Cyclopropylamines as LSD1 inhibitors

1. A method of treating cancer comprising administering to a patient a therapeutically effective amount of a compound of formula,

or a pharmaceutically acceptable salt thereof, wherein:

ring A is phenyl;

ring C is 6 membered heteroaryl having carbon and 1 or 2 nitrogen atoms;

R 4 is C 1-6 alkyl, C 1-6 haloalkyl, CN, NR c3 R d3 , C(O)OR a3 , or C(O)NR c3 R d3 , wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, NO 2 , OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , NR c3 C(O)NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , N c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ;

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-, and (5-6 membered heteroaryl)-C 1-4 alkyl- are each optionally substituted by halo, CN, C(O)NR c4 R d4 , or OR a4

each R a3 , R b3 , R c3 , R d3 , R a4 , R c4 , and R d4 is independently selected from H and C 1-6 alkyl;

each R e3 is independently selected from H, C 1-4 alkyl, and CN; and

q is 0 or 1;

wherein said cancer is selected from myelodysplasia syndrome, acute myelogenous leukemia, undifferentiated small cell lung cancer, Ewing's sarcoma, and primary myelofibrosis.

2. The method of claim 1 , wherein q is 0.

3. The method of claim 1 , wherein q is 1.

4. The method of claim 1 , wherein R 4 is C 1-6 alkyl, C 1-6 haloalkyl, 4-CN, or C(O)NR c3 R d3 , wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, NO 2 , OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , NR c3 C(O)NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 .

5. The method of claim 1 , 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 halo, CN, or OR a4 .

6. The method of claim 1 , wherein R Z is C 1-4 alkyl.

7. The method of claim 1 , wherein R Z is C 1-4 alkyl substituted by CN or methoxy.

8. The method of claim 1 , wherein R Z is phenyl-C 1-4 alkyl-substituted by fluoro.

9. The method of claim 1 , wherein R Z is methyl, cyanomethyl, methoxymethyl, or 4-fluorophenylmethyl.

10. The method of claim 1 , wherein R Z is C 1-4 alkyl substituted by CN.

11. The method of claim 1 , wherein R Z is cyanomethyl.

12. The method of claim 1 , wherein R Z is H.

13. The method of claim 1 , wherein the compound is a compound having a trans configuration with respect to the di-substituted cyclopropyl group depicted in the formula of claim 1 .

14. The method of claim 1 , wherein the compound is:

{4-{[(trans-2-Phenylcyclopropyl)amino]methyl}-1-[3-(trifluoromethyl)pyridin-2-yl]piperidin-4-yl}acetonitrile;

or a pharmaceutically acceptable salt thereof.

15. The method of claim 1 , wherein the compound is selected from:

6-[4-(4-fluorobenzyl)-4-({[(1R,2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]pyridine-2-carboxylic acid;

5-[4-(4-fluorobenzyl)-4-({[(1R,2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]pyridine-2-carboxylic acid;

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

6-[4-(methoxymethyl)-4-({[(1R,2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]pyridine-2-carboxylic acid;

5-[4-methyl-4-({[(1R, 2 S)-2-phenylcyclopropyl]amino methyl)piperidin-1-yl]pyridine-2-carboxylic acid;

6-[4-methyl-4-({[(1R, 2 S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]pyridine-2-carboxylic acid;

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

N,N-dimethyl-5-[4-methyl-4-0 [(1R, 2 S)-2-phenylcyclopropyl]amino methyl)piperidin-1-yl]pyridine-2-carboxamide; and

N-methyl-5-[4-methyl-4-0 [(1R, 2 S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]pyridine-2-carboxamide;

or a pharmaceutically acceptable salt of any of the aforementioned.

16. The method of claim 1 , wherein said cancer is myelodysplasia syndrome.

17. The method of claim 1 , wherein said cancer is acute myelogenous leukemia.

18. The method of claim 1 , wherein said cancer is undifferentiated small cell lung cancer.

19. The method of claim 1 , wherein said cancer is Ewing's sarcoma.

20. The method of claim 1 , wherein said cancer is primary myelofibrosis.