Quinoline alkenes 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, solvate, or hydrate thereof; wherein:
R 2 is (a) hydrogen or (b) methyl;
R 4 , R 5 , and R 6 are each independently (a) hydrogen, cyano, or halo; (b) C 1-6 alkyl; or (c) —C(O)R 1a , C(O)OR 1a , C(O)NR 1b R 1c , —C(NR 1a )NR 1b R 1c , —OR 1a , —OS(O)NR 1b R 1c , —OS(O) 2 NR 1b R 1c , —NR 1b R 1c , —NR 1a C(O)R 1d , —NR 1a C(O)OR 1d , —NR 1a C(O)NR 1b R 1c , —NR 1a S(O)R 1d , —NR 1a S(O) 2 R 1d ;
each R 1a , R 1b , R 1c , and R 1d is independently (i) hydrogen or (ii) C 1-6 alkyl;
R 3 and R 7 are each independently (a) hydrogen or cyano; (b) C 1-6 alkyl; or (c) —C(O)R 1a , —C(O)OR 1a , —C(O)NR 1b R 1c , —C(NR 1a )NR 1b R 1c , —OR 1a , —OS(O)NR 1b R 1c , —OS(O) 2 NR 1b R 1c , —NR 1b R 1c , —NR 1a C(O)R 1d , —NR 1a C(O)OR 1d , —NR 1a C(O)NR 1b R 1c , —NR 1a S(O)R 1d , —NR 1a S(O) 2 R 1d ;
each R 1a , R 1b , R 1c , R 1d is independently (i) hydrogen or (ii) C 1-6 alkyl; and
R 1 is optionally substituted phenyl, thiophenyl, or furanyl; with the proviso that R 1 is not Ph, 4-NH 2 -Ph, 4-Me-Ph, 4-OMe-Ph, 4-Br-Ph, 4-OH-Ph, 4-COOMe-Ph, 4-CN-Ph, 4-Ph-Ph, 2-Naphthyl, or 4-NO 2 -Ph.
2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is methyl.
3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 , R 4 , R 5 , R 6 , and R 7 are hydrogen.
4. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is methyl and R 3 , R 4 , R 5 , R 6 , and R 7 are hydrogen.
5. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is mono or disubstituted phenyl or mono or disubstituted 2-thienyl with the proviso that R 1 is not Ph, 4-Me-Ph, 4-OMe-Ph, 4-Br-Ph, 4-OH-Ph, 4-COOMe-Ph, 4-CN-Ph, 4-Ph-Ph, 2-Naphthyl, or 4-NO 2 -Ph.
6. The compound according to claim 1 selected from the group consisting of: