Multifunctional radical quenchers

Patent metadata

Field	Value
Publication number	US-9957214-B2
Application number	US-201314434725-A
Country	US
Kind code	B2
Filing date	Oct 10, 2013
Priority date	Oct 10, 2012
Publication date	May 1, 2018
Grant date	May 1, 2018

Abstract

The invention provides a compound of formula (I): [insert formula (I)] wherein X, Y, and R 1 -R 4 have any of the values defined in the specification, and salts thereof, as well as compositions comprising the compounds or salts. The compounds are useful for treating diseases associated with impaired mitochondrial function in an animal.

First claim

The invention claimed is:

1. A compound of formula Ib:

wherein:
R 2 is H, cyano, nitro, halo, aryloxy, —OC 1 -C 20 alkyl, —OC 2 -C 20 alkenyl, —OC 2 -C 20 alkynyl, —NR b R c , —C(═O)NR b R c , or —C(═O)OR d ;
Y and R 3 taken together are H, cyano, nitro, halo, aryloxy, —OC 1 -C 20 alkyl, —NR a (C 1 -C 20 alkyl), —NR a (aryl), —C 1 -C 20 alkyl, —C 2 -C 20 alkenyl, or —C 2 -C 20 alkynyl;
R 4 is a C 1 -C 20 alkyl, C 2 -C 20 alkenyl, or C 2 -C 20 alkynyl;
R a is H, C 1 -C 20 alkyl, C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, or C 1 -C 20 alkanoyl;
R x is C 1 -C 16 alkyl, C 2 -C 16 alkenyl, C 2 -C 16 alkynyl, aryl, —OC 1 -C 16 alkyl, —OC 2 -C 16 alkenyl, —OC 2 -C 16 alkynyl, aryloxy, —N(H)C 1 -C 16 alkyl, —N(H)C 2 -C 16 alkenyl, —N(H)C 2 -C 16 alkynyl, or —N(H)aryl;
or a salt thereof.

2. A compound selected from:

and salts thereof.

3. A compound selected from:

4. A compound of formula I:

wherein:
X is NR a or —C(═O)N(R a )—;
R a is H or methyl;
R 1 is a C 1 -C 20 straight or branched, saturated or unsaturated carbon chain, wherein one or more carbon atoms can optionally be replaced with —O—, —NH—, a divalent phenyl group, or a divalent C 3 -C 6 cycloalkyl group; wherein R 1 can be optionally substituted with one or more groups independently selected from halo, aryl, and oxo (═O);
R 2 is H or methyl;
Y and R 3 taken together are methoxy, 3-(tert-butoxycarbonyl)prop-1-yloxy, N-(3-(butoxycarbonyl)prop-1-yl)amino, N-(3-(hexyloxycarbonyl)prop-1-yl)amino, 3-(butoxycarbonyl)prop-1-yloxy, or 3-(hexyloxycarbonyl)prop-1-yloxy; and
R 4 is tridecyl, hexadecyl, or 10-undecen-1-yl;
or a salt thereof;
provided the compound is not:

5. The compound of claim 4 wherein X is NR a .

6. The compound of claim 4 wherein R a is H.

7. The compound of claim 4 wherein R 1 is a C 1 -C 20 straight or branched, saturated or unsaturated carbon chain, wherein one or more carbon atoms can optionally be replaced with —O—; wherein R 1 can be optionally substituted with one or more groups independently selected from aryl and oxo (═O).

8. A compound of formula I:

wherein:
X is NR a , or —C(═O)N(R a )—;
R 1 is a C 1 -C 20 straight or branched, saturated or unsaturated carbon chain, wherein one or more carbon atoms can optionally be replaced with —O—, —NH—, a divalent phenyl group, or a divalent C 3 -C 6 cycloalkyl group; wherein R 1 can be optionally substituted with one or more groups independently selected from halo, aryl, and oxo (═O);
R 2 is H,
Y is O,
R 3 is aryl, or a C 1 -C 20 straight or branched, saturated or unsaturated carbon chain other than methyl;
R 4 is a C 1 -C 20 straight or branched, saturated or unsaturated carbon chain, wherein one or more carbon atoms can optionally be replaced with a divalent phenyl group, or a divalent C 3 -C 6 cycloalkyl group; wherein R 4 can be further optionally substituted with one or more groups independently selected from halo, oxo (═O), carboxy, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, nitro, —SO 3 H, or tetrazolyl; or R 1 and R 4 taken together form a C 3 -C 18 straight or branched, saturated or unsaturated carbon chain that can be optionally substituted with one or more groups independently selected from halo and oxo (═O); and
R a is H;

or a salt thereof.

Assignees

• Univ Arizona State

Inventors

• Madathil Manikandadas Mathilakathu
• Khdour Omar
• Hecht Sidney

Classifications

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P39/06

  Free radical scavengers or antioxidants · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title