Therapeutic compounds

Patent metadata

Field	Value
Publication number	US-11560360-B2
Application number	US-202016924763-A
Country	US
Kind code	B2
Filing date	Jul 9, 2020
Priority date	Aug 25, 2016
Publication date	Jan 24, 2023
Grant date	Jan 24, 2023

Abstract

The invention provides compounds having the general formula I:and pharmaceutically acceptable salts thereof, wherein the variables R1, R2, R3, R4, subscript m and n, have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.

First claim

What is claimed is:

1. A method of treating mitochondrial disease in an animal comprising administering to the animal an effective amount of compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein:
R 1 is C 1-20 alkyl, C 2-20 alkenyl or C 2-20 alkynyl, and wherein the C 1-20 alkyl, C 2-20 alkenyl and C 2-20 alkynyl are optionally substituted with one or more groups independently selected from —F, —Cl, —Br, —I, —OR a , —SR a , —NR a R b , oxo, —NO 2 and —CN;

R 2 is C 1-20 alkyl, C 2-20 alkenyl or C 2-20 alkynyl, and wherein the C 1-20 alkyl, C 2-20 alkenyl and C 2-20 alkynyl are optionally substituted with one or more groups independently selected from —F, —Cl, —Br, —I, —OR a , —SR a , —NR a R b , oxo, —NO 2 and —CN; or
R 1 and R 2 taken together with the nitrogen to which they are attached form a 3-12 membered heterocycle that is optionally substituted with one or more groups independently selected from C 1-4 alkyl, C 1-4 haloalkyl, —F, —Cl, —Br, —I, —OR a , —SR a , —NR a R b , oxo, —NO 2 and —CN;
each R 3 is independently selected from the group consisting of —F, —Cl, —Br, —I, —OH, —OR a , —SR a , —NR a R b , —CN, C 1-4 alkyl, C 2-4 alkenyl and C 2-4 alkynyl, and wherein the C 1-4 alkyl, C 2-4 alkenyl and C 2-4 alkynyl are optionally substituted with one or more groups independently selected from —F, —Cl, —Br, —I, —OR a , —SR a , —NR a R b , oxo, —NO 2 and —CN;
each R 4 is independently selected from the group consisting of —F, —Cl, —Br, —I, —OR a , —SR a , —NR a R b , —NO 2 , —CN, C 1-4 alkyl, C 2-4 alkenyl and C 2-4 alkynyl, and wherein the C 1-4 alkyl, C 2-4 alkenyl and C 2-4 alkynyl are optionally substituted with one or more groups independently selected from —F, —Cl, —Br, —I, —OR a , —SR a , —NR a R b , oxo, —NO 2 and —CN;
each R a is independently hydrogen or C 1-4 alkyl;
each R b is independently hydrogen or C 1-4 alkyl;
the subscript m is 0, 1, 2 or 3; and
the subscript n is 0, 1, 2, or 3.

2. The method of claim 1 , wherein the compound or salt is a compound of formula Ia:

or a pharmaceutically acceptable salt thereof.

3. The method of claim 2 , wherein R 1 is C 12-20 alkyl, C 12-20 alkenyl or C 12-20 alkynyl, and wherein the C 12-20 alkyl, C 12-20 alkenyl and C 12-20 alkynyl are optionally substituted with one or more groups independently selected from —F, —Cl, —Br, —I, —OR a , —SR a , —NR a R b , oxo, —NO 2 and
—CN;
each R a is independently hydrogen or C 1-4 alkyl; and
each R b is independently hydrogen or C 1-4 alkyl.

4. The method of claim 1 wherein the compound or salt is selected from the group consisting of:

and pharmaceutically acceptable salts thereof.

5. The method of claim 1 , wherein the compound or salt is a compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:
R 1 is C 12-20 alkyl, C 12-20 alkenyl or C 12-20 alkynyl, and wherein the C 12-20 alkyl, C 12-20 alkenyl and C 12-20 alkynyl are optionally substituted with one or more groups independently selected from —F, —Cl, —Br, —I, —OR a , —SR a , —NR a R b , oxo, —NO 2 and —CN;
R 2 is methyl each R 3 is independently selected from the group consisting of —F, —Cl, —Br, —I, —OH, —OR a , —SR a , —NR a R b , —CN, C 1-4 alkyl, C 2-4 alkenyl and C 2-4 alkynyl, and wherein the C 1-4 alkyl, C 2-4 alkenyl and C 2-4 alkynyl are optionally substituted with one or more groups independently selected from —F, —Cl, —Br, —I, —OR a , —SR a , —NR a R b , oxo, —NO 2 and —CN;
each R 4 is independently selected from the group consisting of —F, —Cl, —Br, —I, —OR a , —SR a , —NR a R b , —NO 2 , —CN, C 1-4 alkyl, C 2-4 alkenyl and C 2-4 alkynyl, and wherein the C 1-4 alkyl, C 2-4 alkenyl and C 2-4 alkynyl are optionally substituted with one or more groups independently selected from —F, —Cl, —Br, —I, —OR a , —SR a , —NR a R b , oxo, —NO 2 and —CN;
each R a is independently hydrogen or C 1-4 alkyl;
each R b is independently hydrogen or C 1-4 alkyl;
the subscript m is 0, 1, 2 or 3; and
the subscript n is 0, 1, 2, or 3.

6. The method of claim 5 , wherein the compound or salt is a compound of formula Ia:

or a pharmaceutically acceptable salt thereof.

7. The method of claim 1 , wherein R 1 is n-pentadecyl.

8. The method of claim 1 , wherein the compound or salt is selected from the group consisting of:

and
pharmaceutically acceptable salts thereof.

9. The method of claim 2 , wherein R 1 is C 1-20 alkyl.

10. The method of claim 2 , wherein R 2 is C 1-20 alkyl.

11. The method of claim 2 , wherein R 2 is C 1 alkyl.

12. The method of claim 2 , wherein R 1 is C 1-20 alkyl; R 2 is C 1 alkyl.

13. The method of claim 2 , wherein, R 1 is n-butyl, n-decyl or n-pentadecyl.

14. The method of claim 2 , wherein, R 2 is methyl, n-butyl, n-decyl or n-pentadecyl.

15. The method of claim 2 , wherein, R 1 is n-decyl; and R 2 is methyl.

Assignees

• Univ Arizona State

Inventors

• Hecht Sidney
• Khdour Omar
• Chowdhury Sandipan Roy
• Visavadiya Nishant P

Classifications

• A61P39/06

  Free radical scavengers or antioxidants · CPC title

• C07D279/18 Primary

  [b, e]-condensed with two six-membered rings · CPC title

• C07D279/14

  condensed with carbocyclic rings or ring systems · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title