Granted Patent B2

US 12,582,644 · App. 17/271,793 · Granted Mar 24, 2026

Inventors: Suzanne Walker Kahne (Cambridge, MA); Sara Evelyn Schwanger Martin (Cambridge, MA); Craig Joseph Thomas (Gaithersburg, MD); Damien Yves Duveau (Germantown, MD)

Assignees: President and Fellows of Harvard College; The United States of America, as represented by the Secretary, Department of Health and Human Services

A61K31/4709A61K45/06C07D409/12

Abstract

Claims (30)

1 . A compound of Formula (I-A):

or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, wherein

X is —SO 2 —, —SO—, or —C(═O)—;

Ring Y is 5-membered heterocyclyl or 5-membered heteroaryl with 1-2 heteroatoms selected from the group consisting of N and S;

R 1 is chloro;

R 2 is unsubstituted methyl;

R 3 is halogen, —CN, —SCN, —NO 2 , —N 3 , optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR a , —N(R b ) 2 , or —SR a ;

each instance of R a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

each instance of R b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

R 4 is hydrogen, optionally substituted alkyl, or a nitrogen protecting group;

R 5 is hydrogen, optionally substituted alkyl, or a nitrogen protecting group;

R 6 is hydrogen, optionally substituted alkyl, or a nitrogen protecting group; and

n is 0, 1, 2, 3, 4, or 5.

2 . The compound of claim 1 , wherein Ring Y is thiophenyl, isothiazolyl, or thiazolyl.

3 . The compound of claim 1 , wherein R 6 is optionally substituted C 1-6 alkyl.

4 . The compound of claim 3 , wherein R 6 is of the formula: —(CH 2 ) x C(═O)OR 4b or —(CH 2 ) x C(═O)N(R 4c ) 2 , wherein:

x is 1, 2, 3, 4, 5, or 6;

R 4b is hydrogen or optionally substituted C 1-6 alkyl; and

each instance of R 4c is independently hydrogen or optionally substituted C 1-6 alkyl.

5 . The compound of claim 4 , wherein R 6 is of the formula:

—(CH 2 )C(═O)OH, —(CH 2 )C(═O)OMe, —(CH 2 )C(═O)OEt, —(CH 2 )C(═O)NH(Me),

—(CH 2 )C(═O)NH(Et), —(CH 2 )C(═O)NH(n-propyl), or —(CH 2 )C(═O)NH(CH 2 ) 2 OMe.

6 . The compound of claim 1 , wherein R 4 is hydrogen.

7 . The compound of claim 1 , wherein R 5 is hydrogen.

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

or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof.

9 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof.

10 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof, and a pharmaceutically acceptable excipient.

11 . A method for treating an O-linked N-acetylglucosamine transferase (OGT)-associated disease or condition in a subject in need of such treatment, the method comprising administering to the subject a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof.

12 . A method for inhibiting OGT activity in a biological sample, the method comprising contacting the biological sample with an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled compound, or prodrug thereof.

Assignments (3)

Continuity (2)

References Cited (400)