Amide derivatives as positive allosteric modulators and methods of use thereof

1. A method of treating a disorder or condition selected from the group consisting of acute pain, post-surgical pain, inflammatory pain, and neuropathic pain, comprising administering a therapeutically effective amount of a compound of formula (I):

wherein,

A is —C(O)NH—;

R a , R b , and are independently hydrogen, alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, alkylthio, cyano, haloalkoxy, haloalkyl, or halogen;

R x at each occurrence is independently acyloxy, alkoxy, alkyl, haloalkyl, halogen, or hydroxy;

n is 0, 1, 2, 3, or 4;

R 1 is hydrogen or halogen;

R 2 and R 3 are independently hydrogen, alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, alkylthio, cyano, haloalkoxy, haloalkyl, halogen or NR 5 R 6 , provided that at least one of R 2 or R 3 is NR 5 R 6 ;

R 5 and R 6 are independently hydrogen, alkenyl, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, arylalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, heteroarylalkyl, heterocycle, or heterocyclealkyl;

or a pharmaceutically acceptable salt, ester, or amide thereof.

2. The method of claim 1 , further comprising administering in combination with atypical antipsychotics, cholinesterase inhibitors, histamine M3 antagonists, 5HT2 c antagonists, 5HT-6 antagonists, dopamine D1 agonists, muscarinic receptor antagonists, potassium channel blockers, α7 NNR ligands, or α4β2 NNR ligands.

3. The method of claim 1 , wherein R 1 is hydrogen or fluorine.

4. The method of claim 1 , wherein R 5 and R 6 are independently selected from hydrogen, alkyl, alkoxycarbonyl, alkylcarbonyl, alkylsulfonyl, arylalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, and heteroarylalkyl.

5. The method of claim 1 , wherein the compound is selected from the group consisting of:

N-[4-(acetylamino)benzyl]-4-[(trifluoromethyl)thio]benzamide;

N-[4-(diethylamino)benzyl]-4-[(trifluoromethyl)thio]benzamide;

N-{3-[(methylsulfonyl)amino]benzyl}-4-[(trifluoromethyl)thio]benzamide;

N-[3-(methylamino)benzyl]-4-[(trifluoromethyl)thio]benzamide;

N-{4-[(methylsulfonyl)amino]benzyl}-4-[(trifluoromethyl)thio]benzamide;

N-[3-(dimethylamino)benzyl]-4-[(trifluoromethyl)thio]benzamide;

N-{3-[acetyl(methyl)amino]benzyl}-4-[(trifluoromethyl)thio]benzamide;

N-[4-(dimethylamino)benzyl]-4-[(trifluoromethyl)thio]benzamide;

N-(4-aminobenzyl)-4-[(trifluoromethyl)thio]benzamide;

N-[4-(methylamino)benzyl]-4-[(trifluoromethyl)thio]benzamide;

4-[(difluoromethyhthio]-N-[4-(dimethylamino)benzyl]benzamide; and

4-[(difluoromethyhthio]-N-[4-(methylamino)benzyl]benzamide;

or a pharmaceutically acceptable salt thereof.