Therapeutic piperazines

1. A compound of formula I:

wherein:

R 1 is (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, R a R b N(C 1 -C 6 )alkyl, hydroxy(C 1 -C 6 )alkyl, alkoxy(C 1 -C 6 )alkyl, het(C 1 -C 6 )alkyl, het(C 1 -C 6 )haloalkyl, aryl(C 1 -C 6 )alkyl, aryl(C 1 -C 6 )haloalkyl, aryl-(C═O)—, or het-(C═O)—;

Y is a direct bond, —CH 2 —, or —(C═O)—;

n is an integer from 0 to 6 inclusive;

each of the n instances of A is independently a direct bond or —(CR c R d )—;

R 4 is aryl or heteroaryl;

Z is a phenyl ring substituted with one or more substituents independently selected from halogen, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy, (C 3 -C 8 )cycloalkoxy, and (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkoxy; piperidinyloxy, piperidinyloxy (C 1 -C 6 )alkyl, or cyano;

each R a and R b is independently H, (C 1 -C 6 )alkyl, aryl, aryl(C 1 -C 6 )alkyl, het, or het(C 1 -C 6 )alkyl;

each R c and R d is independently H, OH, NH 2 , (C 1 -C 6 )alkyl, or R c and R d taken together may join to form a 3- to 5-member ring consisting of C atoms and optionally one or more O atom(s) and/or N(X), wherein X is absent, H, O, OH, (C 1 -C 4 )alkyl, phenyl or benzyl;

wherein any phenyl, aryl, het or heteroaryl of R 1 or R 4 is optionally substituted at any position with one or more substituents independently selected from (C 1 -C 6 )alkyl, hydroxy, hydroxy(C 1 -C 6 )alkyl, phenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkoxycarbonyl, (C 1 -C 6 )alkanoyloxy, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyloxy, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkoxy, halo(C 1 -C 6 )alkoxy, cyano, nitro, halo, (C 1 -C 6 )carboxy or NR c R d ; and wherein the piperazine core ring of compound I is optionally substituted at one or more carbon atom(s) with one or more substituents independently selected from oxo, halogen, (C 1 -C 6 )alkyl or (C 1 -C 6 )alkoxy;

and when R 1 is C 1 alkyl, Y-(A) n -R 4 taken together is not aryl(C 1 -C 6 )alkyl or hydroxy(C 1 -C 6 )alkyl;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein Z is a phenyl ring substituted with one or more substituents independently selected from (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, CN or halogen.

3. The compound of claim 2 , wherein Z is:

wherein:

R 2 and R 3 are each independently H, (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl or halo(C 1 -C 6 )alkyl; and

M 1 , M 2 and M 3 are each independently H, CN, halogen or (C 1 -C 2 )alkyl.

4. The compound of claim 3 , wherein R 2 is methyl, ethyl or difluoromethyl.

5. The compound of claim 3 , wherein R 3 is cyclopropyl, methylcyclopropyl, cyclobutyl, cyclopentyl, isopropyl, difluoromethyl, 1,3-difluoroisopropyl, N-methylpyrrolidinyl or N-methylpiperidnyl.

6. The compound of claim 1 , wherein R 1 is (C 2 -C 6 )alkyl, aryl, aryl(C 1 -C 6 )alkyl, het or het(C 1 -C 6 )alkyl.

7. The compound of claim 6 , wherein R 1 is ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, benzyl, indolyl, indolylmethyl, phenyl, 2-methylpropyl, 2-, 3- or 4-methylbenzyl, benzhydryl, phenethyl, phenylpropyl, 1-naphthylmethyl, 2-naphthylmethyl, bipyridyl, 2-, 3- or 4-phenylbenzyl, 2-, 3- or 4-methoxybenzyl, 2-, 3- or 4-ethoxybenzyl, cyclohexylmethyl, morpholinomethyl, N-methyl-N-benzylmethyl, pyrrolidinylmethyl, pyrrolylmethyl, tetrahydroisoquinolinylmethyl, isoindolinylmethyl, pryazolylmethyl or fluorobenzyl.

8. A pharmaceutical composition, comprising:

(a) a compound of claim 1 ; and

(b) a pharmaceutically acceptable diluent or carrier.

9. A pharmaceutical composition, comprising:

(a) a pharmaceutically acceptable salt of a compound of claim 1 ; and

(b) a pharmaceutically acceptable diluent or carrier.

10. A compound selected from the group consisting of:

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(thiophen-2-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(furan-2-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(thiophen-3-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-3-(1H-imidazol-5-yl)propan-1-one;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(1H-imidazol-5-yl)ethanone;

(S)-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)(1H-imidazol-4-yl)methanone;

(S)-1-(2-(1H-imidazol-5-yl)ethyl)-2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazine;

(S)-1-(4-(3-(cyclopentyloxy)-4-methoxyphenyl)-2-(pyrrolidin-1-ylmethyl)piperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanone;

(S)-1-(4-(3-(cyclopentyloxy)-4-methoxyphenyl)-2-(morpholinomethyl)piperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanone;

(R)-1-(2-((1H-pyrazol-1-yl)methyl)-4-(3-(cyclopentyloxy)-4-ethoxyphenyl)piperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanone;

(S)-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)(2,4-dimethylthiazol-5-yl)methanone;

(S)-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)(3,4-dihydroxyphenyl)methanone;

(S)-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)(3-hydroxyphenyl)methanone;

(S)-4-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazine-1-carbonyl)-1H-imidazol-2(3H)-one;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(2-methyl-1H-imidazol-1-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(1H-imidazol-1-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(thiazol-5-yl)ethanone;

(S)-3-(2-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-oxoethyl)-1H-1,2,4-triazol-5(4H)-one;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(2H-tetrazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(2,4-dimethylthiazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(furan-2-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(1H-imidazol-2-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(1H-imidazol-4-yl)ethanone;

(S)-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)(1H-pyrazol-3-yl)methanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(5-methyl-1H-pyrazol-3-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(1H-pyrrol-2-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(1H-pyrrol-3-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(4-methylthiazol-2-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(furan-2-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(2,4-dimethylthiazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(1-methyl-1H-imidazol-4-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(1-methyl-1H-imidazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(1-methyl-1H-imidazol-2-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(1H-pyrrol-3-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(5-nitro-1H-1,2,4-triazol-3-yl)ethanone;

(S)-1-(2-benzyl-4-(3-isopropoxy-4-methoxyphenyl)piperazin-1-yl)-2-(1H-imidazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3-isopropoxy-4-methoxyphenyl)piperazin-1-yl)-2-(1H-pyrrol-3-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanone;

(S)-1-(2-benzyl-4-(3-isopropoxy-4-methoxyphenyl)piperazin-1-yl)-2-(3-methyl-1H-1,2,4-triazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(3-methyl-1H-1,2,4-triazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3,4-bis(difluoromethoxy)phenyl)piperazin-1-yl)-2-(3-methyl-1H-1,2,4-triazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3-isopropoxy-4-methoxyphenyl)piperazin-1-yl)-2-(2H-tetrazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(1H-1,2,3-triazol-1-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(2H-tetrazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3-isopropoxy-4-methoxyphenyl)piperazin-1-yl)-2-(5-nitro-1H-1,2,4-triazol-3-yl)ethanone;

(S)-2-(3-amino-1H-1,2,4-triazol-5-yl)-1-(2-benzyl-4-(3-isopropoxy-4-methoxyphenyl)piperazin-1-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(5-nitro-1H-1,2,4-triazol-3-yl)ethanone;

(S)-2-(5-amino-1H-1,2,4-triazol-3-yl)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(pyrimidin-2-yl)ethanone;

(S)-1-(2-benzyl-4-(3-isopropoxy-4-methoxyphenyl)piperazin-1-yl)-2-(pyridin-2-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(pyridin-2-yl)ethanone;

(S)-1-(2-benzyl-4-(3-isopropoxy-4-methoxyphenyl)piperazin-1-yl)-2-(pyrimidin-2-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-(difluoromethoxy)phenyl)piperazin-1-yl)-2-(1H-imidazol-4-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-(difluoromethoxy)phenyl)piperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(difluoromethoxy)-4-methoxyphenyl)piperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(difluoromethoxy)-4-methoxyphenyl)piperazin-1-yl)-2-(1H-imidazol-4-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-(difluoromethoxy)phenyl)piperazin-1-yl)-2-(pyrimidin-2-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(difluoromethoxy)-4-methoxyphenyl)piperazin-1-yl)-2-(pyrimidin-2-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(difluoromethoxy)-4-methoxyphenyl)piperazin-1-yl)-2-(pyridin-2-yl)ethanone;

(S)-5-((2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)methyl)-2,4-dimethylthiazole;

(S)-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)(4-(hydroxymethyl)phenyl)methanone;

(S)-3-((2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)methyl)phenol;

(S)-4-((2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)methyl)phenol;

(S)-1-(4-(3-(cyclopentyloxy)-4-methoxyphenyl)-2-isobutylpiperazin-1-yl)-2-(1H-imidazol-4-yl)ethanone;

(S)-1-(4-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-isobutylpiperazin-1-yl)-2-(1H-imidazol-4-yl)ethanone;

(S)-1-(4-(3-(cyclopentyloxy)-4-(difluoromethoxy)phenyl)-2-isobutylpiperazin-1-yl)-2-(1H-imidazol-4-yl)ethanone;

(S)-1-(4-(3-cyclobutoxy-4-methoxyphenyl)-2-isobutylpiperazin-1-yl)-2-(1H-imidazol-4-yl)ethanone;

(S)-1-(4-(3-cyclobutoxy-4-methoxyphenyl)-2-isobutylpiperazin-1-yl)-2-(1-methyl-1H-imidazol-4-yl)ethanone;

(S)-1-(4-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-isobutylpiperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanone;

(S)-1-(4-(3-(cyclopentyloxy)-4-(difluoromethoxy)phenyl)-2-isobutylpiperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanone;

(S)-1-(2-isobutyl-4-(3-isopropoxy-4-methoxyphenyl)piperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanone;

(S)-2-(1H-imidazol-4-yl)-1-(2-isobutyl-4-(3-isopropoxy-4-methoxyphenyl)piperazin-1-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(pyridin-2-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(pyridin-3-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(pyridin-4-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(pyrazin-2-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(pyrimidin-2-yl)ethanone;

(S)-1-(4-(3-(cyclopentyloxy)-4-methoxyphenyl)-2-isobutylpiperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(pyrimidin-4-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(2-fluorophenyl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(2,6-difluorophenyl)ethanone;

(S)-1-(4-(3-cyclobutoxy-4-methoxyphenyl)-2-isobutylpiperazin-1-yl)-2-(oxazol-5-yl)ethanone;

(S)-1-(4-(3-cyclobutoxy-4-methoxyphenyl)-2-isobutylpiperazin-1-yl)-2-(3-methyl-1,2,4-oxadiazol-5-yl)ethanone;

(S)-1-(4-(3-cyclobutoxy-4-methoxyphenyl)-2-(4-fluorobenzyl)piperazin-1-(1H-pyrazol-4-yl)ethanone;

(S)-1-(4-(3-cyclobutoxy-4-methoxyphenyl)-2-(4-fluorobenzyl)piperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanone;

(S)-1-(4-(3-cyclobutoxy-4-methoxyphenyl)-2-(4-fluorobenzyl)piperazin-1-yl)-2-(pyrimidin-2-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(4H-1,2,4-triazol-3-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(1H-pyrazol-4-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(oxazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(3-methyl-1,2,4-oxadiazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclopropoxy-4-methoxyphenyl)piperazin-1-yl)-2-(4H-1,2,4-triazol-3-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(oxazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(3-methyl-1,2,4-oxadiazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(1H-pyrazol-4-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(2-methyloxazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(3-isopropyl-1H-1,2,4-triazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(3-ethyl-1H-1,2,4-triazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(1-methyl-1H-pyrazol-4-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(4H-1,2,4-triazol-3-yl)ethanone;

(S)-1-(2-benzyl-4-(3-isopropoxy-4-methoxyphenyl)piperazin-1-yl)-2-(4H-1,2,4-triazol-3-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-(difluoromethoxy)phenyl)piperazin-1-yl)-2-(4H-1,2,4-triazol-3-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-(difluoromethoxy)phenyl)piperazin-1-yl)-2-(1H-imidazol-4-yl)ethanone;

(S)-1-(2-benzyl-4-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)piperazin-1-yl)-2-(1H-imidazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3,4-bis(difluoromethoxy)phenyl)piperazin-1-yl)-2-(1H-imidazol-5-yl)ethanone;

1-((S)-2-benzyl-4-(4-methoxy-3-((S)-1-methylpyrrolidin-3-yloxy)phenyl)piperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanone;

(S)-2-(5-amino-1H-1,2,4-triazol-3-yl)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)ethanone;

(S)-1-(2-benzyl-4-(4-methoxy-3-(1-methylpiperidin-4-yloxy)phenyl)piperazin-1-yl)-2-(5-methyl-4H-1,2,4-triazol-3-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclopropoxy-4-methoxyphenyl)piperazin-1-yl)-2-(3-methyl-1H-1,2,4-triazol-5-yl)ethanone;

(S)-1-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)-2-(2-methyl-1H-imidazol-5-yl)ethanone;

(S)-2-(2-benzyl-4-(3-cyclobutoxy-4-methoxyphenyl)piperazin-1-yl)pyrimidine; and

(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(1-isopropyl-1H-imidazol-4-yl)ethanone.