Imidazothiadiazole and imidazopyrazine derivatives as protease activated receptor 4 (PAR4) inhibitors for treating platelet aggregation

Patent metadata

Field	Value
Publication number	US-9688695-B2
Application number	US-201314396771-A
Country	US
Kind code	B2
Filing date	Apr 24, 2013
Priority date	Apr 26, 2012
Publication date	Jun 27, 2017
Grant date	Jun 27, 2017

Abstract

The present invention provides thiazole compounds of Formula I wherein W, Y, R 0 , R 2 , R 4 , R 5 , R 6 , R 7 , X 1 , X 2 , X 3 and X 4 are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.

First claim

What we claim is:

1. A compound, wherein the compound is selected from

or pharmaceutically acceptable salt thereof.

2. A compound of Formula

or pharmaceutically acceptable salt thereof.

3. A method for the treatment of a thromboembolic disorder or the primary or secondary prophylaxis of a thromboembolic disorder, which comprises the steps of administering to a patient in need thereof a therapeutically effective amount of a compound as defined in claim 2 , or pharmaceutically acceptable salts thereof, wherein the thromboembolic disorder is selected from the group consisting of arterial cardiovascular thromboembolic disorders, venous cardiovascular thromboembolic disorders, cerebrovascular thromboembolic disorders, and thromboembolic disorders in the chambers of the heart or in the peripheral circulation.

4. A method of inhibiting or preventing platelet aggregation, which comprises the step of administering to a subject in need thereof a therapeutically effective amount of a PAR4 antagonist, as defined in claim 2 .

5. A compound of Formula

or pharmaceutically acceptable salt thereof.

6. A method for the treatment of a thromboembolic disorder or the primary or secondary prophylaxis of a thromboembolic disorder, which comprises the steps of administering to a patient in need thereof a therapeutically effective amount of a compound as defined in claim 5 , or pharmaceutically acceptable salts thereof, wherein the thromboembolic disorder is selected from the group consisting of arterial cardiovascular thromboembolic disorders, venous cardiovascular thromboembolic disorders, cerebrovascular thromboembolic disorders, and thromboembolic disorders in the chambers of the heart or in the peripheral circulation.

7. A method of inhibiting or preventing platelet aggregation, which comprises the step of administering to a subject in need thereof a therapeutically effective amount of a PAR4 antagonist, as defined in claim 5 .

8. A compound of Formula

or pharmaceutically acceptable salt thereof.

9. A method for the treatment of a thromboembolic disorder or the primary or secondary prophylaxis of a thromboembolic disorder, which comprises the steps of administering to a patient in need thereof a therapeutically effective amount of a compound as defined in claim 8 , or pharmaceutically acceptable salts thereof, wherein the thromboembolic disorder is selected from the group consisting of arterial cardiovascular thromboembolic disorders, venous cardiovascular thromboembolic disorders, cerebrovascular thromboembolic disorders, and thromboembolic disorders in the chambers of the heart or in the peripheral circulation.

10. A method of inhibiting or preventing platelet aggregation, which comprises the step of administering to a subject in need thereof a therapeutically effective amount of a PAR4 antagonist, as defined in claim 8 .

11. A compound of Formula

or pharmaceutically acceptable salt thereof.

12. A method for the treatment of a thromboembolic disorder or the primary or secondary prophylaxis of a thromboembolic disorder, which comprises the steps of administering to a patient in need thereof a therapeutically effective amount of a compound as defined in claim 11 , or pharmaceutically acceptable salts thereof, wherein the thromboembolic disorder is selected from the group consisting of arterial cardiovascular thromboembolic disorders, venous cardiovascular thromboembolic disorders, cerebrovascular thromboembolic disorders, and thromboembolic disorders in the chambers of the heart or in the peripheral circulation.

13. A method of inhibiting or preventing platelet aggregation, which comprises the step of administering to a subject in need thereof a therapeutically effective amount of a PAR4 antagonist, as defined in claim 11 .

14. A compound of Formula

or pharmaceutically acceptable salt thereof.

15. A method for the treatment of a thromboembolic disorder or the primary or secondary prophylaxis of a thromboembolic disorder, which comprises the steps of administering to a patient in need thereof a therapeutically effective amount of a compound as defined in claim 14 , or pharmaceutically acceptable salts thereof, wherein the thromboembolic disorder is selected from the group consisting of arterial cardiovascular thromboembolic disorders, venous cardiovascular thromboembolic disorders, cerebrovascular thromboembolic disorders, and thromboembolic disorders in the chambers of the heart or in the peripheral circulation.

16. A method of inhibiting or preventing platelet aggregation, which comprises the step of administering to a subject in need thereof a therapeutically effective amount of a PAR4 antagonist, as defined in claim 14 .

17. A compound of Formula

or pharmaceutically acceptable salt thereof.

18. A method for the treatment of a thromboembolic disorder or the primary or secondary prophylaxis of a thromboembolic disorder, which comprises the steps of administering to a patient in need thereof a therapeutically effective amount of a compound as defined in claim 17 , or pharmaceutically acceptable salts thereof, wherein the thromboembolic disorder is selected from the group consisting of arterial cardiovascular thromboembolic disorders, venous cardiovascular thromboembolic disorders, cerebrovascular thromboembolic disorders, and thromboembolic disorders in the chambers of the heart or in the peripheral circulation.

19. A method of inhibiting or preventing platelet aggregation, which comprises the step of administering to a subject in need thereof a therapeutically effective amount of a PAR4 antagonist, as defined in claim 17 .

20. A compound having the formula

or pharmaceutically acceptable salt thereof.

21. A method for the treatment of a thromboembolic disorder or the primary or secondary prophylaxis of a thromboembolic disorder, which comprises the steps of administering to a patient in need thereof a therapeutically effective amount of a compound as defined in claim 20 , or pharmaceutically acceptable salts thereof, wherein the thromboembolic disorder is selected fr

Assignees

• Bristol Myers Squibb Co
• Univ Montreal

Inventors

• Banville Jacques
• Rémillard Roger
• Ruediger Edward H
• Deon Daniel H
• Gagnon Marc
• Dubé Laurence
• Guy Julia
• Priestley Eldon Scott
• Posy Shoshana L
• Maxwell Brad D
• Wong Pancras C
• Lawrence R Michael
• Miller Michael M

Classifications

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• 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

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title