Selective octahydro-cyclopenta[C] pyrrole negative modulators of NR2B

1. A compound of Formula I:

or pharmaceutically acceptable salt, tautomer, or stereoisomer thereof

wherein:

L 1 is straight or branched C 2 -C 4 alkyl optionally substituted with one or more substituents selected from the group consisting of OH, D, OR 10 , NH 2 , NHR 10 , and N(R 10 )(R 10′ ), provided that no more than one oxygen or nitrogen is attached to any carbon;

or

L 1 is selected from the group consisting of —CO—C 1 -C 2 alkylenyl-, —S(O) 2 —, —S(O) 2 NH—, —C(O)NH—, —C(O)NR 10 —, —C 1 -C 3 alkylenyl-C(O)—C 1 -C 3 alkylenyl-, and a bond, wherein the C 1 -C 2 alkylenyl and C 1 -C 3 alkylenyl is optionally substituted with C 1 -C 4 alkyl;

Each R 10 and R 10′ is independently selected from the group consisting of H; O—C 1 -C 5 alkyl; C 1 -C 6 alkyl optionally substituted with one or more substituents selected from the group consisting of OH, O—C 1 -C 5 alkyl, —OP(O)(OH) 2 , OP(O)O 2 −2 M 2 , —OC(O)alkyl, —OC(O)Oalkyl, and aryl; and cycloalkyl optionally substituted with one or more substituents selected from the group consisting of OH and O—C 1 -C 5 alkyl;

provided that no more than one oxygen is attached to any carbon of R 10 and R 10′ ;

M is a monovalent metal cation;

R 1 is aryl optionally substituted with one or more substituents selected from the group consisting of OH, CN, halogen, —O—R 10 , —OP(O)(OH) 2 , OP(O)O 2 −2 M 2 , —SH, —S—R 10 , C 1 -C 5 alkyl, branched alkyl, —C 1 -C 6 haloalkyl, NH 2 , NHR 10 , —C 1 -C 6 hydroxyalkyl, N(R 10 )(NR 10′ ), —NHS(O) 2 R 10 , —O-alkylaryl, —O—(CH 2 )—C(O)-aryl, and NHCOR 10 ; M is a monovalent metal cation; or

R 1 is cycloalkyl;

X is selected from the group consisting of H, halogen, OH, O—C 1 -C 6 alkyl, O-branched alkyl, C 1 -C 5 straight alkyl and C 1 -C 5 branched alkyl;

Y and Y′ are independently H, F, or methyl;

L 2 is —(CH 2 ) n — or —(CHR 11 ) n —, or a bond;

Each R 11 is independently selected from the group consisting of H, —C 1 -C 5 alkylenyl-, —C(O)—C 1 -C 5 alkylenyl-, and -alkylenyl-CO-alkylenyl-;

R 2 is C 3 -C 8 cycloalkyl; phenyl, or naphthyl, each of which is optionally substituted with one or more substituents selected from the group consisting of halogen, OH, C 1 -C 6 alkyl, OR 10 , CN, NH 2 , NHR 10 , N(R 10 )(R 10′ ), SH, SR 10 , SOR 10 , SO 2 R 10 , SO 2 NHR 10 , SO 2 N(R 10 )(R 10′ ), CONH 2 , CONR 10 , and CON(R 10 )(R 10′ ); and

n is 1, 2, or 3.

2. The compound of claim 1 wherein R 1 is aryl substituted with one or more substituents selected from the group consisting of OH, OR 10 , SH, SR 10 , NH 2 , NHR 10 and NHCOR 10 .

3. The compound of claim 1 wherein R 1 is aryl substituted with one substituent selected from the group consisting of OH, OR 10 , SH, SR 10 , NH 2 , NHR 10 and NHCOR 10 .

4. The compound of claim 1 wherein Y and Y′ are hydrogen.

5. The compound of claim 1 wherein L 2 is a bond.

6. The compound of claim 1 wherein R 2 is phenyl optionally substituted with one or more halogen, OH, OR 10 , CN, NH 2 , NHR 10 , N(R 10 )(R 10′ ), SH, SR 10 , SOR 10 , SO 2 R 10 , SO 2 NHR 10 , SO 2 N(R 10 )(R 10′ ), CONH 2 , CONR 10 , CON(R 10 )(R 10′ ).

7. The compound of claim 1 wherein R 2 is phenyl substituted with one or more halogen.

8. The compound of claim 1 wherein L 1 is branched C 2 -C 4 alkyl substituted with one or more substituents selected from the group consisting of OH, OR 10 , NH 2 , NHR 10 , and N(R 10 )(R 10′ ) provided that no more than one oxygen or nitrogen is attached to any carbon of L 1 .

9. The compound of claim 1 wherein L 1 is straight C 1 -C 5 alkyl substituted with one or more substituents selected from the group consisting of OH, OR 10 , NH 2 , NHR 10 , and N(R 10 )(R 10′ ) provided that no more than one oxygen or nitrogen is attached to any carbon of L 1 .

10. A compound of claim 1 of Formula (Ia):

or pharmaceutically acceptable salt, tautomer, or stereoisomer thereof

wherein:

A, B, C and D are CH;

X is CH or C;

Y is OH or O;

R 3 is H or CH 3

n is 0, 1, or 2;

R is H, OH or F; and

R 1 is H or F.

11. The compound of claim 10 wherein X and Y form a carbonyl, or X is CH and Y is OH.

12. The compound of claim 10 wherein R 3 is H; R is H or OH.

13. A compound of claim 1 of Formula (Ib):

or pharmaceutically acceptable salt, tautomer, or stereoisomer thereof

wherein:

A, B, C, and D are independently CR x ;

X is CH or C;

Y is OH or O;

R 3 is H

n is 0, 1, or 2;

R is H, or CH 3 ; and

R x is H, C 1-6 alkyl, halogen, —OH, or —OC 1-6 alkyl.

14. A compound of claim 1 of Formula (Ic):

or pharmaceutically acceptable salt, tautomer, or stereoisomer thereof

wherein:

A is CR x ;

U is C═O, or C(R x ) m ;

V is C═O, or C(R X ) m ;

each W is independently C═O, or C(R X ) m ;

is an optional double bond which allows the E ring to be partially or fully saturated;

X is CH or C;

Y is OH or O;

R 3 is H;

n is 0, 1, or 2;

each m is independently 1 or 2;

R is H, OH, or CH 3 ;

R x is H, C 1-6 alkyl, halogen, —OH, or —OC 1-6 alkyl; and

R y is H, or C 1-6 alkyl.

15. A compound of claim 1 of Formula (Id):

or pharmaceutically acceptable salt, tautomer, or stereoisomer thereof

wherein:

A, B, C, and D are independently CR x ;

X is CH or C;

Y is OH or O;

R 3 is H;

n is 0, 1, or 2;

R is F;

R x is H, C 1-6 alkyl, halogen, —OH, or —OC 1-6 alkyl.

16. A compound of claim 1 of Formula (Ie):

or pharmaceutically acceptable salt, tautomer, or stereoisomer thereof

wherein:

A is CR x ;

U is C═O, or C(R X ) m ;

V is C═O, or C(R X ) m ;

each W is independently C═O, or C(R X ) m ;

is an optional double bond which allows the E ring to be partially or fully saturated;

X is CH or C;

Y is OH or O;

R 3 is H;

n is 0, 1, or 2;

each m is independently 1 or 2;

R is H, OH, or CH 3 ;

R x is H, C 1-6 alkyl, halogen, —OH, or —OC 1-6 alkyl; and

R y is H, or C 1-6 alkyl.

17. A compound selected from the group consisting of

5-hydroxy-N-(4-methoxyphenyl)-5-phenylhexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide;

5-(4-cyanophenyl)-5-hydroxy-N-(4-methoxyphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-hydroxy-N-(4-methylphenyl)-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-(3-chlorophenyl)-5-hydroxy-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-hydroxy-5-phenyl-N-[3-(trifluoromethyl)phenyl]-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-(4-fluorophenyl)-5-hydroxy-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-hydroxy-N-(3-methoxyphenyl)-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-hydroxy-N-(4-methoxyphenyl)-5-(2-methylphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-hydroxy-5-(2-methylphenyl)-N-(4-methylphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-hydroxy-N-(3-methoxyphenyl)-5-(2-methylphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-(3-chlorophenyl)-5-hydroxy-5-(2-methylphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-hydroxy-5-(2-methylphenyl)-N-[3-(trifluoromethyl)phenyl]-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-(4-fluorophenyl)-5-hydroxy-5-(2-methylphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-hydroxy-5-(3-methoxyphenyl)-N-(4-methylphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-(3-chlorophenyl)-5-hydroxy-5-(3-methoxyphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-hydroxy-5-(3-methoxyphenyl)-N-[3-(trifluoromethyl)phenyl]-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-hydroxy-5-(3-methoxyphenyl)-N-(4-methoxyphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-hydroxy-N,5-bis(3-methoxyphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-(2,4-difluorophenyl)-5-hydroxy-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-[(1R)-1-(4-chlorophenyl)ethyl]-5-hydroxy-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-hydroxy-N-[(2-methoxyphenyl)methyl]-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

Methyl 4-(5-hydroxy-5-(o-tolyl)octahydrocyclopenta[c]pyrrole-2-carboxamido)benzoate;

5-hydroxy-N-(2-methoxy-5-methylphenyl)-5-(2-methylphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-[4-chloro-3-(trifluoromethyl)phenyl]-5-hydroxy-5-(2-methylphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-hydroxy-N,5-diphenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-(3-cyanophenyl)-5-hydroxy-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-hydroxy-N-(2-methoxy-5-methylphenyl)-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

methyl 4-[({5-hydroxy-5-phenyl-octahydrocyclopenta[c]pyrrol-2-yl}carbonyl)amino]benzoate;

5-hydroxy-5-(3-methoxyphenyl)-N-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-hydroxy-5-(2-methylphenyl)-N-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-(3-cyanophenyl)-5-hydroxy-5-(2-methylphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-[4-chloro-3-(trifluoromethyl)phenyl]-5-hydroxy-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-hydroxy-N-(2-methoxy-5-methylphenyl)-5-(3-methoxyphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-[4-chloro-3-(trifluoromethyl)phenyl]-5-hydroxy-5-(3-methoxyphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N,5-bis(4-fluorophenyl)-5-hydroxy-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-(4-fluorophenyl)-5-hydroxy-N-(4-methylphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-(4-fluorophenyl)-5-hydroxy-N-(3-methoxyphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-(4-fluorophenyl)-5-hydroxy-N-[3-(trifluoromethyl)phenyl]-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-(3-chlorophenyl)-5-(4-fluorophenyl)-5-hydroxy-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-(3-cyanophenyl)-5-(4-fluorophenyl)-5-hydroxy-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-(4-fluorophenyl)-5-hydroxy-N-(2-methoxy-5-methylphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-[4-chloro-3-(trifluoromethyl)phenyl]-5-(4-fluorophenyl)-5-hydroxy-octahydrocyclopenta[c]pyrrole-2-carboxamide;

methyl 4-({[5-hydroxy-5-(3-methoxyphenyl)-octahydrocyclopenta[c]pyrrol-2-yl]carbonyl}amino)benzoate;

N-(2,4-dimethylphenyl)-5-hydroxy-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-(2,4-dimethylphenyl)-5-hydroxy-5-(2-methylphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-(2,4-dimethylphenyl)-5-hydroxy-5-(3-methoxyphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

methyl 4-({[5-(4-tert-butylphenyl)-5-hydroxy-octahydrocyclopenta[c]pyrrol-2-yl]carbonyl}amino)benzoate;

5-(4-tert-butylphenyl)-5-hydroxy-N-(3-methoxyphenyl)-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-(4-tert-butylphenyl)-N-(3-cyanophenyl)-5-hydroxy-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-(4-tert-butylphenyl)-N-[4-chloro-3-(trifluoromethyl)phenyl]-5-hydroxy-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-(4-tert-butylphenyl)-5-hydroxy-N-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-(4-tert-butylphenyl)-5-hydroxy-N-[3-(trifluoromethyl)phenyl]-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-(4-tert-butylphenyl)-N-(3-chlorophenyl)-5-hydroxy-octahydrocyclopenta[c]pyrrole-2-carboxamide;

2-(5-hydroxy-5-phenylhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-phenylethanone;

rac-2-(2-hydroxy-2-phenylethyl)-5-phenyloctahydrocyclopenta[c]pyrrol-5-ol;

2-[5-hydroxy-5-(3-methoxyphenyl)-octahydrocyclopenta[c]pyrrol-2-yl]-1-phenylethan-1-one;

rac-2-(2-hydroxy-2-phenylethyl)-5-(3-methoxyphenyl)-octahydrocyclopenta[c]pyrrol-5-ol;

1-(3-fluorophenyl)-2-{5-hydroxy-5-phenyl-octahydrocyclopenta[c]pyrrol-2-yl}ethan-1-one;

1-(3-fluorophenyl)-2-[5-hydroxy-5-(3-methoxyphenyl)-octahydrocyclopenta[c]pyrrol-2-yl]ethan-1-one;

rac-2-[2-(3-fluorophenyl)-2-hydroxyethyl]-5-(3-methoxyphenyl)-octahydrocyclopenta[c]pyrrol-5-ol;

rac-2-[2-(3-fluorophenyl)-2-hydroxyethyl]-5-phenyl-octahydrocyclopenta[c]pyrrol-5-ol;

2-{5-hydroxy-5-phenyl-octahydrocyclopenta[c]pyrrol-2-yl}-1-(4-hydroxyphenyl)ethan-1-one;

2-{5-hydroxy-5-phenyl-octahydrocyclopenta[c]pyrrol-2-yl}-1-(4-methoxyphenyl)ethan-1-one;

rac-2-[2-hydroxy-2-(4-methoxyphenyl)ethyl]-5-phenyl-octahydrocyclopenta[c]pyrrol-5-ol;

rac-2-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-5-phenyl-octahydrocyclopenta[c]pyrrol-5-ol;

2-(5-hydroxy-5-phenylhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-(2-hydroxypropan-2-yl)phenyl)ethanone;

rac-2-(2-hydroxy-2-(4-(2-hydroxypropan-2-yl)phenyl)ethyl)-5-phenyloctahydrocyclopenta[c]pyrrol-5-ol;

rac-5-(4-(tert-butyl)phenyl)-2-(2-hydroxy-2-(3-(trifluoromethyl)phenyl)ethyl)octahydrocyclopenta[c]pyrrol-5-ol;

rac-5-(4-tert-butylphenyl)-2-[2-(3-fluorophenyl)-2-hydroxyethyl]-octahydrocyclopenta[c]pyrrol-5-ol;

rac-2-{2-hydroxy-2-[3-(trifluoromethyl)phenyl]ethyl}-5-(2-methylphenyl)-octahydrocyclopenta[c]pyrrol-5-ol;

rac-2-{2-hydroxy-2-[3-(trifluoromethyl)phenyl]ethyl}-5-(3-methoxyphenyl)-octahydrocyclopenta[c]pyrrol-5-ol;

rac-2-[2-(2,4-dichlorophenyl)-2-hydroxyethyl]-5-(3-methoxyphenyl)-octahydrocyclopenta[c]pyrrol-5-ol;

rac-5-(4-fluorophenyl)-2-{2-hydroxy-2-[3-(trifluoromethyl)phenyl]ethyl}-octahydrocyclopenta[c]pyrrol-5-ol;

rac-2-[2-(2,4-dichlorophenyl)-2-hydroxyethyl]-5-(4-fluorophenyl)-octahydrocyclopenta[c]pyrrol-5-ol;

rac-2-[2-hydroxy-2-(3-methoxyphenyl)ethyl]-5-(3-methoxyphenyl)-octahydrocyclopenta[c]pyrrol-5-ol;

rac-2-(1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl)-5-(3-methoxyphenyl)octahydrocyclopenta[c]pyrrol-5-ol;

2-(4-fluorobenzyl)-5-(4-fluorophenyl)octahydrocyclopenta[c]pyrrol-5-ol;

rac-2-(5-hydroxy-5-phenylhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)propan-1-one;

rac-2-(1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl)-5-phenyloctahydrocyclopenta[c]pyrrol-5-ol;

rac-2-[5-(4-fluorophenyl)-5-hydroxy-octahydrocyclopenta[c]pyrrol-2-yl]-1-(4-hydroxyphenyl)propan-1-one;

rac-2-[5-(4-tert-butylphenyl)-5-hydroxy-octahydrocyclopenta[c]pyrrol-2-yl]-1-(4-hydroxyphenyl)propan-1-one;

rac-2-[5-hydroxy-5-(2-methylphenyl)-octahydrocyclopenta[c]pyrrol-2-yl]-1-(4-hydroxyphenyl)propan-1-one;

rac-2-[1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl]-5-(2-methylphenyl)-octahydrocyclopenta[c]pyrrol-5-ol;

rac-5-(4-tert-butylphenyl)-2-[1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl]-octahydrocyclopenta[c]pyrrol-5-ol;

(5-hydroxy-5-phenylhexahydrocyclopenta[c]pyrrol-2(1H)-yl)(4-hydroxyphenyl)methanone;

3-(5-hydroxy-5-phenylhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)propan-1-one;

2-(3-hydroxy-3-(4-hydroxyphenyl)propyl)-5-phenyloctahydrocyclopenta[c]pyrrol-5-ol;

2N-(4-methoxyphenyl)-5-phenylhexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide;

N-(4-hydroxyphenyl)-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-(4-fluorophenyl)-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N,5-diphenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

methyl 4-[({5-phenyl-octahydrocyclopenta[c]pyrrol-2-yl}carbonyl)amino]benzoate;

N-(3-methoxyphenyl)-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

5-phenyl-N-[3-(trifluoromethyl)phenyl]-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-(3-chlorophenyl)-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-(3-cyanophenyl)-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-[4-chloro-3-(trifluoromethyl)phenyl]-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-(2-methoxy-5-methylphenyl)-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-(2,4-dimethylphenyl)-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-[(2-methoxyphenyl)methyl]-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

N-[(1R)-1-(4-chlorophenyl)ethyl]-5-phenyl-octahydrocyclopenta[c]pyrrole-2-carboxamide;

1-(4-hydroxyphenyl)-2-(5-phenylhexahydrocyclopenta[c]pyrrol-2(1H)-yl)ethanone;

4-(1-hydroxy-2-(5-phenylhexahydrocyclopenta[c]pyrrol-2(1H)-yl)ethyl)phenol;

rac-2-(5-phenylhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(3-(trifluoromethyl)phenyl)ethanol;

rac-1-(3-methoxyphenyl)-2-{5-phenyl-octahydrocyclopenta[c]pyrrol-2-yl}ethan-1-ol;

(3aR,5r,6aS)-5-benzyl-N-(3-chlorophenyl)-5-hydroxyhexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide;

(3aR,5r,6aS)-5-benzyl-5-hydroxy-N-(3-methoxyphenyl)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide;

(3aR,5r,6aS)-5-benzyl-N-(4-chloro-3-(trifluoromethyl)phenyl)-5-hydroxyhexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide;

(3aR,5r,6aS)-5-benzyl-N-(2,4-dimethylphenyl)-5-hydroxyhexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide;

(3aR,5r,6aS)-5-benzyl-5-hydroxy-N-phenylhexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide;

(3aR,5r,6aS)-5-benzyl-N-(3-cyanophenyl)-5-hydroxyhexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide;

(3aR,5r,6aS)-5-benzyl-5-hydroxy-N-(2-methoxy-5-methylphenyl)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide;

(3aR,5r,6aS)-5-benzyl-5-hydroxy-N-(p-tolyl)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide

(3aR,5r,6aS)-5-benzyl-5-hydroxy-N-(4-methoxyphenyl)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide;

(3aR,5r,6aS)-5-benzyl-5-hydroxy-N-(2-(trifluoromethyl)phenyl)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide;

(3aR,5r,6aS)-5-benzyl-5-hydroxy-N-(2-methoxyphenyl)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide;

(3aR,5r,6aS)-5-benzyl-5-hydroxy-N-(m-tolyl)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)ethanone;

rac-(3aR,5r,6aS)-5-benzyl-2-(2-hydroxy-2-(4-hydroxyphenyl)ethyl)octahydrocyclopenta[c]pyrrol-5-ol;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-methoxyphenyl)ethanone;

3-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)propan-1-one;

2-((3aR,5r,6aS)-5-(4-fluorobenzyl)-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)ethanone;

rac-(3aR,5r,6aS)-5-(4-fluorobenzyl)-2-(2-hydroxy-2-(4-hydroxyphenyl)ethyl)octahydrocyclopenta[c]pyrrol-5-ol;

(3aR,5R,6aS)-5-benzyl-2-((R)-2-hydroxy-2-(4-hydroxyphenyl)ethyl)octahydrocyclopenta[c]pyrrol-5-ol;

(3aR,5S,6aS)-5-benzyl-2-((S)-2-hydroxy-2-(4-hydroxyphenyl)ethyl)octahydrocyclopenta[c]pyrrol-5-ol;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-(2-hydroxypropan-2-yl)phenyl)ethanone;

rac-(3aR,5r,6aS)-5-benzyl-2-(2-hydroxy-2-(4-(2-hydroxypropan-2-yl)phenyl)ethyl)octahydrocyclopenta[c]pyrrol-5-ol;

N-(4-(2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)acetyl)phenyl)acetamide;

(3aR,5R,6aS)-5-benzyl-2-((R)-2-hydroxy-2-(4-hydroxyphenyl)ethyl)octahydrocyclopenta[c]pyrrol-5-ol;

(3aR,5S,6aS)-5-benzyl-2-((S)-2-hydroxy-2-(4-hydroxyphenyl)ethyl)octahydrocyclopenta[c]pyrrol-5-ol;

1-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-3-(4-hydroxyphenyl)propan-2-one;

N-(4-(2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)acetyl)phenyl)methanesulfonamide;

rac-N-(4-(2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-hydroxyethyl)phenyl)acetamide;

rac-N-(4-(2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-hydroxyethyl)phenyl)methanesulfonamide;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(3-fluoro-4-hydroxyphenyl)ethanone;

(3aR,5S,6aS)-5-benzyl-2-((S)-2-(3-fluoro-4-hydroxyphenyl)-2-hydroxyethyl)octahydrocyclopenta[c]pyrrol-5-ol;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(3,5-difluoro-4-hydroxyphenyl)ethanone;

rac-(3aR,5r,6aS)-5-benzyl-2-(2-(3,5-difluoro-4-hydroxyphenyl)-2-hydroxyethyl)octahydrocyclopenta[c]pyrrol-5-ol;

1-(3-fluoro-4-hydroxyphenyl)-2-((3aR,5r,6aS)-5-(4-fluorobenzyl)-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)ethanone;

2-((3aR,5r,6aS)-5-benzyl-5-methoxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(3-fluoro-4-hydroxyphenyl)ethanone;

rac-(3aR,5r,6aS)-2-(2-(3-fluoro-4-hydroxyphenyl)-2-hydroxyethyl)-5-(4-fluorobenzyl)octahydrocyclopenta[c]pyrrol-5-ol;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(3-fluoro-4-(2-(3-fluoro-4-hydroxyphenyl)-2-oxoethoxy)phenyl)ethanone;

2-(2-fluoro-4-(2-((3aR,5r,6aS)-5-(4-fluorobenzyl)-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)acetyl)phenoxy)-1-(3-fluoro-4-hydroxyphenyl)ethanone;

2-((3aR,5r,6aS)-5-benzyl-5-methoxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)ethanone;

rac-4-(2-((3aR,5r,6aS)-5-benzyl-5-methoxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-hydroxyethyl)-2-fluorophenol;

rac-4-(2-((3aR,5r,6aS)-5-benzyl-5-methoxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-hydroxyethyl)phenol;

2-((3aR,5r,6aS)-5-hydroxy-5-(4-methylbenzyl)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)ethanone;

(3aR,5R,6aS)-5-benzyl-2-((R)-2-(3-fluoro-4-hydroxyphenyl)-2-hydroxyethyl)octahydrocyclopenta[c]pyrrol-5-ol;

(3aR,5S,6aS)-5-benzyl-2-((S)-2-(3-fluoro-4-hydroxyphenyl)-2-hydroxyethyl)octahydrocyclopenta[c]pyrrol-5-ol;

rac-(3aR,5R,6aS)-2-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-5-[(4-methylphenyl)methyl]-octahydrocyclopenta[c]pyrrol-5-ol;

2-((3aR,5r,6aS)-5-hydroxy-5-(2-methylbenzyl)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)ethanone;

2-[(3aR,5R,6aS)-5-hydroxy-5-[(4-methoxyphenyl)methyl]-octahydrocyclopenta[c]pyrrol-2-yl]-1-(4-hydroxyphenyl)ethan-1-one;

rac-(3aR,5r,6aS)-2-(2-hydroxy-2-(4-hydroxyphenyl)ethyl)-5-(2-methylbenzyl)octahydrocyclopenta[c]pyrrol-5-ol;

rac-(3aR,5r,6aS)-2-(2-hydroxy-2-(4-hydroxyphenyl)ethyl)-5-(4-methoxybenzyl)octahydrocyclopenta[c]pyrrol-5-ol;

2-((3aR,5r,6aS)-5-hydroxy-5-(3-methoxybenzyl)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)ethanone;

rac-(3aR,5r,6aS)-2-(2-hydroxy-2-(4-hydroxyphenyl)ethyl)-5-(3-methoxybenzyl)octahydrocyclopenta[c]pyrrol-5-ol;

2-[(3aR,5R,6aS)-5-(cyclohexylmethyl)-5-hydroxy-octahydrocyclopenta[c]pyrrol-2-yl]-1-(4-hydroxyphenyl)ethan-1-one;

rac-(3aR,5R,6aS)-5-(cyclohexylmethyl)-2-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-octahydrocyclopenta[c]pyrrol-5-ol;

2-((3aR,5r,6aS)-5-(cyclopropylmethyl)-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)ethanone;

rac-(3aR,5r,6aS)-5-(cyclopropylmethyl)-2-(2-hydroxy-2-(4-hydroxyphenyl)ethyl)octahydrocyclopenta[c]pyrrol-5-ol;

2-[(3aR,5R,6aS)-5-[(3,5-dimethylphenyl)methyl]-5-hydroxy-octahydrocyclopenta[c]pyrrol-2-yl]-1-(4-hydroxyphenyl)ethan-1-one;

rac-(3aR,5R,6aS)-5-[(3,5-dimethylphenyl)methyl]-2-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-octahydrocyclopenta[c]pyrrol-5-ol;

2-[(3aR,5R,6aS)-5-hydroxy-5-{[4-(trifluoromethyl)phenyl]methyl}-octahydrocyclopenta[c]pyrrol-2-yl]-1-(4-hydroxyphenyl)ethan-1-one;

rac-(3aR,5R,6aS)-2-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-5-{[4-(trifluoromethyl)phenyl]methyl}-octahydrocyclopenta[c]pyrrol-5-ol;

2-((3aR,5r,6aS)-5-(2-fluorobenzyl)-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)ethanone;

rac-(3aR,5r,6aS)-5-(2-fluorobenzyl)-2-(2-hydroxy-2-(4-hydroxyphenyl)ethyl)octahydrocyclopenta[c]pyrrol-5-ol;

2-(5-(2,4-difluorobenzyl)-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)ethanone;

2-[(3aR,5R,6aS)-5-[(2,6-difluorophenyl)methyl]-5-hydroxy-octahydrocyclopenta[c]pyrrol-2-yl]-1-(4-hydroxyphenyl)ethan-1-one;

rac-5-(2,4-difluorobenzyl)-2-(2-hydroxy-2-(4-hydroxyphenyl)ethyl)octahydrocyclopenta[c]pyrrol-5-ol;

2-((3aR,5r,6aS)-5-(2,3-difluorobenzyl)-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)ethanone;

2-((3aR,5r,6aS)-5-(4-fluoro-2-methylbenzyl)-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)ethanone;

2-((3aR,5r,6aS)-5-(3,4-difluorobenzyl)-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)ethanone;

rac-(3aR,5r,6aS)-5-(3,4-difluorobenzyl)-2-(2-hydroxy-2-(4-hydroxyphenyl)ethyl)octahydrocyclopenta[c]pyrrol-5-ol;

rac-(3aR,5r,6aS)-5-(4-fluoro-2-methylbenzyl)-2-(2-hydroxy-2-(4-hydroxyphenyl)ethyl)octahydrocyclopenta[c]pyrrol-5-ol;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4′-hydroxy-[1,1′-biphenyl]-4-yl)ethanone;

1-([1,1′-biphenyl]-4-yl)-2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)ethanone;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4′-methoxy-[1,1′-biphenyl]-4-yl)ethanone;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(2′-methyl-[1,1′-biphenyl]-4-yl)ethanone;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(3′-fluoro-[1,1′-biphenyl]-4-yl)ethanone;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4′-fluoro-[1,1′-biphenyl]-4-yl)ethanone;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4′-methoxy-[1,1′-biphenyl]-3-yl)ethanone;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(3′-methyl-[1,1′-biphenyl]-4-yl)ethanone;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(3′-methoxy-[1,1′-biphenyl]-4-yl)ethanone;

1-([1,1′-biphenyl]-3-yl)-2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)ethanone;

2-[5-hydroxy-5-(2-phenylethyl)-octahydrocyclopenta[c]pyrrol-2-yl]-1-(4-phenylphenyl)ethan-1-one;

1-[4-(3-fluorophenyl)phenyl]-2-[5-hydroxy-5-(2-phenylethyl)-octahydrocyclopenta[c]pyrrol-2-yl]ethan-1-one;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(3′-fluoro-[1,1′-biphenyl]-3-yl)ethanone;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(3′-methoxy-[1,1′-biphenyl]-3-yl)ethanone;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4′-fluoro-[1,1′-biphenyl]-3-yl)ethanone;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4′-hydroxy-[1,1′-biphenyl]-3-yl)ethanone;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(3′-methyl-[1,1′-biphenyl]-3-yl)ethanone;

2-[5-hydroxy-5-(2-phenylethyl)-octahydrocyclopenta[c]pyrrol-2-yl]-1-[4-(3-methylphenyl)phenyl]ethan-1-one;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(2′-methyl-[1,1′-biphenyl]-3-yl)ethanone;

rac-(3aR,5R,6aS)-5-benzyl-2-[2-hydroxy-2-(4-hydroxyphenyl)propyl]-octahydrocyclopenta[c]pyrrol-5-ol;

deuterated rac-(3aR,6aS)-5-benzyl-2-((S)-2-hydroxy-2-(4-hydroxyphenyl)ethyl)octahydrocyclopenta[c]pyrrol-5-ol;

rac-(3aR,5r,6aS)-5-benzyl-2-(2-(2,4-dichlorophenyl)-2-hydroxyethyl)octahydrocyclopenta[c]pyrrol-5-ol;

rac-(3aR,5r,6aS)-5-benzyl-2-(2-hydroxy-2-(3-(trifluoromethyl)phenyl)ethyl)octahydrocyclopenta[c]pyrrol-5-ol;

rac-(3aR,5r,6aS)-5-benzyl-2-(2-(4-fluorophenyl)-2-hydroxyethyl)octahydrocyclopenta[c]pyrrol-5-ol;

2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)ethanone;

(3aR,5R,6aS)-5-benzyl-2-((R)-2-hydroxy-2-(4-hydroxyphenyl)ethyl)octahydrocyclopenta[c]pyrrol-5-ol;

(3aR,5S,6aS)-5-benzyl-2-((S)-2-hydroxy-2-(4-hydroxyphenyl)ethyl)octahydrocyclopenta[c]pyrrol-5-ol;

rac-2-((3aR,5r,6aS)-5-benzyl-5-hydroxyhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)propan-1-one;

(3aR,6aS)-5-benzyl-N-(3-methoxyphenyl)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide;

2-((3aR,6aS)-5-benzylhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)ethanone;

rac-2-((3aR,6aS)-5-benzylhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)propan-1-one;

2-{5-benzyl-octahydrocyclopenta[c]pyrrol-2-yl}-1-(3-fluoro-4-hydroxyphenyl)ethan-1-one;

rac-4-(2-((3aR,6aS)-5-benzylhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-hydroxyethyl)phenol;

rac-4-{2-[(3aR,5S,6aS)-5-benzyl-octahydrocyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl}-2-fluorophenol;

rac-4-{2-[(3aR,5R,6aS)-5-benzyl-octahydrocyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl}-2-fluorophenol;

2-[(3aR,5S,6aS)-5-benzyl-octahydrocyclopenta[c]pyrrol-2-yl]-1-(4-hydroxyphenyl)ethan-1-onefluorophenol;

rac-4-{2-[(3aR,5S,6aS)-5-benzyl-octahydrocyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl}phenol;

2-[(3aR,5R,6aS)-5-benzyl-octahydrocyclopenta[c]pyrrol-2-yl]-1-(4-hydroxyphenyl)ethan-1-one;

rac-4-{2-[(3aR,5R,6aS)-5-benzyl-octahydrocyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl}phenol;

2-[(3aR,5S,6aS)-5-benzyl-octahydrocyclopenta[c]pyrrol-2-yl]-1-(3-fluoro-4-hydroxyphenyl)ethan-1-one;

2-[(3aR,5R,6aS)-5-benzyl-octahydrocyclopenta[c]pyrrol-2-yl]-1-(3-fluoro-4-hydroxyphenyl)ethan-1-one;

rac-2-((3aR,6aS)-5-benzylhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(3-(trifluoromethyl)phenyl)ethanol;

2-((3aR,5s,6aS)-5-benzyl-5-fluorohexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)ethanone;

rac-4-(2-((3aR,5s,6aS)-5-benzyl-5-fluorohexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-hydroxyethyl)phenol;

4-(2-((3aR,5s,6aS)-5-benzyl-5-fluorohexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-hydroxyethyl)phenol;

rac-4-(2-((3aR,5r,6aS)-5-benzyl-5-fluorohexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-hydroxyethyl)phenol;

4-((R)-2-((3aR,5S,6aS)-5-benzyl-5-fluorohexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-hydroxyethyl)phenol;

4-((S)-2-((3aR,5R,6aS)-5-benzyl-5-fluorohexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-hydroxyethyl)phenol;

rac-4-(2-((3aR,5s,6aS)-5-benzyl-5-fluorohexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-hydroxyethyl)-2-fluorophenol;

rac-2-((3aR,5s,6aS)-5-benzyl-5-fluorohexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)propan-1-one;

rac-4-(2-((3aR,5s,6aS)-5-benzyl-5-fluorohexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-hydroxypropyl)phenol;

rac-2-(5-hydroxy-5-phenethylhexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)propan-1-one;

rac-2-(1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl)-5-phenethyloctahydrocyclopenta[c]pyrrol-5-ol;

rac-2-(2-hydroxy-2-(4-hydroxyphenyl)ethyl)-5-phenethyloctahydrocyclopenta[c]pyrrol-5-ol;

rac-1-(4-hydroxyphenyl)-2-[(5R)-5-(2-phenylethyl)-octahydrocyclopenta[c]pyrrol-2-yl]propan-1-one;

1-(4-hydroxyphenyl)-2-(5-phenethylhexahydrocyclopenta[c]pyrrol-2(1H)-yl)ethanone;

1-(4-hydroxyphenyl)-2-((3aR,5r,6aS)-5-phenethylhexahydrocyclopenta[c]pyrrol-2(1H)-yl)ethanone; and

1-(4-hydroxyphenyl)-2-((3aR,5r,6aS)-5-phenethylhexahydrocyclopenta[c]pyrrol-2(1H)-yl)propan-1-one.

18. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof.