HETEROCYCLIC COMPOUNDS AS LSD1 INHIBITORS

• US 20190055250A1
• Filed: 03/07/2018
• Published: 02/21/2019
• Est. Priority Date: 04/03/2015
• Status: Active Grant

• Current Assignee: Incyte Corporation, Incyte Holdings Corporation (Incyte Corporation)
• Original Assignee: Incyte Corporation
• Inventors: He, Chunhong, Li, Zhenwu, Wu, Liangxing, Yao, Wenqing, Zhang, Fenglei
• Granted Patent: US 10,800,779 B2
• Time in Patent Office: Days
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

The present invention is directed to compounds of Formula I which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

Claims

1. A compound of Formula I:

2. The compound of claim 1, having Formula II:

3. The compound of claim 1, having Formula III:

4. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein U is CR^U.

5. The compound of claim 1, having Formula IIIa:

6. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Y is N.

7. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Y is CR⁴.

8. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Z is N.

9. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Z is CR⁵.

10. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Y and Z are each CH.

11. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein ring A is C_6-10 aryl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein the 5-10 membered heteroaryl or 4-10 membered heterocycloalkyl of ring A each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms selected from N, O, and S, wherein N or S is optionally oxidized;

and wherein a ring-forming carbon atom of the 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group.

12. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein ring A is C_6-10 aryl.

13. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein ring A is phenyl.

14. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein ring A is 5-10 membered heteroaryl.

15. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein ring A is pyridyl, 1H-indazolyl, 1H-pyrrolo[2,3-b]pyridinyl, or 1H-benzo[d]imidazolyl.

16. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein ring A is pyridyl.

17. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein ring A is 4-10 membered heterocycloalkyl having at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms selected from N, O, and S, wherein N or S is optionally oxidized, and wherein a ring-forming carbon atom is optionally substituted by oxo to form a carbonyl group.

18. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein ring A is 2-oxo-2,3-dihydro-1H-indolyl;

2-oxo-2,3-dihydro-1,3-benzoxazolyl;

3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl;

3-oxo-3,4-dihydro-2H-1,4-benzoxazinyl;

1H-pyrazolo[3,4-b]pyridinyl, 3-methyl-2-oxo-3,4-dihydro-2H-1,3-benzoxazin-7-yl;

2-oxo-2,3-dihydro-1H-benzimidazolyl;

1H-benzimidazolyl;

2-oxo-2,3-dihydro[1,3]oxazolo[4,5-b]pyridinyl, or 2,3-dihydro-1-benzofuranyl.

19. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein ring A is 2-oxo-2,3-dihydro-1H-indolyl;

2-oxo-2,3-dihydro-1,3-benzoxazolyl;

3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl;

3-oxo-3,4-dihydro-2H-1,4-benzoxazinyl;

or 2,3-dihydro-1-benzofuranyl.

20. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein ring A is phenyl;

2,3-dihydro-1,4-benzodioxine;

2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl;

5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl;

2-oxo-1,2,3,4-tetrahydroquinolin-7-yl;

pyridyl;

2-oxo-2,3-dihydro-1,3-benzoxazolyl;

1,3-benzothiazol-5-yl;

2,3-dihydro-1H-inden-5-yl;

1H-pyrrolo[2,3-b]pyridinyl;

8-quinoxalin-6-yl;

2-oxo-1,2,3,4-tetrahydroquinolin-6-yl;

or 1H-pyrazolo[3,4-b]pyridinyl.

21. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R³, at each occurrence, is independently selected from Cy², C_1-6 alkyl, CN, OR^a2, C(O)NR^c2R^d2, and NR^c2R^d2;

wherein the C_1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from Cy², C(O)R^b2, and C(O)NR^c2R^d2.

22. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein two adjacent R³ substituents on ring A taken together with the atoms to which they are attached form a fused 5- or 6-membered heterocycloalkyl ring, a fused C_3-6 cycloalkyl ring, or a fused 5- or 6-membered heteroaryl ring, each of which is optionally substituted with 1 or 2 independently selected R^A substituents;

wherein a ring carbon of the fused 5- or 6-membered heterocycloalkyl ring or fused C_3-6 cycloalkyl ring is optionally replaced by a carbonyl group;

alternatively, two R^A substituents attached to the same carbon of the fused 5- or 6-membered heterocycloalkyl or fused C_3-6 cycloalkyl taken together form a C_3-6 cycloalkyl or 4- to 7-membered heterocycloalkyl ring.

23. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein two adjacent R³ substituents on ring A taken together with the atoms to which they are attached form a fused ring selected from 1-methylpyrrolidine, 4-methyl-3-oxo-morpholine, 1-methylimidazole, 1-methylpiperidine, 1-methyl-2-oxopyrrolidine, and 1-methylpyrazole, each of which is optionally substituted with 1 or 2 R^A substituents.

24. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R³ is C_1-6 alkyl, halo, C_1-6 hydroxyalkyl, C_1-6 haloalkyl, CN, OR^a2, 1-pyrrolidinyl, 2-oxo-1-pyrrolidinyl, NR^c2C(O)OR^a2, —

(C_1-6 alkyl)-NR^c2C(O)OR^a2, C(O)NR^c2R^d2, NR^c2R^d2, piperazinylmethyl, 4-methylpiperazinylmethyl, piperidinyl, morpholinyl, 4-methylpiperazinylcarbonylmethyl, morpholinylmethyl, or 3-cyano-1-pyrrolidinyl.

25. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R³ is C_1-6 alkyl, CN, OR^a2, 1-pyrrolidinyl, 2-oxo-1-pyrrolidinyl, C(O)NR^c2R^d2, NR^c2R^d2, piperazinylmethyl, 4-methylpiperazinylmethyl, piperidinyl, morpholinyl, 4-methylpiperazinylcarbonylmethyl, morpholinylmethyl, or 3-cyano-1-pyrrolidinyl.

26. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R³ is, at each occurrence, CN, F, hydroxymethyl, (CH₃O)C(O)N(CH₃)—

, (CH₃O)C(O)N(CH₃)-methyl, difluoromethyl, amino, methyl, methoxy, 1-pyrrolidinyl, 2-oxo-1-pyrrolidinyl, —

C(O)N(CH₃)₂, dimethylamino, 4-methylpiperazinylmethyl, morpholinyl, 4-methylpiperazinylcarbonylmethyl, morpholinylmethyl, morpholinoethyl, or 3-cyano-1-pyrrolidinylmethyl.

27. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R³ is, at each occurrence, CN, methyl, methoxy, 1-pyrrolidinyl, 2-oxo-1-pyrrolidinyl, —

C(O)N(CH₃)₂, dimethylamino, 4-methylpiperazinylmethyl, morpholinyl, 4-methylpiperazinylcarbonylmethyl, morpholinylmethyl, morpholinoethyl, or 3-cyano-1-pyrrolidinylmethyl.

28. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R³ is, at each occurrence, CN, F, hydroxymethyl, (CH₃O)C(O)N(CH₃)—

, (CH₃O)C(O)N(CH₃)-methyl, difluoromethyl, methyl, methoxy, —

C(O)N(CH₃)₂, dimethylamino, morpholinylmethyl, (CH₃)S(O₂)N(CH₃)-methyl, (CH₃)₂NC(O)N(CH₃)-methyl, Cl, 1-hydroxyethyl, methoxymethyl, isopropyl, ethyl, (CH₃)S(O₂)N(CH₃)—

, or ethoxy.

29. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R¹ is -L¹-R⁶ or -L²-NR⁷R⁸.

30. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R¹ is -L²-NR⁷R⁸, wherein L² is a bond, —

C(O)—

, —

C_1-4 alkylene-, —

O—

C_1-4 alkylene, —

C_1-4 alkylene-O—

, —

C_1-4 alkylene-NH—

, or —

NH—

C_1-4 alkylene-.

31. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R¹ is OR^a1.

32. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R¹ is OR^a1, wherein R^a1 is C_1-6 alkyl substituted with Cy⁴.

33. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R¹ is OR^a1, wherein R^a1 is methylene substituted with Cy⁴.

34. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R¹ is OR^a1, wherein R^a1 is methylene substituted with 4-10 membered heterocycloalkyl optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^Cy.

35. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R¹ is (1-methylpiperidin-3-yl)methoxy, (1-ethylpiperidin-3-yl)methoxy, (2-cyanoethylpiperidin-3-yl)methoxy, (2-hydroxyethylpiperidin-3-yl)methoxy, (2-methoxyethylpiperidin-3-yl)methoxy, 4-dimethylaminopiperidin-1-yl, 3-dimethylaminopyrrolidin-1-yl, 7-methyl-2,7-diazaspiro[4.4]non-2-yl, or (1-methylpyrrolidin-3-yl)methoxy.

36. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R¹ is (1-methylpiperidin-3-yl)methoxy or (1-methylpyrrolidin-3-yl)methoxy.

37. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R¹ is (1-methylpiperidin-3-yl)methoxy, (1-ethylpiperidin-3-yl)methoxy, (2-cyanoethylpiperidin-3-yl)methoxy, 4-dimethylaminopiperidin-1-yl, 3-dimethylaminopyrrolidin-1-yl, (2-hydroxypropylpiperidin-3-yl)methoxy, or 2-hydroxy-2-methylpropyl)piperidin-3-yl]methoxy.

38. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R² is H.

39. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R⁴ is H.

40. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R⁵ is H.

41. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein m is 1.

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

43. The compound of claim 1, having Formula IVa, IVb, IVc, IVd, IVe, or IVf:

44. The compound of claim 1, having Formula IVg, IVh, or IVi:

45. The compound of claim 1, having Formula IVa or IVb:

46. The compound of claim 1, having Formula VIa, VIb, or VIc:

47. The compound of claim 1, having Formula V:

48. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:

4-(8-(4-methylphenyl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-(4-methylphenyl)-5-{[(3R)-1-methylpyrrolidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-(6-methoxypyridin-3-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-[6-(dimethylamino)pyridin-3-yl]-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-[5-{[(3R)-1-methylpiperidin-3-yl]methoxy}-8-(6-pyrrolidin-1-ylpyridin-3-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-(8-(1-methyl-2-oxo-2,3-dihydro-1H-indol-5-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-(1-methyl-1H-indazol-5-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-{4-[(4-methylpiperazin-1-yl)methyl]phenyl}-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-{4-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]phenyl}-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-{5-{[(3R)-1-methylpiperidin-3-yl]methoxy}-8-[4-(2-morpholin-4-ylethyl)phenyl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-{5-{[(3R)-1-methylpiperidin-3-yl]methoxy}-8-[4-(morpholin-4-ylmethyl)phenyl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

(3 S)-1-[4-(7-(4-cyanophenyl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-8-yl)benzyl]pyrrolidine-3-carbonitrile,

4-(8-(4-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-(4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-{5-{[(3R)-1-methylpiperidin-3-yl]methoxy}-8-[6-(2-oxopyrrolidin-1-yl)pyridin-3-yl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-(8-(1-methyl-1H-benzimidazol-5-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-(1-methyl-1H-indazol-6-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-[5-{[(3R)-1-methylpiperidin-3-yl]methoxy}-8-(1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

5-(7-(4-cyanophenyl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-8-yl)-N,N-dimethyl-2,3-dihydro-1-benzofuran-2-carboxamide,

4-(8-[6-(dimethylamino)pyridin-3-yl]-5-{[(3R)-1-methylpyrrolidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-[5-{[(3R)-1-methylpyrrolidin-3-yl]methoxy}-8-(6-pyrrolidin-1-ylpyridin-3-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-(8-(1-methyl-2-oxo-2,3-dihydro-1H-indol-5-yl)-5-{[(3R)-1-methylpyrrolidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-(4-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-5-{[(3R)-1-methylpyrrolidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-(1-methyl-1H-benzimidazol-5-yl)-5-{[(3R)-1-methylpyrrolidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)-5-{[(3R)-1-methylpyrrolidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile, and

4-(8-(1-methyl-1H-indazol-5-yl)-5-{[(3R)-1-methylpyrrolidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile.

49. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:

4-[5-{[(3R)-1-methylpiperidin-3-yl]methoxy}-8-(1-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-{[(3R)-1-ethylpiperidin-3-yl]methoxy}-8-(1-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-(8-[3-fluoro-4-(hydroxymethyl)-5-methylphenyl]-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-[3-fluoro-4-(hydroxymethyl)phenyl]-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-[3,5-difluoro-4-(hydroxymethyl)phenyl]-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-[5-{[(3R)-1-(2-cyanoethyl)piperidin-3-yl]methoxy}-8-(1-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-{[(3R)-1-(2-hydroxyethyl)piperidin-3-yl]methoxy}-8-(1-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-(8-[4-(hydroxymethyl)-3-methylphenyl]-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-[4-(hydroxymethyl)phenyl]-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(1-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]-8-(1-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-(7-methyl-2,7-diazaspiro[4.4]non-2-yl)-8-(1-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

methyl [4-(7-(4-cyanophenyl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-8-yl)-2-fluorobenzyl]methylcarbamate,

4-[5-{[(3R)-1-(2-methoxyethyl)piperidin-3-yl]methoxy}-8-(1-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-(8-(3-amino-1-methyl-1H-indazol-5-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-(3-methyl-2-oxo-3,4-dihydro-2H-1,3-benzoxazin-7-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-(1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-(5-fluoro-3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(1-methyl-1H-indazol-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(6-methoxypyridin-3-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(5-fluoro-6-methoxypyridin-3-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-{5-[4-(dimethylamino)piperidin-1-yl]-8-[6-(2-oxopyrrolidin-1-yl)pyridin-3-yl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-{8-[2-(difluoromethyl)-1-methyl-1H-benzimidazol-5-yl]-5-[4-(dimethylamino)piperidin-1-yl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(6-methoxy-5-methylpyridin-3-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(5-fluoro-3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-{[(3R)-1-ethylpiperidin-3-yl]methoxy}-8-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-{[(3R)-1-(2-hydroxyethyl)piperidin-3-yl]methoxy}-8-(6-methoxypyridin-3-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-(8-(5-fluoro-6-methoxypyridin-3-yl)-5-{[(3R)-1-(2-hydroxyethyl)piperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(4-fluoro-3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-(8-(4-fluoro-3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(3-methyl-2-oxo-2,3-dihydro[1,3]oxazolo[4,5-b]pyridin-6-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-(8-(3-methyl-2-oxo-2,3-dihydro[1,3]oxazolo[4,5-b]pyridin-6-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(1-methyl-2-oxo-2,3-dihydro-1H-indol-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(1,2-dimethyl-1H-benzimidazol-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-(8-[2-(difluoromethyl)-1-methyl-1H-benzimidazol-5-yl]-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-(1,2-dimethyl-1H-benzimidazol-5-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

5-{7-(4-cyanophenyl)-5-[4-(dimethylamino)piperidin-1-yl]imidazo[1,2-c]pyrimidin-8-yl}-2-methylnicotinonitrile,

methyl (5-{7-(4-cyanophenyl)-5-[4-(dimethylamino)piperidin-1-yl]imidazo[1,2-c]pyrimidin-8-yl}pyridin-2-yl)methylcarbamate,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(5,6-dimethylpyridin-3-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-(8-(6-methoxy-5-methylpyridin-3-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

5-(7-(4-cyanophenyl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-8-yl)-2-methylnicotinonitrile,

4-(8-[3-(hydroxymethyl)-4-methylphenyl]-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-[2-(hydroxymethyl)-4-methylphenyl]-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-[5-{[(3R)-1-methylpiperidin-3-yl]methoxy}-8-(6-methylpyridin-3-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-(8-(5-fluoro-6-methylpyridin-3-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile, and

methyl [4-(7-(4-cyanophenyl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-8-yl)-2-fluorophenyl]methylcarbamate.

50. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:

7-(7-(4-cyanophenyl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-8-yl)-N,N-dimethyl-2,3-dihydro-1,4-benzodioxine-2-carboxamide,

4-(8-(1-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-[5-{[(3R)-1-methylpiperidin-3-yl]methoxy}-8-(8-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-(8-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-[3-fluoro-4-(morpholin-4-ylmethyl)phenyl]-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-[5-{[(3R)-1-(2-cyanoethyl)piperidin-3-yl]methoxy}-8-(5-fluoro-6-methoxypyridin-3-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-{8-[6-(dimethylamino)-5-fluoropyridin-3-yl]-5-[4-(dimethylamino)piperidin-1-yl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-[5-{[(3R)-1-(2-cyanoethyl)piperidin-3-yl]methoxy}-8-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

N-[4-(7-(4-cyanophenyl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1, 2-c]pyrimidin-8-yl)-2-fluorobenzyl]-N-methylmethanesulfonamide,

N-[4-(7-(4-cyanophenyl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1, 2-c]pyrimidin-8-yl)-2-fluorobenzyl]-N,N′

,N′

-trimethylurea,

N-[4-(7-(4-cyanophenyl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1, 2-c]pyrimidin-8-yl)benzyl]-N,N′

,N′

-trimethylurea,

methyl [4-(7-(4-cyanophenyl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-8-yl)benzyl]methylcarbamate,

4-(8-(5-chloro-6-methoxypyridin-3-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-{5-[4-(dimethylamino)piperidin-1-yl]-8-[3-fluoro-4-(hydroxymethyl)-5-methylphenyl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-{8-[3,5-difluoro-4-(hydroxymethyl)phenyl]-5-[4-(dimethylamino)piperidin-1-yl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-{5-[4-(dimethylamino)piperidin-1-yl]-8-[4-(hydroxymethyl)-3-methylphenyl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-(8-(5-chloro-6-methylpyridin-3-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-[3-(1-hydroxyethyl)-4-methylphenyl]-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-[4-(methoxymethyl)phenyl]-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-[2-fluoro-4-(morpholin-4-ylmethyl)phenyl]-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

5-(7-(4-cyanophenyl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-8-yl)-2-methylbenzonitrile,

N-(4-{7-(4-cyanophenyl)-5-[4-(dimethylamino)piperidin-1-yl]imidazo[1,2-c]pyrimidin-8-yl}-2-fluorobenzyl)-N,N′

,N′

-trimethylurea,

4-{5-[4-(dimethylamino)piperidin-1-yl]-8-[3-fluoro-4-(morpholin-4-ylmethyl)phenyl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-{5-{[(3R)-1-ethylpiperidin-3-yl]methoxy}-8-[3-(hydroxymethyl)-4-methylphenyl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-{5-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]-8-[3-(hydroxymethyl)-4-methylphenyl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-(8-[3-chloro-4-(hydroxymethyl)phenyl]-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-{5-[4-(dimethylamino)piperidin-1-yl]-8-[3-(hydroxymethyl)-4-methylphenyl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-{8-(5-chloro-6-methylpyridin-3-yl)-5-[4-(dimethylamino)piperidin-1-yl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-{8-(5-chloro-6-methoxypyridin-3-yl)-5-[4-(dimethylamino)piperidin-1-yl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

5-{7-(4-cyanophenyl)-5-[4-(dimethylamino)piperidin-1-yl]imidazo[1,2-c]pyrimidin-8-yl}-2-methoxynicotinonitrile,

methyl [5-(7-(4-cyanophenyl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-8-yl)-2-methylphenyl]methylcarbamate,

4-(8-(6-ethylpyridin-3-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-(6-isopropylpyridin-3-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-{5-{[(3R)-1-ethylpiperidin-3-yl]methoxy}-8-[3-fluoro-4-(hydroxymethyl)-5-methylphenyl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-{5-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]-8-[3-fluoro-4-(hydroxymethyl)-5-methylphenyl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-{5-[4-(dimethylamino)piperidin-1-yl]-8-[2-(hydroxymethyl)-4-methylphenyl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(6-methylpyridin-3-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(5-fluoro-6-methylpyridin-3-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

methyl (4-{7-(4-cyanophenyl)-5-[4-(dimethylamino)piperidin-1-yl]imidazo[1, 2-c]pyrimidin-8-yl}phenyl)methylcarbamate,

N-(5-{7-(4-cyanophenyl)-5-[4-(dimethylamino)piperidin-1-yl]imidazo[1,2-c]pyrimidin-8-yl}pyridin-2-yl)-N-methylmethanesulfonamide,

methyl (4-{7-(4-cyanophenyl)-5-[4-(dimethylamino)piperidin-1-yl]imidazo[1, 2-c]pyrimidin-8-yl}-2-fluorophenyl)methylcarbamate,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(6-ethoxypyridin-3-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(6-isopropylpyridin-3-yl)imidazo[1, 2-c]pyrimidin-7-yl]benzonitrile,

4-{5-{[(3R)-1-ethylpiperidin-3-yl]methoxy}-8-[2-(hydroxymethyl)-4-methylphenyl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-{8-(1,3-benzothiazol-5-yl)-5-[4-(dimethylamino)piperidin-1-yl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(3-hydroxy-2,3-dihydro-1H-inden-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(2-hydroxy-2,3-dihydro-1H-inden-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-(8-(3-hydroxy-2,3-dihydro-1H-inden-5-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-(8-(2-hydroxy-2,3-dihydro-1H-inden-5-yl)-5-{[(3R)-1-methylpiperidin-3-yl]methoxy}imidazo[1,2-c]pyrimidin-7-yl)benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-{5-[4-(dimethylamino)piperidin-1-yl]-8-quinoxalin-6-ylimidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(4-fluoro-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(7-fluoro-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(6-fluoro-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-[4-(dimethylamino)piperidin-1-yl]-8-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-{8-[5-(difluoromethyl)-6-methylpyridin-3-yl]-5-[4-(dimethylamino)piperidin-1-yl]imidazo[1,2-c]pyrimidin-7-yl}benzonitrile,

4-[5-({(3R)-1-[(2R)-2-hydroxypropyl]piperidin-3-yl}methoxy)-8-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-({(3R)-1-[(2S)-2-hydroxypropyl]piperidin-3-yl}methoxy)-8-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-{[(3R)-1-(2-hydroxy-2-methylpropyl)piperidin-3-yl]methoxy}-8-(3-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-({(3R)-1-[(2R)-2-hydroxypropyl]piperidin-3-yl}methoxy)-8-(1-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile,

4-[5-({(3R)-1-[(2 S)-2-hydroxypropyl]piperidin-3-yl}methoxy)-8-(1-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile, and

4-[5-{[(3R)-1-(2-hydroxy-2-methylpropyl)piperidin-3-yl]methoxy}-8-(1-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[1,2-c]pyrimidin-7-yl]benzonitrile.

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

52. A method for inhibiting lysine specific demethylase-1 (LSD1), said method comprising contacting a compound of claim 1, or a pharmaceutically acceptable salt thereof, with the LSD1.

53. A method for treating a disease comprising:

administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein said disease is cancer.

54. The method of claim 53, wherein the cancer is a hematological cancer.

55. The method of claim 54, wherein said hematological cancer is selected from acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), acute promyelocytic leukemia (APL), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, non-Hodgkin lymphoma (including relapsed or refractory NHL and recurrent follicular), Hodgkin lymphoma, primary myelofibrosis (PMF), polycythemia vera (PV), essential thrombocytosis (ET), myelodysplasia syndrome (MDS), or multiple myeloma.

56. The method of claim 53, wherein the cancer is a sarcoma, lung cancer, gastrointestinal cancer, genitourinary tract cancer, liver cancer, bone cancer, nervous system cancer, gynecological cancer, or skin cancer.

57. A method of treating a disease comprising:

administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the disease is a viral disease or a beta-globinopathy.