IP Library › Granted Patent US 12,570,622
Granted Patent B2
US 12,570,622 · App. 18/070,993 · Granted Mar 10, 2026

Therapeutic compounds

Inventors: Sidney Hecht (Phoenix, AZ); Omar Khdour (Phoenix, AZ); Sandipan Roy Chowdhury (Tempe, AZ); Nishant P. Visavadiya (Tempe, AZ)
Assignee: ARIZONA BOARD OF REGENTS ON BEHALF OF ARIZONA STATE UNIVERSITY
C07D279/18A61K31/5415A61P3/10A61P9/00A61P25/28A61P35/00A61P39/06C07D279/14
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Quick Facts
Patent No.
US 12,570,622
App. No.
18/070,993
Granted
Mar 10, 2026
Kind
B2
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.

Claims (78)

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 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.

5 . The method of claim 1 , wherein the compound of formula I is compound of formula Ia:

or a pharmaceutically acceptable salt thereof.

6 . The method of claim 2 , wherein the compound of formula I is a compound of formula Ia:

or a pharmaceutically acceptable salt thereof.

7 . The method of claim 3 , wherein the compound of formula I is a compound of formula Ia:

or a pharmaceutically acceptable salt thereof.

8 . The method of claim 4 , wherein the compound of formula I is a compound of formula Ia:

or a pharmaceutically acceptable salt thereof.

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

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

11 . The method of claim 3 , wherein R 1 is C 1-20 alkyl and R 2 is C 1-20 alkyl.

12 . The method of claim 4 , wherein R 1 is C 1-20 alkyl and R 2 is C 1-20 alkyl.

13 . The method of claim 1 , 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.

14 . 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.

15 . The method of claim 3 , 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.

16 . The method of claim 14 , 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.

17 . The method of claim 1 , wherein the compound of formula I is selected from the group consisting of:

and

and pharmaceutically acceptable salts thereof.

18 . The method of claim 2 , wherein the compound of formula I is selected from the group consisting of:

and pharmaceutically acceptable salts thereof.

19 . The method of claim 3 , wherein the compound of formula I is selected from the group consisting of:

and pharmaceutically acceptable salts thereof.

20 . The method of claim 4 , wherein the compound of formula I is selected from the group consisting of:

and pharmaceutically acceptable salts thereof.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 20, 2023
From: HECHT, SIDNEY; KHDOUR, OMAR; CHOWDHURY, SANDIPAN ROY; VISAVADIYA, NISHANT P.
To: ARIZONA BOARD OF REGENTS ON BEHALF OF ARIZONA STATE UNIVERSITY
Reel/Frame 064973/0356 →
Continuity (4)
Continuation 16924763 · Jul 9, 2020
Division 16327284
Provisional Application 62379654 · Aug 25, 2016
Related Publication 20230295101A1 · Sep 21, 2023
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