1,2,4 oxadiazole compounds and methods of use thereof

1. A compound of formula (II):

wherein

Ar 2 is bicyclic heteroaryl selected from the group consisting of azaindolyl, benzimidazolyl, benzo[d][1,3]dioxolyl, benzofuranyl, benzoxadiazolyl, benzo[d]imidazolyl, benzo[d]imidazole-2(3H)-thione, benzoisoxazole, benzoisothiazole, benzooxazole, benzooxazolone, benzo[d][1,2,3]thiadiazolyl, 1,3-benzothiazolyl, benzothiophenyl, benzo[d][1,2,3]triazolyl, 2,2-difluorobenzo[d][1,3]dioxolyl, furopyridine, imidazopyridinyl, indolyl, indazolyl, isobenzofuran, isoindolyl, oxazolopyridine, pyrazolopyrimidinyl, pyrrolopyridinyl, thienopyridinyl, and [1,2,4]triazolopyridinyl; and

Ar 3 is independently pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, or triazinyl, substituted independently with 0, 1, 2, 3, or 4 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkoxycarbonylamino, alkoxycarbonylaminoalkyl, alkyl, alkylamino, alkylcarbonyl, alkylsulfonyl, amido, amino, aminoalkyl, carboxy, dialkylamino, dialkylaminoalkyl, halo, haloalkyl, haloalkylcarbonyl, heteroaryl, heterocycle, hydroxy, hydroxyalkyl, cyano, nitro, oxo, sulfonamide and dialkylsulfonylformimidamide;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Ar 3 is pyrimidinyl or pyridazinyl.

3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Ar 3 is independently pyridazinyl, pyridinyl, or pyrimidinyl.

4. The compound of claim 1 , selected from the group consisting of

5-(imidazo[1,5-a]pyridin-6-yl)-3-(pyridin-3-yl)-1,2,4-oxadiazole;

5-(1H-indol-6-yl)-3-(pyridin-3-yl)-1,2,4-oxadiazole;

5-(2,7-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)-3-(pyridin-3-yl)-1,2,4-oxadiazole;

5-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-3-(pyridin-3-yl)-1,2,4-oxadiazole;

5-(2-methylbenzofuran-5-yl)-3-(pyridin-3-yl)-1,2,4-oxadiazole;

5-(benzo[d][1,2,3]thiadiazol-5-yl)-3-(pyridin-3-yl)-1,2,4-oxadiazole;

5-(1H-benzo[d]imidazol-5-yl)-3-(pyridin-3-yl)-1,2,4-oxadiazole;

5-(1H-benzo[d][1,2,3]triazol-5-yl)-3-(pyridin-3-yl)-1,2,4-oxadiazole;

5-(benzo[d]thiazol-5-yl)-3-(pyridin-3-yl)-1,2,4-oxadiazole;

3-(pyridin-3-yl)-5-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1,2,4-oxadiazole;

5-(1H-indol-5-yl)-3-(pyridin-3-yl)-1,2,4-oxadiazole;

5-(benzofuran-5-yl)-3-(pyridin-3-yl)-1,2,4-oxadiazole;

5-(1-methyl-1H-benzo[d]imidazol-5-yl)-3-(pyridin-3-yl)-1,2,4-oxadiazole;

5-(1H-indazol-5-yl)-3-(pyridin-3-yl)-1,2,4-oxadiazole;

5-([1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-(pyridin-3-yl)-1,2,4-oxadiazole;

5-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)benzo[d]oxazol-2(3H)-one;

5-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)-1H-benzo[d]imidazole-2(3H)-thione;

1,3-dimethyl-5-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)-1H-benzo[d]imidazol-2(3H)-one;

6-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)benzo[d]oxazol-2(3H)-one;

5-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)-1H-benzo[d]imidazol-2(3H)-one;

6-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)benzo[d]oxazol-2-amine;

6-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)benzo[d]oxazole; and

5-(benzo[d][1,3]dioxol-5-yl)-3-(pyridin-3-yl)-1,2,4-oxadiazole;

or a pharmaceutically acceptable salt thereof.

5. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , or a salt thereof, and a pharmaceutically acceptable carrier or excipient.

6. The composition of claim 5 , further comprising a nicotinic acetylcholine receptor ligand.

7. The composition of claim 6 , wherein the nicotinic acetylcholine receptor ligand is a nicotinic acetylcholine receptor subtype α4β2 ligand demonstrating a Ki value that as measured by [3H]-cytisine binding assay (Ki Cyt) of about 0.001 nanomolar to about 100 micromolar.

8. The composition of claim 6 , wherein the nicotinic acetylcholine receptor ligand is a nicotinic acetylcholine receptor subtype α4β2 agonist or partial agonist.