Oxadiazole compounds

Abstract

The present invention relates to a compound of formula (I) or (II) or a stereoisomer, enantiomer, racemic, or tautomer thereof, (I) (II) wherein R 1 , R 2 , R 3 , L 1 , L 2 , L 3 , L 4 , L 5 and n, have the same meaning as that defined in the claims and the description. The present invention also relates to compositions, in particular pharmaceuticals, comprising such compounds, and to uses of such compounds and compositions for the prevention and/or treatment of metabolic disorders and/or neurodegenerative diseases, an protein misfolding disorders.

1 . A compound of formula (I) or (II); or a stereoisomer, enantiomer, racemic, or tautomer thereof, 
       
         
           
           
               
               
           
         
         wherein, 
         n is an integer selected from 0, 1, 2 or 3; 
         R 1  is selected from the group consisting of C 1-6  alkyl, halo, haloC 1-6  alkyl, and haloC 1-6 alkyloxy; 
         R 2  is selected from the group consisting of C 6-12  aryl, hydrogen, C 1-6  alkyl, C 3-12 cycloalkyl, heterocyclyl, heteroaryl, C 6-12 arylC 1-6 alkyl, C 6-12 arylC 1-6 alkylC 6-12 aryl, halo, hydroxyl, —OR 15 , —SR 16 , haloC 1-6  alkyl, haloC 1-6  alkyloxy, amino, —NR 17 R 18 , and cyano; and wherein said C 6-12 aryl, C 1-6 alkyl, C 3-12 cycloalkyl, heterocyclyl, heteroaryl, C 6-12 arylC 1-6 alkyl, or C 6-12 arylC 1-6 alkylC 6-12 aryl can be unsubstituted or substituted with one or more Z 1 ; 
         R 3  is selected from the group consisting of C 6-12  aryl, hydrogen, C 1-6  alkyl, C 3-12 cycloalkyl, heterocyclyl, heteroaryl, C 6-12 arylC 1-6 alkyl, C 6-12 arylC 1-6 alkylC 6-12 aryl, halo, hydroxyl, —OR 15 , —SR 16 , haloC 1-6  alkyl, haloC 1-6  alkyloxy, —NR 17 R 18 , and cyano; and wherein said C 6-12  aryl, C 1-6 alkyl, C 3-12 cycloalkyl, heterocyclyl, heteroaryl, C 6-12 arylC 1-6 alkyl, or C 6-12  arylC 1-6 alkylC 6-12 aryl can be unsubstituted or substituted with one or more Z 2 ; 
         L 1  is a single bond, or is a group of formula (i); 
       
       
         
           
           
               
               
           
         
         
           wherein the left side of the group of formula (i) is attached to R 2  and the right side thereof is attached to the oxadiazole ring; and wherein, 
           m is an integer selected from 0, 1, 2, 3 or 4; 
           p is an integer selected from 0, 1, 2, 3 or 4; 
           L 4  is a single bond, or is selected from the group consisting of —O—, and —NR 8 —; 
           R 4  is selected from the group consisting of hydrogen, C 1-6  alkyl, halo, hydroxyl, —OR 15 , —SR 16 , haloC 1-6 alkyl, and haloC 1-6 alkyloxy; 
           R 5  is selected from the group consisting of hydrogen, C 1-6  alkyl, halo, hydroxyl, —OR 15 , —SR 16 , haloC 1-6 alkyl, and haloC 1-6 alkyloxy; 
           or R 4  and R 5  together with the carbon atom to which they are attached form a saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered ring; 
           R 6  is selected from the group consisting of hydrogen, C 1-6  alkyl, halo, hydroxyl, —OR 15 , —SR 16 , haloC 1-6 alkyl, and haloC 1-6 alkyloxy; 
           R 7  is selected from the group consisting of hydrogen, C 1-6  alkyl, halo, hydroxyl, —OR 15 , —SR 16 , haloC 1-6 alkyl, and haloC 1-6 alkyloxy; 
           or R 6  and R 7  together with the carbon atom to which they are attached form a saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered ring; 
           R 8  is selected from the group consisting of hydrogen, and C 1-6 alkyl; 
         
         L 2  is a single bond or is selected from the group consisting of —SO 2 —, —PO 4 —, —PO 3 —, and —(CR 9 R 10 ) q —; wherein,
 q is an integer selected from 1, 2 or 3; 
 R 9  is selected from the group consisting of hydrogen, C 1-6  alkyl, halo, hydroxyl, —OR 15 , —SR 16 , haloC 1-6 alkyl, and haloC 1-6 alkyloxy; 
 R 10  is selected from the group consisting of hydrogen, C 1-6  alkyl, halo, hydroxyl, —OR 15 , —SR 16 , haloC 1-6 alkyl, and haloC 1-6 alkyloxy; 
 or R 9  and R 10 together with the carbon atom to which they are attached form a saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered ring; 
 
         L 3  is a single bond or is selected from the group consisting of —(CR 11 R 12 ) r —, —O—, and —NR 13 —; wherein,
 r is an integer selected from 1, 2 or 3; 
 R 11  is selected from the group consisting of hydrogen, C 1-6  alkyl, halo, hydroxyl, —OR 15 , —SR 16 , haloC 1-6 alkyl, and haloC 1-6 alkyloxy; 
 R 12  is selected from the group consisting of hydrogen, C 1-6  alkyl, halo, hydroxyl, —OR 15 , —SR 16 , haloC 1-6 alkyl, and haloC 1-6 alkyloxy; 
 or R 11  and R 12  together with the carbon atom to which they are attached form a saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered ring; 
 R 13  is selected from the group consisting of hydrogen, and C 1-6 alkyl; 
 wherein at least one of L 2 , L 3  is not a single bond; 
 
         L 5  is a single bond or —CO—; 
         each R 15  is independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6  alkynyl, C 6-12  aryl, C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, C 6-12 arylC 1-6 alkyl, heterocyclyl, heteroaryl, heterocyclylC 1-6 alkyl, heteroarylC 1-6 alkyl, and cyanoC 1-6 alkyl;
 and wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6  alkynyl, C 6-12 aryl, C 3-8 cycloalkyl, C 6-12 arylC 1-6 alkyl, heterocyclyl, heteroaryl, heterocyclylC 1-6 alkyl, heteroarylC 1-6 alkyl, and cyanoC 1-6  alkyl, can be unsubstituted or substituted with one or more Z 1 ; 
 and wherein at least one carbon atom or heteroatom of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-12  aryl, C 3-8 cycloalkyl, C 6-12  arylC 1-6  alkyl, heterocyclyl, heteroaryl, heterocyclylC 1-6 alkyl, heteroarylC 1-6  alkyl, or cyanoC 1-6  alkyl can be oxidized to form at least one C═O, C═S, N═O, N═S, S═O or S(O) 2 ; 
 
         each R 16  is independently selected from the group consisting of hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6 alkynyl, C 6-12 aryl, C 3-8 cycloalkyl, C 6-12 arylC 1-6 alkyl, heterocyclyl, heteroaryl, heterocyclylC 1-6 alkyl, heteroarylC 1-6 alkyl, and cyanoC 1-6 alkyl; and wherein said C 1-6  alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-12 aryl, C 3-8 cycloalkyl, C 6-12 arylC 1-6 alkyl, heterocyclyl, heteroaryl, heterocyclylC 1-6 alkyl, heteroarylC 1-6 alkyl, and cyanoC 1-6 alkyl, can be unsubstituted or substituted with one or more Z 2 ;
 and wherein at least one carbon atom or heteroatom of said C 1-6  alkyl, C 2-6 alkenyl, C 2-6  alkynyl, C 6-12 aryl, C 3-8 cycloalkyl, C 6-12 arylC 1-6 alkyl, heterocyclyl, heteroaryl, heterocyclylC 1-6 alkyl, heteroarylC 1-6  alkyl, or cyanoC 1-6 alkyl can be oxidized to form at least one C═O, C═S, N═O, N═S, S═O or S(O) 2 ; 
 
         each R 17  is independently selected from the group consisting of hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6 alkynyl, C 6-12 aryl, C 3-8 cycloalkyl, C 6-12 arylC 1-6 alkyl, heterocyclyl, heteroaryl, heterocyclylC 1-6 alkyl, and heteroarylC 1-6 alkyl;
 and wherein at least one carbon atom or heteroatom of said C 1-6  alkyl, C 2-6 alkenyl, C 2-6  alkynyl, C 6-12 aryl, C 3-8 cycloalkyl, C 6-12 arylC 1-6 alkyl, heterocyclyl, heteroaryl, heterocyclylC 1-6 alkyl, or heteroarylC 1-6  alkyl can be oxidized to form at least one C═O, C═S, N═O, N═S, S═O or S(O) 2 ; 
 
         each R 18  is independently selected from the group consisting of hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6 alkynyl, C 6-12 aryl, C 3-8 cycloalkyl, C 6-12 arylC 1-6 alkyl, heterocyclyl, heteroaryl, heterocyclylC 1-6 alkyl, and heteroarylC 1-6 alkyl;
 and wherein at least one carbon atom or heteroatom of said C 1-6  alkyl, C 2-6 alkenyl, C 2-6  alkynyl, C 6-12 aryl, C 3-8 cycloalkyl, C 6-12 arylC 1-6 alkyl, heterocyclyl, heteroaryl, heterocyclylC 1-6 alkyl, or heteroarylC 1-6  alkyl can be oxidized to form at least one C═O, C═S, N═O, N═S, S═O or S(O) 2 ; 
 
         or wherein R 17  and R 18  together with the nitrogen atom to which they are attached form a 5-, 6-, or 7-membered heterocyclyl; and wherein at least one carbon atom or heteroatom of said heterocyclyl can be oxidized to form at least one C═O, C═S, N═O, N═S, S═O or S(O) 2 ; 
         each R 19  is independently selected from the group consisting of hydrogen, hydroxyl, C 1-6 alkyl, C 2-6  alkenyl, C 2-6 alkynyl, C 6-12 aryl, C 3-8 cycloalkyl, C 6-12 arylC 1-6 alkyl, heterocyclyl, heteroaryl, heterocyclylC 1-6 alkyl, and heteroarylC 1-6 alkyl;
 wherein at least one carbon atom or heteroatom of said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-12  aryl, C 3-8 cycloalkyl, C 6-12  arylC 1-6  alkyl, heterocyclyl, heteroaryl, heterocyclylC 1-6 alkyl, or heteroarylC 1-6  alkyl can be oxidized to form at least one C═O, C═S, N═O, N═S, S═O or S(O) 2 ; 
 
         each R 20  is independently selected from the group consisting of hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6 alkynyl, C 6-12 aryl, C 3-8 cycloalkyl, C 6-12 arylC 1-6 alkyl, heterocyclyl, heteroaryl, heterocyclylC 1-6 alkyl, and heteroarylC 1-6 alkyl;
 and wherein at least one carbon atom or heteroatom of said C 1-6  alkyl, C 2-6 alkenyl, C 2-6  alkynyl, C 6-12 aryl, C 3-8 cycloalkyl, C 6-12 arylC 1-6 alkyl, heterocyclyl, heteroaryl, heterocyclylC 1-6 alkyl, and heteroarylC 1-6  alkyl can be oxidized to form at least one C═O, C═S, N═O, N═S, S═O or S(O) 2 , 
 
         each R 21  is independently selected from the group consisting of C 1-6 alkylene, C 2-6 alkenylene, C 2-6 alkynylene, C 6-12  arylene, C 3-8 cycloalkylene, C 6-12 aryleneC 1-6 alkylene*, heterocyclylene, heteroarylene, heterocyclyleneC 1-6  alkylene*, and heteroaryleneC 1-6  alkylene*; wherein * represents where R 21  is bound to —CO—;
 and wherein at least one carbon atom or heteroatom of said C 1-6 alkylene, C 2-6 alkenylene, C 2-6  alkynylene, C 6-12 arylene, C 3-8 cycloalkylene, C 6-12 aryleneC 1-6 alkylene, heterocyclylene, heteroarylene, heterocyclyleneC 1-6  alkylene, or heteroaryleneC 1-6  alkylene can be oxidized to form at least one C═O, C═S, N═O, N═S, S═O or S(O) 2 ; 
 
         each Z 1  is independently selected from the group consisting of halo, hydrogen, C 1-6  alkyl, haloC 1-6 alkyl, haloC 1-6 alkyloxy, C 3-12 cycloalkyl, C 6-12 aryl, C 1-6 alkylC 6-12 aryl, heterocyclyl, heterocyclylC 1-6 alkyl, heteroaryl, heteroarylC 1-6 alkyl, hydroxyl, —OR 15 , —SR 16 , cyano, amino, —NR 17 R 18 , —CO 2 R 19 , —C(O)NR 17 R 18 , —C(O)R 19 , —S(O)R 19 , —S(O) 2 R 19 , —SO 2 NR 17 R 18 , nitro, —NR 20 C(O)R 19 , —R 21 —C(O)NR 17 R 18 , —NR 20 S(O) 2 R 19 , and NR 20 C(O)NR 17 R 18 ; and wherein two Z 1  together with the atom to which they are attached can form a 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of said ring, C 1-6  alkyl, C 3-8 cycloalkyl, C 6-12  aryl, C 1-6  alkylC 6-12 aryl, heterocyclyl, heterocyclylC 1-6 alkyl, heteroaryl, or heteroarylC 1-6  alkyl can be oxidized to form at least one C═O, C═S, N═O, N═S, S═O or S(O) 2 ; 
         each Z 2  is independently selected from the group consisting of halo, hydrogen, C 1-6  alkyl, haloC 1-6 alkyl, haloC 1-6 alkyloxy, C 3-12 cycloalkyl, C 6-12 aryl, C 1-6 alkylC 6-12 aryl, heterocyclyl, heterocyclylC 1-6 alkyl, heteroaryl, heteroarylC 1-6 alkyl, hydroxyl, —OR 15 , —SR 16 , cyano, amino, —NR 17 R 18 , —CO 2 R 19 , —C(O)NR 17 R 18 , —C(O)R 19 , —S(O)R 19 , —S(O) 2 R 19 , —SO 2 NR 17 R 18 , nitro, —NR 20 C(O)R 19 , —R 21 —C(O)NR 17 R 18 , —NR 20 S(O) 2 R 19 , and —NR 20 C(O)NR 17 R 18 ; and wherein two Z 2  together with the atom to which they are attached can form a 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of said ring, C 1-6  alkyl, C 3-8 cycloalkyl, C 6-12  aryl, C 1-6  alkylC 6-12 aryl, heterocyclyl, heterocyclylC 1-6 alkyl, heteroaryl, or heteroarylC 1-6 alkyl can be oxidized to form at least one C═O, C═S, N═O, N═S, S═O or S(O) 2 ; 
         and with the proviso that for a compound of formula (I) when R 2  is C 6-12  aryl; L 3  is a single bond, —(CR 11 R 12 ) r —, —O—, or —NR 13 —; then R 3  is not hydrogen, C 1-6 alkyl, hydroxyl, or —OR 15 ; 
         and with the proviso that for a compound of formula (I) when L 1  is a single bond, R 2  is not hydrogen; 
         and with the proviso that said compound is not 
         5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 
         5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 
         3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 
         3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 
         1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 
         5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 
         2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 
         5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 
         3-phenyl-5-(4-(2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 
         5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 
         5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 
         5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 
         5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 
         5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 
         5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 
         5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 
         5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 
         5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 
         5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 
         3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 
         3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 
         3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 
         3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 
         5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 
         3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 
         5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 
         5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 
         5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 
         3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 
         3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 
         5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 
         5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; 
         N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 
         3-(4-bromophenyl)-5-[4-(2-nitrophenyl)sulfonylpiperazin-1-yl]-1,2,4-oxadiazole; 
         5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 
         5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole; 
         or a solvate, hydrate, pharmaceutically acceptable salt, or prodrug thereof. 
       
     
     
         2 . The compound according to  claim 1 , having structural formula (IA) or (IIA), 
       
         
           
           
               
               
           
         
         wherein L 1 , L 3 , L 5 , n, R 1 , R 2  and R 3  have the same meaning as that defined in  claim 1 . 
       
     
     
         3 . The compound according to  claim 1 , having structural formula (IB) or (IIB), 
       
         
           
           
               
               
           
         
         wherein, L 1 , n, R 1 , R 2  and R 3  have the same meaning as that defined in  claim 1 . 
       
     
     
         4 . The compound according to  claim 1 , having structural formula (IC) or (IIC), 
       
         
           
           
               
               
           
         
         wherein, L 3 , n, R 1 , R 2  and R 3  have the same meaning as defined in  claim 1 . 
       
     
     
         5 . The compound according to  claim 1 , having structural formula (ID) or (IID), 
       
         
           
           
               
               
           
         
         wherein, L 3 , n, R 1 , R 2 , R 3 , R 4 , and R 5 , have the same meaning as defined in  claim 1 . 
       
     
     
         6 . The compound according to  claim 1 , having structural formula (IE) or (IIE), 
       
         
           
           
               
               
           
         
         wherein, L 1 , L 2 , L 3 , L 5 , n, R 1 , R 2 , R 3 , and Z 1  have the same meaning as that defined in  claim 1 ; and wherein, w is an integer selected from 1, 2, or 3. 
       
     
     
         7 . The compound according to  claim 1 , having structural formula (IF) or (IIF), 
       
         
           
           
               
               
           
         
         wherein, L 1 , L 3 , L 5 , n, R 1 , R 3 , and Z 1  have the same meaning as that defined in  claim 1 ; and wherein w is an integer selected from 1, 2, or 3. 
       
     
     
         8 . The compound according to  claim 1 , having structural formula (IG) or (IIG), 
       
         
           
           
               
               
           
         
         wherein, L 2 , L 3 , L 5 , n, R 1 , R 3 , R 4 , R 5 , and Z 1  have the same meaning as defined in  claim 1 , and wherein, w is an integer selected from 1, 2, or 3. 
       
     
     
         9 . The compound according to  claim 1 , having structural formula (IH) or (IIH), 
       
         
           
           
               
               
           
         
         wherein, L 3 , L 5 , n, R 1 , R 3 , R 4 , R 5 , and Z 1  and w have the same meaning as defined in  claim 1 , and wherein, w is an integer selected from 1, 2, or 3. 
       
     
     
         10 . The compound according to  claim 1 , wherein n is 0. 
     
     
         11 . A compound selected from the group consisting of 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(4-Methylbenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(2-(2-Methoxypyridin-4-yl)ethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 4-(2-(4-(3-Phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; 5-(4-Isopentylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-(4-Chlorobenzyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-((4-(Oxazol-5-yl)phenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-((4-(Difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 3-(p-Tolyl)-5-(4-((4-(trifluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-((4-Fluorophenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-((4-Isopropylphenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 3-(p-Tolyl)-5-(4-((4-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(4-((4-(3-(p-Tolyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)phenyl)pyrrolidin-2-one; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(4-chlorophenyl)-1,2,4-oxadiazole; 3-(4-Chlorophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 3-(4-Chlorophenyl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-Chlorophenyl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-Chlorophenyl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(3-chlorophenyl)-1,2,4-oxadiazole; 3-(3-Chlorophenyl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3-Chlorophenyl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3-chlorophenyl)-1,2,4-oxadiazole; 2-((4-(3-(3-Chlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzonitrile; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3-fluorophenyl)-1,2,4-oxadiazole; 3-(3-Fluorophenyl)-5-(4-(4-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(3-fluorophenyl)-1,2,4-oxadiazole; 3-(3-Fluorophenyl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole; 4-(2-(4-(3-(3-Fluorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; 3-(3-Fluorophenyl)-5-(4-isopentylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3,4-difluorophenyl)-1,2,4-oxadiazole; 1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(3,4-difluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-Benzo[1,3]dioxol-5-ylmethyl-4-(3-benzyl-[1,2,4]oxadiazol-5-yl)-piperazine; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(2-methyl-benzyl)-piperazine; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; 5-((4-(3-Benzyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)benzo[d]oxazol-2(3H)-one; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole; 1-(4-Ethoxy-benzenesulfonyl)-4-[3-(1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole; 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole; 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole; 1-(4-Methoxy-benzenesulfonyl)-4-[3-((S)-1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(4-Methoxy-benzenesulfonyl)-4[3-((R)-1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-Benzo[1,3]dioxol-5-ylmethyl-4-[3-(4-chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; 5-((4-(3-(4-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)benzo[d]oxazol-2(3H)-one; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methyl-benzyl)-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(4-chloro-phenyl)-ethyl]-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(6-methoxy-pyridin-3-yl)-ethyl]-piperazine; 3-(4-Chlorobenzyl)-5-(4-(2-fluorobenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(2-Chloro-benzyl)-4-[3-(4-chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methyl-benzyl)-piperazine; 4-{4-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-butyronitrile; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-ethoxy-ethyl)-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-propyl-piperazine; 3-(4-Chlorobenzyl)-5-(4-isopentylpiperazin-1-yl)-1,2,4-oxadiazole; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4,4,4-trifluoro-butyl)-piperazine; 3-(4-Chlorobenzyl)-5-(4-((tetrahydro-2H-pyran-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 4-(2-(4-(3-(4-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; 3-(4-Chlorobenzyl)-5-(4-isopropylpiperazin-1-yl)-1,2,4-oxadiazole; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methyl-benzyl)-piperazine; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; 5-{4-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine-1-sulfonyl}-3H-benzooxazol-2-one; 4-(3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)-N,N-dimethylpiperazine-1-sulfonamide; 4-(3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)-N,N-diethylpiperazine-1-sulfonamide; 4-((4-(3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)morpholine; 3-(3-Chlorobenzyl)-5-(4-(pyrrolidin-1-ylsulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(Azepan-1-ylsulfonyl)piperazin-1-yl)-3-(3-chlorobenzyl)-1,2,4-oxadiazole; 3-(3-Chlorobenzyl)-5-(4-((4-methoxypiperidin-1-yl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-(4-Fluoro-benzenesulfonyl)-4[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; N-(4-{4-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine-1-sulfonyl}-phenyl)-acetamide; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-trifluoromethoxy-benzenesulfonyl)-piperazine; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(3-trifluoromethyl-benzenesulfonyl)-piperazine; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(3-methyl-benzyl)-piperazine; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; 1-(4-Ethoxy-benzenesulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-isopropoxy-benzenesulfonyl)-piperazine; 3-(4-((4-(3-(3-Fluorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)phenoxy)propanenitrile; 1-(2,3-Dihydro-benzofuran-5-sulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 3-(3-Fluorobenzyl)-5-(4-((4-isopropoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(4-Chloro-benzyl)-4-[3-(3,4-difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(3,4-difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(6-methoxy-pyridin-3-yl)-ethyl]-piperazine; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methyl-benzyl)-piperazine; 1-{3-[1-(4-Fluoro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-(4-Ethoxy-benzenesulfonyl)-4-{3-[1-(4-fluoro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-piperazine; 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(4-((4-(trifluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-{3-[1-(4-Fluoro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazole; 5-(4-((2,2-Difluorobenzo[d][1,3]dioxol-5-yl)methyl)piperazin-1-yl)-3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazole; 1-{3-[1-(4-Fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-piperazine; 1-(4-Ethoxy-benzenesulfonyl)-4-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-piperazine; 1-{3-[1-(4-Fluoro-phenyl)-1-methyl-ethyl][1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 3-(2-(4-Fluorophenyl)propan-2-yl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-(4-Fluorophenyl)propan-2-yl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-(4-fluorophenyl)propan-2-yl)-1,2,4-oxadiazole; 1-(4-Methoxy-benzenesulfonyl)-4[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(4-Ethoxy-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 1-(4-Methylsulfanyl-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 5-(4-((2,2-Difluorobenzo[d][1,3]dioxol-5-yl)methyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 5-(4-(4-Methylbenzyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 5-(4-(2-(2-Methoxypyridin-4-yl)ethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 4-(2-(4-(3-(1-Phenylcyclopropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; 5-(4-Isopentylpiperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(difluoro(4-fluorophenyl)methyl)-1,2,4-oxadiazole; 3-(Difluoro(4-fluorophenyl)methyl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 1-[3-(Difluoro-phenyl-methyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-[3-(Difluoro-phenyl-methyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(difluoro-phenyl-methyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 3-(Cyclopropylmethyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(Cyclopropylmethyl)-5-(4-((4-(difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(Cyclopropylmethyl)-5-(4-((4-(methylthio)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(Cyclopropylmethyl)-5-(4-((4-ethoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(4-((4-Ethoxyphenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(4-((4-(Difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(4-((4-(Methylthio)phenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 1-(4-Methoxy-benzenesulfonyl)-4-[3-(2-methyl-pyridin-4-ylmethyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-((2-methylpyridin-4-yl)methyl)-1,2,4-oxadiazole; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 5-(4-((4-(Methylthio)phenyl)sulfonyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 5-(4-((4-(Difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 5-(4-(2-(2-Methoxypyridin-4-yl)ethyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 2-((4-(3-(3,3,3-Trifluoropropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzonitrile; 5-(4-Isopentylpiperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 4-(2-(4-(3-(3,3,3-Trifluoropropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; 4-(4-(3-(3,3,3-Trifluoropropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)butanenitrile; 5-(4-((6-Methylpyridin-2-yl)methyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(4-trifluoromethyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(2-chlorobenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(4-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(4-chlorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole; 4-(2-(4-(3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-isopentylpiperazin-1-yl)-1,2,4-oxadiazole; 3-(Bicyclo[2.2.1]heptan-2-yl)-5-(4-(4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(Bicyclo[2.2.1]heptan-2-yl)-5-(4-((4-(methylthio)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(Bicyclo[2.2.1]heptan-2-yl)-5-(4-((4-(difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-Cyclopropyl-5-(4-(4-ethoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-Cyclopropyl-5-(4-(4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(2-(2-methylpyridin-4-yl)propan-2-yl)-1,2,4-oxadiazole; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(1-methyl-1-phenyl-ethyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(4-Methoxy-benzenesulfonyl)-4-[3-(1-methyl-1-phenyl-ethyl)-[1,2,4]oxadiazol-5-yl]-piperazine; (5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazol-3-yl)methanol; 3-(Methoxymethyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-((4-Chlorophenoxy)methyl)-5-(4-((4-methoxyphenyl) sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-((3-Chlorophenoxy)methyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(phenoxymethyl)-1,2,4-oxadiazole; 3-((Cyclopropylmethoxy)methyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-((pyridin-3-yloxy)methyl)-1,2,4-oxadiazole; 4-((5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazol-3-yl)methoxy)benzonitrile; 3-((4-Fluorophenoxy)methyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-propyl-1,2,4-oxadiazole; 3-Butyl-5-(4-(4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(Tert-butyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-Cyclohexyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-Isopropyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-Methoxyethyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(7-(4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole; 5-(7-((4-Methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(7-((4-(Methylthio)phenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(7-((4-Ethoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(7-((4-(Difluoromethoxy)phenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; (3-(4-Fluorobenzyl)-1,2,4-oxadiazol-5-yl)(7-(4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)methanone; 3-(4-Fluorobenzyl)-5-(7-(4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole; 3-(2-Methoxyethyl)-5-(7-((4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole; and a solvate, hydrate, pharmaceutically acceptable salt thereof. 
     
     
         12 . A pharmaceutical composition comprising one or more pharmaceutically excipients and a therapeutically effective amount of a compound according to  claim 1 ; or a therapeutically effective amount of a compound selected from the group consisting of 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof. 
     
     
         13 . A compound according to  claim 1  or a compound selected from the group consisting of 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof; or a pharmaceutical composition thereof for use as a medicament. 
     
     
         14 . A compound according to  claim 1 , or a compound selected from the group consisting of 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 3-(4-bromophenyl)-5-[4-(2-nitrophenyl)sulfonylpiperazin-1-yl]-1,2,4-oxadiazole, 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof; or a pharmaceutical composition thereof for use as a medicine for the prevention and/or treatment of metabolic disorders and/or neurodegenerative diseases; and/or protein misfolding disorders. 
     
     
         15 . A compound according to  claim 1 , or a compound selected from the group consisting of 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-S-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 3-(4-bromophenyl)-5-[4-(2-nitrophenyl)sulfonylpiperazin-1-yl]-1,2,4-oxadiazole; 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof; or a pharmaceutical composition thereof for use as a medicine for the prevention and/or treatment of diabetes mellitus, Parkinson's disease, Alzheimer's disease, diffuse Lewy body disease, amyotrophic lateral sclerosis, Niemann-Pick disease, Hallervorden-Spatz syndrome, Down syndrome, neuroaxonal dystrophy, multiple system atrophy, Huntington's disease, frontotemporal lobar degeneration (FTLD), multiple system atrophy, cystic fibrosis, Creutzfeld-Jacob's disease, impaired glucose tolerance, hyperglycemia, hypoglycemia, glyceraldehyde-3-phosphate dehydrogenase deficiency, hyperinsulinism, impaired insulin production, impaired insulin sensitivity, metabolic syndrome, insulin resistance syndrome, obesity, lipidoses, cardiac lipidoses, dyslipidemia, fatty liver, lipodistrophy, cardiovascular diseases and hypertension.