Cyclophilin D inhibitors
A compound that can function as a Cyclophilin D can include a structure of Formula 1 or Formula 2 or Formula 3 or Formula 4 or Formula 5 or Formula 6 or Formula 7 or Formula 8, derivative thereof, prodrug thereof, salt thereof, or stereoisomer thereof, or having any chirality at any chiral center, or tautomer, polymorph, solvate, or combination thereof, as presented herein. The Cyclophilin D inhibitors can inhibit onset or treat neurodegenerative disease, such as Alzheimer's disease, or can be used for inhibiting progression or treating diabetes. An example of such a compound is provided by Formula 1A
1. A compound of a structure of Formula 1A, salt thereof, or stereoisomer thereof, or tautomer, polymorph, solvate, or combination thereof:
wherein R 1 , R 2 , and/or R 3 are independently any substituent; and
X is S or O.
2. The compound of claim 1 , wherein R 1 , R 2 , and/or R 3 are independently hydrogen, alkyl, alkenyl, alkynyl, aryl, alkaryl, aralkyl, halo, hydroxyl, sulfhydryl, alkoxy, alkenyloxy, alkynyloxy, aryloxy, acyl, alkylcarbonyl, arylcarbonyl, acyloxy, alkoxycarbonyl, aryloxycarbonyl, halocarbonyl, alkylcarbonato, arylcarbonato, carboxy, carboxylato, carbamoyl, mono-(alkyl)-substituted carbamoyl, di-(alkyl)-substituted carbamoyl, mono-substituted aryl carbamoyl, thiocarbamoyl, carbamido, cyano, isocyano, cyanato, isocyanato, isothiocyanato, azido, formyl, thioformyl, amino, mono- and di-(alkyl)-substituted amino, mono- and di-(aryl)-substituted amino, alkylamido arylamido, imino, alkylimino, arylimino, nitro, nitroso, sulfo, sulfonato, alkylsulfanyl, arylsulfanyl, alkylsulfinyl, arylsulfinyl, alkyl sulfonyl, aryl sulfonyl, phosphono, phosphonato, phosphinato, phospho, phosphino, any with or without hetero atoms substituting one or more carbons in a chain or ring or added to a chain or ring, and combinations thereof.
3. The compound of claim 1 , wherein the compound has R 1 is an amino.
4. The compound of claim 3 , wherein the compound has the structure of Compound 9:
5. The compound of claim 3 , wherein the compound has the structure of Compound 9A:
6. The compound of claim 1 , wherein the compound has the structure of Compound 9B:
7. The compound of claim 1 , wherein the compound has the structure of Compound 9C:
8. A pharmaceutical composition comprising:
a compound of claim 1 ; and
a pharmaceutically acceptable carrier.
9. A method of inhibiting Cyclophilin D, comprising:
providing a compound of claim 1 ; and
administering the compound to Cyclophilin D.
10. A method of rescuing Aβ-mediated mitochondrial dysfunction, comprising:
providing a compound of claim 1 ; and
administering the compound to Cyclophilin D.
11. The compound of claim 1 , wherein R 2 is an alkyl.
12. The compound of claim 1 , wherein R 3 is an alkyl.
13. The compound of claim 1 , with R 1 being a straight or branched alkyl or aryl substituted or unsubstituted, alkoxy, amino or hydroxyl, R 2 being a straight or branched alkyl or aryl substituted or unsubstituted, and R 3 being a straight or branched alkyl or aryl substituted or unsubstituted.
14. The compound of claim 1 , wherein R 1 is an amino, R 2 is a straight or branched alkyl, and R 3 is a methyl.
15. The compound of claim 1 , with R 2 being a methyl, ethyl, or propyl.