Compositions and methods using the same for treatment of neurodegenerative and mitochondrial disease
The disclosure is directed to compounds and pharmaceutically acceptable salts thereof for the treatment and/or prevention of neurodegenerative and/or mitochondrial diseases, such as Parkinson's disease and Leigh's disease. The compounds and pharmaceutically acceptable salts thereof are of the class of nitrogenous bases, for example, pyrimidines, purines, pteridines and pharmaceutically acceptable salts thereof.
1. A compound comprising the following formula or pharmaceutically acceptable salt thereof:
wherein X is independently selected from a C—H, C—CH 3 , C—CH 2 CH 3 , C—CH 2 CH 2 CH 3 , or CR 3 , wherein R 3 is independently selected from a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl;
L 1 is a bond, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene;
R 1 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and R 4 is hydrogen, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 2 is N;
R 5 is CH, CCH 3 , or CC 6 H 5 ; and
R 6 is N;
wherein the compound does not comprise kinetin or cytokinin.
2. The compound of claim 1 , wherein the compound has the Formula I, Ib, IIa, II, or VII.
3. The compound of claim 1 , wherein X is C—H or C—CH 3 .
4. The compound of claim 1 , wherein R 2 is N; X is C—H or C—CH 3 ; R 4 is hydrogen, and wherein R 6 is N.
5. The compound of claim 1 , wherein X is CR 3 , and R 3 is selected from the group consisting of: H, CH 3 , substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted tetrahydrofuranyl, substituted or unsubstituted 2,5-dihydrofuranyl, substituted or unsubstituted tetrahydrothienyl, substituted or unsubstituted 2,5-dihydrothienyl, substituted or unsubstituted pyrrolidinyl, substituted or unsubstituted 2,5-dihydro-1H-pyrrolyl, substituted or unsubstituted cyclopentyl, substituted or unsubstituted cyclopentenyl, or substituted or unsubstituted 1,3-oxathiolanyl, substituted or unsubstituted tetrahydrofuranyl, substituted or unsubstituted 2,5-dihydrofuranyl, substituted or unsubstituted tetrahydrothienyl, substituted or unsubstituted 2,5-dihydrothienyl, unsubstituted pyrrolidinyl, substituted or unsubstituted 2,5-dihydro-1H-pyrrolyl, substituted or unsubstituted cyclopentyl, substituted or unsubstituted cyclopentenyl, substituted or unsubstituted 1,3-oxathiolanyl; and wherein L 1 is a bond or an amine.
6. The compound of claim 1 , wherein L 1 is N—H.
7. The compound of claim 1 , wherein L 1 is N—H, R 2 is N; R 3 is saturated carbon; R 4 is hydrogen, R 6 is N; and wherein R 1 is a substituted or unsubstituted alkyl group or heteroakyl group.
8. The compound of claim 1 , wherein L 1 is N—H, R 2 is N; R 3 is saturated carbon; R 4 is hydrogen, R 6 is N; and wherein R 1 is a substituted carbon, propyl, butyl, propylene, or butylene group.
9. The compound of claim 1 , wherein the compound is
10. A pharmaceutical composition comprising: (i) a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof; and (ii) a pharmaceutically acceptable carrier.
11. The compound of claim 1 , wherein R 1 is the substituted or unsubstituted heteroaryl.
12. The compound of claim 1 , wherein R 1 is the substituted or unsubstituted alkyl, and wherein the substituted or unsubstituted alkyl is a substituted or unsubstituted alkenyl.
13. The compound of claim 1 , wherein the compound is selected from: