PCSK9 antagonist compounds

Patent metadata

Field	Value
Publication number	US-12209145-B2
Application number	US-202217854379-A
Country	US
Kind code	B2
Filing date	Jun 30, 2022
Priority date	Jun 21, 2018
Publication date	Jan 28, 2025
Grant date	Jan 28, 2025

Abstract

Disclosed are compounds of Formula I, or a salt thereof:

where A, B, D, X, R 1 , R 2 and R 8 are as defined herein, which compounds have properties for antagonizing PCSK9. Also described are pharmaceutical formulations comprising the compounds of Formula I or their salts, and methods of treating cardiovascular disease and conditions related to PCSK9 activity, e.g. atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions.

First claim

What is claimed is:

1. A compound selected from the group consisting of:

or any other pharmaceutically acceptable salt form thereof.

2. A composition comprising at least one compound of claim 1 , or any other pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

3. A method of treating hypercholesterolemia, comprising administering to a patient in need thereof a therapeutically effective amount of a composition of claim 2 .

4. A method of treating hypercholesterolemia, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 , or any other pharmaceutically acceptable salt thereof.

5. A compound selected from the group consisting of:

wherein A − is a pharmaceutically acceptable anion.

6. A composition comprising at least one compound of claim 5 and at least one pharmaceutically acceptable excipient.

7. A method of treating hypercholesterolemia, comprising administering to a patient in need thereof a therapeutically effective amount of a composition of claim 6 .

8. A method of treating hypercholesterolemia, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 5 .

9. A compound having the structure:

10. A composition comprising the compound of claim 9 , and at least one pharmaceutically acceptable excipient.

11. A method of treating hypercholesterolemia, comprising administering to a patient in need thereof a therapeutically effective amount of a composition of claim 10 .

12. A compound having the structure:

wherein A − is a pharmaceutically acceptable anion.

13. A composition comprising the compound of claim 12 , and at least one pharmaceutically acceptable excipient.

14. A method of treating hypercholesterolemia, comprising administering to a patient in need thereof a therapeutically effective amount of a composition of claim 13 .

15. A compound of claim 12 , wherein the compound is:

16. A composition comprising the compound of claim 15 , and at least one pharmaceutically acceptable excipient.

17. A method of treating hypercholesterolemia, comprising administering to a patient in need thereof a therapeutically effective amount of a composition of claim 16 .

18. A compound having the structure:

wherein A − is a pharmaceutically acceptable anion.

19. A composition comprising the compound of claim 18 , and at least one pharmaceutically acceptable excipient.

20. A method of treating hypercholesterolemia, comprising administering to a patient in need thereof a therapeutically effective amount of a composition of claim 19 .

21. A compound of claim 18 , wherein the compound is:

22. A composition comprising the compound of claim 21 , and at least one pharmaceutically acceptable excipient.

23. A method of treating hypercholesterolemia, comprising administering to a patient in need thereof a therapeutically effective amount of a composition of claim 22 .

24. A compound having the structure:

wherein A − is a pharmaceutically acceptable anion.

25. A composition comprising the compound of claim 24 , and at least one pharmaceutically acceptable excipient.

26. A method of treating hypercholesterolemia, comprising administering to a patient in need thereof a therapeutically effective amount of a composition of claim 25 .

27. A compound of claim 24 , wherein the compound is:

Assignees

• Merck Sharp & Dohme Llc

Inventors

• Wood Harold B
• Josien Hubert B
• Tucker Thomas Joseph
• Kerekes Angela Dawn
• Tong Ling
• Walji Abbas M
• Nair Anilkumar G
• Ding Fa-Xiang
• Bianchi Elisabetta
• Branca Danila
• Wu Chengwei
• Xiong Yusheng
• Ha Sookhee Nicole
• Liu Jian
• Boga Sobhana Babu

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• C12Y304/21061

  Kexin (3.4.21.61), i.e. proprotein convertase subtilisin/kexin type 9 · CPC title

• C12N9/6454

  Dibasic site splicing serine proteases, e.g. kexin (3.4.21.61); furin (3.4.21.75) and other proprotein convertases · CPC title