Benzoxazole carboxamides for treating CINV and IBS-D

1. A compound of formula

wherein

R 1 , R 2 and R 3 are independently selected from hydrogen, halogen, amino, alkylamino, dialkylamino, acylamino, morpholinyl, —O-loweralkyl, hydroxy, loweralkyl, fluoroloweralkyl, —O-lowerfluoroalkyl, methylenedioxy, ethylenedioxy, alkoxy-loweralkyl and hydroxyloweralkyl;

R 4 is a saturated nitrogen heterocycle or methyl-substituted saturated nitrogen heterocycle, in which said nitrogen is tertiary, said heterocycle containing at least one 5 or 6-membered ring; and

Ar is chosen from the group consisting of

(i) aryl;

(ii) heteroaryl;

(iii) substituted aryl;

(iv) substituted heteroaryl; and

(v) dihydroheteroaryl.

2. A compound according to claim 1 of formula

wherein

R 1 , R 2 and R 3 are independently selected from hydrogen, halogen, amino, alkylamino, dialkylamino, acylamino, morpholinyl, —O-loweralkyl, hydroxy, loweralkyl, fluoroloweralkyl, —O-lowerfluoroalkyl, methylenedioxy, ethylenedioxy, alkoxy-loweralkyl and hydroxyloweralkyl;

represents a saturated nitrogen heterocycle or methyl-substituted saturated nitrogen heterocycle, in which said nitrogen is tertiary, said heterocycle containing at least one 5 or 6-membered ring; and

Ar is chosen from the group consisting of:

(i) aryl;

(ii) heteroaryl other than 2-pyridinyl and 3-pyridinyl, provided that when

is methyl azabicyclo[3.3.1]nonane, Ar may additionally be 3-pyridinyl;

(iii) aryl substituted with from one to four substitutents chosen from lower alkoxy, phenoxy, trialkylsilylacetylenyl, anilino, lower alkynyl, lower alkyl, halogen, nitro, cyano, hydroxy, amino, methylenedioxy, alkylamino, dialkylamino, phenyl, heterocyclyl, methylheterocyclyl, methylenedioxy and acylamino;

(iv) heteroaryl substituted with one or two substitutents chosen from oxo, halogen, and alkyl; and

(v) dihydroheteroaryl;

with the proviso that, when Ar is phenyl and

is 1-azabicyclo[2.2.2]oct-3-yl, R 2 cannot be chloro.

3. A compound of formula

wherein

R 1 , R 2 and R 3 are independently selected from hydrogen, halogen, amino, alkylamino, dialkylamino, acylamino, morpholinyl, —O-loweralkyl, hydroxy, loweralkyl, fluoroloweralkyl, —O-lowerfluoroalkyl, methylenedioxy, ethylenedioxy, alkoxy-loweralkyl and hydroxyloweralkyl;

R 4 is a saturated nitrogen heterocycle or methyl-substituted saturated nitrogen heterocycle, in which said nitrogen is tertiary, said heterocycle containing at least one 5 or 6-membered ring; and

Ar is chosen from the group consisting of

(i) aryl;

(ii) heteroaryl;

(iii) substituted aryl;

(iv) substituted heteroaryl; and

(v) dihydroheteroaryl.

4. A compound according to claim 3 of formula

wherein

R 1 , R 2 and R 3 are independently selected from hydrogen, halogen, amino, alkylamino, dialkylamino, acylamino, morpholinyl, —O-loweralkyl, hydroxy, loweralkyl, fluoroloweralkyl, —O-lowerfluoroalkyl, methylenedioxy, ethylenedioxy, alkoxy-loweralkyl and hydroxyloweralkyl;

represents a saturated nitrogen heterocycle or methyl-substituted saturated nitrogen heterocycle, in which said nitrogen is tertiary, said heterocycle containing at least two 6-membered rings; and

Ar is chosen from the group consisting of

(i) aryl;

(ii) heteroaryl other than 2-pyridinyl and 3-pyridinyl;

(iii) aryl substituted with from one to four substitutents chosen from lower alkoxy, phenoxy, trialkylsilylacetylenyl, anilino, lower alkynyl, lower alkyl, halogen, nitro, cyano, hydroxy, amino, acetylamino, methylenedioxy, alkylamino, dialkylamino, phenyl, heterocyclyl, methylheterocyclyl, methylenedioxy and acylamino;

(iv) heteroaryl substituted with one or two substitutents chosen from oxo, halogen, and alkyl; and

(v) dihydroheteroaryl;

with the proviso that, when

is 1-azabicyclo[2.2.2]oct-3-yl and all of R 1 , R 2 and R 3 are H, Ar cannot be phenyl or phenyl substituted with halogen.

5. A compound according to claim 2 wherein

is chosen from:

wherein

m=1, 2, 3 or 4;

n=0, 1, 2, 3 or 4; and

R 5 is hydrogen or methyl.

6. A compound according to claim 4 wherein

is chosen from:

wherein

m=1, 2, 3 or 4;

n=0, 1, 2, 3 or 4; and

R 5 is hydrogen or methyl.

7. A compound according to claim 5 wherein

is chosen from quinuclidine, tropane, azabicyclo[3.3.1]nonane and methyl azabicyclo[3.3.1]nonane.

8. A compound according to claim 6 wherein

is chosen from quinuclidine, tropane, azabicyclo[3.3.1]nonane and methyl azabicyclo[3.3.1]nonane.

9. A compound according to claim 1 or 3 , wherein R 1 , R 2 and R 3 are hydrogen.

10. A compound according to claim 1 or 3 , wherein one of R 1 , R 2 and R 3 is halogen.

11. A compound according to claim 1 or 3 , wherein R 1 and R 3 are hydrogen and R 2 is chosen from amino, halogen, methoxy, hydroxy, acetylamino, and 4-morpholinyl.

12. A compound according to claim 1 or 3 wherein Ar is chosen from the group consisting of phenyl and phenyl substituted with from 1 to 4 groups independently selected from (C 1 to C 4 )alkyl, phenyl, phenoxy, halogen, (C 1 to C 4 )alkoxy, amino, (C 1 to C 4 )alkylamino, di(C 1 to C 4 )alkylamino, anilino, heterocyclyl, methylheterocyclyl, methylenedioxy, (C 1 to C 4 )acylamino, (C 1 to C 4 )alkynyl and nitro.

13. A compound according to claim 12 wherein Ar is chosen from the group consisting of phenyl and phenyl substituted with one or two residues chosen independently from (C 1 to C 4 )alkyl, 4-methylpiperazinl-yl, morpholin-4-yl, pyridin-4-yl, phenyl, phenoxy, amino, anilino, halogen, methoxy, dimethylamino, methylenedioxy, acetylamino, propyn-1-yl and nitro.

14. A compound according to claim 1 or 3 wherein Ar is chosen from the group consisting of heteroaryl, dihydroheteroaryl and substituted heteroaryl.

15. A compound according to claim 14 wherein Ar is chosen from thiophene, cyclopenta[b]thiophene, furan, thiazole, isoxazole dihydrobenzofuran, benzofuran, pyridine, benzothiophene, 3-pyridine-2-one, and their methylated and halogenated congeners.

16. A compound according to claim 1 or 3 chosen from the group consisting of:

N-(1-Methylpiperidin-4-yl)-2-phenylbenzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-phenylbenzoxazole-4-carboxamide,

N-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yl)-2-phenylbenzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-6-chloro-2-phenylbenzoxazole-4-carboxamide,

N-(Piperidin-4-yl)-2-phenylbenzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-phenylbenzoxazole-4-carboxamide,

N-(1-Methyl-piperidin-4-yl)-6-chloro-2-phenylbenzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-chloro-2-phenylbenzoxazole-4-carboxamide,

N-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yl)-6-chloro-2-phenylbenzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-chlorophenyl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(4-chlorophenyl)benzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-methoxyphenyl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(4-methoxyphenyl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(4-fluorophenyl)benzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-fluorophenyl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-phenylbenzoxazole-7-carboxamide,

N-(1-Methylpiperidin-4-yl)-2-phenylbenzoxazole-7-carboxamide,

N-(Piperidin-4-yl)-2-phenylbenzoxazole-7-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-phenylbenzoxazole-7-carboxamide,

N-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yl)-2-phenylbenzoxazole-7-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-5-chloro-2-phenyl-benzoxazole-7-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-5-chloro-2-phenyl-benzoxazole-7-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(4-fluorophenyl)benzoxazole-7-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-methoxyphenyl)benzoxazole-7-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(4-methoxyphenyl)benzoxazole-7-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-chlorophenyl)benzoxazole-7-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(4-chlorophenyl)benzoxazole-7-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-phenylbenzothiazole-7-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-chloro-2-phenylbenzoxazole-4-carboxamide,

N-(9-Methyl-3-oxa-9-azabicyclo[3.3.1]non-7-yl)-2-phenylbenzoxazole-4-carboxamide,

N-(9-Methyl-3-oxa-9-azabicyclo[3.3.1]non-7-yl)-6-chloro-2-phenylbenzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(2-methoxyphenyl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(2-methoxyphenyl)benzoxazole-4-carboxamide Hydrochloride,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(3-methoxyphenyl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(2-hydroxyphenyl)benzoxazole-4-carboxamide, Hydrochloride,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(2-hydroxyphenyl)benzoxazole-4-carboxamide Hydrochloride,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(2-bromophenyl)benzoxazole-4-carboxamide Hydrochloride,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(2-aminophenyl)benzoxazole-4-carboxamide Dihydrochloride,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(biphenyl-2-yl)benzoxazole-4-carboxamide Hydrochloride,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(2-pyridine-4-yl)phenylbenzoxazole-4-carboxamide Dihydrochloride,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-p-tolylbenzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-p-tolylbenzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-nitrophenyl)benzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-aminophenyl)benzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-acetylaminophenyl)benzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-dimethylaminophenyl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(4-dimethylaminophenyl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(2-dimethylaminophenyl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(2-dimethylaminophenyl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-6-chloro-2-(2-dimethylaminophenyl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-chloro-2-(2-dimethylaminophenyl)benzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-cyanophenyl)benzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-iodophenyl)benzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-trimethylsilylethynylphenyl)benzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-propyn-1-ylphenyl)benzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-ethynylphenyl)benzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-biphenyl-4-ylbenzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-phenoxyphenyl)benzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-phenylaminophenyl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-benzo[1,3]dioxol-5-ylbenzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-benzo[1,3]dioxol-5-yl-benzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-benzofuran-5-ylbenzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(2,3-dihydrobenzofuran-5-yl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(2,4-dimethoxyphenyl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(2,4-dimethoxyphenyl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(2,4-dichlorophenyl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(2,4-dichlorophenyl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-chloro-2-methoxyphenyl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(4-chloro-2-methoxyphenyl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-methoxy-2-methylphenyl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(4-methoxy-2-methylphenyl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-chloro-2-methylphenyl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(4-chloro-2-methylphenyl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl-2-(2,6-dimethylphenyl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(2,6-dichlorophenyl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(2,6-dichlorophenyl)benzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-chloro-2-p-tolylbenzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-6-chloro-2-p-tolylbenzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-chloro-2-(4-methoxyphenyl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-6-chloro-2-(4-methoxyphenyl)benzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-bromo-2-phenylbenzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-6-bromo-2-phenylbenzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-bromo-2-p-tolylbenzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-6-bromo-2-p-tolylbenzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-bromo-2-(4-methoxyphenyl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-6-bromo-2-(4-methoxyphenyl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-6-amino-2-phenylbenzoxazole-4-carboxamide Dihydrochloride,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-5-bromo-2-phenylbenzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-5-bromo-2-phenylbenzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-7-bromo-2-phenylbenzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-7-bromo-2-phenylbenzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-iodo-2-phenylbenzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-6-iodo-2-phenylbenzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-morpholine-2-phenylbenzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-amino-2-phenylbenzoxazole-4-carboxamide,

N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-acetylamino-2-phenylbenzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-methoxy-2-phenylbenzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-6-methoxy-2-phenylbenzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-hydroxy-2-phenylbenzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-fluoro-2-phenylbenzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-6-fluoro-2-phenyl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-fluoro-2-(2-methoxyphenyl)benzoxazole-4-carboxamide Hydrochloride,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-6-fluoro-2-(2-methoxyphenyl)benzoxazole-4-carboxamide, Hydrochloride,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-pyridin-4-ylbenzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-furan-2-ylbenzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-furan-2-ylbenzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-thiophen-2-ylbenzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-thiophen-2-ylbenzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-6-chloro-2-thiophen-2-ylbenzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-chloro-2-thiophen-2-ylbenzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-thiophen-3-ylbenzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-thiophen-3-ylbenzoxazole-4-carboxamide,

N-(9-Methyl-3-oxa-9-azabicyclo[3.3.1]non-7-yl)-6-chloro-2-thiophen-3-ylbenzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-6-chloro-2-thiophen-3-ylbenzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-chloro-2-thiophen-3-ylbenzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-benzo[b]thiophen-2-ylbenzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-benzo[b]thiophen-2-yl benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-benzofuran-2-ylbenzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-benzofuran-2-ylbenzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(3-methylthiophen-2-yl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(3-methylthiophen-2-yl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-6-chloro-2-(3-methylthiophen-2-yl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(3-chlorothiophen-2-yl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(3-chlorothiophen-2-yl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(3-bromothiophen-2-yl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(3-bromothiophen-2-yl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-chloro-2-(3-chlorothiophen-2-yl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-6-chloro-2-(3-chlorothiophen-2-yl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(5-methylthiophen-2-yl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(5-chloro-thiophen-2-yl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(5-chlorothiophene-2-yl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(5-bromothiophene-2-yl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(5-bromothiophene-2-yl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-chloro-2-(5-methylthiophen-2-yl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-6-chloro-2-(5-methylthiophen-2-yl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(3,5-dimethylisoxazole-4-yl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(3,5-dimethylisoxazole-4-yl)benzoxazole-4-carboxamide,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(4-methylthiazol-5-yl)benzoxazole-4-carboxamide, Hydrochloride,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(4-methylthiazol-5-yl)benzoxazole-4-carboxamide Hydrochloride,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(thiazole-4-yl)benzoxazole-4-carboxamide, Hydrochloride

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(thiazol-4-yl)benzoxazole-4-carboxamide Hydrochloride,

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(2-oxo-1,2-dihydropyridin-3-yl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(2-oxo-1,2-dihydropyridin-3-yl)benzoxazole-4-carboxamide,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(2-morpholinophenyl)benzoxazole-4-carboxamide Maleate,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-[2-(4-methylpiperazin-1-yl)phenyl]benzoxazole-4-carboxamide Maleate,

N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(2-isopropylphenyl)benzoxazole-4-carboxamide Hydrochloride, and

(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-(2-isopropylphenyl)benzoxazole-4-carboxamide Hydrochloride.

17. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to claim 1 or 3 .

18. A pharmaceutical composition according to claim 17 additionally comprising a second antiemetic agent.

19. A pharmaceutical composition according to claim 18 wherein said second antiemetic agent is a neurokinin antagonist.

20. A method of treating irritable bowel syndrome or emesis, which comprises administering to a patient in need of such treatment a therapeutically effective amount of a compound according to claim 1 or 3 .

21. A method according to claim 20 for treating irritable bowel syndrome.

22. A method according to claim 20 for treating emesis.