Biphenyl compounds useful as muscarinic receptor antagonists
This invention provides compounds of formula I: wherein a, b, c, d, m, n, p, s, t, Ar 1 , R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , and W are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.
1. A compound of formula I:
wherein:
a is 0 or 1; R 1 is halo;
b is 0 or 1; R 2 is halo;
m is 0 or 1;
R 4 is selected from hydrogen and (1-4C)alkyl;
s is 0, 1 or 2;
Ar 1 represents a phenylene group substituted with (R 5 ) q where q is 0 or an integer from 1 to 4 and each R 5 is selected independently from halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy;
t is 0, 1 or 2;
n is 1;
p is 0 or 1; and
R 7 and R 8 are independently hydrogen or (1-4C)alkyl;
wherein each alkyl and alkoxy group in R 5 , R 7 , and R 8 is optionally substituted with 1 to 5 fluoro substituents;
or a pharmaceutically acceptable salt or stereoisomer thereof.
2. The compound of claim 1 , wherein a and b each represent 0.
3. The compound of claim 1 , wherein m and s each represents 0, and t is 1.
4. The compound of claim 1 , wherein the —CONR 7 R 8 group is in the para position and p represents 0.
5. The compound of claim 1 , wherein Ar 1 represents phen-1,4-ylene, wherein the phenylene group is optionally substituted with one or two R 5 substituents.
6. The compound of claim 5 where q is 0.
7. The compound of claim 5 wherein q is 1 or 2 and R 5 is selected independently from hydroxy, halo, (1-4C)alkyl, and (1-4C)alkoxy, wherein each alkyl and alkoxy group is optionally substituted with from 1 to 3 fluoro substituents.
8. The compound of claim 1 wherein a, b, m, p, and s each represent 0; t is 1; Ar 1 represents phen-1,4-ylene optionally substituted with one or two R 5 substituents; and the —CONR 7 R 8 group is in the para position.
9. The compound of claim 1 , wherein R 4 is hydrogen or methyl.
10. The compound of claim 1 , wherein R 8 is hydrogen.
11. The compound of claim 10 , wherein R 7 is hydrogen.
12. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 .