrogen or C 1 -C 4 alkyl.
6. 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 a compound of Formula I:
or an enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt thereof; wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R Y are each as defined herein;
R 1 is phenyl or heteroaryl, each optionally substituted with one or more substituents selected from halo, nitro, cyano, —CF 3 , —O—(C 1 -C 4 alkyl), C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, hydroxyl, and —N(C 1 -C 4 alkyl) 2 , with the proviso that R 1 is not pyridone, substituted pyridone, 2-pyridyl, pyrazole, —(H 5 )Ph, or -(2,6-di-Cl)Ph; and
R 2 , R 3 , R 4 , R 5 , R 6 , are each independently hydrogen, halo, nitro, cyano, —CF 3 , —O—(C 1 -C 4 alkyl), C 1 -C 6 alkyl, and —N(C 1 -C 4 alkyl) 2 ; and
R Y is hydrogen or C 1 -C 4 alkyl.
7. The method of claim 6 wherein the diabetes is type 1.
8. The method of claim 6 wherein the diabetes is type 2.
9. The method of claim 5 wherein the compound is selected from the following:
10. The method of claim 6 wherein the compound is selected from the following: