NSD family inhibitors and methods of treatment therewith

Patent metadata

Field	Value
Publication number	US-12364688-B2
Application number	US-202217729836-A
Country	US
Kind code	B2
Filing date	Apr 26, 2022
Priority date	Dec 7, 2017
Publication date	Jul 22, 2025
Grant date	Jul 22, 2025

Abstract

Provided herein are small molecule inhibitors of NSD1, NSD2 and/or NSD3 activity, and methods of use thereof for the treatment of disease, including leukemia, breast cancer, osteosarcoma, lung and prostate cancers and other solid tumors as well as other diseases dependent on the activity of NSD1, NSD2 and/or NSD3.

First claim

The invention claimed is:

1. A composition comprising a compound having a structure of

or a salt thereof;
wherein X is CH 2 or NH;
wherein R 2 is selected from H and C 1 -C 4 alky;
wherein R 4 is selected from H, halogen, OH, OCH 3 , OCH 2 CH 3 , CH 2 OH, NH 2 , CH 2 NH 3 , NHCH 3 , CH 3 , CH 2 CH 3 , trihalomethyl, trihaloethyl, dihalomethyl, dihaloethyl, halomethyl, and haloethyl;
wherein R 5 is selected from H, CH 3 , CH 2 CH 3 , OH, OCH 3 , NH 2 , and halogen;
wherein Z is NH, S, O, CH 2 , or is absent;
wherein A is selected from a 5- or 6-membered aryl ring, 5- or 6-membered heteroaryl ring, 5- or 6-membered cycloalkyl ring, or a 5- or 6-membered heterocyclic ring;
wherein A is unsubstituted or substituted with one or more of halogen, OH, OCH 3 , OCH 2 CH 3 , OCH (CH 3 ) 2 , OCH 2 CH (CH 3 ) 2 , CH 2 OCH 3 , NH 2 , CH 2 NH 3 , NHCH 3 , CH 3 , CH 2 CH 3 , CH 2 CH (CH 3 ) 2 , and amide;
wherein L is —NHC (O) CH 2 —, —NHC (O) (CH 2 ) 2 —, —NHC (O) (CH 2 ) 3 —, —NHC (O) CH═CH—, —NHCH 2 —, —NH (CH 2 ) 2 —, —NH (CH 2 ) 3 —, —O—, —OCH 2 —, —O (CH 2 ) 2 —, —O (CH 2 ) 3 —, —CH 2 —, —CH 2 O—, or absent;
wherein E is selected from a 5- or 6-membered aryl ring, 5- or 6-membered heteroaryl ring, 5- or 6-membered cycloalkyl ring, or a 5- or 6-membered heterocyclic ring;
wherein Y is absent or a Michael acceptor;
wherein R 7 is H, D, F, OH, NH 2 , or CH 3 .

2. The composition of claim 1 , wherein the compound is selected from:

3. The composition of claim 1 , wherein is Y is selected from propenal, 3-buten-2-one, acrylamide, vinyl sulfonamide, propynamide, ethyl propenoate, propenanamide, propenenitrile, or nitroethylene.

Assignees

• Univ Michigan Regents

Inventors

• Cierpicki Tomasz
• Grembecka Jolanta
• Huang Huang
• Zari Sergei
• Cho Hyo Je
• Potopnyk Mykhaylo
• Dudkin Sergii
• Chen Wenbing
• Adam Yassir
• Howard Christina
• Kim Eungi

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07D277/64

  with only hydrocarbon or substituted hydrocarbon radicals attached in position 2 · CPC title

• C07D417/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D277/84

  Naphthothiazoles · CPC title

• C07D277/60

  condensed with carbocyclic rings or ring systems · CPC title