Compounds for therapeutic use

1. A method of treating a major depressive disorder or persistent depressive disorder, comprising administering to a patient in need thereof a therapeutically effective amount of a compound, or pharmaceutically acceptable salt thereof, of Formula (I):

wherein:

R 1 is —H; or

R 1 is —C 1-6 alkyl, optionally substituted with one or more members, each independently selected from the group consisting of: -halo, -hydroxy, -alkoxy, -amino and -carboxyl; or

R 1 is —C 3-8 alkenyl or —C 3-8 alkynyl, each optionally substituted with one or more members, each independently selected from the group consisting of: -halo, -hydroxy, —C 1-4 alkyl, —C 1-4 alkoxy, and amino; or

R 1 is —(CH 2 ) n aryl, —(CH 2 ) n heteroaryl, —(CH 2 ) n cycloalkyl, or —(CH 2 ) n heterocycloalkyl, each optionally substituted with one or more members, each independently selected from the group consisting of: -halo, -hydroxy, —C 1-4 alkyl, —C 1-4 alkoxy, and -amino, wherein n is independently an integer selected from 0, 1, 2, 3, and 4; or

R 1 is —COR 2 , —CONR 3 R 4 , —CR 5 R 6 NR 7 R 8 , —CHR 9 R 10 , or —C(OH)R 11 R 12 ,

wherein R 2 , R 3 , R 4 , R 7 and R 8 are each independently selected from the group consisting of: —H, —C 1-8 alkyl, and —C 1-8 haloalkyl;

R 5 and R 6 are each independently selected from the group consisting of: —H, -halo, —NH 2 , —C 1-8 alkyl, —C 1-8 haloalkyl, —(CH 2 ) n CONH 2 , —(CH 2 ) n COOH, —(CH 2 ) n aryl, —(CH 2 ) n heteroaryl, —(CH 2 ) n cycloalkyl, and —(CH 2 ) n heterocycloalkyl, each optionally substituted with one or more members, each independently selected from the group consisting of: -guanidyl, -urea, -halo, -alkyl, -hydroxy, -amino, -alkoxy, -2,3-dihydro-1H-pyrrole-1-carboxamide, —(CH 2 ) n CONR 1A R 1B , —(CH 2 ) n NHC(═O)R 1A , —(CH 2 ) n NR 1A R 1B , —(CH 2 ) n ORC, —(CH 2 ) n SR 1C and —(CH 2 ) n SeR 1C , wherein n is independently an integer selected from 0, 1, 2, 3, and 4;

each R 1A is independently selected from the group consisting of: —H —C 1-8 alkyl, —(CH 2 ) n CONH 2 , and —(CH 2 ) n heterocycloalkyl, wherein n is independently an integer selected from 0, 1, 2, 3, and 4;

each R 1B is independently selected from the group consisting of: —H, —C 1-8 alkyl, and —(CH 2 ) n CONH 2 , wherein n is independently an integer selected from 0, 1, 2, 3, and 4;

each R 1C is independently selected from the group consisting of: —H —C 1-8 alkyl, —C 1-8 haloalkyl, —(CH 2 ) n CONH 2 , —(CH 2 ) n COOH, —(CH 2 ) n aryl, —(CH 2 ) n heteroaryl, —(CH 2 ) n cycloalkyl, and —(CH 2 ) n heterocycloalkyl, wherein n is independently an integer selected from 0, 1, 2, 3, and 4;

R 9 and R 10 are each independently selected from the group consisting of: —H, —C 1-8 alkyl, and —C 1-8 haloalkyl, said alkyl optionally substituted with up to 3 members, each independently selected from the group consisting of: -amino, -hydroxy and -carboxyl; or optionally R 9 and R 10 taken together with the carbon to which they are attached form an optionally substituted five membered heteroaryl or heterocycloalkyl ring; and

R 11 and R 12 are independently selected from the group consisting of: —H, —C 1-6 alkyl, and —C 1-6 haloalkyl, said —C 1-6 alkyl, and —C 1-6 haloalkyl optionally substituted with up to 3 members, each independently selected from the group consisting of: —hydroxy and amino.

2. The method of claim 1 , wherein:

R 1 is —H; or

R 1 is —C 1-6 alkyl, optionally substituted with one or more members, each independently selected from the group consisting of: -halo, -hydroxy, -alkoxy, -amino and -carboxyl; or

R 1 is —C 3-8 alkenyl or —C 3-8 alkynyl, each optionally substituted with one or more members, each independently selected from the group consisting of: -halo, -hydroxy, —C 1-4 alkyl, —C 1-4 alkoxy, and amino; or

R 1 is —(CH 2 ) n aryl, —(CH 2 ) n heteroaryl, —(CH 2 ) n cycloalkyl, or —(CH 2 ) n heterocycloalkyl, each optionally substituted with one or more members, each independently selected from the group consisting of: -halo, -hydroxy, —C 1-4 alkyl, —C 1-4 alkoxy, and -amino, wherein n is independently an integer selected from 0, 1, 2, 3, and 4; or

R 1 is —CR 5 R 6 NR 7 R 8 , —CHR 9 R 10 , or —C(OH)R 1 R 12 ,

wherein R 7 and R 8 are independently selected from the group consisting of: —H, —C 1-8 alkyl, and —C 1-8 haloalkyl;

R 5 and R 6 are each independently selected from the group consisting of: —H, -halo, —NH 2 , —C 1-8 alkyl, —C 1-8 haloalkyl, —(CH 2 ) n CONH 2 , —(CH 2 ) n COOH, —(CH 2 ) n aryl, —(CH 2 ) n heteroaryl, —(CH 2 ) n cycloalkyl, and —(CH 2 ) n heterocycloalkyl, each optionally substituted with one or more members, each independently selected from the group consisting of: -guanidyl, -urea, -halo, -alkyl, -hydroxy, -amino, -alkoxy, -2,3-dihydro-1H-pyrrole-1-carboxamide, —(CH 2 ) n NR 1A R 1B , —(CH 2 ) n OR 1C , —(CH 2 ) n SR 1C and —(CH 2 ) n SeR 1C , wherein n is independently an integer selected from 0, 1, 2, 3, and 4;

each R 1A is independently selected from the group consisting of: —H —C 1-8 alkyl, and —(CH 2 ) n heterocycloalkyl, wherein n is independently an integer selected from 0, 1, 2, 3, and 4;

each R 1B is independently selected from the group consisting of: —H and —C 1-8 alkyl, wherein n is independently an integer selected from 0, 1, 2, 3, and 4;

each R 1C is independently selected from the group consisting of: —H, —C 1-8 alkyl, —C 1-8 haloalkyl, —(CH 2 ) n aryl, —(CH 2 ) n heteroaryl, —(CH 2 ) n cycloalkyl, and —(CH 2 ) n heterocycloalkyl, wherein n is independently an integer selected from 0, 1, 2, 3, and 4;

R 9 and R 10 are each independently selected from the group consisting of: —H, —C 1-8 alkyl, and —C 1-8 haloalkyl, said alkyl optionally substituted with up to 3 members, each independently selected from the group consisting of -amino, -hydroxy, and -carboxyl; or optionally R 9 and R 10 taken together with the carbon to which they are attached can form an optionally substituted five membered heteroaryl or heterocycloalkyl ring; and

R 11 and R 12 are each independently selected from the group consisting of: —H, —C 1-6 alkyl, and —C 1-6 haloalkyl, said —C 1-6 alkyl, and —C 1-6 haloalkyl optionally substituted with up to 3 members, each independently selected from the group consisting of: -hydroxy and -amino.

3. The method of claim 1 , wherein:

R 1 is —CR 5 R 6 NR 7 R 8 or —CR 9 R 10 ,

wherein R 5 and R 6 are independently selected from the group consisting of: —H, —F, —Cl, —Br, —NH 2 , -methyl, -ethyl, -n-propyl, -isopropyl, -butyl, -pentyl, —NH 2 , —C 1-8 haloalkyl, —(CH 2 ) n CONH 2 , —(CH 2 ) n COOH, —(CH 2 ) n aryl, —(CH 2 ) n benzyl, —(CH 2 ) n heteroaryl, —(CH 2 )indole, —(CH 2 )imidazole, —(CH 2 ) n cycloalkyl, —(CH 2 ) n heterocycloalkyl, —(CH 2 ) n pyrrolidine, —(CH 2 )furan, and —(CH 2 ) n thiophene, optionally substituted with up to 3 members, each independently selected from the group consisting of: -guanidyl, -urea, -halo, -alkyl, -hydroxy, -amino, -alkoxy, -2,3-dihydro-1H-pyrrole-1-carboxamide, —(CH 2 ) n NR 1A R 1B , —(CH 2 ) n OR 1C , —(CH 2 ) n SR 1C and —(CH 2 ) n SeR 1C , wherein n is independently an integer selected from 0, 1, 2, 3, and 4;

each R 1A is independently selected from the group consisting of: —H, —C 1-8 alkyl, and —(CH 2 ) n heterocycloalkyl, wherein n is independently an integer selected from 0, 1, 2, 3, and 4;

each R 1B is independently selected from the group consisting of: —H and —C 1-8 alkyl, wherein n is independently an integer selected from 0, 1, 2, 3, and 4;

each R 1C is independently selected from the group consisting of: —H —C 1-8 alkyl, —C 1-8 haloalkyl, —(CH 2 ) n aryl, —(CH 2 ) n heteroaryl, —(CH 2 ) n cycloalkyl, and —(CH 2 ) n heterocycloalkyl, wherein n is independently an integer selected from 0, 1, 2, 3, and 4;

R 7 and R 8 are —H; and

R 9 and R 10 are independently selected from the group consisting of: —H, —C 1-8 alkyl, and —C 1-8 haloalkyl; or optionally R 9 and R 10 taken together with the carbon to which they are attached can form an optionally substituted five membered heteroaryl or heterocycloalkyl ring.

4. The method of claim 1 , wherein the therapeutically effective amount is an amount sufficient to achieve remission on a depression symptoms rating scale.

5. A method of treating a major depressive disorder or persistent depressive disorder comprising administering to a patient in need thereof a therapeutically effective amount of a compound selected from the group consisting of:

(1R,5R)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-5-(2-chlorophenyl)-3-methyl-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R, 5R)-5-(2-chlorophenyl)-3-(1-hydroxyethyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-((S)-1-amino-2-methylpropyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-(aminomethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-5-(2-chlorophenyl)-3-fluorocarbonyl-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-5-(2-chlorophenyl)-3-((S)-1,5-diaminopentyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-((S)-1-aminoethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-5-(2-chlorophenyl)-3-phenyl-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-((1 S,2R)-1-amino-2-methylbutyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-((S)-1-amino-3-methylbutyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-((S)-1-amino-2-phenylethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-((S)-1-amino-2-(4-hydroxyphenyl)ethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-((S)-1-amino-2-(1H-indol-3-yl)ethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-((S)-1-amino-2-(1H-imidazol-4-yl)ethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-5-(2-chlorophenyl)-3-(pyrrolidin-2-yl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(S)-3-amino-3-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)propanoic acid;

(S)-4-amino-4-((1R, 5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)butanoic acid;

(S)-4-amino-4-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)butanamide;

(S)-3-amino-3-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)propanamide;

(1R,5R)-3-((S)-1-amino-3-(methylthio)propyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-((R)-1-amino-2-mercaptoethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-((S)-1-amino-2-hydroxyethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-((S)-1-amino-2-methoxyethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

1-((S)-4-amino-4-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)butyl)guanidine;

(1R,5R)-5-(2-chlorophenyl)-3-ethyl-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

3-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)-2-hydroxypropanoic acid;

2-(((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)methyl)-2-hydroxysuccinic acid;

5-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)pentanoic acid;

3-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)-2,3-dihydroxypropanoic acid;

3-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)propanoic acid;

(1R,5R)-5-(2-chlorophenyl)-3-heptyl-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-(1-amino-2-hydroselenoethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-5-(2-chlorophenyl)-3-(2-(methylamino)ethyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-5-(2-chlorophenyl)-3-(1,2-diaminoethyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-(2-amino-1-hydroxyethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-(3-aminopropyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-(4-aminobutyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-(3-aminopentyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-(1-amino-3-hydroxypropyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-5-(2-chlorophenyl)-3-(1,4-diaminobutyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

4-amino-4-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)-N-ethylbutanamide;

(1R,5R)-5-(2-chlorophenyl)-3-(1,5-diamino-4-hydroxypentyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

1-(4-amino-4-((1R, 5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)butyl)urea;

1-(5-amino-5-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)pentyl)urea;

1-(5-amino-5-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)pentyl)guanidine;

1-(2-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)ethyl)guanidine;

(1R,5R)-3-(1-amino-2-methylbutyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-(1-amino-2-(5-hydroxy-1H-indol-3-yl)ethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-(1-amino-2-(5-methyl-1H-indol-3-yl)ethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3:1]non-3-en-9-one;

(1R,5R)-3-(2-(1H-indol-3-yl)-1-(methylamino)ethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-5-(2-chlorophenyl)-3-(4-hydroxypyrrolidin-2-yl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-(1-amino-2-hydroxy-3-methylbutyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-5-(2-chlorophenyl)-3-(1-(methylamino)ethyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-(2-aminopropyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

N-(5-amino-5-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)pentyl)-3-methyl-3,4-dihydro-2H-pyrrole-2-carboxamide;

(1R,5R)-3-(1-amino-3-hydroxy-2-methylbutyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-(1-amino-2,2-dimethylpropyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-(amino(3-amino-4-hydroxyphenyl)methyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-(1-amino-2-hydroxy-2-phenylethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-(1-amino-2-(4-methoxyphenyl)ethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-5-(2-chlorophenyl)-3-methyl-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-5-(2-chlorophenyl)-3-(1-hydroxyethyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-3-((S)-1-amino-2-methylpropyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-3-(aminomethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5S)-5-(2-chlorophenyl)-3-fluorocarbonyl-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-5-(2-chlorophenyl)-3-((S)-1,5-diaminopentyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1S,5 S)-3-((S)-1-aminoethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-5-(2-chlorophenyl)-3-phenyl-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1S,5 S)-3-((1 S,2R)-1-amino-2-methylbutyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-3-((S)-1-amino-3-methylbutyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-3-((S)-1-amino-2-phenylethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-3-((S)-1-amino-2-(4-hydroxyphenyl)ethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-3-((S)-1-amino-2-(1H-indol-3-yl)ethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5S)-3-((S)-1-amino-2-(1H-imidazol-4-yl)ethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-5-(2-chlorophenyl)-3-(pyrrolidin-2-yl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(S)-3-amino-3-((1 S,5 S)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)propanoic acid;

(S)-4-amino-4-((1 S,5 S)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)butanoic acid;

(S)-4-amino-4-((1 S,5 S)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)butanamide;

(S)-3-amino-3-((1 S,5S)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)propanamide;

(1 S,5 S)-3-((S)-1-amino-3-(methylthio)propyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-3-((R)-1-amino-2-mercaptoethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-3-((S)-1-amino-2-hydroxyethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-3-((S)-1-amino-2-methoxyethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

1-((S)-4-amino-4-((1 S,5 S)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)butyl)guanidine;

(1 S,5 S)-5-(2-chlorophenyl)-3-ethyl-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

3-((1 S,5 S)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)-2-hydroxypropanoic acid;

2-(((1 S,5 S)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)methyl)-2-hydroxysuccinic acid;

5-((1 S, 5 S)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)pentanoic acid;

3-((1 S,5 S)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)-2,3-dihydroxypropanoic acid;

3-((1 S,5 S)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)propanoic acid;

(1 S,5 S)-5-(2-chlorophenyl)-3-heptyl-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-3-(1-amino-2-hydroselenoethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-5-(2-chlorophenyl)-3-(2-(methylamino)ethyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-5-(2-chlorophenyl)-3-(1,2-diaminoethyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1S,5 S)-3-(2-amino-1-hydroxyethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-3-(3-aminopropyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1S,5 S)-3-(4-aminobutyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-3-(3-aminopentyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1S,5 S)-3-(1-amino-3-hydroxypropyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-5-(2-chlorophenyl)-3-(1,4-diaminobutyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

4-amino-4-((1 S,5 S)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)-N-ethylbutanamide;

(1 S,5 S)-5-(2-chlorophenyl)-3-(1,5-diamino-4-hydroxypentyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

1-(4-amino-4-((1 S,5 S)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)butyl)urea;

1-(5-amino-5-((1 S,5 S)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)pentyl)urea;

1-(5-amino-5-((1 S,5S)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)pentyl)guanidine;

1-(2-((1 S,5 S)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)ethyl)guanidine;

(1S,5S)-3-(1-amino-2-methylbutyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1S,5 S)-3-(1-amino-2-(5-hydroxy-1H-indol-3-yl)ethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1S,5S)-3-(1-amino-2-(5-methyl-1H-indol-3-yl)ethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1S,5 S)-3-(2-(1H-indol-3-yl)-1-(methylamino)ethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5S)-5-(2-chlorophenyl)-3-(4-hydroxypyrrolidin-2-yl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1S,5 S)-3-(1-amino-2-hydroxy-3-methylbutyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-5-(2-chlorophenyl)-3-(1-(methylamino)ethyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-3-(2-aminopropyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

N-(5-amino-5-((1S,5 S)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)pentyl)-3-methyl-3,4-dihydro-2H-pyrrole-2-carboxamide;

(1 S,5 S)-3-(1-amino-3-hydroxy-2-methylbutyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-3-(1-amino-2,2-dimethylpropyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-3-(amino(3-amino-4-hydroxyphenyl)methyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5S)-3-(1-amino-2-hydroxy-2-phenylethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1 S,5 S)-3-(1-amino-2-(4-methoxyphenyl)ethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

and pharmaceutically acceptable salts thereof.

6. The method of claim 5 , wherein the compound is selected from the group consisting of:

(1R,5R)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(S)-3-amino-3-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)propanoic acid;

(S)-4-amino-4-((1R, 5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)butanoic acid;

(S)-4-amino-4-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)butanamide;

(S)-3-amino-3-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)propanamide;

(1R,5R)-3-((S)-1-amino-3-(methylthio)propyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(1R,5R)-3-((R)-1-amino-2-mercaptoethyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

1-((S)-4-amino-4-((1R, 5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)butyl)guanidine;

3-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)-2-hydroxypropanoic acid;

2-(((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)methyl)-2-hydroxysuccinic acid;

5-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)pentanoic acid;

3-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)-2,3-dihydroxypropanoic acid;

3-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)propanoic acid;

4-amino-4-((1, R, 5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)-N-ethylbutanamide;

1-(4-amino-4-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)butyl)urea;

1-(5-amino-5-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)pentyl)urea;

1-(5-amino-5-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)pentyl)guanidine;

1-(2-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)ethyl)guanidine;

N-(5-amino-5-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)pentyl)-3-methyl-3,4-dihydro-2H-pyrrole-2-carboxamide;

and pharmaceutically acceptable salts thereof.

7. The method of claim 5 , wherein the compound is selected from the group consisting of:

(1R,5R)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

(S)-3-amino-3-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)propanoic acid;

(S)-4-amino-4-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)butanoic acid;

(S)-4-amino-4-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)butanamide;

(S)-3-amino-3-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)propanamide;

(1R,5R)-3-((S)-1-amino-3-(methylthio)propyl)-5-(2-chlorophenyl)-2-oxa-4-azabicyclo[3.3.1]non-3-en-9-one;

1-((S)-4-amino-4-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)butyl)guanidine;

3-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)-2-hydroxypropanoic acid;

3-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)-2,3-dihydroxypropanoic acid;

3-((1R,5R)-5-(2-chlorophenyl)-9-oxo-2-oxa-4-azabicyclo[3.3.1]non-3-en-3-yl)propanoic acid;

and pharmaceutically acceptable salts thereof.

8. The method of claim 5 , wherein the therapeutically effective amount is an amount sufficient to achieve remission on a depression symptoms rating scale.