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

Patent metadata

Field	Value
Publication number	US-12084452-B2
Application number	US-202217902618-A
Country	US
Kind code	B2
Filing date	Sep 2, 2022
Priority date	Apr 26, 2012
Publication date	Sep 10, 2024
Grant date	Sep 10, 2024

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 is claimed is:

1. A compound of Formula I:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or prodrug thereof, wherein:
W is or O or S;
R 0 is R 1 ;
Y is S;
R 1 is OCH 3 or —CH(CH 3 )F;
R 2 is H;
X 1 is CH;
X 2 , X 3 and X 4 are independently selected from CR 3 or N;
R 3 is OCH 3 or F;
R 4 and R 5 are each H;

R 6 is selected from the group consisting of

R 7 is H or CH 3 .

2. A pharmaceutical composition, which comprises a pharmaceutically acceptable carrier and a compound as defined in claim 1 , or stereoisomers, tautomers, pharmaceutically acceptable salts, or solvates thereof, alone or in combination with another therapeutic agent.

3. A method for the treatment of a thromboembolic disorder or the primary or secondary prophylaxis of a thromboembolic disorder, which comprises the step of administering to a patient in need thereof a therapeutically effective amount of a compound as defined in claim 1 , or stereoisomers, tautomers, pharmaceutically acceptable salts, or solvates 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, wherein the PAR4 antagonist is a compound as defined in claim 1 .

5. A compound selected from the group consisting of

6. A compound selected from the group consisting of

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

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title

• C07B59/002

  Heterocyclic compounds · CPC title

• A61K51/0453

  having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole · CPC title

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• A61K31/5386

  spiro-condensed or forming part of bridged ring systems · CPC title