Claims
- 1. A crystalline polymorph Form 1 of Compound 2 of the formula:
- 2. The crystalline polymorph of Compound 2 of claim 1 that exhibits a powder x-ray diffraction pattern having characteristic peak locations of 9.9, 11.2, 16.4, 19.2, 21.0, 22.1, 23.7 and 26.7 degrees 2θ.
- 3. The crystalline polymorph of Compound 2 of claim 1 that exhibits a powder x-ray diffraction pattern having characteristic peak locations of 9.9, 11.2, 12.6, 14.5, 16.4, 19.2, 21.0, 22.1, 23.7, 26.7, 28.2 and 30.8 degrees 2θ.
- 4. The crystalline polymorph of Compound 2 of claim 1 that exhibits a powder x-ray diffraction pattern substantially the same as the powder x-ray diffraction pattern shown in FIG. 1.
- 5. A crystalline polymorph Form 1 of Compound 2 of the formula:
- 6. A process for preparing Compound 2 from Compound 1 according to the reaction:
- 7. The process of claim 6, wherein the organic solvent is selected from the group consisting of alcohols, nitrites, esters, ketones, ethers and mixtures thereof.
- 8. The process of claim 7, wherein the organic solvent is acetonitrile.
- 9. The process of claim 6 wherein the sulfuric acid is in a mixture with acetonitrile.
- 10. The process of claim 6 wherein the temperature is about 50° C.
- 11. A pharmaceutical composition comprising the crystalline polymorph Form 1 of Compound 2 according to claim 1, and at least one excipient or carrier.
- 12. A method of inhibiting thrombin receptors comprising administering to a mammal in need of such treatment an effective amount of the crystalline polymorph Form 1 of Compound 2 of claim 1.
- 13. A method of treating thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, myocardial infarction, glomerulonephritis, thrombotic stroke, thromboembolic stroke, peripheral vascular diseases, inflammatory disorders, cerebral ischemia or cancer, comprising administering to a mammal in need of such treatment an effective amount of the crystalline polymorph Form 1 of Compound 2 of claim 1.
- 14. A method of treating thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, myocardial infarction, glomerulonephritis, thrombotic stroke, thromboembolytic stroke, peripheral vascular diseases, inflammatory disorders, cerebral ischemia or cancer, comprising administering to a mammal in need of such treatment an effective amount of the crystalline polymorph Form 1 of Compound 2 of claim 1 in combination with at least one additional cardiovascular agent.
- 15. The method of claim 14 wherein the at least one additional cardiovascular agent is selected from the group consisting of thromboxane A2 biosynthesis inhibitors, GP IIb/IIIa antagonists, thromboxane antagonists, adenosine diphosphate inhibitors, cyclooxygenase inhibitors, angiotensin antagonists, endothelin antagonists, angiotensin converting enzyme inhibitors, neutral endopeptidase inhibitors, anticoagulants, diuretics, and platelet aggregation inhibitors.
- 16. The method of claim 15 wherein the at least one additional cardiovascular agent is aspirin or clopidogrel bisulfate.
- 17. A purified form of the crystalline polymorph Form 1 of Compound 2 of claim 1.
- 18. A crystalline polymorph Form 1 of Compound 2 that is the product of the process of claim 6.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a Continuation-in-Part of: 1) a co-pending U.S. Continuation-in-Part application Ser. No. 10/705,282 filed Nov. 10, 2003; which is a Continuation-in-Part of U.S. application Ser. No. 10/671,216 filed Sep. 25, 2003, which claims the benefit of U.S. application Ser. No. 09/880,222 filed Jun. 13, 2001, which claims the benefit of U.S. Provisional Application No. 60/211,724 filed Jun. 15, 2000, and 2) U.S. application Ser. No. 10/412,982 filed Apr. 14, 2003, which claims the benefit of U.S. Provisional Application No. 60/373,072, filed Apr. 16, 2002, the complete text and claims of which are incorporated by reference herein as if fully set forth.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60211724 |
Jun 2000 |
US |
|
60373072 |
Apr 2002 |
US |
Continuation in Parts (4)
|
Number |
Date |
Country |
Parent |
10705282 |
Nov 2003 |
US |
Child |
10755066 |
Jan 2004 |
US |
Parent |
10671216 |
Sep 2003 |
US |
Child |
10705282 |
Nov 2003 |
US |
Parent |
09880222 |
Jun 2001 |
US |
Child |
10671216 |
Sep 2003 |
US |
Parent |
10412982 |
Apr 2003 |
US |
Child |
10755066 |
Jan 2004 |
US |