Therapeutic compounds

Patent metadata

Field	Value
Publication number	US-12570622-B2
Application number	US-202218070993-A
Country	US
Kind code	B2
Filing date	Nov 29, 2022
Priority date	Aug 25, 2016
Publication date	Mar 10, 2026
Grant date	Mar 10, 2026

Abstract

The invention provides compounds having the general formula I:

and pharmaceutically acceptable salts thereof, wherein the variables R 1 , R 2 , R 3 , R 4 , subscipt 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 preserving mitochondrial function in an animal comprising administering to the animal an effective amount of compound of formula (I);

or 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 alkenyl, C 2-20 alkynyl 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 . A method of protecting cells from oxidative stress in an animal comprising administering to the animal an effective amount of compound of formula (I);

or 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, —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 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 , oxo, —NO 2 and —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 subscnpt n is 0, 1, 2, or 3.

3 . A method of preserving mitochondrial membrane potential and/or augmenting ATP production in an animal comprising administering to the animal an effective amount of compound of formula (I);

or 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 , oxo, —NO 2 and —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.

4 . A method of preserving mitochondrial membrane potential and/or augmenting ATP production of a cell in vitro comprising contacting the cell with an effective amount of compound of formula (I);

or 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 substitu

Assignees

• Univ Arizona State

Inventors

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

Classifications

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · 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

• C07D279/14

  condensed with carbocyclic rings or ring systems · CPC title