IP Library › Granted Patent US 9,850,225

Granted Patent B2

US 9,850,225 · App. 14/681,772 · Granted Dec 26, 2017

Compounds useful as immunomodulators

Inventors: Louis S. Chupak (Old Saybrook, CT); Min Ding (Glastonbury, CT); Scott W. Martin (Middletown, CT); Xiaofan Zheng (Cheshire, CT); Piyasena Hewawasam (Middletown, CT); Timothy P. Connolly (Portland, CT); Ningning Xu (Wallingford, CT); Kap-Sun Yeung (Madison, CT); Juliang Zhu (North Haven, CT); David R. Langley (Meriden, CT); Paul Michael Scola (Glastonbury, CT)

Assignee: Bristol-Myers Squibb Company

C07D319/18 A61K31/165 A61K31/277 A61K31/357 A61K31/40 A61K31/4015 A61K31/416 A61K31/4178 A61K31/427 A61K31/4245 A61K31/4433 A61K31/453 A61K31/4545 A61K31/47 A61K31/472 A61K31/496 A61K31/505 A61K31/5377 A61K31/541 A61K45/06 C07C233/36 C07C235/42 C07C255/13 C07C255/54 C07C271/28 C07C317/22 C07D207/26 C07D207/335 C07D213/30 C07D215/14 C07D215/18 C07D217/16 C07D231/56 C07D239/26 C07D261/08 C07D271/06 C07D405/04 C07D405/12 C07D405/14 C07D413/12 C07D417/12

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Quick Facts

Patent No.: US 9,850,225
App. No.: 14/681,772
Granted: Dec 26, 2017
Kind: B2

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Abstract

The present disclosure generally relates to compounds useful as immunomodulators. Provided herein are compounds, compositions comprising such compounds, and methods of their use. The disclosure further pertains to pharmaceutical compositions comprising at least one compound according to the disclosure that are useful for the treatment of various diseases, including cancer and infectious diseases.

Claims (527)

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

m is 0, 1, or 2;

R 1 is selected from hydrogen, —(CH 2 ) n X and —(CH 2 ) n Ar; wherein

n is 1, 2, 3, or 4;

X is selected from —CH 3 , —CF 3 , CN, —CO 2 R 4 , —C(O)NH 2 , OR 4 , and pyrrolidonyl;

R 4 is H or C 1 -C 3 alkyl;

Ar is selected from benzodioxanyl, indazolyl, isoquinolinyl, isoxazolyl, naphthyl, oxadiazolyl, phenyl, pyridinyl, pyrimidinyl, and quinolinyl; wherein each ring is optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1 -C 4 alkoxy, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkoxycarbonylamino, C 1 -C 4 alkyl, (C 1 -C 4 alkyl)carbonyl, (C 1 -C 4 alkyl)sulfonyl, amido, aminocarbonyl, aminocarbonyl(C 1 -C 3 alkyl), —(CH 2 ) q CO 2 C 1 -C 4 alkyl, —(CH 2 ) q OH, carboxy, cyano, formyl, halo, haloC 1 -C 4 alkyl, haloC 1 -C 4 alkoxy, nitro, phenyl optionally substituted with one cyano group, phenyloxy optionally substituted with one halo group, phenylcarbonyl, pyrrole, and tetrahydropyran; and wherein q is 0, 1, 2, 3, or 4;

R 2 is selected from

wherein Y is selected from cyano, chloro, and methyl;

R q is selected from hydrogen, C 1 -C 3 alkyl, and benzyl;

R 3 is selected from

wherein R z is selected from C 1 -C 3 alkyl, C 1 -C 3 alkylsulfonylC 1 -C 3 alkyl, C 1 -C 3 alkylsulfoxylC 1 -C 3 alkyl, amidoC 1 -C 3 alkyl, aminoC 1 -C 4 alkyl, carboxyC 1 -C 3 alkyl, cyanoC 1 -C 3 alkyl, dimethylamidoC 1 -C 3 alkyl, dimethylaminoC 1 -C 4 alkyl, haloC 1 -C 3 alkyl, hydroxyC 1 -C 3 alkyl, C 1 -C 3 alkylsulfanylC 1 -C 3 alkyl, pyridinylC 1 -C 3 alkyl, tetrazolylC 1 -C 3 alkyl, imidazolylC 1 -C 3 alkyl wherein the imidazole is optionally substituted with methyl or a benzyl group, phenylC 1 -C 3 alkyl wherein the phenyl is optionally substituted with cyano, methyl, or hydroxy, thiazolylC 1 -C 3 alkyl;

R 6 is selected from hydrogen, benzyl, and methyl;

each R 6′ is independently selected from hydrogen and methyl;

R 7 is selected from hydrogen, C 1 -C 3 alkyl, and benzyl;

o is 1 or 2;

X is CH or N;

p is 0 or 1;

R a is hydroxy; and

R b is selected from hydrogen, benzyl, and methyl; or

R 3 and R q , together with the nitrogen atom to which they are attached, form a ring selected from

s is 0 or 1;

z is 1, 2, or 3; and

R 8 is selected from hydroxy and —NHSO 2 R 11 ;

R 9 is selected from hydrogen and —CO 2 H;

R 10 is selected from halo and hydroxy;

R 11 is selected from trifluoromethyl, cyclopropyl, C 1 -C 3 alkyl, dimethylamino, and imidazolyl substituted with a methyl group;

Q is selected from CH 2 , S, O, and NCH 3 ; and

R 5 is selected from C 2 -C 4 alkenyl, C 1 -C 4 alkyl, cyano, methoxy, halo, and trifluoromethyl.

2. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is

3. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is

4. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

R 2 is

and

R 3 is

5. A compound selected from

N-(2-(2-(3-cyanobenzyloxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-6-methylbenzylamino)ethyl)acetamide;

(R)-2-(2-(3-cyanobenzyloxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-6-methylbenzylamino)-3-hydroxy-2-methylpropanoic acid;

(R)-2-(2-(3-cyanobenzyloxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-6-methylbenzylamino)-3-hydroxypropanoic acid;

(S)-4-(2-(3-cyanobenzyloxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-6-methylbenzylamino)-3-hydroxybutanoic acid;

(S)-1-(2-(3-cyanobenzyloxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-6-methylbenzyl)piperidine-2-carboxylic acid;

N-(2-(2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-6-methylbenzylamino)ethyl)acetamide;

(S)-4-(2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-6-methylbenzylamino)-3-hydroxybutanoic acid;

(R)-2-(2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-6-methylbenzylamino)-3-hydroxypropanoic acid;

(R)-2-(2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-6-methylbenzylamino)-3-hydroxy-2-methylpropanoic acid;

(S)-1-(2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-6-methylbenzyl)piperidine-2-carboxylic acid;

(S)-2-(2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-6-methylbenzylamino)-3-hydroxy-2-methylpropanoic acid;

(S)-4-(2-(3-cyanobenzyloxy)-4-((2-methylbiphenyl-3-yl)methoxy)benzylamino)-3-hydroxybutanoic acid;

(2S,3S)-2-((2-((3-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxybutanoic acid;

(2R,3R)-2-((2-((3-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxybutanoic acid;

2-((2-((3-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(2R,3S)-2-((2-((3-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxybutanoic acid;

(R)-2-((2-((3-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxypropanoic acid;

2-((2-((3-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxypropanoic acid;

(S)-2-((2-((3-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxypropanoic acid;

(S)-2-((2-((3-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

2-((2-((3-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-2-(hydroxymethyl)-3-methylbutanoic acid;

(S)-3-((2-((3-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-4-hydroxybutanoic acid;

(R)-3-((2-((3-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-4-hydroxybutanoic acid;

(R)-2-((2-((3-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

N-(2-((2-(benzyloxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((3-methylbenzyl)oxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-(2,2,2-trifluoroethoxyl)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-propoxybenzyl)amino)ethyl)acetamide;

N-(2-((2-((3-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((4-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-(2-hydroxyethoxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

2-(2-(((2-acetamidoethyl)amino)methyl)-5-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)acetamide;

methyl 5-(2-(((2-acetamidoethyl)amino)methyl)-5-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)pentanoate;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-phenethoxybenzyl)amino)ethyl)acetamide;

methyl 3-((2-(((2-acetamidoethyl)amino)methyl)-5-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)benzoate;

N-(2-((2-(3-hydroxypropoxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

methyl 4-(2-(((2-acetamidoethyl)amino)methyl)-5-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)butanoate;

N-(2-((2-((3-(hydroxymethyl)benzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((2-(hydroxymethyl)benzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

4-((2-(((2-acetamidoethyl)amino)methyl)-5-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)benzamide;

N-(2-((2-((4-acetylbenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((2-(methylsulfonyl)benzyl)oxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-(3-methoxypropoxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

4-((2-(((2-acetamidoethyl)amino)methyl)-5-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)benzoic acid;

N-(2-((2-ethoxy-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((2-methylbenzyl)oxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((4-(tert-butyl)benzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((4-methylbenzyl)oxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((2-fluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((2,6-difluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3-fluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((3-(trifluoromethyl)benzyl)oxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((4-(trifluoromethyl)benzyl)oxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((2-chlorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3-chlorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((2-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-(naphthalen-2-ylmethoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((2-nitrobenzyl)oxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((4-nitrobenzyl)oxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3,4-difluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((2,5-difluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3,5-bis(trifluoromethyl)benzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3,5-difluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-(naphthalen-1-ylmethoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((2,4-difluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3,5-dimethylbenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((2-(trifluoromethyl)benzyl)oxy)benzyl)amino)ethyl)acetamide;

methyl 4-((2-(((2-acetamidoethyl)amino)methyl)-5-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)benzoate;

N-(2-((2-((4-chlorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3,4-dichlorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((2-fluoro-3-methylbenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((2,3-difluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3-chloro-2-fluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3-benzoylbenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-(quinolin-8-ylmethoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((4-fluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((3-nitrobenzyl)oxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3-(2-fluorophenoxyl)benzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3-(4-fluorophenoxyl)benzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((2-fluoro-3-(trifluoromethyl)benzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((2-fluoro-5-(trifluoromethyl)benzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3-fluoro-5-(trifluoromethyl)benzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((3-(trifluoromethoxy)benzyl)oxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((4-chloro-2-(trifluoromethyl)quinolin-6-yl)methoxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((4-(methylsulfonyl)benzyl)oxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((2-(difluoromethoxy)benzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3-methoxybenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((2-(trifluoromethoxy)benzyl)oxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((4-(difluoromethoxy)benzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((2′-cyano-[1,1′-biphenyl]-4-yl)methoxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((4-methoxybenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3-chloro-5-fluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((2,6-difluoro-3-methoxybenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((4-fluoro-3-methoxybenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((2-fluoro-5-methylbenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((5-cyano-2-fluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3-fluoro-5-methoxybenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((4-bromo-2-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((1H-indazol-5-yl)methoxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((1-(tetrahydro-2H-pyran-2-yl)-1H -indazol-5-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-(pyrimidin-4-ylmethoxy)benzyl)amino)ethyl)acetamide;

methyl 2-(3-((2-(((2-acetamidoethyl)amino)methyl)-5-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)phenyl)acetate;

N-(2-((2-((1H-indazol-6-yl)methoxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

methyl 3-((2-(((2-acetamidoethyl)amino)methyl)-5-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)-4-fluorobenzoate;

N-(2-((2-((5-methyl-1,2,4-oxadiazol-3-yl)methoxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

tert-butyl 3-((2-(((2-acetamidoethyl)amino)methyl)-5-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)benzoate;

N-(2-((2-((3-fluoro-5-(trifluoromethoxy)benzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3,5-dimethoxybenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((4-fluoro-3-methylbenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((5-chloro-2-fluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3-chloro-4-fluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-(pyridin-4-ylmethoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3-(1H-pyrrol-1-yl)benzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3-fluoro-5-methylbenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3-cyano-4-fluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-(5-methylisoxazol-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-((3-(difluoromethoxy)benzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-(pyridin-3-ylmethoxy)benzyl)amino)ethyl)acetamide;

N-(2-((2-(isoquinolin-1-ylmethoxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

tert-butyl (3-((2-(((2-acetamidoethyl)amino)methyl)-5-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)phenyl)carbamate;

(S)—N-(2-((4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((5-oxopyrrolidin-2-yl)methoxy)benzyl)amino)ethyl)acetamide;

(S)-4-(2-(3-cyanobenzyloxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzylamino)-3-hydroxybutanoic acid;

2-((2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxypropanoic acid;

(2R,3S)-2-((2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxybutanoic acid;

2-((2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(2R,3R)-2-((2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxybutanoic acid;

(S)-3-((2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-4-hydroxybutanoic acid;

(R)-2-((2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(S)-2-((2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(R)-3-((2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-4-hydroxybutanoic acid;

N-(2-(2-((4-cyanopyridin-2-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzylamino)ethyl)acetamide;

(R)-2-(2-((4-cyanopyridin-2-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzylamino)-3-hydroxy-2-methylpropanoic acid;

(S)-1-(2-((4-cyanopyridin-2-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzyl)piperidine-2-carboxylic acid;

(S)-4-((2-((3-cyanobenzyl)oxy)-6-methoxy-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxybutanoic acid;

(R)-2-((2-((3-cyanobenzyl)oxy)-6-methoxy-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxypropanoic acid;

(2R,3S)-2-((2-((3-cyanobenzyl)oxy)-6-methoxy-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxybutanoic acid;

(2S,3S)-2-((2-((3-cyanobenzyl)oxy)-6-methoxy-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxybutanoic acid;

2-((2-((3-cyanobenzyl)oxy)-6-methoxy-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(2R,3R)-2-((2-((3-cyanobenzyl)oxy)-6-methoxy-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxybutanoic acid;

(R)-2-((2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-6-methoxybenzyl)amino)-3-hydroxypropanoic acid;

(S)-4-((2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-6-methoxybenzyl)amino)-3-hydroxybutanoic acid;

(S)-2-((2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-6-methoxybenzyl)amino)-3-hydroxypropanoic acid;

(S)-2-((2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-6-methoxybenzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(R)-2-((2-(4-cyanobutoxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxypropanoic acid;

(S)-4-((2-(4-cyanobutoxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxybutanoic acid;

(S)-1-(4-(2-chloro-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-(3-cyanobenzyloxyl)benzyl)piperidine-2-carboxylic acid;

(R)-2-(4-(2-chloro-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-(3-cyanobenzyloxyl)benzylamino)-3-hydroxypropanoic acid;

(S)-4-(4-(2-chloro-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-(3-cyanobenzyloxyl)benzylamino)-3-hydroxybutanoic acid;

(R)-2-(4-(2-chloro-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-(3-cyanobenzyloxyl)benzylamino)-3-hydroxy-2-methylpropanoic acid;

(S)-2-(4-(2-chloro-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-(3-cyanobenzyloxyl)benzylamino)-3-hydroxy-2-methylpropanoic acid;

N-(2-(4-(2-chloro-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-(3-cyanobenzyloxyl)benzylamino)ethyl)acetamide;

5-((5-(2-chloro-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-((2-hydroxyethylamino)methyl)-4-methylphenoxy)methyl)nicotinonitrile;

(S)-1-(4-(2-chloro-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-((5-cyanopyridin-3-yl)methoxy)-5-methylbenzyl)piperidine-2-carboxylic acid;

(R)-2-(4-(2-chloro-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-((5-cyanopyridin-3-yl)methoxy)-5-methylbenzylamino)-3-hydroxypropanoic acid;

(S)-2-(4-(2-chloro-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-((5-cyanopyridin-3-yl)methoxy)-5-methylbenzylamino)-3-hydroxy-2-methylpropanoic acid;

(R)-1-(4-(2-chloro-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-((5-cyanopyridin-3-yl)methoxy)-5-methylbenzyl)piperidine-2-carboxylic acid;

(R)-2-(4-(2-chloro-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-((5-cyanopyridin-3-yl)methoxy)-5-methylbenzylamino)-3-hydroxy-2-methylpropanoic acid;

(R)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxypropanoic acid;

(S)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)succinic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(3-hydroxyphenyl)propanoic acid;

(R)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(methylthio)propanoic acid;

(R)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-2-(4-hydroxyphenyl)acetic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3,3,3-trifluoropropanoic acid;

(2R,3R)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxybutanoic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(1H-imidazol-4-yl)propanoic acid;

1-(5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)pyrrolidine-2-carboxylic acid;

(2R,4R)-1-(5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)-4-hydroxypyrrolidine-2-carboxylic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(5-hydroxy-1H-indol-3-yl)propanoic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(1-methyl-1H-indol-3-yl)propanoic acid;

(R)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)propanoic acid;

3-((4-chloro-5-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-2-(((2-hydroxyethyl)amino)methyl)phenoxy)methyl)benzonitrile;

(S)-2-(benzyl(5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxypropanoic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(dimethylamino)propanoic acid;

(S)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-6-(dimethylamino)hexanoic acid;

(2S)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-4-(methylsulfinyl)butanoic acid;

(R)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)succinic acid;

(S)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(1-methyl-1H-imidazol-4-yl)propanoic acid;

1-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)cyclopropanecarboxylic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(thiazol-2-yl)propanoic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-methoxy-3-methylbutanoic acid;

(S)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-cyanopropanoic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(2-hydroxyphenyl)propanoic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-4-(methylsulfonyl)butanoic acid;

(S)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)(methyl)amino)-3-hydroxypropanoic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-methoxypropanoic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)propanoic acid;

(S)-3-(1-benzyl-1H-imidazol-4-yl)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)propanoic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(4-hydroxyphenyl)propanoic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)(methyl)amino)propanoic acid;

(2S,3S)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxybutanoic acid;

(2S,3R)-1-(5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)piperidine-2,3-dicarboxylic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(1H-imidazol-4-yl)-2-methylpropanoic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(1H-indol-3-yl)propanoic acid;

(R)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)butanoic acid;

(R)-3-(benzyloxy)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)propanoic acid;

(2R,3S)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxybutanoic acid;

(2S,4S)-1-(5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)-4-hydroxypyrrolidine-2-carboxylic acid;

(2S,4R)-1-(5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)-4-hydroxypyrrolidine-2-carboxylic acid;

(R)-1-(5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)piperidine-2-carboxylic acid;

(2R,4S)-1-(5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)-4-hydroxypyrrolidine-2-carboxylic acid;

(S)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-4-(methylsulfonyl)butanoic acid;

(S)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)butanoic acid;

(S)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-4-(methylthio)butanoic acid;

(S)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)(methyl)amino)succinic acid;

(2S,3R)-1-(5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)-3-hydroxypyrrolidine-2-carboxylic acid;

(R)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-4-hydroxybutanoic acid;

(R)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(thiazol-4-yl)propanoic acid;

(S)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(1-methyl-1H-imidazol-5-yl)propanoic acid;

(S)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(thiazol-4-yl)propanoic acid;

1-(5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)azetidine-2-carboxylic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxy-3-methylbutanoic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-2-(1H-indol-3-yl)acetic acid;

3-((4-chloro-5-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-2-(((2-hydroxy-3-morpholinopropyl)amino)methyl)phenoxy)methyl)benzonitrile;

4-(5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)morpholine-3-carboxylic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-2-(hydroxymethyl)-3-methylbutanoic acid;

(2S,4R)-1-(5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)-4-fluoropyrrolidine-2-carboxylic acid;

2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-4,4,4-trifluorobutanoic acid;

(S)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(3-cyanophenyl)propanoic acid;

2-benzyl-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxypropanoic acid;

(2S,3S)-1-(5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)-3-hydroxypyrrolidine-2-carboxylic acid;

4-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-1-methylpiperidine-4-carboxylic acid;

(S)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(pyridin-2-yl)propanoic acid;

(S)-4-(5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)thiomorpholine-3-carboxylic acid;

3-((4-chloro-5-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-2-(((2-methyl-1-(4-methylpiperazin-1-yl)propan-2yl)amino)methyl)phenoxy)methyl)benzonitrile;

1-(5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)-4-methylpiperazine-2-carboxylic acid;

3-((4-chloro-5-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-2-(((2-hydroxy-3-(2-oxopyrrolidin-1-yl)propyl)amino)methyl)phenoxy)methyl)benzonitrile;

5-(5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-4-carboxylic acid;

(S)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-(2H-tetrazol-2-yl)propanoic acid;

(R)-3-(1-benzyl-1H-imidazol-4-yl)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)propanoic acid;

3-((2-((((1H-tetrazol-5-yl)methyl)amino)methyl)-4-chloro-5-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)phenoxy)methyl)benzonitrile;

(S)-1-(5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)piperidine-2-carboxylic acid;

(R)-2-((3-chloro-2-((3-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxypropanoic acid;

(S)-4-((3-chloro-2-((3-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxybutanoic acid;

(S)-1-(3-chloro-2-((3-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)piperidine-2-carboxylic acid;

N-(2-((3-chloro-2-((3-cyanobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

(R)-2-((3-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxypropanoic acid;

(S)-1-(3-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)piperidine-2-carboxylic acid;

N-(2-((3-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)ethyl)acetamide;

(S)-2-((3-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(R)-2-((3-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(S)-4-((3-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxybutanoic acid;

(R)-2-((5-chloro-4-((2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyl)oxy)-2-((3-cyanobenzyl)oxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(R)-2-((5-chloro-4-((2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyl)oxy)-2-((3-cyanobenzyl)oxy)benzyl)amino)-3-hydroxypropanoic acid;

3-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)oxetane-3-carboxylic acid;

(R)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(S)-2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(S)-4-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxybutanoic acid;

N-(2-((5-chloro-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)ethyl)acetamide;

(R)-2-((5-chloro-2-((5-cyanopyridin-3-yl)methoxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(R)-2-((5-chloro-2-((5-cyanopyridin-3-yl)methoxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxypropanoic acid;

(S)-4-((5-chloro-2-((5-cyanopyridin-3-yl)methoxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxybutanoic acid;

N-(2-((5-chloro-2-((5-cyanopyridin-3-yl)methoxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)ethyl)acetamide;

(S)-2-(5-chloro-2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzylamino)-3-hydroxy-2-methylpropanoic acid;

(S)-1-(5-chloro-2-((5-cyanopyridin-3-yl)methoxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)piperidine-2-carboxylic acid;

(R)-2-(2-((5-bromopyridin-3-yl)methoxy)-5-chloro-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzylamino)-3-hydroxy-2-methylpropanoic acid;

N-(2-(2-((5-bromopyridin-3-yl)methoxy)-5-chloro-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzylamino)ethyl)acetamide;

(S)-1-(5-chloro-2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzyl)-N-(methylsulfonyl)piperidine-2-carboxamide;

(S)-1-(5-chloro-2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzyl)-N-(N,N-dimethylsulfamoyl)piperidine-2-carboxamide;

(S)-1-(5-chloro-2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzyl)-N-(trifluoromethylsulfonyl)piperidine-2-carboxamide;

(S)-1-(5-chloro-2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzyl)-N-(cyclopropylsulfonyl)piperidine-2-carboxamide;

(S)-1-(5-chloro-2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzyl)-N-(isopropylsulfonyl)piperidine-2-carboxamide;

(S)-1-(5-chloro-2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzyl)-N-(1-methyl-1H-imidazol-4-ylsulfonyl)piperidine-2-carboxamide;

(S)-1-(5-chloro-2-((5-cyanopyridin-3-yl)methoxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)-N-((4-methylpiperazin-1-yl)sulfonyl)piperidine-2-carboxamide;

(R)-2-(5-chloro-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-2-hydroxybenzylamino)-3-hydroxy-2-methylpropanoic acid;

N-(2-((2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methylbenzyl)amino)ethyl)acetamide;

(S)-4-((2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methylbenzyl)amino)-3-hydroxybutanoic acid;

(S)-2-((2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methylbenzyl)amino)-3-hydroxypropanoic acid;

(S)-2-((2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methylbenzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(S)-1-(2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methylbenzyl)piperidine-2-carboxylic acid;

(R)-2-((2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methylbenzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(S)-4-((2-((3-cyano-4-fluorobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methylbenzyl)amino)-3-hydroxybutanoic acid;

N-(2-((2-((3-cyano-4-fluorobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methylbenzyl)amino)ethyl)acetamide;

(S)-1-(2-((3-cyano-4-fluorobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methylbenzyl)piperidine-2-carboxylic acid;

(R)-2-((2-((3-cyano-4-fluorobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methylbenzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(S)-2-((2-((3-cyano-4-fluorobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methylbenzyl)amino)-3-hydroxypropanoic acid;

(S)-2-((2-((3-cyano-4-fluorobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methylbenzyl)amino)-3-hydroxy-2-methylpropanoic acid;

N-(2-((4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methyl-2-(pyridin-3-ylmethoxy)benzyl)amino)ethyl)acetamide;

(S)-2-((4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methyl-2-(pyridin-3-ylmethoxy)benzyl)amino)-3-hydroxypropanoic acid;

(S)-4-((4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methyl-2-(pyridin-3-ylmethoxy)benzyl)amino)-3-hydroxybutanoic acid;

(S)-1-(4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methyl-2-(pyridin-3-ylmethoxy)benzyl)piperidine-2-carboxylic acid;

(S)-2-((4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methyl-2-(pyridin-3-ylmethoxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(R)-2-((4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)-5-methyl-2-(pyridin-3-ylmethoxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

N-(2-(2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-5-methylbenzylamino)ethyl)acetamide;

(S)-4-(2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-5-methylbenzylamino)-3-hydroxybutanoic acid;

(S)-2-(2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-5-methylbenzylamino)-3-hydroxypropanoic acid;

(S)-1-(2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-5-methylbenzyl)piperidine-2-carboxylic acid;

(S)-2-(2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-5-methylbenzylamino)-3-hydroxy-2-methylpropanoic acid;

(R)-2-(2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-5-methylbenzylamino)-3-hydroxy-2-methylpropanoic acid;

(R)-1-(2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-5-methylbenzyl)piperidine-2-carboxylic acid;

N-(2-(2-(3-cyanobenzyloxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-5-ethylbenzylamino)ethyl)acetamide;

(S)-2-(2-(3-cyanobenzyloxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-5-ethylbenzylamino)-3-hydroxy-2-methylpropanoic acid;

(R)-2-(2-(3-cyanobenzyloxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-5-ethylbenzylamino)-3-hydroxy-2-methylpropanoic acid;

N-(2-(2-(3-cyanobenzyloxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-5-vinylbenzylamino)ethyl)acetamide;

(S)-1-(2-(3-cyanobenzyloxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-5-vinylbenzyl)piperidine-2-carboxylic acid;

N-(2-(2-(4-cyanobutoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-5-methylbenzylamino)ethyl)acetamide;

(S)-4-(2-(4-cyanobutoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-5-methylbenzylamino)-3-hydroxybutanoic acid;

(S)-1-(2-(4-cyanobutoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-5-methylbenzyl)piperidine-2-carboxylic acid;

(S)-2-(2-(4-cyanobutoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-5-methylbenzylamino)-3-hydroxy-2-methylpropanoic acid;

(S)-1-(5-bromo-2-((5-cyanopyridin-3-yl)methoxy)-4-(2-methylbiphenyl-3-yl)methoxy)benzyl)piperidine-2-carboxylic acid;

N-(2-((5-bromo-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)ethyl)acetamide;

(S)-4-((5-bromo-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxybutanoic acid;

(S)-2-((5-bromo-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxypropanoic acid;

(S)-1-(5-bromo-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)piperidine-2-carboxylic acid;

(R)-2-((5-bromo-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(S)-2-((5-bromo-2-((3-cyanobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

N-(2-(4-(2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-((5-cyanopyridin-3-yl)methoxy)-5-methylbenzylamino)ethyl)acetamide;

5-((5-(2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-((2-hydroxyethylamino)methyl)-4-methylphenoxy)methyl)nicotinonitrile;

(S)-4-(4-(2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-((5-cyanopyridin-3-yl)methoxy)-5-methylbenzylamino)-3-hydroxybutanoic acid;

(S)-2-(4-(2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-((5-cyanopyridin-3-yl)methoxy)-5-methylbenzylamino)-3-hydroxy-2-methylpropanoic acid;

(S)-1-(4-(2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-((5-cyanopyridin-3-yl)methoxy)-5-methylbenzyl)piperidine-2-carboxylic acid;

(R)-2-(4-(2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-((5-cyanopyridin-3-yl)methoxy)-5-methylbenzylamino)-3-hydroxypropanoic acid;

(R)-2-(4-(2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyloxy)-2-((5-cyanopyridin-3-yl)methoxy)-5-methylbenzylamino)-3-hydroxy-2-methylpropanoic acid;

(S)-2-((5-bromo-4-((2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyl)oxy)-2-((3-cyanobenzyl)oxy)benzyl)amino)-3-hydroxypropanoic acid;

(S)-1-(5-bromo-4-((2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyl)oxy)-2-((3-cyanobenzyl)oxy)benzyl)piperidine-2-carboxylic acid;

(S)-4-((5-bromo-4-((2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyl)oxy)-2-((3-cyanobenzyl)oxy)benzyl)amino)-3-hydroxybutanoic acid;

N-(2-((5-bromo-4-((2-cyano-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)benzyl)oxy)-2-((3-cyanobenzyl)oxy)benzyl)amino)ethyl)acetamide;

(S)-4-(5-bromo-2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzylamino)-3-hydroxybutanoic acid;

N-(2-(5-bromo-2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzylamino)ethyl)acetamide;

(S)-2-(5-bromo-2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzylamino)-3-hydroxypropanoic acid;

(S)-1-(5-bromo-2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzyl)piperidine-2-carboxylic acid;

(R)-2-(5-bromo-2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzylamino)-3-hydroxy-2-methylpropanoic acid;

(S)-2-(5-bromo-2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzylamino)-3-hydroxy-2-methylpropanoic acid;

5-((4-bromo-5-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)-2-((2-hydroxyethylamino)methyl)phenoxy)methyl)nicotinonitrile;

(R)-1-(5-bromo-2-((5-cyanopyridin-3-yl)methoxy)-4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyloxy)benzyl)piperidine-2-carboxylic acid;

(R)-2-((2-((5-cyano-4-methylpyridin-3-yl)methoxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxypropanoic acid;

(R)-2-((2-((3-carbamoylbenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxypropanoic acid;

(R)-2-((2-((3-carbamoylbenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(R)-2-((2-((5-cyanopyridin-3-yl)methoxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxypropanoic acid;

(S)-4-((2-((5-cyanopyridin-3-yl)methoxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxybutanoic acid;

(S)-1-(2-((5-cyanopyridin-3-yl)methoxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)piperidine-2-carboxylic acid;

(S)-4-((2-((3-cyano-4-fluorobenzyl)oxy)-4-((3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-methylbenzyl)oxy)benzyl)amino)-3-hydroxybutanoic acid;

(S)-4-((2-((3-cyano-4-fluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxybutanoic acid;

(R)-2-((2-((3-cyano-4-fluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxypropanoic acid;

(R)-2-((2-((3-cyano-4-fluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)-3-hydroxy-2-methylpropanoic acid;

(S)-1-(2-((3-cyano-4-fluorobenzyl)oxy)-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)piperidine-2-carboxylic acid; and

N-(2-((2-methoxy-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzyl)amino)ethyl)acetamide;

or a pharmaceutically acceptable salt thereof.

6. A compound selected from