3-Quinuclidinyl amino-substituted biaryl derivatives

1. A compound of the formula (I):

or a pharmaceutically acceptable salt, thereof, wherein:

A is N or N + —O −

n is 0, 1, or 2;

Y is selected from the group consisting of O, S, and —N(R 1 )—;

Ar 1 is a group of the formula:

Ar 2 is a group of the formula:

X 1 , X 2 , x 3 , and X 4 are each independently selected from the group consisting of N and —C(R 2 );

one of X 5 , X 6 , X 7 , X 8 and X 9 is —C and the others are each independently selected from the group consisting of N and —C(R 5 ), and group (b) is attached to Ar 1 through one of X 5 , X 6 , X 7 , X 8 and X 9 that is represented by C;

one of H 10 , X 11 , X 12 , and X 13 is C and the others are each independently selected from the group consisting of N, —N(R 1 ), O, S and —C(R 5 ) and group (c) is attached to Ar 1 through one of X 10 , X 11 , X 12 , and X 13 that is represented by C;

R 1 is hydrogen or alkyl;

R 2 at each occurrence is independently selected from the group consisting of hydrogen, halogen, alkyl, —OR 3 , and —NHR 4 ;

R 2a is halogen or alkyl;

R 3 and R 4 are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, and arylcarbonyl;

R 5 is selected from the group consisting of hydrogen, halogen, nitro, alkyl, aryl, alkylcarbonyl, arylcarbonyl, —OR 6 and —NR 8 R 9 ;

R 6 is independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, and arylcarbonyl; and

R 8 and R 9 are each independently selected from the group consisting of hydrogen, alkyl, aryl, arylalkyl, cycloalkylalkyl, alkylcarbonyl, —N═C(alkyl)(alkoxycarbonyl), alkoxycarbonyl, arylcarbonyl, aryloxycarbonyl, and alkylsulfonyl.

2. The compound of claim 1 , wherein Ar 1 is selected from the group consisting of:

wherein R 2 t is as defined in claim 1 .

3. The compound of claim 1 , wherein Ar 2 is selected from the group consisting of:

wherein:

R 2a is halogen or alkyl;

R 5 is selected from the group consisting of hydrogen, halogens nitro, alkyl, aryl, alkylcarbonyl, arylcarbonyl, —OR 6 and —NR 8 R 9 ;

R 6 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, and arylcarbonyl;

R 8 and R 9 are each independently selected from the group consisting of hydrogen, alkyl, benzyl, methanesulfonyl, phenyl, 4-methylphenyl, benzyloxycarbonyl, acetyl, cyclohexylmethyl, tert-butyloxycarbonyl and —N═C(methyl)(ethoxycarbonyl).

4. The compound of claim 3 , wherein R 8 is hydrogen or alkyl; and R 9 is selected from the group consisting of hydrogen, alkyl, benzyl, methanesulfonyl, phenyl, 4-methylphenyl, benzyloxycarbonyl, acetyl, cyclohexylmethyl, tert-butyloxycarbonyl and —N═C(methyl)(ethoxycarbonyl).

5. The compound of claim 1 , or a pharmaceutically acceptable salt, thereof, selected from the group consisting of:

4′-(1-azabicyclo[2.2.2]oct-3-yloxy)-1,1′-biphenyl-3-amine;

4′-[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy]-1,1′-biphenyl-3-amine;

4′-(1-azabicyclo[2.2.2]oct-3-yloxy)-4-methyl-1,1′-biphenyl-3-amine;

4′-[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy]-4-methyl-1,1′-biphenyl-3-amine;

4′-(1-azabicyclo[2.2.2]oct-3-yloxy)-1,1′-biphenyl-4-amine;

4′-[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy]-1,1′-biphenyl-4-amine;

4′-[(3S)-1-azabicyclo[2.2.2]oct-3-yloxy]-1,1′-biphenyl-4-amine;

N-[4′-(1-azabicyclo[2.2.2]oct-3-yloxy)-1,1′-biphenyl-4-yl]-N-methylamine;

N-{4′-[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy]-1,1′-biphenyl-4-yl}-N,N-dimethylamine;

N-[4′-(1-azabicyclo[2.2.2]oct-3-yloxy)-1,1′-biphenyl-4-yl]methanesulfonamide;

N-[4′-(1-azabicyclo[2.2.2]oct-3-yloxy)-1,1′-biphenyl-4-yl]-N-phenylamine;

3-[6-(1-azabicyclo[2.2.2]oct-3-yloxy)pyridin-3-yl]aniline;

4-[5-(1-azabicyclo[2.2.2]oct-3-yloxy)pyrazin-2-yl]aniline;

4-{5-[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy]pyrazin-2-yl}aniline;

4-{5-[(3S)-1-azabicyclo[2.2.2]oct-3-yloxy]pyrazin-2-yl}aniline;

N-{4-[5-(1-azabicyclo[2.2.2]oct-3-yloxy)pyrazin-2-yl]phenyl}-N,N-dimethylamine;

N-{4-[5-(1-azabicyclo[2.2.2]oct-3-yloxy)pyrazin-2-yl]phenyl}acetamide;

4-[2-(1-azabicyclo[2.2.2]oct-3-yloxy)pyrimidin-5-yl]aniline;

4-{2-[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy]pyrimidin-5-yl}aniline;

3-[2-(1-azabicyclo[2.2.2]oct-3-yloxy)pyrimidin-5-yl]aniline;

3-{2-[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy]pyrimidin-5-yl}aniline;

3-{2-[(3S)-1-azabicyclo[2.2.2]oct-3-yloxy]pyrimidin-5-yl}aniline;

5-[2-(1-azabicyclo[2.2.2]oct-3-yloxy)pyrimidin-5-yl]-2-methylaniline;

N-1-azabicyclo[2.2.2]oct-3-yl-1,1′-biphenyl-4,4′-diamine;

4′-(1-oxy-1-aza-bicyclo[2.2.2]oct-3-yloxy)-biphenyl-3-ylamine;

[4′-(1-aza-bicyclo[2.2.2]oct-3-yloxy)-biphenyl-4-yl]-p-tolyl-amine;

[4′-(1-aza-bicyclo[2.2.2]oct-3-yloxy)-biphenyl-4-yl]-cyclohexylmethyl-amine;

2-[4-(1-aza-bicyclo[2.2.2]oct-3-yloxy)-phenyl]-8-iodo-6H,12H-5,11-methano-dibenzo[b,f][1,5]diazocine;

4-{6-[(3R)-1-aza-bicyclo[2.2.2]oct-3-yloxy]-pyridazin-3-yl}-phenylamine;

4-{6-[(3R)-1-aza-bicyclo[2.2.2]oct-3-yloxy]-pyridazin-3-yl}-2-bromo-phenylamine;

4-{6-[(3R)-1-aza-bicyclo[2.2.2]oct-3-yloxy]-pyridazin-3-yl}-2,6-dibromo-phenylamine;

2-({4-{6-[(3R)-1-aza-bicyclo[2.2.2]oct-3-yloxy]-pyridazin-3-yl}-phenyl}-hydrazono)-propionic acid ethyl ester;

(R)-N-{4-[6-(1-aza-bicyclo[2.2.2]oct-3-yloxy)-pyridazin-3-yl]-phenyl}-acetamide;

4-{6-[(3R)-1-aza-bicyclo[2.2.2]oct-3-yloxy]-pyridazin-3-yl}-2-nitro-phenylamine;

4-{6-[(3R)-1-aza-bicyclo[2.2.2]oct-3-yloxy]-pyridazin-3-yl}-benzene-1,2-diamine;

4-{2-[(3R)-1-aza-bicyclo[2.2.2]oct-3-yloxy]-pyrimidin-5-yl}-2-nitro-phenylamine; and

2-amino-4-{2-[(3R)-1-aza-bicyclo[2.2.2]oct-3-yloxy]-pyrimidin-5-yl}-phenol.

6. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically acceptable carrier.