Claims for Patent: 7,368,438

Summary for Patent: 7,368,438

Title:	Non-nucleotide compositions and method for inhibiting platelet aggregation
Abstract:	This invention is directed to a method of preventing or treating diseases or conditions associated with platelet aggregation. The method is also directed to a method of treating thrombosis or related disorders. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a non-nucleotide compound, preferably a P2Y.sub.12 receptor antagonist compound, wherein said amount is effective to inhibit platelet aggregation. The compounds useful for this invention include compounds of general Formula I and III-XI, or salts, hydrates, and solvates thereof. The present invention also provides novel compounds according to Formula I and III-XI.
Inventor(s):	Plourde, Jr.; Robert (Chapel Hill, NC), Shaver; Sammy R. (Chapel Hill, NC), Boyer; Jose L. (Chapel Hill, NC), Abreo; Melwyn A. (Jamul, CA), Alfaro-Lopez; Lorenzo J. (San Marcos, CA), Feng; Yangbo (Palm Beach Gardens, FL), Harvey; Daniel F. (San Diego, CA), Khasonova; Tatyana V. (San Diego, CA), Tu; Chi (San Diego, CA)
Assignee:	Inspire Pharmaceuticals, Inc. (Durham, NC)
Application Number:	10/971,766
Patent Claims:	1. A method of treating diseases or conditions associated with increased platelet aggregation comprising: administering to a subject a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula III, or a pharmaceutically acceptable hydrate, solvate or salt thereof, wherein said amount is effective to inhibit platelet aggregation, ##STR00071## wherein R is H, or saturated or unsaturated C.sub.1-8 alkyl; R.sub.a and R.sub.c is H; R.sub.b is selected from the group consisting of: saturated or unsaturated C.sub.1-8 alkyl, saturated or unsaturated C.sub.3-7 cycloalkyl, aralkyl, and aryl; where all rings or chains optionally bear one or more desired substituents; R.sub.d and R.sub.d' are independently selected from the group consisting of: H, saturated or unsaturated C.sub.1-8 alkyl, saturated or unsaturated C.sub.3-7 cycloalkyl, aralkyl, aryl; R.sub.e is absent; R.sub.f and R.sub.g are independently selected from the group consisting of: H, halogen, saturated or unsaturated C.sub.1-8 alkyl, saturated or unsaturated C.sub.3-7 cycloalkyl, aryl, aralkyl; G is O; J is carbon: X.sub.1 is selected from the group consisting of: N and C-M; and M is selected from the group consisting of: --H, halogen, --CF.sub.3, saturated or unsaturated C.sub.1-8 alkyl, saturated or unsaturated C.sub.3-7 cycloalkyl, --OH, saturated or unsaturated C.sub.1-6 alkoxy, amino, --N-substituted amino, and N,N-disubstituted amino. 2. The method according to claim 1, wherein said compound is selected from the group consisting of: 2-{2-Phenyl-6-[6-(3-phenyl-ureido)-purin-9-yl]-tetrahydro-furo[3,4-d][1,3- ]dioxol-4-ylmethoxy}-nicotinic acid; 2-{2-Biphenyl-3-yl-6-[6-(3-phenyl-ureido)-purin-9-yl]-tetrahydro-furo[3,4- -d][1,3]dioxol-4-ylmethoxy}-nicotinic acid; 2-{2-Naphthalen-2-yl-6-[6-(3-phenyl-ureido)-purin-9-yl]-tetrahydro-furo[3- ,4-d][1,3]dioxol-4-ylmethoxy}-nicotinic acid; 2-{6-[6-(3-Hexyl-ureido)-purin-9-yl]-2-phenyl-tetrahydro-furo[3,4-d][1,3]- dioxol-4-ylmethoxy}-nicotinic acid; 2-{6-[6-(3-Ethyl-ureido)-purin-9-yl]-2-phenethyl-tetrahydro-furo[3,4-d][1- ,3]dioxol-4-ylmethoxy}-nicotinic acid; 2-{6-[6-(3-Ethyl-ureido)-purin-9-yl]-2-phenylethynyl-tetrahydro-furo[3,4-- d][1,3]dioxol-4-ylmethoxy}-nicotinic acid; 2-{6-[6-(3-Ethyl-ureido)-purin-9-yl]-2-phenyl-tetrahydro-furo[3,4-d][1,3]- dioxol -4-ylmethoxy}-nicotinic acid; 2-{2-(2-Bromo-phenyl)-6-[6-(3-ethyl-ureido)-purin-9-yl]-tetrahydro-furo[3- ,4-d][1,3]dioxol-4-ylmethoxy}-nicotinic acid; 2-{6-[6-(3-Cyclopentyl-ureido)-purin-9-yl]-2-phenethyl-tetrahydro-furo[3,- 4-d][1,3]dioxol-4-ylmethoxy}-nicotinic acid; 2-{6-[6-(3-Cyclopentyl-ureido)-purin-9-yl]-2-p-tolyl-tetrahydro-furo[3,4-- d][1,3]dioxol-4-ylmethoxy}-nicotinic acid; 2-{2-Biphenyl-4-yl-6-[6-(3-hexyl-ureido)-purin-9-yl]-tetrahydro-furo[3,4-- d][1,3]dioxol-4-ylmethoxy}-nicotinic acid; 2-{2-(4-Acetylamino-phenyl)-6-[6-(3-cyclopentyl-ureido)-purin-9-yl]-tetra- hydro-furo[3,4-d][1,3]dioxol-4-ylmethoxy}-nicotinic acid; and 2-{2-tert-Butyl-6-[6-(3-phenyl-ureido)-purin-9-yl]-tetrahydro-furo[3,4-d]- [1,3]dioxol-4-ylmethoxy}-nicotinic acid. 3. The method according to claim 1, wherein said pharmaceutical composition comprises a pharmaceutically-acceptable carrier. 4. The method according to claim 1, wherein said compound is used in combination with a therapeutic agent that is useful for treating platelet aggregation disorders or diseases. 5. The method according to claim 4, wherein said therapeutic agent is selected from the group consisting of: a GP IIb/IIIa antagonist, Abciximab, a thrombin inhibitor, hirudin, aspirin, heparin, low molecular weight heparin, warfarin, and an adenosine A.sub.2a receptor agonist. 6. The method according to claim 1, wherein said compound is administered orally, topically, or parenterally, in an amount effective to reduce platelet aggregation in a subject in need of such treatment. 7. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Formula III, as defined in claim 1, or a pharmaceutically acceptable hydrate, solvate or salt thereof. 8. The method according to claim 1, wherein said disease is stroke or angina. 9. The method according to claim 1, wherein said disease is myocardial infarction or peripheral arterial disease. 10. The method according to claim 1, wherein said condition is coronary angioplasty. 11. The method according to claim 1, wherein said condition is thrombus formation. 12. The method according to claim 1, wherein said compound is ##STR00072## 13. The pharmaceutical composition according to claim 7, wherein said compound is selected from the group consisting of: 2-{2-Phenyl-6-[6-(3-phenyl-ureido)-purin-9-yl]-tetrahydro-furo[3,4-d][1,3- ]dioxol-4-ylmethoxy}-nicotinic acid; 2-{2-Biphenyl-3-yl-6-[6-(3-phenyl-ureido)-purin-9-yl]-tetrahydro-furo[3,4- -d][1,3]dioxol-4-ylmethoxy}-nicotinic acid; 2-{2-Naphthalen-2-yl-6-[6-(3-phenyl-ureido)-purin-9-yl]-tetrahydro-furo[3- ,4-d][1,3]dioxol-4-ylmethoxy}-nicotinic acid; 2-{6-[6-(3-Hexyl-ureido)-purin-9-yl]-2-phenyl-tetrahydro-furo[3,4-d][1,3]- dioxol-4-ylmethoxy}-nicotinic acid; 2-{6-[6-(3-Ethyl-ureido)-purin-9-yl]-2-phenethyl-tetrahydro-furo[3,4-d][1- ,3]dioxol-4-ylmethoxy}-nicotinic acid; 2-{6-[6-(3-Ethyl-ureido)-purin-9-yl]-2-phenyl-tetrahydro-furo[3,4-d][1,3]- dioxol-4-ylmethoxy}-nicotinic acid; 2-{6-[6-(3-Ethyl-ureido)-purin-9-yl]-2-phenyl-tetrahydro-furo[3,4-d][1,3]- dioxol-4-ylmethoxy}-nicotinic acid; 2-{2-(2-Bromo-phenyl)-6-[6-(3-ethyl-ureido)-purin-9-yl]-tetrahydro-furo[3- ,4-d][1,3]dioxol-4-ylmethoxy}-nicotinic acid; 2-{6-[6-(3-Cyclopentyl-ureido)-purin-9-yl]-2-phenethyl-tetrahydro-furo[3,- 4-d][1,3]dioxol-4-ylmethoxy}-nicotinic acid; 2-{6-[6-(3-Cyclopentyl-ureido)-purin-9-yl]-2-p-tolyl-tetrahydro-furo[3,4-- d][1,3]dioxol-4-ylmethoxy}-nicotinic acid; 2-{2-Biphenyl-4-yl-6-[6-(3-hexyl-ureido)-purin-9-yl]-tetrahydro-furo[3,4-- d][1,3]dioxol-4-ylmethoxy}-nicotinic acid; 2-{2-(4-Acetylamino -phenyl)-6-[6-(3-cyclopentyl-ureido)-purin-9-yl]-tetrahydro-furo[3,4-d][1- ,3]dioxol-4-ylmethoxy}-nicotinic acid; and 2-{2-tert-Butyl-6-[6-(3-phenyl-ureido)-purin-9-yl]-tetrahydro-furo[3,4-d]- [1,3]dioxol-4-ylmethoxy}-nicotinic acid. 14. A method of inhibiting platelet aggregation in blood and blood products that contain platelets, comprising administering to the blood or blood products an effective amount of a compound of Formula III, or a pharmaceutically acceptable hydrate, solvate or salt thereof, wherein said amount is effective to inhibit platelet aggregation in the blood or blood products, ##STR00073## wherein R is H, or saturated or unsaturated C.sub.1-8 alkyl; R.sub.a and R.sub.c is H; R.sub.b is selected from the group consisting of: hydrogen, saturated or unsaturated C.sub.1-8 alkyl, saturated or unsaturated C.sub.3-7 cycloalkyl, aralkyl, and aryl; where all rings or chains optionally bear one or more desired substituents; R.sub.d and R.sub.d' are independently selected from the group consisting of: H, saturated or unsaturated C.sub.1-8 alkyl, saturated or unsaturated C.sub.3-7 cycloalkyl, aralkyl, aryl; R.sub.e is absent; R.sub.f and R.sub.g are independently selected from the group consisting of: H, halogen, saturated or unsaturated C.sub.1-8 alkyl, saturated or unsaturated C.sub.3-7 cycloalkyl, aryl, aralkyl; G is O; J is carbon: X.sub.1 is selected from the group consisting of: N and C-M: and M is selected from the group consisting of: --H, halogen, --CF.sub.3, saturated or unsaturated C.sub.1-8 alkyl, saturated or unsaturated C.sub.3-7 cycloalkyl, OH, saturated or unsaturated C.sub.1-6 alkoxy, amino, --N-substituted amino, and N,N-disubstituted amino.

Details for Patent 7,368,438

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Janssen Biotech, Inc.	REOPRO	abciximab	Injection	103575	12/22/1994		2023-10-21