.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 7,271,171

« Back to Dashboard

Details for Patent: 7,271,171

Title:Adenosine A.sub.3 receptor modulators
Abstract: The compounds of the following formula: ##STR00001## wherein R, R.sup.2, R.sup.3 and A have the meanings given in the specification, are endowed with selective A.sub.3 adenosine receptor antagonist activity. These compounds can be used in a pharmaceutical composition to treat disorders caused by excessive activation of the A.sub.3 receptor, or can be used in a diagnostic application to determine the relative binding of other compounds to the A.sub.3 receptor. The compounds can be labeled, for example with fluorescent or radiolabels, and the labels used in vivo or in vitro to determine the presence of tumor cells which possess a high concentration of adenosine A.sub.3 receptors.
Inventor(s): Baraldi; Pier Giovanni (Ferrara, IT), Borea; Pier Andrea (Ferrara, IT)
Assignee: King Pharmaceuticals Research and Development, Inc. (Cary, NC)
Filing Date:Jun 27, 2005
Application Number:11/169,311
Claims:1. A method of inhibiting mast cell degranulation, comprising administering to a patient in need thereof an effective amount of a compound of the following formula: ##STR00024## wherein: A is imidazole, pyrazole, or triazole; R.sup.2 is hydrogen, alkyl, substituted alkyl, alkenyl, aralkyl, substituted aralkyl, heteroaryl, substituted heteroaryl or aryl; R.sup.3 is furan; R.sup.4 is hydrogen, alkyl, amino, substituted alkyl, alkyl substituted amino, alkyl di-substituted amino, alkenyl, aralkyl, substituted aralkyl, heteroaryl, substituted heteroaryl, heterocycle, aryl, substituted aryl, sulfonyl or substituted sulfonyl; or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 wherein R.sup.2 is selected from the group consisting of hydrogen, alkyl, alkenyl and aryl.

3. The method of claim 1 wherein A is a pyrazolo ring.

4. The method of claim 1 wherein A is a triazolo ring.

5. A method of treating cancer disease expressing adenosine A.sub.3 receptors, comprising administering to a patient in need of treatment thereof an effective amount of a compound of the following formula: ##STR00025## wherein: A is imidazole, pyrazole, or triazole; R.sup.2 is hydrogen, alkyl, substituted alkyl, alkenyl, aralkyl, substituted aralkyl, heteroaryl, substituted heteroaryl or aryl; R.sup.3 is furan; R.sup.4 is hydrogen, alkyl, amino, substituted alkyl, alkyl substituted amino, alkyl di-substituted amino, alkenyl, aralkyl, substituted aralkyl, heteroaryl, substituted heteroaryl, heterocycle, aryl, substituted aryl, sulfonyl or substituted sulfonyl; or a pharmaceutically acceptable salt thereof; and wherein the cancer disease is selected from the group consisting of leukemia and lymphoma.

6. The method of claim 5 wherein R.sup.2 is selected from the group consisting of hydrogen, alkyl, alkenyl and aryl.

7. The method of claim 5 wherein A is a pyrazolo ring.

8. The method of claim 5 wherein A is a triazolo ring.

9. A method of treating allergic disease, comprising administering to a patient in need of treatment thereof an effective amount of a compound selected from the group of compounds consisting of: 5-[[(3-Chlorophenyl)amino] carbonyl]amino-8-methyl-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]- pyrimidine, 5-[[(4-Methoxyphenyl)amino]carbonyl]amino-8-methyl-2-(2-furyl)-pyrazolo[4- ,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(3-Chlorophenyl)amino]carbonyl]amino-8-ethyl-2-(2-furyl)-pyrazolo[4,3- -e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(4-Methoxyphenyl)amino]carbonyl]amino-8-ethyl-2-(2-furyl)-pyrazolo[4,- 3-e]- 1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(3-Chlorophenyl)amino]carbonyl]amino-8-propyl-2-(2-furyl)-pyrazolo[4,- 3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(4-Methoxyphenyl)amino]carbonyl]amino-8-propyl-2-(2-furyl)-pyrazole[4- ,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(3-Chlorophenyl)amino]carbonyl]amino-3-butyl-2-(2-furyl)-pyrazolo[4,3- -e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(4-Methoxyphenyl)amino]carbonyl]amino-8-butyl-2-(2-furyl)-pyrazolo[4,- 3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(3-Chlorophenyl)amino]carbonyl]amino-8-isopentyl-2-(2-furyl)-pyrazolo- [4,3-e]-1,2,4triazolo[1,5-c]pyrimidine, 5-[[(4-Methoxyphenyl)amino]carbonyl]amino-8-isopentyl-2-(2-furyl)-pyrazol- o[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(3-Chlorophenyl)amino]]carbonyl]amino-8-(2-isopentenyl)-2-(2-furyl)py- razolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(4-Methoxyphenyl)amino]carbonyl]amino-8-(2-isopentenyl)-2-(2-furyl)-p- yrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(3-Chlorophenyl)amino]carbonyl]amino-8-(2-(phenyl)ethyl)-2-(2-furyl)-- pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(4-Methoxyphenyl)amino]carbonyl]amino-8-(2-(phenyl)ethyl)-2-(2-furyl)- -pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(3-Chlorophenyl)amino]carbonyl]amino-8-(3-(phenyl)propyl)-2-(2-furyl)- -pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(4-Methoxyphenyl)amino]carbonyl]amino-8-(3-(phenyl)propyl)-2-(2-furyl- )-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[(Benzyl)carbonyl]amino-8-isopentyl-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-t- riazolo[1,5-c]pyrimidine, 5-[(Benzyl)carbonyl]amino-8-(3-(phenyl)propyl)-2-(2-furyl)-pyrazolo[4,3-e- ]-1,2,4-triazolo[1,5-c]pyrimidine, N-[4-(diethylamino)phenyl]-N-[2-(2-furyl)-8-methyl-8H-pyrazolo [4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl]urea, N-[8-methyl-2-(2-furyl)-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin- -5-yl]-N-'[4-(dimethylamino)phenyl]urea hydrochloride, N-[8-methyl-2-(2-furyl)-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin- -5-yl[-N'-[4-(dimethylamino)phenyl]urea hydrochloride, N-(2-(2-furyl)-8-methyl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin- -5-yl)-N'-[4-(morpholin-4-ylsulfonyl)phenyl]urea, N-[2-(2-furyl)-8-methyl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin- -5-yl]-N'-{4-[(4-methylpiperazin-l-yl)sulfonyl]-phenyl}urea, N-[2-(2-furyl)-8-methyl-8H-pyrazolo[4,3-e][1,2,4triazolo[1,5-c]pyrimidin-- 5-yl]-N'-pyridin-4-yl urea, N-[2-(2-furyl)-8-methyl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin- -5-yl]-N'-pyridin-4-ylurea hydrochloride, 5-[[(4-methoxyphenyl)amino]carbonyl]amino-8-propyl-2-(2-furyl)-pyrazolo[4- ,3-e]1,2,4-triazolo[1,5-c]pyrimidine, and 5-[[(4-methoxyphenyl)amino]carbonyl]amino-8-ethyl-2-(2-furyl)-pyrazolo[4,- 3-e]1,2,4-triazolo[1,5-c]pyrimidine; and wherein the allergic disease is asthma.

10. A method of treating cancer disease expressing adenosine A.sub.3 receptors, comprising administering to a patient in need of treatment thereof an effective amount of a compound selected from the group of compounds consisting of: 5-[[(3-Chlorophenyl)amino]carbonyl]amino-8-methyl-2-(2-furyl)-pyrazolo[4,- 3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(4-Methoxyphenyl)amino]carbonyl]amino-8-methyl-2-(2-furyl)-pyrazolo[4- ,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(3-Chlorophenyl)amino]carbonyl]amino-8-ethyl-2-(2-furyl)-pyrazolo[4,3- -e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(4-Methoxyphenyl)amino]carbonyl]amino-8-ethyl-2-(2-furyl)-pyrazolo[[4- ,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(3-Chlorophenyl)amino]carbonyl]amino-8-propyl-2-(2-furyl)-pyrazolo[4,- 3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(4-Methoxyphenyl)amino]carbonyl]amino-8-propyl-2-(2-furyl)-pyrazolo[4- ,3-e]-1,2,4-triazolo[5-c]pyrimidine, 5-[[(3-Chlorophenyl)amino]carbonyl]amino-8-butyl-2-(2-fury9-pyrazolo[4,3-- e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(4-Methoxyphenyl)amino]carbonyl]amino-8-butyl-2-(2-furyl)-pyrazolo[4,- 3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(3-Chlorophenyl)amino]carbonyl]amino-8-isopentyl-2-(2-furyl)-pyrazolo- [4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(4-Methoxyphenyl)amino]carbonyl]amino-8-isopentyl-2-(2-furyl)-pyrazol- o[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(3-Chlorophenyl)amino]]carbonyl]amino-8-(2-isopentenyl)-2-(2-furyl)py- razolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(4-Methoxyphenyl)amino]carbonyl]amino-8-(2-isopentenyl)-2-(2-furyl)-p- yrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(3-Chlorophenyl)amino]carbonyl]amino-8-(2-(phenyl)ethyl)-2-(2-furyl)-- pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(4-Methoxyphenyl)amino]carbonyl]amino-8-(2-(phenyl)ethyl)-2-(2-furyl)- -pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(3-Chlorophenyl)amino]carbonyl]amino-8-(3-(phenyl)propyl)-2-(2-furyl)- -pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[[(4-Methoxyphenyl)amino]carbonyl]amino-8-(3-(phenyl)propyl)-2-(2-furyl- )-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine, 5-[(Benzyl)carbonyl]amino-8-isopentyl-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-t- riazolo[1,5-c]pyrimidine, 5-[(Benzyl)carbonyl]amino-8-(3-(phenyl)propyl)-2-(2-furyl)-pyrazolo[4,3-e- ]-1,2,4-triazolo[1,5-c]pyrimidine, N-4-[(diethylamino)phenyl-N'-[2-(2-furyl)-8-methyl-8H-pyrazolo[4,3-e][1,2- ,4]triazolo[1,5-c]pyrimidin-5-yl]urea, N-[8-methyl-2-(2-furyl)-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin- -5-yl]-N'-[4-(dimethylamino)phenyl]urea hydrochloride, N-[8-methyl-2-(2-furyl)-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin- -5-yl-N'-4-(dimethylamino)phenyl]urea hydrochloride, N-(2-(2-furyl)-8-methyl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin- -5-yl)-N'-[4-(morpholin-4-ylsulfonyl)phenyl]urea, N-[2-(2-furyl)-8-methyl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin- -5-yl]-N'-{4-[(4-methylpiperazin-l-yl)sulfonyl]-phenyl}urea, N-[2-(2-furyl)-8-methyl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin- -5-yl]-N'-pyridin-4-yl urea, N[-2-(2-furyl)-8-methyl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin- -5-yl]-N'-pyridin-4-ylurea hydrochloride, 5-[[(4-methoxyphenyl)amino]carbonyl]amino-8-propyl-2-(2-furyl)-pyrazolo[4- ,3-e]1,2,4-triazolo[1,5-c]pyrimidine, and 5-[[(4-methoxyphenyl)amino]carbonyl]amino-8-ethyl-2-(2-furyl)-pyrazolo[4,- 3-e]1,2,4-triazolo[1,5-c]pyrimidine; and wherein the cancer disease is selected from the group consisting of leukemia and lymphoma.

11. A method of inhibiting mast cell degranulation, comprising administering to a patient in need thereof an effective amount of a compound of the following formula: ##STR00026## wherein: A is imidazole, pyrazole, or triazole; R.sup.2 is hydrogen, alkyl, substituted alkyl, alkenyl, aralkyl, substituted aralkyl, heteroaryl, substituted heteroaryl or aryl; R.sup.3 is furan; R.sup.6 is heteroaryl or substituted heteroaryl; or a pharmaceutically acceptable salt thereof.

12. The method of claim 11 wherein R.sup.2 is selected from the group consisting of hydrogen, alkyl, alkenyl and aryl.

13. The method of claim 11 wherein A is a pyrazolo ring.

14. The method of claim 11 wherein A is a triazolo ring.

15. A method of treating cancer disease expressing adenosine A.sub.3 receptors, comprising administering to a patient in need of treatment thereof an effective amount of a compound of the following formula: ##STR00027## wherein: A is imidazole, pyrazole, or triazole; R.sup.2 is hydrogen, alkyl, substituted alkyl, alkenyl, aralkyl, substituted aralkyl, heteroaryl, substituted heteroaryl or aryl; R.sup.3 is furan; R.sup.6 is heteroaryl or substituted heteroaryl; or a pharmaceutically acceptable salt thereof; and wherein the cancer disease is selected from the group consisting of leukemia and lymphoma.

16. The method of claim 15 wherein R.sup.2 is selected from the group consisting of hydrogen, alkyl, alkenyl and aryl.

17. The method of claim 15 wherein A is a pyrazolo ring.

18. The method of claim 15 wherein A is a triazolo ring.

19. The method of claim 5 wherein A is a pyrazolo ring, R.sup.2 is methyl, and R.sup.4 is dimethylamino or diethylamino.

20. The method of claim 15, wherein the compound is N-[2-(2-furyl)-8-methyl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin- -5-yl]N'-pyridin-4-yl urea; or a pharmaceutically acceptable salt thereof.

21. The method of claim 20, wherein the pharmaceutically acceptable salt is the hydrochloride salt.

22. A method of treating hypertension, cardiac hypoxia and cerebral ischemia, comprising administering to a patient in need of treatment thereof an effective amount of a compound of the following formula: ##STR00028## wherein: A is imidazole, pyrazole, or triazole; R.sup.2 is hydrogen alkyl substituted alkyl, alkenyl, aralkyl, substituted aralkyl, heteroaryl, substituted heteroaryl or aryl; R.sup.3 is furan; R.sup.6 is heteroaryl or substituted heteroaryl; or a pharmaceutically acceptable salt thereof.

23. The method of claim 22 wherein R.sup.2 is selected from the group consisting of hydrogen, alkyl, alkenyl and aryl.

24. The method of claim 22 wherein A is a pyrazolo ring.

25. The method of claim 22 wherein A is a triazolo ring.

26. A method of treating hypertension, cardiac hypoxia and cerebral ischemia, comprising administering to a patient in need of treatment thereof an effective amount of a compound of the following formula: ##STR00029## wherein: A is imidazole, pyrazole, or triazole; R.sup.2 is hydrogen, alkyl, substituted alkyl, alkenyl, aralkyl, substituted aralkyl, heteroaryl, substituted heteroaryl or aryl; R.sup.3 is furan; R.sup.4 is hydrogen, alkyl, amino, substituted alkyl, alkyl substituted amino, alkyl di-substituted amino, alkenyl, aralkyl, substituted aralkyl, heteroaryl, substituted heteroaryl, heterocycle, aryl, substituted aryl, sulfonyl or substituted sulfonyl; or a pharmaceutically acceptable salt thereof.

27. The method of claim 26 wherein R.sup.2 is selected from the group consisting of hydrogen, alkyl, alkenyl and aryl.

28. The method of claim 26 wherein A is a pyrazolo ring.

29. The method of claim 26 wherein A is a triazolo ring.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc