PTPRD inhibitors and uses thereof

Patent metadata

Field	Value
Publication number	US-11987564-B2
Application number	US-202217734897-A
Country	US
Kind code	B2
Filing date	May 2, 2022
Priority date	Apr 30, 2021
Publication date	May 21, 2024
Grant date	May 21, 2024

Abstract

Disclosed are small molecule PTPRD inhibitors and uses thereof. Methods of using the PTPRD inhibitors include methods of treating, preventing, or delaying the progression of a disorder responsive to PTPRD inhibition, including for example nicotine dependence, addiction, obesity, metabolic syndrome, and substance-use disorders such as stimulant-use disorders and opioid-use disorders.

First claim

What is claimed is:

1. A compound having a structure represented by Formula (I):

wherein R 1 is hydrogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C2-C4 alkoxy, C2-C4 haloalkoxy, C1-C4 alkylamino, C1-C4 acetyl, or (C1-C4)(C1-C4) dialkylamino;
R 2 is C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C2-C4 alkoxy, C2-C4 haloalkoxy, C1-C4 alkylamino, or (C1-C4)(C1-C4) dialkylamino;
R 3 is hydrogen or has a structure represented by the formula:

wherein R 9 -R 13 , when present, are independently hydrogen, methyl, —OCH 3 , —CN, —CF 3 , —OCF 3 , or halide;
R 14 , when present, is hydrogen or halide;
R 15 , when present, is methyl or halide;
Y, when present, is CH or N; and
R 16-18 , when present, are independently hydrogen, hydroxyl, or halide;
or a pharmaceutically acceptable salt thereof,
provided that when R 1 is hydrogen and R 2 is methyl, then R 3 is not

2. The compound of claim 1 , wherein:
R 1 is hydrogen or C1-C2 alkyl; and
R 2 is C1-C2 alkyl.

3. The compound of claim 1 , having a structure represented by Formula (II):

4. The compound of claim 1 , wherein R 3 has a structure represented by the formula:

wherein X 1 and X 2 , when present, is independently —Cl, —Br, —I, or —F.

5. The compound of claim 1 , having a structure represented by the formula:

6. The compound of claim 1 , having a structure represented by the formula:

7. The compound of claim 1 , having a structure represented by the formula:

8. A method for treating a disorder responsive to inhibition of receptor-type tyrosine-protein phosphatase delta (PTPRD), the method comprising administering to a subject in need thereof an effective amount of the compound of claim 1 , wherein the disorder is a substance-use disorder, nicotine dependence, obesity, or metabolic syndrome.

9. The method of claim 8 , wherein:
R 1 is hydrogen or C1-C2 alkyl; and
R 2 is C1-C2 alkyl.

10. The method of claim 8 , wherein the compound has a structure represented by Formula (II):

11. The method of claim 8 , wherein R 3 has a structure represented by the formula:

wherein X 1 and X 2 , when present, are independently —Cl, —Br, —I, or —F.

12. The method of claim 8 , wherein the compound has a structure represented by the formula:

13. The method of claim 8 , wherein the compound has a structure represented by the formula:

14. The method of claim 8 , wherein the compound has a structure represented by the formula:

15. The method of claim 8 , wherein the substance-use disorder is a stimulant-use disorder.

16. The method of claim 8 , wherein the substance-use disorder is an opioid-use disorder.

Assignees

• Us Gov Veterans Affairs
• Univ Arizona
• The Us Gov As Respresented By The Department Of Veterans Affairs
• The Univ Of Kentucky Research Foundation

Inventors

• Uhl George Richard
• Henderson Ian M
• Wang Wei
• Prisinzano Thomas

Classifications

• C07D311/54 Primary

  substituted in the carbocyclic ring · CPC title

• C07D405/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D409/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D417/12

  linked by a chain containing hetero atoms as chain links · CPC title