IP Library Granted Patent US 12,514,850
Granted Patent B2
US 12,514,850 · App. 17/359,857 · Granted Jan 6, 2026

Synthesis of small molecule histone deacetylase 6 degraders, compounds formed thereby, and pharmaceutical compositions containing them

Inventors: Weiping Tang (Middleton, WI); Ka Yang (Madison, WI); Hao Wu (Madison, WI)
Assignee: Wisconsin Alumni Research Foundation
A61K31/4439C07D401/14
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Quick Facts
Patent No.
US 12,514,850
App. No.
17/359,857
Granted
Jan 6, 2026
Kind
B2
Abstract

Histone deacetylase (“HDAC”)-selective inhibitors covalently bonded to a linker covalently bonded to an E3 ubiquitin ligase ligand, and salts thereof; pharmaceutical compositions containing them; methods of using the composition to inhibit neoplastic cell growth in mammals, including humans.

Claims (34)

1 . A compound comprising a histone deacetylase 6 (“HDAC6”)-selective inhibitor covalently bonded to a linker, covalently bonded to an E3 ubiquitin ligase ligand:

wherein:

the HDAC6-selective inhibitor is selected from the group consisting of:

wherein each R 1 is independently selected from —O— or —(NH)—, each R 2 is independently selected from —(CH 2 )— or —(NH)—, each Z is independently selected from —N— or —(CH)—, and each “n” is an integer of from 1 to 12;

the linker is a C 1 -C 12 linear or branched alkylene, alkenylene, or alkynylene, —O—(CH 2 ) n —, or —NH—(CH 2 ) n —, wherein “n” is an integer of from 1 to 12; and

the E3 ubiquitin ligase ligand is selected from:

wherein R 3 is hydrogen, C 1 -C 6 -alkyl, or ═O, R 4 is hydrogen or halogen, Y is —(C═O)— or —(CH 2 )—, and “m” is an integer of from 1 to 6; and

salts thereof.

2 . The compound of claim 1 , wherein the linker is C 1 -C 12 linear or branched alkylene, alkenylene, or alkynylene.

3 . The compound of claim 2 , wherein each Z is —N—.

4 . The compound of claim 2 , wherein each Z is —(CH)—.

5 . The compound of claim 2 , wherein Y is —(C═O)—.

6 . The compound of claim 2 , wherein Y is —(CH 2 )—.

7 . The compound of claim 1 , wherein the linker is —O—(CH 2 ) m —.

8 . The compound of claim 7 , wherein each Z is —N—.

9 . The compound of claim 7 , wherein each Z is —(CH)—.

10 . The compound of claim 7 , wherein Y is —(C═O)—.

11 . The compound of claim 7 , wherein Y is —(CH 2 )—.

12 . The compound of claim 1 , wherein the linker is —NH—(CH 2 ) m .

13 . The compound of claim 12 , wherein each Z is —N—.

14 . The compound of claim 12 , wherein each Z is —(CH)—.

15 . The compound of claim 12 , wherein Y is —(C═O)—.

16 . The compound of claim 12 , wherein Y is —(CH 2 )—.

17 . A method to inhibit neoplastic cell growth, the method comprising contacting a cell with one or more compounds as recited in claim 1 , wherein the neoplastic cell is selected from the group consisting of multiple myeloma, malignant melanoma, and leukemia.

18 . A method to inhibit neoplastic cell growth, the method comprising administering to a subject a neoplastic cell growth inhibiting-effective amount of one or more compounds as recited in claim 1 , wherein the neoplastic cell is selected from the group consisting of multiple myeloma, malignant melanoma, and leukemia.

19 . A pharmaceutical composition comprising an amount of one or more compounds as recited in claim 1 , in combination with a pharmaceutically suitable carrier.

20 . The compound of claim 1 , wherein the HDAC6-selective inhibitor is selected from the group consisting of:

21 . The compound of claim 1 , wherein the HDAC6-selective inhibitor is selected from the group consisting of:

22 . The compound of claim 1 , wherein the HDAC6-selective inhibitor is selected from the group consisting of:

23 . The compound of claim 1 , wherein the HDAC6-selective inhibitor is selected from the group consisting of:

24 . The compound of claim 1 , wherein the HDAC6-selective inhibitor is selected from the group consisting of:

25 . The compound of claim 1 , wherein the HDAC6-selective inhibitor is selected from the group consisting of:

26 . The compound of claim 1 , wherein the HDAC6-selective inhibitor is selected from the group consisting of:

27 . The compound of claim 1 , wherein the HDAC6-selective inhibitor is selected from the group consisting of:

Assignments (2)
CONFIRMATORY LICENSE Recorded Dec 26, 2023
From: UNIVERSITY OF WISCONSIN MADISON
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 066128/0721 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 5, 2021
From: TANG, WEIPING; YANG, KA; WU, HAO
To: WISCONSIN ALUMNI RESEARCH FOUNDATION
Reel/Frame 058034/0897 →
Continuity (6)
Continuation 16517943 · Jul 22, 2019
Provisional Application 62844784 · May 8, 2019
Provisional Application 62831817 · Apr 10, 2019
Provisional Application 62701892 · Jul 23, 2018
Related Publication 20210322398A1 · Oct 21, 2021
Related Publication 20230310400A9 · Oct 5, 2023
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