Targeted nitroxide agents

Patent metadata

Field	Value
Publication number	US-9890192-B2
Application number	US-201514943965-A
Country	US
Kind code	B2
Filing date	Nov 17, 2015
Priority date	Jul 17, 2008
Publication date	Feb 13, 2018
Grant date	Feb 13, 2018

Abstract

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.

First claim

We claim:

1. A compound having the structure:

wherein X is one of

R 1 and R 2 are hydrogen, C 1 -C 6 straight or branched-chain alkyl, or a C 1 -C 6 straight or branched-chain alkyl further comprising a phenyl (C 6 H 5 ) group, that is unsubstituted or is methyl-, hydroxyl- or fluoro-substituted; R 4 is hydrogen, C 1 -C 6 straight or branched-chain alkyl, or a C 1 -C 6 straight or branched-chain alkyl further comprising a phenyl (C 6 H 5 ) group, that is unsubstituted or is methyl-, hydroxyl- or fluoro-substituted; R is —C(O)—R 6 , —C(O)O—R 6 , or —P(O)—(R 6 ) 2 , wherein R 6 is C 1 -C 6 straight or branched-chain alkyl or C 1 -C 6 straight or branched-chain alkyl further comprising one or more phenyl (—C 6 H 5 ) groups that are independently unsubstituted, or methyl-, ethyl-, hydroxyl- or fluoro-substituted; and
wherein
R 3 is

2. The compound of claim 1 , in which R is Ac, Boc, Cbz, or —P(O)—Ph 2 .

3. The compound of claim 1 , in which R 1 , R 2 , R 4 and R 6 are independently chosen from hydrogen, methyl, ethyl, propyl, 2-propyl, butyl, t-butyl, pentyl, hexyl, benzyl, hydroxybenzyl, phenyl and hydroxyphenyl.

4. The compound of claim 1 , wherein when X is —CH═CR 4 —, R 4 is hydrogen, methyl or ethyl.

5. The compound of claim 1 having the structure

6. The compound of claim 1 having the structure

7. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , and a pharmaceutically acceptable carrier.

8. The compound of claim 1 , wherein X is

Assignees

• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Wipf Peter
• Frantz Marie Celine

Classifications

• A61P39/06

  Free radical scavengers or antioxidants · CPC title

• A61P17/18

  Antioxidants, e.g. antiradicals (preparations for protection against sunlight A61Q17/00) · CPC title

• C07D279/06

  not condensed with other rings · CPC title

• C07D211/58

  attached in position 4 · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title