COMPOUNDS AND COMPOSITIONS AS MODULATORS OF GPR119 ACTIVITY
The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of GPR119.
1 . A compound of Formula I:
in which:
Q is a divalent or trivalent radical selected from C 6-10 aryl, C 1-10 heteroaryl, C 3-8 cycloalkyl and C 3-8 heterocycloalkyl; wherein said aryl, heteroaryl, cycloalkyl or heterocycloalkyl of Q is optionally substituted with up to 3 radicals independently selected from halo, C 1-6 alkyl, halo-substituted-C 1-6 alkyl, C 1-6 alkoxy, halo-substituted-C 1-6 alkoxy, —C(O)R 20 and —C(O)OR 20 ; wherein R 20 is selected from hydrogen and C 1-6 alkyl; and optionally connecting a carbon adjacent to W 2 through a CR 31 , O, S or NR 31 with a carbon of Q to form a 5-membered ring fused to rings A and Q; wherein R 31 is selected from hydrogen and C 1-6 alkyl;
W 1 and W 2 are independently selected from CR 21 and N; wherein R 21 is selected from hydrogen, cyano, C 1-6 alkyl and —C(O)OR 25 ; wherein R 25 is selected from hydrogen and C 1-6 alkyl; ring A can have up to 2 ring carbons substituted with a group selected from —C(O)—, —C(S)— and —C(═NOR 30 )— and can be partially unsaturated with up to 2 double bonds; wherein R 30 is selected from hydrogen and C 1-6 alkyl;
L is selected from C 1-6 alkylene, C 2-6 alkenylene, —(CH 2 ) n O—, —OC(O)(CH 2 ) n —, —C(O)O(CH 2 ) n —, —NR 26 (CH 2 ) n — and — 0 (CH 2 ) n —; wherein R 26 is selected from hydrogen and C 1-6 alkyl; and n is selected from 0, 1, 2, 3, 4 and 5; wherein any alkyl of L can be optionally substituted with 1 to 3 radicals independently selected from halo, C 1-6 alkyl, halo-substituted-C 1-6 alkyl, C 1-6 alkoxy, halo-substituted-C 1-6 alkoxy, —C(O)R 22 and —C(O)OR 22 ; wherein R 22 is selected from hydrogen and C 1-6 alkyl;
m is selected from 0, 1, 2, 3 and 4;
q is selected from 0, 1, 2, 3 and 4;
t 1 t 2 , t 3 and t 4 are each independently selected from 0, 1 and 2;
R 1 is selected from —X 1 S(O) 0-2 X 2 R 6a , —X 1 S(O) 0-2 X 2 OR 6a , —X 1 S(O) 0-2 X 2 C(O)R 6a , —X 1 S(O) 0-2 X 2 C(O)OR 6a , —X 1 S(O) 0-2 X 2 OC(O)R 6a and —X 1 S(O) 0-2 NR 6a R 6b ; wherein X 1 is selected from a bond, O, NR 7a R 7b and C 1-4 alkylene; X 2 is selected from a bond and C 1-4 alkylene; R 6a is selected from hydrogen, halo, C 1-6 alkyl, C 2-6 alkenyl, C 6-10 aryl, C 1-10 heteroaryl, C 3-8 heterocycloalkyl and C 3-8 cycloalkyl; wherein said aryl, heteroaryl, cycloalkyl and heterocycloalkyl of R 6a is optionally substituted with 1 to 3 radicals independently selected from hydroxy, halo, C 1-6 alkyl, halo-substituted-C 1-6 alkyl, hydroxy-substituted-C 1-6 alkyl, cyano-substituted-C 1-6 alkyl, C 1-6 alkoxy, halo-substituted-C 1-6 alkoxy and C 6-10 aryl-C 1-4 alkoxy; R 6b is selected from hydrogen and C 1-6 alkyl; and R 7a and R 7b are independently selected from hydrogen and C 1-6 alkyl;
R 2 and R 3 are independently selected from hydrogen, halo, hydroxy, C 1-6 alkyl, halo-substituted-C 1-6 alkyl, hydroxy-substituted-C 1-6 alkyl, C 1-6 alkoxy, halo-substituted-C 1-6 alkoxy, —C(O)R 23 , and —C(O)OR 23 ; wherein R 23 is selected from hydrogen and C 1-6 alkyl;
R 4 is selected from R 8 and —C(O)OR 8 ; wherein R 8 is selected from C 1-6 alkyl, C 6-10 aryl, C 1-10 heteroaryl, C 3-8 cycloalkyl and C 3-8 heterocycloalkyl; wherein said aryl, heteroaryl, cycloalkyl or heterocycloalkyl of R 8 is optionally substituted with 1 to 3 radicals independently selected from halo, C 1-6 alkyl, C 3-8 cycloalkyl, C 3-8 heterocycloalkyl, halo-substituted-C 1-6 alkyl, hydroxy-substituted-C 1-6 alkyl, C 1-6 alkoxy and halo-substituted-C 1-6 alkoxy;
R 5 is selected from hydrogen, C 1-6 alkyl, halo-substituted-C 1-6 alkyl, hydroxy-substituted-C 1-6 alkyl, C 1-6 alkoxy and halo-substituted-C 1-6 alkoxy; or the pharmaceutically acceptable salts thereof.
2 . The compound of claim 1 of Formula Ia:
in which:
Q is a divalent or trivalent radical selected from C 6-10 aryl, C 1-10 heteroaryl, C 3-8 cycloalkyl and C 3-8 heterocycloalkyl; wherein said aryl, heteroaryl, cycloalkyl or heterocycloalkyl of Q is optionally substituted with up to 3 radicals independently selected from halo, C 1-6 alkyl, halo-substituted-C 1-6 alkyl, C 1-6 alkoxy, halo-substituted-C 1-6 alkoxy, —C(O)R 20 and —C(O)OR 20 ; wherein R 20 is selected from hydrogen and C 1-6 alkyl; and optionally connecting a carbon adjacent to W 2 through a CR 31 or O with a carbon of Q to form a 5-membered ring fused to rings A and Q; wherein R 31 is selected from hydrogen and C 1-6 alkyl;
W 1 and W 2 are independently selected from CR 21 and N; wherein R 21 is selected from hydrogen, cyano, C 1-6 alkyl and —C(O)OR 25 ; wherein R 25 is selected from hydrogen and C 1-6 alkyl; ring A can have up to 2 ring carbons substituted with a group selected from —C(O)—, —C(S)— and —C(═NOR 30 )— and can be partially unsaturated with up to 2 double bonds; wherein R 30 is selected from hydrogen and C 1-6 alkyl;
L is selected from C 1-6 alkylene, C 2-6 alkenylene, —(CH 2 ) n O—, —NR 26 (CH 2 ) n —, —OC(O)(CH 2 ) n —, —C(O)O(CH 2 ) n — and —O(CH 2 ) n —; wherein R 26 is selected from hydrogen and C 1-6 alkyl; wherein n is selected from 0, 1, 2, 3, 4 and 5; wherein any alkyl of L can be optionally substituted with 1 to 3 radicals independently selected from halo, C 1-6 alkyl, halo-substituted-C 1-6 alkyl, C 1-6 alkoxy, halo-substituted-C 1-6 alkoxy, —C(O)R 22 and —C(O)OR 22 ; wherein R 22 is selected from hydrogen and C 1-6 alkyl;
t 1 and t 2 are each independently selected from 0, 1 and 2;
q is selected from 0, 1, 2, 3 and 4;
R 1 is selected from —X 1 S(O) 0-2 X 2 R 6a , —X 1 S(O) 0-2 X 2 OR 6a , —X 1 S(O) 0-2 X 2 C(O)OR 6a , —X 1 S(O) 0-2 X 2 OC(O)R 6a and —X 1 S(O) 0-2 NR 6a R 6b ; wherein X 1 is selected from a bond, O, NR 7a R 7b and C 1-4 alkylene; X 2 is selected from a bond and C 1-4 alkylene; R 6a is selected from hydrogen, halo, C 1-6 alkyl, C 2-6 alkenyl, C 6-10 aryl, C 1-10 heteroaryl, C 3-8 heterocycloalkyl and C 3-8 cycloalkyl; wherein said aryl, heteroaryl, cycloalkyl and heterocycloalkyl of R 6a is optionally substituted with 1 to 3 radicals independently selected from hydroxy, halo, C 1-6 alkyl, halo-substituted-C 1-6 alkyl, hydroxy-substituted-C 1-6 alkyl, cyano-substituted-C 1-6 alkyl, C 1-6 alkoxy, halo-substituted-C 1-6 alkoxy and C 6-10 aryl-C 1-4 alkoxy; R 6b is selected from hydrogen and C 1-6 alkyl; and R 7a and R 7b are independently selected from hydrogen and C 1-6 alkyl;
R 3 is selected from hydrogen, halo, hydroxy, C 1-6 alkyl, halo-substituted-C 1-6 alkyl, hydroxy-substituted-C 1-6 alkyl, C 1-6 alkoxy, halo-substituted-C 1-6 alkoxy, —C(O)R 23 , and —C(O)OR 23 ; wherein R 23 is selected from hydrogen and C 1-6 alkyl;
R 4 is selected from R 8 and —C(O)OR 8 ; wherein R 8 is selected from C 1-6 alkyl, C 6-10 aryl, C 1-10 heteroaryl, C 3-8 cycloalkyl and C 3-8 heterocycloalkyl; wherein said aryl, heteroaryl, cycloalkyl or heterocycloalkyl of R 8 is optionally substituted with 1 to 3 radicals independently selected from halo, C 1-6 alkyl, C 3-8 cycloalkyl, C 3-8 heterocycloalkyl, halo-substituted-C 1-6 alkyl, hydroxy-substituted-C 1-6 alkyl, C 1-6 alkoxy and halo-substituted-C 1-6 alkoxy;
R 5 is selected from hydrogen, C 1-6 alkyl, halo-substituted-C 1-6 alkyl, hydroxy-substituted-C 1-6 alkyl, C 1-6 alkoxy and halo-substituted-C 1-6 alkoxy.
3 . The compound of claim 2 in which Q is a divalent or trivalent radical selected from phenyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, 1,2,4-oxadiazolyl, and thiazolyl; wherein said phenyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl and thiazolyl of Q is optionally substituted with up to 3 radicals independently selected from halo, C 1-6 alkyl, C 1-6 alkoxy, halo-substituted-C 1-6 alkyl, —C(O)OR 20 and —C(O)R 20 ; wherein R 20 is selected from hydrogen and C 1-6 alkyl; and optionally connecting a carbon adjacent to W 2 through a CR 31 or O with a carbon of Q to form a 5-membered ring fused to rings A and Q; wherein R 31 is selected from hydrogen and C 1-6 alkyl.
4 . The compound of claim 3 in which: W 1 and W 2 are independently selected from CR 21 and N; wherein R 21 is selected from hydrogen, cyano, C 1-6 alkyl and —C(O)OR 25 ; wherein R 25 is selected from hydrogen and C 1-6 alkyl; with a group selected from —C(O)—, —C(S)— and —C(═NOR 30 )— and can be partially unsaturated with a double bond; wherein R 30 is selected from hydrogen and C 1-6 alkyl; and L is selected from —O(CH 2 ) 0-4 —, —(CH═CH)—, —OC(O)—, —NH(CH 2 ) 0-4 —, —NCH 3 (CH 2 ) 0-4 — and —(CH 2 ) 1-4 —.
5 . The compound of claim 4 in which: R 1 is selected from —X 1 S(O) 0-2 X 2 R 6a , —X 1 S(O) 0-2 X 2 OR 6a , —X 1 S(O) 0-2 X 2 C(O)OR 6a , —X 1 S(O) 0-2 X 2 OC(O)R 6a and —X 1 S(O) 0-2 NR 6a R 6b ; wherein X 1 is selected from a bond and O; X 2 is selected from a bond and C 1-4 alkylene; R 6a is selected from hydrogen, halo, cyano, methyl, ethyl, propyl, isopropyl, ethenyl, pyridinyl, pyrrolidinyl, piperidinyl, morpholino, isoxazolyl, tetrazolyl, phenyl and imidazolyl; wherein said piperidinyl, pyridinyl, pyrrolidinyl, morpholino, isoxazolyl, tetrazolyl, phenyl or imidazolyl of R 6a is optionally substituted with 1 to 3 radicals independently selected from hydroxy, halo, C 1-6 alkyl and benzoxy; and R 6b is selected from hydrogen, methyl and ethyl.
6 . The compound of claim 5 in which: R 4 is selected from R 8 and —C(O)OR 8 ; wherein R 8 is selected from isopropyl, cyclopropyl, t-butyl, 1,2,4-oxadiazolyl, pyrimidinyl, pyridinyl, pyridazinyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, oxetanyl, 2H-tetrazolyl and thiazolyl; wherein said cyclopropyl, 1,2,4-oxadiazolyl, pyrimidinyl, pyridinyl, pyridazinyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, oxetanyl, 2H-tetrazolyl or thiazolyl of R 8 is optionally substituted with 1 to 3 radicals independently selected from halo, trifluoromethyl, isopropyl, t-butyl, methyl, ethyl and cyclopropyl optionally substituted with methyl; and R 5 is selected from hydrogen and methoxy.
7 . The compound of claim 1 selected from: 1-Methylcyclopropyl 4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate, isopropyl 4-((4-((4-methanesulfonylpiperazin)-1-yl)phenoxy)methyl)piperidine-1-carboxylate, isopropyl 4-(2-(4-(4-(methylsulfonyl)piperazin-1-yl)phenoxy)ethyl)piperidine-1-carboxylate, isopropyl 4-(3-(4-(4-(methylsulfonyl)piperazin-1-yl)phenoxy)propyl)piperidine-1-carboxylate, isopropyl 4-(4-(4-(4-(methylsulfonyl)piperazin-1-yl)phenoxy)butyl)piperidine-1-carboxylate, Isopropyl 4-((6-(4-(methylsulfonyl)piperazin-1-yl)pyridin-3-yloxy)methyl)piperidine-1-carboxylate, tert-Butyl 4-((6-(4-(methylsulfonyl)piperazin-1-yl)pyridin-3-yloxy)methyl)piperidine-1-carboxylate, Isopropyl 4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate, tert-Butyl 4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate, 3-Cyclopropyl-5-(4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidin-1-yl)-1,2,4-oxadiazole, 5-Cyclopropyl-3-(4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidin-1-yl)-1,2,4-oxadiazole, 2-(4-(Methylsulfonyl)piperazin-1-yl)-5-((1-(5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)methoxy)pyrazine, 5-Isopropyl-3-(4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidin-1-yl)-1,2,4-oxadiazole, Tetrahydro-2H-pyran-4-yl 4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate, (S)-Tetrahydrofuran-3-yl 4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate, (R)-Tetrahydrofuran-3-yl 4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate, 2-Isopropyl-5-(4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidin-1-yl)thiazole, 2-((1-(2-methyl-2H-tetrazol-5-yl)piperidin-4-yl)methoxy)-5-(4-(methylsulfonyl)piperazin-1-yl)pyrazine, Oxetan-3-yl 4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate, Isopropyl 4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyridin-2-yloxy)methyl)piperidine-1-carboxylate, Isopropyl 4-((6-(4-(methylsulfonyl)piperazin-1-yl)pyridazin-3-yloxy)methyl)piperidine-1-carboxylate, Isopropyl 4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyrimidin-2-yloxy)methyl)piperidine-1-carboxylate, (E)-isopropyl 4-(2-(6-(4-(methylsulfonyl)piperazin-1-yl)pyridin-3-yl)vinyl)piperidine-1-carboxylate, Isopropyl 4-(2-(6-(4-(methylsulfonyl)piperazin-1-yl)pyridin-3-yl)ethyl)piperidine-1-carboxylate, (E)-Isopropyl 4-(2-(2-(4-(methylsulfonyl)piperazin-1-yl)pyrimidin-5-yl)vinyl)piperidine-1-carboxylate, 5-Ethyl-2-(4-((6-(4-(methylsulfonyl)piperazin-1-yl)pyridin-3-yloxy)methyl)piperidin-1-yl)pyrimidine, 1-(Methylsulfonyl)-4-(5-((1-(5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)methoxy)pyridin-2-yl)piperazine, 5-Ethyl-2-(4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidin-1-yl)pyrimidine, 2-((1-(5-Methylpyridin-2-yl)piperidin-4-yl)methoxy)-5-(4-(methylsulfonyl)piperazin-1-yl)pyrazine, 1-Methylcyclopropyl 4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyridin-2-yloxy)methyl)piperidine-1-carboxylate, 5-Ethyl-2-(4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyridin-2-yloxy)methyl)piperidin-1-yl)pyrimidine, 3-Isopropyl-5-(4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidin-1-yl)-1,2,4-oxadiazole, 3-Isopropyl-5-(4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyridin-2-yloxy)methyl)piperidin-1-yl)-1,2,4-oxadiazole, 1-Methylcyclopropyl 4-((6-(4-(methylsulfonyl)piperazin-1-yl)pyridin-3-yloxy)methyl)piperidine-1-carboxylate, 5-Isopropyl-3-(4-((6-(4-(methylsulfonyl)piperazin-1-yl)pyridin-3-yloxy)methyl)piperidin-1-yl)-1,2,4-oxadiazole, 2-((1-(5-Fluoropyridin-2-yl)piperidin-4-yl)methoxy)-5-(4-(methylsulfonyl)piperazin-1-yl)pyrazine, 3-Isopropyl-5-(4-((6-(4-(methylsulfonyl)piperazin-1-yl)pyridin-3-yloxy)methyl)piperidin-1-yl)-1,2,4-oxadiazole, tert-Butyl 4-((5-(4-(methylsulfonyl)-1,4-diazepan-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate, tert-Butyl 4-((5-(4-(methylsulfonyl)-1,4-diazepan-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate, tert-butyl 4-((5-(4-(methylsulfonyl)piperidin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate, 1-Methylcyclopropyl 4-((5-(4-(methylsulfonyl)piperidin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate, tert-Butyl 4-(2-(3-(4-(methylsulfonyl)piperazin-1-yl)-1,2,4-oxadiazol-5-yl)ethyl)piperidine-1-carboxylate, tert-Butyl 4-(3-(3-(4-(methylsulfonyl)piperazin-1-yl)-1,2,4-oxadiazol-5-yl)propyl)piperidine-1-carboxylate, 5-(3-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)propyl)-3-(4-(methylsulfonyl)piperazin-1-yl)-1,2,4-oxadiazole, Isopropyl 4-(3-(3-(4-(methylsulfonyl)piperazin-1-yl)-1,2,4-oxadiazol-5-yl)propyl)piperidine-1-carboxylate, 3-Isopropyl-5-(4-(2-(5-(4-(methylsulfonyl)piperazin-1-yl)thiazol-2-yl)ethyl)piperidin-1-yl)-1,2,4-oxadiazole, Isopropyl 4-((4-(1-methanesulfonyl-1,2,3,6-tetrahydropyridin-4-yl)phenoxy)methyl)piperidine-1-carboxylate, isopropyl 4-(4-(1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)phenoxy)piperidine-1-carboxylate, isopropyl 4-(2-(4-(1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)phenoxy)ethyl)piperidine-1-carboxylate, isopropyl 4-(3-(4-(1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)phenoxy)propyl)piperidine-1-carboxylate, isopropyl 4-(4-(4-(1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)phenoxy)butyl)piperidine-1-carboxylate, 1-methylcyclopropyl 4-((4-(1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)phenoxy)methyl)piperidine-1-carboxylate, 5-isopropyl-3-(4-((4-(1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)phenoxy)methyl)piperidin-1-yl)-1,2,4-oxadiazole, Isopropyl 4-((4-(1-methanesulfonyl)piperidin-4-yl)phenoxy)methyl)piperidine-1-carboxylate, isopropyl 4-(4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)piperidine-1-carboxylate, isopropyl 4-(2-(4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)ethyl)piperidine-1-carboxylate, isopropyl 4-(3-(4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)propyl)piperidine-1-carboxylate, isopropyl 4-(4-(4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)butyl)piperidine-1-carboxylate, 1-Methylcyclopropyl 4-((4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidine-1-carboxylate, 2-(4-((4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidin-1-yl)-5-(trifluoromethyl)pyridine, 5-isopropyl-3-(4-((4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidin-1-yl)-1,2,4-oxadiazole, 3-chloro-2-(4-((4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidin-1-yl)-5-(trifluoromethyl)pyridine, 5-chloro-2-(4-((4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidin-1-yl)pyridine, 3-chloro-6-(4-((4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidin-1-yl)pyridazine, 5-bromo-2-(4-((4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidin-1-yl)pyrimidine, 5-ethyl-2-(4-((4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidin-1-yl)pyrimidine, 5-fluoro-2-(4-((4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidin-1-yl)pyridine, 3-isopropyl-5-(4-((4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidin-1-yl)-1,2,4-oxadiazole, 3-tert-butyl-6-(4-((4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidin-1-yl)pyridazine, 5-fluoro-2-(4-((4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidin-1-yl)pyrimidine, Isopropyl 4-(2-(3-(1-methanesulfonyl-1,2,3,6-tetrahydropyridin-4-yl)phenoxy)ethyl)piperidine-1-carboxylate, 1-Methylcyclopropyl 4-methoxy-4-((5-(4-(methylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate, 1-methylcyclopropyl 4-((6-formyl-5-(4-(methylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate, 1-Methylcyclopropyl 4-((6-chloro-5-(4-(methylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate, 1-Methylcyclopropyl 4-((5-(4-(3-methoxy-3-oxopropylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate, 3-(4-(5-((1-((1-methylcyclopropoxy)carbonyl)-piperidin-4-yl)methoxy)pyrazin-2-yl)piperazin-1-ylsulfonyl)propanoic acid, 3-(4-(5-((1-((1-methylcyclopropoxy)carbonyl)piperidin-4-yl)methoxy)pyrazin-2-yl)piperazin-1-ylsulfonyl)propanoic acid, 3-(4-(5-((1-((1-methylcyclopropoxy)carbonyl)piperidin-4-yl)methoxy)pyrazin-2-yl)piperazin-1-ylsulfonyl)propanoic acid, 3-(4-(5-((1-((1-methylcyclopropoxy)carbonyl)piperidin-4-yl)methoxy)pyrazin-2-yl)piperazin-1-ylsulfonyl)propanoic acid, 3-(4-(5-((1-((1-methylcyclopropoxy)carbonyl)piperidin-4-yl)methoxy)pyrazin-2-yl)piperazin-1-ylsulfonyl)propanoic acid, 3-(4-(5-((1-((1-methylcyclopropoxy)carbonyl)piperidin-4-yl)methoxy)pyrazin-2-yl)piperazin-1-ylsulfonyl)propanoic acid; 1-methylcyclopropyl 4-((5-(4-(3-cyanopropylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((5-(4-(3-(1H-tetrazol-5-yl)propylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((5-(4-(vinylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((5-(4-(2-(piperidin-1-yl)ethylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((5-(4-(2-morpholinoethylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((5-(4-(2-(dimethylamino)ethylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; tert-butyl 4-((5-(4-(3-chloropropylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; tert-butyl 4-((5-(4-(3-acetoxypropylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((5-(4-(3-aminopropylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((5-(4-(2-ethoxyethylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((5-(4-(3-(pyrrolidin-1-yl)propylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((5-(4-(3-(2-methyl-1H-imidazol-1-yl)propylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((5-(4-(3-(dimethylamino)propylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((5-(4-(propylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((5-(4-(ethylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((5-(4-(isopropylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((5-(4-(isobutylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((5-(4-(sec-butylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((5-(4-(3-acetoxy-2,2-dimethylpropylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((5-(4-(3-hydroxy-2,2-dimethylpropylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-Methylcyclopropyl 4-((5-(4-(2-(pyridin-3-yl)ethylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-Methylcyclopropyl 4-((5-(4-(2-(pyridin-4-yl)ethylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-Methylcyclopropyl 4-((5-(4-sulfamoylpiperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; tert-Butyl 4-((5-(4-(morpholinosulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((6-(4-(ethylsulfonyl)piperazin-1-yl)pyridin-3-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((6-(4-(ethylsulfonyl)piperazin-1-yl)pyridin-3-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((6-(4-(ethylsulfonyl)piperazin-1-yl)pyridin-3-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((6-(4-(ethylsulfonyl)piperazin-1-yl)pyridin-3-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((6-(4-(ethylsulfonyl)piperazin-1-yl)pyridin-3-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((6-(4-(ethylsulfonyl)piperazin-1-yl)pyridin-3-yloxy)methyl)piperidine-1-carboxylate; 1-Methylcyclopropyl 4-((5-fluoro-6-(4-(methylsulfonyl)piperazin-1-yl)pyridin-3-yloxy)methyl)piperidine-1-carboxylate; tert-Butyl 4-((5-(4-(methylsulfonyl)-2-oxopiperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-Methylcyclopropyl 4-((5-(4-(methylsulfonyl)-2-oxopiperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-Methylcyclopropyl 4-((5-(2-oxo-4-(propylsulfonyl)piperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-Methylcyclopropyl 4-((5-(4-(isopropylsulfonyl)-2-oxopiperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-Methylcyclopropyl 4-((5-(4-(isopropylsulfonyl)-2-oxopiperazin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((6-(2-oxo-4-(propylsulfonyl)piperazin-1-yl)pyridin-3-yloxy)methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-((6-(4-(isopropylsulfonyl)-2-oxopiperazin-1-yl)pyridin-3-yloxy)methyl)piperidine-1-carboxylate; 1-(5-((1-(5-Ethylpyrimidin-2-yl)piperidin-4-yl)methoxy)pyrazin-2-yl)-4-(methylsulfonyl)piperazin-2-one; 1-(5-((1-(5-Ethylpyrimidin-2-yl)piperidin-4-yl)methoxy)pyridin-2-yl)-4-(methylsulfonyl)piperazin-2-one; tert-Butyl 4-((2,6-difluoro-4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidine-1-carboxylate; tert-butyl 4-((2-methyl-4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidine-1-carboxylate; tert-butyl 4-((3-methoxy-4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidine-1-carboxylate; tert-butyl 4-((2,6-dimethyl-4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidine-1-carboxylate; tert-butyl 4-((2,5-dimethyl-4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidine-1-carboxylate; tert-butyl 4-((2-(methoxycarbonyl)-4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidine-1-carboxylate; tert-butyl 4-((2-chloro-4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidine-1-carboxylate; tert-butyl 4-((3-methyl-4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidine-1-carboxylate; tert-butyl 4-((2,3-dimethyl-4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidine-1-carboxylate; tert-butyl 4-((2-fluoro-4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidine-1-carboxylate; tert-butyl 4-((4-(1-(methylsulfonyl)piperidin-4-yl)-2-(trifluoromethyl)phenoxy)methyl)piperidine-1-carboxylate; 2-(4-((2,6-Difluoro-4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidin-1-yl)-5-ethylpyrimidine; 1-Methylcyclopropyl 4-((2,6-difluoro-4-(1-(methylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidine-1-carboxylate; 3-(4-(4-((1-(5-Ethylpyrimidin-2-yl)piperidin-4-yl)methoxy)-3,5-difluorophenyl)piperidin-1-ylsulfonyl)propyl acetate; 1-Methylcyclopropyl 4-((4-(1-(3-acetoxypropylsulfonyl)piperidin-4-yl)-2,6-difluorophenoxy)methyl)piperidine-1-carboxylate; 3-(4-(4-((1-(5-Ethylpyrimidin-2-yl)piperidin-4-yl)methoxy)-3,5-difluorophenyl)piperidin-1-ylsulfonyl)propan-1-ol; 1-Methylcyclopropyl 4-((2,6-difluoro-4-(1-(3-hydroxypropylsulfonyl)piperidin-4-yl)phenoxy)methyl)piperidine-1-carboxylate; Isopropyl 4-((5-(1,2,3,6-tetrahydro-1-methanesulfonylpyridin-4-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate; 1-Methylcyclopropyl 4-((6-(1,2,3,6-tetrahydro-1-methanesulfonylpyridin-4-yl)pyridin-3-yloxy)methyl)piperidine-1-carboxylate; Isopropyl 4-(2-(6-(1,2,3,6-tetrahydro-1-methanesulfonylpyridin-4-yl)pyridin-3-yloxy)ethyl)piperidine-1-carboxylate; 2-(4-((5-(1,2,3,6-Tetrahydro-1-methanesulfonylpyridin-4-yl)pyrazin-2-yloxy)methyl)piperidin-1-yl)-5-ethylpyrimidine; 2-(4-((6-(1,2,3,6-Tetrahydro-1-methanesulfonylpyridin-4-yl)pyridin-3-yloxy)methyl)piperidin-1-yl)-5-ethylpyrimidine; 2-((1-(5-Ethylpyrimidin-2-yl)piperidin-4-yl)methoxy)-5-(1-methanesulfonylpiperidin-4-yl)pyrazine; 2-(4-((6-(1-Methanesulfonylpiperidin-4-yl)pyridin-3-yloxy)methyl)piperidin-1-yl)-5-ethylpyrimidine; 3-((1-(5-Ethylpyrimidin-2-yl)piperidin-4-yl)methoxy)-6-(1-methanesulfonylpiperidin-4-yl)pyridazine; 2-(4-((5-(1-Methanesulfonylpiperidin-4-yl)pyridin-2-yloxy)methyl)piperidin-1-yl)-5-ethylpyrimidine; 1-tert-Butyl 4-(4-(1-(methylsulfonyl)piperidin-4-yl)phenyl)piperazine-1,4-dicarboxylate; N-((1-(5-Ethylpyrimidin-2-yl)piperidin-4-yl)methyl)-4-(1-(methylsulfonyl)piperidin-4-yl)aniline; N-((1-(5-Ethylpyrimidin-2-yl)piperidin-4-yl)methyl)-N-methyl-4-(1-(methylsulfonyl)piperidin-4-yl)aniline; 4-(4-((1-(5-fluoropyrimidin-2-yl)piperidin-4-yl)methoxy)phenyl)-1-(methyl sulfonyl)piperidine-4-carboxylic acid; 2-[(2-{4-[5-({1-[(1-methylcyclopropoxy)carbonyl]piperidin-4-yl}methoxy)pyrazin-2-yl]-3-oxopiperazine-1-sulfonyl}ethyl)amino]acetic acid; 1-methylcyclopropyl 4-{[(5-{4-[(2-carbamimidamidoethane)sulfonyl]-2-oxopiperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[(3-methyl-3-nitrobutane)sulfonyl]-2-oxopiperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({5-[4-(1-benzylpyrrolidine-3-sulfonyl)-2-oxopiperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[5-{4-[(carbamoylmethane)sulfonyl]-2-oxopiperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[(1-carbamoyl-1-methylethane)sulfonyl]-2-oxopiperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(2-oxo-4-{[2-(pyrrolidin-1-yl)ethane]sulfonyl}piperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[2-(morpholin-4-yl)ethane]sulfonyl}-2-oxopiperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[3-(dimethylamino)propane]sulfonyl}-2-oxopiperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[2-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)ethane]sulfonyl}-2-oxopiperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[(dimethylcarbamoyl)methane]sulfonyl}-2-oxopiperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[1-(2-methylpropyl)pyrrolidine-3-sulfonyl]-2-oxopiperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(2-oxo-4-{[3-(1H-pyrazol-1-yl)propane]sulfonyl}piperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({5-[2-oxo-4-(pyrrolidine-3-sulfonyl)piperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[(2-amino-2-methylpropane)sulfonyl]-2-oxopiperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[(1-methylpyrrolidin-3-yl)methane]sulfonyl}-2-oxopiperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[2-(azetidin-1-yl)ethane]sulfonyl}-2-oxopiperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(2-oxo-4-{[2-(1H-pyrazol-1-yl)ethane]sulfonyl}piperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({5-[4-(1-methylpyrrolidine-3-sulfonyl)-2-oxopiperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[1-(dimethylcarbamoyl)-1-methylethane]sulfonyl}-2-oxopiperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[2-(3,3-difluoroazetidin-1-yl)ethane]sulfonyl}-2-oxopiperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[3-(dimethylamino)-3-methylbutane]sulfonyl}-2-oxopiperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[(2-{[2-(tert-butoxy)-2-oxoethyl]amino}ethane)sulfonyl]-2-oxopiperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({5-[4-(azetidine-3-sulfonyl)-2-oxopiperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[3-(3,3-difluoroazetidin-1-yl)propane]sulfonyl}-2-oxopiperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[3-(azetidin-1-yl)propane]sulfonyl}-2-oxopiperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{2-oxo-4-[(3S)-pyrrolidine-3-sulfonyl]piperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[(3S)-1-methylpyrrolidine-3-sulfonyl]piperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[(3R)-1-methylpyrrolidine-3-sulfonyl]piperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[(3S)-pyrrolidine-3-sulfonyl]piperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[(3R)-pyrrolidine-3-sulfonyl]piperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({5-[4-(azetidine-3-sulfonyl)piperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{2-oxo-4-[(pyrrolidin-3-ylmethane)sulfonyl]piperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({5-[4-(1-hydroxy-2-methylpropane-2-sulfonyl)piperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[(2-hydroxyethane)sulfonyl]piperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[(azetidin-3-ylmethane)sulfonyl]piperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[(1-methylpyrrolidin-2-yl)methane]sulfonyl}-2-oxopiperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{2-oxo-4-[(3R)-pyrrolidine-3-sulfonyl]piperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({5-[4-(1-methylazetidine-3-sulfonyl)piperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({5-[4-(1-methylazetidine-3-sulfonyl)-2-oxopiperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[(1-methylazetidin-3-yl)methane]sulfonyl}-2-oxopiperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[(1-methylazetidin-3-yl)methane]sulfonyl}piperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({5-[4-({3-[(3S,4S)-3,4-dihydroxypyrrolidin-1-yl]propane}sulfonyl)-2-oxopiperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({5-[4-({2-[(3S,4S)-3,4-dihydroxypyrrolidin-1-yl]ethane}sulfonyl)-2-oxopiperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[(azetidin-3-ylmethane)sulfonyl]-2-oxopiperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{2-oxo-4-[(pyrrolidin-2-ylmethane)sulfonyl]piperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[(3-aminopropane)sulfonyl]-2-oxopiperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[(2-aminoethane)sulfonyl]-2-oxopiperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(3-methanesulfonamidoazetidin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[2-(dimethylamino)ethane]sulfonyl}-2-oxopiperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(2-oxo-4-{[3-(pyrrolidin-1-yl)propane]sulfonyl}piperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[3-(morpholin-4-yl)propane]sulfonyl}-2-oxopiperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[(3-methyloxetan-3-yl)methane]sulfonyl}piperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[3-(acetyloxy)propane]sulfonyl}-2-oxopiperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[3,3,3-trifluoropropane)sulfonyl]piperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({5-[(2E)-2-(hydroxyimino)-4-methanesulfonylpiperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[(3-chloropropane)sulfonyl]-2-oxopiperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[(3-hydroxypropane)sulfonyl]-2-oxopiperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({5-[4-({[1-(dimethylamino)cyclopropyl]methane}sulfonyl)-2-oxopiperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({5-[4-({[1-(dimethylamino)cyclopropyl]methane}sulfonyl)piperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[(3-hydroxy-3-methylbutane)sulfonyl]piperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{2-oxo-4-[(3R)-oxolane-3-sulfonyl]piperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{2-oxo-4-[(3S)-oxolane-3-sulfonyl]piperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[3-(acetyloxy)-3-methylbutane]sulfonyl}piperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({6-[4-({[1-(azetidin-1-yl)cyclopropyl]methane}sulfonyl)piperazin-1-yl]pyridin-3-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({5-[4-({[1-(benzylamino)cyclopropyl]methane}sulfonyl)piperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({5-[4-({[1-(azetidin-1-yl)cyclopropyl]methane}sulfonyl)piperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[(1-hydroxycyclopropyl)methane]sulfonyl}piperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[2-(1-hydroxycyclopropyl)ethane]sulfonyl}piperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({5-[4-({2-[1-(acetyloxy)cyclopropyl]ethane}sulfonyl)piperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({5-[4-({[1-(benzyloxy)cyclopropyl]methane}sulfonyl)piperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[(1-aminocyclopropyl)methane]sulfonyl}piperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[2-(1-hydroxycyclopropyl)ethane]sulfonyl}-2-oxopiperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-{2,6-difluoro-4-[3-(N-methylmethanesulfonamido)azetidin-1-yl]phenoxymethyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-[2,6-difluoro-4-(3-methanesulfonamidoazetidin-1-yl)phenoxymethyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-{2,6-difluoro-4-[3-(2-methylpropane-1-sulfonamido)azetidin-1-yl]phenoxymethyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-{4-[3-(N,2-dimethylpropane-1-sulfonamido)azetidin-1-yl]-2,6-difluorophenoxymethyl}piperidine-1-carboxylate; 5-ethyl-2-{4-[({2-methanesulfonyl-1H,2H,3H,4H-pyrazino[1,2-a]indol-8-yl}oxy)methyl]piperidin-1-yl}pyrimidine; 11-{[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]oxy}-5-methanesulfonyl-8-oxa-5-azatricyclo[7.4.0.0{2,7}]-trideca-1(13),2(7),9,11-tetraene; 11-{[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]methoxy}-5-methanesulfonyl-8-oxa-5-azatricyclo[7.4.0.0{2,7}]-trideca-1(13),2(7),9,11-tetraene; tert-butyl 4-[({2-methanesulfonyl-1H,2H,3H,4H-pyrazino[1,2-a]indol-8-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({2-methanesulfonyl-1H,2H,3H,4H-pyrazino[1,2-a]indol-8-yl}oxy)methyl]piperidine-1-carboxylate; propan-2-yl 4-{3-[3-(1-methanesulfonylpiperidin-4-yl)phenoxy]propyl}piperidine-1-carboxylate; propan-2-yl 4-{2-[3-(1-methanesulfonylpiperidin-4-yl)phenoxy]ethyl}piperidine-1-carboxylate; propan-2-yl 4-[3-(1-methanesulfonylpiperidin-4-yl)phenoxymethyl]piperidine-1-carboxylate; propan-2-yl 4-{3-[3-(1-methanesulfonyl-1,2,3,6-tetrahydropyridin-4-yl)phenoxy]propyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-methanesulfonyl-2-sulfanylidenepiperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl (3S,4S)-3-hydroxy-4-{[(6-{4-[(2-methylpropane)sulfonyl]piperazin-1-yl}pyridin-3-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl (3R,4S)-3-hydroxy-4-{[(6-{4-[(2-methylpropane)sulfonyl]piperazin-1-yl}pyridin-3-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-hydroxy-4-{[(6-{4-[(2-methylpropane)sulfonyl]piperazin-1-yl}pyridin-3-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(6-{4-[(2-hydroxy-2-methylpropane)sulfonyl]piperazin-1-yl}pyridin-3-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl (3S,4R)-3-methoxy-4-{[(6-{4-[(2-methylpropane)sulfonyl]piperazin-1-yl}pyridin-3-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[3-(3,3-difluoroazetidin-1-yl)propane]sulfonyl}piperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[3-(azetidin-1-yl)propane]sulfonyl}piperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(5-{4-[3-methoxypropane)sulfonyl]piperazin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(6-{4-[(3-chloropropane)sulfonyl]-2-oxopiperazin-1-yl}pyridin-3-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[2-(azetidin-1-yl)ethane]sulfonyl}piperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[6-(4-{[3-(azetidin-1-yl)propane]sulfonyl}piperazin-1-yl)pyridin-3-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-[({5-[4-(pyrrolidine-3-sulfonyl)piperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[5-(4-{[2(3,3-difluoroazetidin-1-yl)ethane]sulfonyl}piperazin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-{[(6-{4-[(3-hydroxypropane)sulfonyl]-2-oxopiperazin-1-yl}pyridin-3-yl)oxy]methyl}piperidine-1-carboxylate; 1-methylcyclopropyl 4-({[6-(4-{[3-(azetidin-1-yl)propane]sulfonyl}-2-oxopiperazin-1-yl)pyridin-3-yl]oxy}methyl)piperidine-1-carboxylate; 1-methylcyclopropyl 4-[2,6-difluoro-4-(4-methanesulfonyl-2-oxopiperazin-1-yl)phenoxymethyl]piperidine-1-carboxylate; and 1-methylcyclopropyl 4-[({5-[4-(oxetane-3-sulfonyl)-2-oxopiperazin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate.
8 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically acceptable excipient.
9 . A method for modulating GPR119 activity, comprising administering to a system or a subject in need thereof, a therapeutically effective amount of the compound of claim 1 or pharmaceutically acceptable salts or pharmaceutical compositions thereof, thereby modulating said GPR119 activity.
10 . The method of claim 9 , wherein the compound of claim 1 directly contacts GPR119.
11 . The method of claim 10 , wherein the contacting occurs in vitro or in vivo.
12 . A method for treating a disease or condition wherein modulation of GPR119 activity can prevent, inhibit or ameliorate the pathology and/or symptomology of the disease or condition, comprising administering to a subject a therapeutically effective amount of the compound of claim 1 or pharmaceutically acceptable salts or pharmaceutical compositions thereof.
13 . The method of claim 12 , wherein said disease or condition is selected from obesity, type 1 diabetes, type 2 diabetes mellitus, hyperlipidemia, idiopathic type 1 diabetes, latent autoimmune diabetes in adults, early-onset type 2 diabetes, youth-onset atypical diabetes, maturity onset diabetes of the young, malnutrition-related diabetes and gestational diabetes.
14 . The method of claim 12 , wherein said disease or condition is selected from coronary heart disease, ischemic stroke, restenosis after angioplasty, peripheral vascular disease, intermittent claudication, myocardial infarction, dyslipidemia, post-prandial lipemia, conditions of impaired glucose tolerance, conditions of impaired fasting plasma glucose, metabolic acidosis, ketosis, arthritis, osteoporosis, hypertension, congestive heart failure, left ventricular hypertrophy, peripheral arterial disease, diabetic retinopathy, macular degeneration, cataract, diabetic nephropathy, glomerulosclerosis, chronic renal failure, diabetic neuropathy, metabolic syndrome, syndrome X, premenstrual syndrome, coronary heart disease, angina pectoris, thrombosis, atherosclerosis, myocardial infarction, transient ischemic attacks, stroke, vascular restenosis, hyperglycemia, hyperinsulinemia, hyperlipidemia, hypertrygliceridemia, insulin resistance, impaired glucose metabolism, conditions of impaired glucose tolerance, conditions of impaired fasting plasma glucose, obesity, erectile dysfunction, skin and connective tissue disorders, foot ulcerations and ulcerative colitis, endothelial dysfunction and impaired vascular compliance.