Asymmetric ureas and medical uses thereof

1. A method of treating cachexia or gastroparesis by agonizing activity of a ghrelin receptor in a human subject comprising administering to said subject an effective amount of a ghrelin receptor agonist selected from the group consisting of 3-(1-(2,3-dichloro-4-methoxyphenyl)ethyl)-1-methyl-1-(1,3,3-trimethylpiperidin-4-yl)urea, 1-hydroxy-3-(1-(4-methoxynaphthalen-1-yl)ethyl)-1-(1-methylpiperidin-4-yl)urea, and 3-(1-(2,3-dichloro-4-methoxyphenyl)ethyl)-1-hydroxy-1-(1-methylpiperidin-4-yl)urea, or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , for the treatment of cachexia resulting from cancer, congestive heart failure, wasting due to ageing, or AIDS.

3. The method of claim 1 , wherein said cachexia results from cancer.

4. The method of claim 3 , wherein said cachexia results from congestive heart failure.

5. The method of claim 1 , wherein said cachexia results from wasting due to ageing.

6. The method of claim 1 , wherein said cachexia results from AIDS.

7. The method of claim 1 , wherein said agonist or a pharmaceutically acceptable salt thereof, is administered by one or more routes selected from the group consisting of rectal, buccal, sublingual, intravenous, subcutaneous, intradermal, transdermal, intraperitoneal, oral, eye drops, parenteral and topical administration.

8. The method of claim 7 , wherein said administration is accomplished by administering an oral form of said agonist or a pharmaceutically acceptable salt thereof.

9. The method of claim 1 , wherein said agonist or a pharmaceutically acceptable salt thereof, is administered in an amount of from about 0.01 microgram per Kg g/Kg) body weight per day to about 100 mg/Kg body weight per day, from about 0.1 μg/Kg/day to about 10 mg/Kg/day, from about 1 μg/Kg/day to about 5 mg/Kg/day, from about 10 μg/Kg/day to about 5 mg/Kg/day, from about 100 μg/Kg/day to about 5 mg/Kg/day, or from about 500 μg/Kg/day to about 5 mg/Kg/day.

10. The method of claim 1 , wherein the subject has been identified as needing treatment for the disease or the administration.

11. The method of claim 1 for the treatment of gastroparesis.

12. The method of claim 1 wherein said compound is 3-(1-(2,3-dichloro-4-methoxyphenyl)ethyl)-1-methyl-1-(1,3,3-trimethylpiperidin-4-yl)urea, or a pharmaceutically acceptable salt thereof.

13. The method of claim 1 wherein said compound is 1-hydroxy-3-(1-(4-methoxynaphthalen-1-yl)ethyl)-1-(1-methylpiperidin-4-yl)urea, or a pharmaceutically acceptable salt thereof.

14. The method of claim 1 wherein said compound is 3-(1-(2,3-dichloro-4-methoxyphenyl)ethyl)-1-hydroxy-1-(1-methylpiperidin-4-yl)urea, or a pharmaceutically acceptable salt thereof.

15. A method of treating cachexia or gastroparesis by agonizing activity of a ghrelin receptor in a human subject comprising administering to said subject an effective amount of a ghrelin receptor agonist represented by formula (I):

or a pharmaceutically acceptable salt thereof,

wherein:

R is selected from the group consisting of aryl, arylalkyl, optionally substituted with one or more independent R 103 substituents;

R 1 is selected from the group consisting of hydroxy, amino, alkyl, alkenyl, cycloalkyl, halogen, alkoxy, alkoxyalkyl, aryl, arylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl and heteroarylalkyl, each optionally independently substituted with one or more independent R 103 substituents;

R 2 is hydrogen;

R 3 is selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, aryl, arylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, —C(O)R 101 , —C(O)OR 101 , —C(O)NR 101 R 102 , —S(O) 2 R 102 , —SR 101 and —S(O) 2 NR 101 R 102 , optionally substituted with one or more independent R 103 substituents;

R 4 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, aryl, arylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, —OR 103 , NR 101 R 102 , —C(O)R 101 , —C(O)OR 101 , —C(O)NR 101 R 102 , -alkylNR 101 R 102 , —S(O) 2 R 102 , —SR 101 and —S(O) 2 NR 101 R 102 , optionally substituted with one or more independent R 103 substituents;

R 5 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, heteroarylalkyl, oxide (═O), —C(O)R 101 , —C(O)OR 101 , —C(O)NR 101 R 102 , —S(O) 2 R 102 , —SR 101 and —S(O) 2 NR 101 R 102 ;

R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 and R 14 are each independently selected from the group consisting of hydrogen, cyano, —NO 2 , —OR 101 , hydroxy, amino, alkyl, alkenyl, cycloalkyl, halogen, alkoxy, alkoxyalkyl, aryl, arylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, —C(O)R 101 , —C(O)OR 101 , —C(O)NR 101 R 102 , —NR 101 R 102 , —NR 101 S(O) 2 R 102 , —NR 101 C(O)R 102 , —S(O) 2 R 102 , —SR 101 and —S(O) 2 NR 101 R 102 , each optionally independently substituted with one or more independent R 103 substituents; and

R 101 , R 102 and R 103 are each independently selected from the group consisting of hydrogen, cyano, —NO 2 , —OR 104 , hydroxy, amino, alkyl, alkenyl, cycloalkyl, halogen, alkoxy, alkoxyalkyl, aryl, arylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, —C(O)R 104 , —C(O)OR 104 , —C(O)NR 104 R 105 , —NR 104 R 105 , —NR 104 S(O) 2 R 105 , —NR 104 C(O)R 105 , —S(O) 2 R 104 , —SR 104 and —S(O) 2 NR 104 R 105 , each optionally independently substituted with one or more independent R 103 substituents; or R 101 , R 102 , together with the atoms connecting the same, form a fused or non-fused mono, bicyclic or tricyclic heterocyclic or carbocyclic ring which is optionally independently substituted with one or more R 103 substituents; and

R 104 and R 105 are each independently selected from the group consisting of hydrogen, cyano, —NO 2 , hydroxy, hydroxyalkyl, amino, alkyl, alkenyl, cycloalkyl, halogen, alkoxy, alkoxyalkyl, aryl, arylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl and heteroarylalkyl.

16. The method of claim 15 , for the treatment of cachexia from cancer, congestive heart failure, wasting due to ageing or AIDS.

17. The method of claim 16 , wherein said cachexia results from cancer.

18. The method of claim 16 , wherein said cachexia results from congestive heart failure.

19. The method of claim 16 , wherein said cachexia results from wasting due to ageing.

20. The method of claim 15 , wherein said cachexia results from AIDS.

21. The method of claim 15 , wherein said compound or a pharmaceutically acceptable salt thereof, is administered by one or more routes selected from the group consisting of rectal, buccal, sublingual, intravenous, subcutaneous, intradermal, transdermal, intraperitoneal, oral, eye drops, parenteral and topical administration.

22. The method of claim 21 , wherein said administration is accomplished by administering an oral form of said compound or a pharmaceutically acceptable salt thereof.

23. The method of claim 15 , wherein said compound or a pharmaceutically acceptable salt thereof, is administered in an amount of from about 0.01 microgram per Kg g/Kg) body weight per day to about 100 mg/Kg body weight per day, from about 0.1 μg/Kg/day to about 10 mg/Kg/day, from about 1 μg/Kg/day to about 5 mg/Kg/day, from about 10 μg/Kg/day to about 5 mg/Kg/day, from about 100 μg/Kg/day to about 5 mg/Kg/day, or from about 500 μg/Kg/day to about 5 mg/Kg/day.

24. The method of claim 22 , wherein the subject has been identified as needing treatment for the disease or the administration.

25. The method of claim 15 , wherein R is aryl.

26. The method of claim 15 , wherein R is phenyl or naphthalene which is optionally independently substituted with from one to six substituents independently selected from the group consisting of hydrogen, chloro, fluoro, bromo, trifluoromethyl, cyano, methoxy, ethoxy, methyl and ethyl.

27. The method of claim 15 , wherein R 1 is selected from the group consisting of alkoxy, alkoxyalkyl, —OR 101 , hydroxy, hydroxyalkyl, amino, alkyl, alkenyl, cycloalkyl, aryl, arylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl and heteroarylalkyl.

28. The method of claim 15 , wherein R 1 is selected from the group consisting of alkyl, cycloalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl and heteroarylalkyl.

29. The method of claim 15 , wherein R 1 is selected from the group consisting of methyl, —CH 2 OH, and —CH 2 —O—CH 2 -phenyl.

30. The method of claim 15 , wherein R 3 is hydrogen, alkyl or cycloalkyl.

31. The method of claim 15 , wherein R 4 is selected from the group consisting of alkyl, cycloalkyl, hydroxy, amino, alkoxy, alkylamino, aryl, arylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl and aminoalkyl.

32. The method of claim 15 , wherein R 4 is methyl, ethyl, benzyl, or benzyl substituted with from one to five substituents independently selected from the group consisting of methyl, fluoro, chloro, trifluoromethyl, methoxy, cyano and hydroxy.

33. The method of claim 15 , wherein R 5 is selected from the group consisting of alkyl, cycloalkyl, oxide (═O), aryl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, —C(O)R 101 , —C(O)OR 101 and —C(O)NR 101 R 102 .

34. The method of claim 15 , wherein R 5 is methyl.

35. The method of claim 15 , wherein R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 and R 14 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, —C(O)OR 101 , and -alkylOR 103 .

36. The method of claim 15 , wherein R 8 and R 9 are each independently hydrogen, alkyl, cycloalkyl, —C(O)OR 101 , or -alkylOR 103 .

37. The method of claim 15 , wherein R 8 and R 9 are each independently hydrogen, methyl, ethyl, —C(═O)OEt, or —CH 2 OH.

38. The method of claim 15 for the treatment of gastroparesis.

39. A method of treating cachexia or gastroparesis by agonizing activity of a ghrelin receptor in a human subject comprising administering to said subject an effective amount of a ghrelin receptor agonist selected from one of the following compounds, or a pharmaceutically acceptable salt thereof:

GA1

1-methyl-3-((R)-1-(naphthalen-1- yl)ethyl)-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA2

1-methyl-3-((S)-1-(naphthalen-1- yl)ethyl)-1-(1,3,3,- trimethylpiperidin-4-yl)urea,

GA3

1-methyl-3-(1-(naphthalen-1- yl)ethyl)-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA4

3-(1-(4-methoxynaphthalen-1- yl)ethyl)-1-methyl-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA5

1-benzyl-3-((R)-1-(naphthalen-1- yl)ethyl)-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA6

3-(1-(2,3-dichlorophenyl)ethyl)-1- (3-methoxybenzyl)-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA7

3-(1-(2,3-dichlorophenyl)ethyl)-1- (2-fluorobenzyl)-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA9

3-(1-(2,3-dichlorophenyl)ethyl)-1- methyl-1-(1,3,3-trimethylpiperidin- 4-yl)urea,

GA10

3-((R)-1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-(1,3- dimethylpiperidin-4-yl)-1-(3- methoxybenzyl)urea,

GA11

1-benzyl-3-(1-(2,3- dichlorophenyl)propyl)-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA12

3-((S)-1-(2,3- dichlorophenyl)ethyl)-1-methyl-1- (1,3,3-trimethylpiperidin-4-yl)urea,

GA13

3-((R)-1-(2,3- dichlorophenyl)ethyl)-1-methyl-1- (1,3,3-trimethylpiperidin-4-yl)urea,

GA14

3-(1-(2,3-dichlorophenyl)ethyl)-1- methyl-1-(1,3,3-trimethylpiperidin- 4-yl)urea,

GA15

1-benzyl-3-((S)-1-(naphthalen-1- yl)ethyl)-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA16

1-benzyl-3-((R)-1-(naphthalen-1- yl)ethyl)-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA17

1-benzyl-3-(1-(naphthalen-1- yl)ethyl)-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA18

3-(1-(2,3-dichlorophenyl)propyl)- 1-methyl-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA19

3-(1-(2,3-difluorophenyl)ethyl)-1- methyl-1-(1,3,3-trimethylpiperidin- 4-yl)urea,

GA20

1-benzyl-3-(1-(2,3- dichlorophenyl)ethyl)-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA21

1-benzyl-3-(1-(2,3- difluorophenyl)ethyl)-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA22

1-benzyl-3-(1-(4- methoxynaphthalen-1-yl)ethyl)-1- (1,3,3-trimethylpiperidin-4-yl)urea,

GA23

3-(1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-methyl-1- (1,3,3-trimethylpiperidin-4-yl)urea,

GA24

3-(1-(2,3-dichlorophenyl)ethyl)-1- methyl-1-(1,2,2,5,5- pentamethylpiperidin-4-yl)urea,

GA25

methyl 2-(3-methyl-3-(1,3,3- trimethylpiperidin-4-yl)ureido)-2- (naphthalen-1-yl)acetate,

GA26

3-(2-hydroxy-1-(naphthalen-1- yl)ethyl)-1-methyl-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA27

1-(4-chlorobenzyl)-3-(1-(2,3- dichlorophenyl)ethyl)-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA28

1-benzyl-1-(3,3-diethyl-1- methylpiperidin-4-yl)-3-((S)-1- (naphthalen-1-yl)ethyl)urea,

GA29

1-benzyl-1-(3,3-diethyl-1- methylpiperidin-4-yl)-3-((R)-1- (naphthalen-1-yl)ethyl)urea,

GA30

1-benzyl-1-(3,3-diethyl-1- methylpiperidin-4-yl)-3-(1- (naphthalen-1-yl)ethyl)urea,

GA31

3-(2-(benzyloxy)-1-(naphthalen-1- yl)ethyl)-1-methyl-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA32

ethyl 4-(1-benzyl-3-(1-(2,3- dichlorophenyl)ethyl)ureido)-1,3- dimethylpiperidine-3-carboxylate,

GA33

3-((R)-1-(2,3- dichlorophenyl)ethyl)-1-(3- methoxybenzyl)-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA34

3-(2-cyclopropyl-1-(2,3- dichlorophenyl)ethyl)-1-(3- methoxybenzyl)-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA35

3-(1-(2,3-dichlorophenyl)ethyl)-1- (3-hydroxybenzyl)-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA36

1-benzyl-3-(1-(2,3- dichlorophenyl)ethyl)-1-(3- (hydroxymethyl)-1,3- dimethylpiperidin-4-yl)urea,

GA37

1-benzyl-3-(1-(2,3- dihydroxyphenyl)ethyl)-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA38

3-((R)-1-(2,3- dichlorophenyl)ethyl)-1-(3-(2- hydroxyethoxy)benzyl)-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA39

3-(1-(2,3-difluoro-4- methoxyphenyl)ethyl)-1-methyl-1- (1,3,3-trimethylpiperidin-4-yl)urea,

GA40

3-(1-(2,3-dihydro-4- hydroxyphenyl)ethyl)-1-methyl-1- (1,3,3-trimethylpiperidin-4-yl)urea,

GA41

4-(1-benzyl-3-(1-(2,3- dichlorophenyl)ethyl)ureido)-1,3- dimethylpiperidine-3-carboxylic acid,

GA42

ethyl 4-(3-(1-(2,3- dichlorophenyl)ethyl)-1- methylureido)-1,3- dimethylpiperidine-3-carboxylate,

GA43

3-(1-(2,3-dichlorophenyl)ethyl)-1- (3-(hydroxymethyl)-1,3- dimethylpiperidin-4-yl)-1- methylurea,

GA44

4-(3-(1-(2,3-dichlorophenyl)ethyl)- 1-methylureido)-1,3,3- trimethylpiperidine 1-oxide,

GA45

3-(1-benzo[d][1,3]dioxol-5- yl)ethyl)-1-benzyl-1-(1,3,3- trimethylpiperidin-4-yl)urea,

GA46

1-ethyl-1-(1-methylpiperidin-4-yl)- 3-(1-(naphthalen-1-yl)ethyl)urea,

GA47

3-(1-(4-methoxynaphthalen-1- yl)ethyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea,

GA48

3-(2-hydroxy-1-(naphthalen-1- yl)ethyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea,

GA49

3-(2-hydroxy-1-(4- methoxynaphthalen-1-yl)ethyl)-1- methyl-1-(1-methylpiperidin-4- yl)urea,

GA50

1-(1-methylpiperidin-4-yl)-3-(1- (naphthalen-1-yl)ethyl)-1-(pyridin- 3-ylmethyl)urea,

GA51

1-cyclopentyl-1-(1- methylpiperidin-4-yl)-3-(1- (naphthalen-1-yl)ethyl)urea,

GA52

1-methyl-3-(1-(naphthalen-1- yl)ethyl)-1-(piperidin-4-yl)urea,

GA53

1-(1-acetylpiperidin-4-yl)-1- methyl-3-(1-(naphthalen-1- yl)ethyl)urea,

GA54

1-methyl-1-(1- (methylsulfonyl)piperidin-4-yl)-3- (1-(naphthalen-1-yl)ethyl)urea,

GA55

1-methyl-3-(1-(naphthalen-1- yl)ethyl)-1-(1-(pyridin-3- ylmethyl)piperidin-4-yl)urea,

GA56

1-cyclohexyl-1-(1-methylpiperidin- 4-yl)-3-(1-(naphthalen-1- yl)ethyl)urea,

GA57

1-(cyclohexylmethyl)-1-(1- methylpiperidin-4-yl)-3-(1- (naphthalen-1-yl)ethyl)urea,

GA58

1-isopropyl-1-(1-methylpiperidin- 4-yl)-3-(1-(naphthalen-1- yl)ethyl)urea,

GA59

1-(2-methoxyethyl)-1-(1- methylpiperidin-4-yl)-3-(1- (naphthalen-1-yl)ethyl)urea,

GA60

1-(1-ethylpiperidin-4-yl)-1-methyl- 3-(1-(naphthalen-1-yl)ethyl)urea,

GA61

1-ethyl-4-(1-methyl-3-(1- (naphthalen-1- yl)ethyl)ureido)piperidine 1-oxide,

GA62

1-(cyclopropylmethyl)-1-(1- methylpiperidin-4-yl)-3-(1- (naphthalen-1-yl)ethyl)urea,

GA63

3-(1-(2-methoxynaphthalen-1- yl)ethyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea,

GA64

1-methyl-1-(1-methylpiperidin-4- yl)-3-(1-(quinolin-4-yl)ethyl)urea,

GA65

tert-butyl 4-(1-methyl-3-(1- (naphthalen-1- yl)ethyl)ureido)piperidine-1- carboxylate

GA66

1-(1-formylpiperidin-4-yl)-1- methyl-3-(1-(naphthalen-1- yl)ethyl)urea,

GA67

3-(2-methoxy-1-(naphthalen-1- yl)ethyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea,

GA68

3-(3-methoxy-1-(naphthalen-1- yl)propyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea,

GA69

1-methyl-1-(1-methylpiperidin-4- yl)-3-(1-(naphthalen-1- yl)propyl)urea,

GA70

1-methyl-1-(1-methylpiperidin-4- yl)-3-(1-(quinolin-5-yl)ethyl)urea,

GA71

1-methyl-1-(1-methylpiperidin-4- yl)-3-(2-(naphthalen-1-yl)propan- 2-yl)urea,

GA72

3-(1-(2-chloroquinolin-4-yl)ethyl)- 1-methyl-1-(1-methylpiperidin-4- yl)urea,

GA73

(S)-1-(1-methylpiperidin-4-yl)-3- (1-(naphthalen-1-yl)ethyl)-1- (pyridin-3-ylmethyl)urea,

GA74

(R)-1-(1-methylpiperidin-4-yl)-3- (1-(naphthalen-1-yl)ethyl)-1- (pyridin-3-ylmethyl)urea,

GA75

1-isobutyl-1-(1-methylpiperidin-4- yl)-3-(1-(naphthalen-1- yl)ethyl)urea,

GA76

1-(cyclobutylmethyl)-1-(1- methylpiperidin-4-yl)-3-(1- (naphthalen-1-yl)ethyl)urea,

GA77

1-butyl-1-(1-methylpiperidin-4-yl)- 3-(1-(naphthalen-1-yl)ethyl)urea,

GA78

3-(1-(2-methoxyquinolin-4- yl)ethyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea,

GA79

1-(1-methylpiperidin-4-yl)-3-(1- (naphthalen-1-yl)ethyl)-1-(pyridin- 2-ylmethyl)urea,

GA80

1-(1-methylpiperidin-4-yl)-3-(1- (naphthalen-1-yl)ethyl)-1-(pyridin- 4-ylmethyl)urea,

GA81

(S)-1-ethyl-3-(1-(2- methoxyquinolin-4-yl)ethyl)-1-(1- methylpiperidin-4-yl)urea,

GA82

(R)-1-ethyl-1-(1-methylpiperidin- 4-yl)-3-(1-(naphthalen-1- yl)ethyl)urea,

GA83

3-(2-hydroxy-1-(4- methoxynaphthalen-1-yl)ethyl)-1- methyl-1-(1-methylpiperidin-4- yl)urea,

GA84

3-(2-hydroxy-1-(naphthalen-1- yl)ethyl)-1-(1-methylpiperidin-4- yl)-1-(pyridin-3-ylmethyl)urea,

GA85

3-(2-methoxy-1-(4- methoxynaphthalen-1-yl)ethyl)-1- methyl-1-(1-methylpiperidin-4- yl)urea,

GA86

3-(1-(2,3-dichlorophenyl)ethyl)-1- (3-hydroxybenzyl)-1-(1- methylpiperidin-4-yl)urea,

GA87

1-benzyl-1-(1,3-dimethylpiperidin- 4-yl)-3-((R)-1-(naphthalen-1- yl)ethyl)urea,

GA88

1-(1,3-dimethylpiperidin-4-yl)-1- methyl-3-((R)-1-(naphthalen-1- yl)ethyl)urea,

GA89

3-(1-(4-methoxynaphthalen-1- yl)ethyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea,

GA90

(R)-3-(1-(4-methoxynaphthalen-1- yl)ethyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea,

GA91

(S)-3-(1-(4-methoxynaphthalen-1- yl)ethyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea,

GA92

3-(1-(4,8-dimethoxynaphthalen-1- yl)ethyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea,

GA93

3-(1-(4- (methoxymethoxy)naphthalen-1- yl)ethyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea,

GA94

3-(2-(benzyloxy)-1-(2,3- dichlorophenyl)ethyl)-1-methyl-1- (1-methylpiperidin-4-yl)urea,

GA95

(R)-3-(2-(benzyloxy)-1-(2,3- dichlorophenyl)ethyl)-1-methyl-1- (1-methylpiperidin-4-yl)urea,

GA96

(S)-3-(2-(benzyloxy)-1-(2,3- dichlorophenyl)ethyl)-1-methyl-1- (1-methylpiperidin-4-yl)urea,

GA97

3-(1-(2,3-dichlorophenyl)ethyl)-1- methyl-1-(1-methylpiperidin-4- yl)urea,

GA98

1-benzyl-3-(1-(2,3- dichlorophenyl)ethyl)-1-(1- methylpiperidin-4-yl)urea,

GA99

3-(1-(2,3-dichlorophenyl)ethyl)-1- (3-fluorobenzyl)-1-(1- methylpiperidin-4-yl)urea,

GA100

1-(2-chlorobenzyl)-3-(1-(2,3- dichlorophenyl)ethyl)-1-(1- methylpiperidin-4-yl)urea,

GA101

3-(1-(3,5-difluorophenyl)ethyl)-1- methyl-1-(1-methylpiperidin-4- yl)urea,

GA102

3-(1-(2-chlorophenyl)ethyl)-1- methyl-1-(1-methylpiperidin-4- yl)urea,

GA103

3-(1-(3-fluorophenyl)ethyl)-1- methyl-1-(1-methylpiperidin-4- yl)urea,

GA104

3-(1-(4-chlorophenyl)ethyl)-1- methyl-1-(1-methylpiperidin-4- yl)urea,

GA105

3-(1-(2,4-difluorophenyl)ethyl)-1- methyl-1-(1-methylpiperidin-4- yl)urea,

GA106

1-methyl-1-(1-methylpiperidin-4- yl)-3-(1-(o-tolyl)ethyl)urea,

GA107

1-methyl-1-(1-methylpiperidin-4- yl)-3-(1-(4- (methylsulfonyl)phenyl)ethyl)urea,

GA108

1-(cyclohexylmethyl)-3-(1-(2,3- dichlorophenyl)ethyl)-1-(1- methylpiperidin-4-yl)urea,

GA109

1-(cyclopropylmethyl)-3-(1-(2,3- dichlorophenyl)ethyl)-1-(1- methylpiperidin-4-yl)urea,

GA110

3-(1-(2,3-dichlorophenyl)ethyl)-1- ethyl-1-(1-methylpiperidin-4- yl)urea,

GA111

3-(1-(2,3-dichlorophenyl)ethyl)-1- (1-methylpiperidin-4-yl)-1- (pyridin-3-ylmethyl)urea,

GA112

3-(1-(3-chlorophenyl)ethyl)-1- methyl-1-(1-methylpiperidin-4- yl)urea,

GA113

1-benzyl-3-(1-(3- chlorophenyl)ethyl)-1-(1- methylpiperidin-4-yl)urea,

GA114

1-(3-chlorobenzyl)-3-(1-(2,3- dichlorophenyl)ethyl)-1-(1- methylpiperidin-4-yl)urea,

GA115

3-(1-(2,3-dichlorophenyl)ethyl)-1- (2-methoxybenzyl)-1-(1- methylpiperidin-4-yl)urea,

GA116

3-(1-(2,3-dichlorophenyl)ethyl)-1- (3-methoxybenzyl)-1-(1- methylpiperidin-4-yl)urea,

GA117

3-(1-(2,3-dichlorophenyl)ethyl)-1- (4-fluorobenzyl)-1-(1- methylpiperidin-4-yl)urea,

GA118

3-(1-(2,3-dichlorophenyl)ethyl)-1- (2-fluorobenzyl)-1-(1- methylpiperidin-4-yl)urea,

GA119

1-(4-chlorobenzyl)-3-(1-(2,3- dichlorophenyl)ethyl)-1-(1- methylpiperidin-4-yl)urea,

GA120

3-(1-(3,4-dichlorophenyl)ethyl)-1- methyl-1-(1-methylpiperidin-4- yl)urea,

GA121

3-(1-(2,3-dichlorophenyl)ethyl)-1- (4-methoxybenzyl)-1-(1- methylpiperidin-4-yl)urea,

GA122

3-(1-(2,3-dichlorophenyl)propyl)- 1-ethyl-1-(1-methylpiperidin-4- yl)urea,

GA123

1-(cyclohexylmethyl)-3-(1-(2,3- dichlorophenyl)propyl)-1-(1- methylpiperidin-4-yl)urea,

GA124

3-(1-(2,3-difluorophenyl)ethyl)-1- methyl-1-(1-methylpiperidin-4- yl)urea,

GA125

1-benzyl-3-(1-(2,3- difluorophenyl)ethyl)-1-(1- methylpiperidin-4-yl)urea,

GA126

1-(cyclohexylmethyl)-3-(1-(2,3- difluorophenyl)ethyl)-1-(1- methylpiperidin-4-yl)urea,

GA127

(R)-3-(1-(2,3- dichlorophenyl)ethyl)-1-ethyl-1-(1- methylpiperidin-4-yl)urea,

GA128

1-benzyl-3-(1-(2,3- dichlorophenyl)ethyl)-1-(1,3- dimethylpiperidin-4-yl)urea,

GA129

3-(1-(2,3-dichlorophenyl)ethyl)-1- (1,3-dimethylpiperidin-4-yl)-1- methylurea,

GA130

(S)-3-(1-(2,3- dichlorophenyl)ethyl)-1-ethyl-1-(1- methylpiperidin-4-yl)urea,

GA131

(R)-3-(1-(2,3- dichlorophenyl)ethyl)-1-ethyl-1-(1- methylpiperidin-4-yl)urea,

GA132

3-(1-(2,3-dichlorophenyl)ethyl)-1- ethyl-1-(1-methylpiperidin-4- yl)urea,

GA133

3-((R)-1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-(1,3- dimethylpiperidin-4-yl)-1-(3- methoxybenzyl)urea,

GA134

3-((S)-1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-(1,3- dimethylpiperidin-4-yl)-1-(3- methoxybenzyl)urea,

GA135

3-(1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-(1,3- dimethylpiperidin-4-yl)-1-(3- methoxybenzyl)urea,

GA136

3-(1-(2,3-difluorophenyl)ethyl)-1- (1,3-dimethylpiperidin-4-yl)-1-(3- methoxybenzyl)urea,

GA137

3-(1-(2,3-dichlorophenyl)ethyl)-1- (4-(hydroxymethyl)benzyl)-1-(1- methylpiperidin-4-yl)urea,

GA138

methyl 4-((3-(1-(2,3- dichlorophenyl)ethyl)-1-(1- methylpiperidin-4- yl)ureido)methyl)benzoate,

GA139

3-(2-cyclopropyl-1-(2,3- dichlorophenyl)ethyl)-1-methyl-1- (1-methylpiperidin-4-yl)urea,

GA140

3-(1-(2,3-dichlorophenyl)-2- hydroxyethyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea,

GA141

(R)-1-(2-chlorobenzyl)-3-(1-(2,3- dichlorophenyl)ethyl)-1-(1- methylpiperidin-4-yl)urea,

GA142

(S)-1-(2-chlorobenzyl)-3-(1-(2,3- dichlorophenyl)ethyl)-1-(1- methylpiperidin-4-yl)urea,

GA143

1-(2-chlorobenzyl)-3-(1-(2,3- dichlorophenyl)ethyl)-1-(1- methylpiperidin-4-yl)urea,

GA144

3-(1-(2,3-dimethoxyphenyl)ethyl)- 1-methyl-1-(1-methylpiperidin-4- yl)urea,

GA145

3-(1-(2,3-difluoro-4- methoxyphenyl)ethyl)-1-methyl-1- (1-methylpiperidin-4-yl)urea,

GA146

3-(1-(2,3-dichlorophenyl)-2- methoxyethyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea,

GA147

N-(2,3-dichloro-4-(1-(3-methyl-3- (1-methylpiperidin-4- yl)ureido)ethyl)phenyl)acetamide,

GA148

3-(1-(4-amino-2,3- dichlorophenyl)ethyl)-1-methyl-1- (1-methylpiperidin-4-yl)urea,

GA149

3-(1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-methyl-1- (1-methylpiperidin-4-yl)urea,

GA150

1-ethyl-1-(1-methylpiperidin-4-yl)- 3-(1-(naphthalen-1-yl)-3-(3- (pyridin-3- yloxy)phenyl)propyl)urea,

GA151

1-methyl-1-(1-methylpiperidin-4- yl)-3-(1-(naphthalen-1-yl)-3- (pyridin-3-yl)propyl)urea,

GA152

1-methyl-1-(1-methylpiperidin-4- yl)-3-(3-morpholino-1- (naphthalen-1-yl)propyl)urea,

GA153

1-ethyl-3-(3-(3-methoxyphenyl)-1- (naphthalen-1-yl)propyl)-1-(1- methylpiperidin-4-yl)urea,

GA154

3-(3-(3-(benzyloxy)phenyl)-1- (naphthalen-1-yl)propyl)-1-ethyl-1- (1-methylpiperidin-4-yl)urea,

GA155

1-ethyl-1-(1-methylpiperidin-4-yl)- 3-(1-(naphthalen-1-yl)-3-(pyridin- 3-yl)propyl)urea,

GA156

3-(3-(3-(benzyloxy)phenyl)-1- (naphthalen-1-yl)propyl)-1-(1- methylpiperidin-4-yl)-1-(pyridin-3- ylmethyl)urea,

GA157

3-(3-(3-(benzyloxy)phenyl)-1-(2,3- dichlorophenyl)propyl)-1-methyl- 1-(1-methylpiperidin-4-yl)urea,

GA158

3-(2-(benzyloxy)-1-(2,3- dichlorophenyl)ethyl)-1-methyl-1- (1-methylpiperidin-4-yl)urea,

GA159

3-(2-(benzyloxy)-1-(2,3- dichlorophenyl)ethyl)-1-methyl-1- (1-methylpiperidin-4-yl)urea,

GA160

3-(1-(2,3-dichlorophenyl)-2-((3- (hydroxymethyl)benzyl)oxy)ethyl)- 1-methyl-1-(1-methylpiperidin-4- yl)urea,

GA161

3-(2-(benzyloxy)-1-(2,3- dichlorophenyl)ethyl)-1-(2- chlorobenzyl)-1-(1- methylpiperidin-4-yl)urea,

GA162

3-(2-(benzyloxy)-1-(2,3- dichlorophenyl)ethyl)-1-(4- (hydroxymethyl)benzyl)-1-(1- methylpiperidin-4-yl)urea,

GA163

3-(1-(2,3-dichlorophenyl)-2-((4- methoxybenzyl)oxy)ethyl)-1- methyl-1-(1-methylpiperidin-4- yl)urea,

GA164

3-(1-(2,3-dichlorophenyl)-2- (pyridin-4-ylmethoxy)ethyl)-1- methyl-1-(1-methylpiperidin-4- yl)urea,

GA165

3-(1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-methoxy- 1-(1-methylpiperidin-4-yl)urea,

GA166

(S)-3-(1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-methoxy- 1-(1-methylpiperidin-4-yl)urea,

GA167

(R)-3-(1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-methoxy- 1-(1-methylpiperidin-4-yl)urea,

GA168

1-hydroxy-3-(1-(4- methoxynaphthalen-1-yl)ethyl)-1- (1-methylpiperidin-4-yl)urea,

GA169

(R)-1-hydroxy-3-(1-(4- methoxynaphthalen-1-yl)ethyl)-1- (1-methylpiperidin-4-yl)urea,

GA170

(S)-1-hydroxy-3-(1-(4- methoxynaphthalen-1-yl)ethyl)-1- (1-methylpiperidin-4-yl)urea,

GA171

3-(1-(2,3-dichlorophenyl)ethyl)-1- methoxy-1-(1-methylpiperidin-4- yl)urea,

GA172

(R)-3-(1-(2,3- dichlorophenyl)ethyl)-1-methoxy- 1-(1-methylpiperidin-4-yl)urea,

GA173

(S)-3-(1-(2,3- dichlorophenyl)ethyl)-1-methoxy- 1-(1-methylpiperidin-4-yl)urea,

GA174

1-methoxy-3-(1-(4- methoxynaphthalen-1-yl)ethyl)-1- (1-methylpiperidin-4-yl)urea,

GA175

(R)-1-methoxy-3-(1-(4- methoxynaphthalen-1-yl)ethyl)-1- (1-methylpiperidin-4-yl)urea,

GA176

(S)-1-methoxy-3-(1-(4- methoxynaphthalen-1-yl)ethyl)-1- (1-methylpiperidin-4-yl)urea,

GA177

3-(1-(2,3-dichlorophenyl)ethyl)-1- hydroxy-1-(1-methylpiperidin-4- yl)urea,

GA178

(R)-3-(1-(2,3- dichlorophenyl)ethyl)-1-hydroxy- 1-(1-methylpiperidin-4-yl)urea,

GA179

(S)-3-(1-(2,3- dichlorophenyl)ethyl)-1-hydroxy- 1-(1-methylpiperidin-4-yl)urea,

GA180

3-(1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-hydroxy- 1-(1-methylpiperidin-4-yl)urea,

GA181

(R)-3-(1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-hydroxy- 1-(1-methylpiperidin-4-yl)urea,

GA182

(S)-3-(1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-hydroxy- 1-(1-methylpiperidin-4-yl)urea,

GA183

3-(1-(2,3-dichloro-4- (dimethylamino)phenyl)ethyl)-1- methyl-1-(1-methylpiperidin-4- yl)urea,

GA184

3-(1-(4-((4- methoxybenzyl)oxy)naphthalen-1- yl)ethyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea,

GA185

3-(1-(4-hydroxynaphthalen-1- yl)ethyl)-1-methyl-1-(1- methylpyridin-4-yl)urea,

GA186

3-(1-(4,5-dimethoxynaphthalen-1- yl)ethyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea,

GA187

3-(1-(2,3-dichlorophenyl)-2- (pyridin-3-ylmethoxy)ethyl)-1- methyl-1-(1-methylpiperidin-4- yl)urea,

GA188

3-(1-(4-chlorobenzo[d][1,3]dioxol- 5-yl)ethyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea,

GA189

3-(1-(2-chloro-3,4- dimethoxyphenyl)ethyl)-1-methyl- 1-(1-methylpiperidin-4-yl)urea,

GA190

1-methyl-1-(1-methylpiperidin-4- yl)-3-(1-(2,3,4- trichlorophenyl)ethyl)urea,

GA191

1-methyl-1-(1-methylpiperidin-4- yl)-3-(1-(4-(pyridin-4- ylmethoxy)naphthalen-1- yl)ethyl)urea,

GA192

3-(1-(6-chloro[1,1′-biphenyl]-2- yl)ethyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea,

GA193

3-(1-(3-chloro-2-(pyridin-4- yl)phenyl)ethyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea,

GA194

3-(1-(2,3-dichloro-4- methylphenyl)ethyl)-1-methyl-1- (1-methylpiperidin-4-yl)urea,

GA195

3-(1-(3-chloro-2- methylphenyl)ethyl)-1-methyl-1- (1-methylpiperidin-4-yl)urea,

GA196

3-(1-(2,3-dichlorophenyl)-2-((4- (hydroxymethyl)benzyl)oxy)ethyl)- 1-methyl-1-(1-methylpiperidin-4- yl)urea,

GA197

3-(1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-methyl-1- (1-methylpiperidin-4-yl)urea,

GA198

(R)-3-(1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-methyl-1- (1-methylpiperidin-4-yl)urea,

GA199

(S)-3-(1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-methyl-1- (1-methylpiperidin-4-yl)urea,

GA201

3-((R)-1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-methyl-1- (1,3,3-trimethylpiperidin-4-yl)urea,

GA202

3-((S)-1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-methyl-1- (1,3,3-trimethylpiperidin-4-yl)urea, and

GA203

3-(1-(4-(2- (benzyloxy)ethoxy)naphthalen-1- yl)ethyl)-1-methyl-1-(1- methylpiperidin-4-yl)urea.

40. The method of claim 39 , for the treatment of cachexia from cancer, congestive heart failure, wasting due to ageing or AIDS, chronic liver failure, chronic obstructive pulmonary disease, gastrointestinal disease, or gastric disorder.

41. The method of claim 39 , wherein said cachexia results from cancer.

42. The method of claim 40 , wherein said cachexia results from congestive heart failure.

43. The method of claim 40 , wherein said cachexia results from wasting due to ageing.

44. The method of claim 39 , wherein said cachexia results from AIDS.

45. The method of claim 39 , wherein said compound or a pharmaceutically acceptable salt thereof, is administered by one or more routes selected from the group consisting of rectal, buccal, sublingual, intravenous, subcutaneous, intradermal, transdermal, intraperitoneal, oral, eye drops, parenteral and topical administration.

46. The method of claim 39 , wherein said administration is accomplished by administering an oral form of said compound or a pharmaceutically acceptable salt thereof.

47. The method of claim 39 , wherein said compound or a pharmaceutically acceptable salt thereof, is administered in an amount of from about 0.01 microgram per Kg g/Kg) body weight per day to about 100 mg/Kg body weight per day, from about 0.1 μg/Kg/day to about 10 mg/Kg/day, from about 1 μg/Kg/day to about 5 mg/Kg/day, from about 10 μg/Kg/day to about 5 mg/Kg/day, from about 100 μg/Kg/day to about 5 mg/Kg/day, or from about 500 μg/Kg/day to about 5 mg/Kg/day.

48. The method of claim 39 , wherein the subject has been identified as needing treatment for the disease or the administration.

49. The method of claim 39 for the treatment of gastroparesis.