Substituted aminothiazoles as DGKzeta inhibitors for immune activation

Patent metadata

Field	Value
Publication number	US-11964953-B2
Application number	US-202217944922-A
Country	US
Kind code	B2
Filing date	Sep 14, 2022
Priority date	Apr 24, 2020
Publication date	Apr 23, 2024
Grant date	Apr 23, 2024

Abstract

The present invention covers aminothiazole compounds of general formula (I), in which R 1 , R 2 , R 3 and R 4 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment and/or prophylaxis of diseases, in particular of diacylglycerol kinase zeta (DGKζ) regulated disorders, as a sole agent or in combination with other active ingredients.

First claim

The invention claimed is:

1. A compound having the structure:

or a tautomer, hydrate, or solvate thereof, or a pharmaceutically acceptable salt of any of the foregoing.

2. The compound of claim 1 , wherein the compound is

or a tautomer, hydrate, or solvate thereof, or a pharmaceutically acceptable salt of any of the foregoing.

3. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 , wherein the compound is

5. A pharmaceutical composition comprising a compound of claim 2 , or a tautomer, hydrate, or solvate thereof, or a pharmaceutically acceptable salt of any of the foregoing, and at least one pharmaceutically acceptable excipient.

6. A pharmaceutical composition comprising a compound of claim 3 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

7. A pharmaceutical composition comprising a compound of claim 4 and at least one pharmaceutically acceptable excipient.

8. A method of treating a disease or condition associated with dysregulated immune responses or aberrant DGKζ signaling in a mammal, comprising administering an effective amount of a compound of claim 2 , or a tautomer, hydrate, or solvate thereof, or a pharmaceutically acceptable salt of any of the foregoing, to the mammal.

9. The method of claim 8 , wherein the mammal is a human.

10. The method of claim 8 , wherein the disease is cancer.

11. The method of claim 8 , wherein the disease is non-small cell lung cancer, gastric adenocarcinoma, cancer of the gastroesophageal junction, clear cell renal cell carcinoma, or melanoma.

12. The method of claim 8 , wherein the disease is non-small cell lung cancer.

13. The method of claim 8 , wherein the disease is gastric adenocarcinoma.

14. The method of claim 8 , wherein the disease is cancer of the gastroesophageal junction.

15. The method of claim 8 , wherein the disease is clear cell renal cell carcinoma.

16. The method of claim 8 , wherein the disease is melanoma.

17. A method of treating a disease or condition associated with dysregulated immune responses or aberrant DGKζ signaling in a mammal, comprising administering an effective amount of a compound of claim 3 , or a pharmaceutically acceptable salt thereof, to the mammal.

18. The method of claim 17 , wherein the compound is

19. The method of claim 17 , wherein the mammal is a human.

20. The method of claim 17 , wherein the disease is cancer.

21. The method of claim 17 , wherein the disease is non-small cell lung cancer, gastric adenocarcinoma, cancer of the gastroesophageal junction, clear cell renal cell carcinoma, or melanoma.

22. The method of claim 17 , wherein the disease is non-small cell lung cancer.

23. The method of claim 17 , wherein the disease is gastric adenocarcinoma.

24. The method of claim 17 , wherein the disease is cancer of the gastroesophageal junction.

25. The method of claim 17 , wherein the disease is clear cell renal cell carcinoma.

26. The method of claim 17 , wherein the disease is melanoma.

Assignees

• Bayer Ag
• Deutsches Krebsforsch

Inventors

• Schmees Norbert
• Roehn Ulrike
• Kirchhoff Dennis
• Petersen Kirstin
• Grees Mareike
• Werbeck Nicolas
• Bader Benjamin
• Offringa Rienk
• Link Corinna

Classifications

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P5/50

  for increasing or potentiating the activity of insulin · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61P11/06

  Antiasthmatics · CPC title