Cyclopropylamines as LSD1 inhibitors

1. A compound of Formula (IV) or Formula (V):

wherein:

R 1 is selected from the group consisting of C 1 -C 6 alkyl, —NHSO 2 Me, —NHSO 2 Ph, arylalkoxy, C 3 -C 7 cycloalkyl, —NHC(O)R a , 1-methyl-1H-pyrazol-4-yl, hydroxyl, C 1 -C 4 alkoxy, halogen, amino, substituted amino, and —C(O)OR a ;

R 3 is selected from the group consisting of aryl, heteroaryl —SO 2 R a , —NHC(O)R a , —CH 2 C(O)OR a , —C(O)OR a , —C(O)R a , —C(O)NR a R b , amino, substituted amino, arylalkyl, and heteroarylalkyl;

each R a is independently hydrogen, phenyl, phenylmethyl, 3,5-dimethylisoxazol-4-yl, 1,2-dimethyl-1H-imidazol-4-yl, C 3 -C 7 cycloalkyl, or C 1 -C 6 alkyl;

R b is hydrogen or C 1 -C 3 alkyl; or

R a and R b together form a 5- or 6-membered heterocycloalkyl ring;

R 4 is H;

W is —(CH 2 ) 1-4 or —CH(R c )(CH 2 ) 0-3 , in which R c is —CN or C 1 -C 4 alkyl;

X is N;

Z is (CH 2 ) q , wherein q is 0-2, and wherein when q is 0, Z represents a bond; and

m is 0-3;

or a pharmaceutically acceptable salt thereof.

2. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1 is F, Cl, C 1 -C 4 alkoxy, or C 1 -C 4 alkyl.

3. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein m is 0.

4. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein R 3 is selected from the group consisting of aryl, arylalkyl, heteoaryl, and heteroarylalkyl, wherein any said aryl or heteroaryl are each optionally substituted with one, two, or three groups selected from the group consisting of —COOH, C 1 -C 4 alkoxy, —C(O)OC 1 -C 4 alkyl, C 1 -C 4 alkyl, halogen, —CN, tetrazolyl, —NHSO 2 Me, —SO 2 Me, —C(O)NHSO 2 Me, and —OCH 2 COOH.

5. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein R 3 is selected from the group consisting of —SO 2 R a , —C(O)OR a , —C(O)R a , —C(O)NR a R b , arylalkyl, and heteroarylalkyl, wherein R a is phenyl, phenylmethyl, C 3 -C 7 cycloalkyl, or C 1 -C 6 alkyl; and R b is hydrogen or C 1 -C 3 alkyl.

6. The compound or pharmaceutically acceptable salt thereof according to claim 1 , which is represented by Formula (VI):

wherein:

R 1 is selected from the group consisting of C 1 -C 6 alkyl, —NHSO 2 Me, —NHSO 2 Ph, arylalkoxy, C 3 -C 7 cycloalkyl, —NHC(O)R a , 1-methyl-1H-pyrazol-4-yl, hydroxyl, C 1 -C 4 alkoxy, halogen, amino, substituted amino, and —C(O)OR a ;

each R a is independently hydrogen, phenyl, phenylmethyl, 3,5-dimethylisoxazol-4-yl, 1,2-dimethyl-1H-imidazol-4-yl, C 3 -C 7 cycloalkyl, or C 1 -C 6 alkyl;

W is —(CH 2 ) 1-4 or —CH(R c )(CH 2 ) 0-3 , in which R c is —CN or C 1 -C 4 alkyl;

s is 1 or 2;

m is 0 or 1; and

each R 5 is independently selected from the group consisting of: —COOH, C 1 -C 4 alkoxy, —C(O)OC 1 -C 4 alkyl, C 1 -C 4 alkyl, halogen, CN, tetrazolyl, —NHSO 2 Me, —SO 2 Me, —C(O)NHSO 2 Me, and —OCH 2 COOH.

7. The compound or pharmaceutically acceptable salt thereof according to claim 1 , which is represented by Formula (VII):

wherein:

R 1 is selected from the group consisting of C 1 -C 6 alkyl, —NHSO 2 Me, —NHSO 2 Ph, arylalkoxy, C 3 -C 7 cycloalkyl, —NHC(O)R a , 1-methyl-1H-pyrazol-4-yl, hydroxyl, C 1 -C 4 alkoxy, halogen, amino, substituted amino, and —C(O)OR a ;

each R a is independently hydrogen, phenyl, phenylmethyl, 3,5-dimethylisoxazol-4-yl, 1,2-dimethyl-1H-imidazol-4-yl, C 3 -C 7 cycloalkyl, or C 1 -C 6 alkyl;

W is —(CH 2 ) 1-4 or —CH(R c )(CH 2 ) 0-3 , in which R c is —CN or C 1 -C 4 alkyl;

s is 1 or 2;

m is 0 or 1; and

each R 5 is independently selected from the group consisting of: —COOH, C 1 -C 4 alkoxy, —C(O)OC 1 -C 4 alkyl, C 1 -C 4 alkyl, halogen, CN, tetrazolyl, —NHSO 2 Me, —SO 2 Me, —C(O)NHSO 2 Me, and —OCH 2 COOH.

8. The compound or pharmaceutically acceptable salt thereof according to claim 6 , wherein s is 1 and R 5 is —COOH.

9. The compound or pharmaceutically acceptable salt thereof according to claim 7 , wherein s is 1 and R 5 is —COOH.

10. A compound which is:

1,1-Dimethylethyl 4-({[trans-2-phenylcyclopropyl]amino}methyl)-1-piperidinecarboxylate;

1,1-Dimethylethyl 4-({[(1R,2S)-2-phenylcyclopropyl]amino}methyl)-1-piperidinecarboxylate;

1,1-Dimethylethyl 4-({[(1S,2R)-2-phenylcyclopropyl]amino}methyl)-1-piperidinecarboxylate;

[trans-2-Phenylcyclopropyl]{[1-(phenylmethyl)-4-piperidinyl]methyl}amine;

N-Phenyl-4-(((trans-2-phenylcyclopropyl)amino)methyl)piperidine-1-carboxamide;

Phenyl(4-(((trans-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methanone;

1-(4-(((trans-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethanone;

Benzyl 4-(((trans-2-phenylcyclopropyl)amino)methyl)piperidine-1-carboxylate;

1,1-Dimethylethyl 4-({[trans-2-phenylcyclopropyl]amino}methyl)hexahydro-1H-azepine-1-carboxylate

2-(4-(((trans-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)acetic acid;

4-{[(3R)-3-({[(1R,2S)-2-Phenylcyclopropyl]amino}methyl)-1-pyrrolidinyl]methyl}benzoic acid;

4-{[(3S)-3-({[(1R,2S)-2-Phenylcyclopropyl]amino}methyl)-1-pyrrolidinyl]methyl}benzoic acid;

4-{3-[4-({[(1R,2S)-2-Phenylcyclopropyl]amino}methyl)-1-piperidinyl]propyl}benzoic acid;

trans-2-Phenyl-N-((1-(pyridin-4-ylmethyl)piperidin-4-yl)methyl)cyclopropanamine;

trans-N-((1-(2-Fluorobenzyl)piperidin-4-yl)methyl)-2-phenylcyclopropanamine;

trans-N-((1-(3-Fluorobenzyl)piperidin-4-yl)methyl)-2-phenylcyclopropanamine;

trans-N-((1-(4-Fluorobenzyl)piperidin-4-yl)methyl)-2-phenylcyclopropanamine;

trans-N-((1-(2,4-Difluorobenzyl)piperidin-4-yl)methyl)-2-phenylcyclopropanamine;

Ethyl 4-((4-(((trans-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoate;

trans-N-((1-(4-(Methylsulfonyl)benzyl)piperidin-4-yl)methyl)-2-phenylcyclopropanamine;

2-((4-(((trans-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzonitrile;

trans-2-Phenyl-N-((1-(2-(trifluoromethyl)benzyl)piperidin-4-yl)methyl)cyclopropanamine;

trans-N-((1-((5-Methylisoxazol-3-yl)methyl)piperidin-4-yl)methyl)-2-phenylcyclopropanamine;

trans-N-((1-((1H-Pyrazol-4-yl)methyl)piperidin-4-yl)methyl)-2-phenylcyclopropanamine;

N-(4-((4-(((trans-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)phenyl)acetamide;

4-((4-(((trans-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzo[c][1,2]oxaborol-1(3H)-ol;

5-((4-(((trans-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzo[c][1,2]oxaborol-1(3H)-ol;

(4-((4-(((trans-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)phenyl)boronic acid;

2-((4-(((trans-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

3-((4-(((trans-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

4-((4-(((trans-2-(4-Bromophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

4-((4-(((trans-2-(4-Chlorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

4-((4-(((trans-2-(3,4-Dichlorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

4-((4-(((trans-2-(4-(Trifluoromethyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

4-((4-(((trans-2-(3,4-Dimethoxyphenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

4-((4-(((trans-2-(4-Acetamidophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

4-((4-(((trans-2-(4-Benzamidophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

trans-2-Phenyl-N-((1-phenylpiperidin-4-yl)methyl)cyclopropanamine;

Ethyl 4-(((trans-2-phenylcyclopropyl)amino)methyl)piperidine-1-carboxylate;

trans-4-((4-(((trans-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)cyclohexanecarboxylic acid;

(trans)-N-((1-(Methylsulfonyl)piperidin-4-yl)methyl)-2-phenylcyclopropanamine;

N-ethyl-4-((((trans)-2-phenylcyclopropyl)amino)methyl)piperidine-1-carboxamide;

N-cyclopropyl-4-((((trans)-2-phenylcyclopropyl)amino)methyl)piperidine-1-carboxamide;

N,N-dimethyl-4-((((trans)-2-phenylcyclopropyl)amino)methyl)piperidine-1-carboxamide,

(4-((((trans)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)(pyrrolidin-1-yl)methanone;

trans-N-((1-((cyclopropylsulfonyl)piperidin-4-yl)methyl)-2-phenylcyclopropanamine;

trans-N-((1-((isopropylsulfonyl)piperidin-4-yl)methyl)-2-phenylcyclopropanamine;

trans-N-((1-(3,5-dimethylisoxazol-4-yl)sulfonyl)piperidin-4-yl)methyl)-2-phenylcyclopropanamine;

trans-N-((1-((1,2-dimethyl-1H-imidazol-4-yl)sulfonyl)piperidin-4-yl)methyl)-2-phenylcyclopropanamine;

(trans)-2-Phenyl-N-(2-(1-(pyridin-2-yl)piperidin-4-yl)ethyl)cyclopropanamine;

6-(4-(2-(((trans)-2-Phenylcyclopropyl)amino)ethyl) piperidin-1-yl) nicotinic acid;

trans-2-phenyl-N-(2-(1-(pyridin-4-yl)piperidin-4-yl)ethyl)cyclopropanamine;

trans-2-phenyl-N-(2-(1-(pyrimidin-4-yl)piperidin-4-yl)ethyl)cyclopropanamine;

trans-2-phenyl-N-(2-(1-phenylpiperidin-4-yl)ethyl)cyclopropanamine;

trans-2-phenyl-N-(2-(1-(pyridin-3-yl)piperidin-4-yl)ethyl)cyclopropanamine;

trans-2-phenyl-N-(2-(1-(pyrimidin-2-yl)piperidin-4-yl)ethyl)cyclopropanamine;

3-Cyano-4-((4-((((trans)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

2-fluoro-4-((4-((((trans)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

3-fluoro-4-((4-((((trans)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

3-chloro-4-((4-((((trans)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

3-methoxy-4-((4-((((trans)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

2-chloro-4-((4-((((trans)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

4-(3-(4-(Cyano(((1R,2S)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoic acid;

4-{3-[4-({[(trans))-2-phenylcyclopropyl]amino}methyl)-1-piperidinyl]propyl}benzoic acid;

4-(4-(4-((((1R,2S)-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)butyl)benzoic acid;

4-(4-(4-(Cyano(((1R,2S)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)butyl)benzoic acid;

4-(2-(4-((((trans)-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)benzoic acid;

4-(2-(4-((((1R,2S)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)benzoic acid;

6-((4-((((trans)-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)-2-naphthoic acid;

6-((4-((((1R,2S)-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)-2-naphthoic acid;

(trans)-N-((1-(4-(1H-Tetrazol-5-yl)benzyl)piperidin-4-yl)methyl)-2-phenylcyclopropanamine;

2-(4-((4-((((trans)-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamido)acetic acid;

N-(4-((4-((((trans)-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)phenyl)methanesulfonamide;

(trans)-N-((1-(3-(1H-Tetrazol-5-yl)propyl)piperidin-4-yl)methyl)-2-phenylcyclopropanamine;

4-((4-(2-(((trans)-2-Phenylcyclopropyl)amino)ethyl)piperidin-1-yl)methyl)benzoic acid;

6-((4-((((trans)-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)nicotinic acid;

2-(4-((4-((((trans)-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)phenyl)acetic acid;

2-((4-((((trans)-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)oxazole-4-carboxylic acid;

2-(4-((4-((((trans)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)phenoxy)acetic acid;

N-(Methylsulfonyl)-4-((4-((((trans)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamide;

4-((4-((((trans)-2-(4-Iodophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

4-((trans)-2-(((1-Benzylpiperidin-4-yl)methyl)amino)cyclopropyl)benzoic acid;

4-((4-((((trans)-2-(4-(1-Methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

4-((4-((((trans)-2-(4-Cyclopropylphenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

2-Chloro-4-((4-((((1R,2S)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoic acid;

3-(3-(4-((((trans)-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoic acid; or

2-(4-((4-((((1R,2S)-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)phenyl)acetic acid;

or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof according to claim 1 and a pharmaceutically acceptable excipient.

12. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof according to claim 10 and a pharmaceutically acceptable excipient.