Asymmetric ureas and medical uses thereof
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):
1. A compound of 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)R 101 , —C(O)NR 101 R 102 , -alkylNR 101 R 102 , —S(O) 2 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.
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R is aryl.
3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, 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.
4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, 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.
5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from the group consisting of alkyl, cycloalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl and heteroarylalkyl.
6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from the group consisting of methyl, —CH 2 OH, and —CH 2 —O—CH 2 -phenyl.
7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is hydrogen, alkyl or cycloalkyl.
8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is selected from the group consisting of alkyl, cycloalkyl, hydroxy, amino, alkoxy, alkylamino, aryl, arylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl and aminoalkyl.
9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, 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.
10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, 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 .
11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is methyl.
12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, 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 .
13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 8 and R 9 are each independently hydrogen, alkyl, cycloalkyl, —C(O)OR 101 , or -alkylOR 103 .
14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 8 and R 9 are each independently hydrogen, methyl, ethyl, —C(═O)OEt, or —CH 2 OH.
15. A compound selected from the group consisting of 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,
GA8
3-(1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-methyl- 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-difluoro-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-(benzylamino)-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- methylpiperidin-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,
GA200
3-(1-(2,3-dichloro-4- methoxyphenyl)ethyl)-1-methyl-1- (1,3,3-trimethylpiperidin-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.
16. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 , and one or more pharmaceutically acceptable excipients.
17. 3-(1-(2,3-dichloro-4-methoxyphenyl)ethyl)-1-methyl-1-(1,3,3-trimethylpiperidin-4-yl)urea (GA23), or a pharmaceutically acceptable salt thereof.
18. 1-hydroxy-3-(1-(4-methoxynaphthalen-1-yl)ethyl)-1-(1-methylpiperidin-4-yl)urea (GA168), or a pharmaceutically acceptable salt thereof.
19. 3-(1-(2,3-dichloro-4-methoxyphenyl)ethyl)-1-hydroxy-1-(1-methylpiperidin-4-yl)urea (GA180), or a pharmaceutically acceptable salt thereof.