1. A compound according to formula (I)
wherein:
R1 and R2 are, independently, selected from the group consisting of
pyridyl, benzyl, pyrimidyl, thiazolyl, isothiazolyl and C3-7cycloalkyl;
R3 is hydrogen or hydroxy;
R4 and R5 are, independently, selected from the group consisting of hydrogen and optionally substituted C1-4alkyl;
Rb is, independently, selected from the group consisting of halogen, hydroxy, cyano, nitro, dihalomethyl, trihalomethyl and NR4R5;
Rc is, independently, selected from the group consisting of C1-4alkyl, halogen, hydroxy, cyano, nitro, dihalomethyl, trihalomethyl and NR4R5;
X\u2014 is a physiologically acceptable anion,
Y1 is O or NR4;
Y2 and Y3 are, independently, selected from the group consisting of N and CH; or
s is an integer having a value of 1 to 3.
2. A compound according to claim 1 wherein the anion is 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. A compound according to claim 1 selected from the group consisting of:
(3-Endo)-3-2,2-Bis-(3-hydroxy-phenyl)-ethyl-8,8-dimethyl-8-azonia-bicyclo3.2.1octane bromide;
(3-Endo)-3-2,2-Bis-(3-chloro-phenyl)-ethyl-8,8-dimethyl-8-azonia-bicyclo3.2.1octane iodide;
(3-Endo)-3-2,2-Bis-(5-chloro-2-thienyl)-2-hydroxy-ethyl-8,8-dimethyl-8-azonia-bicyclo3.2.1octane bromide;
(3-Endo)-1,1-Bis-(3-fluoro-phenyl)-2-(8,8-dimethyl-8-azonia-bicyclo3.2.1oct-3-yl)-ethanol iodide;
(3-Endo)-3-2,2-Bis-(3-fluoro-phenyl)-ethyl-8,8-dimethyl-8-azonia-bicyclo3.2.1octane iodide;
(3-Endo)-3-2-(3-Chloro-phenyl)-2-phenyl-ethyl-8,8-dimethyl-8-azonia-bicyclo3.2.1octane iodide;
(3-Endo)-3-(2,2-Bis-(3-thienyl)ethyl)-8,8-dimethyl-8-azoniabicyclo3.2.1octane iodide;
(3-Endo)-3-2-Hydroxy-2,2-bis-(3-methyl-2-thienyl)-ethyl-8,8-dimethyl-8-azonia-bicyclo3.2.1octane bromide;
(3-Endo)-3-2-Hydroxy-2,2-bis-(4-methyl-3-thienyl)-ethyl-8,8-dimethyl-8-azonia-bicyclo3.2.1octane bromide;
(3-Endo)-3-2-Hydroxy-2,2-bis-(5-methyl-2-thienyl)-ethyl-8,8-dimethyl-8-azonia-bicyclo3.2.1octane bromide;
(3-Endo)-3-{2,2-Bis-5-(1,1-difluoro-methyl)-2-thienyl-2-hydroxy-ethyl}-8,8-dimethyl-8-azonia-bicyclo3.2.1octane bromide;
(3-Endo)-1,1-Bis-(3-thienyl)-2-(8,8-dimethyl-8-azoniabicyclo3.2.1oct-3-yl)ethanol iodide;
(3-Endo)-1,1-bis(3,4-difluorophenyl)-2-(8,8-dimethyl-8-azoniabicyclo3.2.1oct-3-yl)ethanol bromide;
(3-Endo)-1,1-bis(3,5-difluorophenyl)-2-(8,8-dimethyl-8-azoniabicyclo3.2.1oct-3-yl)ethanol bromide;
(3-Endo)-1,1-dicyclohexyl-2-(8,8-dimethyl-8-azoniabicyclo3.2.1oct-3-yl)ethanol bromide;
(3-Endo)-1,1-dicyclopentyl-2-(8,8-dimethyl-8-azoniabicyclo3.2.1oct-3-yl)ethanol bromide;
(3-Endo)-1,3-bis(2-fluorophenyl)-2-(8,8-dimethyl-8-azoniabicyclo3.2.1oct-3-yl)methyl-2-propanol bromide;
2-(3-(3-Endo))-8,8-dimethyl-8-azoniabicyclo3.2.1oct-3-yl-1,1-di-2-pyridinylethanol iodide;
(3-Endo)-1,1-Bis-(4-fluoro-phenyl)-2-(8,8-dimethyl-8-azonia-bicyclo3.2.1oct-3-yl)-ethanol iodide;
(3-Endo)-1,1-Bis-(4-chloro-phenyl)-2-(8,8-dimethyl-8-azonia-bicyclo3.2.1oct-3-yl)-ethanol iodide;
(3-Endo)-3-2,2-Bis-(4-fluoro-phenyl)-ethyl-8,8-dimethyl-8-azonia-bicyclo3.2.1octane iodide;
(3-Endo)-1,1-Bis-(3-chloro-phenyl)-2-(8,8-dimethyl-8-azonia-bicyclo3.2.1oct-3-yl)-ethanol iodide;
(3-Endo)-1-(2,3-Fluoro-phenyl)-2-(8,8-dimethyl-8-azonia-bicyclo3.2.1oct-3-yl)-1-phenyl-ethanol iodide; and
(3-Endo)-1-(2,3-Chloro-phenyl)-2-(8,8-dimethyl-8-azonia-bicyclo3.2.1oct-3-yl)-1-phenyl-ethanol iodide.
4. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier thereof.
5. (canceled)
6. A method of treating a muscarinic acetylcholine receptor mediated disease, wherein acetylcholine binds to said receptor, comprising administering a safe and effective amount of a compound according to claim 1.
7. A method according to claim 6 wherein the disease is selected from the group consisting of chronic obstructive lung disease, chronic bronchitis, asthma, chronic respiratory obstruction, pulmonary fibrosis, pulmonary emphysema and allergic rhinitis.
8. A method according to claim 7 wherein administration is via inhalation via the mouth or nose.
9. A method according to claim 8 wherein administration is via a medicament dispenser selected from a reservoir dry powder inhaler, a multi-dose dry powder inhaler or a metered dose inhaler.
10. A method according to claim 9 wherein the compound is administered to a human
11. A method according to claim 10 wherein the compound and has a duration of action of 12 hours
12. (canceled)
13. The compound according to claim 1 wherein R1 and R2 are independently selected from group A.
14. The compound according to claim 1 wherein R1 and R2 are independently selected from group B.
15. The compound according to claim 1 wherein R1 and R2 are independently selected from group C.
16. The compound according to claim 1 wherein R1 and R2 are independently selected from benzyl, pyrimidinyl, thiazolyl, isothiazolyl or C3-7 cycloaklyl.
17. The compound according to claim 13 wherein Rb is independently selected from halogen.
18. The compound according to claim 16 wherein s is 1 or 2.
19. The compound according to claim 1 wherein R1 and R2 are selected from 3-hydroxyphenyl, 3-chlorophenyl, 4-chlorophenyl, 3-fluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 4-fluorophenyl, 2-fluorophenyl, 2,3-difluorophenyl, or 2,3-dichlorophenyl.
20. The compound according to claim 14 wherein Rb is are selected from C1-4 alkyl, halogen, or dihalomethyl.
21. The compound according to claim 19 wherein s is 1 or 2.
22. The compound according to claim 1 wherein R1 and R2 are selected from 5-chloro-thiophen-2-yl, 3-thienyl, 3-methyl-thiophen-2-yl, 4-methyl-thiophen-3-yl, 5-methyl-thiophen-2-yl, or 1,1-difluoromethyl-thiophen-2-yl.
23. The compound according to claim 1 wherein R1 and R2 are selected from pyridine.
24. The compound according to claim 1 wherein R1 and R2 are selected from C3-C7 cycloalkyl.
25. The compound which is:
(3-Endo)-1,1-bis(5-fluoro-2-methylphenyl)-2-(8,8-dimethyl-8-azoniabicyclo3.2.1oct-3-yl)ethanol bromide;
(3-Endo)-3-2-Hydroxy-2,2-bis-(3-methoxy-phenyl)-ethyl-8,8-dimethyl-8-azonia-bicyclo3.2.1octane iodide;
(3-Endo)-3-2,2-bis(3,4-difluorophenyl)ethyl-8,8-dimethyl-8-azoniabicyclo3.2.1octane bromide;
(3-Endo)-3-2,2-bis(3,5-difluorophenyl)ethyl-8,8-dimethyl-8-azoniabicyclo3.2.1octane bromide;
(3-Endo)-1,1-bis5-fluoro-2-(methyloxy)phenyl-2-(8,8-dimethyl-8-azoniabicyclo3.2.1oct-3-yl)ethanol bromide;
(3-Endo)-1,1-bis(3-fluoro-2-methylphenyl)-2-(8,8-dimethyl-8-azoniabicyclo3.2.1oct-3-yl)ethanol bromide; or
(3-Endo)-3-2,2-bis(5-fluoro-2-methylphenyl)ethyl-8,8-dimethyl-8-azoniabicyclo3.2.1octane iodide.
26. A pharmaceutical composition comprising a compound according to claim 25 and a pharmaceutically acceptable carrier thereof.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A seed of a soybean variety designated 0487686 wherein a sample of seed was deposited under ATCC Accession No. PTA-6362.
2. A soybean plant, or a part thereof, of variety 0487686, wherein a sample of seed of said variety was deposited under ATCC Accession No. PTA-6362.
3. Pollen of the plant of claim 2.
4. An ovule of the plant of claim 2.
5. A tissue culture of regenerable cells or protoplasts produced from the plant of claim 2.
6. The tissue culture according to claim 5, wherein said cells or protoplasts of the tissue culture are produced from a tissue selected from the group consisting of leaves, pollen, embryos, cotyledons, hypocotyl, meristematic cells, roots, root tips, anthers, flowers, seeds, stems and pods.
7. A soybean plant regenerated from the tissue culture of claim 5, wherein the regenerated plant has all of the morphological and physiological characteristics of soybean cultivar 0487686 and wherein a sample of seed was deposited under ATCC Accession No. PTA-6362.
8. A method for producing a hybrid soybean seed comprising crossing a first parent soybean plant with a second parent soybean plant and harvesting the resultant hybrid soybean seed, wherein said first parent soybean plant or said second parent soybean plant is the soybean plant of claim 2.
9. A method of producing an herbicide resistant soybean plant wherein the method comprises transforming the soybean plant of claim 2 with a transgene that confers herbicide resistance.
10. An herbicide resistant soybean plant produced by the method of claim 9.
11. A method of producing an insect resistant soybean plant wherein the method comprises transforming the soybean plant of claim 2 with a transgene that confers insect resistance.
12. An insect resistant soybean plant produced by the method of claim 11.
13. A method of producing a disease resistant soybean plant wherein the method comprises transforming the soybean plant of claim 2 with a transgene that confers disease resistance.
14. A disease resistant soybean plant produced by the method of claim 13.
15. A method of producing a soybean plant with modified fatty acid or carbohydrate metabolism wherein the method comprises transforming the soybean plant of claim 2 with a transgene encoding a protein selected from the group consisting of fructosyltransferase, levansucrase, \u03b1-amylase, invertase and starch branching enzyme or encoding an antisense of stearyl-ACP desaturese.
16. A soybean plant having modified fatty acid or carbohydrate metabolism produced by the method of claim 15.