Granted Patent B2

US 12,629,424 · App. 17/309,179 · Granted May 19, 2026

Inventors: Peng Ji (Wilmette, IL); Gary E. Schiltz (Naperville, IL); Rama K. Mishra (Chicago, IL); Atul D. Jain (Chicago, IL)

Assignee: Northwestern University

A61K47/55A61K47/54A61P35/00C07D403/06C07D409/14

Abstract

Claims (21)

1 . A compound having the following formula or a salt, hydrate, or solvate thereof:

wherein:

V is hydrogen, hydroxyl, or keto;

W is hydrogen, hydroxyl, or alkyoxy;

X is 1H-indol-3-yl, N-alkyl-indol-3-yl, 1H-indazol-3-yl, or N-alkyl-indazol-3-yl optionally substituted at one or more positions with a substituent selected from alkyl, cycloalkyl, cycloheteroalkyl, alkoxy, halo, haloalkyl, amino, and cyano;

Y is a 5-membered or 6-membered carbocycle or heterocycle which optionally is saturated or unsaturated at one or more bonds and optionally is substituted at one or more positions with a substituent selected from alkyl, cycloalkyl, cycloheteroalkyl, alkoxy, halo, haloalkyl, amino, and cyano; and

Z is selected from —NR 3 R 4 or —OR 5 , wherein R 3 and R 4 together form a 5-membered heterocycle which is saturated or unsaturated at one or more bonds and optionally is substituted at one or more positions with a substituent selected from alkyl, cycloalkyl, cycloheteroalkyl, alkoxy, halo, haloalkyl, hydroxyalkyl, amino, and cyano; R 5 is selected from hydrogen, alkyl, and cycloalkyl.

2 . The compound of claim 1 , wherein V is keto and W is hydroxyl.

3 . The compound of claim 1 having a formula selected from:

wherein R 1 is selected from alkyl, cycloalkyl, cycloheteroalkyl, alkoxy, halo, haloalkyl, amino, and cyano.

4 . The compound of claim 1 , wherein X is selected from:

5 . The compound of claim 1 , wherein Y is selected from phenyl, pyridinyl, and thiophenyl, optionally substituted at one or more positions with a substituent selected from alkyl, cycloalkyl, cycloheteroalkyl, alkoxy, halo, haloalkyl, aryl, amino, and cyano.

6 . The compound of claim 1 , wherein Y is selected from:

7 . The compound of claim 1 , wherein Z is —NR 3 R 4 and R 3 and R 4 together form a 5-membered heterocycle which is saturated or unsaturated at one or more bonds and optionally is substituted at one or more positions with a substituent selected from alkyl, cycloalkyl, cycloheteroalkyl, alkoxy, halo, haloalkyl, amino, and cyano.

8 . The compound of claim 1 , wherein Z is —OR 5 and R 5 is selected from hydrogen, alkyl, and cycloalkyl.

9 . The compound of claim 1 , wherein Z is selected from:

10 . The compound of claim 1 , having a formula of:

11 . A conjugate comprising the compound of claim 1 further conjugated to an E3 ligase recruiter of a formula:

12 . The conjugate of claim 11 , wherein the conjugation is via a linker, optionally wherein the linker comprises a moiety having a formula —(OCH 2 CH 2 ) n —NHC(O)— and n is 1-6.

13 . A pharmaceutical composition comprising the compound of claim 1 and a suitable pharmaceutical carrier.

14 . A method for treating a cell proliferative disease or disorder in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition of claim 13 , wherein the cell proliferative disease or disorder is a Philadelphia chromosome (Ph)-negative myeloproliferative neoplasm (MPN) or acute myeloid leukemia (AML).

Assignments (2)

Continuity (2)

References Cited (116)