Targeted nitroxide agents

Patent metadata

Field	Value
Publication number	US-9732105-B2
Application number	US-201514941466-A
Country	US
Kind code	B2
Filing date	Nov 13, 2015
Priority date	Feb 18, 2011
Publication date	Aug 15, 2017
Grant date	Aug 15, 2017

Abstract

A compound having a structure of:

First claim

We claim:

1. A compound of Formula 3 or Formula 4 below:

wherein X is

R 1 , R 1a , R 2 , R 2a , R 4 and R 20 are each independently hydrogen, halo, a 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, wherein the C 1 -C 6 straight or branched-chain alkyl group or the C 1 -C 6 straight or branched-chain alkyl group comprising a phenyl group is unsubstituted or is methyl-, hydroxyl- or halo-substituted;
R 3 is —NH—R 5 , —O—R 5 or —CH 2 —R 5 , wherein R 5 is an —N—O·, —N—OH or —N═O containing group;
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 optionally comprising one or more phenyl (—C 6 H 5 ) groups, and that optionally are methyl-, ethyl-, hydroxyl- or fluoro-substituted;
provided that if X is:

then
at least one of R 4 or R 20 is halo, or R 3 is

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein R 3 is

3. The compound of claim 2 , wherein the compound is:

4. The compound of claim 1 or claim 2 , wherein X is

wherein at least one of R 4 or R 20 is a halo.

5. The compound of claim 1 , wherein the compound is in the form of a nitroxide, a hydroxylamine, or a nitroxonium ion.

6. The compound of claim 1 , wherein the compound is in the form of a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition comprising a compound of claim 1 , and at least one pharmaceutically acceptable additive.

8. The compound of claim 1 , wherein R 20 is halo, or a halo-substituted C 1 -C 6 straight or branched-chain alkyl.

9. The compound of claim 1 , wherein X is:

wherein R 4 is halo, a 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, wherein the C 1 -C 6 straight or branched-chain alkyl group or the C 1 -C 6 straight or branched-chain alkyl group comprising a phenyl group is unsubstituted or is methyl-, hydroxyl- or halo-substituted.

10. A compound of Formula 3 or Formula 4 below:

R 1 , R 1a , R 2 , and R 2a are each independently hydrogen, halo, a 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, wherein the C 1 -C 6 straight or branched-chain alkyl group or the C 1 -C 6 straight or branched-chain alkyl group comprising a phenyl group is unsubstituted or is methyl-, hydroxyl- or halo-substituted;
R 3 is —NH—R 5 ;
R 5 is

and
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 optionally comprising one or more phenyl (—C 6 H 5 ) groups, and that optionally are methyl-, ethyl-, hydroxyl- or fluoro-substituted; or a pharmaceutically acceptable salt thereof.

11. A compound of Formula 3 or Formula 4 below:

R 1 , R 1a , R 2 , R 2a , and R 21 are each independently hydrogen, halo, a 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, wherein the C 1 -C 6 straight or branched-chain alkyl group or the C 1 -C 6 straight or branched-chain alkyl group comprising a phenyl group is unsubstituted or is methyl-, hydroxyl- or halo-substituted;
R 3 is

and
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 optionally comprising one or more phenyl (—C 6 H 5 ) groups, and that optionally are methyl-, ethyl-, hydroxyl- or fluoro-substituted; or a pharmaceutically acceptable salt thereof.

Assignees

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

Inventors

• Wipf Peter
• Frantz Marie-Celine

Classifications

• C07D451/14

  containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; Cyclic acetals thereof · CPC title

• C07F9/598 Primary

  Chemistry & Metallurgy · mapped topic

• C07D471/08

  Bridged systems · CPC title

• C07D211/94

  Oxygen atom, e.g. piperidine N-oxide · CPC title

• C07F5/022

  without C-boron linkages · CPC title