NK

1. A compound having the formula (I):

or a pharmaceutically acceptable salt thereof, wherein

Ar 1 is phenyl, wherein said phenyl can be unsubstituted or substituted with 1 to 3 fluoro;

Ar 2 is bis(trifluoromethyl)phenyl;

X 1 is —O—;

R 1 and R 2 are independently selected from the group consisting of H, C 1 -C 6 alkyl or hydroxyl (C 1 -C 3 alkyl), providing that at least one of R 1 and R 2 is H;

R 3 is H;

R 6 and R 7 are each H;

n 2 is 2;

R 4 and R 5 are each independently selected from the group consisting of —(CR 28 R 29 ) n1 -G, where,

n 1 is 0-5; and G is

H, —NR 13 R 14 , —NR 12 C(O)R 14 , —C(O)NR 13 R 14 , —OC(O)NR 13 R 14 , NR 12 C(O)OR 13 , —NR 12 (C(O)NR 13 R 14 ), —NR 12 S) 2 R 13 , R 19 -heteroaryl, R 19 -aryl, wherein heteroaryl is selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, furanyl, benzofuranyl, thienyl, benzothienyl, thiazolyl, thiadiazolyl, imidazolyl, pyrazolyl, triazoyl, tetrazolyl, isothiazolyl, benzothiazolyl, benzoxazolyl, oxazolyl, pyrrolyl, isoxazolyl, 1,3,5-triazinyl or indolyl and aryl is selected from phenyl, —OH, —O(C 1 -C 6 alkyl), —C(OR 12 )(R 13 )(R 14 ), —OC(O)R 14 , ——C(O)R 13 , heterocycloalkenyl optionally substituted by 1 substituent independently selected from the group consisting of R 30 and R 31 ,

provided that R 4 and R 5 are not both selected from the group consisting of H, alkyl and cycloalkyl;

further provided that, when one of R 4 and R 5 is —OH, then the other one of R 4 and R 5 is not alkyl or (R 19 aryl);

R 12 is H, C 1 -C 6 alkyl or C 3 -C 8 cycloalkyl;

R 13 and R 14 are reach independently selected from the group consisting of H, C 1 -C 6 alkyl, —CH 2 CF 3 , C 3 -C 6 cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, phenyl or pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, furanyl, benzofuranyl, thienyl, benzothienyl, thiazolyl, thiadiazolyl, imidazolyl, pyrazolyl, triazoyl, tetrazolyl, isothiazolyl, benzothiazolyl, benzoxazolyl, oxazolyl, pyrrolyl, isoxazolyl, 1,3,5-triazinyl or indolyl; or

R 13 and R 14 , together with the nitrogen atom to which they are both attached, form a 5- to 6-membered saturated or unsaturated ring that is optionally substituted with —OR 12 , where one of the carbon atoms in the ring is optionally replaced by a heteroatom selected from —O—;

n 6 is 0, 1 or 2;

R 18 is H;

each R 19 is a substituent on the aryl or heteroaryl ring to which it is attached and is independently selected from the group consisting of H or C 1 -C 6 alkyl;

R 23 and R 24 are each independently selected from the group consisting of H and C 1 -C 6 alkyl; or R 23 and R 24 , together with the carbon atom to which they are both attached, form a C═O or cyclopropyl group;

R 27 is H, —OH or C 1 -C 6 alkyl;

R 28 and R 29 are each independently selected from the group consisting of H and C 1 -C 2 alkyl;

R 30 and R 31 are each independently selected from the group consisting of H, —OH, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl and —C(0)NR 13 R 14 ; or R 30 and R 31 , together with the carbon atom to which they are both attached, form ═O, ═S, a cyclopropyl ring or ═NR 36 ;

R 32 and R 33 are each H;

R 34 is H, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl or hydroxyl(C 2 -C 6 )alkyl;

R 35 is H, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, -P(0)(OH) 2 , allyl, hydroxyl(C 2 -C 6 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, —SO 2 R 15 or —(CH 2 ) 2 —N(R 12 )—SO 2 —R 15 ;

R 36 is H, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, —NO 2 , —CN or OR 12 ;

R 37 is 1 to 3 substituents independently selected from the group consisting of H, C 1 -C 6 alkyl, —OH, C 1 -C 6 alkoxy and halogen;

r is 1to 3;

X 2 is —NR 35 —, —O—, —S—, —S(O)—, —S(O 2 —, —CH 2 —, —CF 2 — or —CR 12 F—;

X 3 is —NR 34 —, —N(CONR 13 R 14 )—, —N(CO 2 R 15 )—, —N(COR 12 )—, —N(SO 2 NHR 13 )—, —O—, —S—, —S(O)—, SO 2 —, —CH 2 —, —CF 2 —, or CR 12 F—;

n 3 is 1 to 5; and

n 5 is 1 to 3;

or a diastereomer, enantiomer, stereoisomer, regiostereomer, rotomer, or tautomer thereof.

2. The compound or salt according to claim 1 wherein R 4 is —NR 13 R 14 , —NR 12 C(O)R 14 , NR 12 C(O)OR 13 , NR 12 (C(O)NR 13 R 14 , —OH, —O—(C 1 -C 6 )alkyl, —O—(C 3 -C 8 cycloalkyl, —OC(O)R 14 , —OC(O)NR 13 R 14 , —NR —SO 2 NR 13 R 14 , R 19 -heteroaryl,

wherein X 2 is —O—, —S—, —CH 2 — or —NR 35 ; and R 5 is —C(O)OR 13 or —C(O)NR 13 R 14 .

3. The compound or salt according to claim 2 where R12 and R27 are independently selected from the group consisting of H and —CH3; n3 is 2 or 3; and n5 is 1 or 2.

4. the compound or salt according to claim 2 , wherein R12 and R27 are H; n3 is 2 or 3; and n5 is 1 or 2.

5. A compound having the following structure:

and pharmaceutically acceptable salts thereof.

6. A compound having the following structure:

and pharmaceutically acceptable salts thereof.

7. A compound having the following structure:

and pharmaceutically acceptable salts thereof.

8. The compound or salt according to claim 1 , wherein the compound is:

9. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of claim 1 in a pharmaceutically acceptable carrier.

10. The pharmaceutical composition according to claim 9 , further comprising at least one serotonin reuptake inhibitor.

11. The pharmaceutical composition according to claim 9 , further comprising at least one serotonin 5-HT3 receptor antagonist, or at least one corticosteroid or at least one substituted benzamide.

12. The pharmaceutical composition according to claim 9 , further comprising at least one serotonin 5-HT3 receptor antagonist and at least one corticoid steroid.

13. The pharmaceutical composition according to claim 9 , further comprising at least one substituted benzamide and at least one corticosteroid.

14. The pharmaceutical composition according to claim 10 , where the selective serotonin reuptake inhibitor is fluoxetine, fluvoxamine, paroxetine, sertraline, or a pharmaceuticall acceptable salt thereof.

15. The pharmaceutical composition according to claim 11 , where the serotonin 5-HT3 receptor antagonist is ondansetron, dolasetron, palonsetron or granisetron, the corticosteroid is dexamethasone, and the substituted benzamide is metoclopramide.

16. The pharmaceutical composition according to claim 12 where the serotonin 5-HT3 receptor antagonist is ondansetron, dolasetron, palosetron or granisetron, the corticosteroid is dexamethasone.

17. The pharmaceutical composition according to claim 11 , wherein the corticosteroid is dexamethasone, and the substituted benzamide is metoclopramide.

18. The pharmaceutical composition according to claim 13 , where the corticosteroid is dexamethasone and the substituted benzamide is metoclopramide.

19. A compound selected from the group consisting of:

and pharmaceutically acceptable salts thereof.