Granted Patent B2

US 12,648,917 · App. 18/403,100 · Granted Jun 9, 2026

Inventors: Laura Ranum (Gainesville, FL); Tao Zu (Gainesville, FL)

Assignee: University of Florida Research Foundation, Incorporated

A61K31/155

Abstract

Claims (29)

1 . A method of treating a neurological disease associated with repeat expansions in a subject in need thereof, the method comprising administering to the subject in need thereof an effective amount of a compound of Formula (I):

or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein:

each instance of is a single bond or double bond, as valency permits;

each instance of R 2A is independently hydrogen or substituted or unsubstituted C 1-6 alkyl;

R 3 is hydrogen or unsubstituted C 1-6 alkyl;

each instance of R 4 is independently hydrogen, unsubstituted C 1-6 alkyl, or absent, as valency permits;

each instance of R 6 is independently hydrogen, unsubstituted C 1-6 alkyl, or absent, as valency permits; and

R 7 is hydrogen, unsubstituted C 1-6 alkyl, or absent, as valency permits;

wherein the neurological disease associated with repeat expansions is spinocerebellar ataxia type 1, 2, 3, 6, 7, 8, 12, or 17.

2 . The method of claim 1 , wherein the compound is of Formula (I-A):

or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof.

3 . The method of claim 1 , wherein the compound is of formula:

or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof.

4 . The method of claim 1 , wherein at least one instance of R 2A is substituted or unsubstituted C 1-6 alkyl.

5 . The method of claim 1 , wherein R 3 is hydrogen.

6 . The method of claim 1 , wherein at least one instance of R 6 is hydrogen.

7 . The method of claim 1 , wherein the compound is of formula:

or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof.

8 . The method of claim 1 , wherein the compound is of formula:

or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof.

9 . The method of claim 1 , whereby the method comprises reducing the level of one or more repeat associated non-ATG (RAN) proteins, and/or reducing the translation of one or more RAN proteins.

10 . The method of claim 1 , wherein the neurological disease associated with repeat expansions is spinocerebellar ataxia type 8.

11 . The method of claim 1 , wherein the neurological disease associated with repeat expansions is spinocerebellar ataxia type 1, spinocerebellar ataxia type 2, spinocerebellar ataxia type 3, spinocerebellar ataxia type 6, spinocerebellar ataxia type 7, spinocerebellar ataxia type 12, or spinocerebellar ataxia type 17.

12 . The method of claim 1 , wherein each instance of R 4 is independently hydrogen or absent, as valency permits; and R 7 is hydrogen or absent, as valency permits.

13 . The method of claim 1 , wherein the method comprises administering to the subject in need thereof an effective amount of the compound, or a pharmaceutically acceptable salt thereof.

14 . The method of claim 1 , wherein the method comprises administering to the subject in need thereof an effective amount of a compound of the formula:

or a pharmaceutically acceptable salt thereof.

15 . The method of claim 1 , wherein the method comprises administering to the subject in need thereof an effective amount of a compound of the formula:

or a pharmaceutically acceptable salt thereof.

Assignments (1)

Continuity (3)

References Cited (272)