Biphenyl derivatives
This invention provides biphenyl derivatives of formula I: wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , W, a, b and c are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The biphenyl derivatives of this invention possess both β 2 adrenergic receptor agonist and muscarinic receptor antagonist activity and therefore, such biphenyl derivatives are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.
1. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of the formula:
wherein
o is an integer from 2 to 7;
p is an integer from 1 to 6; provided that o+p is an integer from 3 to 8;
the phen-1,4-ylene group is optionally substituted with from 1 to 4 substituents independently selected from halo, (1-4C)alkyl, (1-4C)alkoxy, —S-(1-4C)alkyl, —S(O)-(1-4C)alkyl, —S(O) 2 -(1-4C)alkyl, —C(O)O(1-4C)alkyl, carboxy, cyano, hydroxy, nitro, trifluoromethyl and trifluoromethoxy;
or a pharmaceutically acceptable salt or stereoisomer thereof.
2. The pharmaceutical composition of claim 1 , wherein o is 2 or 3.
3. The pharmaceutical composition of claim 1 , wherein o is 2.
4. The pharmaceutical composition of claim 1 , wherein p is 1 or 2.
5. The pharmaceutical composition of claim 1 , wherein p is 1.
6. The pharmaceutical composition of claim 1 , wherein o is 2 and p is 1.
7. The pharmaceutical composition of claim 1 , wherein the phen-1,4-ylene group has one substituent.
8. The pharmaceutical composition of claim 1 , wherein the phen-1,4-ylene group has two substituents.
9. The pharmaceutical composition of claim 1 , wherein the phen-1,4-ylene group is substituted with from 1 to 4 substituents and at least one of the substituents is halo.
10. The pharmaceutical composition of claim 1 , wherein the phen-1,4-ylene group is substituted with from 1 to 4 substituents and at least one of the substituents is chloro.
11. The pharmaceutical composition of claim 1 , wherein the phen-1,4-ylene group is substituted with from 1 to 4 substituents and at least one of the substituents is (1-4C)alkoxy.
12. The pharmaceutical composition of claim 1 , wherein the phen-1,4-ylene group is substituted with from 1 to 4 substituents and at least one of the substituents is methoxy.
13. The pharmaceutical composition of claim 1 , wherein the phen-1,4-ylene group is substituted with from 1 to 4 substituents and at least one of the substituents is (1-4C)alkyl.
14. The pharmaceutical composition of claim 1 , wherein the phen-1,4-ylene group is substituted with from 1 to 4 substituents and at least one of the substituents is methyl.
15. The pharmaceutical composition of claim 1 , wherein the compound has the (R) configuration at the carbon atom of the group —CH(OH)—.
16. The pharmaceutical composition of claim 1 , wherein the compound is in the form of a pharmaceutically acceptable salt.
17. The pharmaceutical composition of claim 1 , wherein the compound is in the form of a free base.
18. The pharmaceutical composition of claim 1 , wherein the composition is an aerosol or a powder.
19. The pharmaceutical composition of claim 1 , wherein the composition is micronized.
20. A method of treating a patient having chronic obstructive pulmonary disease or asthma, the method comprising administering to the patient a therapeutically effective amount of a composition of any one of claims 1 to 19 .
21. A method of producing bronchodilation in a patient, the method comprising administering to the patient a therapeutically effective amount of a composition of any one of claims 1 to 19 .