Claims for Patent: 9,303,044

Summary for Patent: 9,303,044

Title:	7-(piperazin-1-yl)-5H-[1,3,4]thiadiazolo[3,2-A]pyrimidin-5-ones for the treatment of thrombotic disorders
Abstract:	The present invention relates to compounds and compositions of Formula P useful for inhibiting and/or reducing platelet deposition, adhesion and/or aggregation. The definitions of variables A, B, R.sub.2, R.sub.3, R.sub.4, R.sub.a, R.sub.a\', R.sub.b, R.sub.b\', R.sub.c, R.sub.d, R.sub.d\', R.sub.e, and R.sub.e\' are provided in the disclosure. The present invention further relates to methods for the treatment or prophylaxis of thrombotic disorders, including stroke, myocardial infarction, unstable angina, peripheral vascular disease, abrupt closure following angioplasty or stent placement and thrombosis as a result of vascular surgery.
Inventor(s):	Coller; Barry S. (New York, NY), Thomas; Craig (Rockville, MD), Filizola; Marta (New York, NY), McCoy; Joshua (Portland, ME), Huang; Wenwei (Rockville, MD), Shen; Min (Boyds, MD), Jiang; Jian-Kang (Columbia, MD)
Assignee:	THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES (Washington, DC) THE ROCKEFELLER UNIVERSITY (New York, NY) ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI (New York, NY)
Application Number:	14/372,488
Patent Claims:	1. A compound of Formula P: ##STR00044## wherein: i) A is nitrogen and B is carbon; or B is nitrogen and A is carbon and R.sub.3 is absent; ii) R.sub.2 is H or halo; iii) R.sub.a, R.sub.a', R.sub.b, R.sub.b', R.sub.c, R.sub.d, R.sub.d', R.sub.e, and R.sub.e' are H; iv) R.sub.3, when present, and R.sub.4 are independently hydrogen, halo, C.sub.1-4alkyl, haloC.sub.1-4alkyl, hydroxy-C.sub.1-4alkyl, or acetyl; in free or salt form. 2. A compound of Formula I: ##STR00045## wherein: i) R.sub.2 is H; ii) R.sub.a, R.sub.a', R.sub.b, R.sub.b', R.sub.c, R.sub.d, R.sub.d', R.sub.e, and R.sub.e' are H; iii) R.sub.3 and R.sub.4 are independently hydrogen, halo, C.sub.1-4alkyl, haloC.sub.1-4alkyl, hydroxy-C.sub.1-4alkyl or acetyl, provided R.sub.3 and R.sub.4, are not both hydrogen; in free or salt form. 3. The compound according to claim 1, selected from the group consisting of: ##STR00046## 4. The compound according to claim 2, selected from the group consisting of: ##STR00047## ##STR00048## ##STR00049## in free or salt form. 5. A compound of Formula P-II, in free or salt form: ##STR00050## wherein: A is carbon or nitrogen; and R.sub.2 is H or halo. 6. The compound according to claim 5, which is selected from: ##STR00051## in free or salt form. 7. A compound of salt thereof of claim 1, wherein the compound is ##STR00052## 8. A compound of salt thereof of claim 1, wherein the compound is ##STR00053## 9. A compound of salt thereof of claim 1, wherein the compound is ##STR00054## 10. A pharmaceutical composition comprising the compound of claim 1, in combination or association with a pharmaceutically acceptable diluent or carrier. 11. A method for the treatment of a thrombotic disorder comprising administering to a subject at risk of thrombotic disorder an effective amount of the compound of claim 1, in free or pharmaceutically acceptable salt form, such that platelet aggregation and/or adhesion is reduced. 12. The method according to claim 11, wherein both platelet aggregation and adhesion are reduced. 13. The method of claim 11, wherein said thrombotic disorders is selected from a group consisting of stroke, myocardial infarction, unstable angina, abrupt closure following angioplasty or stent placement, thrombosis induced by peripheral vascular surgery, peripheral vascular disease or thrombotic disorders resulting from atrial fibrillation or inflammation. 14. The method of claim 11, wherein said thrombotic disorder is thrombosis induced by peripheral vascular surgery. 15. The method of claim 11, further comprises administering to said subject an effective amount of at least one therapeutic agent selected from a group consisting of anti-coagulant, antiplatelet, and fibrinolytic agents in conjunction with the compound according to claim 1, in free or pharmaceutically acceptable salt form. 16. The method according to claim 12, wherein said therapeutic agent is selected from a group consisting of heparin, low molecular weight heparins, bivalirudin, Fondaparinux, warfarin, Acenocoumarol, Phenprocoumon, Phenindione, Abbokinase (urokinase), streptokinase, alteplase, retaplase, tenecteplase, prasugrel, aspirin, ticlopidine, clopidogrel, ticagrelor, abciximab, eptifibatide and tirofiban. 17. The method of claim 11, further comprising administering heparin. 18. A method for inhibiting or reducing platelet aggregation and adhesion comprising administering an effective amount of the compound of claim 1, in free or pharmaceutically acceptable salt form, such that platelet aggregation and adhesion is reduced. 19. A method for the treatment of a thrombotic disorder comprising administering to a subject having a thrombotic disorder or at risk of a thrombotic disorder an effective amount of the compound of claim 2, in free or pharmaceutically acceptable salt form, such that platelet aggregation and/or adhesion is reduced. 20. A method for the treatment of a thrombotic disorder comprising administering to a subject having a thrombotic disorder or at risk of a thrombotic disorder an effective amount of the compound of claim 5, in free or pharmaceutically acceptable salt form, such that platelet aggregation and/or adhesion is reduced.

Details for Patent 9,303,044

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Microbix Biosystems Inc.	KINLYTIC	urokinase	For Injection	021846	01/16/1978		2032-01-16
Genentech, Inc.	ACTIVASE	alteplase	For Injection	103172	11/13/1987		2032-01-16
Genentech, Inc.	CATHFLO ACTIVASE	alteplase	For Injection	103172	09/04/2001		2032-01-16
Janssen Biotech, Inc.	REOPRO	abciximab	Injection	103575	12/22/1994		2032-01-16
Genentech, Inc.	TNKASE	tenecteplase	For Injection	103909	06/02/2000		2032-01-16