Biphenyl compounds useful as muscarinic receptor antagonists

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;

A is selected from:

where m is 0 or 1; s is 0, 1 or 2; t is 0, 1 or 2; R 4 is hydrogen or (1-4C)alkyl; and Ar 1 represents a (3-5C)heteroarylene group selected from pyrrole, imidazole, thiazole, oxazole, furan, thiophene, pyrazole, isoxazole, isothiazole, pyridine, pyrazine, pyridazine and pyrimidine;

n is 1 or 2;

R 7 is selected from hydrogen, —OH, -(1-4C)alkyleneOH, —NR 7a R 7b , —C(O)NR 7c R 7d , and —CH 2 C(O)NR 7c R 7d , where R 7a , R 7b , and R 7c are independently selected from hydrogen, (1-4C)alkyl, hydroxy, (1-4C)alkoxy, (1-4C)alkyleneOR 7e , (3-6C)cycloalkyl, phenyl optionally substituted with hydroxy, and (1-4C)alkyleneC(O)NR 7f R 7g ; and R 7d is selected from hydroxy, (1-4C)alkoxy, (1-4C)alkyleneOR 7h , (3-6C)cycloalkyl, phenyl optionally substituted with hydroxy, and (1-4C)alkyleneC(O)NR 7i R 7j ; where said (3-6C)cycloalkyl is unsubstituted or substituted with 1 or 2 (1-6C)alkyl or —NR 7k R 7l groups, and where each of R 7e , R 7f , R 7g , R 7h , R 7i , R 7j , R 7k , and R 7l is independently hydrogen or (1-4C)alkyl; or R 7c is taken together with R 7d to form a 3-7 membered ring, optionally substituted with hydroxyl;

wherein each alkyl and alkoxy group in R 7a-l 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 is 0.

4. The compound of claim 1 , wherein R 4 is hydrogen or methyl.

5. The compound of claim 1 , wherein A is:

where m is 0; s is 0 or 2; t is 1; R 4 is hydrogen or methyl; and Ar 1 represents 2,5-thienylene, 2,5-pyrrolylene, or 2,5-furylene.

6. The compound of claim 1 , wherein R 7 is hydrogen.

7. The compound of claim 1 , wherein R 7 is —OH.

8. The compound of claim 1 , wherein R 7 is —CH 2 OH or —(CH 2 ) 2 OH.

9. The compound of claim 1 , wherein R 7 is —C(O)NR 7c R 7d , where R 7c is hydrogen, and R 7d is selected from —(CH 2 ) 2 OH, —(CH 2 ) 2 OCH 3 , cyclopropyl, cyclopentyl, phenyl optionally substituted with hydroxy, and —(CH 2 )C(O)NH 2 .

10. The compound of claim 1 , wherein R 7 is —C(O)NR 7c R 7d , where R 7c is taken together with R 7d to form pyrrolidine, piperidine, 3-hydroxypiperidine, or 4-hydroxypiperidine.

11. The compound of claim 1 , having the formula:

12. The compound of claim 1 , selected from:

biphenyl-2-ylcarbamic acid 1-{2-[methyl-(5-pyrrolidin-1-ylmethylthiophene-2-carbonyl)amino]ethyl}piperidin-4-yl ester;

biphenyl-2-ylcarbamic acid 1-(2-{[5-(4-hydroxymethylpiperidin-1-ylmethyl) thiophene-2-carbonyl]methylamino}ethyl)piperidin-4-yl ester;

biphenyl-2-ylcarbamic acid 1-(2-{[5-(3-hydroxypyrrolidin-1-ylmethyl)thiophene-2-carbonyl]methylamino}ethyl)piperidin-4-yl ester;

biphenyl-2-ylcarbamic acid 1-(2-{[5-(4-hydroxymethylpiperidin-1-ylmethyl) thiophene-2-carbonyl]amino}ethyl)piperidin-4-yl ester;

biphenyl-2-ylcarbamic acid 1-(2-{[5-(3-hydroxypyrrolidin-1-ylmethyl)thiophene-2-carbonyl]amino}ethyl)piperidin-4-yl ester;

biphenyl-2-ylcarbamic acid 1-(2-{[5-(4-hydroxymethylpiperidin-1-ylmethyl)-1H-pyrrole-2-carbonyl]methylamino}ethyl)piperidin-4-yl ester;

biphenyl-2-ylcarbamic acid 1-{2-[methyl-(5-pyrrolidin-1-ylmethyl-1H-pyrrole-2-carbonyl)amino]ethyl}piperidin-4-yl ester;

biphenyl-2-ylcarbamic acid 1-(2-{[5-(4-hydroxymethylpiperidin-1-ylmethyl)furan-2-carbonyl]amino}ethyl)piperidin-4-yl ester; and

biphenyl-2-ylcarbamic acid 1-(2-{[5-(3-hydroxypyrrolidin-1-ylmethyl)furan-2-carbonyl]amino}ethyl)piperidin-4-yl ester;

or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of claim 1 .