NK 1 ANTAGONISTS

1 . A method of treating a physiological disorder, symptom or disease, comprising:

administering to a patient in need thereof an effective amount of at least one compound of formula I:

or pharmaceutically acceptable salts and/or solvates thereof, wherein:

R 1 and R 2 are each independently selected from the group consisting of H, alkyl, haloalkyl, alkyl substituted with one or more hydroxyl groups, —CN, alkynyl, —N(R 6 ) 2 , —N(R 6 )—S(O 2 )-alkyl, —N(R 6 )—C(O)—N(R 9 ) 2 , -alkylene-CN, -cycloalkylene-CN, -alkylene-O-alkyl, —C(O)-alkyl, —C(═N—OR 5 )-alkyl, —C(O)—N(R 9 ) 2 , —C(O)—O-alkyl, -alkylene-C(O)-alkyl, -alkylene-C(O)—O-alkyl, -alkylene-C(O)—N(R 9 ) 2 ,

with the proviso that at least one of R 1 and R 2 is —CN,

W is ═C(R 8 )— or ═N—;

X is —C(O)— or —S(O 2 )—;

Y is selected from the group consisting of —CH 2 —, —O—, and —N(R 6 )—C(O)—, with the proviso that:

(a) the nitrogen atom of —N(R 6 )—C(O)— is bonded to X, and

(b) if R 1 and/or R 2 is

and Y is —O—, X is not —S(O 2 )—;

Z is —C(R 7 ) 2 —, —N(R 6 )—, or —O—;

R 3 is selected from the group consisting of H, —CH 2 OR 5 , and alkyl;

R 4 is selected from the group consisting of H, alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, aryl, acyl, aroyl, alkylsulfonyl, and arylsulfonyl;

R 5 is H or alkyl;

R 6 is selected from the group consisting of H, alkyl, cycloalkyl, and aryl;

each R 7 is independently H or alkyl; or

each R 7 , together with the ring carbon to which they are shown attached, form a cycloalkylene ring;

R 8 is selected from the group consisting of H, alkyl, alkyl substituted with one or more hydroxyl groups, —N(R 6 ) 2 , —N(R 6 )—S(O 2 )-alkyl, —N(R 6 )—S(O 2 )-aryl, —N(R 6 )—C(O)-alkyl, —N(R 6 )—C(O)-aryl, alkylene-O-alkyl, and —CN;

R 9 is selected from the group consisting of H, alkyl, and aryl, or each R 9 , together with the nitrogen to which they are shown attached, form a heterocycloalkyl ring;

Ar 1 and Ar 2 are each independently selected from the group consisting of unsubstituted aryl and aryl substituted with 0 to 3 substituents selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, —CN, —OH, and —NO 2 ;

n is 0, 1, or 2; and

m is 1, 2, or 3,

wherein the physiological disorder, symptom or disease is selected from the group consisting of respiratory diseases, inflammatory diseases, skin disorders, ophthalmalogical disorders, central nervous system conditions, depression, anxiety, phobia, bipolar disorder, addictions, alcohol dependence, psychoactive substance abuse, epilepsy, nociception, psychosis, schizophrenia, Alzheimer's disease, AIDS related dementia, Towne's disease, stress related disorders, obsessive/compulsive disorders, eating disorders, bulimia, anorexia nervosa, binge eating, sleep disorders, mania, premenstrual syndrome, gastrointestinal disorders, atherosclerosis, fibrosing disorders, obesity, Type II diabetes, pain related disorders, headache, neuropathic pain, post-operative pain, chronic pain syndrome, bladder disorders or genitourinary disorders.

2 . The method of claim 1 , wherein the physiological disorder, symptom or disease is depression, anxiety, a bladder disorder or a genitourinary disorder and the compound is selected from the group consisting of a compound having the Formula IB

wherein R 1 and R 2 are selected from the group consisting of:

Compound

R 1

R 2

 1

—CN

 2

—CN

 3

 4

 5

—CH 2 CN

 6

—CH 3

 7

—CN

 8

—C(O)—O—CH 3

 9

—CN

10

—C(O)—NH 2

11

—CH 2 C(OH)(CH 3 ) 2

12

—CH 2 OH

13

—CH 2 OCH 3

14

—CH 2 OCH 3

15

—CH 2 —NH—S(O 2 )—CH 3

16

CH 2 C(O)—NH(CH 2 CH 3 )

17

CH 2 —C(O)O—CH 2 CH 3

18

—C(═N—OH)—CH 2 CH 3

19

—C(O)—CH 2 CH 3

20

—CH 2 OCH 3

21

—C(O)—NH(CH 3 )

22

C(O)—NH(CH 3 )

23

—CH 2 OH

24

—CH 2 CH 2 OH

25

—CH 2 CH 2 CH 3

26

—CH 2 OCH 3

27

—CH 2 OCH 3

28

H

29

—CH 2 C(O)—NH 2

30

—CH 2 —C(O)—CH 3

31

—CH 2 —C(O)O—CH 3

32

—CN

33

—CN

34

—CN

35

—CN

36

NH—S(O 2 )—CH 3

—CN

37

—CN

—NH—S(O 2 )—CH 3

38

—CH 2 CN

39

—CN

—NH 2

40

—NH 2

—CN

41

NH—C(O)—NH 2

—CN

42

—CN

43

H

44

H

45

H

46

H

47

H

48

H

49

H

50

H

51

—C(O)—NH 2

52

—C(═N—OCH 3 )—CH 3

53

—C(O)—CH 3

54

—C(═N—OH)—CH 3

55

—C(O)OCH 3

56

—CH 2 Cl

57

—CH 3

58

C(═N—OCH 3 )—CH 2 CH 3

59

—NHC(O)CH 3

60

H

61

H

3 . The method of claim 2 , wherein the physiological disorder, symptom or disease is a bladder disease or a urinogenital disease or disorder and the compound is selected from a compound having the formula:

4 . The method of claim 3 , further comprising administering to the patient an effective amount of at least one anti-depressant agent and/or at least one anti-anxiety agent.

5 . The method of claim 4 , further comprising:

administering to the patient an effective amount of at least one selective serotonin reuptake inhibitor, and

wherein the physiological disorder, symptom or disease is depression.

6 . The method according to claim 5 , further comprising:

administering an effective amount of at least one active ingredient selected from the group consisting of other NK 1 receptor antagonists, selective serotonin reuptake inhibitors, dopamine receptor agonists, serotonin 5-HT 3 receptor antagonists, serotonin 5-HT 2c receptor agonists, nociceptin receptor agonists, glucocorticoids and inhibitors of multidrug resistance protein 5; and

wherein the physiological disorder, symptom or disease is selected from the group consisting of: a respiratory disease, depression, anxiety, phobia, bipolar disorder, alcohol dependence, psychoactive substance abuse, nociception, psychosis, schizophrenia, stress related disorder, obsessive/compulsive disorder, bulimia, anorexia nervosa, binge eating, sleep disorder, mania, premenstrual syndrome, gastrointestinal disorder, obesity, headache, neuropathic pain, post-operative pain, chronic pain syndrome, bladder disorder or genitourinary disorder.