Targeted nitroxide agents

摘要

Provided herein are compositions and related methods useful for free radical scavenging, with particular selectivity for mitochondria. The compounds comprise a nitroxide-containing group attached to a mitochondria-targeting group. The compounds can be cross-linked into dimers without loss of activity. Also provided herein are methods, for preventing, mitigating and treating damage caused by radiation. The method comprises delivering a compound, as described herein, to a patient in an amount and dosage regimen effective to prevent, mitigate or treat damage caused by radiation.

主权项

1. A method of making a targeted antioxidant compound, comprising:
a. reacting an aldehyde of structure R1—C(O)—H— with (R)-2-methylpropane-2-sulfinamide to foam an imine, in which R1 is C1-C6 straight or branched-chain alkyl, optionally including a phenyl (C6H5) group, that optionally is methyl-, hydroxyl- or fluoro-substituted; b. reacting a terminal alkyne-1-ol (HCC—R2—CH2—OH), in which R2 is not present or is branched or straight-chained alkylene, with a t-butyldiphenylsilane- salt to produce an alkyne; c. reacting the imine with the alkyne in the presence of an organozirconium catalyst to produce an alkene; d. acylating the alkene to produce a carbamate; e. removing the t-butyldiphenylsilyl group from the carbamate to produce an alcohol; f. oxidizing the alcohol to produce a carboxylic acid; and g. reacting carboxylic acid with a nitroxide-containing compound comprising one of a hydroxyl or amine in a condensation reaction to produce the antioxidant compound.