Muscarinic acetylcholine receptor antagonists
Muscarinic Acetylcholine Receptor Antagonists and methods of using them are provided.
1. A compound of formula (I)
wherein:
R1 is
R2 and R3 are independently selected from the group consisting of:
where F, G, H, K, and L are independently selected from the group consisting of hydrogen, halogen, —C 1-4 alkyl, halosubstituted —C 1-4 alkyl, hydroxyl substituted alkyl, and —C 1-4 alkoxy;
l is an integer having a value of 1 or 2;
n is an integer having a value of 1 to 4;
M is O or CH 2 ;
V is O or CH 2 ;
X − is a pharmaceutically acceptable anion.
2. The compound according to claim 1 wherein X − is a pharmaceutically acceptable anion selected from the group consisting of chloride, bromide, iodide, hydroxide, sulfate, nitrate, phosphate, acetate, trifluoroacetate, fumarate, citrate, tartrate, oxalate, succinate, mandelate, methanesulfonate, and p-toluenesulfonate.
3. The compound according to claim 1 wherein M is O.
4. The compound according to claim 3 wherein n is 2.
5. The compound according to claim 4 wherein l is 2.
6. The compound according to claim 1 wherein V is CH 2 .
7. The compound according to claim 1 wherein V is O.
8. The compound according to claim 1 wherein M is CH 2 .
9. The compound according to claim 1 wherein l is 1.
10. The compound according to claim 1 wherein l is 2.
11. The compound according to claim 2 wherein one of R2 and R3 is:
12. The compound according to claim 2 wherein both R2 and R3 are independently selected from:
13. The compound according to claim 2 wherein one of R2 and R3 is:
14. The compound according to claim 2 wherein one of R2 and R3 is:
15. The compound according to claim 1 which is:
4-[hydroxy(diphenyl)methyl]-1-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-1-azoniabicyclo[2.2.2]octane bromide.
16. A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable carrier thereof.
17. A pharmaceutical composition comprising a compound according to claim 15 , and a pharmaceutically acceptable carrier thereof.
18. A pharmaceutical composition according to claim 1 in a form suitable for administration by oral or nasal inhalation.
19. A pharmaceutical composition according to claim 18 wherein the form is suitable for administration by inhalation via a medicament dispenser selected from a reservoir dry powder inhaler, a multi-dose dry powder inhaler, or a metered dose inhaler.
20. A pharmaceutical composition according to claim 19 which is a dry powder composition.