# US 9,751,836 B2 · Asymmetric ureas and medical uses thereof

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 9,751,836 B2
- Document ID: US9751836B2
- Status: Granted
- Kind: B2
- Application number: 14/150,360
- Filed: 2014-01-08
- Published: 2014-05-01
- Granted: 2017-09-05
- Earliest claimed: 2011-02-25
- Assignees: Helsinn Healthcare SA
- Applicants: Helsinn Healthcare SA
- Inventors: Silvina Garcia Rubio; Claudio Pietra; Claudio Giuliano; Zhigang Li
- Web page: https://patentgrep.com/patent/US9751836B2

## CPC

- C07D 211/58: attached in position 4
- A61K 31/4468: having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
- A61K 31/4525: containing a five-membered ring with oxygen as a ring hetero atom
- A61K 31/4545: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
- A61K 31/5375: 1,4-Oxazines, e.g. morpholine
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/06: Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
- A61P 1/14: Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/06: Antihyperlipidemics
- A61P 3/08: for glucose homeostasis (pancreatic hormones A61P5/48)
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/48: of the pancreatic hormones
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/30: for treating abuse or dependence
- A61P 25/32: Alcohol-abuse
- A61P 25/36: Opioid-abuse
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 211/60: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 211/94: Oxygen atom, e.g. piperidine N-oxide
- C07D 211/96: Sulfur atom
- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the ghrelin receptor. The compounds have the general formula (I):

## Claims

### Claim 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.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 3)

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

### Claim 5 (depends on 1)

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

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 1)

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.

### Claim 8 (depends on 7)

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

### Claim 9 (depends on 1)

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.

### Claim 10 (depends on 1)

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

### Claim 11 (depends on 1)

The method of claim 1 for the treatment of gastroparesis.

### Claim 12 (depends on 1)

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.

### Claim 13 (depends on 1)

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.

### Claim 14 (depends on 1)

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.

### Claim 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 R103 substituents;
R1 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 R103 substituents;
R2 is hydrogen;
R3 is selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, aryl, arylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, —C(O)R101, —C(O)OR101, —C(O)NR101R102, —S(O)2R102, —SR101 and —S(O)2NR101R102, optionally substituted with one or more independent R103 substituents;
R4 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, aryl, arylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, —OR103, NR101R102, —C(O)R101, —C(O)OR101, —C(O)NR101R102, -alkylNR101R102, —S(O)2R102, —SR101 and —S(O)2NR101R102, optionally substituted with one or more independent R103 substituents;
R5 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, heteroarylalkyl, oxide (═O), —C(O)R101, —C(O)OR101, —C(O)NR101R102, —S(O)2R102, —SR101 and —S(O)2NR101R102;
R6, R7, R8, R9, R10, R11, R12, R13 and R14 are each independently selected from the group consisting of hydrogen, cyano, —NO2, —OR101, hydroxy, amino, alkyl, alkenyl, cycloalkyl, halogen, alkoxy, alkoxyalkyl, aryl, arylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, —C(O)R101, —C(O)OR101, —C(O)NR101R102, —NR101R102, —NR101S(O)2R102, —NR101C(O)R102, —S(O)2R102, —SR101 and —S(O)2NR101R102, each optionally independently substituted with one or more independent R103 substituents; and
R101, R102 and R103 are each independently selected from the group consisting of hydrogen, cyano, —NO2, —OR104, hydroxy, amino, alkyl, alkenyl, cycloalkyl, halogen, alkoxy, alkoxyalkyl, aryl, arylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, —C(O)R104, —C(O)OR104, —C(O)NR104R105, —NR104R105, —NR104S(O)2R105, —NR104C(O)R105, —S(O)2R104, —SR104 and —S(O)2NR104R105, each optionally independently substituted with one or more independent R103 substituents; or R101, R102, 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 R103 substituents; and
R104 and R105 are each independently selected from the group consisting of hydrogen, cyano, —NO2, hydroxy, hydroxyalkyl, amino, alkyl, alkenyl, cycloalkyl, halogen, alkoxy, alkoxyalkyl, aryl, arylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl and heteroarylalkyl.

### Claim 16 (depends on 15)

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

### Claim 17 (depends on 16)

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

### Claim 18 (depends on 16)

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

### Claim 19 (depends on 16)

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

### Claim 20 (depends on 15)

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

### Claim 21 (depends on 15)

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.

### Claim 22 (depends on 21)

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

### Claim 23 (depends on 15)

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.

### Claim 24 (depends on 22)

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

### Claim 25 (depends on 15)

The method of claim 15, wherein R is aryl.

### Claim 26 (depends on 15)

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.

### Claim 27 (depends on 15)

The method of claim 15, wherein R1 is selected from the group consisting of alkoxy, alkoxyalkyl, —OR101, hydroxy, hydroxyalkyl, amino, alkyl, alkenyl, cycloalkyl, aryl, arylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl and heteroarylalkyl.

### Claim 28 (depends on 15)

The method of claim 15, wherein R1 is selected from the group consisting of alkyl, cycloalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl and heteroarylalkyl.

### Claim 29 (depends on 15)

The method of claim 15, wherein R1 is selected from the group consisting of methyl, —CH2OH, and —CH2—O—CH2-phenyl.

### Claim 30 (depends on 15)

The method of claim 15, wherein R3 is hydrogen, alkyl or cycloalkyl.

### Claim 31 (depends on 15)

The method of claim 15, wherein R4 is selected from the group consisting of alkyl, cycloalkyl, hydroxy, amino, alkoxy, alkylamino, aryl, arylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl and aminoalkyl.

### Claim 32 (depends on 15)

The method of claim 15, wherein R4 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.

### Claim 33 (depends on 15)

The method of claim 15, wherein R5 is selected from the group consisting of alkyl, cycloalkyl, oxide (═O), aryl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, —C(O)R101, —C(O)OR101 and —C(O)NR101R102.

### Claim 34 (depends on 15)

The method of claim 15, wherein R5 is methyl.

### Claim 35 (depends on 15)

The method of claim 15, wherein R6, R7, R8, R9, R10, R11, R12, R13 and R14 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, —C(O)OR101, and -alkylOR103.

### Claim 36 (depends on 15)

The method of claim 15, wherein R8 and R9 are each independently hydrogen, alkyl, cycloalkyl, —C(O)OR101, or -alkylOR103.

### Claim 37 (depends on 15)

The method of claim 15, wherein R8 and R9 are each independently hydrogen, methyl, ethyl, —C(═O)OEt, or —CH2OH.

### Claim 38 (depends on 15)

The method of claim 15 for the treatment of gastroparesis.

### Claim 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.

### Claim 40 (depends on 39)

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.

### Claim 41 (depends on 39)

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

### Claim 42 (depends on 40)

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

### Claim 43 (depends on 40)

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

### Claim 44 (depends on 39)

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

### Claim 45 (depends on 39)

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.

### Claim 46 (depends on 39)

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

### Claim 47 (depends on 39)

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.

### Claim 48 (depends on 39)

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

### Claim 49 (depends on 39)

The method of claim 39 for the treatment of gastroparesis.