Cyclopropylamines as LSD1 inhibitors

1. A compound of formula:

or a pharmaceutically acceptable salt thereof, wherein:

ring A is phenyl;

ring C is cyclobutyl or cyclopentyl;

L is C 1-4 alkylene;

each R 1 is independently selected from halo, C 1-6 alkyl and —O—(C 1-6 alkyl);

R 5 is H;

R 6 is H, CN or C 1-4 alkyl;

R Z is C 1-4 alkyl, phenyl-C 1-4 alkyl-, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 alkyl, or (5-6 membered heteroaryl)-C 1-4 alkyl-, wherein the C 1-4 alkyl, phenyl-C 1-4 alkyl-, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 alkyl and (5-6 membered heteroaryl)-C 1-4 alkyl- are each optionally substituted with 1 or 2 substituents independently selected from CN, halo, C 1-6 alkoxy, C 1-4 cyanoalkyl and C(O)NH(C 1-6 alkyl);

R 4 is COOH or COO(C 1-6 alkyl);

n is 0, 1 or 2; and

q is 1.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 0.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 1.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 2.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 1 is independently selected from halo and —O—(C 1-6 alkyl).

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 1 is independently selected from F and methoxy.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6 is H.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6 is selected from H and C 1-4 alkyl.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6 is methyl.

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein L is —(CH 2 ) r —, wherein r is 1, 2, or 3.

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein L is —CH 2 —.

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein ring C is cyclobutyl.

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z is C 1-4 alkyl, phenyl-C 1-4 alkyl-, or (5-6 membered heteroaryl)-C 1-4 alkyl, wherein said C 1-4 alkyl, phenyl-C 1-4 alkyl-, or (5-6 membered heteroaryl)-C 1-4 alkyl, are each optionally substituted by CN, halo, C 1-6 alkoxy, or C 1-4 cyanoalkyl.

14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z is C 1-4 alkyl or phenyl-C 1-4 alkyl-, wherein said C 1-4 alkyl and phenyl-C 1-4 alkyl- are each optionally substituted by CN, halo, C 1-6 alkoxy, or C 1-4 cyanoalkyl.

15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z is C 1-4 alkyl.

16. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z is phenyl-C 1-4 alkyl- substituted by fluoro or cyanomethyl.

17. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z is C 1-4 alkyl substituted by methoxy or CN.

18. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z is (5-6 membered heteroaryl)-C 1-4 alkyl substituted by methoxy or F.

19. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z is methyl, cyanomethyl, methoxymethyl, 4-fluorophenylmethyl or 4-(cyanomethyl)phenylmethyl.

20. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z is methyl, cyanomethyl, methoxymethyl, ethoxymethyl, 4-fluorophenylmethyl, 3-cyanophenylmethyl, 4-cyanophenylmethyl, 6-methoxypyridin-3-yl)methyl, 4-cyano-2-fluorobenzyl, (5-fluoropyridin-2-yl)methyl, 4-methoxyphenylmethyl, or 4-(cyanomethyl)phenylmethyl.

21. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z is C 1-4 alkyl substituted by CN.

22. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z is cyanomethyl.

23. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z is methoxymethyl.

24. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, having a trans configuration with respect to the di-substituted cyclopropyl group depicted in the formula of claim 1 .

25. The compound of claim 1 selected from:

1-{[4-(4-fluorobenzyl)-4-({[(1R,2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid; and

1-{[4-methyl-4-({[(1R,2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid;

or a pharmaceutically acceptable salt of any one of the aforementioned.

26. The compound of claim 1 selected from:

1-{[4-({[(1R,2S)-2-(2-fluorophenyl)cyclopropyl]amino}methyl)-4-(methoxymethyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid;

1-{[4-({[(1R,2S)-2-(3,4-difluorophenyl)cyclopropyl]amino}methyl)-4-(methoxymethyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid;

1-{[4-(3-cyanobenzyl)-4-({[(1R,2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid;

1-{[4-(4-methoxybenzyl)-4-({[(1R,2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid;

1-{[4-(methoxymethyl)-4-({[2-(2-methoxyphenyl)cyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid;

1-{[4-(methoxymethyl)-4-({[2-(4-methoxyphenyl)cyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid;

1-{[4-(methoxymethyl)-4-(1-{[(1R,2S)-2-phenylcyclopropyl]amino}ethyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid;

1-{[4-[(5-fluoropyridin-2-yl)methyl]-4-({[(1R,2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid; and

1-{[4-[4-(cyanomethyl)benzyl]-4-({[(1R,2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclobutanecarboxylic acid;

or a pharmaceutically acceptable salt of any one of the aforementioned.

27. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

28. The pharmaceutical composition of claim 27 , further comprising another therapeutic agent.

29. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein ring C is cyclopentyl.