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Claims for Patent: 8,183,257

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Claims for Patent: 8,183,257

Title:Muscarinic acetylcholine receptor antagonists
Abstract: Muscarinic Acetylcholine Receptor Antagonists and methods of using them are provided.
Inventor(s): Laine; Dramane I. (King of Prussia, PA), Palovich; Michael R. (King of Prussia, PA), McCleland; Brent W. (King of Prussia, PA), Neipp; Christopher E. (King of Prussia, PA), Thomas; Sonia M. (King of Prussia, PA)
Assignee: Glaxo Group Limited (Greenford, Middlesex, GB)
Application Number:12/353,436
Patent Claims: 1. A method of inhibiting the binding of acetylcholine to an acetylcholine receptor in the respiratory tract of a human in need thereof, which comprises contacting the acetylcholine receptor with an effective amount of a compound ##STR00047## wherein X.sup.- is a pharmaceutically acceptable anion, and wherein the method of contacting the receptor is via inhalation by the mouth or nose of said human.

2. The method according to claim 1 wherein the pharmaceutically acceptable anion is chloride, bromide, iodide, hydroxide, sulfate, nitrate, phosphate, acetate, trifluoroacetate, fumarate, citrate, tartrate, oxalate, succinate, mandelate, methanesulfonate or p-toluenesulfonate.

3. The method according to claim 2 wherein the pharmaceutically acceptable anion is bromide.

4. The method according to claim 2 wherein the pharmaceutically acceptable anion is iodide.

5. The method according to claim 1 wherein the method of contacting the receptor is via the mouth.

6. The method according to claim 1 wherein the method of contacting the receptor is via the nose.

7. The method according to claim 1 wherein the method of contacting is by administration of the compound from a medicament dispenser selected from a reservoir dry powder inhaler, a multi-dose dry powder inhaler or a metered dose inhaler.

8. The method according to claim 1 wherein the compound is 4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicycl- o[2.2.2]octane bromide.

9. The method according to claim 7 wherein the compound is 4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicycl- o[2.2.2]octane bromide.

10. A method of inhibiting the binding of acetylcholine to a M.sub.3 muscarinic acetylcholine receptor in the respiratory tract of a mammal in need thereof, which comprises contacting the M.sub.3 muscarinic acetylcholine receptor with an effective amount of a compound which is 4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicycl- o[2.2.2]octane bromide, and wherein the method of contacting the receptor with the compound is via inhalation by the mouth or nose of the mammal.

11. The method according to claim 10 wherein the binding of the M3 muscarinic acetylcholine receptor is useful in the treatment of chronic obstructive lung disease, chronic bronchitis, asthma, chronic respiratory obstruction, pulmonary fibrosis, pulmonary emphysema or allergic rhinitis.

12. The method according to claim 10 wherein the method of contacting the receptor is via the mouth.

13. The method according to claim 10 wherein the method of contacting the receptor is via the nose.

14. The method according to claim 10 wherein the method of contacting is by administration of the compound from a medicament dispenser selected from a reservoir dry powder inhaler, a multi-dose dry powder inhaler or a metered dose inhaler.

15. A method of treating chronic obstructive lung disease, chronic bronchitis, asthma, chronic respiratory obstruction, pulmonary fibrosis, pulmonary emphysema or allergic rhinitis in a human in need thereof, comprising administering to said human by inhalation via the mouth or nose, an effective amount of a compound ##STR00048## wherein X.sup.- is a pharmaceutically acceptable anion.

16. The method according to claim 15 wherein the pharmaceutically acceptable anion is chloride, bromide, iodide, hydroxide, sulfate, nitrate, phosphate, acetate, trifluoroacetate, fumarate, citrate, tartrate, oxalate, succinate, mandelate, methanesulfonate or p-toluenesulfonate.

17. The method according to claim 16 wherein the pharmaceutically acceptable anion is bromide.

18. The method according to claim 16 wherein the pharmaceutically acceptable anion is iodide.

19. The method according to claim 16 wherein the treatment is of chronic obstructive lung disease.

20. The method according to claim 16 wherein the treatment is of chronic respiratory obstruction.

21. The method according to claim 16 wherein the treatment is of pulmonary emphysema.

22. A method of inhibiting the binding of acetylcholine to an acetylcholine receptor in a human in need thereof, which comprises contacting the acetylcholine receptor with an effective amount of a compound ##STR00049## wherein X.sup.-is a pharmaceutically acceptable anion, and wherein the method of contacting the receptor is by topical application to said human.

23. The method according to claim 22 wherein the pharmaceutically acceptable anion is chloride, bromide, iodide, hydroxide, sulfate, nitrate, phosphate, acetate, trifluoroacetate, fumarate, citrate, tartrate, oxalate, succinate, mandelate, methanesulfonate or p-toluenesulfonate.

24. The method according to claim 23 wherein the pharmaceutically acceptable anion is bromide.

25. The method according to claim 23 wherein the pharmaceutically acceptable anion is iodide.

26. The method according to claim 22 wherein the compound is 4-[hydroxy(diphenyl)methyl]-1- {2-[(phenylmethyl)oxy]ethyl}-1-azonia-bicyclo[2.2.2]octane bromide.

27. A method of inhibiting the binding of acetylcholine to a M.sub.3 muscarinic acetylcholine receptor in a human in need thereof, which comprises contacting the M.sub.3 muscarinic acetylcholine receptor topically, with an effective amount of a compound which is ##STR00050## wherein X.sup.-is a pharmaceutically acceptable anion.

28. The method according to claim 27 wherein the pharmaceutically acceptable anion is chloride, bromide, iodide, hydroxide, sulfate, nitrate, phosphate, acetate, trifluoroacetate, fumarate, citrate, tartrate, oxalate, succinate, mandelate, methanesulfonate or p-toluenesulfonate.

29. The method according to claim 28 wherein the pharmaceutically acceptable anion is bromide.

30. The method according to claim 27 wherein the pharmaceutically acceptable anion is iodide.

31. The method according to claim 27 wherein the compound is 4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azonia-bicyc- lo[2.2.2]octane bromide.
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