IP Library › Granted Patent US 11,358,932

Granted Patent B2

US 11,358,932 · App. 16/274,117 · Granted Jun 14, 2022

N-(1-hydroxy-3-(pyrrolidinyl)propan-2-yl)pyrrolidine-3-carboxamide derivatives as glucosylceramide synthase inhibitors

Inventor: Bing Wang (San Jose, CA)

C07D207/16 C07D319/16 C07D401/04 C07D401/12 C07D401/14 C07D403/12 C07D405/12 C07D405/14 C07D409/04 C07D409/12 C07D409/14 C07D417/14 C07D471/04

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Patent No.: US 11,358,932
App. No.: 16/274,117
Granted: Jun 14, 2022
Kind: B2

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Abstract

Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or conditions associated with the enzyme glucosylceramide synthase (GCS).

Claims (570)

1. A method of treating a disease or disorder, the method comprising administering to a subject an effective amount of a compound having a structure of Formula I:

where

R 1 is N—(R 6 )-azetidinyl, N—(R 6 )-pyrrolidinyl, or N—(R 6 )-piperidinyl, each of which is attached to the C(O) group by a carbon atom and is optionally substituted with hydroxy;

R 2 and R 3 together with the nitrogen to which they are attached form a 4-6 membered heterocycloalkyl ring with 1 or 2 nitrogen atoms, which is optionally substituted with 1 or 2 R 8 ;

R 4 is aryl or heteroaryl each of which is optionally substituted with 1, 2, or 3 R 9 groups;

R 5 is halo, hydroxy, —N 3 , —NH 2 , —NHC(O)CH 3 , —NH(OCH 3 ), or —NHC(O)H and R 5 a is hydrogen, halo, alkyl, or deuterium; or R 5 and R 5 a together with the carbon to which they are attached form C(O) or C(NOH);

R 6 is alkyl, alkoxycarbonyl, aryl, arylalkyl, arylcarbonyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, or —C(O)NR 6a R 6b ; wherein each aryl and heteroaryl, whether alone or as part of another group, is optionally substituted with 1 or 2 R 10 groups; and wherein each heterocycloalkyl and cycloalkyl, whether alone or as part of another group, is optionally substituted with 1 or 2 groups independently selected from hydroxy, halo, haloalkyl, alkoxy, alkyl, alkylcarbonyl, and alkoxycarbonyl;

R 6a is hydrogen or alkyl, and R 6b is aryl or heteroaryl each of which is optionally substituted with 1 or 2 halo; or R 6a and R 6b together with the nitrogen to which they are attached form a heterocycloalkyl optionally substituted with alkyl, hydroxy, alkylcarbonyl, or alkoxycarbonyl;

each R 8 , when present, is independently deuterium, amino, alkylamino, dialkylamino, alkyl, hydroxy, alkoxy, halo, haloalkyl, or cycloalkyl;

each R 9 , when present, is independently cyano, nitro, amino, alkylamino, dialkylamino, halo, haloalkyl, alkyl, —NR 11 C(O)NR 11a R 11b , hydroxy, alkoxy, haloalkoxy, hydroxyalkoxy, alkenyloxy, cycloalkyloxy, cycloalkylalkyloxy, cycloalkylthio, heterocycloalkyl, heterocycloalkyloxy, heterocycloalkylalkyloxy, or phenyl; where the phenyl is optionally substituted with 1 or 2 R 9a ; where each heterocycloalkyl, either alone or as part of another group, is optionally substituted with 1 or 2 groups independently selected from alkyl, hydroxy, alkylcarbonyl, and alkoxycarbonyl;

each R 9a , when present, is independently selected from alkyl, hydroxy, alkoxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyl, amino, alkylamino, and dialkylamino;

each R 10 , when present, is independently cyano, nitro, amino, alkylamino, dialkylamino, halo, haloalkyl, alkyl, alkenyl, alkynyl, —NR 11 C(O)NR 11a R 11b , alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cycloalkyl, hydroxy, alkoxy, haloalkoxy, hydroxyalkoxy, alkenyloxy, cycloalkyloxy, cycloalkylalkyloxy, cycloalkylthio, aryl, arylalkyl, aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heterocycloalkyl, heterocycloalkyloxy, or heterocycloalkylalkyloxy; where each aryl or heteroaryl either alone or as part of another group, is independently optionally substituted with 1, 2 or 3 R 10a ; and each heterocycloalkyl, either alone or as part of another group, is optionally substituted with 1 or 2 groups independently selected from alkyl, hydroxy, alkylcarbonyl, and alkoxycarbonyl groups;

each R 10a , when present, is independently selected from cyano, halo, alkyl, alkenyl, haloalkyl, hydroxyalkyl, and cycloalkyl; and

R 11 , R 11a , and R 11b are independently hydrogen, alkyl, or cycloalkyl; and

optionally a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally a pharmaceutically acceptable salt thereof;

wherein the disease or disorder is selected from the group consisting of: a glycolipid storage disease, hyperglycemia, hyperinsulemia, polycystic kidney disease, and diabetes mellitus.

2. The method of claim 1 , wherein the compound has a structure according to Formula I(a):

optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.

3. The method of claim 1 , wherein the compound has a structure according to Formula I(d1):

optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.

4. The method of claim 1 , wherein R 5 is hydroxy and R 5a is hydrogen; optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.

5. The method of claim 1 , wherein R 6 is aryl, optionally independently substituted with 1 or 2 R 10 groups; optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.

6. The method of claim 1 , wherein R 6 is heterocycloalkyl or heteroaryl, each optionally independently substituted with 1 or 2 R 10 groups; optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.

7. The method of claim 1 , wherein:

R 4 is aryl or heteroaryl each of which is optionally substituted with 1 or 2 R 9 groups;

R 5 is hydroxy, and R 5a is hydrogen;

R 6 is alkyl, aryl, arylalkyl, arylcarbonyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl; wherein each aryl and heteroaryl, whether alone or as part of another group, is optionally substituted with 1 or 2 R 10 groups; and wherein each heterocycloalkyl and cycloalkyl, whether alone or as part of another group, is optionally substituted with 1 or 2 groups independently selected from hydroxy, halo, haloalkyl, alkoxy, and alkyl;

each R 8 , when present, is independently alkyl, hydroxy, alkoxy, halo, or haloalkyl;

each R 9 , when present, is independently cyano, nitro, halo, haloalkyl, alkyl, hydroxy, alkoxy, haloalkoxy, hydroxyalkoxy, alkenyloxy, cycloalkyloxy, cycloalkylalkyloxy, cycloalkylthio, heterocycloalkyl, heterocycloalkyloxy, or heterocycloalkylalkyloxy; where each heterocycloalkyl, whether alone or as part of another group, is optionally substituted with 1 or 2 groups independently selected from alkyl, hydroxy, alkylcarbonyl, and alkoxycarbonyl;

each R 10 , when present, is independently is cyano, halo, haloalkyl, alkyl, hydroxy, alkoxy, haloalkoxy, cycloalkyloxy, cycloalkylalkyloxy, aryl, aryloxy, heteroaryloxy, heterocycloalkyl, heterocycloalkyloxy, or heterocycloalkylalkyloxy; where each aryl or heteroaryl either alone or as part of another group, is independently optionally substituted with 1 or 2 halo or alkyl groups; and each heterocycloalkyl, either alone or as part of another group, is optionally substituted with 1 or 2 groups independently selected from alkyl and hydroxy; and

optionally a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally a pharmaceutically acceptable salt thereof.

8. The method of claim 1 , is according to Formula I(c):

optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.

9. The method of claim 1 , is according to Formula I(d2):

optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.

10. The method of claim 1 , wherein:

R 1 is N—(R 6 )-pyrrolidinyl attached to the C(O) by a carbon atom;

R 2 and R 3 together with the nitrogen to which they are attached form azetidinyl or pyrrolidinyl;

R 5 is hydroxy and R 5 a is hydrogen; and optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.

11. The method of claim 1 , wherein R 6 is aryl or heteroaryl, wherein the aryl is optionally independently substituted with 1 or 2 halo, alkyl, cycloalkyloxy, or heterocycloalkyloxy; and the heteroaryl is optionally independently substituted with 1 or 2 halo, alkyl, or cycloalkyloxy; and optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.

12. The method of claim 1 , wherein R 6 is heterocycloalkyl optionally independently substituted with 1 or 2 halo, hydroxy, or alkyl; and optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof.

13. The method of claim 1 , wherein the disease or disorder is the glycolipid storage disease selected from the group consisting of Tay Sachs, Sandhoffs, GMI gangliosidosis, Niemanns-Pick, Fabry diseases, and Gaucher disease.

14. A method of treating a disease or disorder, the method comprising administering to a subject an effective amount of a compound selected from the group consisting of:

(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

1-(4-chlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)pyrrolidine-3-carboxamide;

N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)pyrrolidine-3-carboxamide;

(R)-1-(3,4-dichlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

1-(3,4-dichlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(3,4-dichlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidine-3-carboxamide;

N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidine-3-carboxamide;

1-cyclopentyl-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(2,4-dichlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(2,4-dichlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-chlorobenzyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

1-(4-chlorobenzyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(4-chlorobenzyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(thiazol-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(thiazol-2-yl)pyrrolidine-3-carboxamide;

1-(4-chloro-3-cyclopropoxyphenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(3-chloro-4-cyclopropoxyphenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

1-(3-chloro-4-cyclopropoxyphenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(3-chloro-4-cyclopropoxyphenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-chlorophenethyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

1-(4-chlorophenethyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(4-chlorophenethyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(pyridin-2-yl)pyrrolidine-3-carboxamide;

N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(pyridin-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(pyridin-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;

N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

1-cyclohexyl-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(5-chloropyridin-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

1-(5-chloropyridin-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(5-chloropyridin-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

1-butyl-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)pyrrolidine-3-carboxamide;

N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

1-(4-chlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;

N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(pyridin-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(pyridin-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(benzo[b]thiophen-6-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

1-(benzo[b]thiophen-6-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(benzo[b]thiophen-6-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(2,3-dihydro-1H-inden-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

1-(2,3-dihydro-1H-inden-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(2,3-dihydro-1H-inden-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(2-cyclopropoxypyridin-4-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

1-(2-cyclopropoxypyridin-4-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(2-cyclopropoxypyridin-4-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(6-cyclopropoxypyridin-3-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(6-cyclopropoxypyridin-3-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(1-methyl-1H-indazol-6-yl)pyrrolidine-3-carboxamide;

N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(1-methyl-1H-indazol-6-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(1-methyl-1H-indazol-6-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)pyrrolidine-3-carboxamide;

N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)pyrrolidine-3-carboxamide;

N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2,2-dimethylchroman-6-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(quinolin-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(quinolin-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2,2-dimethylchroman-7-yl)pyrrolidine-3-carboxamide;

N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2,2-dimethylchroman-7-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2,2-dimethylchroman-7-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(quinolin-2-yl)pyrrolidine-3-carboxamide;

N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(quinolin-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(quinolin-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(2-chlorobenzo[b]thiophen-6-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

1-(2-chlorobenzo[b]thiophen-6-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(2-chlorobenzo[b]thiophen-6-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

N-[2-(2H,3H-benzo[e]1,4-dioxan-6-yl)(1R,2R)-2-hydroxy-1-(pyrrolidinylmethyl)ethyl][1-(4-chlorophenyl)pyrrolidin-3-yl]carboxamide;

(R)—N-((1R,2R)-3-(azetidin-1-yl)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-3-(azetidin-1-yl)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

N-((1R,2R)-3-(azetidin-1-yl)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-3-(azetidin-1-yl)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidine-3-carboxamide;

N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2,6-dimethylpyridin-4-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2,6-dimethylpyridin-4-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(quinoxalin-6-yl)pyrrolidine-3-carboxamide;

N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(quinoxalin-6-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(quinoxalin-6-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(1-chloro-6-fluoronaphthalen-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

1-(1-chloro-6-fluoronaphthalen-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(1-chloro-6-fluoronaphthalen-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-chloronaphthalen-2-yl)pyrrolidine-3-carboxamide;

N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-chloronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(6-chloronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(1,5-naphthyridin-3-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(1,5-naphthyridin-3-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(benzo[b]thiophen-6-yl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(benzo[b]thiophen-6-yl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(6-chloroquinolin-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

1-(6-chloroquinolin-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(6-chloroquinolin-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(6-chloroquinolin-2-yl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-chloro-3-(pyridin-2-yloxy)phenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(quinolin-7-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(2-chlorobenzo[b]thiophen-6-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-chloro-3-(pyridin-2-yloxy)phenyl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(2-chlorobenzo[b]thiophen-6-yl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(6-(4-chlorophenoxy)pyridin-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(6-(4-chlorophenoxy)pyridin-2-yl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-(4-fluorophenoxy)pyridin-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-(4-fluorophenoxy)pyridin-2-yl)pyrrolidine-3-carboxamide;

(R)-1-benzoyl-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-benzoyl-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-(4-fluorophenyl)pyridin-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-(4-fluorophenyl)pyridin-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(1-methyl-1H-indazol-5-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(5-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(1-methyl-1H-indazol-6-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-3-(azetidin-1-yl)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxypropan-2-yl)-1-(1-methyl-1H-indazol-6-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-hydroxy-3-(pyrrolidin-1-yl)-1-(8-(trifluoromethyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-(tert-butyl)phenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(5-chloro-6-(4-fluorophenyl)pyridin-2-yl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-3-hydroxypyrrolidine-3-carboxamide; and

(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-3-hydroxypyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-(trifluoromethyl)phenyl)pyrrolidine-3-carboxamide;

N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-(trifluoromethoxy)phenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-isopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(3-chloro-4-isopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-((1-methylpiperidin-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(3-chloro-4-((1-methylpiperidin-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(pyridin-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(pyridin-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5-chloropyridin-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5-chloropyridin-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-(oxetan-3-yloxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(4-(2-(azetidin-1-yl)ethoxy)-3-chlorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(4-(2-(azetidin-1-yl)ethoxy)-3-chlorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(4-cyclopropoxy-3-fluorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(piperidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(4-cyclopropoxy-3-fluorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(4-cyclopropoxy-3-fluorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-3-(azetidin-1-yl)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxypropan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-morpholinophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(3-chloro-4-morpholinophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(3-(pyridin-2-yloxy)phenyl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(3-(pyridin-2-yloxy)phenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-3-(azetidin-1-yl)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxypropan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-(2-hydroxy-2-methylpropoxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(R)-1-(benzo[b]thiophen-6-yl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(benzo[b]thiophen-6-yl)-N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-3-(azetidin-1-yl)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-chloroquinolin-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2-chlorobenzo[b]thiophen-6-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-(2-hydroxy-2-methylpropoxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-chloro-3-(pyridin-2-yloxy)phenyl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-(2-hydroxy-2-methylpropoxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(naphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2-chlorobenzo[b]thiophen-6-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-(4-chlorophenoxy)pyridin-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-(4-fluorophenoxy)pyridin-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-(oxetan-3-yloxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(2-chloro-5-(pyridin-2-yloxy)phenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-3-(azetidin-1-yl)-1-(3-chloro-4-(oxetan-3-yloxy)phenyl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-(4-fluorophenyl)pyridin-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(1-methyl-1H-indazol-5-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-chloro-3-(4-fluorophenoxy)phenyl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-benzoyl-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-chloro-3-((6-methylpyridin-2-yl)oxy)phenyl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(1-methyl-1H-indazol-6-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(4-(tert-butoxy)-3-chlorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(R)-1-(4-chloro-3-(cyclohexyloxy)phenyl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(6-chloro-4′-fluoro-[1,1′-biphenyl]-3-yl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-(tert-butyl)phenyl)-N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclobutoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-(cyclopentyloxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-(cyclopropylthio)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(5-chloro-6-(4-fluorophenyl)pyridin-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-(vinyloxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-phenylpyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-phenylpyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(4-cyclopropoxy-3-fluorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-phenylpyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-cyanophenyl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-cyanophenyl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(3-chloro-4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(p-tolyl)pyrrolidine-3-carboxamide;

(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(4-chlorophenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(benzo[b]thiophen-6-yl)-N-((1R,2R)-1-(4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-3-(azetidin-1-yl)-1-(4-cyclopropoxyphenyl)-1-hydroxypropan-2-yl)-1-(benzo[b]thiophen-6-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-3-(azetidin-1-yl)-1-(4-cyclopropoxyphenyl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-3-(azetidin-1-yl)-1-(4-cyclopropoxyphenyl)-1-hydroxypropan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(4-(difluoromethoxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(4-(difluoromethoxy)phenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-phenylpyrrolidine-3-carboxamide; and

(R)—N-((1R,2R)-1-(4-cyclopropoxyphenyl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(6-fluoronaphthalen-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(6-cyclopropoxypyridin-3-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(6-cyclopropoxypyridin-3-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)—N-((1R,2R)-1-(6-cyclopropoxypyridin-3-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;

(S)—N-((1R,2R)-1-(6-cyclopropoxypyridin-3-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-fluorophenyl)pyrrolidine-3-carboxamide;

(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-hydroxy-1-(6-isopropoxypyridin-3-yl)-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(4-chlorophenyl)-N-((1R,2R)-1-hydroxy-1-(6-isopropoxypyridin-3-yl)-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-fluorophenyl)-N-((1R,2R)-1-hydroxy-1-(6-isopropoxypyridin-3-yl)-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-hydroxy-3-(pyrrolidin-1-yl)-1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(4-chlorophenyl)-N-((1R,2R)-1-hydroxy-3-(pyrrolidin-1-yl)-1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-fluorophenyl)-N-((1R,2R)-1-hydroxy-3-(pyrrolidin-1-yl)-1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(4-fluorophenyl)-N-((1R,2R)-1-hydroxy-3-(pyrrolidin-1-yl)-1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-(2,2-dimethylchroman-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(S)-1-(4-chlorophenyl)-N-((1R,2R)-1-(2,2-dimethylchroman-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide;

(R)-1-(4-chlorophenyl)-N-((1R,2R)-1-hydroxy-1-(6-(oxetan-3-yloxy)pyridin-3-yl)-3-(pyrrolidin-1-yl)propan-2-yl)pyrrolidine-3-carboxamide; and

(R)—N-((1R,2R)-1-(benzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)-1-(4-chlorophenyl)pyrrolidine-3-carboxamide; and

optionally as a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally as a pharmaceutically acceptable salt thereof;

wherein the disease or disorder is selected from the group consisting of: a glycolipid storage disease, hyperglycemia, hyperinsulemia, polycystic kidney disease, and diabetes mellitus.

15. The method of claim 14 , wherein the disease or disorder is the glycolipid storage disease selected from the group consisting of Tay Sachs, Sandhoffs, GMI gangliosidosis, Niemanns-Pick, Fabry diseases, and Gaucher disease.

16. A method of treating a disease or disorder, the method comprising administering to the subject a pharmaceutical composition comprising:

i) an effective amount of a compound of Formula I:

and

ii) a pharmaceutically acceptable excipient or carrier;

wherein:

R 1 is N—(R 6 )-azetidinyl, N—(R 6 )-pyrrolidinyl, or N—(R 6 )-piperidinyl, each of which is attached to the C(O) group by a carbon atom and is optionally substituted with hydroxy;

R 2 and R 3 together with the nitrogen to which they are attached form a 4-6 membered heterocycloalkyl ring with 1 or 2 nitrogen atoms, which is optionally substituted with 1 or 2 R 8

R 4 is aryl or heteroaryl each of which is optionally substituted with 1, 2, or 3 R 9 groups;

each R 8 , when present, is independently deuterium, amino, alkylamino, dialkylamino, alkyl, hydroxy, alkoxy, halo, haloalkyl, or cycloalkyl;

each R 9a , when present, is independently selected from alkyl, hydroxy, alkoxy, halo, haloalkyl, haloalkoxy, alkoxycarbonyl, amino, alkylamino, and dialkylamino;

each R 10a , when present, is independently selected from cyano, halo, alkyl, alkenyl, haloalkyl, hydroxyalkyl, and cycloalkyl; and

R 11 , R 11a , and R 11b are independently hydrogen, alkyl, or cycloalkyl; and

optionally a tautomer, a single stereoisomer or mixture of stereoisomers thereof and additionally optionally a pharmaceutically acceptable salt thereof, and

wherein the disease or disorder is selected from the group consisting of: a glycolipid storage B disease, hyperglycemia, hyperinsulemia, polycystic kidney disease, and diabetes mellitus.

17. The method of claim 16 , wherein the disease or disorder is the glycolipid storage disease selected from the group consisting of Tay Sachs, Sandhoffs, GMI gangliosidosis, Niemanns-Pick, Fabry diseases, and Guacher disease.

18. The method of claim 14 , wherein the compound of Formula I is selected from the group consisting of: