abstract |
Compositions and methods for treating mitochondrial disorders are provided. The compositions include compounds having a mitochondrial targeting moiety, for example a lipophilic cation. Certain compounds are effective for increasing the ratio of phosphocreatine/creatine in a host, for example a mammal. Other compounds decrease the ratio of phophocreatine/creating in a host. An exemplary compound is defined by the following structure (Formula Ia): wherein R 1 is H or phosphate and the double bond is between N 1 and C 1 or between N 2 and C 1 ; R 2 is a mitochondrial targeting moiety; R 3 an alkyl, alkylaryl, alkylheteroaryl spacer group, a cleavable linker, or absent; R 4 is H or an alkyl, aryl, or heteroaryl group; and R 5 is alkyl, aryl, or heteroaryl; or N 1 C 1 , and N together form a heterocyclic ring containing at least 5 atoms, wherein N 1 , N 3 , and R 1 -R 5 are as defined above, or N 3 and R 5 together form a heterocyclic ring containing at least four atoms; or a pharmaceutically acceptable salt or prodrug thereof. |